Miracle-dz/UniFAR-FTUs huggingface dataset:
Fall Risk Evaluation Tool for Acquired Brain Injury: A Validation of a Multifactorial Assessment: A Pilot Study

Objective: The purpose of this study examined the reliability and validity of FRET to predict falls in community-dwelling individuals with acquired brain injuries (ABI). Method: The target population was English speaking, community-dwelling individuals 18 years or older who have sustained an ABI. Individuals were excluded if they had neurodegenerative diseases, used a wheelchair for more than 25% of the day, or were classified as globally confused. Global confusion was assessed using the first threequestions on the Saint Louis University Mental Examination (SLUMS). A total of 12 participants were recruited for the study, two were excluded and there was one attrition. After the Fall Risk Evaluation Tool (FRET) was administered, participants were instructed to record whenever they had a fall in the following three months in the provided fall journal. Researchers made telephone calls every two weeks to remind the participants to record falls. At the end of the three months, each participant returned the fall journal by mail in a self-addressed envelope. Results: A Spearman’s Rank correlation was used to analyze the data to detect any correlation between the risk rank as determined by FRET and the fall rank determined by the number of times a participant fell. There was a positive relationship between the risk rank and the fall rank. Conclusion: There is a lack of valid and reliable multifactorial assessments to assess fall risk in individuals with ABI. FRET was developed to assess fall risk in individuals with ABI. Although we had a small sample size, our pilot study returned significant data that FRET may be a valid and reliable multifactorial tool for assessing individuals with ABI who are at risk for falling.
Periodontal disease and effects of antipsychotic medications in patients newly diagnosed with schizophrenia: a population-based retrospective cohort

Abstract Aim Compared with the general population, individuals with schizophrenia have a higher risk of periodontal disease, which can potentially reduce their life expectancy. However, evidence for the early development of periodontal disease in schizophrenia is scant. The current study investigated risk factors for periodontal disease in patients newly diagnosed with schizophrenia. Methods We identified a population-based cohort of patients in Taiwan with newly diagnosed schizophrenia who developed periodontal disease within 1 year of their schizophrenia diagnosis. Treatment with antipsychotics and other medications was categorised according to medication type and duration, and the association between medication use and the treated periodontal disease was assessed through logistic regression. Results Among 3610 patients with newly diagnosed schizophrenia, 2373 (65.7%) had an incidence of treated periodontal disease during the 1-year follow-up. Female sex (adjusted odds ratios [OR] 1.40; 95% confidence interval [CI] 1.20–1.63); young age (adjusted OR 0.99; 95% CI 0.98–0.99); a 2-year history of periodontal disease (adjusted OR 2.45; 95% CI 1.84–3.26); high income level (adjusted OR 2.24; 95% CI 1.64–3.06) and exposure to first-generation (adjusted OR 1.89; 95% CI 1.54–2.32) and secondary-generation (adjusted OR 1.33; 95% CI 1.11–1.58) antipsychotics, anticholinergics (adjusted OR 1.24; 95% CI 1.03–1.50) and antihypertensives (adjusted OR 1.91; 95% CI 1.64–2.23) were independent risk factors for periodontal disease. Hyposalivation – an adverse effect of first-generation antipsychotics (FGAs) (adjusted OR 2.00; 95% CI 1.63–2.45), anticholinergics (adjusted OR 1.27; 95% CI 1.05–1.53) and antihypertensives (adjusted OR 1.90; 95% CI 1.63–2.22) – was associated with increased risk of periodontal disease. Therefore, hypersalivation due to FGA use (adjusted OR 0.72; 95% CI 0.59–0.88) was considered a protective factor. Conclusions The current study highlights that early prevention of periodontal disease in individuals with schizophrenia is crucial. Along with paying more attention to the development of periodontal disease, assessing oral health regularly, helping with oral hygiene, and lowering consumption of sugary drinks and tobacco, emphasis should also be given by physicians to reduce the prescription of antipsychotics to the extent possible under efficacious pharmacotherapy for schizophrenia.
Prediction system for risk of allograft loss in patients receiving kidney transplants: international derivation and validation study

Abstract Objective To develop and validate an integrative system to predict long term kidney allograft failure. Design International cohort study. Setting Three cohorts including kidney transplant recipients from 10 academic medical centres from Europe and the United States. Participants Derivation cohort: 4000 consecutive kidney recipients prospectively recruited in four French centres between 2005 and 2014. Validation cohorts: 2129 kidney recipients from three centres in Europe and 1428 from three centres in North America, recruited between 2002 and 2014. Additional validation in three randomised controlled trials (NCT01079143, EudraCT 2007-003213-13, and NCT01873157). Main outcome measure Allograft failure (return to dialysis or pre-emptive retransplantation). 32 candidate prognostic factors for kidney allograft survival were assessed. Results Among the 7557 kidney transplant recipients included, 1067 (14.1%) allografts failed after a median post-transplant follow-up time of 7.12 (interquartile range 3.51-8.77) years. In the derivation cohort, eight functional, histological, and immunological prognostic factors were independently associated with allograft failure and were then combined into a risk prediction score (iBox). This score showed accurate calibration and discrimination (C index 0.81, 95% confidence interval 0.79 to 0.83). The performance of the iBox was also confirmed in the validation cohorts from Europe (C index 0.81, 0.78 to 0.84) and the US (0.80, 0.76 to 0.84). The iBox system showed accuracy when assessed at different times of evaluation post-transplant, was validated in different clinical scenarios including type of immunosuppressive regimen used and response to rejection therapy, and outperformed previous risk prediction scores as well as a risk score based solely on functional parameters including estimated glomerular filtration rate and proteinuria. Finally, the accuracy of the iBox risk score in predicting long term allograft loss was confirmed in the three randomised controlled trials. Conclusion An integrative, accurate, and readily implementable risk prediction score for kidney allograft failure has been developed, which shows generalisability across centres worldwide and common clinical scenarios. The iBox risk prediction score may help to guide monitoring of patients and further improve the design and development of a valid and early surrogate endpoint for clinical trials. Trial registration Clinicaltrials.gov NCT03474003.
Protective roles of Pyracantha fortuneana extract on acute renal toxicity induced by cadmium chloride in rats 1

Abstract Purpose: To investigate the protective roles of pyracantha fortune fruit extract (PFE) on acute renal toxicity induced by cadmium chloride (CdCl2) in rats. Methods: Rats were pretreated with PFE and consecutively injected with CdCl2 (6.5 mg/kg) for 5 days. Results: The concentration of Cd, kidney weight, malondialdehyde (MDA), and nitric oxide (NO) production were remarkably increased in CdCl2 group as well as the levels of plasma uric acid, urea, and creatinine (P < 0.001). However, the body weight and glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione peroxidase (GR) levels were markedly reduced by CdCl2 treatment (P < 0.001). Histological manifestations of renal tissue showed severely adverse changes. Moreover, CdCl2 treatment significantly decreased the B-cell lymphoma-2 (Bcl-2) expression while increased the Bcl-2-Associated X Protein (Bax), tumor necrosis factor-α (TNF-α) expression (P < 0.001). Additionally, the expression of Nrf2/Keap 1 related proteins Keap-1 gained a significant increase (P < 0.001), whereas the Nrf2, HO-1, γ-GCS, GSH-Px and NQO1 expression decreased by CdCl2 treatment (P < 0.05). These rats were pretreated with PFE to improve the changes caused by CdCl2 treatment. Conclusion: PFE could protect the kidney against acute renal toxicity induced by CdCl2.
The role of small diffusion-weighted imaging lesions in cerebral small vessel disease

Objective To investigate the prevalence of asymptomatic diffusion-weighted imaging–positive (DWI+) lesions in individuals with cerebral small vessel disease (SVD) and identify their role in the origin of SVD markers on MRI. Methods We included 503 individuals with SVD from the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Imaging Cohort (RUN DMC) study (mean age 65.6 years [SD 8.8], 56.5% male) with 1.5T MRI in 2006 and, if available, follow-up MRI in 2011 and 2015. We screened DWI scans (n = 1,152) for DWI+ lesions, assessed lesion evolution on follow-up fluid-attenuated inversion recovery, T1 and T2* images, and examined the association between DWI+ lesions and annual SVD progression (white matter hyperintensities [WMH], lacunes, microbleeds). Results We found 50 DWI+ lesions in 39 individuals on 1,152 DWI (3.4%). Individuals with DWI+ lesions were older (p = 0.025), more frequently had a history of hypertension (p = 0.021), and had a larger burden of preexisting SVD MRI markers (WMH, lacunes, microbleeds: all p < 0.001) compared to individuals without DWI+ lesions. Of the 23 DWI+ lesions with available follow-up MRI, 14 (61%) evolved into a WMH, 8 (35%) resulted in a cavity, and 1 (4%) was no longer visible. Presence of DWI+ lesions was significantly associated with annual WMH volume increase and yearly incidence of lacunes and microbleeds (all p < 0.001). Conclusion Over 3% of individuals with SVD have DWI+ lesions. Although DWI+ lesions play a role in the progression of SVD, they may not fully explain progression of SVD markers on MRI, suggesting that other factors than acute ischemia are at play.
Biotechnology and Bioengineering

Correspondence David Marchat, Mines Saint‐Etienne, Univ Lyon, Univ Jean Monnet, INSERM, U 1059 Sainbiose, Centre CIS, F‐42023 Saint‐Etienne, France. Email: marchat@emse.fr Abstract Reliably producing functional in vitro organ models, such as organ‐on‐chip systems, has the potential to considerably advance biology research, drug development time, and resource efficiency. However, despite the ongoing major progress in the field, three‐dimensional bone tissue models remain elusive. In this review, we specifically investigate the control of perfusion flow effects as the missing link between isolated culture systems and scientifically exploitable bone models and propose a roadmap toward this goal.
Elevated mutation and selection in wild emmer wheat in response to 28 years of global warming

Significance The realized threats of global warming to biodiversity have catalyzed the search for a solution to protect and conserve extant plant genetic resources. Part of the solution, however, is dependent on the knowledge of how plant populations respond genetically to these threats, which is largely lacking. We conducted a unique genomic characterization of genetic responses in 10 wild emmer wheat populations in Israel that were sampled twice in 1980 and 2008. After the 28 y of global warming, these populations displayed elevated selection, reduced diversity and temporal divergence, and carried increased mutational burdens forward. However, some populations still showed the ability to acquire beneficial alleles for future adaptation. The patterns of genetic response to rainfall and temperature were complex. Global warming has been documented to threaten wild plants with strong selection pressures, but how plant populations respond genetically to the threats remains poorly understood. We characterized the genetic responses of 10 wild emmer wheat (Triticum dicoccoides Koern.; WEW) populations in Israel, sampling them in 1980 and again in 2008, through an exome capture analysis. It was found that these WEW populations were under elevated selection, displayed reduced diversity and temporal divergence, and carried increased mutational burdens forward. However, some populations still showed the ability to acquire beneficial alleles via selection or de novo mutation for future adaptation. Grouping populations with mean annual rainfall and temperature revealed significant differences in most of the 14 genetic estimates in either sampling year or over the 28 y. The patterns of genetic response to rainfall and temperature varied and were complex. In general, temperature groups displayed more temporal differences in genetic response than rainfall groups. The highest temperature group had more deleterious single nucleotide polymorphisms (dSNPs), higher nucleotide diversity, fewer selective sweeps, lower differentiation, and lower mutational burden. The least rainfall group had more dSNPs, higher nucleotide diversity, lower differentiation and higher mutational burden. These characterized genetic responses are significant, allowing not only for better understanding of evolutionary changes in the threatened populations, but also for realistic modeling of plant population adaptability and vulnerability to global warming.
Sociodemographic and health profile of TB/HIV co-infection in Brazil: a systematic review.

OBJECTIVE to ascertain the epidemiological profile of TB/HIV co-infection in Brazilian scenarios. METHOD this is a systematic review conducted via electronic search in databases PubMed, EMBASE, LILACS and SciELO, having as inclusion criterion articles based on the Brazilian scenario of TB/HIV co-infection. RESULTS of the total 174 studies, 15 were selected, revealing the epidemiological profile of the co-infection in different scenarios: male, economically active age, low education level, brown/black ethnicity, low income, heterosexual, pulmonary clinical form, alcoholism and Directly Observed Therapy. CONCLUSION the sociodemographic and epidemiological profile of people with TB/HIV co-infection has an expected occurrence pattern, which corroborates articles found in the literature, either at national level or by grouping the studies according to region or state.
Serum Anti-NMDA (N-Methyl-D-Aspartate)-Receptor Antibodies and Long-Term Clinical Outcome After Stroke (PROSCIS-B).

Background and Purpose- NMDAR1-abs (anti-N-Methyl-D-Aspartate receptor GluN1 antibodies), predominantly known in the context of autoimmune encephalitis, have been observed in serum of healthy individuals. A previous study found smaller stroke magnetic resonance imaging lesion growth in seronegative patients, suggesting a neuroprotective effect of these antibodies. The impact of NMDAR1-abs seropositivity on long-term functional outcome and recurrent vascular events and death after first-ever stroke remains unclear. Methods- Data from the Prospective Cohort with Incident Stroke-Berlin were used. NMDAR1-abs (ie, IgM, IgA, and IgG) were measured in serum within 7 days after first stroke. Outcomes of interest included modified Rankin Scale at one year and the time-to-event of a combined end point (recurrent stroke, myocardial infarction, and all-cause mortality) within 3 years. We calculated odds ratios from adjusted partial proportional odds models and subsequently compared outcome of patients with low titers (1:10; 1:32; and 1:100), and high titers (1:320; 1:1000) to seronegative patients. Furthermore, we estimated hazard ratios for a secondary vascular event or death in NMDAR1-abs seropositive compared with patients with seronegative in models adjusted for confounders. Results- The analyses included 583 patients with antibody measurements (39% female, median National Institutes of Health Stroke Scale:2, IQR:1-4), and NMDAR1-abs were observed in 76 (13%) patients. NMDAR1-abs seroprevalence was not associated with functional outcome (odds ratio=1.27; 95% CI, 0.77-2.09); sub-group analyses, however, showed worse outcome in patients with high titers (odds ratio=3.47; 95% CI, 1.54-7.80). Seropositive patients had an increased risk for a secondary vascular event or death (hazard ratios =1.83, 95% CI, 1.10-3.05). Conclusions- In our study, NMDAR1-abs seropositivity was not associated with functional outcome at one year after stroke, however, high titers (≥1:320) were associated with poor functional outcome. Furthermore, NMDAR1-abs seropositivity was associated with increased cardiovascular risk within 3 years after first stroke, independently from other risk factors. Clinical Trial Registration- URL: https://www.clinicaltrials. gov. Unique identifier: NCT01363856.
Safe Discharge of Patients From an Ambulatory Care Center After Incidental Durotomy During Minimally Invasive Spine Surgery

ABSTRACT Background Incidental durotomy is a well-known complication of spinal surgery that may occur occasionally. Increasingly, minimally invasive techniques are being used for spinal decompressions in an ambulatory surgical center (ASC) setting. The management of this complication in an ASC setting has not been reported. Methods A total of 832 consecutive minimally invasive decompressive spinal surgeries were performed by a single surgeon in an ASC during the course of 1 year. Incidental durotomies with cerebrospinal fluid leakage were repaired and patients were discharged to home. Patients with a watertight suture dural repair did not receive any modifications to the usual discharge activities allowed. All other patients were treated with bed rest overnight and head of bed restrictions. A protocol for close patient follow-up after discharge was followed. The complications were collected prospectively and analyzed retrospectively. Results There were 30 incidental durotomies (3.6%), with all occurring in the lumbar spine. Suture repair was accomplished in 28 patients (93%). Patch repair was performed in 2 patients (7%). All patients were discharged to home from the ASC. There were 2 short-term complications noted after discharge. The patient safety protocols in place identified the complications and allowed timely interventions. Conclusions Incidental durotomy occurring during minimally invasive spinal decompressive surgery is an occasional event. Suture repair of the laceration is feasible in most instances. Lumbar spine patients may be safely discharged to home from the ASC. Patients can be stratified into those with, or without, a watertight suture dural closure. Those with such a closure, who are without symptoms of intracranial hypotension, do not require modification of their activities. A short period of bedrest with head of bed modification successfully treated the remainder. Hospitalization or routine prolonged bed rest is not necessary. Protocols must be put in place to identify and timely manage potentially serious sequelae.
Centrosomal cohesion deficits as cellular biomarker in lymphoblastoid cell lines from LRRK2 Parkinson's disease patients

Leucine-rich repeat kinase 2 (LRRK2) is a promising therapeutic target for the treatment of Parkinson's disease (PD), and orally bioavailable, brain penetrant and highly potent LRRK2 kinase inhibitors are in early stages of clinical testing. Detection of LRRK2 phosphorylation, as well as phosphorylation of Rab10, a LRRK2 kinase substrate, have been proposed as target engagement biomarkers for LRRK2 inhibitor clinical trials. However, these readouts do not seem able to stratify patients based on enhanced LRRK2 kinase activity. Here, we describe a robust cell biological assay based on centrosomal cohesion alterations which were observed in peripheral blood mononuclear cell-derived lymphoblastoid cell lines (LCLs) from patients with G2019S LRRK2 mutations as compared with healthy controls, and could also be detected in a subset of sporadic PD patient samples. We suggest that LCLs may be a valuable resource for LRRK2 research, and that determination of centrosomal cohesion deficits may assist in the stratification of a subset of sporadic PD patients.
PTPN1/2-mediated dephosphorylation of MITA/STING promotes its 20S proteasomal degradation and attenuates innate antiviral response

Significance MITA/STING is an essential adaptor protein for innate immune response to DNA virus or damaged cellular DNA. In this study, we identified 2 protein phosphatases, PTPN1 and PTPN2, as negative regulators of MITA/STING. After the onset of innate immune response to DNA virus, PTPN1/2 dephosphorylate MITA/STING, which subsequently causes its degradation by the ubiquitin-independent 20S proteasomes. This study reveals a striking mechanism on how innate immune response to DNA virus is attenuated and therefore would help for drug or vaccine development against DNA virus infection. Upon cytosolic viral DNA stimulation, cGMP-AMP synthase (cGAS) catalyzes synthesis of 2′3′cGMP-AMP (cGAMP), which binds to the adaptor protein MITA (mediator of IRF3 activation, also called STING, stimulator of IFN genes) and induces innate antiviral response. How the activity of MITA/STING is regulated to avoid excessive innate immune response is not fully understood. Here we identified the tyrosine-protein phosphatase nonreceptor type (PTPN) 1 and 2 as MITA/STING-associated proteins. PTPN1 and PTPN2 are associated with MITA/STING following viral infection and dephosphorylate MITA/STING at Y245. Dephosphorylation of MITA/STING leads to its degradation via the ubiquitin-independent 20S proteasomal pathway, which is dependent on the intrinsically disordered region (IDR) of MITA/STING. Deficiencies of PTPN1 and PTPN2 enhance viral DNA-induced transcription of downstream antiviral genes and innate antiviral response. Our findings reveal that PTPN1/2-mediated dephosphorylation of MITA/STING and its degradation by the 20S proteasomal pathway is an important regulatory mechanism of innate immune response to DNA virus.