Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular Analysis of Renal Allograft Biopsies: Where Do We Stand and Where Are We Going?

A renal core biopsy for histological evaluation is the gold standard for diagnosing renal transplant pathology. However, renal biopsy interpretation is subjective and can render insufficient precision, making it difficult to apply a targeted therapeutic regimen for the individual patient. This warrants a need for additional methods assessing disease state in the renal transplant. Significant research activity has been focused on the role of molecular analysis in the diagnosis of renal allograft rejection. The identification of specific molecular expression patterns in allograft biopsies related to different types of allograft injury, could provide valuable information about the processes underlying renal transplant dysfunction and can be used for the development of molecular classifier scores, which could improve our diagnostic and prognostic ability and could guide treatment. Molecular profiling has the potential to be more precise and objective than histological evaluation and may identify injury even before it becomes visible on histology, making it possible to start treatment at the earliest time possible. Combining conventional diagnostics (histology, serology and clinical data) and molecular evaluation will most likely offer the best diagnostic approach. We believe that the use of state-of-the-art molecular analysis will have a significant impact in diagnostics after renal transplantation. In this review, we elaborate on the molecular phenotype of both acute and chronic T cell-mediated rejection and antibody-mediated rejection and discuss the additive value of molecular profiling in the setting of diagnosing renal allograft rejection and how this will improve transplant patient care.
Iterative Weighted Group Thresholding Method for Group Sparse Recovery

This article proposes a novel iterative weighted group thresholding method for group sparse recovery of signals from underdetermined linear systems. Based on an equivalent weighted group minimization problem with <inline-formula> <tex-math notation="LaTeX">$\ell _{p}^{p}$ </tex-math></inline-formula>-norm (<inline-formula> <tex-math notation="LaTeX">$0 < p \leq 1$ </tex-math></inline-formula>), we derive closed-form solutions for a subproblem with respect to some specific values of <inline-formula> <tex-math notation="LaTeX">$p$ </tex-math></inline-formula> when using the proximal gradient method. Then, we design the corresponding algorithmic framework, including stopping criterion and the method of nonmonotone line search, and prove that the solution sequence generated by the proposed algorithm converges under some mild conditions. Moreover, based on the proposed algorithm, we develop a homotopy algorithm with an adaptively updated group threshold. Extensive computational experiments on the simulated and real data show that our approach is competitive with state-of-the-art methods in terms of exact group selection, estimation accuracy, and computation time.
Parasternal Versus Apical View in Cardiac Natural Mechanical Wave Speed Measurements

Shear wave speed measurements can potentially be used to noninvasively measure myocardial stiffness to assess the myocardial function. Several studies showed the feasibility of tracking natural mechanical waves induced by aortic valve closure in the interventricular septum, but different echocardiographic views have been used. This article systematically studied the wave propagation speeds measured in a parasternal long-axis and in an apical four-chamber view in ten healthy volunteers. The apical and parasternal views are predominantly sensitive to longitudinal or transversal tissue motion, respectively, and could, therefore, theoretically measure the speed of different wave modes. We found higher propagation speeds in apical than in the parasternal view (median of 5.1 m/s versus 3.8 m/s, <inline-formula> <tex-math notation="LaTeX">${p} < {0.01}$ </tex-math></inline-formula>, <inline-formula> <tex-math notation="LaTeX">${n} = {9}$ </tex-math></inline-formula>). The results in the different views were not correlated (<inline-formula> <tex-math notation="LaTeX">${r} = {0.26}$ </tex-math></inline-formula>, <inline-formula> <tex-math notation="LaTeX">${p} = {0.49}$ </tex-math></inline-formula>) and an unexpectedly large variability among healthy volunteers was found in apical view compared with the parasternal view (3.5–8.7 versus 3.2–4.3 m/s, respectively). Complementary finite element simulations of Lamb waves in an elastic plate showed that different propagation speeds can be measured for different particle motion components when different wave modes are induced simultaneously. The <italic>in vivo</italic> results cannot be fully explained with the theory of Lamb wave modes. Nonetheless, the results suggest that the parasternal long-axis view is a more suitable candidate for clinical diagnosis due to the lower variability in wave speeds.
Discriminative Accuracy of Procalcitonin and Traditional Biomarkers in Pediatric Acute Musculoskeletal Infection

Supplemental digital content is available in the text. Objectives Septic arthritis (SA) is responsible for 20% of pediatric musculoskeletal infections (MSKI) and can have significant consequences. Early detection of SA is critical, and procalcitonin (PCT) has emerged as a promising biomarker. This study assessed the test performance of PCT and traditional biomarkers for suspected SA. Methods We conducted a prospective study at two pediatric emergency departments (ED). Data collected measured serum levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell (WBC) count, and PCT. Box and whisker plots were generated to compare the of the biomarkers by positive MSKI or a non-MSKI diagnosis. The diagnostic performance of biomarkers was examined using the area under the receiver operating characteristic curve (AUC), and optimal cut -points were identified using the Liu method. Results Procalcitonin performed reasonably well for detection of MSKI (AUC, 0.72; confidence interval [95% CI], 0.59–0.84). However, CRP and ESR performed better (AUC, 0.88 and 0.78, respectively). White blood cell count was not predictive of MSKI. Patients with a PCT value >0.1 ng/mL, ESR values >19.5 mm/h, and a temperature higher than 99.0°F were more than twice as likely to have acute MSKI. A high CRP level was most predictive of acute MSKI, and patients with levels >2.38 mg/dL were 3.5 times more likely to have acute MSKI. Conclusions Procalcitonin is a potential biomarker for the clinical differential of MSKI in the pediatric ED. Additional research is warranted to establish the optimal diagnostic level for PCT, to increase sample size, and to examine any impact on cost.
Derivation and validation of a novel severity scoring system for pneumonia at ICU admission.

BACKGROUND Severity stratification scores developed in Intensive Care Units (ICUs) are used in interventional studies to identify the most critically ill. Studies that evaluate accuracy of these scores in ICU patients admitted with pneumonia are lacking. This study aims to determine performance of severity scores as predictors of mortality in critically ill patients admitted with pneumonia. METHODS Prospective cohort study in a general ICU in Brazil. ICU severity scores (SAPS 3 and qSOFA), prognostic scores of pneumonia (CURB-65 and CRB-65), clinical and epidemiological variables in the first 6 hours of hospitalization were analyzed. RESULTS A total of 200 patients were included between August 2015 and July 2018 with a median age of 81 years (IQR 67-90) and female predominance (52%) primarily admitted from the emergency department (65%) with community acquired pneumonia (80.5%). Poor discriminative performance in predicting mortality was found with SAPS 3, CURB-65, CRB-65 and qSOFA. Multivariate regression identified variables independently associated with mortality that were used to develop a novel pneumonia specific ICU severity score (Pneumonia SHOCK score) that outperformed SAPS3, CURB-65 and CRB-65 (AUC 0.80 vs 0.74, 0.65 and 0.63, respectively). Discriminate function of the Pneumonia SHOCK score was validated in an external multi-center cohort of critically ill patients admitted with community acquired pneumonia (AUC 0.81). CONCLUSIONS We created a parsimonious score system that accurately identifies elderly and non-elderly patients with pneumonia at highest risk of ICU death. These findings are critical to accurately stratify patients with severe pneumonia in therapeutic trials that aim to reduce pneumonia mortality.
Expansion of the genetic landscape of ERLIN2‐related disorders

ERLIN2‐related disorders are rare conditions of the motor system and clinical details are limited to a small number of prior descriptions. We here presented clinical and genetic details in five individuals (four different families) where three subjects carried a common homozygous p.Asn292ArgfsX26, associated also with sensorineural hearing loss in one child. One further subject had a de novo p.Gln63Lys and one harbors the homozygous p.Val136Gly because of maternal isodisomy of chromosome 8. Overall, we expanded the clinical and genetic spectrum of ERLIN2‐related disorders and we reiterate that autosomal‐dominant transmission is a potential mode of inheritance. Future research will elucidate disease mechanisms.
Real-World Adherence and Persistence to Direct Oral Anticoagulants in Patients With Atrial Fibrillation

Supplemental Digital Content is available in the text. Background: Stroke reduction with direct oral anticoagulants (DOACs) in atrial fibrillation (AF) is dependent on adherence and persistence in the real-world setting. Individual study estimates of DOAC adherence/persistence rates have been discordant. Our aims were to characterize real-world observational evidence for DOAC adherence/persistence and evaluate associated clinical outcomes in patients with AF. Methods and Results: PubMed, EMBASE, and CINAHL were searched from inception to June 2018. Observational studies that reported real-world DOAC adherence/persistence in patients with AF were included. Study quality was assessed using the Newcastle-Ottawa Scale. Meta-analyses for pooled estimates were performed using DerSimonian and Laird random-effects models. Outcomes included DOAC mean proportion of days covered or medication possession ratio, proportion of good adherence (proportion of days covered/medication possession ratio ≥80%), persistence, DOAC versus vitamin K antagonists persistence, and clinical outcomes associated with nonadherence/nonpersistence. Forty-eight observational studies with 594 784 unique patients with AF (59% male; mean age 71 years) were included. The overall pooled mean proportion of days covered/medication possession ratio was 77% (95% CI, 75%–80%), proportion of patients with good adherence was 66% (95% CI, 63%–70%), and proportion persistent was 69% (95% CI, 65%–72%). The pooled proportion of patients with good adherence was 71% (95% CI, 64%–78%) for apixaban, 60% (95% CI, 52%–68%) for dabigatran, and 70% (95% CI, 64%–75%) for rivaroxaban. Similar patterns were found for pooled persistence by agent. The pooled persistence was higher with DOACs than vitamin K antagonists (odds ratio, 1.44 [95% CI, 1.12–.86]). DOAC nonadherence was associated with an increased risk of stroke (hazard ratio, 1.39 [95% CI, 1.06–1.81]). Conclusions: Suboptimal adherence and persistence to DOACs was common in patients with AF, with 1 in 3 patients adhering to their DOAC <80% of the time, which was associated with poor clinical outcomes in nonadherent patients. Although it is convenient that DOACs do not require laboratory monitoring, greater effort in monitoring for and interventions to prevent nonadherence may be necessary to optimize stroke prevention. Increased clinician awareness of DOAC nonadherence may help identify at-risk patients.
CancerLivER: a database of liver cancer gene expression resources and biomarkers

Abstract Liver cancer is the fourth major lethal malignancy worldwide. To understand the development and progression of liver cancer, biomedical research generated a tremendous amount of transcriptomics and disease-specific biomarker data. However, dispersed information poses pragmatic hurdles to delineate the significant markers for the disease. Hence, a dedicated resource for liver cancer is required that integrates scattered multiple formatted datasets and information regarding disease-specific biomarkers. Liver Cancer Expression Resource (CancerLivER) is a database that maintains gene expression datasets of liver cancer along with the putative biomarkers defined for the same in the literature. It manages 115 datasets that include gene-expression profiles of 9611 samples. Each of incorporated datasets was manually curated to remove any artefact; subsequently, a standard and uniform pipeline according to the specific technique is employed for their processing. Additionally, it contains comprehensive information on 594 liver cancer biomarkers which include mainly 315 gene biomarkers or signatures and 178 protein- and 46 miRNA-based biomarkers. To explore the full potential of data on liver cancer, a web-based interactive platform was developed to perform search, browsing and analyses. Analysis tools were also integrated to explore and visualize the expression patterns of desired genes among different types of samples based on individual gene, GO ontology and pathways. Furthermore, a dataset matrix download facility was provided to facilitate the users for their extensive analysis to elucidate more robust disease-specific signatures. Eventually, CancerLivER is a comprehensive resource which is highly useful for the scientific community working in the field of liver cancer.Availability: CancerLivER can be accessed on the web at https://webs.iiitd. edu.in/raghava/cancerliver.
SIF: Self-Inspirited Feature Learning for Person Re-Identification

The re-identification (ReID) task has received increasing studies in recent years and its performance has gained significant improvement. The progress mainly comes from searching for new network structures to learn person representations. However, limited efforts have been made to explore the potential performance of existing ReID networks directly by better training scheme, which leaves a large space for ReID research. In this paper, we propose a Self-Inspirited Feature Learning (SIF) method to enhance the performance of given ReID networks from the viewpoint of optimization. We design a simple adversarial learning scheme to encourage a network to learn more discriminative person representation. In our method, an auxiliary branch is added into the network only in the training stage, while the structure of the original network stays unchanged during the testing stage. In summary, SIF has three aspects of advantages: 1) it is designed under general setting; 2) it is compatible with many existing feature learning networks on the ReID task; 3) it is easy to implement and has steady performance. We evaluate the performance of SIF on three public ReID datasets: Market1501, DuckMTMC-reID, and CUHK03(both labeled and detected). The results demonstrate significant improvement in performance brought by SIF. We also apply SIF to obtain state-of-the-art results on all the three datasets. Specifically, mAP / Rank-1 accuracy are: 87.6%/95.2% (without re-rank) on Market1501, 79.4%/89.8% on DuckMTMC-reID, 77.0%/79.5% on CUHK03 (labeled) and 73.9%/76.6% on CUHK03 (detected), respectively.
Therapeutic efficacy of combined glucocorticoid, intravenous cyclophosphamide, and double-filtration plasmapheresis for skin sclerosis in diffuse systemic sclerosis

Abstract We treated skin sclerosis with triple therapy consisting of a glucocorticoid, intravenous cyclophosphamide, and double-filtration plasmapheresis. The objective of this study was to analyze its effectiveness in a case series of patients who received triple therapy. We enrolled 8 patients with diffuse cutaneous systemic sclerosis (dcSSc) who received triple therapy at our hospital from 2008 to 2016. We analyzed the mean change in the modified Rodnan skin score (mRSS), percentage of the predicted forced vital capacity (%FVC), percentage of the predicted carbon monoxide diffusing capacity (%DLCO), and serum KL-6 levels from baseline to follow-up. All patients were treated with an intermediate dose of oral prednisolone (30.6 ± 2.1 mg/day) initially. The mean cumulative dose of intravenous cyclophosphamide was 1.4 ± 0.2 g. The mean mRSS decreased significantly at follow-up compared with that at baseline (27.0 ± 3.3 vs 15.8 ± 3.5; P = .03). At the end of the treatment, the mean %FVC and %DLCO were improved moderately, although the differences were not significant. The serum KL-6 levels decreased from 578.9 ± 146.5 to 205.3 ± 43.1 U/ml (P = .02). No significant correlation was found between the change in mRSS or disease duration and the initial skin score severity. Triple therapy may improve skin sclerosis, with effectiveness equal or superior to other reported treatments. This preliminary case series demonstrates the potential of triple therapy for treating dcSSc. However, prospective studies with long-term follow-up should be performed to assess its role.
Road Safety Culture Among Car Drivers and Motorcycle Riders in Greece: Examining Influencing Factors

The aims of this study are to: 1) Compare road safety behaviours among car drivers and motorcyclists in Rhodes and Athens, 2) Examine the factors influencing road safety behaviours, focusing on community road safety culture (RSC), 3) Examine the factors influencing RSC among the two modes of transport in the two geographical areas. The study is based on a questionnaire survey, focusing on three types of road safety behaviours: aggressive driving, over speeding and driving under the influence of alcohol. Although previous research has found important differences between motorcyclists and car drivers on the two former behaviours, drivers’ and riders’ behaviours were shared within the geographical communities and significantly different across communities. The study concludes that this to a large extent can be attributed to different community RSCs, in the two areas, which was found primarily to be influenced by the perceived level of police enforcement.
Dantrolene Ameliorates Impaired Neurogenesis and Synaptogenesis in Induced Pluripotent Stem Cell Lines Derived from Patients with Alzheimer’s Disease

Background: Overactivation of ryanodine receptors and the resulting impaired calcium homeostasis contribute to Alzheimer’s disease–related pathophysiology. This study hypothesized that exposing neuronal progenitors derived from induced pluripotent stems cells of patients with Alzheimer’s disease to dantrolene will increase survival, proliferation, neurogenesis, and synaptogenesis. Methods: Induced pluripotent stem cells obtained from skin fibroblast of healthy subjects and patients with familial and sporadic Alzheimer’s disease were used. Biochemical and immunohistochemical methods were applied to determine the effects of dantrolene on the viability, proliferation, differentiation, and calcium dynamics of these cells. Results: Dantrolene promoted cell viability and proliferation in these two cell lines. Compared with the control, differentiation into basal forebrain cholinergic neurons significantly decreased by 10.7% (32.9 ± 3.6% vs. 22.2 ± 2.6%, N = 5, P = 0.004) and 9.2% (32.9 ± 3.6% vs. 23.7 ± 3.1%, N = 5, P = 0.017) in cell lines from sporadic and familial Alzheimer’s patients, respectively, which were abolished by dantrolene. Synapse density was significantly decreased in cortical neurons generated from stem cells of sporadic Alzheimer’s disease by 58.2% (237.0 ± 28.4 vs. 99.0 ± 16.6 arbitrary units, N = 4, P = 0.001) or familial Alzheimer’s disease by 52.3% (237.0 ± 28.4 vs.113.0 ± 34.9 vs. arbitrary units, N = 5, P = 0.001), which was inhibited by dantrolene in the familial cell line. Compared with the control, adenosine triphosphate (30 µM) significantly increased higher peak elevation of cytosolic calcium concentrations in the cell line from sporadic Alzheimer’s patients (84.1 ± 27.0% vs. 140.4 ± 40.2%, N = 5, P = 0.049), which was abolished by the pretreatment of dantrolene. Dantrolene inhibited the decrease of lysosomal vacuolar-type H+-ATPase and the impairment of autophagy activity in these two cell lines from Alzheimer’s disease patients. Conclusions: Dantrolene ameliorated the impairment of neurogenesis and synaptogenesis, in association with restoring intracellular Ca2+ homeostasis and physiologic autophagy, cell survival, and proliferation in induced pluripotent stem cells and their derived neurons from sporadic and familial Alzheimer’s disease patients. Survival, proliferation, and differentiation of neuronal progenitors derived from patients with Alzheimer’s disease are impaired when compared with healthy counterparts. Chronic exposure of induced pluripotent stem cells, derived from patients with Alzheimer’s disease, to dantrolene improves the survival, proliferation, and differentiation of these cells. Supplemental Digital Content is available in the text.
Simulation of Flow over a Cavity Using Multi-Relaxation Time Thermal Lattice Boltzmann Method

This article provides numerically study of the multi-relaxation time thermal lattice Boltzmann method (LBM) for compute the flow and isotherm characteristics in the bottom heated cavity located o n a floor of horizontal channel . A double-distribution function (DFF) was coupled with MRT thermal LBM to study the effects of various grashof number (Gr), Reynolds number (Re) and Aspect Ratio (AR) on the flow and isotherm characteristic. The results we re compared with the conventional single-relaxation time lattice Boltzmann scheme and benchmark solution for such flow configuration. The results of the numer ical simulation indicate that multi-relaxation time thermal lattice Boltzmann scheme demonstrated good agreement, which supports its validity in computing fluid flow problem.
ALK and ROS1 rearrangement tested by ARMS‐PCR in non‐small‐cell lung cancer patients via cytology specimens: The experience of Shanghai Pulmonary Hospital

Cytology specimens are the main samples used for the diagnosis of advanced lung cancer. The objective of our study was to assess anaplastic lymphoma kinase (ALK) and c‐ros oncogene 1 receptor tyrosine kinase (ROS1) genes by an amplification refractory mutation system (ARMS)‐polymerase chain reaction (PCR) using cytology specimens and to then evaluate the mutation frequency of ALK and ROS1 in non‐small‐cell lung cancer (NSCLC) patients.
Can a Digital Awareness Campaign Change Knowledge and Beliefs Regarding Cochlear Implants? A Study in Older Adults in 5 European Countries

There are 466 million people living with a disabling hearing loss and the challenges of managing this public health crisis cannot be underestimated. Yet, adult utilization of cochlear implants is poor with less than 10% of suitable candidates receiving one. The aim of this study was to investigate the awareness levels regarding cochlear implants in older adults after a digital campaign to raise awareness of cochlear implantation in this population. To address the lack of awareness of the cochlear implants in the general population, adverts were placed in online medical magazines and mainstream newspapers. Data were collected in 400 subjects via an online market research questionnaire, in Germany, Austria, Sweden, and the United Kingdom, and compared with baseline data collected in a previous study. Median click rates were in line with expectations for the medical industry and approximately 22 000 individuals clicked through to the cochlear implant Web site. However, there were few significant differences between the 2 sets of data. The Internet was consulted as much as the doctor for medical information in Germany, Austria, and Sweden. The study reinforces the importance of the Internet in accessing information about health, including hearing loss. The click through rates shows that there is interest in learning about cochlear implants. Further work is needed to assess the impact of this type of campaign on individuals who have already been identified as hearing impaired.