BackgroundCardiac rehabilitation (CR) improves outcomes in patients with heart disease. We investigated the differences in outcomes of comprehensive phase II CR in obese and non-obese patients.MethodsWe performed a retrospective analysis of functional outcomes including metabolic equivalents (METS), heart rate (chronotropic competence - CC), and blood pressure response (BPR) in 178 patients undergoing CR based on underlying body mass index (BMI). Demographic and clinical variables were assessed for age, gender, race, smoking, hypertension, hyperlipidemia, diabetes mellitus, coronary artery disease, stroke, heart failure, medication use, and several sessions attended.ResultsInitial CC and METS were impaired in majority of patients attending CR, whereas BPR to exercise was mostly preserved. Significant improvement occurred in CC  and METS . Post-CR obese patients were able to reach similar level of physical activity as non-obese patients . Improvement in BPR was only seen in non-obese patients . Improvement in functional variables occurred despite increase in BMI in non-obese , and there was no significant change in BMI in obese .ConclusionCR concurrently improves functional outcomes in both obese and non-obese patients despite no associated weight loss. The difference in BPR, however, is seen in only non-obese individuals. Future studies are needed to validate the role of weight-optimized CR protocols as a potential target for improving cardiac outcomes. We also assessed whether functional outcomes were associated with weight loss. A pre- and post-CR BMI was calculated in obese and non-obese subgroups to look for statistical significance.Assessment of these variables was done before and after the completion of CR, followed by subgroup analysis of change in BMI in non-obese , BPR (delta SBP), and METS were performed Table . WilcoxoAmong 178 patients included in our study, 87 patients were non-obese and 91 patients were obese. Baseline demographic and clinical characteristics were well distributed for age, gender, race, HTN, HLD, DM, CVA, CHF, antiplatelet agents, ACEIs/ARBs, beta-blockers, and OMT  and CC , whereas BPR only showed improvement in non-obese patients  (Table In this institutional study involving 178 patients who underwent CR post-hospital admission for various cardiovascular conditions, we found that cardiorespiratory fitness and CC improved regardless of the BMI. More importantly, there was no correlation between weight loss and improved functional outcomes.CR is a multidisciplinary intervention that is aiming to optimize the physical, psychological, and social well-being of patients or even regression of underlying atherosclerotic processes to reduce cardiovascular morbidity and mortality . It faci2 [Previous research demonstrated that CR improves exercise capacity and physical functioning in both home-based and center-based settings . However2 ,9. Sever2 -18.2. This is similar to prior studies suggesting a higher prevalence of obese patients undergoing CR. This growing set of obese population behaved differently than non-obese patients only concerning SBP response. The improvement was observed despite <50% of patients being on OMT out of a cohort of patients where almost 70% of patients had ischemic heart disease. The fact that non-obese and obese patients behave differently in outcomes of BPR despite overall benefit in physical endurance and CC likely points toward different physiological subsets undergoing similar lifestyle risk factor modification. Whether this ultimately translates into a difference in morbidity and mortality outcomes in these patients is yet to be studied. Based on our study, weight loss is not the likely target for improving functional outcomes. In fact, weight gain and an increase in BMI are likely to occur as patients recover from underlying heart disease. Long-term follow-up of outcomes in CR patients based on BMI may unravel interesting results leading to changes in our approach toward the different protocols of CR being applied in these patients.We found that CR through its physical conditioning, strength training, and psychosocial risk factor modification tends to improve functional variables, which are directly related to cardiac outcomes irrespective of weight loss. There is an overall improvement in CC and cardiorespiratory fitness, whereas the SBP response continued to show a normal response of >20 mmHg with completion of CR. More than half of the patients who participated in our CR study were obese, with a mean BMI of 35.30 ± 5.60 kg/mStudy limitationsThe limitation of our study is predominantly related to it being a retrospective, single-center observational study. In our study, the subgroup of obese patients showed a higher incidence of DM with more use of ACEIs/ARBs and OMT. The results were related to a short-term follow-up, with few patients dropping out before completion of phase II of CR. Whether outcomes continue to differ in long term with valid implications on cardiac morbidity and mortality need to be further studied.Retrospective analysis of functional outcomes including METS, HR, and BPR in those undergoing CR based on underlying BMI showed that CR improves functional outcomes in patients with heart disease in both obese and non-obese patients. This improvement tends to occur irrespective of weight loss and BMI. The difference in BP is seen only in non-obese patients. Further long-term studies on CR may help establish a weight-based protocol for improved cardiac functional outcomes.


Background: Living with kidney failure and undergoing hospital haemodialysis (HD) is associated with a high prevalence of mental health problems and poor quality of life. However, the COVID-19 pandemic has brought additional challenges for this patient population. Objectives: To understand the impact on mental health and well-being during the COVID-19 pandemic in people receiving HD. Methods: An online survey using a cross-sectional study design. Two validated assessment tools ; Personal Wellbeing Index (PWI)), binary, Likert and free-text qualitative questions were included. Individuals with kidney failure receiving HD, over 18 years of age, were recruited online between July and August 2020. Results: Forty-four participants were recruited. Approximately, 54% of respondents were tested for COVID-19; however, no positive results were reported by patients or associated family members. Scores of GHQ-12 and PWI were compared with those from previous studies. Mental health distress was higher in prevalence (68.2%) and severity (M = 18.3) in this study when compared to that of the general population in Northern Ireland during COVID-19 (April 2020). In addition, well-being  was poorer when compared to that of a pre-COVID-19 dialysis patient population. Conclusion: During the current pandemic, individuals receiving hospital HD have heightened mental health distress, and their well-being is impacted negatively. This study reinforces the need to provide appropriate psychosocial care as well as supportive interventions for mental distress to patients with kidney failure during and after the COVID-19 pandemic. Haemodialysis (HD) is the most frequently used renal replacement therapy for kidney failure  with apThe COVID-19 pandemic has brought additional challenges for this patient population, whereby patients receiving hospital HD are considered to be at higher risk of developing severe COVID-19 due to their immunocompromised status and frail condition . GovernmPrevious pandemics have also shown individuals, including patients, are at an increased risk of developing post-traumatic stress symptoms. After the 2003 Severe Acute Respiratory Syndrome (SARS) epidemic, it was found that poor understanding of SARS and how it spread resulted in high rates of post-traumatic stress disorders . This haThere is an urgent need to understand the impact of the current pandemic on patients receiving hospital HD. This study aims to assess factors of mental health and well‐being using validated assessment tools, in addition to exploring patients’ experiences of shielding.Design: This study was carried out using a cross-sectional study design. It was conducted over six weeks between July and August 2020. Sample: Individuals were recruited via an online survey link advertised within the Northern Ireland Kidney Patient Association (NIKPA) which has approximately 450 members. Those receiving hospital HD were included using the following inclusion criteria: patients with kidney failure receiving HD in Northern Ireland, over 18 years of age and ability to complete an online survey to capture qualitative and quantitative data. The study was approved by the Faculty of Medicine, Health and Life Sciences ethical committee (MHLS 20_77) within the host institution, and all methods were performed in accordance with the relevant guidelines and regulations. All participants completed an online informed consent form. ®, Provo, Utah, USA). The study included author-designed binary, Likert and free-text qualitative questions to investigate experiences and personal concerns during the pandemic. In addition, two validated assessment tools were included. The General Health Questionnaire-12 (GHQ-12) was used to evaluate mental health status in the present study. It is a highly reliable and validated screening instrument for mental health [Measures: This study combined validated questionnaires, demographic information and free-text qualitative questions via a web-based survey tool  investigated patient well-being and contains seven items of satisfaction, each one corresponding to a quality-of-life domain, i.e., standard of living, health, achieving in life, relationships, safety, community connectedness and future security . PWI is ®  for GHQ-12 mean scores (p < 0.05). Qualitative open-text responses were analysed using thematic analysis [Analysis: Descriptive statistics were provided for demographic information including a narrative description of binary and Likert responses. Mean and standard deviations (+SD scores) were calculated for standardised measures of mental health (GHQ-12) and well-being (PWI). A t-test was conducted using GraphPad Prism 9analysis . n = 1 not identified). The majority of respondents were ≥45 years old (n = 32), with the largest cohort ≥ 65 years old (n = 16), which is representative of UK patients , indicating poorer well-being. Scores for all items were lower than those of the comparative group, in particular, statistically significant differences were reported for personal relationships , personal safety , community connectedness ) and future security . The total average score of the PWI was 37.16 . The moUndoubtedly, the current pandemic has fast-tracked the urgency for future research to understand psychological distress and social dysfunction in kidney failure. Patients with kidney failure undergoing hospital HD should be screened regularly to assess for mental health symptoms, and prompt referral and treatment must be initiated where required. By addressing needs, appropriate policies and supportive interventions that seek to prevent and reduce perceived isolation and psychological distress can be developed to monitor and manage patients at significant risk of reduced mental health and well-being. This study provides a unique snapshot of individuals attending hospital HD during the current COVID-19 pandemic, using validated assessments measures. There is an urgent need to support mental health and the development of supportive interventions that may help improve psychosocial care in patients with kidney failure, particularly during and after the COVID-19 pandemic.


In the fight against cancer, early diagnosis is critical for effective treatment. Traditional cancer diagnostic technologies, on the other hand, have limitations that make early detection difficult. Therefore, multi-functionalized nanoparticles (NPs) and nano-biosensors have revolutionized the era of cancer diagnosis and treatment for targeted action via attaching specified and biocompatible ligands to target the tissues, which are highly over-expressed in certain types of cancers. Advancements in multi-functionalized NPs can be achieved via modifying molecular genetics to develop personalized and targeted treatments based on RNA interference. Modification in RNA therapies utilized small RNA subunits in the form of small interfering RNAs (siRNA) for overexpressing the specific genes of, most commonly, breast, colon, gastric, cervical, and hepatocellular cancer. RNA-conjugated nanomaterials appear to be the gold standard for preventing various malignant tumors through focused diagnosis and delivering to a specific tissue, resulting in cancer cells going into programmed death. The latest advances in RNA nanotechnology applications for cancer diagnosis and treatment are summarized in this review. Despite decades of basic and clinical investigation, as well as trials of new therapeutic modalities, cancer remains a substantial cause of mortality worldwide . VariousSimilarly, biodegradable and biocompatible natural and engineered biomolecules  have been broadly examined to synthesize nanostructures ,27. BiomIt is scientifically established that nucleic acids can be manipulated and designed to create many nanostructures . In the Due to its increased thermodynamic stability, the RNA structure can be more flexible while folding into different structures , and it produces diverse building blocks for numerous therapeutic applications , includiNanomedicine has led to the development of a variety of nanoscale therapeutics and diagnostics to treat a variety of diseases, specifically cancer ,44,45,46In the past, numerous RNA-NPs have been prepared by an automated self-assembly process and studied in the context of cancer research ,51. A keThe conjugation of polymeric NPs with RNA molecules, such as RNA aptamers, cause these bio-conjugates to be easily absorbed by specific tumor cells, and therefore, can be considered as a beneficial strategy towards the controlled release of polymeric drug delivery vehicles . In the Using in-vitro and in-vivo experimental models, Yin et al. exploited RNA-based technology to efficiently deliver anti-microRNA to cancer cells derived from breast tissue . GhimireRNA therapies provide new insights for cancer treatment. The escalating growth of RNA nanotechnology in cancer theranostics demands the preparation of an updated review. This article comprehensively discusses recent findings and highlights the promising avenues of RNA nanotechnology implemented to design stable RNA nanostructures for diagnostic and prognostic purposes. Finally, we will discuss strategies to improve and overcome many technical obstacles in this field.Biosensors are diagnostic systems that convert a natural response into a programmable signal . The calRNA NPs are discrete entities, quite different from classical therapeutic RNA, including siRNA, anti-miRNA, miRNA, mRNA, ribosomal-RNA, and viral immune-stimulatory RNA. These traditional RNAs have a broad fundamental history of research in the RNA field. These small RNAs are caught by cells, and they stimulate RNA-sensing pattern recognition receptors (PRRs). Some of these are reported to be immunogenic.d, i.e., 1.2 L/kg of pRNA NPs, indicates the presence of a valuable amount in peripheral tissues, especially in a tumor. The comparatively small amount of clearance (Cl) value indicates the insufficient filtration of the NPs from the kidneys. A specific targeted delivery can be achieved by incorporating traditional RNA into NPs by taking advantage of these properties. These NPs show specific targeted delivery, higher therapeutic efficacy, and an increased in-vivo half-life [There are a lot of benefits of RNA NPs as compared to traditional RNA, for example: (a) enhanced permeability and retention (EPR) effect, (b) the small size offers to promise pharmacokinetic and pharmacodynamic properties, (c) decreased liver accumulation, (d) Small non-coding RNAs or microRNAs serve as scaffolding and active elements in the bottom-up self-assembly of more complex nanomaterials, and (d) untraceable toxicity in-vivo . Multinaalf-life .Cancer nanotechnology faces a serious challenge of non-specific accumulation of delivered NPs in healthy organs, such as lungs, liver, spleen, and kidneys . The nonThe nano-biosensor is an innovative unit that creates nano-conjugated biological systems, which function as signaling mediators to detect the specific contents of medical, biochemical, or physical agents. The related data is transferred in the form of signals using thermometric, piezoelectric, optical, magnetic, electrochemical, and micromechanical methods. The signals produced by these methods depend on the bio-recognition of a cancer cells-related surface or intracellular biomarkers through bio-ligands or antibodies. In a new era of research, nano-biosensors will increasingly be classified based on bio-recognition and signal transduction elements. RNA-based nano-biosensors are displayed in In the basic structure of a sensor, there are two main components: (i) the target analyte that can be a nucleic acid, antibody, drug, protein, or cell-surface molecule; and (ii) the transducer used for altering a signal into a form of energy. It can be detected electrochemically by detecting the energy it produces (voltage and current), (absorption and luminescence), and mechanically (resonance). The exclusive and tunable physicochemical properties of nanostructures, such as enhanced electric conductivity, greater area to volume ratio, high reactivity, unique magnetic properties, and powerful scattering and absorption, make them a fascinating tool for bio-sensing. The nanomaterials’ ability to interact effectively with biologically important analytes and convert those interactions into considerably enhanced signals has enabled a new class of early diagnostic procedures. Gold NPs (AuNPs) and QDs are excellent signal transducers because the existence of a specific analyte regulates the signal generated by the material’s optical properties. Nano and microsensors reduce the size of the receptor to improve their responsiveness. Increased signal-to-noise (S/N) ratio is responsible for this enhanced sensitivity. However, a running device’s success depends on its ability to detect a tremendously low concentration in a reasonable amount of time.The overall sensitivities of a sensor are often affected by mass transport limitations, such as when the substance is transported to the receptor by diffusion mechanism. The limiting factor in saturating the receptor for a specific geometry of the sensor is the time required by the analytes to reach the sensor area. As the receptor area becomes smaller, the time grows higher. The decreased number of analytes obstructs the detection of extremely dilute solutions. Many practical solutions have been tested to concentrate the dilute solution straight onto the sensor surface. For example, Melli et al. formulated a unique solution with a series of micropillars with superhydrophobic surfaces to simplify the management of samples with a low concentration of analytes. A diluted solution can be placed on these micropillars, the target molecule will become concentrated by the evaporation of liquid, and the detection time is significantly decreased .Halo et al. used the same theory to detect colorectal cells by mRNA quantification. They developed a NanoFlare platform comprising a single layer of single-stranded DNA (ssDNA) coated on spherical AuNP. A fluorescent reporter was added to a short DNA counterpart that was hybridized to the ssDNA recognition sequence. The reporter fluorophore was slaked while it was close to the AuNPs, but it broadened when the target mRNA displaced the DNA, allowing the fluorescence reading. The detection limit of the nanosensor was about 100 cancer cells/mL blood .A particular type of RNA aptamer that causes small-molecule fluorophores to emit fluorescence is called a light-up aptamer. Several new light-up aptamers have been developed that can bind to different biocompatible fluorogenic ligands and make their way to the design of modern RNA-based molecular strategies for sensing applications. The Systemic Evolution of Ligands by EXponential enrichment (SELEX) is a combinatorial procedure for identifying such aptamers. RNA aptamer libraries were exposed to recurrent cycles of collection and amplification in this procedure, resulting in RNA aptamers having the strongest selectivity for the target ligand. Various RNA NPs can be coupled with light-up aptamers having programmable sensing capabilities to create dynamic reporting entities .2 group of the RNA fragment, and similarly, thiol to maleimide and alkyne to azide, etc. RNA was directly manufactured, and classical pairing reactive groups, e.g., amino –NH2-COOH, azide, maleimide, alkyne, and thiol, were incorporated by similar methods for the production of polyvalent RNA NPs [RNA/DNA nano-biosensors can measure the responses produced by aptamer hybridization or nucleic acid conversion processes as promising diagnostic tools . As apta RNA NPs . Single- RNA NPs .RNA polymer is conjugated with NPs , and a sequence of research studies used siRNA, pRNA, and phi29 for this purpose. The siRNA was coupled with many nano-based imaging agents to form multifunctional NPs exhibiting diagnostic and therapeutic moieties.apt/3WJ/Bio) theme for the conjugation of pRNA-3WJ to the quantum dot (QD). Firstly, the SEPapt/3WJ/Bio was attached to G-100 resin, and then the streptavidine-labeled quantum dot was linked to SEPapt/3WJ/Bio by streptavidine-biotin coupling on Sephadex G-100 and STV/QD-SEPapt/3WJ/Bio conjugates were subjected to dissociation in the elution buffer. Later, the STV/QD-Bio/3WJb, 3WJa, and SEPapt/3WJc were split by elution buffer. After that, the STV/QD-Bio/3WJb fragment was filtered and reconvened with pRNA 3WJa and thiol-labeled pRNA 3WJc for resistive biomemory application. Hence, the RNA polymer can be easily incorporated with other NPs and used for various diagnostic, therapeutic, and bio-electronic fields [Bhatia et al. established tumor-highlighted peptides (F3) and siRNA coupled to the PEGylated QDs core as a framework. The F3 peptide was conjugated to amine group-modified QD via sulfo-LC-SPDP (sulfosuccinimidyl 6-(3′-(2-pyridyldithio)-propionamido) hexanoate as a heterofunctional cross-linker, and thiol modified siRNA used sulfo-SMCC  cyclohexane-1-carboxylate) for conjugation. The QD-siRNA/F3 conjugate NPs were proficiently transported to HeLa cells and unconfined from their endosomal setup, which provided the demolished EGFP signal. These siRNA-NPs conjugates exhibited both imaging and therapeutic properties. Furthermore, the siRNA was coupled to iron oxide NPs, which showed magnetic characteristics for biomedical applications. The linkage of siRNA to iron NPs exhibited a double response, such as the in-vivo delivery of siRNA and gathering of siRNA in the tumor by MRI and the near-infrared fluorescent (NIRF) in-vivo optical imaging. The amine groups of iron oxide NPs were treated with m-maleimidobenzoyl N-hydroxysuccinimde ester (MBS) for linkage between siRNA and magnetic NPs. After that, the reduced thiol group of RNA was treated, and magnetic NPs were coupled with and near-infrared Cy5.5 dye and membrane translocation peptides. The MRI and NIRF were used simultaneously to see the siRNA-magnetic NP uptake. The coupling of AuNPs with RNA is studied to enhance the accessibility of tethered RNA splicing enhancers. Guo et al., in 2007, produced a pRNA of the phi29 and DNA-packaging motor linkage to AuNPs to study the phage assembly. In this case, the SH-labeled DNA oligonucleotide was merged with 3′ terminal of pRNA to incorporate the thiol (-SH) group into pRNA. Then, the thiol-treated pRNA was conjugated to gold NPs. The pRNA/AuNPs conjugate was attached to procapsid by an in-vitro phage assembly. Guo’s group proved that the RNA polymer was coupled with the AuNPs effortlessly, and this procedure can be used for imaging purposes. Currently, pRNA-3WJ was coupled straight to the quantum dot for resistive biomemory applications. They introduced a sephadex G-100 resin-recognizing RNA aptamer in the biotin-labeled pRNA/3WJ  for the exosomal analysis of GBM. Three functional sections were combined by iMER, i.e., real-time RNA analysis, targeted up-gradation of extracellular vesicles, and on-chip RNA isolation. The up-gradation or enrichment process detached the cancer exosomes immunomagnetically from host-derived exosomes, and the later analysis was executed on enriched populations. Later, a glass-bead filter was used to pass the lysate collected after the lysation of exosomes. RNA was immobilized onto glass beads by forming electrostatic bonds during this method and then extracted and quantified by qPCR. Magnetic microbeads with anti-epidermal growth factor receptor (EGFR) antibodies were used to identify and enrich GBM-derived exosomes. These GBM-derived exosomes were incubated with beads, and the whole surface seemed thickly covered. A large quantity of mRNA was found in these vesicles, having mRNA of nuclear proteins as well .Spherical nucleic acids SNA are a type of NPs that are made up of a NP core treated with oligonucleotide structures and comprised of RNA interference RNAi reporter molecules and therapeutics. The exclusive 3D SNA structures are resilient to nuclease degradation and co-opt into the cells despite the lack of transfection agents. SNAs act as diagnostic agents and have the potential to detect two unique mRNA sites at a time inside of a cell . These SIqbal et al. sequestered an anti-RNA aptamer from purified human protein by creative selection. The authors confirmed the ‘aptamer’s ability to detect and seize murine and human GBM cells after its immobilization on a glass substrate. Aptamer binds with wild-type and mutant EGFR with excellent specificity and affinity (Kd = 2.4 nM). This technique is used for the initial detection and analysis of residual disease. Similarly, Iqbal’s group fabricated a flow-through lab-on-chip tool that used surface-attached aptamer’s affinity for GBM’s overexpressed biomarker, i.e., EGFR, to prove that a microfluidic-based technique can be used to detect and capture GBM cells. Later, the same group took radical steps in diagnostics related to anti-EGFR aptamers and came up with two succeeding articles on tracing the differential dynamics of GBM cell structure on substrates grafted with aptamers. They analyzed the dynamic morphology of GBM in computational single-cell metrics to identify and capture tumor cells ,81.Choulier et al. linked cell-SELEX and protein to separate RNA aptamers. These aptamers have the potential to bind specifically to integrin α5β1, which is an αβ heterodimeric receptor related to cancer angiogenesis and GBM ferociousness. The authors used in histo-fluorescence analysis on patient-based xenografts and a fluorescence-related analysis on cell lines to verify the diagnostic capability of tagged aptamers . RecentlRich et al. designed a pool of DNA aptamers distinguishing TICs with an extremely low dissociation constant (Kd between 0.12 and 3.75), and an aptamer-Cy3-related fluorescence proved the binding. In 2019, Affinito et al. used an RNA library on basic human GSCs to design a 20-F-RNA aptamer A40s, which was explicitly related to the GBM cells. The authors established the detection of A40s-based analysis in GBM cells and GSCSs of human tissue sections . Here, tCurrently, three-dimensional RNA NPs with tetrahedral structures have been designed. RNA tetrahedrons are used in various applications in nanomedicine and nanomaterials because of their structural permanence and mechanical rigidity. The EGFR aptamer was bonded with the RNA tetrahedron structure to target triple-negative breast cancer cells. After IV administration, the drug-loaded NPs face a sequence of biological blockades. NPs face quick opsonization and succeeding sequestration by local macrophages under physiological conditions. As a result, healthy organs, such as the spleen and liver, accumulate very high levels of NPs . To addrIn another study, QD-mi RNA let-7a-gold NPs (QD-RNA-Au NP) were conjugated with Chitosan-based nano-formulation, including negatively charged poly (g-glutamic acid) (PGA) for transfer to breast cancer cells. In the cells, the QDs were separated by dicer-mediated release and showed fluorescence for theranostic applications .Mediley et al. described the use of an AuNP aggregation-related colorimetric sensor for straight cancer cell detection. However, the signal produced by aptamers after binding with cancerous cells was too low to detect CCRF-CM cells due to their weak binding affinity. To solve this problem, Lu et al. used S6 RNA aptamer-linked multifunctional oval-shaped AuNPs and the monoclonal anti-HER2/c-erb-2 antibody for multivalent attachment of AuNPs with target cells for extremely sensitive analysis of SK-BR-3 breast cancer cells. AuNP-linked colorimetric techniques are used for initial and sensitive in-vitro recognition of cancerous cells .Sioss et al. fabricated a nanowire-resonator array sensor for signal detection using oligonucleotide-treated AuNPs to analyze RNA in circulating tumor cells (CTCs). In this method, RNAs were attached to AuNPs previously immobilized on the sensor by hybridization. The resonance frequency of the sensor was changed by AuNPs after adding mass to it. The authors calculated this change in resonance frequency and detected PCA3 RNA, a nucleic acid prostate cancer marker. After measurement of RNA and volume used, they calculated that the level of development was 1 CTC/10 mL blood. The sensors used were extremely sensitive and specific, showing a single-nucleotide inconsistency calculation. AuNPs have a large surface area, and they are used as a support to increase signal formation by enhancing molecular binding events .The prostate-specific antigen (PSA) was spotted in prostate cancer cells and the neovasculature of many types of malicious neoplasms, such as breast cancer , lung 8, and somMohamadi et al. fabricated a microelectrode biosensor based on the PSA mRNA and magnetic NPs-based circulating tumor cells. Another study demonstrated aptamer-based in-vivo targeting by pRNA-3WJ NPs containing the anti-prostate-specific membrane antigen (PSA) RNA aptamer. On the other hand, folate can be coupled with pRNA-3WJ NPs as an innovative strategy for improving nanocarrier distribution.The pRNA-3WJ-folate conjugates have been used in many cancer cells in which FR is overexpressed, such as colorectal, gastric, head and neck cancers, and glioblastoma. The in-vivo distribution of RNA NPs was studied using pRNA-X NPs containing fluorophore or folate. These NPs were injected into athymic mice with KB cells xenografts. Whole-body images were taken at different time intervals and indicated the high accumulation of RNA NPs in cancer cells within 4 h. Specific localization of pRNA-X NPs in the tumor was calculated at the 8th hour of organ imaging, without accumulating in healthy organs .Cationic lipids (CLs) are used for liposome-oriented DNA/miRNA transport. These lipids are made up of a linker to which a hydrophobic part is linked to a cationic head part. The positively charged head group is attached to the negatively charged phosphate group of nucleic acids . Liposom3O4) NPs were used in this study. These magnetic NPs showed highly efficient in-vivo imaging along with increased (human gastric cancer cell line 7901) SGC7901 sensitivity to the drug Adriamycin [Chen et al. developed an MRI-visible system based on superparamagnetic iron oxide NPs (PEG-g-PEI-SPION) and polyethylenimine conjugated to polyethylene glycol (PEG) for the delivery of siRNA to gastric cancer. Despite its use in cancer gene down-regulation, this PEG-g-PEI-SPION has verified itself as an extremely effective contrast agent for in-vivo MRI scanning as well. In the same way, Sun et al. designed Micro-RNA-16-loaded magnetic NPs to solve drug resistance challenges in the mouse gastric cancer model. Polyethylene glycol (PEG)-coated iron oxide  is composed of glycoproteins, elastin, collagen, and hyaluronic for providing solid structural support for cellular processes, i.e., proliferation, cell migration, and growth . MoreoveConventional cancer treatment has failed to mitigate the impact of malignancies . TherefoRNA-based drugs are often entrapped or attached to the surface of different nanovehicles to deliver the cargo to the cells. These nanovehicles can be modified with various moieties, including polyethylene glycol (PEG) and cholesterol, which enhance them by the membrane of target cells, where the nanovehicle can enter the target cells via endocytosis A. MeanwhThe miRNA or siRNA possesses the capability to bind with the enzyme-containing molecule RNA-induced silencing complex (RISC), resulting in the enzymatic cleavage of the target mRNA . TargeteMoreover, all the RNA-based nanoparticles tend to adopt various advanced strategies to provide the targeted and efficacious treatment against various metastatic cancer, as shown in 2O. The precipitated were re-dissolved and purified by the ion-pair reverse phase HPLC in a PTX-labeled RNA for assembling NPs. Finally, an RNA four-way junction NP (4WJ-X nanostructure) with ultra-thermodynamic stability to solubilize and load PTX for targeted cancer therapy was developed by a 3D computational model generated using Swiss PDB Viewer and PyMOL Molecular Graphics System. Assembly of NPs was confirmed using a specified buffer solution. EGFR NPs were also conjugated with one of the aptameric RNA oligomers and 4WJ-X-24 PTXs. It was observed that each RNA NPs was found to be successfully attached via covalent interaction to twenty-four molecules of PTX as a prodrug. The developed RNA-PTX complex was found to be structurally stable and rigid. It was concluded that RNA NPs proved to help increase the water solubility of the BCS class II drug PTX by 32,000-fold, which possesses the issue of low water solubility. This treatment strategy of RNA functionalization in the form of intravenous injections resulted in the specified cancer targeting. RNA ligand proved to dramatically inhibit the growth of breast cancer with non-detectable toxicity and immune responses in mice. Moreover, no mortalities were observed at the LD50 dose of PTX [Cancer of the breast is the deadliest disease in the world . Breast e of PTX .By using nanotechnology for RNA, we are able to overcome many shortcomings of naked RNA molecules, such as poor chemical stability, easy degradation by nucleases, and extremely short half-lives for in-vivo applications. NPs act as a multipurpose and targeted system for the safe transfer of naked RNA molecules. The NP-based protect RNA from enzymatic cleavage and immune system threats. Because of their EPR properties, these nanostructures facilitate excellent RNA accumulation at the tumor site. Nowadays, the nanocarriers used for RNA delivery are lipid-based nanosystems , polymerRNA NPs can easily include targeting ligands, counting RNA aptamers, and chemical ligands to impart specific targeting against proteins, fluorescent chemicals, and cell surface receptors. Chemical ligands, e.g., folate, are attached to the end of the RNA strand while the RNA is synthesized by modified RNA phosphoamidites. These ligands can also be attached to the RNA strand after RNA synthesis by the chemical conjugation method. The RNA aptamer strand, such as EGFR aptamer, can be manufactured by elongation of the scaffold strand.The binding efficiency in-vitro and in-vivo of RNA NPs with ligands is tested by labeling them with radioisotopes and fluorescent dyes . The labFolate receptors are overexpressed in epithelial cancer cells surfaces, permitting the folic acid conjugated NPs to target these cancer cells at a frequency higher than the normal cells.RNA NPs can efficiently target cancer metastasis that is difficult to target because of the spread of cancerous cells to far-off cells and lymph nodes. Folic acid was used as a targeting agent by RNA NPs to simultaneously target colon cancer cells in the chief sites of metastasis, such as lungs, liver, and lymph nodes . The 3WJSmall interfering RNA (siRNA) showed great potential in advanced therapeutics because of its highly sequential ability for silencing genes . One of Furthermore, Derlin 1-siRNA can be adjunct to the formulated conjugate of RGDfC-SeNPs via electrostatic interaction. The RGDfC-Se@siRNA successful conjugation and synthesis was confirmed via size determination by a zeta sizer, transmission electron microscopy (TEM), and Fourier transform infrared spectroscopy (FTIR). Elemental compositions of RGDfC-SeNPs were studied by energy dispersive spectroscopy (EDS). RGDfC-Se@siRNA characterization results proved that it followed Clathrin-mediated endocytosis for specifically reaching HeLa cancer cell lines and exhibited triggered siRNA release in a tumor microenvironment as compared to the biological microenvironment. However, in qPCR and Western blotting assays, both techniques showed eminent chances of gene silencing in HeLa cells. RGDfC-Se@siRNA was found to suppress the tumor invasion and division in HeLa cells via triggering the apoptosis pathway. Moreover, another crucial mechanistic approach of mitochondrial membrane disruption and reactive oxygen species generation (ROS) in HeLa cells was quite convincing in understanding that mitochondrial dysfunction mediated by ROS might play a significant role in RGDfC-Se@siRNA-induced apoptosis. Interestingly, advanced nanotherapeutics also presented substantial antitumor activity in a HeLa tumor-bearing mouse model .Prostate cancer malignancy is one of the significant reasons for mortality worldwide. Prostate cancer is a non-skin malignancy causing the second biggest number of deaths in men when differentiated with different tumors. Conventional therapies are expected to cause erectile dysfunction, libido, obesity, and bone mass loss. Nanotechnology has modernized the field of medication to sidestep conventional therapies against metastatic cancers and different intracellular infections . Xiao di3O4 NPs (SPIONs) [Globally, death from gastric cancer accounts for the majority of deaths. Conventional treatments have not been able to alleviate the consequences of this deadly disease. The development of targeted therapies for gastric cancer requires new technologies . The mos(SPIONs) . SPIONs (SPIONs) .Hepatocellular carcinoma (HCC) is the most common malignancy of the liver and the most common cause of morbidity and mortality ,122. A fTimely diagnosis and therapy are the prime responsibility of the healthcare system . SeveralMesoporous silica NPs (MSNs) have been considered the most promising nanocarriers for attached targeted moieties owing to unique features of tunable pore structure, greater surface area, and pore volume ,127,128.Thanks to their selectivity and enhanced sensitivity, RNA-based theragnostic approaches have tremendously improved current methods for diagnosis and provided versatile delivery systems for the treatment of a variety of cancers. This is important because in-vivo applications of the naked RNA molecule face many challenges that need to be tackled. For instance, the naked RNA molecules have poor chemical solubility, extremely short half-lives, and are easily degraded by nucleases ,130,131.A number of nanovehicles have been studied for their ability to deliver RNA molecules to target locations. For instance, it has been documented that lipid-based nanostructures , polymer-based nanomaterials, inorganic NPs, and bio-inspired nanovehicles can be used for the targeted delivery of nucleic acids, such as RNA. The majority of these nanocarriers have the advantages of easy preparation, good biocompatibility and bioavailability, low cost of production, controlled release, easy modification, and easy uptake. However, they have shown poor solubility, rapid clearance, easy leakage of cargo, dose-dependent toxicity, and stability concerns .The application of RNA technology has a major advantage of exploiting cellular machinery that permits the targeting of complementary transcripts, resulting in a dramatic decrease in the expression of a target gene. The main limitations of this approach are ineffective in-vivo delivery, off-target effects, and the induction of type I interferon responses. .The RNA molecule itself is unable to cross cell membranes. In addition, prompt degradation of the therapeutic agent in the endocytic pathway, called the endosomal escape, could be a great challenge in ligand-mediated endocytosis for the specific delivery of siRNA . A cruciIn this review, we highlighted advancements in the use of RNA nanotechnology in cancer diagnosis and treatment. The development of novel RNA nanotechnology-based tools for cancer diagnosis and treatment has been studied extensively in recent years. Compared to presently available cancer diagnosis and treatment in clinics, a number of RNA-based NPs demonstrated improved sensitivity and selectivity or provided whole new capabilities that could not be attained with conventional techniques. Compared with conventional diagnosis and therapies, an RNA functionalized nanocarrier-mediated anticancer drug delivery leads to high therapeutic efficacy, targeted binding with the ligand, more accurate diagnosis, lower toxicity, and site-specific delivery, resulting in cytotoxicity management and cost-effectiveness. The barriers to the diagnosis and treatment of cancers and the killing of healthy cells have been minimized using biocompatible polymers ligands. Promising advances in cancer treatment and detection, such as RNA-functionalization and biocompatible ligands, are rapidly paved the way in addressing the disadvantages of existing approaches by effectively enhancing the treatment and diagnosis of metastatic tumors. Recently, significant advances have been made in the area of RNA nanotechnology for cancer diagnosis and treatment, and our knowledge of this topic has significantly expanded. However, just a few RNA-based NPs have progressed to clinical trials, and RNA nanotechnology is expected to enter the clinic in the coming years with collaborative efforts among scientists, technologists, and therapists. RNA nanotechnology, with its excellent specificity, accuracy, and multiplexed measuring capabilities, has significant potential for improving cancer diagnosis and treatment, finally leading to a higher cancer patients’ chance of survival.


Hydrocharismorsus-ranae L.; EFB) is a free-floating aquatic plant invasive in Canada, the United States and India. It is native to Europe and northern and western Asia and is believed to have first been introduced to North America in Ottawa, Ontario in 1932. It has since spread by way of the St. Lawrence River and connected waterways to southern Ontario and Quebec and parts of the northern United States. Invasive European frog-bit occurs in freshwater coastal wetlands and inland waters, where it can form dense mats that have the potential to limit recreational and commercial use of waterways, alter water chemistry and impact native species and ecosystems. Data on the past and present distribution of this invasive species provide geospatial information that can be used to infer the pattern of invasion and inform management and monitoring targeted at preventing secondary spread. Our EFB dataset contains 12,037 preserved specimen and observation-based occurrence records, including 9,994 presence records spanning two Canadian provinces and ten U.S. states and 2,043 absence records spanning five U.S. states. The aggregated EFB dataset provides a curated resource that has been used to guide a Michigan management strategy and provide information for ongoing efforts to develop invasion risk assessments, species distribution models and decision-support tools for conservation and management.European frog-bit (Specimen-based and observation-based occurrence data were accessed through nine digital data repositories or aggregators and three primary sources. Twenty-six percent of the data are new records not previously published to a data repository or aggregator prior to this study. We removed duplicate data and excluded records with incorrect species identifications. Occurrence records without coordinates were georeferenced from recorded locality descriptions. Data were standardised according to Darwin Core. This aggregated dataset is the most complete account of EFB occurrence records in its North American invasive range. Hydrocharismorsus-ranae L.; EFB) is a free-floating aquatic plant, native to Europe and northern and western Asia and invasive to North America and India  across North America.Aggregated occurrence records of invasive European frog-bit  dating from 1932 to July 2021 in the dataset. The data represent occurrence records from two Canadian provinces (Ontario and Quebec) and thirteen U.S. states, ten of which have recorded EFB presence  and three of which have recorded absence only . This project contributed 328 total absence records spanning Illinois, Indiana and Ohio.Central Hardwood Invasives Plant Network Joint Aquatic Invasive Species Survey (CHIP-N) - Regional effort launched in 2009 to survey invasive species in the central midwestern United States  - Research funded in 2020 to assess EFB abundance and ecosystem impacts in Saginaw Bay, St. Clair Flats and Lake Erie in Michigan. Data were collected using standard methodologies . This prThe total number of records by observation-based data provider or herbarium collection is given in Table Field names and contents of raw data were standardised to ensure consistent capitalisation, spelling, grammar, taxon naming conventions and formatting to conform to Darwin Core standards, as described in the Darwin Core Quick Reference Guide .We identified and consolidated duplicate observation-based records held by multiple online repositories, retaining all record numbers to ensure each merged record would be traceable to every online source that houses it. We merged specimen-based records only when they were taken from the same specimen sheet  or associated with an observation-based record. When specimens were known to be physical duplicates  or when images were not available, specimen-based records were retained.We standardised information in the eventDate and eventTime fields to conform to ISO 8601-1:2019 and recorded original dates in the verbatimEventDate field, as per Darwin Core standards . OccurreOne hundred and fifty digitised specimen images were provided by Agriculture and Agri-Food Canada's National Collection of Vascular Plants DAO; . Image lData were corrected and modified only to the extent necessary to improve clarity and usability; original content was maintained whenever possible. When locality strings were updated using associated data or linked records, original locality strings were retained in verbatimLocality, as per Darwin Core standards . We corrWhen provided, original geographic coordinates were retained. When no coordinates of any kind were available (290 records), we georeferenced records using the GEOLocate Web Application  and follRecords in the dataset span two Canadian provinces and thirteen U.S. states Table , Fig. 1.30.3207 and 49.7652 Latitude; -121.9681 and -69.8762 Longitude.Hydrocharismorsus-ranae L.) Higher classifications were obtained from This dataset contains records from a single species, European frog-bit  across North America.Aggregated occurrence records of invasive European frog-bit (https://www.gbif.org/dataset/71454d8a-6e9c-49f5-bf37-353f9ad2e2b91Hydrocharismorsus-ranae L. occurrence records.Aggregated Darwin Core Archive892021-07-15Hydrocharismorsus-ranae L.) and is freely available to download (Data fields and contents have been standardised to 89 Darwin Core Archive columns. The following table lists column names and descriptions as they appear in the Darwin Core quick reference guide . The datdownload .


Stent-graft infection is a rare but potentially life-threatening complication of endovascular aortic repair. There are currently no consensus guidelines for treating stent-graft infections, but surgical treatment is generally considered preferable due to the low overall survival rate of patients receiving conservative therapy; however, the revascularization method remains controversial. We report a case in which stent-graft infection after endovascular aneurysm repair was successfully treated by stent-graft removal and extra-anatomical bypass (EAB). EAB is an effective method of revascularization for stent-graft infection. Among post-EVAR AAA-related complications, endoleak and graft infection are the most important. The frequency of post-EVAR stent-graft infection is low at 0.2%–0.7%. However, the complications are life-threatening, with the mortality rate within 30 days after surgery being approximately 17%. The treatment strategies for stent-graft infection are selected from among conservative methods such as antibacterial agent administration, drainage, lavage, and surgical methods involving extra-anatomical bypass (EAB) or in situ bypass.Endovascular aneurysm repair (EVAR) is an effective treatment method for abdominal aortic aneurysm (AAA) rupture and impending rupture, infected AAA, etc.We report the case of a patient whose stent-graft infection after EVAR for impending AAA rupture was treated by EAB.The patient was a 64-year-old man. At the age of 61 years, magnetic resonance imaging was performed as part of a detailed examination by a local physician for low back pain. Impending AAA rupture was diagnosed, and the patient was urgently transferred to the authors’ hospital. Enhanced computed tomography (CT) was performed, and it revealed an AAA surrounded by diverse cystic structures up to 52 mm in diameter (18F-fluorodeoxyglucose positron emission tomography (FDG-PET) showed a marked uptake of FDG, consistent with the mass lesions shown by CT  concentrations at 13400 cells/µL and 21.5 mg/dL, respectively. Contrast CT showed an enlarged mass opacity below the renal artery surrounding the stent-graft , a right axillary-bifemoral bypass was created to ensure blood flow to the legs and intrapelvic organs. We closed and draped the skin incision of the bypass, followed by laparotomy. After taping using a 4-millimeter vessel loop and clamping, the abdominal aorta was severed, and the stent-graft was exposed. Following ligation and dissection of both legs of the stent-graft, the legs were pulled out of the left and right common iliac arteries, and each of these arteries was ligated. Next, the tip of the 20-milliliter syringe was cut off, and the main body of the stent-graft was inserted inside the syringe  treatment is controversial. A recent systematic review found no difference in mortality between the two groups, but the EVAR group was reported to have less bowel ischemia.Staphylococcus was the most common causative bacteria at 30.1%, followed by Streptococcus at 14.8%. In approximately 27%–30% of patients, the culture results are negative due to preoperative administration of antibacterial agents. Recently, FDG-PET has gained attention as a useful diagnostic method for stent-graft infection; nevertheless, no standards for this have been established to date. No clear diagnostic criteria for stent-graft infection have been established, and it is not unusual for diagnosis to be challenging. This patient was administered antibacterial agents for 7 days before surgery, and the blood and stent-graft culture results were negative. However, there was no improvement in the initial physical examination or inflammatory response.Stent-graft infection is diagnosed comprehensively based on clinical symptoms, contrast CT, and culture with samples collected from the blood, the stent-graft, and the drainage from around the aorta.Additionally, FDG-PET at the same sites showed significant FDG uptake; therefore, we diagnosed graft infection. Since the patient was 64 years old and relatively young, we believed that conservative treatment alone might cause repeated infections in the future; therefore, we opted for surgical intervention. Recently, gene amplification and sequencing have been established as a method for detecting and identifying microorganisms. Such methods may also be useful in identifying causative organisms. Furthermore, CT-guided puncture culture before the second surgery may have been useful in diagnosing the causative organism.Staphylococcus epidermidis. In addition, the nature of late infection often lacks the signs of sepsis. The treatment may include long-term administration of antibacterial agents. There is no consensus on the appropriate duration of postoperative antibiotic therapy. A previous report showed that it should be continued for 6 weeks or longer. However, the reinfection occurred 3.5 years after surgery. Laohapensang et al. showed that antibiotic therapy should be continued as life-long therapy. Therefore, we believe that oral antibiotics should be continued as long-life therapy in this patient.In this patient, a late stent-graft infection occurred 3.5 years after EVAR. Late infections are typically mild and result from colonization by low-virulence organisms, such as  Contrarily, the survival rate of patients who undergo surgical resection is approximately 58%. Therefore, surgical treatment is considered preferable if the stent-graft infection is operable.There are no consensus guidelines for the treatment of stent-graft infections. According to Li et al., the overall survival rate of patients receiving conservative treatment based on antibacterial agents is only 33%. In the present case, although the proximal side of the stent-graft was not barbed, a method to maximally reduce vascular wall damage while pulling the stent-graft out was used, and it was removed safely. Additionally, depending on the condition of the aneurysm, it is a viable option to place the stent-graft lower to allow the space for the aortic clamp when placing a stent-graft for an infected aneurysm. Non-barbed stent-graft, such as Excluder (W. L. Gore and Associates), might be a more appropriate option in anticipation of subsequent stent-graft removal.The surgical techniques used to treat stent-graft infections are broadly divided into stent-graft removal and vascular reconstruction. Stent-graft removal involves risks of vascular wall damage by the stent-graft, and particularly, there are several problems with removing stent grafts that are barbed on the proximal site. A previous report suggested that a method for handling this involves severing the tip region of a 20-milliliter syringe and pulling the stent-graft out simultaneously while inserting it inside the syringe. However, it necessitates procedures such as omental implantation and is thus not appropriate for severe infection. On the other hand, EAB involves concerns about long-term graft patency and risks of aortic stump rupture and renal arterial occlusive complications, but the surgery duration is short; this method is useful for patients with severe infection around the graft. To avoid aortic stump rupture, we should strictly control the blood pressure. In addition, the reinfection at the aortic stump site promotes tissue fragility and may lead to rupture. Therefore, we believe that the long-term administration of antibiotic therapy and strict blood pressure control are necessary.Vascular reconstruction such as in situ or EAB is required. Aortic stump formation can be more readily avoided in situ than EAB, and the former also has a higher patency rate.In the present case, severe infection around the stent-graft made it impossible to predict the safety of the intrapelvic organs during aortic clamping or the leg clamping tolerance time, and EAB was selected to prevent repeated infection of the prosthetic graft after replacement. It will be necessary to continue monitoring this patient carefully regarding long-term patency and complications. The patient’s progression has been favorable to date.Stent-graft removal and EAB were performed for stent-graft infection, and the outcome was favorable. An in situ technique or EAB is selected for vascular reconstruction after stent-graft removal to treat stent-graft infection. However, EAB may be one of the appropriate therapies in cases of severe intraperitoneal infection.


Escherichia coli (57%) and Klebsiella pneumoniae (16%). The most frequent resistance mechanism was production of extended-spectrum beta lactamases. MDR-GNB carriage was associated to liver cirrhosis , previous MDR-GNB carriage , digestive surgery  and length of hospital stay . Several risk factors for MDR-GNB carriage upon admission to a high-risk setting were identified; the main comorbidity was liver cirrhosis.Multidrug-resistant Gram-negative bacteria (MDR-GNB) are microorganisms that have acquired resistance to extended-spectrum antibacterials and constitute an emerging threat to public health. Although carriers are an important source of transmission in healthcare settings, data about risk factors for MDR-GNB carriage are limited. Therefore, we aimed to identify risk factors for MDR-GNB carriage upon intensive care unit (ICU) admission and to optimise screening strategies. We conducted a case–control study. Admissions of adult patients to the ICU of a 1000-bed hospital during a year were included. We collected sociodemographic, clinical and microbiological data and performed a multivariate logistic regression model. A total of 1342 patients resulted in 1476 episodes of ICU admission, 91 (6.2%) of whom harboured MDR-GNB . The most frequently isolated pathogens were  Multidrug-resistant Gram-negative bacteria (MDR-GNB) are microorganisms that have acquired, through a variety of mechanisms, resistance to extended-spectrum antibacterials, for instance third-generation cephalosporins, fluoroquinolones and carbapenems . The gutKlebsiella pneumoniae, MDR-Acinetobacter baumannii and MDR-Escherichia coli have been described as the main emerging MDR-GNB: in 2019, more than half of the E. coli isolates and more than a third of the K. pneumoniae isolates were resistant to at least one antimicrobial group under surveillance. Multidrug resistance is not homogeneous in the region, with countries in Southern and Eastern Europe showing higher percentages of resistant bacteria [The frequency of HAIs caused by MDR-GNB has increased dramatically  and consbacteria .Klebsiella pneumoniae (ST512) at our hospital from 2012 to 2015 [An essential preventive measure included in several clinical practice guidelines is the systematic screening of patients at risk, which allows for the early identification of carriers . Severaloniae ST5 at our hThis study targets two hurdles: limited data about the frequency and risk factors for carriage of MDR-GNB and suboptimal use of resources due to routine screening to all patients .Our main objective was to identify risk factors for MDR-GNB carriage to better target the screening strategy upon ICU admission for patients at risk. We also describe the prevalence of MDR-GNB carriage and the pathogens involved.The study hypothesis was that previous antibacterial therapy and history of stay in healthcare settings or long-term care facilities are associated with a higher risk of carrying MDR-GNB.A non-matched, hospital-based, case-control study was conducted to investigate which factors were associated with an increased risk of MDR-GNB carriage upon ICU admission. Cases were defined as episodes of admission to the ICU in which patients had a positive result to any of the MDR-GNB screened upon admission in the ICU. Prevalent cases, which were excluded from the analysis to avoid Neyman bias, were defined as cases with detection  of carbapenemase-producing GNB in the previous 24 months, or MDR-GNB other than carbapenemase-producing in the previous 12 months. This definition follows criteria from national and international organisations ,13, adapEscherichia coli, Enterobacter cloacae, Pseudomonas aeruginosa and Klebsiella sp. (notably K. pneumoniae). Extended spectrum betalactamases (ESBL) are, by far, the most frequent mechanism of resistance, but carbapenem-resistant Enterobacterales (CRE) are on the rise.The study population was all critically ill patients admitted to the adult ICU of Reina Sofía University Hospital, a tertiary 1000-bed hospital, during the study period. The adult ICU has 42 beds, six modules  and has an average of 1500 admissions per year. The main MDR-GNB causing HAIs in the ICU over the past years have been Eligibility criteria and study period. All adult patients (aged ≥16 years) admitted to the ICU from 1 November 2018 to 31 October 2019 were eligible.Variables. The independent variables were: (a) sociodemographic: age, sex and stay in congregate settings ; (b) clinical: APACHE II score, referring ward, previous carriage of MDR-GNB, chronic comorbidities , previous antibacterial therapy (defined by at least seven days in the last month), gastrointestinal surgery in the last year, gastrointestinal endoscopy in the last year, history of previous transplantation (type), cancer chemotherapy, dialysis, presence of open wounds, biliary drainage, number and length of hospital admissions in the last 12 months , hospital admission date and ICU admission date; and (c) microbiological: microorganism(s) isolated and mechanism(s) of antimicrobial resistance. The dependent variable was the result of the MDR-GNB screening. Variables included were qualitative, with the exception of age, APACHE II score, number and length of hospital admissions, which were quantitative.This study was devised following the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) recommendations  see Sup.Patient information was obtained through direct interview with the patient or the responsible physician and from the patient’s clinical records. Rectal swab specimens were collected in all study participants within the first 24 h of ICU admission to assess bacterial colonisation. Swabs collected were placed in sterile round bottom tubes containing 1 mL sterile Copan transport medium and immediately transferred to the Clinical Microbiology Laboratory for analysis. Details on the analysis can be found in P. aeruginosa, A. baumannii and S. maltophilia) can be consulted elsewhere [We considered MDR-GNB as that with mechanisms of resistance requiring contact precautions for infection control and followed international expert criteria  adapted lsewhere .T-test was used for mean comparison in quantitative variables and Wald’s test was used to obtain crude (non-adjusted) estimators for quantitative variables. Non-parametric tests were used when appropriate.In the descriptive analysis, qualitative variables were expressed as absolute numbers and their relative frequencies, whereas quantitative variables, tested for normal distribution by the Shapiro–Wilk test, were expressed as mean and standard deviation (SD) if normally distributed, or as median and interquartile range (IQR) if not. In the bivariate analysis, Pearson’s chi-square was used to compare categorical variables, Student’s p-value <0.30, as well as key sociodemographic variables, were included in a backward, multivariate logistic regression model. Collinearity of the model was measured by the variance inflation factors, setting the threshold of non-collinearity at <2.5. Linear relation between quantitative independent variables and the dependent variable was examined by the added-variable plot. Calibration of the model was assessed by Hosmer–Lemeshow test. Discrimination of the model was assessed by receiver-operator curve (ROC) characteristics with 95% confidence interval (CI). Significance of the regression coefficients was assessed by Wald’s test.We performed a backward, conditional, 10-fold cross-validated stepwise multivariate logistic regression model to preselect predictive variables. Overall goodness of fit was analysed by Akiake’s Information Criteria (AIC). These preselected variables, along with those associated with MDR-GNB in the bivariate analysis with a First, we built an explanatory model maximising accuracy to achieve the primary objective. Then, we prioritszed sensitivity, by lowering the threshold for positivity from 0.5 to 0.05, in a pragmatic approach to achieve the secondary objectives. Finally, we compared the performance of both models, through sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV) and accuracy for different breakpoints.p-value of 0.05 or less were considered significant. The analyses were performed using R software version 4.0.3 .All statistical tests were two-sided, and variables with a From 1 November 2018 to 31 October 2019, there were 1342 patients admitted to the ICU, resulting in 1487 episodes of ICU admission. Of these 1487 episodes, 102 (6.86%) were identified as cases, of which 91 (89.22%) were incident cases. Only 11 subjects were classified as prevalent cases and consequently excluded from the analysis; the characteristics of these patients are reported in Of the 1476 cases (91) and controls (1385) finally included, 491 were female (33.27%) and the median age was 63 years. Baseline characteristics are shown in Regarding the referring ward, cases were more frequently referred from hepatology, general and digestive surgery, whereas controls came more frequently from cardiovascular surgery and the emergency department. We show previous antibacterial therapy administered to cases and controls in Escherichia coli  and Klebsiella pneumoniae , followed by Citrobacter freundii and Klebsiella aerogenes. In terms of antimicrobial resistance mechanisms, ESBL-producing E. coli and other ESBL-producers were the most common  MDR-GNB, followed by derepressed ampC-producers  were unusual.Pathogens identified among cases are displayed in p < 0.01), previous MDR-GNB carriage , digestive surgery in the last year  and length of hospital stay in the last year  were independent risk factors for MDR-GNB carriage upon ICU admission. Our data also suggest that previous gastrointestinal endoscopy, patients classified as non-emergency surgical and medical by the APACHE system, as well as previous antibacterial therapy may confer a higher risk of MDR-GNB carriage, while cancer chemotherapy might be associated with a lower risk. Overall, the model showed a good calibration, (p > 0.05 in the Hosmer–Lemeshow test), and collinearity was low .Multivariate analysis  showed tThe ROC curve  could coE. coli and K. pneumoniae. These findings are consistent across studies of critically ill patients, although the frequency of rectal carriage of MDR bacteria reported in other ICUs is somewhat higher, with rates over 10% [In our study, 7% of screening cultures upon ICU admission were positive for MDR-GNB, mainly ESBL-producing Our study has identified several risk factors independently associated with MDR-GNB carriage upon ICU admission. Interestingly, among them only one comorbidity showed a strong association–liver cirrhosis. Previous studies carried out in Spain have reported liver cirrhosis as a risk factor for MDR colonisation in critically ill patients ; in decoLiver cirrhosis can lead to carriage of MDR-bacteria through a plethora of immunological mechanisms grouped under the term, cirrhosis-associated immune dysfunction. The initial systemic inflammation, responsible for fibrosis and complications, such as portal hypertension, gradually switches to an immunodeficient state, characterised by exposure to gut microbial products that chronically stimulate innate immune cells, impairing their antimicrobial function in advanced disease . Howeverp = 0.067). Surgery in the last year increases the risk of carriage with ESBL-producing bacteria in the ICU and upon hospital admission, and recent surgery that of KPC-producing K. pneumoniae carriage [Digestive disorders other than liver cirrhosis play a role, at least indirectly, in the carriage of MDR-GNB: digestive surgery in the last year was an independent risk factor, and previous gastrointestinal endoscopy, associated with a two-fold risk of carriage, was barely below the level of significance  is usually reported for CRE ,29,30. SS. maltophilia resistant to quinolones and colistin but susceptible to trimethoprim–sulfamethoxazole were classified as controls.Misuse and overuse of antimicrobial agents is a key factor driving multidrug resistance . Even thCertain settings, especially nursing homes, increase the risk of acquiring MDR-GNB . NeverthUnfortunately, it was not possible to develop a risk score for MDR-GNB carriage upon ICU admission. The pragmatic model yielded a sensitivity of 62.6% and a positive predictive value of 9.9%, which we deem insufficient for an adequate detection of carriers because underdiagnosis increases the likelihood of outbreaks by MDR-GNB. Remarkably, similar barriers for prediction have been reported for MDR bacteria colonisation or infection at ICU admission  and, morUntil such uncertainties are addressed, infection prevention and control measures are essential to reduce the spread of MDR-GNB. These include, but are not limited to: (a) compliance with standard and contact precautions ,37  and outcomes  will help find the missing pieces of the multidrug resistance puzzle.


T cells engineered with chimeric antigen receptors (CAR) have demonstrated its widespread efficacy as a targeted immunotherapeutic modality. Yet, concerns on its specificity, efficacy and generalization prevented it from being established into a first-line approach against cancers. By reviewing challenges limiting its clinical application, ongoing efforts trying to resolve them, and opportunities that emerging oncotherapeutic modalities may bring to temper these challenges, we conclude that careful CAR design should be done to avoid the off-tumor effect, enhance the efficacy of solid tumor treatment, improve product comparability, and resolve problems such as differential efficacies of co-stimulatory molecules, cytokine storm, tumor lysis syndrome, myelosuppression and severe hepatotoxicity. As a promising solution, we propose potential synergies between CAR-T therapies and cold atmospheric plasma, an emerging onco-therapeutic strategy relying on reactive species, towards improved therapeutic efficacies and enhanced safety that deserve extensive investigations. Adjuvan viruses , 4  derived from an antibody. The aim is to redirect the specificity and function of immune cells and rapidly generate tumor-targeting T cells. A CAR is comprised of four domains, i.e., an ectodomain that is responsible for tumor antigen recognition, an endodomain that contains one or several stimulatory molecules helping T cells persist, a hinge domain, and a transmembrane domain  has demonstrated its power in generating durable tumor remission; for instance, concomitant expression of CARs targeting CD19/CD20 , CD19/CDin vivo and infiltration into tumors. A recent study reported the feasibility of using CAR-T cocktail immunotherapy, i.e., combined use of CAR-T cells against EGFR and CD133, in the treatment of cholangiocarcinoma, where patients receiving such a therapeutic modality achieved an 8.5- and 4.5-month partial response, respectively . However, it is dangerous to trigger such a dramatic immunogenic response that implies elevated potential for the occurrence of uncontrollable or even lethal side effects. For instance, the British company TeGenero almost killed six volunteers in a phase I study testing the efficacy of TGN1412  in the treatment of B-cell tumors and autoimmune disorders due to the induction of toxic levels of cytokines ne storm . The CARne storm . Norelline storm . Inducibne storm , 80. It ne storm . Activatne storm . Effectine storm ; joint uThe CAR-T cells can persist for years with the potential of preventing cancer relapse. This, however, may lead to serious safety concerns including myelosuppression and severe hepatotoxicity . Han W. Product comparability imposes a great concern towards the large-scale application of CAR-T therapies. It is challenging to clearly define the dosage, design and calculation method of infused CAR-T cells that considerably affect the efficacy of CAR-T therapies. The total number of CAR-T cells infused varies from 108 to 1010, in clinical practice, according to the body surface area and weight of the patient. It is also possible to determine the amount of infused CAR-T cells by the CAR-positive cohort. How to reach consensus on the requirements of these detailed specifications to standardize the use of CAR-T while taking into account the heterogeneous nature of CAR-T therapy remains challenging. Some groups have been exploring the feasibility of using third party donor gene modified T cells for treating viral infections , 47, wit2O2), ozone (O3), singlet oxygen (O), hydroxyl radical (OH·), superoxide (O2−), nitric oxide (NO·), anionic (OONO−) and protonated (ONOOH) forms of peroxynitrite. The cocktail of CAP is comprised of long-lived species such as H2O2 and short-lived species such as O. While long-lived species function inside cells to induce apoptosis or necrosis via imposing oxidative/nitrosative stress to cells, short-lived species could induce immunogenic cell death that kill cancer cells located at the long distance  is an emerging onco-therapeutic tool . It genedistance . Both loexposure .The selectivity of CAP against cancer cells has been demonstrated in several types of malignancies including e.g. melanoma , pancreain vitro and in vivo evidences have demonstrated the efficacy of CAP in inducing ICD in many cancers such as colorectal tumors, pancreatic cancers, glioblastoma, and melanoma  may be tempered by taking the joint use of CAP and immunotherapies by creating synergies. ROS-inducing therapies have been shown capable of stimulating the immune system and sensitizing resistant cancers to chemo- and immunotherapies , Fundamental Research Funds for the Central Universities (Grant No. JUSRP22011), Technology Development Funding of Wuxi (Grant No. WX18IVJN017), Major Project of Science and Technology in Henan Province (Grant No. 192102310437), the Major Project of TCM research in Henan Province . The funding bodies played no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.XD was employed by CAPsoul Biotechnology Company, Ltd, Beijing, China.The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The article depicts a unique dataset of responses from 791 adults to a self-made questionnaire of five sections sent via Google survey tool (Google form) from February 4, 2021, to March 18, 2021  The data set shows the vulnerability of mental health of the young generation in Bangladesh due to the use of SNS.•The data can help researchers finding out the factors for poor mental health concerning the use of SNS among the young Bangladeshi population.•Government authorities and non-government organizations can use this data set as part of their policymaking and developing models to improve mental health related to the use of social media.•This evidence-based study can utilize in designing prevention programs for mental health issues like loneliness, anxiety, depression, and sleep disturbances by policymakers.•The data set can provide in-depth insights into the impacts of social media in our lives by causing mental health problems.1Social media has transformed our way of communication and interaction with people. It explicitly holds a major contributing factor for killing time. Is it good or bad in our day-to-day life - is a big question for us. It is rational to conduct studies on its relation to our mental health condition. As an attempt, this cross-sectional study was planned, designed, and carried out. We constructed the survey questionnaire in separate sections to measure four mental illnesses by following internationally validated scales: the UCLA Loneliness Scale-8 (UCLA-8), Patient Health Questionnaire-9 (PHQ-9), 7-item Generalized Anxiety Disorder (GAD-7) Scale, and Pittsburgh Sleep Quality Index (PSQI) The survey data set provides insights about the usage pattern and triggering factors for mental health problems due to the use of SNS. It also provides perceptions of what people think about social media and SNS-induced depression, anxiety, loneliness, and sleep disorders. We obtained responses from authentic users of a specified age limit and different sociodemographic backgrounds in Bangladesh. The data set comprises (i) assessment of loneliness (UCLA-8) in 2It was not feasible to carry on a face-to-face population-based study due to the ongoing COVID-19 pandemic. Therefore, we designed a self-administered questionnaire using google survey tools (Google Forms) and sent it to the participants through various means like Facebook messenger, email, Instagram, WhatsApp, etc. Inclusion criteria were: any Bangladeshi within 15–40 years who has a social media account or SNS user. Initially, we received 826 responses from February 4, 2021, to March 18, 2021. After careful evaluation of dada, we discarded 35 responses due to the partial or incomplete information. We involved people from different education levels, economic statuses, and occupations in this study. Also, we kept the required option for each question in the Google Form. The survey questionnaire contained five sections. The first section was regarding the socio-demographic profiles and the usage pattern of social media in the respondents. Seven questions regarding socio-demographic profile followed by names of social media use, time spent, number of friends and groups, what they think of social media affecting their mental health, etc. questions were involved.The second section had eight questions about “how often the respondents feel the below statements descriptive of you in the past 30 days?” to figure out loneliness. Each question had four options: I never feel this way, I rarely feel this way, I sometimes feel this way, I often feel this way. The third section had nine questions about “how often the respondents bothered by any of the below problems since last two weeks?” with four options: not at all, several days, more than half of the days, nearly every day to figure out depression among the participants. The fourth section had seven questions about “how often the respondents were bothered by the following problems in the last two weeks?” with the options - not at all, several days, more than half of the days, and nearly every day to measure anxiety among them. The final section was to measure sleep disturbances. This section contained nineteen structured questions about their overall sleep quality during the last month. Finally, these nineteen questions were grouped into seven components to calculate the sleep equally score on a four-point scale Committee for Advanced Studies at the Department of Pharmacy, University of Asia Pacific approved this study protocol (No. UAP/Pharm/2021/01004). We obtained electronic informed consent from all participants for this study. Also, we took informed consent from legal guardians in the case of minors who participated in the study.Md. Rabiul Islam: Visualization, Data curation, Writing – original draft, Supervision. Md. Ismail Tushar: Data curation, Formal analysis, Writing – original draft. Sanjida Jannath: Data curation, Formal analysis, Writing – original draft. Amena Ahmed Moona: Visualization, Data curation, Writing – original draft, Supervision, Formal analysis. Shahinur Akter: Data curation, Formal analysis, Writing – original draft. Sardar Mohammad Ashraful Islam: Visualization, Data curation, Writing – original draft, Supervision.The authors do not have any conflict of interest to declare.


They comprise various T-cell clones with diverse antigen-specific T-cell receptors (TCRs). Thus, elucidating the overall antitumor responses of diverse T-cell clones is an emerging challenge in tumor immunology. With the recent advancement in next-generation DNA sequencers, comprehensive analysis of the collection of TCR genes  is feasible and has been used to investigate the clonal responses of antitumor T cells. However, the immunopathological significance of TCR repertoire indices is still undefined. In this review, we introduce two approaches that facilitate an immunological interpretation of the TCR repertoire data: inter-organ clone tracking analysis and single-cell TCR sequencing. These approaches for TCR repertoire analysis will provide a more accurate understanding of the response of tumor-specific T cells in the tumor microenvironment.CD8 These activated T cells proliferate in the periphery, eliciting responses against the corresponding antigen, including cancer antigens. Conventional preclinical and clinical studies on antitumor T-cell responses have analyzed a limited number of tumor-specific T-cell clones using TCR transgenic mice . TCR is composed of alpha and beta chains, whose specificity is determined by the gene rearrangement that occurs in the thymus. T cells specifically recognize their cognate antigens nic mice  or peptinic mice . Howevernic mice , 4.in vivo, termed as the TCR repertoire, is considered to be a new indicator to evaluate T-cell responses based on antigen specificity. Recent advances in next-generation sequencing (NGS) technology have enabled TCR sequencing (TCRseq), which allows a comprehensive determination of the TCR sequences in individuals , diversity (D), joining (J), and constant (C) gene segments as well as insertions and deletions, resulting in a vast diversity . In TCRsTCR sequences obtained by NGS are aligned to reference sequences of the V, D, and J regions and then assembled into T-cell clones that share the same CDR3 sequence. Algorithms, such as IgBLAST , IMGT/Hi+ and CD8+ tumor-infiltrating lymphocytes (TILs) were not separated prior to TCRseq in these studies. Considering that CD8+ TILs generally exhibit higher clonality than CD4+ . The second is single-cell (sc) TCRseq, in which gene expression profile is integrated into individual T-cell clones.Despite these issues, the diversity and clonality of the TCR repertoire are becoming recognized as factors associated with prognosis and/or therapeutic effects. However, the immunopathological significance of these TCR repertoire indices is still undefined because clonality or diversity as determined by TCR repertoire analysis does not consider the immunological features of individual T-cell clones. In other words, whether a clone is CD8via the peripheral blood  and then infiltrate into the tumor tissue A few studies have performed dLN-tumor overlapping analysis on samples surgically resected from patients with cancer Table 4.+ immunosuppressive cells, including regulatory T cells, and activating tumor-reactive CD8+ T cells  in the tumor, but not in the dLNs; “dLNMajor clones”, which were dominant in the dLNs, but not in the tumor; and “DoubleMajor clones”, which were dominant in both the dLNs and the tumor . Therefore, it is impossible to associate a gene expression profile with a particular clone, which poses a major hurdle to understanding the function of T-cell clones in TCR repertoire analysis.scTCRseq is a potent approach to assigning immunological phenotypes to individual T-cell clones . scTCRseWith the advancements in single-cell analysis, more high-throughput scTCRseq methods are being developed, which can be roughly divided into two types: (1) methods reconstructing TCR sequences by extracting TCR reads from standard scRNAseq data and (2) those amplifying TCR genes selectively from the scRNAseq library and sequencing both the TCR gene and scRNAseq libraries. Experimental overview and characteristics of these two categories of scTCRseq methods are summarized in + T cells  under Grant Number JP 21gm6210025 and JP21fk0210049.HA reports stock for ImmunoGeneTeqs, Inc. SU reports advisory role for ImmunoGeneTeqs, Inc; stock for ImmunoGeneTeqs, Inc, IDAC Theranostics, Inc. SS reports advisory role for ImmunoGeneTeqs, Inc; stock for ImmunoGeneTeqs, Inc, KM reports consulting or advisory role for Kyowa-Hakko Kirin, ImmunoGeneTeqs, Inc; research funding from Kyowa-Hakko Kirin, and Ono; stock for ImmunoGeneTeqs, Inc, IDAC Theranostics, Inc.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.