Background: Diagnosis of cardiac involvement in amyloid A (AA) amyloidosis is challenging since AA amyloidosis is a rare disease and cardiac involvement even less frequent. The diagnostic yield of currently available non-invasive imaging methods is not well-studied and rather limited, and invasive endomyocardial biopsy (EMB) is rarely performed due to the potential risk of this procedure. Cardiovascular magnetic resonance (CMR)-based myocardial tissue characterization by late-gadolinium-enhancement (LGE) imaging and novel-mapping approaches may increase the diagnostic yield in AA amyloidosis.Methods: Two patients with AA amyloidosis in whom cardiac involvement was suspected based on CMR findings and subsequently proven by biopsy work-up are presented. CMR studies were performed on a 1.5-T system and comprised a cine steady-state free precession pulse sequence for ventricular function and a late-gadolinium-enhancement (LGE) sequence for detection of myocardial pathology. Moreover, a modified Look-Locker inversion recovery (MOLLI) T1-mapping sequence was applied in basal, mid and apical short-axes prior to contrast agent administration and ~20 min thereafter to determine native T1 and ECV values.Results: Both patients showed slightly dilated left ventricles (LV) with mild to moderate LV hypertrophy and preserved systolic function. Only a very subtle pattern of LGE was observed in both patients with AA amyloidosis. However, markedly elevated native T1  and extracellular volume fraction (ECV) values  were measured in the myocardium suggesting the presence of cardiac involvement - with subsequent EMB-based proof of AA amyloidosis.Conclusion: We recommend a multi-parametric CMR approach in patients with AA amyloidosis comprising both LGE-based contrast-imaging and T1-mapping-based ECV measurement of the myocardium for non-invasive work-up of suspected cardiac involvement. The respective CMR findings may be used as gatekeeper for additional invasive procedures (such as EMB) and as a non-invasive monitoring tool regarding assessment and modification of ongoing treatments. Amyloidosis is a family of multifaceted, heterogenous diseases based on abnormally folded proteins characterized by pathological accumulation of insoluble, polymeric protein fibrils in the extracellular space of various tissues and organs—sometimes leading to organ dysfunction, organ failure, and death. So far, there are more than 30 different proteins, which have been identified as amyloidogenic—out of which at least 17 can cause systemic disease  are (i) immunoglobulin light chain (AL)  and (ii)To identify the underlying inflammatory process in newly diagnosed AA amyloidosis, several factors ranging from genetic variation to ancestral history of patients have to be taken into consideration. For example, SAA1 genotype is one of those predisposing factors supposed to affect amyloidogenesis  . LikewisAvailable knowledge indicates that SAA does not affect the human heart directly, and significant clinical cardiac manifestations are rare. However, it has been shown that SAA may be deposited in cardiac tissue . If presIn the present report, the use of multi-parametric CMR imaging was crucial to diagnose cardiac involvement in case of systemic AA amyloidosis. We present two similar cases of AA amyloidosis in whom cardiac involvement was suspected based on CMR findings and subsequently proven by biopsy work-up. Importantly, both cases showed only a very subtle pattern of LGE—not resembling the well-known characteristic pattern of LGE that can be found in those patients with ATTR and AL amyloidosis. However, additional ECV measurement based on T1-mapping was highly suggestive of an ongoing infiltrative process in the extracellular space of the myocardium.Early diagnosis of cardiac involvement in amyloidosis can be challenging due to unspecific or missing clinical manifestations. Although non-invasive imaging modalities such as echocardiography (with speckle-based strain measurement), bone scintigraphy  as well CMR has been established as a robust diagnostic tool for the work-up of different cardiac diseases including LV hypertrophy of unknown origin and was recently shown to offer a very high diagnostic yield regarding the diagnosis of cardiac ATTR and AL amyloidosis , 16. An Both subjects were Caucasian males who presented with end stage renal disease (ESRD) requiring dialysis. The first patient was a 44-year-old young male patient with terminal renal insufficiency and was on hemodialysis since 08/2018. A rectal biopsy performed in 11/2019 had revealed SAA depositions. Echocardiography showed a moderate to severe LV hypertrophy with preserved ejection fraction. Additional EMB samples were taken in this patient and confirmed the presence of cardiac AA amyloidosis. Subsequent genetic testing revealed heterozygosity for 2 pathogenic variants of the MEFV-gene and supported the diagnosis of FMF as a plausible cause of AA amyloidosis.The second subject, a 53-year-old male and tobacco-smoking patient, was initially referred from a regional hospital to our university hospital following clinical deterioration of the general condition during dialysis in addition to new-onset of diffuse abdominal pain. Incidental findings comprised a pericardial effusion with a maximal diameter of 2 cm. Noteworthy, he was treated with colchicine since his childhood due to suspected MFM. This treatment was stopped in 2012 due to onset of terminal renal insufficiency leading to haemodialysis. The suspected diagnosis of FMF was confirmed by molecular genetic analysis as an underlying inflammatory cause after SAA deposits were detected in EMB samples. In addition, liver biopsies were also performed and confirmed the aforementioned results. Details of the respective patient characteristics can be found in via a femoral artery access site using a 7F long-sheath without angulation following a retrograde approach) as described previously . EMBs were considered positive for viral infection if viral genomes were detected by nested PCR/reverse transcription PCR, as published previously . EMB speCMR studies were performed on a 1.5-T system . CMR data acquisition was performed according to the standardized protocol suggested by the Society for Cardiovascular Magnetic Resonance (SCMR) . Our CMRBoth patients showed similar results regarding cine-imaging: LVs were slightly dilated, mild to moderately hypertrophied with preserved systolic function. Right ventricles (RV) showed no abnormalities with regard to size and function. Regarding myocardial tissue characterization, a subtle and rather diffuse pattern of LGE was detected in the basal segments of the LV lateral wall. Moreover, a little pericardial effusion was observed . PatientBased on histopathology, there was no evidence of active lymphocytic myocarditis. Using Congo-red staining and immunohistochemistry, the presence of cardiac AA amyloidosis was confirmed with a very subtle and diffuse amyloid pattern in the extracellular space and a marked vascular involvement . In addiCardiac involvement in case of AA amyloidosis is not common and rather challenging to diagnose. An extensive literature search regarding the diagnostic value of non-invasive imaging modalities to diagnose cardiac AA amyloidosis did not result in any landmark studies nor in convincing case reports. Obviously, echocardiography is a widely available tool that has improved significantly the diagnosis of CA after the introduction of speckle-tracking-based strain analysis, however, is still lacking high sensitivity as well as specificity –23. In cin vivo quantification of myocardial edema suggestive of myocardial inflammation  sophisticated work-up of non-ischemic cardiomyopathies, and in this context to differentiate between CA and HCM based on the pattern of LGE. While the LGE pattern in case of CA is rather diffuse, starts mostly from the subendocardial layer of the basal segments and eventually spreads to all myocardial layers and segments , 24, claammation . Myocardammation .Several previous studies have shown that measurement of native T1 and ECV values are useful tools for the work-up of hypertrophic cardiac phenotypes of unknown origin . The degN = 134 non-diabetic patients with chronic kidney disease (CKD) stages 2 to 5 without myocardial ischemia at 1.5-Tesla and found native T1 values of 966 ± 21 ms in stage 2 patients vs. 994 ± 33 ms in stage five patients (p < 0.001) —again at 1.5-Tesla—and documented septal native T1-values of 1002 ± 30 ms and a myocardial ECV value of 28 ± 2%  myocardial fibrosis that in turn may lead to increased myocardial native T1 and ECV values. In this context, Hayer et al. recently studied In summary, unlike other well-known subtypes of amyloidosis (such as ATTR and AL), a characteristic pattern of diffuse LGE is not observed in case of AA amyloidosis based on CMR. However, measurement of myocardial ECV—in addition to myocardial T1-/T2-mapping—may be of paramount diagnostic value to detect cardiac involvement in case of AA amyloidosis—despite a missing characteristic LGE pattern. Therefore, we recommend a comprehensive multi-parametric CMR approach comprising the combined analysis of T1-/T2-mapping, measurement of ECV and careful assessment of LGE-images in patients with AA amyloidosis and suspected cardiac involvement.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.BC devised the project and the main conceptual idea, and wrote the manuscript. SD contributed to sample and data collection. MB and CM provided critical feedback and helped shape the research and analysis. KK performed the histological and immunohistochemical analyses. AY supervised the work, contributed to the interpretation of results, provided critical feedback and helped shape the research, analysis, and manuscript. All authors contributed to the article and approved the submitted version.The 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.


Patients receiving in-center hemodialysis experience disproportionate morbidity and incur high healthcare-related costs. Much of this cost stems from potentially avoidable hospitalizations. Peer mentorship has been used effectively to improve outcomes for patients with complex chronic diseases. We propose testing the efficacy of peer mentorship on hospitalization rates among patients receiving hemodialysis.This is a multicenter parallel group randomized controlled pragmatic trial of patients treated at hemodialysis facilities in Bronx, NY and Nashville, TN. The study has two phases. Phase 1 will enroll and train 16 hemodialysis patients  to be mentors using a program focused on enhancing self-efficacy, dialysis self-management and autonomy-supportive communication skills. Phase 2 will enroll 200 high risk adults receiving hemodialysis , half of whom will be randomized to intervention and half to usual care. Intervention participants are assigned to weekly telephone calls with trained mentors (see Phase 1) for a 3-month period.The primary outcome of Phase 1 will be engagement of mentors with training and change in knowledge scores and autonomy skills from pre- to post-training. The primary outcome of Phase 2 will be the composite count of ED visits and hospitalizations at the end of study follow-up in patient participants assigned to intervention as compared to those assigned to usual care. Secondary outcomes for Phase 2 include the change over the trial period in validated survey scores measuring perception of social support and self-efficacy, and dialysis adherence metrics, among intervention participants as compared to usual care participants.The PEER-HD study will test the feasibility and efficacy of a pragmatic peer-mentorship program designed for patients receiving hemodialysis on ED visit and hospitalization rates. If effective, peer-mentorship holds promise as a scalable patient-centered intervention to decrease hospital resource utilization, and by extension morbidity and cost, for patients receiving maintenance in-center hemodialysis.NCT03595748; 7/23/2018.Clinicaltrials.gov identifier: National Institutes of Diabetes, Digestive and Kidney Disease (NIDDK) 5R18DK118471.Funding for this study was provided by the National Institutes of Diabetes, Digestive and Kidney Disease: R18DK118471.This is an ongoing study and not complete. We are still collecting data for observational follow-up on participants.No related articles for this study have been submitted to any journal.The study sponsor and funders had no role in the design, analysis or interpretation of this data. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.The online version contains supplementary material available at 10.1186/s12882-022-02701-1. The high rate of hospitalization among patients receiving maintenance hemodialysis (MHD) contributes to enormous cost, morbidity and decreased quality of life –3. VariaPeer mentorship has been used to improve self-management behaviors and outcomes in chronic diseases and could be effective in counteracting modifiable mediators of avoidable hospitalization among patients receiving MHD . Peer meThe overarching goal of this research study is to test the effect on the composite rate of ED visits and hospitalizations of a peer mentor intervention for patients receiving MHD.The purpose of this manuscript is to present the study design and protocol, and adaptations implemented after the initial COVID-19 surge, of the PEER-HD trial using the SPIRIT framework, a standardize approach to describing protocols .PEER-HD is a parallel group, randomized, controlled, multi-center pragmatic trial that tests the superiority, as compared to usual care, to precent hospitalizations of a telephone delivered, protocol-guided, mentoring intervention among patient receiving MHD.The study will enroll patients receiving MHD from two geographic locations; the first sample will be from eight dialysis facilities in the Bronx, NY where Einstein/ Montefiore faculty are medical directors and the second sample will be from two Vanderbilt affiliated dialysis facilities in Nashville, TN Fig. .Fig. 1TrMentor participants and patient participants must meet designated inclusion and exclusion criteria that differ for each group to be considered for recruitment Table .Table 1EThe investigators identify and enroll 16 patients to serve as mentors (10 in the Bronx and 6 in Nashville). These mentors are trained using a semi-structured curriculum based on Peer Mentorship curricula developed by Drs. Michele Heisler and Jennifer St Clair Russell and modeled on the “information, motivation, behavior (IMB) model” . TraininThe peer-mentor training manual was designed and written by the study PIs with consultant input. We employed a multidisciplinary team to finalize the training curriculum including 2 dialysis facility social workers, 2 nurse managers and 2 patient representatives (current patients on MHD who serve as ESRD network patient advocates). The curriculum aims to: a) increase knowledge about estimated dry weight (EDW), inter-dialytic weight gain (IDWG) and symptoms of fluid overload; b) increase knowledge about adherence, dialysis clearance, their relationship to each other, to symptoms of uremia and to various outcomes; c) to improve dialysis self-management by identifying a dialysis specific skill set; and d) to increase peer mentor communication skills with a focus on confidentiality, motivational interviewing, non-judgmental listening, social modeling and providing social support , for travel and for up to $15/h of time spent on the telephone while mentoring. Any telephone call lasting between 3 min and 30 min will be treated as ½ hour and any call over thirty minutes to 1 h will be treated as a full hour, for the purpose of calculating telephone intervention compensation. The study will pay up to $150/week.All patient participants undergo an initial assessment immediately after enrollment, an assessment at 3 months (end of intervention period) and a last assessment at the end of observational follow-up (at 12 or 18 months after enrollment) .Patient participants randomized to “intervention” are assigned to mentors using the following criteria: language (English or Spanish), age (within one decade), sex, and race/ethnicity. Every effort is made to match by these criteria. However, because of the limited number of mentor participants priority is given to language ability as the matching criteria. If a patient assigned to intervention becomes hospitalized during the 3-month intervention period, the mentors is instructed to continue calls as per their schedule where feasible.COVID-19 related adaptations were made to the protocol as soon as research study activities were allowed to resume after the initial pandemic surge in New York City (March–June 2020). All three PIs and the study team members were involved in making Data Safety and Monitoring Board (DSMB) and IRB approved adaptations involving the nature of study coordinator interactions with participants (for assessments) and truncation of observational follow-up period. Because of the disruption in trial activities and to meet initial enrollment targets, the DSMB committee recommended to truncate observational follow up from 15 months to 9 months  in all of those participants (mentors and patient participants) with < 12 months of follow-up at the end of April 2021. COVID-19 disrupted all in-person processes; thus, all enrollment and training activities were conducted virtually (using Zoom) and the study protocol and participant consents were amended to reflect these changes. Because the intervention is delivered by telephone, disruptions to study processes introduced by COVID-19 only affected enrollment and study-visit activities, which required conversion from in-person to virtual visits for some encounters until safety protocols to mitigate risk where available.The primary outcome of the randomized controlled trial (RCT) is the composite rate of hospitalizations and ED visits in intervention, as compared to usual care, patient participants.Secondary outcomes include change in knowledge, self-efficacy, perception of social support, coping skills and dialysis adherence metrics gleaned from validated survey tools that were delivered before and after the intervention (see below under “Data collection methods”), in the intervention as compared to the usual care group.Secondary outcomes for mentor participants included ascertainment of the feasibility, efficacy and fidelity of a peer-mentor training program. In addition, changes over the study enrollment period in above parameters using validated survey tools (outlined above for patient participants) will also be ascertained for mentor participants.The study timeline is outlined in Fig. For sample size calculation for evaluation of the primary endpoint, estimates are made based on dialysis facility hospitalization events during 12 months prior to trial start at the primary study enrollment sites. For the usual care group, we expect 0.27 events per month . With 73 patients per group (after 25% drop-out), our study has > 80% power to detect 20% reduction (i.e. a reduction of 0.054 visits per person-month) at type 1 error level 0.05 . RecruitAfter all required regulatory waivers are executed, potential mentors undergo a screening of their electronic health record (EHR) for eligibility criteria. Once deemed eligible, the study staff approach, consent and schedule initial assessments for potential mentor participants. Similar procedures are followed for screening and recruitment of potential patient participants. Eligibility criteria are shown in Table Enrolled patient participants are randomized after completion of informed consent and the baseline study visit, utilizing a computer-generated randomization sequence stratified by center. As each participant is enrolled, sequential envelopes with the random assignment to either the intervention or the usual care control group are given by the coordinators (1:1).post-training assessments. These will include brief surveys assessing the knowledge of training subjects including: fluid (6 items), uremia and infection (6 items), mentor role (5 items). Each of these is scored as correct or incorrect and reported as a percentage correct (0–100%). Each mentor’s confidence with mentor skills is assessed with an 11-item survey with Likert-type responses. Each mentor also provides ratings (11-items) and open-ended comments about their satisfaction and experience with the training sessions.Mentors will be evaluated by Data regarding outcomes is collected monthly using both participant report and health records. The data is self-reported by patients during monthly phone calls made by the study coordinator. Monthly dialysis facility health records and hospital records is reviewed for each patient participant to ascertain the outcome. Dialysis adherence metrics including number of missed monthly minutes of dialysis and mean monthly IDWG are collected monthly from dialysis facility EHR.n = 3) to assess various measures and include: 1- Chronic Hemodialysis Knowledge Survey (CHeKs) [Survey tools will be used during study visits ( (CHeKs)  question (CHeKs) , self-ef (CHeKs) ), coping (CHeKs)  and Mult (CHeKs)  question (CHeKs) , communi (CHeKs)  and heal (CHeKs) , healthc (CHeKs)  are alsoTelephone billing records for all mentor and intervention patient participant phones will be reviewed. All calls will be abstracted including phone number called, date, time, and duration. A summary of weekly minutes between mentor and patient participant pairs will be generated for characterization of intervention dosing as well as evaluation of execution of mentor and patient participant responsibilities. Where possible, random recordings of calls will be submitted to the study team for qualitative review of content. Call logs and self-reported phone calls with duration by mentors and mentees will also be reviewed, coded and characterized for content notes.All data will be recorded in a study REDCap database, with access granted to each enrollment site.The rates of the composite event for the primary endpoint  will be determined as event per patient-month and compared between the intervention and usual care patient-participant groups using Poisson regression with two random intercepts. In the regression model, the composite counts of ED visits and hospitalization for 12- or 18-months follow-up is the outcome variable and the intervention assignment of the patient participants is the primary binary predictor. The log of follow-up time will be included as offset. The random intercepts will account for the correlation between intervention patients who share a common mentor as well as the correlation between patient participants who are from a common dialysis facility . We will control for type 1 error at 0.05. To test the effect of a peer mentor led telephone intervention on patient self-management skills and perceptions of support (secondary endpoints) including 1) dialysis adherence , 2) mean monthly IDWG, 3) monthly albumin level, 4) dialysis knowledge, 5) self-efficacy and 6) social support scores; we will compare each of these outcomes between the two randomization groups using linear regression with two random intercepts . In the We will use the Wilcoxon rank sum test to test the difference in pre- and post-training knowledge assessments in the mentors (Baseline CHeKS and CHeKS-PLUS vs. mid-study and end-of-study visits). The outcome variable for the regression is the difference between pre-and post-training scores and the parameter of interest is the intercept. For qualitative data, we will review the content of the individual interview responses and describe the content including common themes identified.A board of 3 independent physicians from AECOM meet biannually with study investigators to review the study protocol. Study activities, study conduct, adverse events and serious adverse events. The investigators have the option of calling ad-hoc DSMB meetings in case of any event potentially attributable to the study intervention.The PEER-HD program will test the efficacy of a telephone delivered peer mentorship on ED visit and hospitalization rates in patients receiving maintenance hemodialysis. Using a training curriculum developed by the study PIs to improve self-management skills specific to hemodialysis and communication skills Fig. , mentor Hospitalizations drive up to 40% of the cost for dialysis care –37. PatiLimitations of our study design deserve mention. The patient population that this study targets represents the highest utilizers of hospitalization services because of various health burdens and social challenges. These qualities make them difficult to recruit in research studies resulting in risk for selection bias and under-representation of the population of most interest. However, this multi-site collaboration increases the potential diversity of the study population and its subsequent generalizability. Cognitive and health literacy challenges may result in lack of effect of the intervention. The study will, however, measure and include these potential confounders to reduce the risk of their impact on interpretation of the findings. Finally, variables not considered in the study design (such as the COVID-19 pandemic) may contribute to attrition and lack of fidelity to training and intervention schedules. Adaptations of the study protocol are instructive for future studies experiencing similar unexpected scenarios.In conclusion, the PEER-HD pragmatic randomized clinical trial promises to shed light on the feasibility of a mentor training program, and the efficacy of a telephone delivered peer mentorship intervention on hospitalization and emergency room visit rates in patients receiving MHD. Advances in understanding this approach to deliver information, emotional and logistical support is required to inform future expansion of peer initiatives in dialysis care.Additional file 1.


Nature Communications 10.1038/s41467-022-28231-w, published online 22 February 2022.Correction to: The original Article contained two sentences in the Abstract which duplicated the same information. They read “Using surveillance data at fine resolution from Rio de Janeiro, we document a scale-invariant pattern in the size of successive epidemics following DENV4 emergence. Using surveillance data at fine resolution following the emergence of the DENV4 dengue serotype in Rio de Janeiro, we document a pattern in the size of successive epidemics that is invariant to the scale of spatial aggregation.”. The first sentence has now been removed.This correction has been made in both the PDF and HTML versions of the Article.


Telemedicine (TM) can revolutionize the impact of diabetic wound care management, along with tools for remote patient monitoring (RPM). There are no low-cost mobile RPM devices for TM technology to provide comprehensive  clinical assessments. Here, a novel low-cost smartphone-based optical imaging device has been developed to provide physiological measurements of tissues in terms of hemoglobin concentration maps. The device (SmartPhone Oxygenation Tool—SPOT) constitutes an add-on optical module, a smartphone, and a custom app to automate data acquisition while syncing a multi-wavelength near-infrared light-emitting diode (LED) light source . The optimal imaging conditions of the SPOT device were determined from signal-to-noise maps. A standard vascular occlusion test was performed in three control subjects to observe changes in hemoglobin concentration maps between rest, occlusion, and release time points on the dorsal of the hand. Hemoglobin concentration maps were compared with and without applying an image de-noising algorithm, single value decomposition. Statistical analysis demonstrated that the hemoglobin concentrations changed significantly across the three-time stamps. Ongoing efforts are in imaging diabetic foot ulcers using the SPOT device to assess its potential as a smart health device for physiological monitoring of wounds remotely. Complications from diabetes mellitus (DM) are increasing , making The cornerstone of the TM systems for DFU care is the clinical assessment of digital photographic images from high-quality digital cameras or 3D cameras —primarily used by health professionals and not patients. These images can reliably capture and measure ulcer size (or area) across healing. The use of TM was associated with significantly fewer amputations, reduced healing times for hard-to-heal ulcers  and is aNearly 60% of smartphone users gather health-related information on their phones, and 80% of physicians use smartphones and mHealth apps. Recently, researchers have developed smartphone-based apps for (i) 2D and 3D wound image analysis ,14 to esPhysiological assessment of DFUs is vital to augment the clinician’s visual assessment since sub-surface changes in wounds are not visible to the naked eye. The various physiological parameters measured to assess wound healing include tissue oxygenation, temperature, pH, and pressure. Smartphone adaptable thermal sensors  have been developed and used to obtain thermal maps of the wounds and assess their healing status . An optiOxygen supply to DFUs is a key limiting factor for successful healing due to increased demand for reparative processes such as cell proliferation, bacterial defense, angiogenesis, and collagen synthesis . Hence, In this work, the development of our smartphone-based tissue oxygenation measuring device (smartphone oxygenation tool—SPOT) is described. The SPOT device consists of an add-on NIR optical module, a smartphone, and a custom-developed smartphone app that automates the data acquisition process. The optimal imaging conditions in terms of imaging heights and device settings are determined from signal-to-noise ratio studies. The feasibility of the SPOT device to map for oxy- and deoxy-hemoglobin changes in response to a standard vascular occlusion test is demonstrated with and without the application of noise-filtering techniques.The SPOT instrumentation, related app, and data analysis to obtain tissue oxygenation maps are described in this section. The optimal signal-to-noise ratio (SNR) of the device and its feasibility to obtain tissue oxygenation changes in response to vascular occlusion test is determined. The first version of the SPOT device could obtain diffuse reflectance images at a single wavelength (690 nm) . Herein,The SPOT device constitutes an add-on optical module, smartphone, and related app that automated data acquisition . The addThe SPOT hardware is controlled via a custom app that is developed in Android Studio (Java). The custom app communicates with the add-on optical module to control: (i) the number of LEDs to be turned on during imaging studies, (ii) the wavelength(s) of these LEDs that it will illuminate the tissue with , and (iii) sync the source end with the smartphone’s internal camera to control the number of frames acquired, operating at a rate of 30 frames per second. The app also controls the smartphone’s internal camera settings in terms of ISO , focusing, white balance, and exposure . In addition to syncing the NIR source with the smartphone camera and controlling its internal settings, the app connects the distance sensor to provide a readout display of the imaging depth directly onto the camera view. The features that the SPOT app syncs and controls are shown in The smartphone camera collected diffuse reflectance signals as short (~1 sec) video files (30 fps), and these video files were transferred to a computer for further processing. The diffuse reflectance images related to each illuminated wavelength  were extracted from average intensity plots that were distinctly different for each wavelength. During data acquisition, it was observed that the smartphone detector inherently executed focusing corrections when the NIR source multiplexed across the different wavelengths ) for tissue oxygenation analysis. This analysis was achieved using a Modified Beer Lamberts Law (MBLL) approach at two wavelengths (690 and 830 nm) [λ chromophore) associated with oxy- and deoxy-hemoglobin, respectively [refλi ). Calibration images were obtained at each wavelength (690 and 830 nm) using a uniformly diffusing white sheet. The dark noise ) was obtained from the smartphone as the intensity measured with no light entering the camera. The optical density at each wavelength ) was estimated as the ratio of measured diffuse reflectance intensity compared to the calibration image given in Equation (1). Effective concentrations of oxy-hemoglobin (∆HbO) and deoxy-hemoglobin (∆HbR) were estimated from the measured optical densities given in Equations (2) and (3), respectively. The term L × B in Equations (2) and (3) correspond to the unknown values of the optical path length factor (L) and inter-optode geometry (B), which cannot be defined in non-contact NIR imaging. Hence oxy- and deoxy-hemoglobin concentrations are expressed as effective rather than absolute values.The SPOT device captured diffuse reflectance signals at multiple wavelengths (I 830 nm) ,22. The ectively ,24,25,26The SPOT device’s signal-to-noise ratio (SNR) to acquire NIR images at three wavelengths  was determined under various imaging conditions. The SNR was maximized by optimizing the imaging distance  and camera controls  of the SPOT device. For medical imaging applications, SNRs above 20 dB are good, and when these exceed 50 dB, this is considered excellent ,28. HereThe SNR was calculated from diffuse reflectance signals obtained with the LED source turned on and turned off at various locations (Loc #) or regions of interest (ROIs), as given in Equation (4).For each imaging condition, the center of the NIR source was identified within diffuse NIR images by applying a Gaussian filter and auto locating the point of maximum intensity. An ROI was generated directly at this maximum intensity or source beam center as a 25 × 25 boxed pixel region. Twelve additional ROIs (25 × 25) were automatically selected 90° apart to span the concentric circles separated by 100 pixels and centered with respect to the maximum intensity point, as shown in The SPOT device was developed to map for tissue oxygenation changes in terms of ∆HbO and ∆HbR. Herein, a standard vascular occlusion test (VOT)  was perfThree control (>18 years) subjects without any known pre-existing conditions were recruited for this Internal Review Board (IRB) approved study. SPOT device was mounted ~10 cm above the dorsal of the hand, and diffuse reflected NIR images were acquired (at ISO 800 camera settings) at 690 and 830 nm wavelengths. Subjects were seated and asked to breathe normally throughout the study. Calibration images were obtained by placing the diffusing white sheet on the tissue surface. The first point of imaging was conducted at rest, while the blood was flowing normally through the arm and the cuff applied no pressure. The arm pressure cuff was then increased to 160 mmHg and held constant for 60 s, at which point the second set of images were acquired, while blood flow was restricted. Immediately following this, the pressure was released entirely from the arm cuff. The third point of imaging was performed 10 s following the full release of pressure when the blood flow was restored. The three imaging points are shown in The dual-wavelength diffuse reflectance NIR images in response to VOT were processed using the MBLL model in Matlab. As a first step, the imaging area with SNR ≥ 20 dB was demarcated before obtaining the ∆HbO and ∆HbR maps at each timestamp. Noise-filtering techniques were implemented, and their impact on hemoglobin maps was evaluated. The statistical significance of the differences in hemoglobin concentration maps across the three-time stamps was determined.(a)Region of Interest (ROI) selection from SNR mapsDiffuse reflectance NIR images were converted into SNR maps (as described by Equation (5)), and the ROI with SNR ≥20 dB was determined.(b)Noise RemovalSingle value decomposition (SVD)  was applt-test was conducted to determine if there was a significant change in effective ∆HbO and ∆HbR in response to the applied stimulus using the blood pressure cuff. Ten locations or sub-ROIs (25 × 25 pixel regions) were randomly selected within the oxygenation map (similar across ∆HbO and ∆HbR maps) to assess the differences between rest vs. occlusion . A separate randomized set of 10 locations were selected to compare oxygenation differences between occlusion and release time stamps. An example case is shown for ∆HbO in A paired 2 black fiducial marker as the reference. Across the various imaging depths, the estimated imaging area (or field of view with SNR ≥20 dB) was higher at 8–10 cm heights. Hence, these image settings  were used during in vivo feasibility studies. The hemoglobin concentration maps were constructed using diffuse reflectance data obtained at 690 and 830 nm in these preliminary feasibility studies. Hence, the SNR optimization results are only provided for these two wavelengths. The range of SNR values calculated across all ISO settings of the camera and the NIR wavelengths (690 and 830 nm) are given in The forearm comprises two main blood supplies stemming from the subclavical artery known as the axillary and brachial arteries. These extend down the lower arm as the radial and ulnar arteries and to the hand as the deep and superficial palmar arch. Common digital arteries extend from the arch to supply the fingers and thumb with a constant blood supply. In this total occlusion study, changes in oxygenation are expected to occur within the hand, corresponding to regions where this blood net extends through the dorsal of the hand. Past VOT studies by other researchers demonstrated that oxy-hemoglobin decreased, and deoxy-hemoglobin increased during occlusion as oxygen was consumed for normal cell functions and not replaced by newly oxygenated blood flowing in . In the t-test  was distinct from the increased flow of oxygenated blood. In summary, as the pressure was released, ∆HbO increased, and ∆HbR decreased, as observed by past researchers . This cht-tests were conducted at 10 different sub-ROIs within the oxygenation maps (∆HbO and ∆HbR) between rest, occlusion, and release. The paired t-test results are given in Paired Across the 3 subjects, there was a significant difference in ∆HbO and ∆HbR between the three timestamps in a majority of the 10 sub-ROIs sampled. However, the difference is not significant for all sub-ROIs, and this may be due to spatial changes in the vasculature. Since the ROIs were randomly selected and not specifically on the blood vessels where occlusion causes a change in oxygenation, it possibly impacts the total number of ROIs that showed a significant difference between rest-occlusion and occlusion-rest. Sub-ROIs chosen over the vasculature may show a very significant change, while sub-ROIs away from the vasculature may show little to no change. In the future, sampling may be more consistent by segmenting regions expected to correlate with the vasculature. However, the change measured at each sub-ROI was significant in the majority of the 10 locations sampled between time points across all subjects. In addition, the repeatability of these oxygenation changes in response to VOT within subjects will also be assessed as part of our future extensive validation studies. A smartphone-based near-infrared spectroscopy (NIRS) system was developed as a SPOT device that can measure changes in oxy- and deoxy-hemoglobin concentrations across a wide field via non-contact imaging. The SPOT device is currently adaptable to an android based smartphone . The optimal camera settings included ISO 800 for maximum SNR, and the optical imaging depth ranged from 8–10 cm. The add-on optical module is adaptable to other smartphones, with minor changes in the device’s casing design. It aligns with the smartphone’s size and camera location for a snap-on fit.Additionally, the optimal camera settings and image depths may be re-evaluated based on the internal camera of the smartphone. The SPOT app currently automates the data acquisition aspect of imaging such that the add-on optical module and the smartphone’s camera communicate effectively. The SPOT app is presently being expanded to allow for automated data extraction (by wavelength) and analysis to provide hemoglobin concentration maps.The SPOT device’s ability to capture in-vivo hemoglobin concentration changes in response to vascular occlusion has been demonstrated as a feasibility assessment of the technology for tissue oxygenation mapping. While the VOT studies are a first step to observe if the smartphone can detect hemoglobin concentration changes during NIR imaging, there is a need for a systematic phantom study. Phantom studies will be carried out to assess the accuracy and sensitivity of the SPOT device to measure oxy- and deoxy-hemoglobin concentrations. In addition, repeatability studies (both phantom and VOT) will also be carried out to assess the precision of our SPOT device. In an ongoing pilot study, SPOT is also used to map for tissue oxygenation changes in diabetic foot ulcer (DFU) subjects across 4 weeks of treatment. Preliminary studies using SPOT were promising since they observed similar changes in the wound: background tissue oxygenation concentrations  with the healing of a DFU. The accuracy of our SPOT device in tissue oxygenation measurements will also be assessed in comparison with the commercial NIRS device.Many NIR-based optical techniques have been developed to assess oxygenation-based physiological changes in DFUs. Although these devices are either hand-held, low-cost, and/or non-contact commercial devices, they are not readily accessible for mHealth-based TM applications of DFUs. DFU wound care management requires frequent clinical visits that affect patients’ time, effort, finances, and/or travel limitations in remote settings. Non-compliance to regular care and follow-up of chronic DFUs can lead to hospitalization or amputations due to severe infections. TM/mHealth empowers people with DFUs in remote care away from the clinic. While smartphones are constantly used to provide a digital visual assessment of the wound status, they cannot serve as stand-alone devices to provide underlying physiological changes that manifest early on over visual changes, as obtained herein using SPOT. Even if the SPOT device may lack the sensitivity or accuracy of existing (bulky) commercial NIR-based devices for DFUs, its potential to impact a majority of DFU patients via a remote-care approach in the long term is more promising than sophisticated devices available only in interdisciplinary clinics or imaging centers. “Cellphone based tissue oxygenation measuring device” Inventors: A. Godavarty, K. Kaile, US Patent Publication No. 20200352515, Dec 2020


Therefore, lipids should be identified by MSn experiments, where the m/z of interest is repeatedly isolated and fragmented to gain further structural information. In addition, targeted MS employing standards for the subsequent validation of the aforementioned new markers should be performed with spatial information. In conclusion, the study by Khamehgir-Silz et al. represents a methodological advancement for the study of atherosclerosis. It will be exciting to see how much MALDI MSI can contribute to a better understanding of cell-specific lipid dynamics in atherosclerosis. A robust platform for spatio-temporal lipidomics will advance the study of cardiometabolic diseases with strong contributions of aberrant lipid metabolism such as obesity or non-alcoholic fatty liver disease [Atherosclerosis is an immunometabolic disorder underlying coronary artery disease and stroke, which remain the leading cause of death and morbidity worldwide. As atherogenesis results in the formation of complex lipid-laden lesions, a deep spatio-temporal understanding of lipid metabolism during plaque formation is key to developing new therapeutic approaches. The nature of lipid species in atherosclerotic lesions is very complex, and technological advancement in the field of mass spectrometry (MS)–based detection of lipids (“lipidomics”) has helped to understand the etiology of atherosclerosis better . The new disease .Fig. 1MA


Shigella dysenteriae and enterohemorrhagic Escherichia coli (EHEC). These toxins recognize a glycosphingolipid globotriaosylceramide (Gb3/CD77) as their receptor and inhibit protein synthesis in cells by cleaving 28S ribosomal RNA. They are the major cause of life-threatening complications such as hemolytic uremic syndrome (HUS), associated with severe cases of EHEC infection, which is the leading cause of acute kidney injury in children. The threat of Stxs is exacerbated by the lack of toxin inhibitors and effective treatment for HUS. Here, we briefly summarize the Stx structure, subtypes, in vitro and in vivo models, Gb3 expression and HUS, and then introduce recent studies using CRISPR-Cas9-mediated genome-wide screens to identify the host cell factors required for Stx action. We also summarize the latest progress in utilizing and engineering Stx components for biomedical applications.Shiga toxins (Stxs) are classic bacterial toxins and major virulence factors of toxigenic  Shigella dysenteriae in 1897 ..190–297 Pseudomonas aeruginosa exotoxin A (PE) translocation domain (the mature form of residues 252 to 364) can be genetically fused to a variety of substances  and efficiently transport them into the cytosol [Pseudomonas aeruginosa exotoxin A  translocation domain; the C-terminus of TDP was fused to the protein cargo to be delivered. The ER retention sequence (KDEL) was fused to the C-terminus of the cargo for retrograde transport. TDP plays a role in the retrograde transport of the cargo from the ER to the cytosol, and, without TDP, the cargo cannot be released into the cytosol. The authors utilized this system and successfully delivered N8A peptide, which is a mouse double minute 2 (MDM2) inhibitor that blocks the degradation of p53 in cells. The author showed that injection of Stx-B-TDP-N8A suppressed tumor growth in vivo in xenograft mouse models without significant side-effects [Inspired by the fact that the  cytosol , Ryou et-effects . The sam-effects .In 2019, Schmit and Neopane et al. further improved the delivery system by linking Stx2B-ETAII with the Von Hippel-Lindau (VHL)-monobody fusion protein. This system targets cancer cells, with the aim of degrading the endogenous tyrosine kinase Lck in Jurkat T-cells and enhancing the inhibition of T-cell receptor (TCR) signaling . VHL is Systemic immunogenicity from the toxin protein is one possible limitation to the widespread application of the Stx-B-based delivery system. Possible solutions to this inherent problem include the removal of immunogenic epitopes by protein engineering, encapsulation of the protein , and redE. coli outbreak in Germany in 2011, which caused HUS in over 800 patients and 54 deaths, was produced by a new strain, O104:H4 [E. coli instead of the usual EHEC strains but acquired virulence by acquiring an Stx2 gene, illustrating the continual threat of Stx in causing major outbreaks and the need for developing effective countermeasures. Recent progress in uncovering host factors and establishing a molecular understanding of the biosynthesis of Gb3 has provided new targets for developing inhibitors that can protect cells from Stx. The physiological function and tissue distribution of Gb3 in humans remain a key open question. Recent studies have also begun to reveal the potential role of Stx in taming immune responses and established human intestinal organoid models for understanding how Stx actions may benefit the bacteria. The observation that EHEC T3SS also requires Gb3 is intriguing and deserves further exploration. Excitingly, Stx-based therapeutic protein has entered clinical trials, which will pave the way for broader biomedical applications of toxin-based therapeutics and tools.The  O104:H4 . This st


This study examined relationships between COVID-19 exposure and intergenerational support patterns. The data was from the 2020 Health and Retirement Study (HRS) COVID-19 Module (N=3266). The latent class analysis (LCA) was used to identify the types of intergenerational support based on respondents’ reports on whether they provided and received financial and instrumental support from either coresident children or non-coresident children. Two classes were identified, namely, the high interaction group and the low interaction group. Logistic regression showed that respondents who had COVID-19 and had increased spending as a result of COVID-19 were more likely to be in the high interaction group. Other types of COVID-19 exposure, i.e., knowing someone being diagnosed or knowing someone who died from COVID-19 were not significant.


O-monohydroxypropyl-β-cyclodextrin (HPBCD) were investigated. Molecular dynamics simulations (MD) with GLYCAM-06 and AMBER force fields were used to simulate the inclusion complex systems under storage temperature (4 °C) in an aqueous solution. The simulation results suggested that HPBCD is the best encapsulation agent to produce stable host–guest binding with plumbagin. Moreover, the observation of the plumbagin dynamic inside the binding cavity revealed that it tends to orient the methyl group toward the wider rim of HPBCD. Therefore, HPBCD is a decent candidate for the preservation of plumbagin with a promising longer storage life and presents the opportunity to facilitate the slow-release mechanism.Stable encapsulation of medically active compounds can lead to longer storage life and facilitate the slow-release mechanism. In this work, the dynamic and molecular interactions between plumbagin molecule with β-cyclodextrin (BCD) and its two derivatives, which are dimethyl-β-cyclodextrin (MBCD), and 2- Plumbagin, or 2-methyljuglone, is an essential plant-based naphthoquinone that has been extensively used as a medicinal compound in Asian countries . It exhiO-monohydroxypropyl-β-cyclodextrin (HPBCD), which have been reported to substantially improve the solubility of the inclusion complex . I. I12]. IWe performed molecular dynamics simulations of plumbagin–BCDs inclusion complexes, using the AMBER20 program package  for the The system energies were extracted from MD trajectories for observation of inclusion complexes equilibration process. All-atom RMSDs of plumbagin and BCDs throughout simulations, with structure after heating to storage temperature as reference, were used to monitor the structural stability. In addition, the distance between the center of mass of plumbagin and BCDs were collected to fully investigate the dynamic behavior of plumbagin inside encapsulated cavities. However, the substituted functional groups of two BCD derivatives were not included in the center of mass calculation. The reason is that the large dynamic motion of methyl groups in MBCD and single hydroxypropyl in HPBCD could lead to asymmetrical BCDs structure.E) between host–guest complex and individual free-forms is calculated based on the free energy of three states as follows: free-guest (GE), free-host (HE), and inclusion complex (H/GE).One of the well-known methods for the estimation of binding energy between small ligand and biological macromolecules with economical time is molecular mechanics–generalized born surface area continuum solvation (MM/GBSA) . In thisε = 1). The molecule is surrounded by a solvent of a high dielectric constant (ε = 80). The GB model approximates electrostatic energy (gbE) by a formula as shown below:The generalized born (GB) model in AMBER uses a sphere to represent each atom in a molecule; additionally, the interior of the atom is assumed to be uniformly filled with a material of low dielectric constant (npolE) is proportional to the total solvent accessible surface area (SA) of the molecule with a constant derived from experimental solvation energies of small non-polar molecules. Then, a fast LCPO algorithm [The nonpolar energy (lgorithm  is used vdwE) and electrostatic (ΔeleE) energies contributed to the average interaction energy in gas phase (ΔgasG), which was calculated according to the same force fields used in MD simulations. Second, the electrostatic (ΔgbE) and nonpolar (ΔnpolE) energies contributed to solvation-free energy in the implicit aqueous phase (ΔsolG), which were calculated by using the algorithms mentioned above. Thus, the summation between average interaction energy and solvation-free energy is the total energy difference , as follows:The energies difference term can be categorized into four energetic contributions from two phases. First, the van der Waals (ΔTΔS) upon complexation of host and guest molecules at simulated temperature is taken into account to compute the binding energy (Δbind(MM/GBSA)G). The entropy calculation has been performed by quasi-harmonic entropy approximation, as follows:Lastly, the entropy change (MD simulations of plumbagin–BCDs inclusion complexes under storage temperature (4 °C) revealed that the encapsulation of plumbagin with HPBCD was the most efficient, while MBCD could not produce stable encapsulation. BCD can encapsulate plumbagin inside its inner cavity for some period of time, but its structural distortion also triggers the release of plumbagin similar to MBCD. In addition, the sustained hydrogen bonding between plumbagin molecule inside HPBCD cavity as conformation I tend to promote the superior ability of plumbagin encapsulation. The single hydroxypropyl chain attached to the wider rim of HPBCD may also play an important role to facilitate the binding with plumbagin through weak hydrogen bonding. Therefore, we are convinced that HPBCD should be one of the good candidates as an encapsulation agent for plumbagin, which could support the longer storage life and slow-release mechanism.


Background: Few studies have been published about specialty-specific fourth-year medical student leadership in any discipline. This paper provides insight from pediatric educators about the current status and recommendations for pediatric-specific fourth-year leaders. Objective: To identify the prevalence of pediatric fourth-year medical student directors across the US and Canada and to compare current and ideal responsibilities for this role. Methods: Five multi-part questions were written and submitted for the 2019 Council on Medical Student Education in Pediatrics (COMSEP) Annual Survey and subsequently disseminated to all COMSEP member physicians. Anonymous responses were collected and results analyzed. The study was IRB exempt. Results: The program-level survey response rate was 79%. Of 115 respondent medical schools, 37% reported having a pediatric fourth-year director separate from the clerkship director, with an average of 9.8% full-time equivalent (FTE) protected time for the role. In contrast, individuals indicated 20% FTE would be ideal for fourth-year director responsibilities. The most common role identified for pediatric fourth-year directors was directing sub-internships. Respondents indicated it would be ideal for pediatric fourth-year directors to have an increased level of involvement in all areas queried in the survey, especially directing a pediatric residency preparatory course/boot camp, faculty development for educators of fourth-year students, and remediating fourth-year students. Conclusions: As specialty-specific experiences have grown in the fourth year of medical school, there is an increasing demand for faculty leadership separate from direction of the pediatric clerkship. In this national survey, pediatric educators expressed a need for additional protected time to lead fourth-year specific activities. Similar findings in other disciplines would support advocating for more protected time and expanded roles for specialty-specific fourth-year directors nationally. For the purposes of this study, the term ‘fourth year’ refers to the post-clerkship phase of medical school, and ‘specialty-specific fourth-year director’ refers to a leader of the fourth-year medical student program within a specialty .Although formal recommendations have been made about fourth-year curricular content , no publSurvey questions regarding the leadership of the pediatric fourth year were included in the 2019 Council on Medical Student Education in Pediatrics (COMSEP) Annual survey, a survey addressing specific areas of interest to the pediatric education community. We drafted five survey questions based on input from a multi-institutional group of pediatric fourth-year directors on the Curriculum Task Force of COMSEP and then revised them iteratively based on expert review and pilot testing at the authors’ institutions. The COMSEP Annual Survey Committee selected the submitted questions as part of a competitive process, provided blinded peer feedback, and performed additional pilot testing. The study was deemed exempt by the IRB at the University of Vermont.currentamount of protected time available and current roles of the position . Additional questions asked about the ideal amount of protected time for directing the pediatric fourthyear and the ideal roles for the position .Survey questions (shown in Appendix A) included whether a program had a pediatric fourth-year director separate from the clerkship director, and if so, the Demographic data was also collected and linked to the survey data by unique identifiers. COMSEP disseminated the survey by email to all COMSEP member physicians in March 2019 via a personalized link.We used descriptive statistics to analyze the data, including the mean protected time for the position and the frequency of different roles for the position, both current and ideal. To determine the degree of involvement of different roles, we combined ‘mostly’ and ‘completely’ responsible answers for each role and categorized this as ‘High Level of Responsibility’ see . We deteideal mean protected FTE for the role was 20% (median/mode 20%/range 0–74).The 2019 COMSEP Annual Survey was sent to 455 COMSEP member physicians from 146 medical schools. One hundred seventy-two respondents representing 115 unique medical schools (109 from United States/6 from Canada) completed the survey, for a program-level response rate of 79%. Of programs responding, 37% reported having a dedicated pediatric fourth-year director separate from the clerkship director and 63% did not. The mean protected FTE for this role at programs with a dedicated director was 9.8% (mean/mode 10%/range 0–30). In contrast, respondents reported the Roles for fourth-year directors varied greatly . For proThere were 35/115 programs with multiple respondents; the responses were prioritized and one response per program used for data analysis. The remaining repsonses for each program were analyzed for discordance; 12 of these programs had discordant responses regarding the presence of a fourth-year director and 7 regarding current roles, while 11 programs had responses about current FTE that differed by more than 5%.In our study, pediatric educators noted that ideally there would be increased protected time for fourth-year director duties and increased involvement for this role in all areas, particularly in directing a residency preparatory course for graduating students, remediating struggling students, and providing faculty development for others involved in post-clerkship medical student education. These findings are not surprising given the many student needs and programmatic challenges that have been described in the literature about this final phase of medical school training.The fourth year of medical school remains a controversial curricular challenge for medical educators  whose chThe literature also supports the idea that fourth-year directors with specialty-specific expertise are essential in advising students. In a training environment that is becoming increasingly competitive and unpredictable in the wake of the COVID-19 pandemic, it is imperative that institutions identify specialty-specific fourth-year directors who are able to provide a holistic approach to navigating the residency application process . AdvisinThe provision of specialty-specific residency preparedness training for graduating students is another essential role for fourth-year directors that has been recognized in the literature. The AAMC core entrustable professional activies (EPAs) provide a scaffolding of achievable skills for trainees and program directors to reference when determining overall preparedness for residency , and stuThis study has limitations typical of a survey-based design, including sampling bias. Also, in order to establish program-level data, responses were prioritized through a consensus-driven systematic method, but there were discordant responses within some programs, likely related to variability of awareness of the current status of fourth-year leadership. Similar studies in other disciplines would support advocating for protected time for specialty-specific fourth-year leadership, and this oversight may prove beneficial for a successful UME to GME transition.


Juvenile idiopathic arthritis associated uveitis (JIA-U) is the most common extra-articular manifestation of juvenile idiopathic arthritis (JIA) and carries considerable risk to vision. The aim of this systematic review was to synthesise evidence of environmental risk factors for JIA-U and identify risk factors which may be modifiable or used to stratify JIA patients.This systematic review was carried out in accordance with PRISMA guidelines. Four online databases - Cumulative Index of Nursing and Allied Health Literature, Web of Science, MEDLINE and Embase - were searched from database inception to 12th August 2020. Identified studies were screened by two independent reviewers against pre-defined inclusion and exclusion criteria. Data was extracted from all primary studies meeting inclusion criteria and independently checked.We identified three studies from 895 unique records which met the inclusion criteria, each examining a different environmental risk factor. This systematic review includes 973, predominantly female, participants with JIA across these three studies. The use of allergy medication or documentation of “allergy”/“allergic” in the medical records was associated with an increased risk of JIA-U in all models presented. Vitamin D sufficiency was associated with reduced risk of JIA-U. There was insufficient evidence to support an association between seasonality and JIA-U.This review identifies a potential role for allergy and vitamin D in JIA-U. It also illustrates the paucity of data regarding environmental risk factors for JIA-U and highlights the need for further research to both identify additional risk factors and replicate existing findings. Juvenile idiopathic arthritis (JIA) is the most common rheumatic condition of childhood and juvenile idiopathic arthritis associated uveitis (JIA-U) is the most common associated extra-articular manifestation. The estimated prevalence of JIA-U in JIA patients is 11–38% . HoweverJIA-U is considered to be a heterogenous disease, driven by both genetic and environmental factors. There has been increasing literature regarding genetic influences on JIA-U susceptibility  and the https://www.crd.york.ac.uk/prospero/display_record.php? RecordID = 78,306.This study follows guidance from the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement . The proLiterature searching of online bibliographic databases were carried out in order to identify literature on environmental risk factors associated with JIA-U. Expert advice from a database searching specialist was sought prior to designing the search strategy. Each search was carried out in four databases; MEDLINE and Embase via Ovid, Web of Science (WOS) via Clarivate Analytics and Cumulative Index of Nursing and Allied Health Literature (CINAHL) via EBSCOhost. Searches included literature from database inception until 12th August 2020. Table References (including abstracts where available) were downloaded into Endnote X9  and duplicates were removed. All unique references were uploaded to Rayyan  and undeFirst authorStudy titleYear of publicationStudy countryParticipant demographic characteristicsSample sizeDiagnostic criteria usedLength of follow-upOutcomesEvent rates for unexposed/exposed cases and controlsRisk factors listed in univariate and multivariate analysesCovariates adjusted for in analysisSource of risk factor ascertainmentJIA and JIA-U subtypes includedNewcastle-Ottawa scale scoresA data extraction form was created and piloted in Microsoft Excel by SC and KM. Data was extracted from each eligible study by SC and independently checked by KM/HC. Data extraction consisted of:For consistency between studies, the extracted sample size was the sample size of the largest analysis undertaken within a study. All data is presented as odds ratio and 95% confidence intervals where possible.The methodological quality and risk of bias of included studies was assessed using the Newcastle-Ottawa Scale (NOS) for case-control and cohort studies . StudiesNone of the included studies examined overlapping risk factors, thus there was no data suitable for the quantitative meta-analysis. Therefore, as specified in our protocol, the data within this systematic review is synthesised in narrative form. The principal summary measure for this systematic review is unadjusted and adjusted odds ratio. Where this was not reported by a study, or was not possible to derive from the raw data presented within a study, we used the study reported summary measure for data synthesis.Searches of CINAHL, Embase, MEDLINE and WOS on 12th August 2020 identified 1314 JIA-U studies. After collation, 419 studies were identified as duplicates by Endnote X9. The majority of studies were excluded during title and abstract screening. In total, 67 studies were assessed in full and of these, three studies met the inclusion criteria listed in Table The characteristics of the three included studies are shown in Table The NOS score of the included studies ranged from five to seven, with the full breakdown of NOS scores shown in Table p value was > 0.05 , providing insufficient evidence to support an association between seasonality and JIA.Three environmental risk factors from three studies were examined – seasonality, allergy and vitamin D, see Table Both allergy and vitamin D were examined in an adjusted model. Cole et al  reportedThe literature search strategy was designed to capture environmental risk factors for JIA-U in the broadest sense and identify all relevant literature regarding JIA-U risk. Nevertheless, the identification of only three studies highlights the unmet research need in this area., but was not reported in the study by Cole et al. The natural history of JIA-U suggests that 90% of JIA patients develop JIA-U within the first 4 years after JIA diagnosis [The demographic characteristics of the included studies illustrate that they are representative of the JIA community; JIA-U is reported to be more common in younger, female JIA patients as is seen here. The NOS scores of the studies suggest the studies are of generally of good quality. However, all studies lost points for failing to meet adequate follow-up; length of follow up was reported to be 3 years by Sengler et al and a minimum of 2 years by Zulian et aliagnosis , 17. ThuJIA-U is generally considered to be a complex disease, influenced by both genetic and environmental risk factors. The use of broad literature search terms used in this systematic review captured 692 de-duplicated records yet identified only three studies which met the inclusion criteria. Correspondingly we only identified three environmental risk factors which had been examined with regards to JIA-U incidence, none of which overlapped sufficiently to enable statistical comparison. Whilst the primary limitation to performing meta-analysis was lack of replicated risk factors, it should be noted that the included studies used different criteria to ascertain JIA cohorts and define JIA-U status. A number of different criteria have been defined and amended to diagnose JIA over the past 50 years  alongsidMycoplasma pneumoniae [p-value > 0.05) and Sengler et al [There is increasing recognition of the seasonal variation in both the incidence and disease activity of a number of autoimmune diseases. However, the influence of seasonality on autoimmunity is likely complex and multifactorial. Seasonal variation is observed with a number of factors such as infections, ultraviolet light exposure, vitamin D and melatonin . Winter eumoniae  and lateeumoniae . Seasonaeumoniae . In addieumoniae , which peumoniae  though eeumoniae . Whilst eumoniae  found auer et al  reportedTraditionally allergy and autoimmunity were felt to represent different facets of a perturbed immune system under the Th1/Th2 paradigm – with autoimmune diseases presenting in those with a more T helper cell type 1 (Th1) predisposition and allergies presenting in those with a more T helper cell type 2 (Th2) predisposition , 28. HowThe reasons for the high incidence of uveitis in patients with JIA are poorly understood. Whilst identification and examination of the environmental risk factors overlapping JIA and JIA-U is outside of the scope of this study, a recent review of environmental determinants of JIA  reportedThe main strength of this systematic review is its methodology, which was carried out in accordance with PRISMA guidelines  with theWhilst JIA-U is considered a complex disease influenced by genetics and the environment, this systematic review identified a very limited number of studies investigating environmental risk factors and their association with JIA-U incidence, thus illustrating a paucity of research in this area. The data available suggest an association between JIA-U and vitamin D, and JIA-U and allergy/allergy medications however these results must be interpreted with caution as they represent the output of single studies. Further studies are needed to strengthen the evidence of these associations and explore their contexts.A co-ordinated and collaborative effort is needed to identify JIA patient cohorts that not only have sufficient ophthalmic follow-up data over a prolonged period to accurately discern JIA-U case status, but that can also analyse putative patient risk factors whilst accounting for potential confounding. International partnerships are likely to be required to generate enough studies to enable meta-analysis of supposed JIA-U risk factors. Undertaking such work to detect JIA patients with modifiable JIA-U risk factors or identify those who may be at particularly increased risk compared to the current accepted JIA-U risk profile would be of considerable benefit to patients and allow more efficient use of health resources for screening.


We present a rare challenging case of metastatic non-small cell lung cancer with Epstein-Barr virus positivity that was also diagnosed with pulmonary tuberculosis at the same time. Palliative chemotherapy gemcitabine and carboplatin was started after two weeks of anti-tuberculosis treatment with the hopes that this period would be sufficient to keep acid fast bacilli non-viable to minimise risk of tuberculosis re-activation due to chemotherapy induced immunosuppression. She completed four cycles of chemotherapy and six months of anti-tuberculosis treatment with good results and minimal side effects. Two years later, there was disease recurrence in cervical and mediastinal lymph nodes which was treated with local treatment i.e. surgery and palliative radiotherapy. It has been two years since last radiotherapy and overall more than five years since diagnosis with no active disease at present. Given the complexity and rarity of this case, significant multidisciplinary team involvement, including oncologists and radiation oncologists, pulmonologists with special interest in tuberculosis and pathologists was necessary throughout. The possible aetiology link of EBV with development of lung cancer remains controversial. There are a few laboratory-based studies postulating the possible link of EBV with non-small cell lung cancer (NSCLC) however other studies did not find any causative link, 4. In addition, there are numerous studies conducted on the role of tuberculosis (TB) and lung cancer as chronic inflammation and fibrotic changes related to TB can lead to genetic mutations and alterations.The Epstein-Barr virus (EBV) is associated with a variety of lymphoproliferative and neoplastic diseasesEGFR) and anaplastic lymphoma kinase (ALK) mutations negative. Endobronchial biopsy also showed caseating granulomas indicating active mycobacterium TB infection. She was started promptly on anti-TB medications and was referred for anti-cancer management.A 49-year-old woman presented with 6-months history of weight loss and intermittent cough which did not respond to antibiotics or inhalers. She never experienced haemoptysis. Diagnostic workup led to diagnosis of T4N3M1b squamous cell carcinoma (SCC), epidermal growth factor receptor  disation . There wShe tolerated her TB treatment remarkably well despite it being in conjunction with chemotherapy. Thrombocytopenia was the only chemotherapy related side effect she experienced in her last two cycles requiring platelet transfusions.Twenty five months after, there was recurrence in right supraclavicular fossa (treated with neck dissection) and paratracheal region (treated with radiotherapy 30 Gy in 10 fractions). Six months later, there was disease recurrence in her right neck which was treated with further radiotherapy. It has been more than 25 months since last radiotherapy with latest imaging showing no evidence of active disease.et al reported a study involving 127 cases of NSCLC in Taiwan population. EBV positivity was investigated using EBV-encoded RNA-1 (EBER1) transcripts by in situ hybridization and the expression of latent membrane protein-1 (LMP-1) and bcl-2 protein by immunohistochemistry. EBER1 was detected in 11 cases: 6 SCC and 5 lymphoepithelioma-like carcinoma (LEC). Five of the 6 EBV positive SCC showed diffuse but weak staining. Three of the 6 patients with the EBER-1 positive SCC were smokers. Although EBER-1 positive LEC patients were with younger age and a better 2-year survival, this difference was not observed in EBER-1 positive SCC patients. Overall, the presence of EBER-1 transcript showed no correlation with the 2-years survival rate (P > 0.05).Published in 1998, Chen et al suggested that TB related chronic inflammation and fibrosis can induce genetic mutations and alternations. Increasing rates of interleukin (IL)-17 and tumor necrosis factor alpha (TNF-α) as a result of necrosis, apoptosis or TB reactivation, will either decrease P53 activity or increase the expression of B-cell lymphoma-2 (Bcl-2), decrease Bax-T, and cause the inhibition of caspase-3 expression due to decreasing the expression of mitochondria cytochrome oxidase. There are multiple studies being conducted regarding the possible association between TB and risk of lung cancer. Liang et al performed a systematic review of 37 case-control, 4 cohort studies and a meta-analysis of risk estimates where a significant association between TB and adenocarcinoma was found but no significant associations with squamous and small cell type of lung cancer were observed.In relation to TB, Keikha et al concluded that concurrent chemotherapy and TB treatment is effective and safe for treating patients with active TB, following a restrospective study of 30 patients with different types of malignancies and active TB.Hirashima .Apart from rarity of tumour type, this case was of interest due to the unique challenge of treating a dual pathology. There was equal urgency to commence TB treatment and chemotherapy. A clinical decision had to be made with a paucity of supporting published data to inform that decision and a multidisciplinary approach, involving oncologists, radiation oncologists, pulmonologists with especial interest in TB and pathologists was required in order to achieve the best outcome. Multidisciplinary treatment is essential in lung cancer to optimise the survival and quality of life of these patientsThis case in a woman who was brought up in Hong Kong fits with above literature suggesting that this cancer is more common in the Eastern Populations. Similar to EBV driven nasopharyngeal cancer, the cancer in this case was very sensitive to both chemotherapy and radiotherapy. This diagnosis should be considered in patients with squamous lung cancer who live or have lived in the Far East particularly in the setting of unusual clinical factors such as light smoking history, lack of classical molecular abnormalities on sequencing or deep response to chemotherapy.


The ever-increasing use of magnetic particle bioconjugates (MPB) in biosensors calls for methods of comprehensive characterization of their interaction with targets. Label-free optical sensors commonly used for studying inter-molecular interactions have limited potential for MPB because of their large size and multi-component non-transparent structure. We present an easy-to-use method that requires only three 20-min express measurements to determine the key parameters for selection of optimal MPB for a biosensor: kinetic and equilibrium characteristics, and a fraction of biomolecules on the MPB surface that are capable of active targeting. The method also provides a prognostic dependence of MPB targeting efficiency upon interaction duration and sample volume. These features are possible due to joining a magnetic lateral flow assay, a highly sensitive sensor for MPB detection by the magnetic particle quantification technique, and a novel mathematical model that explicitly describes the MPB-target interactions and does not comprise parameters to be fitted additionally. The method was demonstrated by experiments on MPB targeting of cardiac troponin I and staphylococcal enterotoxin B. The validation by an independent label-free technique of spectral-correlation interferometry showed good correlation between the results obtained by both methods. The presented method can be applied to other targets for faster development and selection of MPB for affinity sensors, analytical technologies, and realization of novel concepts of MPB-based biosensing in vivo. Novel sensing systems increasingly use materials and structures based on magnetic particle bioconjugates (MPB) due to their unique properties ,4,5,6,7.To date, the most accurate and efficient tools for investigation of inter-molecular interactions and measuring their kinetic characteristics have been direct label-free optical sensors ,23,24,25Despite remarkable achievements of the label-free sensors in the studies of inter-molecular interactions such as those of antibody–antigen, ligand–receptor, lectin–carbohydrate, etc., their applicability for exploration of MPB–target interactions is confined to a few types of MPB ,42,43. THence, two major challenges for the methods of measuring the kinetic characteristics of MPB are as follows: (i) investigation of entire MPB rather than its biorecognition components; (ii) study of MPB interaction with free, non-sorbed targets.Here, we present a novel method that meets both mentioned challenges and permits accurate determination of target-binding characteristics and kinetics of MPB using as little as three rapid measurements. The method is based on the following centerpieces: (i) an original experimental setup that implements an express magnetic lateral flow (LF) assay with a highly sensitive sensor for MPB detection by the magnetic particle quantification (MPQ) technique; and (ii) a mathematical model that explicitly describes formation and evolution of MPB-target complexes and does not comprise parameters to be fitted additionally. The fast, accurate and convenient procedures for obtaining both kinetic and equilibrium constants, as well as for a prognosis of interaction dynamics have been demonstrated with MPB targeting of two non-sorbed protein macromolecules: a cardiac marker of cardiac troponin I (cTnI) and a bacterial toxin of staphylococcal enterotoxin B (SEB). The obtained characteristics have been validated with an independent label-free method of spectral-correlation interferometry, which showed good correlation of the results.The following reagents were used: mouse monoclonal antibody against cardiac troponin I, 19C7 and 16A11 clones, and troponin I-T-C complex ; mouse monoclonal antibody against staphylococcal enterotoxin B, clones S643 and S222; SEB antigen ; bicinchoninic acid (BCA) Protein Assay Kit ; (3-Aminopropyl)triethoxysilane (APTES); N-(3-Dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (EDC); Tween-20; bovine serum albumin (BSA); N-hydroxysulfosuccinimide sodium salt (sulfo-NHS); succinic anhydride ; 2-(N-morpholino) ethanesulfonic acid (MES) ; sulfuric acid; methanol; dimethylformamide . Superparamagnetic carboxyl-modified (COOH−) particles of ≈200 nm in diameter were purchased from Estapor—Merck Millipore, France . The exact particle size is indicated below according to the manufacturer documents. Sample pads and absorbent sinks/wicking pads were from Ahlstrom CytoSep, Finland; backing cards—from Lohmann, San Jose, CA, USA; nitrocellulose membrane UniSart CN95—from Sartorius Stedim Biotech GmbH, Goettingen, Germany.The magnetic particle bioconjugates were prepared by a carbodiimide method of covalent immobilization of monoclonal antibodies on carboxyl-modified magnetic particles ,46,47. BThe MPQ registration technique pioneered by Nikitin et al.  is intenThe proposed method as a tool for investigation of target recognition by magnetic nanobioconjugates is based on the rapid lateral flow format. The entire measuring procedure, including the lateral flow test, particle detection and data processing, takes 20 min. This tool is applied to investigation of MPB targeting. The targeting process can last any time on demand, e.g., we demonstrate how the method works for targeting durations from 30 min to 24 h before measurements. Importantly, each measurement still takes 20 min. The LF test is realized in the sandwich format ,51 with The sample pad of an LF strip was immersed into a target sample, which migrated along the LF strip toward the absorbent pad. The MPB quantity at the test line was then found using a pre-defined calibration dependence of the MPQ signal upon the amount of MPB trapped at the test line.The SCI method ,53 was uFirst, the microscope cover glass slip surface was carboxilated for further immobilization of biomolecules according to the protocol described in details earlier ,55. In bNext, the carboxilated sensor chips were activated by 15-min incubation in 6.4 mg/mL solution of EDC in MES buffer with further thrice washing with PBS buffer. Then, 1 mL of 25 μg/mL of SEB or cTnI antigen in PBS buffer was deposited onto the carboxylated surface of the chip and incubated for 2 h at room temperature. After that, 1 mL of 10 mg/mL BSA in PBS buffer was added and incubated for 30 min. Then the slips were washed five times in deionized water.A solution of 20 μg/mL of free (non-immobilized) antibody against either cTnI or SEB in PBS-BSA buffer was pumped along the sensor chip surface with the immobilized target for 15 min at a flow rate of 10 μL/min in the liquid handling system of SCI biosensor followed by pumping of PBS buffer. The sensograms of target binding were recorded by the SCI-biosensors in real time as temporal dependences of the biolayer thickness on the sensor chip surface. The kinetic constants of interactions were calculated using the Langmuir model.All the experiments were implemented at least three times. In graphs, each value represents an average, and error bars show standard deviations. Non-linear equations were solved by the generalized reduced gradient method.The setup  realizesMpb—magnetic particle bioconjugates, Tgt—targets, MpbTgt—MPB-target complexes. This relationship implies the following differential equation:[Tgt]—concentration of unbound target molecules; [Mpb]—concentration of MPB multiplied by fractional surface coverage; [MpbTgt]—concentration of MPB-bound target molecules. Here, the initial conditions are as follows:0[Tgt]—initial concentration of target; Mpbm—mass of magnetic particle bioconjugates added to the target sample; AN—Avogadro number; V—volume of the target-containing sample. Additionally, the following relationships are valid:N—initial quantity of target-binding biomolecules (TBB) per one MPB. The analytical solution of the Equations (2)–(7) results in the temporal dependence of concentration of MPB-target complexes:a and b represent the expressions:The model is developed to represent an analytical solution of the equation of the second order bimolecular reaction:The standard relationships between the kinetic and equilibrium constants areonk and offk) and equilibrium (DK and AK) constants of MPB interaction with target, as well as the TBB quantity per MPB (N). Remarkably, this model comprises only the parameters that either are known a priori for a particular assay  or the parameters to be determined, namely, the kinetic  and (11).One of the possible ways to use the proposed method is finding the kinetic and equilibrium constants with the minimal number of rapid and easy-to-use experiments. According to the model, we need as little as three independent measurements by LF tests. These tests differ in (i) duration of the MPB-target interaction prior the LF assay and (ii) sample volume, in which the interaction occurs. After each test, MPB captured at the TL is quantified with the MPQ, and the kinetic constants are calculated using the mathematical model described in The method has been demonstrated by determining the kinetic and equilibrium constants of interactions for two MPB types, each recognizing its own non-sorbed target (cTnI or SEB) as models. For simplicity, we describe below the experimental procedure for any one of the targets. The procedure for the other one was similar. The MPB was functionalized by a monoclonal antibody to the respective target. All the constants were determined using three LF tests as described above. For each MPB type, 12 triples of tests were analyzed. Two tests in each triple were done at the same conditions: 30-min interaction duration and sample volume of 0.3 mL and 10 mL, respectively. For the third test in each triple, the parameters varied: interaction durations—1 h, 2 h, 4 h, or 24 h; sample volumes—0.3 mL, 1 mL, and 3 mL. Therefore, the constants were determined using 12 independent measurements. It can be seen from It should be noted that the membrane pore size (5–30 µm)  consider0[Tgt], which is disenriched by 24-h incubation with MPB followed by magnetic separation. Using the calibration plot, one can find the residual concentration and calculate the concentration [MpbTgt] of target molecules bound by MPB.The proposed method can be used for assessment of the total sorbed amount and the fraction of active target-binding molecules on the surface of magnetic particle bioconjugates. At first, a calibration curve is plotted as a dependence of MPB amount captured at the test line of an LF strip upon concentration of target in sample. Then an LF test is carried out with a solution of target of known initial concentration If the dynamic equilibrium is achieved, one may use the already obtained equilibrium constants  to calcu3 pieces per MPB. Meanwhile, the traditional techniques either do not allow estimating the portion of active-binding molecules or require for this purpose additional labor-intensive and costly procedures. In contrast, the proposed method provides an accurate and cost-efficient LF-based solution.The results of estimation of the sorption characteristics of MPB are shown in As can be seen in An independent validation was implemented by comparison of the kinetic and equilibrium constants obtained with both the proposed method and an optical label-free method of spectral-correlation interferometry. The SCI-based experimental setup and related experimental sensograms registered in real time are shown in The values of kinetic and equilibrium constants obtained by both methods are compared in The specificity of the presented method has been confirmed as follows. In this experimental series, a variety of non-target molecules were added to samples that contained or did not contain targets. The tested non-target molecules included human serum albumin (HSA), thyroid stimulating hormone (TSH) and prostate specific antigen as high-molecular-weight proteins; biotin and chloramphenicol as low-molecular-weight substances; a mixture of human IgG immunoglobulins. The concentrations of these substances were 10 IU/mL for TSH, 1 mg/mL for HSA, and 10 μg/mL for each other substance. The results obtained in these experiments have shown no dependence on the presence of non-target substances in the analyzed samples within the experimental error.It is important that to describe MPB behavior, almost all label-free techniques require an additional estimation of the quantity of binding sites on MPB. In contrast, the developed method investigates MPB per se and does not need such estimations. Moreover, the method represents a unique tool for measuring the number of active target-binding centers on MPB. Hence, when it is MPB-target interaction that should be studied and characterized rather than the inter-molecular interaction with target-binding biomolecules, the proposed method is preferable to label-free techniques.t of MPB-target interaction and sample volume V. To find the prognostic meaning for any arbitrary t and V, one should substitute into Equation (8) the values of kinetic constants and N obtained as described in t in the range of 30 min—24 h, and (ii) V in the range (0.1–10) mL. This figure also shows in blue color the experimentally obtained, MPQ-measured values of MPB trapped at the test line after interaction with target under respective meanings of t and V. As can be seen from the figure, the theoretical and experimental values are the same within the experimental error throughout the whole wide ranges of t and V. This fact suggests exceptional reliability of the method and verifies its suitability for accurate characterization of MPB–target interactions. Another advantage of the developed method is its capacity to provide an accurate prognostic description of MPB interaction with target and predict its dynamics. We have demonstrated this feature by determining the number of MPB-target complexes depending on duration The side-by-side comparison of the developed method with the current techniques for characterization of target binding and kinetics of particle-based bioconjugates is given in The proposed method offers a tool for multi-factor accurate characterization of interaction of magnetic particle bioconjugates with non-sorbed targets. The method is based on magnetic separation, an express magnetic lateral flow quantitative assay and a mathematical model that describes formation and evolution of MPB–target complexes and does not comprise parameters to be fitted additionally.The experimental procedure demonstrated here for cTnI and SEB as model targets needs only three user-friendly lateral flow tests to determine kinetic and equilibrium characteristics, total amount of biomolecules on the MPB surface and the fraction of which capable of active targeting. The method permits plotting a prognostic dependence of MPB targeting capacity upon a wide range of interaction durations and sample volumes. The developed method investigates MPB per se and does not need an additional estimation of the quantity of binding sites on MPB. The results were confirmed by a label-free biosensor based on the spectral-correlation interferometry.In addition, the research presents the first accurate analytical solution for determining the temporal dependence of bimolecular complexes concentration under non-zero initial concentrations of both interacting components. The experimental demonstration and validation of the method indicate its high reliability. The method can become an efficient solution for considerable acceleration of MPB selection for a wide range of applications from development of various affinity sensors to MPB-based biosensing in vivo. The research promises significant opportunities for follow-up studies, e.g., assessment of the fraction of active molecules over a wide range of experimental conditions to find optimal antibody–particle ratios. Importantly, our method, which is here demonstrated for magnetic particles, can be further extended for investigation and characterization of a wide range of other submicron particles such as gold and fluorescent ones, quantum dots, etc. For this purpose, the developed mathematical model and experimental setup can be used in combination with another, e.g., optical method of particle detection.