Miracle-dz/UniFAR-FTUs huggingface dataset:
Frailty in COPD: an analysis of prevalence and clinical impact using UK Biobank

Background Frailty, a state of reduced physiological reserve, is common in people with chronic obstructive pulmonary disease (COPD). Frailty can occur at any age; however, the implications in younger people (eg, aged <65 years) with COPD are unclear. We assessed the prevalence of frailty in UK Biobank participants with COPD; explored relationships between frailty and forced expiratory volume in 1 second (FEV1) and quantified the association between frailty and adverse outcomes. Methods UK Biobank participants (n=3132, recruited 2006–2010) with COPD aged 40–70 years were analysed comparing two frailty measures (frailty phenotype and frailty index) at baseline. Relationship with FEV1 was assessed for each measure. Outcomes were mortality, major adverse cardiovascular event (MACE), all-cause hospitalisation, hospitalisation with COPD exacerbation and community COPD exacerbation over 8 years of follow-up. Results Frailty was common by both definitions (17% frail using frailty phenotype, 28% moderate and 4% severely frail using frailty index). The frailty phenotype, but not the frailty index, was associated with lower FEV1. Frailty phenotype (frail vs robust) was associated with mortality (HR 2.33; 95% CI 1.84 to 2.96), MACE (2.73; 1.66 to 4.49), hospitalisation (incidence rate ratio 3.39; 2.77 to 4.14) hospitalised exacerbation (5.19; 3.80 to 7.09) and community exacerbation (2.15; 1.81 to 2.54), as was frailty index (severe vs robust) (mortality (2.65; 95% CI 1.75 to 4.02), MACE (6.76; 2.68 to 17.04), hospitalisation (3.69; 2.52 to 5.42), hospitalised exacerbation (4.26; 2.37 to 7.68) and community exacerbation (2.39; 1.74 to 3.28)). These relationships were similar before and after adjustment for FEV1. Conclusion Frailty, regardless of age or measure, identifies people with COPD at risk of adverse clinical outcomes. Frailty assessment may aid risk stratification and guide-targeted intervention in COPD and should not be limited to people aged >65 years.
Efficacy of Isothermic Conditioning over Military-Based Heat Acclimatization and Interval Training in Tropical Native Males

ABSTRACT Purpose We compared the effectiveness of three field-based training programs, namely military-based heat acclimatization (MHA), isothermic conditioning (IC) and interval training (IT), in inducing physiological adaptations in tropical natives. Methods Fifty-one untrained tropical native males (mean ± standard deviation: age, 25 ± 2 yr; body mass index, 23.6 ± 3.2 kg·m−2; body fat, 19% ± 5%; 2.4-km run time, 13.2 ± 0.9 min) donned the Full Battle Order attire (22 kg) and performed a treadmill route march heat stress test in an environmental chamber (dry bulb temperature, 29.9°C ± 0.5°C; relative humidity, 70% ± 3%). Heat stress tests were conducted before (PRE) and after (POST) a 2-wk training intervention consisting of either a MHA (n = 17, 10 sessions of military-based heat acclimatization), IC (n = 17, 10 sessions with target gastrointestinal temperature (Tgi) ≥ 38.5°C) or IT (n = 17, six sessions of high-intensity interval training) program. Tgi, HR, mean weighted skin temperature (Tsk), physiological strain index (PSI) and thigh-predicted sweat sodium concentration ([Na+]) were measured and analyzed by one-factor and two-factor mixed design ANOVA with a 0.05 level of significance. Results Field-based IC induced a greater thermal stimulus than MHA (P = 0.029) and IT (P < 0.001) during training. Reductions in mean exercise Tgi (−0.2°C [−0.3°C, 0.0°C]; P = 0.009), PSI (−0.4 [−0.7, −0.1]; P = 0.015) and thigh-predicted sweat [Na+] (−9 [−13, −5 mmol·L−1]; P < 0.001) were observed in IC but not MHA and IT (all P > 0.05). Resting HR (MHA, −4 bpm [−7, 0 bpm]; P = 0.025; IC, −7 bpm [−10, −4 bpm]; P < 0.001; IT, −4 bpm [−8, −1 bpm]; P = 0.008) and mean exercise HR (MHA, −4 [−8, 0 bpm]; P = 0.034; IC, −11 bpm [−15, −8 bpm]; P < 0.001, IT = −5 bpm [−9, −1 bpm]; P = 0.012) were lowered in all groups after training. Isothermic conditioning elicited a greater attenuation in mean exercise HR and thigh-predicted sweat [Na+] relative to MHA (both P < 0.05). No between-group differences were observed when comparing MHA and IT (all P > 0.05). Conclusions Isothermic conditioning induced a more complete heat-adapted phenotype relative to MHA and IT. Interval training may serve as a time efficient alternative to MHA.
In vitro and in vivo evaluation of 3D constructs engineered with human iPSC‐derived chondrocytes in gelatin methacryloyl hydrogel

Articular cartilage defects have limited healing potential and, when left untreated, can lead to osteoarthritis. Tissue engineering focuses on regenerating the damaged joint surface, preferably in an early stage. Here, we investigate the regenerative potential of three‐dimensional (3D) constructs consisting of human induced pluripotent stem cell (iPSC)‐derived chondrocytes in gelatin methacryloyl (GelMA) hydrogel for stable hyaline cartilage production. iPSC‐derived chondrocytes are encapsulated in GelMA hydrogel at low (1 × 107 ml−1) and high (2 × 107 ml−1) density. In a conventional medium, GelMA hydrogel supports the chondrocyte phenotype, as opposed to cells cultured in 3D in absence of hydrogel. Moreover, encapsulated iPSC‐derived chondrocytes preserve their in vivo matrix formation capacity after 21 days in vitro. In differentiation medium, hyaline cartilage‐like tissue forms after 21 days, demonstrated by highly sulfated glycosaminoglycans and collagen type II. Matrix deposition is delayed at low encapsulation density, corroborating with lower transcript levels of COL2A1. An ectopic assay in nude mice demonstrates further maturation of the matrix deposited in vitro. Direct ectopic implantation of iPSC‐derived chondrocyte‐laden GelMA, without in vitro priming, also generates hyaline cartilage‐like tissue, albeit less mature. Since it is unclear what maturity upon implantation is desired for joint surface regeneration, this is an attractive technology to generate immature and more mature hyaline cartilage‐like tissue.
Single-cell glycomics analysis by CyTOF-Lec reveals glycan features defining cells differentially susceptible to HIV

High-parameter single-cell phenotyping has enabled in-depth classification and interrogation of immune cells, but to date has not allowed for glycan characterization. Here, we develop CyTOF-Lec as an approach to simultaneously characterize many protein and glycan features of human immune cells at the single-cell level. We implemented CyTOF-Lec to compare glycan features between different immune subsets from blood and multiple tissue compartments, and to characterize HIV-infected cell cultures. Using bioinformatics approaches to distinguish preferential infection of cellular subsets from viral-induced remodeling, we demonstrate that HIV upregulates the levels of cell-surface fucose and sialic acid in a cell-intrinsic manner, and that memory CD4+ T cells co-expressing high levels of fucose and sialic acid are highly susceptible to HIV infection. Sialic acid levels were found to distinguish memory CD4+ T cell subsets expressing different amounts of viral entry receptors, pro-survival factors, homing receptors, and activation markers, and to play a direct role in memory CD4+ T cells’ susceptibility to HIV infection. The ability of sialic acid to distinguish memory CD4+ T cells with different susceptibilities to HIV infection was experimentally validated through sorting experiments. Together, these results suggest that HIV remodels not only cellular proteins but also glycans, and that glycan expression can differentiate memory CD4+ T cells with vastly different susceptibility to HIV infection.
Pulmonary function of children with tracheomalacia and associated clinical factors

Spirometry is easily accessible yet there is limited data in children with tracheomalacia. Availability of such data may inform clinical practice. We aimed to describe spirometry indices of children with tracheomalacia, including Empey index and flow‐volume curve pattern, and determine whether these indices relate with bronchoscopic features.
Loncastuximab tesirine in relapsed/refractory high-grade B-cell lymphoma: a subgroup analysis from the LOTIS-2 study

Juan P. Alderuccio, Weiyun Z. Ai, John Radford, Melhem Solh, Kirit M. Ardeshna, Matthew A. Lunning, Brian T. Hess, Pier L. Zinzani, Anastasios Stathis, Carmelo Carlo-Stella, Mehdi Hamadani, Brad S. Kahl, David Ungar, Turk Kilavuz, Eric Yu, Yajuan Qin, and Paolo F. Caimi Division of Hematology, Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, FL; Division of Hematology and Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA; The Christie National Health Service (NHS) Foundation Trust, Manchester Cancer Research Centre and Manchester Academic Health Science Centre, Manchester, United Kingdom; Blood and Marrow Transplant Program, Northside Hospital Cancer Institute, Atlanta, GA; Department of Haematology, University College of London Hospitals NHS Foundation Trust, London, United Kingdom; Division of Hematology and Oncology, University of Nebraska Medical Center, Omaha, NE; Hollings Medical Cancer Center, Medical University of South Carolina, Charleston, SC; Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia “Ser agnoli” and Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale Universit a di Bologna, Bologna, Italy; Oncology Institute of Southern Switzerland, Bellinzona, Switzerland; Humanitas University and Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Humanitas Research Hospital, Milano, Italy; Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI; Division of Oncology, Washington University, St Louis, MO; Clinical Development, ADC Therapeutics America, Murray Hill, NJ; and Division of Hematology and Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH
Technological features of blast identification in the cerebrospinal fluid: A systematic review of flow cytometry and laboratory haematology methods

Involvement of the central nervous system (CNS) by acute leukemias (ALs) has important implications for risk stratification and disease outcome. The clinical laboratory plays an essential role in assessment of cerebrospinal fluid (CSF) specimens from patients with ALs at initial diagnosis, at the end of treatment, and when CNS involvement is clinically suspected. The two challenges for the laboratory are 1) to accurately provide a cell count of the CSF and 2) to successfully distinguish blasts from other cell types. These tasks are classically performed using manual techniques, which suffer from suboptimal turnaround time, imprecision, and inconsistent inter‐operator performance. Technological innovations in flow cytometry and hematology analyzer technology have provided useful complements and/or alternatives to conventional manual techniques.
TRIM33 drives prostate tumor growth by stabilizing androgen receptor from Skp2‐mediated degradation

Androgen receptor (AR) is a master transcription factor that drives prostate cancer (PCa) development and progression. Alterations in the expression or activity of AR coregulators significantly impact the outcome of the disease. Using a proteomics approach, we identified the tripartite motif‐containing 33 (TRIM33) as a novel transcriptional coactivator of AR. We demonstrate that TRIM33 facilitates AR chromatin binding to directly regulate a transcription program that promotes PCa progression. TRIM33 further stabilizes AR by protecting it from Skp2‐mediated ubiquitination and proteasomal degradation. We also show that TRIM33 is essential for PCa tumor growth by avoiding cell‐cycle arrest and apoptosis, and TRIM33 knockdown sensitizes PCa cells to AR antagonists. In clinical analyses, we find TRIM33 upregulated in multiple PCa patient cohorts. Finally, we uncover an AR‐TRIM33‐coactivated gene signature highly expressed in PCa tumors and predict disease recurrence. Overall, our results reveal that TRIM33 is an oncogenic AR coactivator in PCa and a potential therapeutic target for PCa treatment.
Operative and Nonoperative Outcomes of Emergency General Surgery Conditions

Objective: To determine the effect of operative versus nonoperative management of emergency general surgery conditions on short-term and long-term outcomes. Background: Many emergency general surgery conditions can be managed either operatively or nonoperatively, but high-quality evidence to guide management decisions is scarce. Methods: We included 507,677 Medicare patients treated for an emergency general surgery condition between July 1, 2015, and June 30, 2018. Operative management was compared with nonoperative management using a preference-based instrumental variable analysis and near-far matching to minimize selection bias and unmeasured confounding. Outcomes were mortality, complications, and readmissions. Results: For hepatopancreaticobiliary conditions, operative management was associated with lower risk of mortality at 30 days [−2.6% (95% confidence interval: −4.0, −1.3)], 90 days [−4.7% (−6.50, −2.8)], and 180 days [−6.4% (−8.5, −4.2)]. Among 56,582 intestinal obstruction patients, operative management was associated with a higher risk of inpatient mortality [2.8% (0.7, 4.9)] but no significant difference thereafter. For upper gastrointestinal conditions, operative management was associated with a 9.7% higher risk of in-hospital mortality (6.4, 13.1), which increased over time. There was a 6.9% higher risk of inpatient mortality (3.6, 10.2) with operative management for colorectal conditions, which increased over time. For general abdominal conditions, operative management was associated with 12.2% increased risk of inpatient mortality (8.7, 15.8). This effect was attenuated at 30 days [8.5% (3.8, 13.2)] and nonsignificant thereafter. Conclusions: The effect of operative emergency general surgery management varied across conditions and over time. For colorectal and upper gastrointestinal conditions, outcomes are superior with nonoperative management, whereas surgery is favored for patients with hepatopancreaticobiliary conditions. For obstructions and general abdominal conditions, results were equivalent overall. These findings may support patients, clinicians, and families making these challenging decisions.
Structural and functional retinal changes in patients with type 2 diabetes without diabetic retinopathy

Abstract Objective The characteristics of the early changes in preclinical diabetic retinopathy (DR) are poorly known. This study aimed to analyse the changes in the structure and function of the fundus in diabetic patients without diabetic retinopathy (NDR). Methods This prospective study enrolled patients with type 2 diabetes and healthy controls from April to December 2020. Retinal sensitivity was measured by microperimetry. The peripapillary retinal nerve fibre layer (p-RNFL) thickness, macular retinal thickness, and retinal volume were measured by optical coherence tomography (OCT). The vessel density (VD) and perfusion density (PD) of the peripapillary area, as well as the foveal avascular zone (FAZ) area, FAZ perimeter, and FAZ circularity, were measured by optical coherence tomographic angiography (OCTA). Results A total of 71 cases (100 eyes) were enrolled in the study, including 34 cases (51 eyes) in the NDR group and 37 cases (49 eyes) in the control group. The mean retinal sensitivity was lower in the NDR group than in the control group for all sectors (all p < .001). Compared with controls, the NDR group showed thinner p-RNFL in the T sector (76.24 ± 14.29 vs. 85.47 ± 19.66 µm, p = .035). The NDR group had a thinner retina in the N2 sector (304.55 ± 16.07 vs. 312.02 ± 12.30 µm, p = .010). The PD of DCP was lower in the N2 sector in the NDR group (44.92 ± 11.77 vs. 50.27 ± 6.37%, p = .044). The VD was higher in the NDR group in RPCP-S/N/I, and the PD was higher in the RPCP-S/N (all p < .05). The frequencies of perifoveal capillary drop-out, notched or punched out borders of the superficial FAZ, and loss of smooth contour were all higher in the NDR group (all p < .05). Conclusion The structure (p-RNFL thickness, VD, and PD) and function (retinal sensitivity) display some changes in diabetic patients even if they had not been found to have DR. Key messages Decreased retinal sensitivity was observed in diabetic patients before the onset of diabetic retinopathy. Compared with the control group, we found the changes in vessel density or perfusion density in a certain area, whether in SCP, DCP, or RPCP in the NDR group. Before the onset of diabetic retinopathy, the structure and function of the retina in diabetic patients had changed.
Automated intraoperative central sulcus localization and somatotopic mapping using median nerve stimulation

Objective. Accurate identification of functional cortical regions is essential in neurological resection. The central sulcus (CS) is an important landmark that delineates functional cortical regions. Median nerve stimulation (MNS) is a standard procedure to identify the position of the CS intraoperatively. In this paper, we introduce an automated procedure that uses MNS to rapidly localize the CS and create functional somatotopic maps. Approach. We recorded electrocorticographic signals from 13 patients who underwent MNS in the course of an awake craniotomy. We analyzed these signals to develop an automated procedure that determines the location of the CS and that also produces functional somatotopic maps. Main results. The comparison between our automated method and visual inspection performed by the neurosurgeon shows that our procedure has a high sensitivity (89%) in identifying the CS. Further, we found substantial concordance between the functional somatotopic maps generated by our method and passive functional mapping (92% sensitivity). Significance. Our automated MNS-based method can rapidly localize the CS and create functional somatotopic maps without imposing additional burden on the clinical procedure. With additional development and validation, our method may lead to a diagnostic tool that guides neurosurgeons and reduces postoperative morbidity in patients undergoing resective brain surgery.
Delineating selective vulnerability of inhibitory interneurons in Alpers' syndrome

Alpers' syndrome is a severe neurodegenerative disease typically caused by bi‐allelic variants in the mitochondrial DNA (mtDNA) polymerase gene, POLG, leading to mtDNA depletion. Intractable epilepsy, often with an occipital focus, and extensive neurodegeneration are prominent features of Alpers' syndrome. Mitochondrial oxidative phosphorylation (OXPHOS) is severely impaired with mtDNA depletion and is likely to be a major contributor to the epilepsy and neurodegeneration in Alpers' syndrome. We hypothesised that parvalbumin‐positive(+) interneurons, a neuronal class critical for inhibitory regulation of physiological cortical rhythms, would be particularly vulnerable in Alpers' syndrome due to the excessive energy demands necessary to sustain their fast‐spiking activity.
Evaluation of aerodigestive disease and diagnosis of sliding hiatal hernia in brachycephalic and nonbrachycephalic dogs

Abstract Background Aerodigestive diseases (AeroD), hybrid disorders between the respiratory and gastrointestinal (GI) tracts, may present without GI signs. Sliding hiatal hernia (sHH) is an important AeroD in brachycephalic dogs linked to respiratory pathology. The spectrum of other AeroD and respiratory clinical signs (CS) in brachycephalic and nonbrachycephalic dogs with sHH is unknown. Objectives Characterize CS of AeroD in dogs with sHH, compare CS between brachycephalic and nonbrachycephalic dogs, and compare thoracic radiographs and videofluoroscopic swallow study (VFSS) for diagnosing sHH. Animals Sixty‐seven client‐owned dogs with sHH. Methods Medical records of dogs with sHH presented to the veterinary teaching hospitals at Auburn University and the University of Missouri between 1 January 2009 and 31 December 2020 were retrospectively reviewed. Between group, comparisons were made using Mann‐Whitney test, Chi‐square analysis, and Spearman correlation (P < .05). Results Dogs with sHH presented with exclusively GI signs (28/67), mixed respiratory and GI signs (22/67), or with exclusively respiratory signs (17/67). Wheras brachycephalic dogs were not significantly more likely to present with respiratory CS (P = .145), they were younger (P < .001), and more likely to present in respiratory distress (P = .02), and with radiographic evidence of aspiration pneumonia (P < .001) compared to nonbrachycephalic dogs. Six of 12 dogs with normal thoracic radiographs having sHH presented with respiratory CS. For detection of sHH, VFSS was superior to radiographs (P < .001). Conclusions and Clinical Importance Dogs with sHH may present with exclusively respiratory signs. Respiratory signs may be more severe in brachycephalic compared to nonbrachycephalic dogs. Videofluoroscopic swallow study was superior to thoracic radiographs for detection of sHH in dogs.
Temporal trends in the management of metacarpal and phalangeal fractures in the 21st century: an analysis of Australian population‐based data

Fractures of the hand, specifically the metacarpals and phalanges, are a common injury. Whilst many of these fractures can be treated non‐operatively, a number of advances have led to the increase in popularity of surgical intervention. The aim of this study was to assess and describe trends in management of phalangeal and metacarpal fractures in Australia over the last two decades.
Minds matter: how COVID-19 highlighted a growing need to protect and promote athlete mental health

The Sports and Exercise Medicine community and other sport stakeholders are becoming increasingly aware of the mental health symptoms (eg, depression, anxiety, substance misuse) reported by athletes. In 2019, this led to the publication of the first International Olympic Committee (IOC) consensus statement on mental health in this cohort and the establishment of the IOC Mental Health Working Group. Over the past 2 years, the COVID19 pandemic and related public health measures have presented additional challenges to the wellbeing of all populations, including athletes. This editorial reflects on how the COVID19 pandemic has highlighted a growing need to protect and promote athlete mental health.
Use of the y-intercept in the evaluation of the anaerobic fitness and performance prediction of trained swimmers

The objective of this study was to verify the use of y-intercept from the critical velocity model in the evaluation of the anaerobic fitness and prediction of maximal performance in trained swimmers in crawl style. Fourteen swimmers with ages ranging from 15 to 18 years participated in this study. The athletes performed the tied swimming test, maximal performances tests and critical velocity (CV) for the determination of anaerobic swimming capacity (AWC). 1) The tied swimming test was applied through maximal effort during 30 seconds fixed to the equipment with load cells for the measurement of the peak force, anaerobic fitness and peak lactate. 2) The subjects also performed maximal performances at distances of 100, 200, 300, 400 and 600 meters with two hours interval between each swim. 3) AWC at CV model was determined utilizing all possible combinations by maximal performances applying the distance-time linear regression model. The AWC value obtained was of 25.07 ± 4.22 m, with linear regression coefficient between 0.99 and 1.00, and linear coefficient error of 19.30 ± 5.9%. AWC was not correlated with all maximal performances, peak force (227.81 ± 63.02 N), anaerobic fitness (85.55 ± 13.05 N), and peak lactate (6.80 ± 1.08 mM). However, the anaerobic fitness was correlated with all maximal performances. Thus, it was concluded that the AWC obtained by y-intercept of the distance/time of swim relation does not seem to be a good parameter for the anaerobic fitness evaluation neither to predict the maximal performances between 100 and 600 meters in crawl style.