Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical–functional characteristics and risk of exacerbation and mortality among more symptomatic patients with chronic obstructive pulmonary disease: a retrospective cohort study

Objectives The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 classified chronic obstructive pulmonary disease (COPD) patients into more and less symptomatic groups. This study aimed to analyze the clinical characteristics, risk of future exacerbation and mortality among patients in more symptomatic group. Design A retrospective cohort study. Setting Data were obtained from patients enrolled in a database setup by Second Xiangya Hospital of Central South University. Participants 1729 stable COPD patients listed from September 2017 to December 2019 in the database. The patients were classified into more and less symptomatic groups based on GOLD 2017 report. Outcomes All patients were followed up for 18 months. We collected baseline data and recorded the number of exacerbations and mortality during follow-up. Results The more symptomatic patients were older, had higher Clinical COPD Questionnaire (CCQ) scores, more severe airflow limitation and higher number of exacerbations and hospitalizations in the past year (P < 0.05). Logistic regression showed that having more symptoms correlated with the CCQ scores and exacerbations in the past year (P < 0.05). After patients were followed up, there were higher numbers of exacerbations, hospitalizations and mortality rates in more symptomatic patients (P < 0.05). The multivariate model showed that age more than 65 years (OR = 2.047, 95% CI = 1.020-4.107) and COPD assessment test scores more than 30 (OR = 2.609, 95% CI = 1.339-5.085) were independent risk factors for mortality, whereas current smoker (OR = 1.565, 95% CI = 1.052-2.328), modified Medical Research Council scores (OR = 1.274, 95% CI = 1.073-1.512) and exacerbations in the past year (OR = 1.061, 95% CI = 1.013-1.112) were independent risk factors for exacerbation in more symptomatic patients (P < 0.05). Conclusions More symptomatic COPD patients have worse outcomes. In addition, several independent risk factors for exacerbation and mortality were identified. Therefore, clinicians should be aware of these risk factors and take them into account during interventions.
Heterozygous OT‐I mice reveal that antigen‐specific CD8 + T cells shift from apoptotic to necrotic killers in the elderly

Numerous alterations in CD8+ T cells contribute to impaired immune responses in elderly individuals. However, the discrimination between cell‐intrinsic dysfunctions and microenvironmental changes is challenging. TCR transgenic OT‐I mice are utilized to investigate CD8+ T‐cell immunity, but their immunodeficient phenotype hampers their use especially in aging. Here, we demonstrate that using a heterozygous OT‐I model minimizes the current limitations and provides a valuable tool to assess antigen‐specific T‐cell responses even at old age. We analyzed phenotypic and functional characteristics of CD8+ T cells from OT‐I+/+ and OT‐I+/− mice to prove the applicability of the heterozygous system. Our data reveal that OVA‐activated CD8+ T cells from adult OT‐I+/− mice proliferate, differentiate, and exert cytolytic activity equally to their homozygous counterparts. Moreover, common age‐related alterations in CD8+ T cells, including naive T‐cell deterioration and decreased proliferative capacity, also occur in elderly OT‐I+/− mice, indicating the wide range of applications for in vivo and in vitro aging studies. We used the OT‐I+/− model to investigate cell‐intrinsic alterations affecting the cytotoxic behavior of aged CD8+ T cells after antigen‐specific in vitro activation. Time‐resolved analysis of antigen‐directed target cell lysis confirmed previous observations that the cytotoxic capacity of CD8+ T cells increases with age. Surprisingly, detailed single cell analysis revealed that transcriptional upregulation of perforin in aged CD8+ T cells shifts the mode of target cell death from granzyme‐mediated apoptosis to rapid induction of necrosis. This unexpected capability might be beneficial or detrimental for the aging host and requires detailed evaluation.
Germline genetic variations in methotrexate pathway are associated with pharmacokinetics, outcome, and toxicity in patients with primary central nervous system lymphoma

ABSTRACT Background High-dose methotrexate (HD-MTX)–based regimens are the standard treatment for patients with primary central nervous system lymphoma (PCNSL); however, MTX has extensive interpatient variability in pharmacokinetics and clinical outcomes, with genetic variation an important factor involved in the variability in drug response. Methods 123 PCNSL patients who received 524 courses of chemotherapy were genotyped for 42 single nucleotide polymorphisms in MTX pathway. The relationship between these polymorphisms and the pharmacokinetics, clinical outcomes, and toxicity of MTX was explored using both univariate and multivariate analyses. Results We found ABCB1 rs2032582 and GGH rs2305558 were substantially associated with the pharmacokinetics of MTX. Patients with GGH rs2305558 T and ABCB1 rs2032582 non-G allele had a higher Cmax increased by 20.5%, area under the concentration-time curve (AUC0-48h) increased by 19.6% and lower clearance decreased by 19.6%. ABCB1 rs1045642 and rs2032582 might be independent predictors of progression-free survival. Patients with ABCB1 rs1045642 non-A and rs2032582 G allele correlated with higher progression risk of the disease. Furthermore, ATIC rs3821353 was associated with MTX-induced hepatotoxicity (Grade ≥ 2). Conclusion These variants may serve as biomarkers to predict the pharmacokinetics, clinical outcomes, and hepatotoxicity of MTX and contribute to personalized therapy for PCNSL patients.
MRI-based morphometric analysis of corpus callosum dimensions of adults in Southeast Nigeria

ABSTRACT The Corpus callosum (CC) is the largest commissural fibre tract, ensuring swift information transfer and integration in both cerebral hemispheres. Variations in morphometry exist. There is a paucity of data on CC dimensions in our subregion, and no standardized reference is available. The study aims to determine the CC dimensions among the adult population in southeast Nigeria. The result will provide reference ranges and form a benchmark for comparisons of CC-related pathologies. A retrospective study of CC morphometric dimensions in normal subjects who had cranial MRI over two years in Memfys Hospital, Enugu, Southeast Nigeria, using a 1.5T GE© 16 channel machine. The CC was segmentalized into seven subregions using the modified Witelson method with special computer software. All measurements were taken twice from the T1 mid-sagittal image, and the mean was used for computation. The results were analyzed using descriptive and inferential statistics. A total of 200 subjects were recruited for the study. The mean length and height of the CC were 75.58 ± 4.52 mm and 24.64 ± 3.40 mm, respectively. The width dimensions of the genu, body, rostrum and splenium were 10.88 ± 1.81 mm, 5.66 ± 1.32 mm, 3.65 ± 1.25 mm, and 10.02 ± 1.70 mm, respectively. No gender variations were noted among the different dimensions of CC (P = 0.90). The length and height of CC increase gradually with age and show a positive correlation. The width dimensions of the genu and splenium increase till middle age and subsequently decreases in line with brain atrophy (p = 0.0000& p = 0.004). Using Pearson’s correlation test, no correlation was noted in the dimensions of the body and rostrum of the corpus callosum when related to age and sex. (P = 0.92 & p = 0.66). Reference ranges of CC dimensions in our subregion were presented, and variations exist in its different morphometric dimensions which are affected by brain atrophy. Gender does not influence the dimensions in our subpopulations.
Dietary fish intake increased the concentration of soluble ACE2 in rats: can fish consumption reduce the risk of COVID-19 infection through interception of SARS-CoV-2 by soluble ACE2?

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the cells after binding to the membrane-bound receptor angiotensin-converting enzyme 2 (ACE2), but this may be prevented through interception by soluble ACE2 (sACE2) or by inhibition of the ACE2 receptor, thus obstructing cell entry and replication. The main objective of this study was to investigate if fish intake affected the concentration of sACE2 in rats. The secondary aim was to evaluate the in vitro ACE2-inhibiting activity of fish proteins. Rats were fed cod muscle as 25 % of dietary protein, and blood was collected after 4 weeks of intervention. Muscle, backbone, skin, head, stomach, stomach content, intestine and swim bladder from haddock, saithe, cod and redfish were hydrolysed with trypsin before ACE2-inhibiting activity was measured in vitro. In vivo data were compared using unpaired Student’s t test, and in vitro data were compared using one-way ANOVA followed by the Tukey HSD post hoc test. The mean sACE2 concentration was 47 % higher in rats fed cod when compared with control rats (P 0·034), whereas serum concentrations of angiotensin II and TNF-α were similar between the two experimental groups. Muscle, backbone, skin and head from all four fish species inhibited ACE2 activity in vitro, whereas the remaining fractions had no effect. To conclude, our novel data demonstrate that fish intake increased the sACE2 concentration in rats and that the hydrolysed fish proteins inhibited ACE2 activity in vitro.
Effects of Acute Stress on Rigid Learning, Flexible Learning, and Value-Based Decision-Making in Spatial Navigation

The current study investigated how stress affects value-based decision-making during spatial navigation and different types of learning underlying decisions. Eighty-two adult participants (42 females) first learned to find object locations in a virtual environment from a fixed starting location (rigid learning) and then to find the same objects from unpredictable starting locations (flexible learning). Participants then decided whether to reach goal objects from the fixed or unpredictable starting location. We found that stress impairs rigid learning in females, and it does not impair, and even improves, flexible learning when performance with rigid learning is controlled for. Critically, examining how earlier learning influences subsequent decision-making using computational models, we found that stress reduces memory integration, making participants more likely to focus on recent memory and less likely to integrate information from other sources. Collectively, our results show how stress impacts different memory systems and the communication between memory and decision-making.
Exploring Dynamics of Changes in Psychological Skills in the Development of Talented Athletes

In this study we examined changes in a psychological skill set, defined as crucial for the growth of talented athletes, through repeated assessments of the six-factor Psychological Characteristics of Development Excellence Questionnaire (PCDEQ). In a first phase of this study, we built and evaluated a French adaptation of the PCDEQ: the PCDEQ-SV (18 items). After confirmatory factor analysis, Cronbach’s alpha revealed that scales for its six factors ranged from very good to just below minimally acceptable as a model fit. The mean inter-item correlations for the scales, built on three items per scale, were optimal, leading us to assume that this short version was reliable. In the second phase, we analyzed the changes in the skill sets of 67 talented Swiss athletes who were given the PCDEQ-SV three times over 1 year. Feedback on the scores was provided to participants in comparison to the test’s cutoffs after T1 and T2. The analysis then focused on those who scored below the cutoffs and their resources for skill improvements. We found that the highest number of participants scored below the cutoffs at testing times, T1 and T2 on Factors 2, 6 and 1. Changes in scores were characterized by overall dynamics of improvement. The resources most used to effect those changes were “personal work with no outside help,” “discussions with significant others,” and “specific work with the coach. ” The results are discussed in relation to the iGen’s resources for self-determination of psychological skills improvement.
Development of Hand Use with and Without Intensive Training Among Children with Unilateral Cerebral Palsy in Scandinavia

ABSTRACT Aim To describe hand use development in children with unilateral cerebral palsy who did/did not participate in constraint-induced movement therapy (CIMT) before 7 years of age. Method The study included 334 participants (18 months–12 years) who were assessed with 1,565 Assisting Hand Assessments (AHAs) and categorized into no intensive training (NIT), CIMT (18 months–7 years), and Baby-CIMT (<18 months) groups. Results AHA performance at 18 months (AHA-18) was positively associated with development regardless of training. The CIMT group had lower AHA-18 performance than the NIT group (p = .028), but higher stable limit (p = .076). The age when 90% of development was reached was highest in the CIMT group (p = .014). Although non-significant, the Baby-CIMT group had higher mean curve than NIT and CIMT combined (AHA-18 p = .459, limit p = .477). Conclusion The CIMT group improved more over time than the NIT group. Intensive training extended the window of development, and Baby-CIMT might promote early development.
Prevalence of taste and smell dysfunction in mild and asymptomatic COVID-19 patients during Omicron prevalent period in Shanghai, China: a cross-sectional survey study

Objectives COVID-19, which is caused by SARS-CoV-2, is a severe threat to human health and the economy globally. This study aimed to investigate the prevalence of taste and/or smell dysfunction and associated risk factors in mild and asymptomatic patients with Omicron infection in Shanghai, China. Design This was a questionnaire-based cross-sectional study. Setting COVID-19 patients at the makeshift hospital in the Shanghai World Expo Exhibition and Convention Centre were recruited from March to April 2022. Participants In total, 686 COVID-19-infected patients who were defined as mild or asymptomatic cases according to the diagnostic criteria of New Coronavirus Pneumonia Prevention and Control Programme ninth edition (National Health Commission of China, 2022) were enrolled. Measures Data to investigate taste and smell loss and to characterise other symptoms were collected by the modified Chemotherapy-induced Taste Alteration Scale and Sino-Nasal Outcome Test-22 questionnaires. The risk factors for the severity of taste/smell dysfunction were analysed by binary logistic regression models. Results 379 males (379/686, 55.2%) and 307 females (307/686, 44.8%) completed the questionnaires to record recent changes in taste and smell ability. A total of 302 patients (44%) had chemosensory dysfunction with Omicron infection, of which 22.7% (156/686) suffered from both taste and smell dysfunction. In addition, cough (60.2%), expectoration (40.5%), fever (33.2%) and sore throat (32.5%) were common symptoms during Omicron infection. The quality-of-life-related indicators were negatively associated with participants’ self-reported taste and smell dysfunction. Conclusions The prevalence of taste or/and smell dysfunction in patients with Omicron infections was 44%. Individuals with chemosensory dysfunction had significantly higher rates of various upper respiratory influenza-like symptoms, xerostomia and bad breath. Moreover, smell dysfunction was a risk factor for the prevalence of taste dysfunction in patients with Omicron infection. Trial registration number ChiCTR 2200059097.
The Chandra survey of Carina OB stars

Abstract We have combined 22 deep Chandra ACIS-I pointings to map over one square degree of the Carina complex. Our x-ray survey detects 69 of 70 known O-type stars and 61 of 130 known early B stars. The majority of single O stars display soft X-ray spectra and have a mean log LX/Lbol ≈ −7.5 suggesting shocks embedded in the O-star winds. Over OB stars show unusually high X-ray luminosities, high shock temperatures or time variability, not predicted for embedded wind shocks.
Estimating uncertainty in read‐out patterns: Application to controls‐based denoising and voxel‐based morphometry patterns in neurodegenerative and neuropsychiatric diseases

Quantifying pathology‐related patterns in patient data with pattern expression score (PES) is a standard approach in medical image analysis. In order to estimate the PES error, we here propose to express the uncertainty contained in read‐out patterns in terms of the expected squared Euclidean distance between the read‐out pattern and the unknown “true” pattern (squared standard error of the read‐out pattern, SE2). Using SE2, we predicted and optimized the net benefit (NBe) of the recently suggested method controls‐based denoising (CODE) by weighting patterns of nonpathological variance (NPV). Multi‐center MRI (1192 patients with various neurodegenerative and neuropsychiatric diseases, 1832 healthy controls) were analysed with voxel‐based morphometry. For each pathology, accounting for SE2, NBe correctly predicted classification improvement and allowed to optimize NPV pattern weights. Using these weights, CODE improved classification performances in all but one analyses, for example, for prediction of conversion to Alzheimer's disease (AUC 0.81 vs. 0.75, p = .01), diagnosis of autism (AUC 0.66 vs. 0.60, p < .001), and of major depressive disorder (AUC 0.62 vs. 0.50, p = .03). We conclude that the degree of uncertainty in a read‐out pattern should generally be reported in PES‐based analyses and suggest using weighted CODE as a complement to PES‐based analyses.
Oracle Properties, Bias Correction, and Inference of the Adaptive Lasso for Time Series Extremum Estimators

We derive new theoretical results on the properties of the adaptive least absolute shrinkage and selection operator (adaptive lasso) for time series regression models. In particular we investigate the question of how to conduct finite sample inference on the parameters given an adaptive lasso model for some fixed value of the shrinkage parameter. Central in this study is the test of the hypothesis that a given adaptive lasso parameter equals zero, which therefore tests for a false positive. To this end we construct a simple (conservative) testing procedure and show, theoretically and empirically through extensive Monte Carlo simulations, that the adaptive lasso combines efficient parameter estimation, variable selection, and valid finite sample inference in one step. Moreover, we analytically derive a bias correction factor that is able to significantly improve the empirical coverage of the test on the active variables. Finally, we apply the introduced testing procedure to investigate the relation between the short rate dynamics and the economy, thereby providing a statistical foundation (from a model choice perspective) to the classic Taylor rule monetary policy model.
Prediabetes in pregnancy – follow-up, treatment, and outcomes compared to overt pregestational diabetes

Abstract Objective There are limited data on follow-up, treatment, and maternal and fetal outcomes in women with prediabetes before or at the beginning of pregnancy. The aim of this study was to comprehensively characterize women with prediabetes compared to women with type 2 diabetes mellitus. Study design This was a retrospective cohort data from a single medical center treating women with pregestational prediabetes mellitus (PDM). Women were compared to pregestational overt type 2 diabetes mellitus (T2DM). Results Data were collected from 120 women in the PDM group and 86 women in the T2DM group. Baseline characteristics were comparable, albeit women in the PDM group arrived at medical attention significantly later, 55% after 15 weeks gestation. Women with PDM needed significantly less treatment to achieve glycemic control and glycated hemoglobin remained lower throughout pregnancy. Maternal and fetal outcomes were similar between groups, although significantly higher rates of macrosomia and neonatal jaundice were observed in the T2DM group. Conclusions The lack of clear guidelines causes a delay in the first prenatal visit of women with PDM. Comparable pregnancy outcomes may tip the balance toward acceptance of early treatment. Establishing clear guidelines will enable primary caregivers to refer prediabetic women sooner for lifestyle modifications and treatment if needed.
Evidence for the Role of a Second Fc-Binding Receptor in Placental IgG Transfer in Nonhuman Primates

This study compared the ability of several human HIV envelope-directed monoclonal antibodies produced in plants with the same antibodies produced in mammalian cells for their ability to cross monkey and mouse placentas. We found that the two types of antibodies have comparable transfer efficiencies in mice, but they are differentially transferred across macaque placentas, consistent with a two-receptor IgG transport model in primates. ABSTRACT Transplacental transfer of maternal antibodies provides the fetus and newborn with passive protection against infectious diseases. While the role of the highly conserved neonatal Fc receptor (FcRn) in transfer of IgG in mammals is undisputed, recent reports have suggested that a second receptor may contribute to transport in humans. We report poor transfer efficiency of plant-expressed recombinant HIV-specific antibodies, including engineered variants with high FcRn affinity, following subcutaneous infusion into rhesus macaques close to parturition. Unexpectedly, unlike those derived from mammalian tissue culture, plant-derived antibodies were essentially unable to cross macaque placentas. This defect was associated with poor Fcγ receptor binding and altered Fc glycans and was not recapitulated in mice. These results suggest that maternal-fetal transfer of IgG across the three-layer primate placenta may require a second receptor and suggest a means of providing maternal antibody treatments during pregnancy while avoiding fetal harm. IMPORTANCE This study compared the ability of several human HIV envelope-directed monoclonal antibodies produced in plants with the same antibodies produced in mammalian cells for their ability to cross monkey and mouse placentas. We found that the two types of antibodies have comparable transfer efficiencies in mice, but they are differentially transferred across macaque placentas, consistent with a two-receptor IgG transport model in primates. Importantly, plant-produced monoclonal antibodies have excellent binding characteristics for human FcRn receptors, permitting desirable pharmacokinetics in humans. The lack of efficient transfer across the primate placenta suggests that therapeutic plant-based antibody treatments against autoimmune diseases and cancer could be provided to the mother while avoiding transfer and preventing harm to the fetus.
A radio continuum study of the Magellanic Clouds - VII. Discrete radio sources in the Magellanic Clouds

We present a study of discrete radio sources in the Magellanic Clouds (MCs) using the latest large-scale radio surveys made with the Parkes radio telescope be- tween 1.4 and 8.55 GHz. These surveys achieved higher sensitivity then previous surveys done with the Parkes telescope and so the number of discrete radio sources de- tected towards the MCs has increased by factor of ve. Also, we have obtained improved positions, flux densities and radio spectral indices for all of these sources. A total of 483 sources towards the Large Magellanic Cloud (LMC) and 224 towards the Small Magellanic Cloud (SMC) have been detected at at least one radio frequency. Most of the MC's sources have been classi- ed in one of three groups: SNRs, H ii regions or back- ground sources according to classication criteria estab- lished here. In total, 209 discrete radio sources in the LMC and the 37 sources in the SMC are classied here to be either H ii regions or SNRs. We investigate their lu- minosity functions as well as the statistics of background sources behind the MCs. Also, we examine the distribu- tion of SNRs and H ii regions in the MCs.