For patients with pancreatic ductal adenocarcinoma (PDAC), surgical resection remains the only potentially curative treatment. Surgery is generally followed by postoperative chemotherapy associated with improved survival, yet neoadjuvant therapy is a rapidly emerging concept requiring to be explored and validated in terms of treatment options and oncological outcomes. In this context, stereotactic body radiation (SBRT) appears feasible and can be safely integrated into a neoadjuvant chemotherapy regimen of modified FOLFIRINOX (mFFX) with promising benefits in terms of R0 resection, local control and survival. However, the optimal therapeutic sequence is still not known, especially for borderline resectable PDAC, and the role of adding SBRT to chemotherapy in the neoadjuvant setting needs to be evaluated in randomised controlled trials. The aim of the STEREOPAC trial is to assess the impact and efficacy of adding isotoxic high-dose SBRT (iHD-SBRT) to neoadjuvant mFFX or Gemcitabine/Nab-Paclitaxel (Gem/Nab-P) in patients with borderline resectable PDAC.This is a randomised comparative multicentre phase II trial, planning to enrol patients (n = 256) diagnosed with a borderline resectable biopsy-confirmed PDAC. Patients will receive 4 cycles of mFFX (or 6 doses of Gem/Nab-P). After full disease restaging, non-progressive patients will be randomised for receiving either 4 additional mFFX cycles (or 6 doses of Gem/Nab-P) (Arm A), or 2 mFFX cycles (or 3 doses of Gem/Nab-P) + iHD-SBRT (35 to 55 Gy in 5 fractions) + 2 mFFX cycles (or 3 doses of Gem/Nab-P) (Arm B). Then curative surgery will be performed followed by adjuvant chemotherapy according to patient’s condition. The co-primary endpoints are R0 resection and disease-free survival after the complete sequence strategy. The secondary endpoints include resection rate, overall survival, locoregional failure / distant metastasis free interval, pathologic complete response, toxicity, postoperative complications and quality of life assessment.This trial will help define the best neoadjuvant treatment sequence for borderline resectable PDAC and aims to evaluate if a total neoadjuvant treatment integrating iHD-SBRT improves the patients’ oncological outcomes.The study was registered at ClinicalTrails.gov (NCT05083247) on October 19th, 2021, and in the Clinical Trials Information System (CTIS) EU CT database (2022-501181-22-01) on July 2022.The online version contains supplementary material available at 10.1186/s12885-023-11327-x. Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with a poor prognosis mainly due to the high frequency of distant metastases or the locally advanced stage of the tumour excluding a surgical procedure from the outset . In BelgAs a standard, surgery is usually followed by adjuvant therapy that significantly improves survival; this concept was proven by several trials : usually 6 months of modified FOLFIRINOX (mFFX) regimen is administrated in fit patients  and in more frail or older patients, gemcitabine monotherapy or in combination with capecitabine is given (improved DFS by 20%) –7. HowevIn recent randomised phase III trials, neoadjuvant chemotherapy (gemcitabine + S1) was shown to be efficacious in resectable tumours in Asian patients while in the PREOPANC trial, gemcitabine-based chemoradiation (CRT) reported, after a median follow-up of 59 months, a limited improvement in survival for resectable/BR PDAC  , 13. RecThe present study proposes now to evaluate the impact and efficacy of incorporating iHD-SBRT to preoperative neoadjuvant mFFX or Gem/Nab-P in patients with BR PDAC in a TNT sequence. We hypothesize that this full sequence strategy of pre-operative treatment is safe and feasible and will improve both the surgical management (R0 resection) and the prognosis of PDAC patients as evaluated by the DFS, as co-primary end-points.The SPIRIT reporting guidelines were used for this protocol and the completed SPIRIT checklist is available in Supplementary Table This study is a multicenter randomised open-label comparative phase II trial. Patients who have been diagnosed with borderline resectable PDAC (according to the NCCN definition ) will beThe randomisation will be performed in subjects after receiving the first 4 cycles doses of FFX (or 6 doses Gem/Nab-P), showing a manageable tolerance and no progressive disease at restaging. Subjects will be centrally and automatically randomised electronically by the RedCap® system.To minimize the imbalance in the distribution of treatment numbers within the levels of each individual prognostic factor, a minimization technique will be used for random treatment allocation stratifying by centers and CA 19.9 levels.https://www.cci-calculator.com/cciCalculator) and quality of life is assessed per EORTC QLQ-C30 version 3.0, QLQ-PAN26 questionnaires and PHQ-9 scale ).The study duration is then estimated to be 111 months .Safety will be assessed after the first 20 patients having received the TNT sequence and surgery. Safety analysis will then be planned every six months. The final decision to terminate the trial in case the criteria for stopping rules and futility are encountered will be done by the sponsor of the study.The statistical analysis of efficacy will consist for DFS on HR testing and for R0 resection on the testing of the difference between R0 resection rates. Analysis will also make use of Kaplan-Meier analysis of DFS, OS and duration of response, in the intention-to-treat population. Multivariable analysis of DFS and OS by means of Cox proportional hazards.Chemotherapy will be administered as standard regimens for both mFFX or Gem/Nab-P.iHD-SBRT will be delivered under a prespecified protocol supervised by the coordinating RT (CB) including QART as followed: each RT site must be credentialed for pancreatic SBRT prior to enrollment (facility questionnaire and dummy run procedure), the first 3 cases treated by iHD-SBRT must be centrally reviewed and approved before the beginning of the treatment (contouring and RT plan) and all the following RT treatments will be centrally reviewed retrospectively.Surgery will be performed by expert pancreatic surgeons in dedicated expert centers as it is currently requested in Belgium by the healthcare program. The coordinating surgeon (JN) will chair an expert surgical committee that will review the procedures and potential complications after TNT.Pathological evaluation and full margins assessment will be centrally reviewed by a committee under the supervision of the coordinating pancreatic pathologist (PD) and reported according to the recommendations from the Pancreatobiliary Pathology Society .Throughout the trial, an external independent expert committee will be responsible for monitoring and reviewing the data and make recommendations. Audits will periodically be performed in each participating center in order to randomly check compliance with the protocol, compliance with in- and exclusion criteria, proper implementation, conduct of Informed Consent procedures, data verification (i.e. crosscheck data in RedCap® with patient dossier and vice versa), and adequate reporting of serious adverse events (SAEs). Adverse events are graded using the CTCAE version 5.0 . SuspectThe termination of the study is at the discretion of the sponsor in any of the following events:Medical or ethical reasons affecting the continued execution of the study.Difficulties in recruiting patients.Occurrence of adverse events unknown to date as to their nature, severity and duration, or unexpected incidence/severity of known adverse events.Study safety data will be reviewed by the sponsor and investigators on an ongoing basis to ensure that continuation of the study is appropriate.The study has been approved by the central Ethical Committee through the Clinical Trials Information System (CTIS) procedure . It has been registered at the ClinicalTrails.gov database (NCT05083247) on October 19th, 2021. The protocol has been designed according to the principles of Good Clinical Practice of the International Conference on Harmonization and of the Declaration of Helsinki. All patients will provide a written informed consent before starting treatment. An additional written inform consent will be obtain for the patients participating in the ancillary translational study for the collection of biological specimens. Subjects are free to discontinue the study at any time without giving their reason(s). Model of inform consent is available in Supplementary Material  at the level of the gross tumour volume (GTV) in a highly conformational way, which makes it possible to reduce the dose and therefore the toxicity to nearby OAR . The SBRThe purpose of this prospective randomised phase II is to evaluate the impact and efficacy of incorporating isotoxic high-dose SBRT into a total neoadjuvant treatment sequence including active chemotherapy for borderline resectable pancreatic adenocarcinoma. Therefore, this trial will help to define the best standard neoadjuvant treatment sequence.Protocol version n°: 1.2 Date: October 18, 2022.Date of beginning of recruitment: March 15, 2023.Approximate date of complete accrual: 1/1/2028.The STEREOPAC trial is a multicenter randomized phase II trial, conducted in 10 initial centers that provide multidisciplinary treatment for pancreatic cancer throughout Belgium. At the time of submission of this paper, all initial centers were activated. The first patient was included on March 24, 2023.Below is the link to the electronic supplementary material.Supplementary Material 1Supplementary Material 2Supplementary Material 3


A short-term immobilization of one hand affects musculoskeletal functions, and the associated brain network adapts to the alterations happening to the body due to injuries. It was hypothesized that the injury-associated temporary disuse of the upper limb would alter the functional interactions of the motor cortical processes and will produce long-term changes throughout the immobilization and post-immobilization period.R) from NIRS Toolbox's connectivity module.The case participant  was scanned using optical imaging technology of fNIRS over immobilization and post-immobilization. Pre-task data was collected for 3 min for RSFC analysis, processed, and analyzed using the Brain AnalyzIR toolbox. Connectivity was measured using Pearson correlation coefficients (The non-affected hand task presented an increased ipsilateral response during the immobilization period, which then decreased over the follow-up visits. The right-hand task showed a bilateral activation pattern following immobilization, but the contralateral activation pattern was restored during the 1-year follow-up visit. Significant differences in the average connection strength over the study period were observed. The average Connection strength decreased from the third week of immobilization and continued to be lower than the baseline value. Global network efficiency decreased in weeks two and three, while the network settled into a higher efficient state during the follow-up periods after post-immobilization.Short-term immobilization of the upper limb is shown to have cortical changes in terms of activations of brain regions as well as connectivity. The short-term dis-use of the upper limb has shifted the unilateral activation pattern to the bilateral coactivation of the motor cortex from both hemispheres. Resting-state data reveals a disruption in the motor cortical network during the immobilization phase, and the network is reorganized into an efficient network over 1 year after the injury. Understanding such cortical reorganization could be informative for studying the recovery from neurological disorders affecting motor control in the future. The human brain adapts to the modifications happening to the body by reorganizing the connections between neurons. This process of brain plasticity initially involves a short-term rearrangement of existing functional connections . Over reA period of immobilization significantly affects musculoskeletal motor functions and causes significant changes in the brain . SensoriThe current study aims to investigate the motor cortical functional connectivity for the immobilized upper right extremity due to a right clavicle fracture. The resting state data were collected to study the intrinsic motor cortex connectivity and the alterations to those connections during the immobilization and recovery phases. It was hypothesized that the injury-associated temporary disuse of the upper limb would alter the functional interactions of the motor cortical processes and will produce changes in the neural networks before and after the immobilization period. Our hypothesis was based on previous investigations that have reported the functional and structural brain reorganization in the sensorimotor cortex , 19, 20.The case participant was a 12-year-old male (Height: 156.94 cm and Weight: 49.9 kg) diagnosed with a lateral right clavicle fracture and prescribed an arm sling immobilizer . The parData were collected using a continuous wave 24-channel fNIRS system . A dual-wavelength (760 and 850 nm) LED source shines light on the subject's scalp. Data were sampled at 10.125 Hz. The cap held eight sources and eight detectors (∼3 cm distance from the source) arranged in a specific montage covering the motor cortex of both hemispheres. The cap was positioned on the head following the 10–20 international system. The center of the cap was aligned with the vertex (Cz), and lateral channels covered the area around the C3 and C4 landmarks which have been shown to detect motor activity that drives hand and arm movement . The eigThe data collection was a longitudinal process. The fNIRS data were collected in six different sessions: Baseline, Week 1–Week 3, Sixth-month post immobilization, and 1-year post immobilization. During the baseline visit, the participant underwent brain imaging using fNIRS. This included a three-minute resting-state period and task period, as shown in the protocol . A relaxData were analyzed using the open-sourced Homer3 v1.26) Toolbox  Toolbox . The rawZ values using Fisher's transformation  analysis. The raw data were then pre-processed and analyzed with the help of the NIRS Brain AnalyzIR toolboxes . A PCA formation , which n(i)Connectivity strength: It is the sum of the connectivity weights of the edges attached to each node. The mean value of the connectivity strength across all the channels will be a metric that can be compared across the immobilization phase to understand the overall changes in the intrinsic connections.(ii)G), the global efficiency is defined as N is the number of nodes and ijL is the shortest path length between ith and jth nodes in the network G. Eg is the efficiency of information exchange in a parallel system in which all nodes are capable of concurrently exchanging information via shortest paths (Network efficiency: For a brain network (st paths .(iii)Nodal degree: It quantifies the total number of edges incident to a node in a binary network. A smaller number of essential nodes receive the majority of connectivity, designating them as nodal hubs that encourage network integration .A network is a collection of nodes and edges, whereas in a macroscale brain network, nodes indicate the channel locations used in the montage, and the edges are the correlation of the time series between each channel. The adjacency matrices were calculated for the entire range of sparsity threshold  and binarized at each threshold for calculating the following network properties.t-test was used to compare the means of HbO values from the ROIs to obtain p-values. A Bonferroni correction was used to control multiple comparisons to get q-values. HbR data were not analyzed or displayed for this study. For the resting data, a one-way repeated measure of ANOVA was conducted to investigate the overall differences in the connectivity strength values for the different data collection time points in the whole study. Post hoc two-sample t-tests were performed to test the differences between specific data collection time points. A corrected p-value of 0.05 was considered significant.For the analysis of task data, a student's The case participant moved more blocks with the non-dominant (intact hand) during immobilized sessions and used both hands during the follow-up visits, conducting the task at his own determined pace. There was a steady increase in the number of blocks moved .p < 0.05) compared to the baseline response for the non-affected hand task. The week 4 task response showed a reduced ipsilateral response for the left-hand task. The bilateral response of the left-hand task was retained after the immobilization period during the 6-month follow-up measurement but was significantly reduced during the second follow-up at 12 months. For the immobilized hand, after immobilization (week 4), strong bilateral activation was observed. However, the 6-month follow-up measurement showed a reduction in bilateral activation for the right-hand task and persisting with contralateral activation pattern even at the 12-month follow-up  = (7.953), p < 0.005] for all the weeks of measurement  = 3.087, Bonferroni corrected p < 0.05], week 4 , sixth-month follow-up  and 12-month follow-up . There was no significant difference in connection strength between the final week and the follow-up months after immobilization.The mean functional connectivity strength was calculated each week for all the channels. It was observed that the average connection strength was significantly different [surement . The posThe network efficiency of the motor cortex is shown in The degree distribution of each node is shown in The current case report examines the changes in cortical responses to a task and resting conditions before, during, and after right upper limb immobilization. The primary findings of the study are: (i) The non-affected left-hand task presented an increased ipsilateral response during the immobilization period, which then decreased over the follow-up visits. The right-hand task showed a bilateral activation pattern immediately after the immobilization period, but the contralateral activation pattern was restored during the 1-year follow-up visit. (ii) During the resting period, the overall average strength of connectivity, network efficiency, and nodal degree in the motor cortex decreased during the immobilization period as opposed to the baseline measurement. The case study investigates the reformation of functional motor area network using resting state fNIRS unlike the previous works.The task based baseline motor cortex measurement of the participant yielded a typical contralateral response for the gross dexterity movement of both hands, as reported in previous investigations , 33. HowThe resting brain connectivity analysis was evaluated during the resting period before the task performance to capture endogenous and spontaneous network activity. To accomplish this objective, we used brain connectivity outcomes, including connection strength, the efficiency of the network, and nodal degree. The average connectivity strength lays out an overall change in the interhemispheric connectivity of the motor cortex . The immThe intrinsic network efficiency decreased during the immobilization weeks at lower connection densities. The cost efficiency (∼30% connection density) for the relatively sparse network configuration is a point after which an increase in edges will not yield a proportional increase in efficiency. Increased functional network efficiency reported towards the 6- and 12-month follow-up sessions at this lower cost (∼20% to 30% connections) implies that the wiring volume and metabolic resources have been reduced compared to the immobilization period , 36, 37.The case study's findings indicate that immobilizing the dominant hand alters the motor cortical response for the immobilized hand, which may be attributed to compensatory use of the non-dominant (unaffected) arm during the immobilization phase. Changes in intrinsic connectivity measures within the motor cortex reflect the disuse of the dominant hand and the adaptive use of the non-dominant left hand. Though the case report is limited in sample size for validating the findings, this understanding of changes in cortical mechanisms during short-term immobilization may be fostered by larger sample sized future studies and aid in developing rehabilitation strategies for recovering from motor control disorders.


The initiation of non-small-cell lung cancer (NSCLC) causes significant changes in a patient’s blood plasma metabolomic profile. Locally and early-advanced NSCLC patients receive a complete surgical resection of the lung tumor, but the level of metabolic changes after this surgical treatment is currently unknown. By collecting multiple blood plasma samples before and after complete NSCLC removal, metabolic changes can be detected by analyzing the patient’s plasma using proton nuclear magnetic resonance (NMR) spectroscopy. Detection of significant changes in the plasma metabolism, a so-called metabolic shift in the patient’s blood plasma after surgical tumor resection, indicates the absence of disease recurrence and thus can provide an indication of a good prognosis.1H-NMR spectroscopy. NMR spectra (s = 222) representing two preoperative and one postoperative plasma metabolite profile at three months after surgical resection were obtained for all patients. In total, 228 predictors, i.e., 228 variables representing plasma metabolite concentrations, were extracted from each NMR spectrum. Two types of supervised multivariate discriminant analyses were used to train classifiers presenting a strong differentiation between the pre- and postoperative plasma metabolite profiles. The validation of these trained classification models was obtained by using an independent dataset. Results: A trained multivariate discriminant classification model shows a strong differentiation between the pre- and postoperative NSCLC profiles with a specificity of 96% (95% CI [86–100]) and a sensitivity of 92% (95% CI [81–98]). Validation of this model results in an excellent predictive accuracy of 90% (95% CI [77–97]) and an AUC value of 0.97 (95% CI [0.93–1]). The validation of a second trained model using an additional preoperative control sample dataset confirms the separation of the pre- and postoperative profiles with a predictive accuracy of 93% (95% CI [82–99]) and an AUC value of 0.97 (95% CI [0.93–1]). Metabolite analysis reveals significantly increased lactate, cysteine, asparagine and decreased acetate levels in the postoperative plasma metabolite profile. Conclusions: The results of this paper demonstrate that surgical removal of NSCLC generates a detectable metabolic shift in blood plasma. The observed metabolic shift indicates that the NSCLC metabolite profile is determined by the tumor’s presence rather than donor-specific features. Furthermore, the ability to detect the metabolic difference before and after surgical tumor resection strongly supports the prospect that NMR-generated metabolite profiles via blood samples advance towards early detection of NSCLC recurrence.Background: Lung cancer can be detected by measuring the patient’s plasma metabolomic profile using nuclear magnetic resonance (NMR) spectroscopy. This NMR-based plasma metabolomic profile is patient-specific and represents a snapshot of the patient’s metabolite concentrations. The onset of non-small cell lung cancer (NSCLC) causes a change in the metabolite profile. However, the level of metabolic changes after complete NSCLC removal is currently unknown. Patients and methods: Fasted pre- and postoperative plasma samples of 74 patients diagnosed with resectable stage I-IIIA NSCLC were analyzed using  Metabolic reprogramming is a key hallmark of cancer initiation, progression, and relapse ,2,3. NutThe metabolite profile is reported to have a donor-intrinsic character, as confirmed by Assfalg et al. They demonstrated the existence of such a donor-specific urine metabolite fingerprint with a 100% identification probability . FurtherThis study aims to determine the effect of complete surgical removal on the plasma metabolite profile of locally and early-advanced-stage NSCLC patients without rapid NSCLC recurrence. By prospectively collecting blood samples at specific pre- and postoperative time points from all eligible patients, patient-specific plasma metabolite profiles before and after surgery can be compared. While it has been reported that the metabolite profile is patient-specific and changes in the function of an acute stress response, the level of metabolic changes after surgical resection of lung cancer, remains currently unknown.Samples were collected during the registered trial with the study number NCT03736993, conducted following the Helsinki Declaration and Good Clinical Practice’s ethical rules. The study protocol was approved by the Medical Committees of ZOL , AZDelta , OLV Ziekenhuis  and Hasselt University . Signed informed consent was obtained from all participants before inclusion.n = 50) and validation (n = 24) cohort are summarized in All study participants were diagnosed with resectable stage I-IIIA NSCLC. The inclusion criteria were (i) no history of, or treatment for, cancer during the last five years, (ii) fasted and no medication intake for at least six hours and (iii) a fasting glucose concentration below 200 mg/dL. Patients who did not receive complete surgical resection or with a postoperative pathological non-malignant diagnosis were excluded from the study. Specifically for this sub-study, all study participants without cancer recurrence six months after surgical resection were selected. The sample size of this sub-study is based on the feasibility and availability of the study participants. An inclusion stop between March and June 2020 due to the COVID-19 pandemic had no further impact on the participants’ planned blood sampling time points. The complete sub-study flow diagram is shown in g, and plasma aliquots of 400 µL were stored at −80 °C until the proton 1H-NMR analysis.All venous blood samples were collected in 6 mL spray-dried lithium-heparin tubes and stored immediately on ice to delay metabolic activity . Within 1H-NMR spectroscopy as described in the protocol of Derveaux et al. ) and specificity of 92% (95% CI [73–99]) in an independent patient cohort. In addition, metabolite analysis reveals that the metabolic shift after NSCLC removal is characterized by a significant increase in the plasma levels of lactate, cysteine and asparagine together with a decrease in the plasma acetate concentration. Furthermore, the metabolic shift between the pre- and postoperative metabolite profiles indicates that the NSCLC metabolite profile is tumor-determined rather than donor-specific, as further confirmed by an additional OPLS-DA model with poor model parameters  between the two preoperative time points. In conclusion, these results reveal that the metabolic difference caused by a tumor’s presence or absence is much larger than the individual’s daily metabolic variance.s = 100 for all trained models) and validation sets (s = 48 for B/E and s = 46 for C/E and B/C models) leaves both groups with a sufficient sample size for discriminative statistical analysis with adequate statistical power. However, no external validation using the data collected at different collaborating centers occurred yet in this sub-study.One of the strengths of this study is the longitudinal design of plasma sampling at different time points. The large number of included patients with only locally and early-advanced resectable NSCLC allows randomly dividing the data into a training and independent validation set and results in reliable multivariate statistical discriminant analyses. However, longitudinal study designs have a high financial cost, are time-consuming and require intensive data management and multidisciplinary collaboration. For this reason, many reported studies are rather limited in the number of patients included. In this explorative study, the discriminative potential of pre- and postoperative plasma metabolite profiles is examined using 222 complete metabolic datasets obtained at three different time points from 74 NSCLC patients. Splitting the data into training , patient-to-patient and sample-to-sample variation in HSA concentration, chemical shift fluctuations of metabolite signals, loss of statistical power due to peak fragmentation caused by shifting of the peaks beyond the limits of defined integration regions, and the absence of a reliable internal standard for normalization and quantification of signal intensities. The methodology as described by Derveaux et al. tackles these obstacles by the addition of (i) 4 mM TSP as a HSA-binding competitor and (ii) maleic acid (MA) as a reliable internal standard  . The preA limitation of the sub-study is the current lack of sufficient patient inclusions who show NSCLC recurrence after surgical resection. Of the 80 eligible patients, only 6 patients (=7.5%) were diagnosed with recurring NSCLC after six months, as shown in the study flow diagram in The use of fasted plasma samples is preferred over non-fasting samples as they were proven to have good reproducibility and minimize the impact of dietary habits ,34. FastRetrospective analysis of the clinical records of the three patients who were incorrectly classified in the B/E validation B revealeThe data presented in this paper supports the findings of Ghini et al. They monitored 12 individuals over ten years and investigated the level of resilience, or metabolic flexibility, of the urine metabolite profile . It was Several long-term studies demonstrated that an individual’s metabolite fingerprint allows a correct subject identification based on a serial collection of samples during a long time interval in case of the absence of disease onset, indicating the donor-intrinsic character of the metabolic profile ,18,19. AThis study demonstrates that a responsive metabolic change occurs in locally and early-advanced NSCLC patients treated by surgical resection. Removing the tumor introduces a significant metabolic change in all 74 study participants who do not show cancer recurrence six months after surgery. This change is demonstrated by the successful differentiation between pre- and postoperative metabolite profiles with 92% specificity and 88% sensitivity. Furthermore, the metabolic shift is characterized by a significant increase in the levels of lactate, cysteine and asparagine, and decreased acetate in the postoperative plasma metabolite profile. The detection of this metabolic shift indicates the potential of the metabolite profile to detect early recurrence of NSCLC metabolism. Further patient inclusion and blood sample collection of NSCLC patients diagnosed with disease progression will provide more data to the constructed models and will further determine how the plasma metabolite profile can be used as a minimally invasive monitoring instrument during therapy follow-up of locally and early-advanced NSCLC patients.


Acute-on-chronic liver failure (ACLF) is a complex syndrome that develops in patients with acutely decompensated cirrhosis. In this condition, dysbalanced immune function and excessive systemic inflammation are closely associated with organ failure and high short-term mortality. In this review, we describe how omic technologies have contributed to the characterization of the hyperinflammatory state in patients with acutely decompensated cirrhosis developing ACLF, with special emphasis on the role of metabolomics, lipidomics and transcriptomics in profiling the triggers (pathogen- and damage-associated molecular patterns [PAMPs and DAMPs]) and effector molecules  that lead to activation of the innate immune system. This review also describes how omic approaches can be invaluable tools to accelerate the identification of novel biomarkers that could guide the implementation of novel therapies/interventions aimed at protecting these patients from excessive systemic inflammation and organ failure. ACLF is a severe syndrome resulting in high short-term mortality evolving in patients with acutely decompensated (AD) liver cirrhosis. ACLF is defined by organ dysfunction and failures in liver, kidney, brain, coagulation and respiratory and circulatory systems, which are defined according to the criteria of the European Association for the Study of the Liver–Chronic Liver Failure (EASL‐CLIF) Consortium , 2], , . In WestRecent advances in understanding the pathophysiology of ACLF have identified an association between systemic inflammation and organ injury in patients with AD cirrhosis developing ACLF , 5], , . ActivatAt present, little is known about the identity of the triggers (either of infectious or noninfectious origin) leading to excessive systemic inflammation in patients with AD cirrhosis evolving to ACLF. Bacterial infections are present in 33% of cases of ACLF  and therThe systemic hyperinflammatory response in patients with ACLF frequently occurs in parallel with the presence of a dysfunctional innate immune system at the humoral, physical and cell-mediated level , 12, 13.As described above, the dysfunctional innate immune system in patients with ACLF is characterized by increased circulating levels of small proteins  and small bioactive lipids (lipid mediators) that signal exuberant inflammatory and immune responses.Cytokines are low-molecular-weight glycoproteins that orchestrate the effectiveness of innate immunity by inducing local inflammation and acute systemic responses , 17. The2 . Un. Un49]. The specific ACLF metabolic fingerprint also contains metabolites indicating depressed mitochondrial ATP-producing fatty acid β-oxidation. In this regard, it is well established that systemic inflammation promotes important changes in mitochondrial function in peripheral organs that preclude appropriate mitochondrial energy production. Indeed, systemic inflammation inhibits both the translocation of fatty acids into the mitochondria and fatty acid β-oxidation and decreases oxidative phosphorylation and ATP production . ConsistCMKLR1) gene, which encodes a G protein-coupled receptor that recognizes RvE1, a small bioactive lipid mediator with potent activity in the resolution of inflammation (see above). Among these SNPs, we identified two polymorphisms belonging to the IL-1 gene cluster (IL-1β and IL-1ra) in strong association with ACLF [The intensity of systemic inflammation and the response of the immune system to PAMPs and DAMPs in patients with AD cirrhosis developing ACLF might also be under the influence of host genetic factors. In this regard, certain single-nucleotide polymorphisms (SNPs) have been demonstrated to modulate the release of inflammatory molecules by innate immune cells or the induction of changes in the expression of TLRs. For example, our laboratory screened a panel of SNPs located in six different genes strongly associated with the inflammatory process in a population of 279 patients with AD cirrhosis, of whom 178 presented ACLF. Specifically, we analyzed two SNPs within the IL-1 gene cluster ; a SNP (rs1800871) in the gene coding for the anti-inflammatory cytokine IL-10 and another SNP (rs4969170) in the suppressor of cytokine signaling (SOCS) 3; the rs31315500 SNP coding for nucleotide-binding oligomerization domain-containing protein 2 (NOD2), a receptor which recognizes bacterial LPS and is primarily expressed in peripheral blood leukocytes; and finally, a SNP (rs1878022) in the chemokine-like receptor 1  are needed to highlight the value of agnostic approaches in the search for genetic variants with pathophysiological implications. Such a study was recently performed by Tan et al. who carried out GWAS among 399 hepatitis B virus (HBV)-related ACLFs and 401 asymptomatic HBV carriers without antiviral treatment and identified HLA-DR as the major locus for susceptibility to HBV-related ACLF . A more Transcriptomics has evolved in the last decade as an invaluable tool for investigating changes in immunological conditions, mainly by the identification of modules of highly co-expressed transcripts that identify specific immune cell subsets . RecentlThe ACLF syndrome represents a new paradigm among the diseases characterized by the presence of an excessive systemic inflammatory response associated with organ failure(s). The ACLF syndrome is, thus, a suitable disease condition to investigate the mechanisms underlying systemic inflammation and tissue damage and to advance the identification of the triggers of systemic inflammatory response associated with end-organ dysfunction. The ACLF syndrome is also a suitable condition for the identification of novel biomarkers, and current ongoing studies using cutting edge technologies and integrated multi-omics approaches are rapidly accelerating this process. The identification and clinical validation of these new biomarkers is of utmost importance to guide the discovery of novel therapies/interventions that reduce inflammation without inducing immunosuppression in these patients.


Supracondylar humeral fractures in children are the most common fractures of the elbow accounting for 16 % of all pediatric fractures. The treatment depends on age, the degree of displacement, and the presence of additional injuries.A case reports a 10-year-old girl with a Gartland type III supracondylar humeral fracture accompanied by anterior interosseous nerve neurapraxia preoperatively. The patient was treated operatively with medial and lateral column cross-pinning using four K-wires due to unsatisfactory closed reduction and lateral pinning only. Follow-up examinations performed in 1 and 6 months postoperatively revealed a 10° flexion contracture of the elbow with good functional and radiological results otherwise.The main intervention was not focused on the AIN neuropraxia itself but on unsatisfactory closed reduction followed by cross-fixation with lateral pinning only. A standard anterior approach to visualize the fracture line, free interposing tissues, and perform stabilization was utilized. The unusual use of an additional medial pin formed a cross-frame to adequately support the medial cortex.Closed reduction and percutaneous pinning are the preferred treatment options for most displaced supracondylar fractures. The open reduction via anterior approach and pinning for Gartland type III fracture gives good outcomes. Medial pinning is mandatory in particular fracture patterns and in case of unsatisfactory closed reduction. In the presented case medial and lateral column cross-pinning technique using four K-wires guaranteed no subsequent displacement on follow-up assessment and good results. •Supracondylar humerus fractures are the most common fractures in children.•Closed reduction and pinning is the preferred treatment method•Medial pinning is necessary for particular fracture patterns. Open 2A 10-year-old girl was admitted to the Pediatric Surgery Department after falling onto an outstretched hand. The radiographs (in two planes including the wrist and elbow joint) revealed a completely displaced supracondylar humerał fracture - Gartland type III . On phys3Supracondylar humeral fractures in children can lead to impairment of the function of the elbow joint . Conserv4Closed reduction and percutaneous pinning are the preferred treatment options for most displaced supracondylar fractures. The open reduction via anterior approach and pinning for Gartland type III fracture gives good outcomes without leading to impairment of function or deformation of the elbow joint. Medial pinning is mandatory in particular fracture patterns and in case of unsatisfactory closed reduction. In the presented case medial and lateral column cross-pinning technique using four K-wires guaranteed no subsequent displacement on follow-up assessment and good results.The patients' parents were informed that data from the research would be submitted for publication and gave their consent.None declared.Study Design AData Collection BStatistical Analysis CData Interpretation DManuscript Preparation ELiterature Search FFunds Collection G1. Author: Slawomir Kiepura, M.D, ABCDEF2. Co-author: Julian Dutka, Ph.D., ADEJulian Dutka.Written informed consent was obtained from the patient's parents/legal guardian for publication and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.None declared. The authors have no financial, consultative, institutional, and other relationships that might lead to bias or conflict of interest.


Older primary central nervous system lymphoma (PCNSL) patients have an inferior prognosis compared to younger patients because available evidence on best treatment is scarce and treatment delivery is challenging due to comorbidities and reduced performance status. High-dose chemotherapy and autologous stem cell transplantation (HCT-ASCT) after high-dose methotrexate (MTX)-based immuno-chemotherapy has become an increasingly used treatment approach in eligible elderly PCNSL patients with promising feasibility and efficacy, but has not been compared with conventional chemotherapy approaches. In addition, eligibility for HCT-ASCT in elderly PCNSL is not well defined. Geriatric assessment (GA) may be helpful in selecting patients for the best individual treatment choice, but no standardized GA exists to date. A randomized controlled trial, incorporating a GA and comparing age-adapted HCT-ASCT treatment with conventional chemotherapy is needed.This open-label, multicenter, randomized phase III trial with two parallel arms will recruit 310 patients with newly diagnosed PCNSL > 65 years of age in 40 centers in Germany and Austria. The primary objective is to demonstrate that intensified chemotherapy followed by consolidating HCT-ASCT is superior to conventional chemotherapy with rituximab, MTX, procarbazine (R-MP) followed by maintenance with procarbazine in terms of progression free survival (PFS). Secondary endpoints include overall survival (OS), event free survival (EFS), (neuro-)toxicity and quality of life (QoL). GA will be conducted at specific time points during the course of the study. All patients will be treated with a pre-phase rituximab-MTX (R-MTX) cycle followed by re-assessment of transplant eligibility. Patients judged transplant eligible will be randomized (1:1). Patients in arm A will be treated with 3 cycles of R-MP followed by maintenance therapy with procarbazine for 6 months. Patients in arm B will be treated with 2 cycles of MARTA (R-MTX/AraC) followed by busulfan- and thiotepa-based HCT-ASCT.The best treatment strategy for elderly PCNSL patients remains unknown. Treatments range from palliative to curative but more toxic therapies, and there is no standardized measure to select patients for the right treatment. This randomized controlled trial will create evidence for the best treatment strategy with the focus on developing a standardized GA to help define eligibility for an intensive treatment approach.German clinical trials registry DRKS00024085 registered March 29, 2023.The online version contains supplementary material available at 10.1186/s12885-023-11193-7. Median age at diagnosis is above 60 years in primary diffuse large B-cell lymphoma (DLBCL) of the central nervous system (PCNSL), a rare lymphoma confined to the cerebral parenchyma, leptomeninges, eyes or spinal cord , 2. StanHowever, toxicities - mainly infectious complications which commonly occur in the 1st treatment cycle - remain major challenges in the treatment of PCNSL patients. In an international retrospective analysis investigating the MATRix regimen in routine clinical practice the 1st cycle of MATRix was associated with the most severe toxicities, with 6% of patients requiring admission to the intensive care unit in comparison to only 1 admission during cycle 2–4 of MATRix . In the ECOG PS (1 point if ECOG > 1), Barthel Index of ADL (1 point if less than full points in ADL) and Lachs geriatric screening (1 point if Lachs > 3), named the EBL Score > 1, seems to be associated with a higher chance of premature end of treatment (EOT) ..44].The sample size calculation is based on the primary endpoint PFS. The control intervention is the R-MP protocol, as previously reported . Within The primary analysis will be performed according to the intention-to-treat (ITT) principle in the full analysis set (FAS). The FAS includes all randomized patients in whom therapy after randomization was started. Patients will be analysed in the treatment arms to which they were randomized, irrespective of whether they refused or discontinued the treatment or whether other protocol deviations are known.The analysis of the primary endpoint PFS will be conducted in the FAS according to the intention-to-treat principle. The treatment effect will be estimated and tested by Cox regression. The regression model will include treatment and, for adjustment, the stratification variable ECOG (0/1 vs. ≥ 2) as independent variables. As estimate of the effect size, the hazard ratio (arm A vs. arm B) will be calculated with a corresponding asymptotic two-sided 95% confidence interval (CI). The two-sided test on the difference between the experimental arm A and the control arm B at two-sided significance level of 5% will be based on the corresponding asymptotic two-sided 95% CI from the Cox regression model.Additionally, PFS rates in the two treatment arms will be estimated by the Kaplan-Meier method.The primary analysis is conducted irrespective of the occurrence of intercurrent events, consistent with the treatment policy strategy of the estimands framework described in the ICH E9 (R1) addendum. Intercurrent events comprise early termination of treatment due to toxicity, treatment failure or patient´s wish. These events are captured in the secondary endpoint EFS in accordance with the composite strategy.As a sensitivity analysis, the analysis will be repeated in the per-protocol (PP) set, excluding patients with major protocol violations.Secondary endpoints will be analyzed descriptively. EFS and OS will be analyzed in the same way as described for PFS. Remission after 2 cycles of induction treatment will be determined after the 2nd cycle of R-MP in arm A and after the 2nd cycle of MARTA in arm B (= RA I in both arms). The endpoint remission after completion of the 3rd cycle of R-MP (arm A) / consolidating HCT-ASCT (arm B) will be determined within 25–35 days after the start of the 3rd cycle of R-MP (arm A) / on day 30 after ASCT (arm B).Sensitivity analyses will be performed by additionally including other relevant prognostic variables: gender, LDH level , involvement of deep structures of the brain (yes vs. no) and protein count of cerebrospinal fluid , to adjust for potential confounding in the regression models proposed above for the primary and the secondary endpoints.Safety analyses will be performed in the safety population (SAF). Patients in the SAF are analyzed as belonging to the treatment arm defined by treatment received. Patients are included in the respective treatment arm, if treatment was started.https://www.secutrial.com/). During data entry, the data will be checked by so-called edit checks. There are study-specific reports programmed and generated with secuTrial® or SAS software that allow to check for completeness, consistency, plausibility, as well as protocol violations and other distinctive problems (e.g. cumulative missing data). All programs which can be used to influence the data or data quality will be validated.The data management will be done with secuTrial® (An independent Data Monitoring Committee (DMC) has been established, that consists of two medical scientists and one statistician with longstanding experience in clinical trials. The DMC’s function is to monitor the study’s course and if necessary, make recommendations to the coordinating or principal investigator for study continuation, modification or discontinuation. The DMC members will be informed about patient recruitment, adherence to the protocol, observed serious adverse events and deaths by receiving the development safety update reports (DSURs) at regular intervals.Treatment strategies for elderly PCNSL patients > 65 years are not well defined reflecting in inferior outcome in comparison to younger patients. Treatment of this vulnerable patient population is challenging because of a frequently poor PS and comorbidities . A recenJudgment of who can profit from an intensive therapy approach remains difficult because standardized tools to define transplant eligibility are missing. We found GA scores like CIRS-G, ECOG PS, Barthel Index of ADL and Lachs geriatric screening to be associated with premature end of treatment as well as decreased PFS and OS in the MARTA and MARiTA study population, whereas age did not seem to play a major role. We haveWe aim to demonstrate the superiority of the MARTA induction protocol followed by consolidation with HCT-ASCT compared to the established standard therapy with conventional chemotherapy with R-MP and procarbazine maintenance, in terms of PFS. The implemented GA will create evidence on how to define transplant eligibility. This is the first randomized controlled trial investigating HCT-ASCT in this population of elderly patients. Results of this multicenter randomized trial will either change the standard of care to an intensive and shorter treatment approach or redefine R-MP as a proven treatment standard.Below is the link to the electronic supplementary material.Additional file 1: Flow Chart - control intervention arm A table  and expe


Our proposed method provides a novel pathway to efficiently fabricate a ring array with a scale of less than 100 nm, which demonstrates excellent performance in preclinical trials.A hole array was fabricated via photolithography to wet the bottoms of holes using oxygen plasma. Amide-terminated silane, a water immiscible compound before hydrolysis, was evaporated for deposition on the plasma-treated hole template surface. The silane compound was hydrolyzed along the edges of circular sides of the hole bottom to form a ring of an initiator after halogenation. Poly(methacrylic acid) (PMAA) was grafted from the ring of the initiator to attract Ag clusters (AgCs) as AgC–PMAA hybrid ring (SPHR) arrays via alternate phase transition cycles. The SPHR arrays were modified with a Yersinia pestis antibody (abY) to detect the antigen of Yersinia pestis (agY) for plague diagnosis. The binding of the agY onto the abY-anchored SPHR array resulted in a geometrical change from a ring to a two-humped structure. The reflectance spectra could be used to analyze the AgC attachment and the agY binding onto the abY-anchored SPHR array. The linear range between the wavelength shift and agY concentration from 30 to 270 pg mL The optical properties of metal nanostructures have attracted considerable attention for both basic and applied research owing to surface plasmon polaritons (SPPs) ,2. The sIn previous studies, nanoring arrays have been widely developed to investigate their fascinating properties in immunoassay , cancer-In polymer brushes, one end of the polymer chain is tethered to a substrate, which can modulate the chemical and physical properties of the surface through the functional groups and molecular weights. The functional groups of polymer brushes with electrostatic charges can be used to adsorb the charged metal nanoparticles . For exaYersinia pestis (Y. pestis). In this regard, the rapid and precise detection of the Y. pestis antigen (agY) is expected to help hinder plague spreading. The SPHR arrays were treated with protein G to bind the Y. pestis antibody (abY) for detecting the agY. The ring structure of abY-modified SPHR resulted in optical property changes in these arrays in the reflectance wavelength after agY treatment  = 10 CFU mL−1 and linearly increased with increasing Y. pestis concentration between 20 and 300 CFU mL−1  calculated using linear regression equations for peak IV and V were 20 and 10 CFU mL−1, respectively. Moreover, blood samples were spiked with inactivated Y. pestis at 100, 200, and 300 CFU mL−1 for post-lysis agY quantitation using both ELISA and the SPHR sensor (p > 0.05) between commercial ELISA and our method for agY quantitation in blood specimens containing 50 CFU mL−1 of Y. pestis, 106 CFU mL−1 of E. coli, and 106 CFU mL−1 of S. aureus. Furthermore, the blood samples were diluted two- or four-fold and post-spiked with agY for recovery tests. The recoveries ranged from 96.21 to 104.98%, and all RSDs were ≤6.34%, which indicated that the spiked agY could be accurately and selectively identified in real complex samples  provides a meager CFU mL−1 a. Ps plaer case. b The aveR sensor . The ELI samples . The othWe developed a simple route consisting of photolithography processes and surface modification technologies to form designable ring patterns. The nanoscale ring patterns could be metalized with AgCs clusters through polymer brushes by the alternate phase transition of “breathing-in” cycles to construct ring arrays as sensor devices. The proposed approach facilitates the practice of nanoring fabrication in industry. Our scale-free approach can self-organize other organic, metallic, and ceramic particles as nanorings. A charge-carrying PMAA brush is appropriate as the matrix to attract the metal particles and anchor aptamers for the fabrication of the SPHR-based devices through the “breathing-in” process. Reflectance spectra can provide information on density of the AgCs inside the PMAA matrix during the “breathing-in” process and detect agY through the redshift with high sensitivity. Notably, agY was predominately filled within the inner of the hydrophobic ring structure because biomolecules possessed higher affinity in the hydrophobic region than in the hydrophilic region. The wavelengths of the reflectance peak of the SPHR redshift linearly with agY concentration, indicating a novel label-free approach to probing antigens with high sensitivity in the preclinical trials. Our proposed detection platform, the SPHR array, could be a potential candidate with reflectance peak wavelengths for biosensing applications.


To the  Editor—Despite a high burden of disease, what drives long COVID remains unknown; however, recent epidemiologic work describing a reduction in risk of long COVID attributable to several interventions  on acute SARS-CoV-2 infection and long COVID. Ensitrelvir demonstrated marked reductions in viral loads early in the course of infection  and was Should long COVID be dependent on the initial peak and duration of SARS-CoV-2 viral load, one strategy for combating long COVID would then entail aggressively reducing viral loads during initial infection. If our hypothesis is supported by more definitive studies, indications for SARS-CoV-2 therapeutics might be liberalized. Our messaging to the public would encourage individuals to continue testing and seeking early antiviral treatment with the aim of preventing long COVID. While much of our focus until now has rightly been on addressing acute SARS-CoV-2 infection, with the waning severity of disease comes an opportunity to address and potentially prevent the long-term consequences of long COVID.


Lateral elbow tendinopathy (LET) is a common overuse injury with complex underlying pathophysiological mechanisms. Although several modes of exercise with or without passive interventions have been recommended as the first-line treatment option of the condition, their effectiveness remains inconclusive. The aim of this case report is to evaluate the effect of wrist extensor exercises with blood flow restriction (BFR) as an add-on intervention to a multi-modal physiotherapy programme to improve outcomes in a patient with LET. A 51-year-old male patient presented with a history of right LET for six months. Interventions included wrist extension exercise with BFR, a two-stage progressive loading training programme of the upper limb, soft-tissue massage, education and a home exercise programme for six weeks (12 visits). A substantial improvement in pain intensity, pain-free grip strength, Patient Rated Tennis Elbow Evaluation score and self-perceived recovery was reported at three-, six-, and 12-week follow-up measurements. A 21% reduction in pressure pain thresholds at the lateral epicondyle was found immediately after wrist extensor exercise with BFR. Based on our findings, adding wrist extensor exercises with BFR to a multimodal physiotherapy programme seems a promising approach to improve the treatment outcome in LET. Nonetheless, further research is needed to confirm the present results. Lateral elbow tendinopathy (LET) or tennis elbow is a frequent musculoskeletal condition that describes a tendinopathy of the common wrist extensors origin ,2. The pDespite the recent advances in research regarding the management of patients with LET, their treatment remains difficult possibly due to the complex underlying pathophysiological mechanisms ,5. VarioRecently, the addition of a novel exercise method using low-load resistance training with blood flow restriction (LLRT-BFR) for the upper limb has been proposed to improve the treatment outcome compared to conventional training in patients with LET . DespiteTherefore, the aim of the present case report was to look at the effect of adding wrist extensor training with BFR in a progressive loading exercise programme for the management of chronic LET. The results of the present report will serve as a pilot study for a future clinical trial of the method in patients with LET.History and clinical examinationA 51-year-old businessman  presented to our clinic with pain over the lateral side of his right elbow (dominant side). The patient is a recreational tennis player for more than 10 years playing two or three times per week. The patient described a pin-point pain showing over the lateral epicondyle that sometimes may radiate distally to the forearm during strenuous activities. The symptoms started six months ago after a hard tennis game. The pain was easily provoked every day during gripping, after 30 minutes to one hour of keyboard typing, when lifting objects like a cup of coffee or a bag etc. Immediately after the onset of the symptoms, the patient visited an orthopaedic surgeon who prescribed non-steroid anti-inflammatory drugs for a week and a home-based exercise programme for a month that did not help. During the patient’s first visit to our clinic, he reported no symptoms during sleeping or in other sites of the body . The patient reported not receiving any medication; no previous trauma or history of elbow tendinopathy; no sensory changes. Review of systems was negative for prior surgery, cancer, diabetes, rheumatoid arthritis or neurological problems.In terms of the clinical examination findings, there were no abnormal findings in posture and gait observation. Also, there were no muscle wasting or inflammatory signs when observing the joints, muscles, and skin of the upper-limbs. Active and passive movements of the neck and shoulders were tested resulting in full range of motion (ROM) and no pain. Assessment of the passive and active movements of the right elbow flexion, extension and pronation were without restriction and pain-free. There was full passive ROM of wrist flexion and extension with the elbow flexed. Active supination and passive wrist flexion with elbow extended provoked patient’s pain over the lateral epicondyle which was self-rated 2 out of 10 in a numerical pain rating scale (NPRS). Active wrist extension with the elbow extended aggravated mostly the patient’s symptom (7 out of 10 in NPRS). The clinical diagnosis of LET was confirmed using the following pain provocation tests: palpation over the lateral epicondyle; resisted wrist extension; resisted middle finger extension; and stretching of the wrist extensors .Outcome measuresDuring the initial visit, pain intensity was measured on an 11-point numeric pain-rating scale assessing the worst level of pain over the last week . To captWe measured pressure pain thresholds (PPTs) with a 1 cm diameter hand-held digital algometer  at the lateral epicondyle at both sides . The PPTWe also used a 6-point Likert-scale as a measure of global rating of change (GROC) from “much worse” to “completely recovered” at six- and 12-week follow-ups .InterventionThe patient followed a six-week physiotherapy programme including soft tissue massage, supervised exercises, advice and education. The exercise protocol was based on a previous randomized controlled trial (RCT) that reported significant improvements in improving function and treatment success following an upper-limb training programme with BFR in patients with LET . DespiteAt the first stage the patient performed wrist flexion, elbow flexion, elbow extension and supination-pronation resistance exercises. At the second stage, more exercises were added such as wall push-up, wrist extension-flexion using a rubber bar, handgrip with a soft ball and rowing with a TheraBand. Each session ended with static stretching of the wrist flexors and extensors (three repetitions X 30 seconds) Tables , 2.ResultsThere was a substantial reduction 42%) in pain intensity from baseline to three-week follow-up and total absence of pain at six- and 12-week follow-ups (Table % in painThe present report monitored the effect of wrist extension exercises with BFR as an add-on intervention to a six-week supervised training programme in chronic LET. Based on our findings, there were significant improvements in pain, function and self-perceived recovery at six- and 12-week follow-ups. Also, a substantial reduction in pain sensitivity was demonstrated immediately after the wrist extension exercise with BFR at the lateral epicondyle. Our results were in agreement with a previous RCT that suggested better treatment outcomes in favor of upper-limb exercises with BFR to a training programme with progressive loading in LET . NotablyBased on multiple research reports LLRT-BFR can improve muscle strength and function in patients with musculoskeletal pathologies; however, in terms of reducing pain intensity research evidence remains inconclusive -21. SpecIt seems that according to the available research evidence selecting the appropriate exercise programme during the management of LET is a challenging procedure. A critical factor for this problem is the paucity of research information regarding the parameters of the proposed training programmes i.e., progression of loading, dosage, volume, time under tension, breaks, acceptable pain level, equipment, frequency and duration. Hence, several modes of exercises have been used in the rehabilitation of patients with LET resulting in conflicting findings . EccentrLET is a common musculoskeletal condition that affects many individuals resulting in a significant functional deficit. Although a multimodal approach including supervised progressive loading exercises is usually recommended, research evidence does not support an optimal training programme for the management of the condition. Based on our findings, the addition of wrist extensor training with BFR to a supervised progressive loading exercise programme along with massage, a home exercise programme and education was effective to reduce pain, improve PFGS and increase function at all follow-up measurements in a patient with LET. Future research using well-designed RCTs is necessary to evaluate the results of the present case report.


There is little research or guidance about clearing patients who are colonized with carbapenemase-producing organisms (CPO). The use of isolation precautions to reduce transmission needs to be balanced with the potential negative impacts of isolation on patient experience, quality of care and non-infection patient safety and outcome measures. Our objective was to develop and implement a standardized provincial protocol for clearing patients of their CPO-positive status.PubMed, Web of Science, EMBASE and Cochrane Library were searched from January 2000 to February 2023. Randomized control trials, retrospective and prospective cohort studies, cross-sectional studies and case series were included. This information was used to create a CPO clearing protocol for use by Alberta Health Services (AHS) Infection Prevention and Control (IPC). The protocol will be monitored through the provincial surveillance system (ProvSurv) to guide future changes.The literature showed that although CPO colonization can be prolonged (more than 12 months), a significant number of patients tested CPO-negative by 3 months since the last positive test. In addition, one-third of patients with 1 or 2 negative swabs subsequently tested CPO-positive. Therefore, the proposed provincial guidance is to re-screen patients 3 months after their last CPO-positive result. Three negative sets (without antibiotic pressure) done at least one week apart are required to clear a CPO flag; where a negative set includes a rectal swab or stool culture, cultures of previously positive sites if still clinically relevant, and additional currently relevant sites.This project aimed to create a standardized provincial protocol for clearing patients of their CPO-positive status to decrease the duration of isolation, while also balancing resource management and patient-centred care. After implementation, next steps include evaluation by monitoring compliance and examining specific CPO-related indicators. There is potential for use by other healthcare institutions and organizations.All Authors: No reported disclosures


Discovered in 1964, Epstein-Barr virus was the first human cancer-causing virus identified. Cancer cells reprogram metabolic pathways to augment their ability to support abnormal rates of proliferation and promote spread through metastatic invasion. Over the course of an infection, EBV drastically alters the metabolic landscape within its host cell, leading to a variety of downstream effects such as contributing to uncontrolled and upregulated cell growth—a hallmark of cancer. In this review, we will provide a comprehensive overview of research hitherto conducted on the means and impact of various metabolic changes that EBV induces, as well as discuss existing and potential treatment options targeting vulnerabilities in EBV-transformed metabolism.The metabolism of cancer cells and Epstein–Barr virus (EBV) infected cells have remarkable similarities. Cancer cells frequently reprogram metabolic pathways to augment their ability to support abnormal rates of proliferation and promote intra-organismal spread through metastatic invasion. On the other hand, EBV is also capable of manipulating host cell metabolism to enable sustained growth and division during latency as well as intra- and inter-individual transmission during lytic replication. It comes as no surprise that EBV, the first oncogenic virus to be described in humans, is a key driver for a significant fraction of human malignancies in the world , both in terms of new diagnoses and attributable deaths each year. Understanding the contributions of metabolic pathways that underpin transformation and virus replication will be important for delineating new therapeutic targets and designing nutritional interventions to reduce disease burden. In this review, we summarise research hitherto conducted on the means and impact of various metabolic changes induced by EBV and discuss existing and potential treatment options targeting metabolic vulnerabilities in EBV-associated diseases. In less than a year, the discovery of Epstein–Barr Virus (EBV) as the first human tumour virus will commemorate its 60th anniversary . While mEBV—also known as human herpesvirus 4—is a double-stranded DNA gammaherpesvirus with a genome of approximately 173 kilobase pairs and has the characteristic ability of herpesviruses of establishing and maintaining lifelong persistency in their hosts through virus-encoded latency programmes . The lifA key evolutionary impetus for EBV to enter latency is to enable immune evasion and life-long persistence in the host. Latency can be categorised into four main programmes ranging from Latency 0 to III depending on the type of viral genes expressed at the protein level, with Latency III cells expressing the most viral genes ,15. In oEBV is capable of driving growth and proliferation in infected cells even as they enter into a state of latency with markedly reduced viral gene expression . As thesMTHFD2 promoter, driving mitochondrial 1C flux as a result  fluoro-D-glucose (FDG-PET/CT) has been established as a standard to diagnose and observe the progression of a variety of cancers. These range from lung, oesopharyngeal, colorectal and even lymphomas . NeoplasInterference with the tricarboxylic acid (TCA) cycle has also become an increasingly popular approach in handling EBV-positive cancers. The TCA cycle is best known to receive acetyl-CoA and transform it into various anaplerotic intermediates to be used in other anabolic reactions. The availability of glutamine is important for the reaction catalysed by glutaminase, where it converts glutamine to glutamate which can then be used to generate α-ketoglutarate that feeds into the TCA cycle . An avenWhile normal cells preferentially obtain fatty acids through uptake from extrinsic sources, cancer cells have a proclivity to generate their own fatty acids via de novo lipogenesis. As EBV induces the immortalisation of B cells; fatty acid synthase (FASN) levels and, by extension, lipogenesis become significantly upregulated. LMP1 was implicated in the induction of FASN in this model, as well as in EBV-associated NPC . FASN isElevated flux through the mevalonate (MVA) and, by extension, the cholesterol biosynthesis pathways has been increasingly associated with being characteristic of cancers. This pathway utilises acetyl-CoA for the production of isoprenoids and sterols that are essential for cancer cell proliferation. MVA is synthesised from hydroxymethylglutaryl coenzyme A (HMG-CoA) and is rate-limited by HMG-CoA reductase (HMGCR) . NotablyTo support high rates of anabolism and redox homeostasis, cancer cells have to establish immense redox capacities, particularly high NADPH/NADP and low NADH/NAD ratios; high levels of NADPH favours reductive synthesis and the accumulation of biomass along with enhanced defence against redox stresses, while increased NAD abundance promotes catabolic flux to generate NADH for energy transduction.High levels of glucose-6-phosphate dehydrogenase (G6PD) contribute to maintaining NADPH levels via the catalysis of G6P to 6-phosphogluconate. This process enables cells to utilise G6PD-induced NADPH counter toxicity through reduced glutathione, a known antioxidant . In EBV-While pronounced upregulation of the cholesterol and lipid pathways are crucial for EBV-induced B cell remodelling see , it alsoBeyond the well-established roles of oxidative phosphorylation (OXPHOS) in generating adenosine triphosphate (ATP) for use as energy, it also has a less appreciated additional role of maintaining the redox balance of NAD/NADH in cells. As B cells transform to become LCLs, OXPHOS and, by extension, oxygen consumption have been observed to be significantly upregulated by EBNA2 and LMP1 ,30. On tThe metabolism of 1C compounds also plays a key role in the production of reducing cofactors required in other metabolic pathways . It involves both the folate and methionine cycles; at its core lies the folate cofactor by which it is mediated. As touched on previously, EBV-infection of primary B cells upregulates a mitochondrial 1C protein not typically expressed in resting B cells and normal adult cells, MTHFD2, via viral EBNA2 and MYC. Knockout of MTHFD2 in EBV-infected LCLs thus demonstrates a significant decrease in cell proliferation as the lack of the enzyme limited the availability of consumable NADPH . The impCancer cells require continuous replication, even in the face of aberrant mutations—EBV cancers are not an exception. To combat the effects of tumour suppressor genes (TSGs) that act as obstacles to their proliferation, EBV employs epigenetic silencing in the form of histone methylation reliant on the availability of universal methyl donor SAM . EBV subPTEN ..99].Twenty years ago, nucleotide synthesis inhibitors became the mainstay of treating EBV cancers. Since then, the community has started looking towards using newer approaches such as immunotherapy . This is evidenced by the increasing number of clinical trials combining these two modalities of treatment. However, caution is warranted in combining standard-of-care nucleotide inhibitors with immunotherapies; effector immune cells need to proliferate in order to perform their anti-tumour functions and inhibitors of nucleotide synthesis squarely prevent that from happening, resulting in minimised therapeutic efficacy. Hence, there is still scope for discovering new metabolic pathways that are cancer specific or which are at least more highly active in cancers than in bystander cells, for therapeutic exploitation.Over the years, much ground has been covered in discovering key metabolic targets against EBV-related B cell malignancies—many of which we have touched upon in this review . Be thatAs alluded to earlier, there is still significant academic and industrial interest in developing metabolic inhibitors that are either more specific or more active in cancer cells. These include inhibitors targeting various metabolic pathways, including one-carbon inhibitors SHIN1  and MTH-For lytic infection, a majority of antivirals directly target viral polymerases instead of working against host pathways that have been specifically modified by the viruses over the course of infection. The former has proven effective in most cases, though it should also be noted that nucleoside analogues mainly target late gene expression which is necessary for virion packaging. IE and E gene products as well as non-coding RNAs can also contribute to the pathogenesis of lytic EBV disease that includes chronic fatigue syndrome, oral hairy leukoplakia and chronic active EBV (CAEBV) ,109,110.


Distal radius fractures (DRFs) are one of the most common types of wrist fracture and can be subdivided into intra- and extra-articular fractures. Compared with extra-articular DRFs which spare the joint surface, intra-articular DRFs extend to the articular surface and can be more difficult to treat. Identification of articular involvement can provide valuable information about the characteristics of fracture patterns. In this study, a two-stage ensemble deep learning framework was proposed to differentiate intra- and extra-articular DRFs automatically on posteroanterior (PA) view wrist X-rays. The framework firstly detects the distal radius region of interest (ROI) using an ensemble model of YOLOv5 networks, which imitates the clinicians’ search pattern of zooming in on relevant regions to assess abnormalities. Secondly, an ensemble model of EfficientNet-B3 networks classifies the fractures in the detected ROIs into intra- and extra-articular. The framework achieved an area under the receiver operating characteristic curve of 0.82, an accuracy of 0.81, a true positive rate of 0.83 and a false positive rate of 0.27 (specificity of 0.73) for differentiating intra- from extra-articular DRFs. This study has demonstrated the potential in automatic DRF characterization using deep learning on clinically acquired wrist radiographs and can serve as a baseline for further research in incorporating multi-view information for fracture classification. Distal radius fractures (DRFs) are one of the most common fractures treated in orthopaedic practice . ProjectIn recent years, deep learning (DL) has made remarkable progress in medical image analysis to assist clinical decision making. However, developing robust machine learning frameworks for fracture classification on wrist X-ray is challenging due to: (1) clinically acquired wrist X-rays vary greatly in image quality, positioning and field of view (FOV); and (2) the wrist has a very complex surrounding anatomy and can have a wide range of injuries from minor to complex traumas . There hA two-stage ensemble DL framework was proposed to classify DRFs as intra- and extra-articular fractures which have different patterns of fragmentation and may require different treatments.The distal radius ROI was firstly localized prior to the classification stage, which allows the framework to focus on the relevant anatomic region and cope with the variation of FOV in wrist radiographs.Ensemble learning strategy was adopted to alleviate the impact of data variance and limited size of the clinical dataset.The recent release of YOLO (You Only Look Once) object detection network , YOLOv5,Evaluated on a clinically acquired wrist X-ray dataset, the proposed DL framework demonstrated effectiveness in differentiating intra- from extra-articular DRFs.This study explores the feasibility of classifying intra- and extra-articular DRFs on wrist radiographs using a two-stage ensemble DL framework. In the first stage, the distal radius regions of interest (ROIs) were automatically localized by an ensemble model of YOLOv5 networks . In the Table This study describes a two-stage DRF classification framework which firstly detects distal radius ROIs using an ensemble model of YOLOv5 networks and then classifies DRFs in the ROIs into intra- or extra-articular using an ensemble model of EfficientNet-B3 networks. The diagram of DRF class prediction is shown in Fig. The YOLO network  is one oEfficientNets describe a family of DL models that uniformly scale all dimensions  of a baseline CNN using a compound coefficient to any target resource constraints , 25. Stapractice . In this1–10 as shown in Fig. For distal radius ROI detection, the YOLOv5s network was trained within a tenfold cross validation, generating 10 base models YOLO r policy  was adopentation  were appentation . The bas1–10 as shown in Fig. The EfficientNet-B3 was also trained within a tenfold cross validation, resulting in 10 base models EfficientNet dAugment  strategyTo extract the distal radius ROIs on the testing images, the model ensembling feature of YOLOv5 was enabled to fuse the 10 YOLO base models’ predictions. The predicted ROIs were then fed into the 10 EfficientNet base models. The predicted probability for each testing instance was calculated by averaging the probabilities across all base models. If a fracture was present in more than one image, the predicted probability of this fracture was set as the average of the probabilities across all images.To perform the binary classification, a probability threshold approach  was adopmentclass2pt{minimWhen applied on the unseen testing data to detect distal radius ROIs, the ensemble of YOLOv5 (YOLOv5s variant) networks achieved a TPR of 1 and a FPR of 0. Figure Comparison experiments were also carried out using other YOLOVv5 variants, including YOLOv5m (medium) with approximately 21.4 M parameters and YOLOv5l (large) with approximately 47.0 M parameters. The YOLOv5m and YOLOv5l ensemble models achieved an average IoU of The DRFs in the distal radius ROIs generated by the YOLO ensemble model were classified by the EfficientNet-B3 ensemble model as intra- or extra-articular fractures. Figure Table Extra-articular and intra-articular fractures are two major types of DRFs. Compared with extra-articular fractures, intra-articular DRFs affect the joint, which may require further evaluation and more complex treatment including surgical fixation. DRFs are challenging to identify due to the high variability and subtlety of fracture patterns. In this study, a two-stage DRF classification system is described which firstly uses the ensemble model of YOLO networks to localize the distal radius ROIs and then classifies the DRF into intra- and extra-articular fractures using the ensemble model of EfficientNet-B3. Evaluated on a clinical wrist X-ray dataset with high variability in imaging parameters and image quality, the proposed framework outperformed the single-stage approach which carries out classification directly on full X-ray images. The EfficientNet ensemble model also demonstrated better performance on DRF classification compared with other DL networks.When examining a radiograph, clinicians often zoom in on the anatomic region of interest . Based oThe second stage of the framework was developed to classify the DRFs in the distal radius ROIs as either intra- or extra-articular. The model ensemble strategy was also adopted to fuse all base models in this stage, as the classification performance of a single model varied substantially during testing as shown in Fig. This work explores the feasibility of DRF classification using DL and has several recognised limitations due to the preliminary phase of study. First, the dataset used for training and evaluating the framework was relatively small. Acquiring a large size DRF X-ray dataset with reliable fracture class annotations is difficult since inter-observer variance often exists and the cases may require multiple clinician labels, which is laborious, time-consuming and resource intensive. For future work, more data will be acquired from collaborating hospitals to enlarge the dataset. Second, this study only used the PA view X-rays to establish the classification framework, however, clinicians normally combine information from all available views  for clinical decision making. In the future, a multi-view network will be built incorporating both PA and lateral view images, which would aim to improve the classification performance.Identifying DRF types can provide useful information for further clinical evaluation and treatment planning. However, DRF classification is a challenging task due to the subtlety and complexity of fracture patterns. In this work, a two-stage ensemble DL framework for DRF classification was proposed. The described framework localizes distal radius ROIs using an ensemble model of YOLO networks and classifies the DRF into intra- and extra-articular fractures with the ensemble model of EfficientNet. Built and evaluated on a clinical wrist X-ray dataset that varies greatly in imaging parameters and image quality, the proposed DL framework achieved promising DRF classification performance with relevant fractured area highlighted using Grad-cam. Future research will expand the study to include a multi-view system with enriched data to assist clinicians in the evaluation of wrist fractures.


In addition to high vaccination levels, COVID-19 control requires uptake and continued adherence to personal hygiene and social distancing behaviors. It is unclear whether residents of a city with successive experience in worldwide pandemics such as SARS, would quickly adopt and maintain preventive behaviors.A population-based, longitudinal telephone survey was conducted between in first local wave of the COVID-19 pandemic (April 2020) and third local wave (December 2020) (n = 403). The study examined factors associated with personal hygiene and social distancing behavior fatigue, as measured by reduced adherence.Over 9 months, face mask use increased . Although habitual hand hygiene remained unchanged (92.0%), blue collar workers and non-working individuals showed higher risk of hand hygiene fatigue. There was a decline (p < 0.05) in avoidance of social gatherings (81.1 to 70.7%), avoidance of public places (52.9–27.5%) and avoidance of international travel (81.9–77.4%) even with rising caseloads. Lowered perception of COVID-19 disease severity was associated with decreased avoidance of social gatherings and public places while lower education was associated with decline in avoidance of social gatherings.Even in regions with past pandemic experience, maintaining social distancing behaviors during a protracted pandemic remains a major public health challenge. Since its emergence in late 2019, the Coronavirus disease 2019 (COVID-19) pandemic has placed enormous strain on national health systems worldwide. Globally, over 670 million reported cases and nearly 6.83 million deaths have been attributed to this coronavirus as of February, 2023 . MoreoveHong Kong is a major travel hub at the juncture of mainland China and South-East Asia. Unlike many regions of the world, however, Hong Kong has experienced many previous major outbreaks in recent decades such as avian influenza A H5N1) first in 1997 and then periodically since 2002, followed by SARS in 2003 and pandemic influenza in 2009. Prior sensitization to these outbreaks was believed to have significantly contributed to voluntarily uptake of preventative behaviors such as face mask use and avoidance of crowded public areas during the current epidemic –13. Sinc first inThe objectives of this study are to examine variations of fatigue in adopting the COVID-19 preventive practices among adults in two successive waves of the local epidemic in March and December 2020 in which 766 and 8725 local cases had been reported, respectively. The results of this study may provide insights about behavioral fatigue for other regions of the world that will experience future pandemics and will provide insights for those countries that remain high-risk COVID-19 regions in the long-term. This study sheds light on possible patterns of pandemic fatigue to other populations with outbreak experience in previous SARS and avian influenza epidemic to inform their future policies in the ongoing COVID-19 pandemic.Using random digit dialing, a baseline telephone survey was conducted during the first local epidemic wave March 2020 (survey conducted from 22nd March to 1st April 2020). The target population was Cantonese-speaking Hong Kong residents aged 18 years old or above, including individuals holding work or study visas. Phone calls were made in the evenings on weekdays, and mornings and afternoons on weekends to prevent overrepresentation of the unemployed. The household members with birthday closest to the interview date were recruited in the baseline survey (‘last birthday’ method ). After In the baseline recruitment, subjects were asked to provide information of their sociodemographic and background characteristics. Respondents were also asked channels to access COVID-19 news: television, internet, smartphone applications (Yes/No). At both baseline and follow-up recruitment participants were asked how frequently they practiced five key infection prevention measures. The baseline and follow-up recruitment was done amid the first and third epidemic wave respectively. During both recruitment periods, the local government had tightened social distancing measures on gathering , travel The characteristics of subjects are summarized with descriptive statistics and Cohen’s W was used to assess differences from the general population. For the comparison between the two waves, sample means were compared via the Student’s t-test and two-proportion z test. Independent associated factors for the continued uptake of various protective behaviors were identified using multiple logistic regression models. In order to ensure the inclusion of important confounders , variablA total of 725 individuals were recruited in the baseline, of which 56% n = 403) responded to follow-up survey. There were no large differences in the demographic attributes of the respondents recruited at baseline and those who were retained in the follow-up 9 months later except that the follow-up sample was comprised of more elderly adults (18.7% at baseline and 22.3% at follow-up). The characteristics of the respondents in this longitudinal study are shown in Table  respondePerceptions of the person-to-person transmissibility of COVID-19 and perceived severity of COVID-19 disease in the first and third wave of the local epidemic are shown in Table The levels of practicing the preventive measures against COVID-19 in the first and third epidemic wave are shown in Table Table The factors associated with social distancing behavior fatigue are shown in Table This follow-up study noted that in Hong Kong, a region with repeated experience with pandemics such as SARS and avian influenza, personal hygiene measures against COVID-19 were quickly adopted and remained high for almost a year, while adherence to various social distancing measures such as avoidance of going to public places and avoidance of using public transport had significantly declined in the follow-up period. Similarly, avoidance of international travel also declined during this period.During the 2003 SARS epidemic, the majority of residents of Hong Kong had adopted mask-wearing and personal hygiene measures as a means of self-protection against respiratory diseases. Unlike many other parts of the world, in which face mask use during epidemics has been a political issue –39, maskAlthough hand hygiene behaviors remained high throughout the study period, it was noted that certain occupational groups were significantly more likely to report declining adherence to hand hygiene. The hand hygiene fatigue reported by retired/unemployed individuals may be due to the lower need to leave their home as compared to working people or people with small children. A previous study suggested that perceived personal risk of infection and health effects are linked to engagement in protective behaviors, but individuals are often poor at perceiving risk unless they are equipped with the pertinent knowledge and health information about the epidemic . Since rMost notable, lower perception of the severity of COVID-19 was associated with social distancing behavior fatigue. Although the daily caseloads of COVID-19 were rising in Hong Kong and in the world, as the pandemic progressed, the case-fatality of the disease began to decrease . During In light of the study’s findings, the role of public health measures is to encourage rapid uptake and long-term maintenance of preventive behaviors in a pandemic. Given that the population reported social distancing and travel avoidance fatigue, measures that encourage continued social distancing need to be reinforced. Since over 90% of the population of Hong Kong commutes via an extensive mass transit system , continuThe main strengths of this study are the generally representative study sample and the examination of important preventive behaviors over a long-term follow-up and inclusion of a wide array of potential confounding variables. Yet, this study has several limitations. Firstly, although the land-based telephone list covered more than 85% of land-based telephones in Hong Kong , the houAs a likely result of Hong Kong’s experience with successive worldwide pandemics such as SARS, personal hygiene preventive measures against COVID-19 were quickly adopted and maintained by the Hong Kong population. Yet, similar to other countries, the practice of social distancing noticeably declined over this 9-month follow-up period indicating that social distancing will be the key challenge for COVID-19 infection control in a protracted pandemic. Other parts of the world that experience future pandemics may also have similar patterns of preventive behaviors whereby personal protection behaviors will be more readily adopted and maintained than social distancing behaviors. Given this, government efforts will need to be directed towards maintaining social distancing during protracted pandemics, particularly in the workplace and in public areas such as mass transport. Individuals who are noted to be prone to greater pandemic fatigue in other regions (e.g. young people) require targeted efforts to emphasize the potential severity of COVID-19 disease. Health education programs aimed at improving awareness of the potential for severe COVID-19 disease may be helpful to improve continued adherence to those targeted groups. The most appropriate use of various public health and social measures in the context of COVID-19 pandemic across different countries around the world warrants further research .


This paper proposes a nature-inspired spider web-shaped ultra-high frequency (UHF) radio frequency identification (RFID) reader antenna and battery-free sensor-based system for healthcare applications. This antenna design consists of eight concentric decagons of various sizes and five straight microstrip lines.These lines are connected to the ground using 50  The UHF RFID system has the advantages of long reading range, many tags reading capabilities, simple tag structure, fast reading speed, etc., and has broad application prospects7. Near-field RFID tag systems are more suitable for item-level tags and environmentally sensitive applications. It is necessary to successfully read valuables goods with 100 % probability such as medicines, and jewelry. However, one of the key technical issues in the design of UHF near-field RFID reader antennas is to generate a sufficiently strong and relatively uniform field distribution15. In addition, low-cost commercial tag antennas are linearly polarized posing orientation sensitivity issues. Therefore, there is a need for a reader antenna with uniform magnetic and electric field characteristics. In addition to this, the near-field reader antenna that solves tag’s orientation sensitivity issues will be more advantageous.Radio frequency identification (RFID) is being combined with the Internet of Things (IoT) to predict exciting applications16, a broadband RFID reader antenna with low far-field gain has been devised for near-field applications. The antenna was made up of several loop units, each of which has an in-phase current running through the loop. It produces a powerful magnetic field that is evenly distributed over a large interrogation zone. The interrogated area can be modified as a result of altering the number of units to accommodate various scenarios. Low far-field gain and broadband characteristics are features of the suggested antenna. However, this antenna has large dimensions 776 mm In17. A near-field RFID reader antenna based on a meander line structure has been proposed in18. This antenna design was composed of one open-ended microstrip meander line structure and another meandered line with 50 A UHF RFID reader antenna based on two microstrip meander lines with open ends. The equivalent currents in two meander lines are reversed in phase and have almost equal amplitudes. Meander-line units were used to create a homogeneous distribution of both magnetic and electric fields. The performance of the proposed reader antenna was analyzed using six pairs of meander lines. This reader antenna achieved small bandwidth of 914 to 929 MHz with a large footprint of 480 mm 19. The antenna was based on a power divider and two 50 20, a wearable Yagi-like near-field reader antenna has been investigated to be integrated into a smart glove together with s small RFID reader. This design is based on a rhombus-shaped folded dipole and parasitic elements (acting as either a reflectors or directors). Different variants of this Yagi antenna were designed on stretchable fabric and their performance is analyzed in terms of near-field distribution and reflection coefficient. A multi-polarized near-field RFID reader antenna based on two symmetrical meandered and open-ended microstrip lines was proposed in19. The 90o phase shift in one of microstrip line achieved multi-polarization and a strong electric field in the near-field region. This reader antenna has a reading volume of 450 mm 21. Most of the aforementioned near-field reader antennas were based on meandered line structures that are quite large and have small bandwidth.The antenna dimensions are 140 Therefore, in this paper, a spider web-shaped ultra-high frequency (UHF) RFID reader antenna for the Internet of Things (IoT) and healthcare applications is proposed. The proposed reader antenna is composed of eight concentric decagons of various sizes and five straight microstrip lines. These lines are connected to the ground from both ends using 50 mentclass2pt{minimFigure Figure Figure Figure Therefore, the initial structure is optimized further using CST Microwave Studio by applying resistive loading at open ends of straight microstrip lines as illustrated in Fig. Figure 15, If the electric field distribution is greater than 85 dB (1 mV/m), the reader antenna can read all tags simultaneously. As a result, the electric field distribution range was set to be between 70 and 90 dB. Furthermore, this reader antenna achieved a tag reading volume reading region of 200 mm Figure 22 as depicted in Fig. Furthermore, a circuit model for near-field magnetic field coupling of UHF RFID systems is discussed in order to understand the magnetic field distribution of the proposed spider-web reader antenna. The UHF RFID near-field technology utilized inductive coupling principles similar to transformer couplingZr/jX1, the current I0 and coupling power can be represented as follows23:As referred to circuit model, Rs and Zr are the reader’s power supply resistance  solution bagsFurthermore, the tagged jewelry items put on cardboard boxes covered in silk cloths were tested to prove the effectiveness of the proposed near-field antenna for expensive item tagging as depicted in Fig. In this paper, a spider web-shaped ultra-high frequency (UHF) RFID reader antenna-based system for the Internet of Things (IoT) and healthcare applications is proposed. The reader antenna is based on eight concentric decagons of various sizes that are connected to the ground using 50 resistors, with the exception of the end that is left open for a feeding port. The reader antenna design has wideband properties be-because it covers the entire UHF RFID band (860–960 MHz) and has fairly strong and uniform electric field characteristics. In order to avoid other tags being misread in the majority of nearfield applications, it also has low gain characteristics. Further, the orientation sensitivity problems with low-cost linearly polarized tag antennas are addressed by the symmetric current distribution throughout the structure in this design. The measurement results demonstrate that tags can read expensive jewelry, tagged medicine pills, intervening solution, and blood bags positioned in different directions. In future, the array based on this reader antenna and small item-level tag can be used for counting and billing of expensive jewellery items in order to realize complete RFID based solution.