Miracle-dz/UniFAR-FTUs huggingface dataset:
Association of wound, ischemia, and foot infection clinical stage with frailty and malnutrition in chronic limb-threatening ischemia patients undergoing endovascular intervention

Objective The Wound, Ischemia, and foot Infection (WIfI) clinical stage has been thought to have a prognostic value in Chronic limb-threatening ischemia (CLTI) patients, and frailty and nutritional status appear to represent pivotal factor affecting prognosis among CLTI patients. The purpose of this study was to examine clinical factors (including frailty and nutritional status) relevant to WIfI clinical stage. Methods This retrospective study investigated 200 consecutive CLTI patients. We individually assessed WIfI clinical stage, frailty according to the Clinical Frailty Scale (CFS) score, and malnutrition according to Geriatric Nutritional Risk Index (GNRI). We then compared mortality after endovascular intervention between a WIfI stage 1, 2 group and a stage 3, 4 group, and investigated associations between baseline characteristics (including CFS and GNRI) and WIfI clinical stage. Results Among 200 patients, 123 patients (62%) showed WIfI stage 1 or 2, and the remaining 77 patients (38%) had WIfI stage 3 or 4. CFS score was significantly higher in the WIfI stage 3, 4 group [median 6.0, interquartile range (IQR) 5.5–7.0] compared with the WIfI stage 1, 2 group (median 5.0, IQR 4.0–6.0, p < 0.001), and GNRI was significantly lower in the WIfI stage 3, 4 group (median 88, IQR 80–97) than in the WIfI stage 1, 2 (median 103, IQR 94–111, p < 0.001). Forty patients (20%) died after endovascular intervention. Incidences of all-cause and cardiac deaths were higher in the WIfI stage 3, 4 group than in the WIfI stage 1, 2 group (27% vs. 15%, p = 0.047 and 12% vs. 3%, p = 0.040, respectively). Kaplan–Meier analysis showed a significantly lower survival rate in the WIfI stage 3, 4 group than in the WIfI stage 1, 2 group (p = 0.002 by log-rank test). Multivariate logistic regression analysis using relevant factors from univariate analysis showed CFS score [odds ratio (OR) 2.06, 95% confidence interval (CI) 1.41–3.13, p < 0.001), diabetes mellitus (OR 3.17, 95%CI 1.17–8.61, p = 0.023) and GNRI (OR 0.93, 95%CI 0.89–0.97, p = 0.002) significantly associated with WIfI stage 3 or 4. In addition, multivariate ordinal logistic regression analysis for WIfI clinical stage showed CFS score (OR 1.43, 95%CI 1.09–1.89, p = 0.011), diabetes mellitus (OR 1.77, 95%CI 1.26–2.54, p < 0.001), and high-sensitivity C-reactive protein (OR 1.14, 95%CI 1.02–1.28, p = 0.041) were positively associated with WIfI clinical stage, and GNRI correlated negatively with WIfI clinical stage (OR 0.95, 95%CI 0.91–0.97, p < 0.001). Conclusions These results indicate that CLTI patients with high WIfI clinical stage may be more frail and malnourished, and be associated with poor prognosis after endovascular intervention.
Diarrhea outbreak caused by coinfections of Cryptosporidium parvum subtype IIdA20G1 and rotavirus in pre-weaned dairy calves.

Diarrhea is one of the most important syndromes in neonatal calves. In industrialized nations with intensive animal farming, Cryptosporidium spp. and rotavirus are primary causes of calf diarrhea, but the role of these and other enteric pathogens is not clear in China. In November and December 2018, a diarrhea outbreak was identified in over 150 pre-weaned calves on a dairy farm in Heilongjiang Province, northeast China and approximately 60 calves died. To determine the cause of the outbreak, we analyzed 131 fecal samples collected from pre-weaned calves (0-2 months) during (n = 114) and after the outbreak (n = 17). Initially, 10 diarrheic samples during the outbreak and 10 non-diarrheic samples after the outbreak were screened for rotavirus, coronavirus, Escherichia coli K99 and Cryptosporidium parvum by using an enzymatic immunoassay (EIA). In addition, 81 other samples were tested specifically for rotavirus by EIA, and all 131 samples were analyzed for Cryptosporidium spp. , Giardia duodenalis and Enterocytozoon bieneusi by PCR. The initial EIA analysis identified C. parvum (8/10) and rotavirus (5/10) as the dominant pathogens in calves during the outbreak, while both pathogens were detected at lower frequency after the outbreak (2/10 and 1/10, respectively). Further PCR analyses indicated that the occurrence of C. parvum infections in calves was significantly higher during the outbreak (75.4%, 86/114) than after the outbreak (11.8%, 2/17; OR = 23.0), and was significantly associated with the occurrence of watery diarrhea (OR = 15.7) and high oocyst shedding intensity. All C. parvum isolates were identified as subtype IIdA20G1. Among other pathogens analyzed, the overall prevalence of rotavirus, G. duodenalis and E. bieneusi was 19.8% (20/101), 38.9% (51/131) and 42.0% (55/131) in calves, respectively, without significant differences during and after the outbreak. Among the three pathogens, only the rotavirus infection was associated with diarrhea in calves. More importantly, coinfections of C. parvum and rotavirus were significantly associated with the occurrence of watery diarrhea in calves and were seen only during the outbreak. Thus, C. parvum subtype IIdA20G1 and rotavirus appeared to be responsible for this diarrhea outbreak. Control measures should be implemented to effectively prevent the concurrent transmission of these enteric pathogens in pre-weaned dairy calves in China. This article is protected by copyright. All rights reserved.
Feasibility of Closed-Loop Insulin Delivery with a Pregnancy Specific Zone Model Predictive Control Algorithm.

OBJECTIVE Evaluating the feasibility of closed-loop insulin delivery with a zone model predictive control (zone-MPC) algorithm designed for pregnancy complicated by type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS Pregnant women with T1D from 14-32 weeks gestation already using continuous glucose monitor (CGM) augmented pump therapy were enrolled in a two-day multi-center supervised outpatient study evaluating pregnancy-specific zone-MPC based closed-loop control (CLC) with the interoperable artificial pancreas system (iAPS) running on an unlocked smartphone. Meals and activities were unrestricted. The primary outcome was the CGM percentage of time between 63-140 mg/dL compared to participants' one-week run-in period. Early (2-hour) postprandial glucose control was also evaluated. RESULTS Eleven participants completed the study (age:30.6±4.1 years, gestational age:20.7±3.5 weeks, weight:76.5±15.3 kg, HbA1c:5.6±0.5%, at enrollment). No serious adverse events occurred. Compared to the one-week run-in, there was an increased percentage of time in 63-140 mg/dL during supervised CLC (CLC:81.5%, run-in:64%, p=0.007) with less time above 140 mg/dL (CLC:16.5%, run-in:30.8%, p=0.029) and time below 63 mg/dL (CLC:2.0%, run-in:5.2%, p=0.039). There was also less time below 54 mg/dL (CLC:0.7%, run-in:1.6%, p=0.030) and above 180 mg/dL (CLC:4.9%, run-in:13.1%, p=0.032). Overnight glucose control was comparable, except for less time above 250 mg/dL (CLC:0%, run-in:3.9%, p=0.030) and lower glucose standard deviation (CLC:23.8 mg/dL, run-in:42.8 mg/dL, p=0.007) during CLC. CONCLUSION In this pilot study, use of the pregnancy-specific zone-MPC was feasible in pregnant women with T1D. Although the duration of our study was short and the number of participants was small, our findings add to the limited data available on the use of CLC systems during pregnancy.
Effects of Disability on Job Search Among Older Workers

This article examines the impact of disability and related variables (age, gender, and education level) on job search behaviours and employment outcomes. Data are from a two-wave study of 681 Australians between the ages of 45 and 65 who were not in paid employment. Regression modelling indicates that disability impedes job search at several stages of the employment process. Although is it unrelated to job search intensity, disability is negatively associated with the probability of engaging in job search, preferred weekly hours of work, and the likelihood of finding work. Gender and age are related to the probability of engaging in job search and gender is also associated with preferred hours to work. These findings indicate that older workers with a disability face multiple disadvantages when seeking employment.
Genotype-phenotype correlations in SCN8A-related epilepsy: a cohort study of Chinese children in southern China

Wereadwithgreatinterestthearticlerecentlypublishedin by Johannesen and colleagues, 1 which revealed the clear genotype-phenotype correlations between the age at seizure onset, type of epilepsy and gain-of-function (GOF) or loss-of-function (LOF) effects of SCN8A variants. The authors collected the largest cohort of individuals with SCN8A -related epilepsy from a multi-country study and found that generalized epilepsy with absence seizures is the main epilepsy phenotype of LOF variant carriers and the extent of the electrophysiological dysfunction of the GOF variants is a main determinant of the severity of the clinical phenotype in focal epilepsies. Their pharmacological data indicated that sodium channel blockers (SCBs) present a treatment option in the SCN8A -related focal epilepsy with onset in the ﬁ rst year of life. 1 We believe that this study constitutes to the understanding of SCN8A -related epilepsy. However,
Histamine H4 Receptor Expression in Triple-negative Breast Cancer: An Exploratory Study

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype. There are neither universally accepted prognostic markers nor molecular targets related to TNBC. The histamine H4 receptor (H4R) has been characterized in TNBC experimental models, demonstrating its critical role in tumor development and progression. In this study, H4R expression was compared in breast cancer subtypes and correlated with clinical features using The Cancer Genome Atlas data (Pan-Cancer Atlas). The H4R status was further evaluated by immunohistochemistry in 30 TNBC human samples in relation to clinicopathological parameters. Results indicate that H4R was downregulated in basal-like/TNBC compared with luminal A and normal breast-like tumors. The higher expression of H4R was associated with improved progression-free and overall survival outcomes in basal-like/TNBC. H4R immunoreactivity was detected in about 70% of tumors, and its expression was positively correlated with the levels in the histologically normal peritumoral tissue. High H4R expression in peritumoral tissue correlated with reduced number of lymph node involvement and unifocal TNBC, while it was associated with increased patient survival. In conclusion, the H4R might represent a potential prognostic biomarker in TNBC. Further studies in large cohorts are needed to better understand the significance of H4R in breast cancer biology:
Ca2+ signalling in interstitial cells of Cajal contributes to generation and maintenance of tone in mouse and monkey lower oesophageal sphincters

The lower oesophageal sphincter (LES) generates tone and prevents reflux of gastric contents. LES smooth muscle cells (SMCs) are relatively depolarised, facilitating activation of Cav1.2 channels to sustain contractile tone. We hypothesised that intramuscular interstitial cells of Cajal (ICC‐IM), through activation of Ca2+‐activated Cl− channels (ANO1), set membrane potentials of SMCs favourable for activation of Cav1.2 channels. In some gastrointestinal muscles, ANO1 channels in ICC‐IM are activated by Ca2+ transients, but no studies have examined Ca2+ dynamics in ICC‐IM within the LES. Immunohistochemistry and qPCR were used to determine expression of key proteins and genes in ICC‐IM and SMCs. These studies revealed that Ano1 and its gene product, ANO1, are expressed in c‐Kit+ cells (ICC‐IM) in mouse and monkey LES clasp muscles. Ca2+ signalling was imaged in situ, using mice expressing GCaMP6f specifically in ICC (Kit‐KI‐GCaMP6f). ICC‐IM exhibited spontaneous Ca2+ transients from multiple firing sites. Ca2+ transients were abolished by cyclopiazonic acid or caffeine but were unaffected by tetracaine or nifedipine. Maintenance of Ca2+ transients depended on Ca2+ influx and store reloading, as Ca2+ transient frequency was reduced in Ca2+ free solution or by Orai antagonist. Spontaneous tone of LES muscles from mouse and monkey was reduced ∼80% either by Ani9, an ANO1 antagonist or by the Cav1.2 channel antagonist nifedipine. Membrane hyperpolarisation occurred in the presence of Ani9. These data suggest that intracellular Ca2+ activates ANO1 channels in ICC‐IM in the LES. Coupling of ICC‐IM to SMCs drives depolarisation, activation of Cav1.2 channels, Ca2+ entry and contractile tone.
Pan‐cancer analysis reveals sex‐specific signatures in the tumor microenvironment

The processes of cancer initiation, progression, and response to therapy are affected by the sex of cancer patients. Immunotherapy responses largely depend on the tumor microenvironment (TME), but how sex may shape some TME features, remains unknown. Here, we analyzed immune infiltration signatures across 19 cancer types from 1771 male and 1137 female patients in The Cancer Genome Atlas to evaluate how sex may affect the tumor mutational burden (TMB), immune scores, stromal scores, tumor purity, immune cells, immune checkpoint genes, and functional pathways in the TME. Pan‐cancer analyses showed higher TMB and tumor purity scores, as well as lower immune and stromal scores in male patients as compared to female patients. Lung adenocarcinoma, lung squamous carcinoma, kidney papillary carcinoma, and head and neck squamous carcinoma showed the most significant sex biases in terms of infiltrating immune cells, immune checkpoint gene expression, and functional pathways. We further focused on lung adenocarcinoma samples in order to identify and validate sex‐specific immune cell biomarkers with prognostic potential. Overall, sex may affect the tumor microenvironment, and sex‐specific TME biomarkers may help tailor cancer immunotherapy in certain cancer types.
Relations of Metabolic Health and Obesity to Brain Aging in Young to Middle‐Aged Adults

Background We aimed to evaluate the association between metabolic health and obesity and brain health measured via magnetic resonance imaging and neurocognitive testing in community dwelling adults. Methods and Results Framingham Heart Study Third Generation Cohort members (n=2170, 46±9 years of age, 54% women) without prevalent diabetes, stroke, dementia, or other neurologic conditions were grouped by metabolic unhealthiness (≥2 criteria for metabolic syndrome) and obesity (body mass index ≥30 kg/m2): metabolically healthy (MH) nonobese, MH obese, metabolically unhealthy (MU) nonobese, and MU obese. We evaluated the relationships of these groups with brain structure (magnetic resonance imaging) and function (neurocognitive tests). In multivariable‐adjusted analyses, metabolically unhealthy individuals (MU nonobese and MU obese) had lower total cerebral brain volume compared with the MH nonobese referent group (both P<0.05). Additionally, the MU obese group had greater white matter hyperintensity volume (P=0.004), whereas no association was noted between white matter hyperintensity volume and either groups of metabolic health or obesity alone. Obese individuals had less favorable cognitive scores: MH obese had lower scores on global cognition, Logical Memory‐Delayed Recall and Similarities tests, and MU obese had lower scores on Similarities and Visual Reproductions‐Delayed tests (all P≤0.04). MU and obese groups had higher free water content and lower fractional anisotropy in several brain regions, consistent with loss of white matter integrity. Conclusions In this cross‐sectional cohort study of younger to middle‐aged adults, poor metabolic health and obesity were associated with structural and functional evidence of brain aging. Improvement in metabolic health and obesity may present opportunities to improve long‐term brain health.
No human respiratory syncytial virus but SARS‐CoV‐2 found in children under 5 years old referred to Children Medical Center in 2021, Tehran, Iran

Acute respiratory infections (ARIs) are one of the leading causes of illness and death among community members worldwide. Viral infections are the most common agents estimated to be involved in these patients. This study aimed to investigate the prevalence of human respiratory syncytial virus (hRSV) and severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) among children with ARIs. This study evaluated the presence of SARS‐CoV‐2 and hRSV in 168 throat and nasopharyngeal swab samples using real‐time RT‐PCR. All samples were collected from children under 5 years old with ARIs who attended Children's Medical Center, Tehran, Iran, and sent to the Iranian National Influenza Center with appropriate conditions in 2021. Chi‐square and Fisher's exact tests were used for comparison of the data of the prevalence of hRSV and SARS‐CoV‐2 infections among children. Of 168 patients examined, 95 (57%) were male and 73 (43%) female. Out of them, 47 (28%) cases were younger than 1 year old and 121 cases (72%) were 1–5 years old. The most common clinical manifestations of patients were cough (78%), nausea (31%), diarrhea (27%), and fever (18%). Among 168 patients, no hRSV was detected, while the SARS‐CoV‐2 genome was identified in 16 (9.5%) patients. Among 16 positive cases of SARS‐CoV‐2, 8 (50%) were under 1 year old and 8 positive cases were 1–5 years old. This study was performed at cold months of the year but due to the coronavirus disease 2019 pandemic and adherence to health protocols, school closures, and virtual classes, no cases of hRSV infections were identified.
Prophylactic scopolamine butylbromide reduced death rattle in patients in the dying phase

SOURCE CITATION van Esch HJ, van Zuylen L, Geijteman ECT, et al. Effect of prophylactic subcutaneous scopolamine butylbromide on death rattle in patients at the end of life: the SILENCE randomized clinical trial. JAMA. 2021;326:1268-76. 34609452.
Nonutility of Diagnostic Testing in Ambulatory Patients With Supraventricular Tachycardia

Background Supraventricular tachycardia (SVT) is the most common arrhythmia in the pediatric population. Patients often present to the emergency department and undergo extensive diagnostic assessment. The objective of this study is to determine the frequency of diagnostic studies obtained in such patients and to assess clinical significance of these results. Methods A retrospective study was performed from 2011 to 2018 in a single-center ED, including patients 21 years of age or younger presenting with SVT without shock. Results A total of 40 patients with 92 encounters were included for analysis. The mean age was 8.58 (±5.51) years; 55% female. A total of 67.4% underwent serologic laboratory evaluation, of which 8 (12.9%) had any abnormality. Only one was deemed clinically significant to warrant intervention. Nearly 30% of patients underwent chest radiography, with no clinically significant findings. Conclusions Patients undergoing ED management of uncomplicated SVT are likely to undergo laboratory investigation and unlikely to have abnormal studies impacting their care. Given the associated risk of false-positive studies, the discomfort to the patient and parent, and cost of these studies, routine laboratory or radiographic investigation in this population may be unwarranted.
Hereditary gynecologic tumors and precision cancer medicine

Gynecologic cancers are more often caused by genetic factors than other cancers. Genetic testing has become a promising avenue for the prevention, prognosis, and treatment of cancers. This review describes molecular features of gynecologic tumors linked to hereditary syndromes, gives an overview of the current state of clinical management, and clarifies the role of gynecology in the treatment of hereditary tumors. Typical hereditary gynecologic tumors include hereditary breast and ovarian cancer, Lynch syndrome, Peutz–Jeghers syndrome, and Cowden syndrome. Multigene panel testing, which analyzes a preselected subset of genes for genetic variants, has recently become the first‐choice test because it can provide more accurate risk assessment than a single test. Furthermore, comprehensive genomic cancer profiling enables personalized cancer treatment and aids in germline findings.
Barriers and facilitators of physical activity in adolescents with intellectual disabilities: An analysis informed by the COM‐B model

Abstract Background Adolescents with intellectual disabilities are insufficiently physically active. Where interventions have been developed and delivered, these have had limited effectiveness, and often lack a theoretical underpinning. Aim Through application of the COM‐B model, our aim is to explore the factors influencing adolescent physical activity within schools. Methods A qualitative methodology, using focus groups with students who have mild/moderate intellectual disabilities, their parents'/carers' and teachers'. The COM‐B model provided the lens through which the data were collected and analysed. Results We identified of a range of individual, interpersonal, and environmental factors influencing physical activity, across all six COM‐B constructs, within the context of the ‘school‐system’. Conclusion This is the first study to use the COM‐B model to explore school‐based physical activity behaviour, for adolescents with intellectual disabilities. Identification of such physical activity behavioural determinants can support the development of effective and sustainable interventions.
Review of disease-modifying drug trials in amyotrophic lateral sclerosis

We analysed clinical trials of pharmacological interventions on patients with amyotrophic lateral sclerosis (ALS), and compared study quality and design features. The systematic review included articles published in PubMed and trials registered in ClinicalTrials.gov. Included studies were randomised double-blind placebo-controlled clinical trials assessing a disease-modifying pharmacological intervention. Studies were excluded if primary end points were safety or dose finding. A total of 28 735 articles and 721 current trials were identified. 76 published articles and 23 ongoing trials met inclusion criteria; they referred to distinct populations comprising 22 817 participants with ALS. Most articles and all current trials had parallel group design; few articles had cross-over design. A run-in observation period was included in about 20% of published studies and ongoing trials. Primary end points included functional assessment, survival, muscle strength, respiratory function, biomarkers and composite measures. Most recent trials had only functional assessment and survival. Risk of bias was high in 23 articles, moderate in 35, low in 18. A disease modification effect was observed for 10 interventions in phase II studies, two of which were confirmed in phase III. Three confirmatory phase III studies are currently underway. The present review provides cues for the design of future trials. Functional decline and survival, as single or composite measures, stand as the reference end points. Post hoc analyses should not be performed, particularly in studies using composite end points. There is a general agreement on diagnostic criteria; but eligibility criteria must be improved. Run-in observations may be used for censoring patients but are discouraged for refining participants’ eligibility. The ALS Functional Rating Scale-Revised needs improvement for use as an ordinal measure of functional decline.