Miracle-dz/UniFAR-FTUs huggingface dataset:
Neighbor-enhanced diffusivity in dense, cohesive cell populations

The dispersal or mixing of cells within cellular tissue is a crucial property for diverse biological processes, ranging from morphogenesis, immune action, to tumor metastasis. With the phenomenon of ‘contact inhibition of locomotion,’ it is puzzling how cells achieve such processes within a densely packed cohesive population. Here we demonstrate that a proper degree of cell-cell adhesiveness can, intriguingly, enhance the super-diffusive nature of individual cells. We systematically characterize the migration trajectories of crawling MDA-MB-231 cell lines, while they are in several different clustering modes, including freely crawling singles, cohesive doublets of two cells, quadruplets, and confluent population on two-dimensional substrate. Following data analysis and computer simulation of a simple cellular Potts model, which faithfully recapitulated all key experimental observations such as enhanced diffusivity as well as periodic rotation of cell-doublets and cell-quadruplets with mixing events, we found that proper combination of active self-propelling force and cell-cell adhesion is sufficient for generating the observed phenomena. Additionally, we found that tuning parameters for these two factors covers a variety of different collective dynamic states.
Correlations between hippocampal functional connectivity, structural changes, and clinical data in patients with relapsing-remitting multiple sclerosis: a case-control study using multimodal magnetic resonance imaging

Multiple sclerosis is associated with structural and functional brain alterations leading to cognitive impairments across multiple domains including attention, memory, and the speed of information processing. The hippocampus, which is a brain important structure involved in memory, undergoes microstructural changes in the early stage of multiple sclerosis. In this study, we analyzed hippocampal function and structure in patients with relapsing-remitting multiple sclerosis and explored correlations between the functional connectivity of the hippocampus to the whole brain, changes in local brain function and microstructure, and cognitive function at rest. We retrospectively analyzed data from 20 relapsing-remitting multiple sclerosis patients admitted to the Department of Neurology at the China-Japan Union Hospital of Jilin University, China, from April 2015 to November 2019. Sixteen healthy volunteers were recruited as the healthy control group. All participants were evaluated using a scale of extended disability status and the Montreal cognitive assessment within 1 week before and after head diffusion tensor imaging and functional magnetic resonance imaging. Compared with the healthy control group, the patients with relapsing-remitting multiple sclerosis had lower Montreal cognitive assessment scores and regions of simultaneously enhanced and attenuated whole-brain functional connectivity and local functional connectivity in the bilateral hippocampus. Hippocampal diffusion tensor imaging data showed that, compared with the healthy control group, patients with relapsing-remitting multiple sclerosis had lower hippocampal fractional anisotropy values and higher mean diffusivity values, suggesting abnormal hippocampal structure. The left hippocampus whole-brain functional connectivity was negatively correlated with the Montreal cognitive assessment score (r = −0.698, P = 0.025), and whole-brain functional connectivity of the right hippocampus was negatively correlated with extended disability status scale score (r = −0.649, P = 0.042). The mean diffusivity value of the left hippocampus was negatively correlated with the Montreal cognitive assessment score (r = −0.729, P = 0.017) and positively correlated with the extended disability status scale score (r = 0.653, P = 0.041). The right hippocampal mean diffusivity value was positively correlated with the extended disability status scale score (r = 0.684, P = 0.029). These data suggest that the functional connectivity and presence of structural abnormalities in the hippocampus in patients with relapse-remission multiple sclerosis are correlated with the degree of cognitive function and extent of disability. This study was approved by the Ethics Committee of China-Japan Union Hospital of Jilin University, China (approval No. 201702202) on February 22, 2017.
Wilson’s Disease: An Analysis of Health Care Use and Cost Burden of Commercially Insured Adults in the United States

The economic and health care use burdens of Wilson’s disease (WD) are unknown. In this study, we aimed to quantify this health care resource use and economic burden. We performed a retrospective case‐control analysis of individuals in the Truven Health MarketScan Commercial Claims database (2007‐2017). Using propensity scores, 424 WD cases were matched 1:1 to chronic liver disease (CLD) controls without WD. Total and service‐specific parameters, expressed in monthly averages, were quantified for the 6‐month pre‐WD diagnosis versus the 12‐month period after diagnosis. Wilcoxon signed‐rank tests and McNemar tests were used to examine incremental differences in burden between cases and controls. Adjusted multivariable generalized linear regression models were used to compare health care burdens. Relative to the 6‐month pre‐WD diagnosis, the 12 months after diagnosis had more claims per patient (2.87 vs. 3.35; P < 0.0001) and increased per patient health care costs (US $2,089 vs. US $3,887; P < 0.0001). WD cases incurred US $1,908 more in total unadjusted costs compared to controls in the 12‐month postindex date monthly averages. The increase in claims was primarily due to outpatient visits (1.62 vs. 1.82) and pharmaceutical claims (1.11 vs. 1.37). Cases also had higher health care costs for inpatient admissions (US $559 vs. US $1,264), outpatient visits (US $770 vs. US $1,037), and pharmaceutical claims (US $686 vs. US $1,489). Conclusion: WD is associated with significant health care cost and use burdens driven by increased inpatient admissions, outpatient visits, and pharmaceutical claims.
Data Matching to Support Analysis of Cancer Epidemiology Among Veterans Compared With Non-Veteran Populations—An Exemplar in Brain Tumors

PURPOSE State and national cancer registries do not systematically include Veteran data, which hinders analysis of the diagnosis patterns, treatment trajectories, and clinical outcomes of Veterans compared with non-Veteran populations. This study used data matching approaches to compare cases included in the Oncology Domain of the Veterans Affairs (VA) Corporate Data Warehouse and the Ohio Cancer Incidence Surveillance System, using brain tumors as an exemplar. METHODS We used direct data matching, on the basis of protected health information (PHI) common to both databases, to compare primary brain tumors from Veterans and non-Veterans diagnosed from 2000 to 2016. Working with this matched data set, we used six data elements that did not contain PHI, to assess the feasibility of using deterministic data matching to compare Veterans and non-Veterans. RESULTS Between 2000 and 2016, 223 Veterans from Ohio had a primary brain tumor; of those, 55 (25%) were not included in Ohio Cancer Incidence Surveillance System. Direct data matching showed that Veterans experienced a greater proportion of glioblastomas (41%) compared with non-Veterans (21%). Sex did not account for this difference. Deterministic data matching within the matched data set found that 75% (126 of 168) of Veterans had exact matches for at least five of six non-PHI variables common to both databases. CONCLUSION This study indicated that direct and deterministic data matching approaches to compare brain tumors in Veterans and in non-Veterans is feasible. This approach has the potential to promote comparisons of the distribution of tumors, the impact of chemical and environmental exposures, treatment trajectories, and clinical outcomes among Veteran and non-Veteran populations with brain tumors as well as other cancers and rare diseases.
Immunomodulatory functions of TRPM7 and its implications in autoimmune diseases

An autoimmune disease is an inappropriate response to one's tissues due to a break in immune tolerance and exposure to self‐antigens. It often leads to structural and functional damage to organs and systemic disorders. To date, there are no effective interventions to prevent the progression of autoimmune diseases. Hence, there is an urgent need for new treatment targets. TRPM7 is an enzyme‐coupled, transient receptor ion channel of the subfamily M that plays a vital role in pathologic and physiologic conditions. While TRPM7 is constitutively activated under certain conditions, it can regulate cell migration, polarization, proliferation and cytokine secretion. However, a growing body of evidence highlights the critical role of TRPM7 in autoimmune diseases, including rheumatoid arthritis, multiple sclerosis and diabetes. Herein, we present (a) a review of the channel kinase properties of TRPM7 and its pharmacological properties, (b) discuss the role of TRPM7 in immune cells (neutrophils, macrophages, lymphocytes and mast cells) and its upstream immunoreactive substances, and (c) highlight TRPM7 as a potential therapeutic target for autoimmune diseases.
Assessing the fear of COVID-19 scale among health care workers in Israel: a psychometric validation study

Abstract We explored the psychometric properties of the Hebrew version of the Fear of COVID-19 (FCV-19S) scale among health care workers in a large medical center in Israel. Participants (N = 705) completed the FCV-19S scale, as well as resilience, subjective well-being, and meaning in life using validated scales. Results showed a two-factor structural model accounting for 79.33% of the total variance. Both factors were negatively associated with resilience and satisfaction with life. Results suggest the FCV-19S has good psychometric properties among health care workers and may be used to assess the effects of the pandemic in this population.
Protective effect of standardised fruit extract of Garcinia cowa Roxb. ex Choisy against ethanol induced gastric mucosal lesions in Wistar rats

Abstract Background and aim The fruit of Garcinia is a rich and valuable source of bioactive compounds and is traditionally used for treating wounds and ulcers. The present study was carried out to investigate the protective effect of chromatographically standardized fruit extract of Garcinia cowa (GCE) on ethanol-induced gastric lesions in rats and its possible mechanisms. Methods The effect of GCE (200 and 400 mg/kg body weight) was evaluated by determining various gastric ulcer parameters like gastric wall mucus, non-protein sulfhydryls (NP-SH) content, microvascular permeability, endogenous antioxidant enzyme, and gastric histopathological study. Results and conclusions Oral administration of GCE at doses of 200 and 400 mg/kg exhibited significant (p < .01) dose-dependent inhibition of ulcer index by 18.94–44.02%, respectively. Pre-treatment of rats with GCE (400 mg/kg) significantly restored the depleted gastric wall mucus level by 34.09% and NP-SH content by 33.35% induced by ethanol administration. In addition, GCE (400 mg/kg) showed a significant decrease in microvascular permeability of Evans Blue by 47.43%, rationalizing its protective effect. Furthermore, a significant increase in oxidative enzyme levels with reduction in malondialdehyde level and elevation of superoxide dismutase (SOD) activity was observed in the GCE treated group as compared to the ulcer control group. The histopathological assessment also confirmed the protective nature of GCE. HPTLC analysis showed the presence of 0.27%, 0.11% w/w gallic acid, and amentoflavone, respectively in GCE. The content of α-mangostin and xanthochymol in the G. cowa extract sample quantified by HPLC-PDA method was 0.72 and 8.46%, respectively. The results obtained indicate that the protective effect of GCE against gastric ulcers in rats through multiple actions confirmed by the reduction of oxidative stress and restoration of adhered gastric mucus, NP-SH content, and histological architecture. KEY MESSAGES Ethanol is the most typical ulcerogenic agent and has been shown to extend the risk of ulcer in humans. Natural products are promising alternative medication for the development of new drugs to regulate gastrointestinal diseases. Garcinia cowa protects the gastric mucosa through multiple actions that include restoration of adhered gastric mucus and inhibition of lipid peroxidation.
Pediatric onset lupus nephritis in western India—is it different from the rest of the country?

Aim To determine the clinicopathological characteristics and outcomes of children diagnosed with lupus nephritis in a tertiary hospital in western Rajasthan and compare it with the data available from other parts of India. Material and methods: A retrospective review of children presenting to a tertiary care center in western Rajasthan, India, with a diagnosis of pediatric Systemic Lupus Erythematosus (p SLE), between July 2017 and July 2020 was done. Comparisons of pediatric lupus in western India to other parts of country were done. Results 19 children with SLE with Renal involvement were enrolled and followed up. The median age at presentation was 15 years (IQR-16–9.5) (73% females). 8/19 (42%) children presented with AKI, of which 62% children presented as rapidly progressive renal failure. Six (37.5%) patients required dialysis at presentation. 84.21% of children were evaluated with renal biopsy, 16 biopsies were done in 19 children, among which class II, III, and IV lupus nephritis were reported in 21%,42%, and 35% respectively(4 crescentic). Antiphospholipid antibodies were positive in 8/15(53%), children which is much higher than a reported incidence of 30% in other Indian studies. Ten patients (52%) had neurological involvement, with seizures being the most common form of presentation (60%). Seven patients (36%) developed hepatitis. We noted many uncommon presentations in the small group like Autoimmune Pancreatitis, Mononeuritis multiplex, and peripheral digital gangrene. Cyclophosphamide was used in 10 out of 19 patients for inducing remission with class 3 and 4 nephritis and MMF in 8 children. 55% patients attained remission (after completing induction), of which 4 relapsed during the follow up. Four patients were lost to follow-up. A total of 27% patients died and 10% patients developed end stage renal failure. It was seen that those who died had more cardiac and neurological involvement at presentation, higher grade of proteinuria, lower GFR, and need for dialysis at admission. Conclusion: We found a more severe form of clinical manifestation in pediatric SLE patients at the time of the first presentation in the form of severe renal and extrarenal manifestation compared to other parts of the country.
Nanosecond heme-to-heme electron transfer rates in a multiheme cytochrome nanowire reported by a spectrally unique His/Met-ligated heme

Significance Multiheme cytochromes have been identified as essential proteins for electron exchange between bacterial enzymes and redox substrates outside of the cell. In microbiology, these proteins contribute to efficient energy storage and conversion. For biotechnology, multiheme cytochromes contribute to the production of green fuels and electricity. Furthermore, these proteins inspire the design of molecular-scale electronic devices. Here, we report exceptionally high rates of heme-to-heme electron transfer in a multiheme cytochrome. We expect similarly high rates, among the highest reported for ground-state electron transfer in biology, in other multiheme cytochromes as the close-packed hemes adopt similar configurations despite very different amino acid sequences and protein folds. Proteins achieve efficient energy storage and conversion through electron transfer along a series of redox cofactors. Multiheme cytochromes are notable examples. These proteins transfer electrons over distance scales of several nanometers to >10 μm and in so doing they couple cellular metabolism with extracellular redox partners including electrodes. Here, we report pump-probe spectroscopy that provides a direct measure of the intrinsic rates of heme–heme electron transfer in this fascinating class of proteins. Our study took advantage of a spectrally unique His/Met-ligated heme introduced at a defined site within the decaheme extracellular MtrC protein of Shewanella oneidensis. We observed rates of heme-to-heme electron transfer on the order of 109 s−1 (3.7 to 4.3 Å edge-to-edge distance), in good agreement with predictions based on density functional and molecular dynamics calculations. These rates are among the highest reported for ground-state electron transfer in biology. Yet, some fall 2 to 3 orders of magnitude below the Moser–Dutton ruler because electron transfer at these short distances is through space and therefore associated with a higher tunneling barrier than the through-protein tunneling scenario that is usual at longer distances. Moreover, we show that the His/Met-ligated heme creates an electron sink that stabilizes the charge separated state on the 100-μs time scale. This feature could be exploited in future designs of multiheme cytochromes as components of versatile photosynthetic biohybrid assemblies.
Power calculation for analyses of cross‐sectional stepped‐wedge cluster randomized trials with binary outcomes via generalized estimating equations

Power calculation for stepped‐wedge cluster randomized trials (SW‐CRTs) presents unique challenges, beyond those of standard parallel cluster randomized trials, due to the need to consider temporal within cluster correlations and background period effects. To date, power calculation methods specific to SW‐CRTs have primarily been developed under a linear model. When the outcome is binary, the use of a linear model corresponds to assessing a prevalence difference; yet trial analysis often employs a nonlinear link function. We propose power calculation methods for cross‐sectional SW‐CRTs under a logistic model fitted by generalized estimating equations. Firstly, under an exchangeable correlation structure, we show the power based on a logistic model is lower than that from assuming a linear model in the absence of period effects. We then evaluate the impact of background prevalence changes over time on power. To allow the correlation among outcomes in the same cluster to change over time and with treatment status, we generalize the methods to more complex correlation structures. Our simulation studies demonstrate that the proposed power calculation methods perform well with the model‐based variance under the true correlation structure and reveal that a working independence structure can result in substantial efficiency loss, while a working exchangeable structure performs well even when the underlying correlation structure deviates from exchangeable. An extension to our methods accounts for variable cluster sizes and reveals that unequal cluster sizes have a modest impact on power. We illustrate the approaches by application to a quality of care improvement trial for acute coronary syndrome.
Arterio-Ureteral Fistula: Systematic Review of 445 Patients

Purpose: Arterio-ureteral fistula (AUF) is an uncommon diagnosis, but increasingly reported and potentially lethal. This systematic review comprehensively presents risk factors, pathophysiology, location and clinical presentation of AUF aiming to increase clinical awareness of this rare but life-threatening condition, and to put this entity into a contemporary perspective with modern diagnostic tools and treatment strategies. Materials and Methods: This review was performed according to the PRISMA (Preferred Reporting Items for a Systematic Review and Meta-Analysis of Individual Participant Data) guidelines. A literature search in PubMed® and EMBASE™ was conducted. In addition, retrieved articles were cross-referenced. Data parameters included oncologic, vascular and urological history, diagnostics, treatment, and followup, and were collected using a standard template by 2 independent reviewers. Results: A total of 245 articles with 445 patients and 470 AUFs were included. Most patients had chronic indwelling ureteral stents (80%) and history of pelvic oncology (70%). Hematuria was observed in 99% of the patients, of whom 76% presented with massive hematuria with or without previous episodes of (micro)hematuria. For diagnosis, angiography had a sensitivity of 62%. The most predominant location of AUF was at the common iliac artery ureteral crossing. AUF-specific mortality before 2000 vs after 2000 is 19% vs 7%, coinciding with increasing use of endovascular stents. Conclusions: AUF should be considered in patients with a medical history of vascular surgery, pelvic oncologic surgery, irradiation and/or chronic indwelling ureteral stents presenting with intermittent (micro)hematuria. A multidisciplinary consultation is necessary for diagnosis and treatment. The most sensitive test is angiography and the preferred initial treatment is endovascular.
Impact of Race‐Adjusted Glomerular Filtration Rate Estimation on Eligibility for Simultaneous Liver‐Kidney Transplantation

Estimated glomerular filtration rate (eGFR) is adjusted for Black race in commonly used formulas. This has potential implications for access to simultaneous liver‐kidney transplantation (SLKT) as qualifying criteria rely on eGFR. We performed a retrospective study of United Network for Organ Sharing national transplant registry data between February 28, 2002, and March 31, 2019, to evaluate the proportion of Black patients who would be reclassified as meeting SLKT criteria (as defined per current policies) if race adjustment were removed from 2 prominent eGFR equations (Modification of Diet in Renal Disease–4 [MDRD‐4] and Chronic Kidney Disease Epidemiology Collaboration [CKD‐EPI]). Of the 7937 Black patients listed for transplant during the study period, we found that 3.6% would have been reclassified as qualifying for chronic kidney disease (CKD)–related SLKT with removal of race adjustment for MDRD‐4, and 3.0% would have been reclassified with CKD‐EPI; this represented 23.7% and 18.7% increases in SLKT candidacy, respectively. Reclassification impacted women more than men (eg, 4.5% versus 3.0% by MDRD‐4; P < 0.05). In an exploratory analysis, patients meeting SLKT criteria by race‐unadjusted eGFR equations were significantly more likely to receive liver transplantation alone (LTA) compared with SLKT. Approximately 2.0% of reclassified patients required kidney transplantation within 1 year of LTA versus 0.3% of nonreclassified patients. In conclusion, race adjustment in eGFR equations may impact SLKT candidacy for 3.0% to 4.0% of Black patients listed for LTA overall. Approximately 2.0% of patients reclassified as meeting SLKT criteria require short‐term post‐LTA kidney transplantation. These data argue for developing novel algorithms for glomerular filtration rate estimation free of race to promote equity.
Nitrogen Fertilization of Soybean Affects Root Growth and Nodulation on Two Soil Types in Mississippi

ABSTRACT Greenhouse studies were conducted to evaluate the influence of nitrogen (N) sources [urea + N-(n-butyl) thiophosphoric triamide, NBPT (urease inhibitor) and polymer-coated urea (PCU)] and rates on soybean root characteristics, nodule formation, and biomass production on two soil types (silt loam and clay) commonly cropped to soybean in Mississippi. About 15% less belowground biomass was produced in clay soil than in silt loam soil directly corresponding to all other root parameters including root length, root area, root diameter, and nodule number. Pooled across N rates, N additions resulted in 19% and 52% decrease in belowground biomass and number of nodules, respectively, across soils compared to soybean receiving no N. The N rate was the most critical factor as it influenced all root growth parameters. Number of nodules were 24% greater with PCU than urea + NBPT. Nitrogen additions and clay soil negatively impacted soybean root growth, nodulation, and belowground biomass production. Abbreviations: Polymer-coated urea, PCU; N-(n-butyl) thiophosphoric triamide, NBPT