Miracle-dz/UniFAR-FTUs huggingface dataset:
Preoperative low muscle mass and early postoperative outcomes in children undergoing living donor liver transplantation: A retrospective study

Low skeletal muscle mass may develop in children with end-stage liver disease, affecting postoperative outcomes. We retrospectively investigated whether preoperative low muscle mass was associated with early postoperative outcomes in pediatric patients undergoing living donor liver transplantation (LDLT). Electronic medical records of children (age below 12 y) who underwent LDLT between February 1, 2007, and January 31, 2018, were reviewed. The cross-sectional areas of psoas, quadratus lumborum, and erector spinae muscles at the level of fourth-fifth lumbar intervertebral disks were measured using abdominal CT images, divided by the square of the height and were added to obtain the total skeletal muscle index (TSMI). The patients were divided into two groups according to the median TSMI in the second quintile (1859.1 mm2/m2). Complications in the early postoperative period (within 30 d after surgery) classified as Clavien-Dindo grade 3 or higher were considered major complications. Logistic regression analyses were performed to determine the association between preoperative low muscle mass and early postoperative outcomes. In the study population of 123 patients (median age, 14 mo; range, 8–38 mo) who underwent LDLT, 29% and 71% were classified in the low (mean TSMI, 1642.5 ± 187.0 mm2/m2) and high (mean TSMI 2188.1 ± 273.5 mm2/m2) muscle mass groups, respectively. The rates of major complications, mechanical ventilation >96 hours, intensive care unit stay >14 days, hospital stay >30 days, and in-hospital mortality were not significantly different between the 2 groups. Additionally, adverse outcomes according to pediatric end-stage liver disease scores and sex were not significantly different between the 2 groups. In conclusion, preoperative low muscle mass defined by TSMI was not associated with early postoperative outcomes in pediatric patients undergoing LDLT.
Metabolic characteristics of obese patients with polycystic ovarian syndrome: a meta-analysis

Abstract Objective Though recent studies have pointed out different manifestations between obese and nonobese patients with polycystic ovarian syndrome (PCOS), there is no clear evidence to confirm this viewpoint. Therefore, the metabolic characteristics of obese and nonobese patients with PCOS were systematically compared through meta-analysis in this study. Methods Data were searched from PubMed, Web of Science, Embase, Cochrane Library, CNKI, and Wanfang databases. Articles on obese and nonobese patients with PCOS published from database inception to January 2022 were included. Meta-analysis was performed using Stata 16.0 statistical software. Results A total of 739 articles were initially retrieved, and ultimately 14 studies were involved in the meta-analysis. Specifically, there were 801 patients in the observation group (obese patients with PCOS) and 925 patients in the control group (nonobese patients with PCOS). Compared with the control group, the observation group had significantly lower levels of sex hormone-binding globulin (SHBG), high-density lipoprotein (HDL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and higher levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL). Nevertheless, there were no significant differences between the two groups in systolic blood pressure (SBP), diastolic blood pressure (DBP), glucose, and testosterone. Conclusion Compared with nonobese patients with PCOS, obese patients with PCOS have worse blood lipid parameters and lower levels of LH and FSH. Also, there are significant differences in metabolic characteristics between the two groups of patients. Most importantly, our findings provide guidance for the clinical diagnosis and treatment of PCOS.
Transfer Learning With Singular Value Decomposition of Multichannel Convolution Matrices

Abstract The task of transfer learning using pretrained convolutional neural networks is considered. We propose a convolution-SVD layer to analyze the convolution operators with a singular value decomposition computed in the Fourier domain. Singular vectors extracted from the source domain are transferred to the target domain, whereas the singular values are fine-tuned with a target data set. In this way, dimension reduction is achieved to avoid overfitting, while some flexibility to fine-tune the convolution kernels is maintained. We extend an existing convolution kernel reconstruction algorithm to allow for a reconstruction from an arbitrary set of learned singular values. A generalization bound for a single convolution-SVD layer is devised to show the consistency between training and testing errors. We further introduce a notion of transfer learning gap. We prove that the testing error for a single convolution-SVD layer is bounded in terms of the gap, which motivates us to develop a regularization model with the gap as the regularizer. Numerical experiments are conducted to demonstrate the superiority of the proposed model in solving classification problems and the influence of various parameters. In particular, the regularization is shown to yield a significantly higher prediction accuracy.
Healthcare Utilization and Advance Care Planning among Older Adults Across Cognitive Levels

This study examined the impact of advance care planning (ACP) on healthcare utilization among older adults with normal cognition and impaired cognition/dementia. Using datasets from the Health and Retirement Study, we conducted a cross-sectional study on 17,698 participants aged 51 years and older. Our analyses included survey descriptive and logistic regression procedures. ACP measures included a living will and durable power of attorney for healthcare. Healthcare utilization was measured using the days spent in hospitals, hospice care, nursing homes, and home care. Of the participants, 77.8% had normal cognition, and 22% had impaired cognition/dementia. The proportion of impaired cognition/dementia was higher among racially minoritized participants, single/widowed participants, and those who lived alone and were less educated. The results showed that having an ACP was associated with longer stays in hospitals, nursing homes, and home healthcare in all participants.
Resistance wheel running improves contractile strength, but not metabolic capacity, in a murine model of volumetric muscle loss injury

The primary objective of this study was to determine if low‐ or high‐resistance voluntary wheel running leads to functional improvements in muscle strength (i.e., isometric and isokinetic torque) and metabolic function (i.e., permeabilized fibre bundle mitochondrial respiration) after a volumetric muscle loss (VML) injury. C57BL/6J mice were randomized into one of four experimental groups at age 12 weeks: uninjured control, VML untreated (VML), low‐resistance wheel running (VML‐LR) and high‐resistance wheel running (VML‐HR). All mice, excluding the uninjured, were subject to a unilateral VML injury to the plantar flexor muscles and wheel running began 3 days post‐VML. At 8 weeks post‐VML, peak isometric torque was greater in uninjured compared to all VML‐injured groups, but both VML‐LR and VML‐HR had greater (∼32%) peak isometric torque compared to VML. All VML‐injured groups had less isokinetic torque compared to uninjured, and there was no statistical difference among VML, VML‐LR and VML‐HR. No differences in cumulative running distance were observed between VML‐LR and VML‐HR groups. Because adaptations in VML‐HR peak isometric torque were attributed to greater gastrocnemius muscle mass, atrophy‐ and hypertrophy‐related protein content and post‐translational modifications were explored via immunoblot; however, results were inconclusive. Permeabilized fibre bundle mitochondrial oxygen consumption was 22% greater in uninjured compared to VML, but there was no statistical difference among VML, VML‐LR and VML‐HR. Furthermore, neither wheel running group demonstrated a change in the relative protein content of the mitochondrial biogenesis transcription factor, peroxisome proliferator‐activated receptor γ coactivator 1‐α (PGC‐1α). These results indicate that resistance wheel running alone only has modest benefits in the VML‐injured muscle.
Impact of Heterotropic Allosteric Modulation on the Time-Dependent Inhibition of Cytochrome P450 3A4

The current study was designed to investigate the influence of allosteric effectors on the metabolism of the prototypical cytochrome P450 (CYP) 3A4 substrate midazolam (MDZ), and on the determination in vitro time-dependent inhibition (TDI) of CYP3A4 using human liver microsomes (HLM). As the concentration of midazolam increased to 250 µM in HLMs, homotropic cooperativity resulted in a decrease in the 1’-hydroxymidazolam to 4-hydroxymidazolam ratio to a maximum of 1.1. The presence of varying concentrations of testosterone, progesterone (PGS), or carbamazepine (CBZ) in HLMs with MDZ could recapitulate the effect of homotropic cooperativity such that the formation rates of the 1’hydroxymidazolam and 4-hydroxymidazolam were equal even at low concentrations of MDZ. The presence of PGS (10 or 100 µM) and CBZ (100 or 1000 µM) in in vitro TDI determination of four known CYP3A4 time-dependent inactivators (clarithromycin, troleandomycin, mibefradil, raloxifene) simultaneously decreased potency and inactivation rate constant, resulting in fold changes in inactivation efficiency on average of 1.6-fold and 13-fold for the low and high concentrations of allosteric modulator tested, respectively. The formation of a metabolic-intermediate complex (MIC) for clarithromycin and troleandomycin decreased in the presence of the allosteric modulators in a concentration-dependent manner, reaching a new steady state formation that could not be overcome with increased incubation time. Maximum reduction of the MIC formed by clarithromycin was up to ∼91%, while troleandomycin MIC decreased up to ∼31%. These findings suggest that the absence of endogenous allosteric modulators may contribute to the poor translation of HLM-based drug–drug interaction predictions. SIGNIFICANCE STATEMENT The reported overprediction of in vitro human liver microsome time-dependent inhibition of CYP3A4 and observed drug interactions in vivo remains an issue in drug development. We provide characterization of allosteric modulators on the CYP3A4 metabolism of the prototypical substrate midazolam, demonstrating the ability of the modulators to recapitulate the homotropic cooperativity of midazolam. Furthermore, we demonstrate that allosteric heterotropic cooperativity of CYP3A4 can impact the time-dependent inhibition kinetics of known mechanisms-based inhibitors, providing a potential mechanism to explain the overprediction.
Detection of proteomic alterations at different stages in a Huntington's disease mouse model via matrix‐assisted laser desorption/ionization mass spectrometry (MALDI‐MS) imaging

Huntington's disease (HD) is a progressive and irreversible neurodegenerative disease leading to the inability to carry out daily activities and for which no cure exists. The underlying mechanisms of the disease have not been fully elucidated yet. Matrix‐assisted laser desorption/ionization mass spectrometry imaging (MALDI‐MSI) allows the spatial information of proteins to be obtained upon the tissue sections without homogenisation. In this study, we aimed to examine proteomic alterations in the brain tissue of an HD mouse model with MALDI‐MSI coupled to LC–MS/MS system. We used 3‐, 6‐ and 12‐month‐old YAC128 mice representing pre‐stage, mild stage and pathological stage of the HD and their non‐transgenic littermates, respectively. The intensity levels of 89 proteins were found to be significantly different in YAC128 in comparison to their control mice in the pre‐stage, 83 proteins in the mild stage, and 82 proteins in the pathological stage. Among them, Tau, EF2, HSP70, and NogoA proteins were validated with western blot analysis. In conclusion, the results of this study have provided remarkable new information about the spatial proteomic alterations in the HD mouse model, and we suggest that MALDI‐MSI is an excellent technique for identifying such regional proteomic changes and could offer new perspectives in examining complex diseases.
On the use of exponential basis functions in the analysis of shear deformable laminated plates

In this report, we introduce a meshfree approach for static analysis of isotropic/orthotropic crossply laminated plates with symmetric/non-symmetric layers. Classical, first and third order shear deformation plate theories are employed to perform the analyses. In this method, the solution is first split into homogenous and particular parts and then the homogenous part is approximated by the summation of an appropriately selected set of exponential basis functions (EBFs) with unknown coefficients. In the homogenous solution the EBFs are restricted to satisfy the governing differential equation. The particular solution is derived using a similar approach and another series of EBFs. The imposition of the boundary conditions and determination of the unknown coefficients are performed by a collocation method through a discrete transformation technique. The solution method allows us to obtain semi-analytical solution of plate problems with various shapes and boundary conditions. The solutions of several benchmark plate problems with various geometries are presented to validate the results.
Immunohistochemical staining seems mandatory for individualizing and shortening follow‐up in unilateral primary aldosteronism

The clinical significance of immunohistochemistry (IHC) for unilateral primary aldosteronism (PA) has been unclear. Individualized follow‐up of PA patients could be in sight. Long‐term outcomes of patients, classified based on IHC, need further investigation. We aimed to assess long‐term clinical outcomes for unilateral PA, classifying patients based on IHC.
Exploring the impact of dexamethasone on gene regulation in myeloma cells

The study uncovers epigenomic changes associated with dexamethasone response heterogeneity in myeloma cells, revealing rewired promoter–enhancer interactions and DNA loop stabilization. Among glucocorticoids (GCs), dexamethasone (Dex) is widely used in treatment of multiple myelomas. However, despite a definite benefit, all patients relapse. Moreover, the molecular basis of glucocorticoid efficacy remains elusive. To determine genomic response to Dex in myeloma cells, we generated bulk and single-cell multi-omics data and high-resolution contact maps of active enhancers and target genes. We show that a minority of glucocorticoid receptor-binding sites are associated with enhancer activity gains, increased interaction loops, and transcriptional activity. We identified and characterized a predominant enhancer enriched in cohesin (RAD21) and more accessible upon Dex exposure. Analysis of four gene-specific networks revealed the importance of the CTCF–cohesin couple and the synchronization of regulatory sequence openings for efficient transcription in response to Dex. Notably, these epigenomic changes are associated with cell-to-cell transcriptional heterogeneity, in particular, lineage-specific genes. As consequences, BCL2L11-encoding BIM critical for Dex-induced apoptosis and CXCR4 protective from chemotherapy-induced apoptosis are rather up-regulated in different cells. In summary, our work provides new insights into the molecular mechanisms involved in Dex escape.
Intracellular glycogen accumulation by human gut commensals as a niche adaptation trait

ABSTRACT The human gut microbiota is a key contributor to host metabolism and physiology, thereby impacting in various ways on host health. This complex microbial community has developed many metabolic strategies to colonize, persist and survive in the gastrointestinal environment. In this regard, intracellular glycogen accumulation has been associated with important physiological functions in several bacterial species, including gut commensals. However, the role of glycogen storage in shaping the composition and functionality of the gut microbiota offers a novel perspective in gut microbiome research. Here, we review what is known about the enzymatic machinery and regulation of glycogen metabolism in selected enteric bacteria, while we also discuss its potential impact on colonization and adaptation to the gastrointestinal tract. Furthermore, we survey the presence of such glycogen biosynthesis pathways in gut metagenomic data to highlight the relevance of this metabolic trait in enhancing survival in the highly competitive and dynamic gut ecosystem. GRAPHICAL ABSTRACT
Strategies, debates, and adversarial collaboration in working memory: The 51st Bartlett Lecture

Frederic Bartlett championed the importance of individual strategy differences when remembering details of events. I will describe how long-running theoretical debates in the area of working memory may be resolved by considering differences across participants in the strategies that they use when performing cognitive tasks, and through adversarial collaboration between rival laboratories. In common with the established view within experimental cognitive psychology, I assume that adults have a range of cognitive functions, evolved for everyday life. However, I will present evidence showing that these functions can be engaged selectively for laboratory tasks, and that how they are deployed may differ between and within individuals for the same task. Reliance on aggregate data, while treating inter- and intra-participant variability in data patterns as statistical noise, may lead to misleading conclusions about theoretical principles of cognition, and of working memory in particular. Moreover, different theoretical perspectives may be focused on different levels of explanation and different theoretical goals rather than being mutually incompatible. Yet researchers from contrasting theoretical frameworks pursue science as a competition, rarely do researchers from competing labs work in collaboration, and debates self-perpetuate. These approaches to research can stall debate resolution and generate ever-increasing scientific diversity rather than scientific progress. The article concludes by describing a recent extended adversarial collaboration (the WoMAAC project) focused on theoretical contrasts in working memory, and illustrates how this approach to conducting research may help resolve scientific debate and facilitate scientific advance.
Weakly Compressible Models for Complex Flows

This work elaborates on numerical methods for high-fidelity analysis of underresolved single- and two-phase, weakly compressible flows. Also, a method is developed that allows to quantify the predictive capability of a numerical algorithm and distinguish regions of higher from those of lower reliability. Validation, verification, and application demonstration basis on selected experimental, analytical, numerical reference incompressible single- and two-phase, turbulent and non-turbulent flows.
A Head-to-head Comparison of De Novo Sirolimus or Everolimus Plus Reduced-dose Tacrolimus in Kidney Transplant Recipients: A Prospective and Randomized Trial

Background. Mammalian target of rapamycin inhibitors (mTORi), sirolimus (SRL) and everolimus (EVR), have distinct pharmacokinetic/pharmacodynamics properties. There are no studies comparing the efficacy and safety of de novo use of SRL versus EVR in combination with reduced-dose calcineurin inhibitor. Methods. This single-center prospective, randomized study included first kidney transplant recipients receiving a single 3 mg/kg antithymocyte globulin dose, tacrolimus, and prednisone, without cytomegalovirus (CMV) pharmacological prophylaxis. Patients were randomized into 3 groups: SRL, EVR, or mycophenolate sodium (MPS). Doses of SRL and EVR were adjusted to maintain whole blood concentrations between 4 and 8 ng/mL. The primary endpoint was the 12-mo incidence of the first CMV infection/disease. Results. There were 266 patients (SRL, n = 86; EVR, n = 90; MPS, n = 90). The incidence of the first CMV event was lower in the mTORi versus MPS groups (10.5% versus 7.8% versus 43.3%, P < 0.0001). There were no differences in the incidence of BK polyomavirus viremia (8.2% versus 10.1% versus 15.1%, P = 0.360). There were no differences in survival-free from treatment failure (87.8% versus 88.8% versus 93.3%, P = 0.421) and incidence of donor-specific antibodies. At 12 mo, there were no differences in kidney function (75 ± 23 versus 78 ± 24 versus 77 ± 24 mL/min/1.73 m2, P = 0.736), proteinuria, and histology in protocol biopsies. Treatment discontinuation was higher among patients receiving SRL or EVR (18.6% versus 15.6% versus 6.7%, P = 0.054). Conclusions. De novo use of SRL or EVR, targeting similar therapeutic blood concentrations, shows comparable efficacy and safety. The reduced incidence of CMV infection/disease and distinct safety profile of mTORi versus mycophenolate were confirmed in this study.
Chromosomal-level reference genome of a wild North American mallard (Anas platyrhynchos)

Abstract The mallard (Anas platyrhynchos) is one of the most common, economically, and socially important birds around the world. Mallards were not only an important food source for early humans but eventually becoming intimately linked with people as they were domesticated over the last 2,000 years. To date, mallard genomes are largely reconstructed from samples of domestic or unknown genetic heritage. Here, we report the first high-quality genome assembly and annotation of a genetically vetted wild mallard from North America (NAwild_v1.0). The genome was assembled using a combination of shotgun libraries, proximity ligation Chicago, and Dovetail Hi-C libraries. The final assembly is ∼1.04 Gb in size, with 98.3% of the sequence located in 30 full or nearly full chromosome-level scaffolds, and with a N50/L50 of 79.1 Mb/4 scaffolds. We used a combination of gene prediction and similarity approaches to annotate a total of 23,584 functional genes, of which 19,242 were associated to GO terms. The genome assembly and the set of annotated genes yielded a 95.4% completeness score when compared with the BUSCO aves_odb10 dataset. Next, we aligned 3 previously published mallard genomes to ours, and demonstrate how runs of homozygosity and nucleotide diversity are substantially higher and lower, respectively, to ours and how these artificially changed genomes resulted in profoundly different and biased demographic histories. Our wild mallard assembly not only provides a valuable resource to shed light onto genome evolution, speciation, and other adaptive processes, but also helping with identifying functional genes that have been significantly altered during the domestication process.