Miracle-dz/UniFAR-FTUs huggingface dataset:
Circadian rhythms in cardiac metabolic flexibility

ABSTRACT Numerous aspects of cardiovascular physiology (e.g., heart rate, blood pressure) and pathology (e.g., myocardial infarction and sudden cardiac death) exhibit time-of-day-dependency. In association with day-night differences in energetic demand and substrate availability, the healthy heart displays remarkable metabolic flexibility through temporal partitioning of the metabolic fate of common substrates (glucose, lipid, amino acids). The purpose of this review is to highlight the contribution that circadian clocks provide toward 24-hr fluctuations in cardiac metabolism and to discuss whether attenuation and/or augmentation of these metabolic rhythms through adjustment of nutrient intake timing impacts cardiovascular disease development.
Chromosome-Scale Genome Assembly of the Resurrection Plant Acanthochlamys bracteata (Velloziaceae)

Abstract Acanthochlamys bracteata (Velloziaceae) is a resurrection plant with cold tolerance. Herein, a chromosome-level reference genome of A. bracteata based on Nanopore, Illumina, and Hi-C data is reported. The high-quality assembled genome was 197.97 Mb, with a scaffold N50 value of 8.64 Mb and a contig N50 value of 6.96 Mb. We annotated 23,509 protein-coding genes. Eight contracted gene families and three expanded gene families were detected. Repeat sequences accounted for approximately 28.63% of the genome. The LEA1 and Dehydrin gene families, which are involved in desiccation resistance, expanded in A. bracteata. We identified genes involved in chilling tolerance, COLD1.
Large‐scale electron microscopic volume imaging of interfascicular oligodendrocytes in the mouse corpus callosum

Single oligodendrocytes produce myelin sheaths around multiple axons in the central nervous system. Interfascicular oligodendrocytes (IOs) facilitate nerve conduction, but their detailed morphologies remain largely unknown. In the present study, we three‐dimensionally reconstructed IOs in the corpus callosum of adult mouse using serial block face scanning electron microscopy. The cell bodies of IOs were morphologically polarized and extended thick processes from the cytoplasm‐rich part of the cell. Processes originating from the cell body of each IO can be classified into two types: one myelinates an axon without branching, while the other type branches and each branch myelinates a distinct axon. Myelin sheaths originating from a particular IO have biased thicknesses, wrapping axons of a limited range of diameters. Consistent with this finding, IOs transduced and visualized with a rabies viral vector expressing GFP showed statistically significant variation in their myelination patterns. We further reconstructed the sheath immediately adjacent to that derived from each of the analyzed IOs; the thicknesses of the pair of sheaths were significantly correlated despite emanating from different IOs. These results suggest that a single axon could regulate myelin sheath thicknesses, even if the sheaths are derived from distinct IOs. Collectively, our results indicate that the IOs have their own myelin profiles defined by myelin thickness and axonal diameter although axons may regulate thickness of myelin sheath.
Hospital outcome of concomitant tricuspid annuloplasty during totally endoscopic mitral valve surgery: a propensity matched study

Background This study aimed to determine how concomitant tricuspid annuloplasty (TAP) affects the clinical outcomes of patients undergoing totally endoscopic mitral valve surgery. Methods This was a single-centre, retrospective study. Between January 2019 and June 2020, 143 patients who underwent totally endoscopic mitral valve surgery in our institution were enrolled. Ninety-two patients who underwent isolated mitral valve surgery were categorized into the minimally invasive mitral valve surgery (MIMVS) group (n=92), and patients who underwent mitral valve surgery with concomitant TAP were categorized into the MIMVS-TAP (n=51) group. Clinical data were collected from all patients, including demographic and perioperative data. We conducted propensity score matching (PSM) by using one-to-one ratio nearest-neighbour matching for baseline demographic data and tricuspid valve-related parameters. Forty patients in each group were matched in this way. Parametric and nonparametric tests were performed for data analysis. Results Statistically, postoperative mortality within 30 days was not significantly different between the two groups (P=1). No differences were found in serious adverse events, such as stroke or third-degree conduction block, between the two groups after 1:1 PSM (P=1 and P=0.480, respectively). The mean operation time for the MIMVS+TAP group was longer (232.13±36.05 min) than that for the MIMVS group (204.25±28.49 min; P<0.001). The same was true for the cardiopulmonary bypass (CPB) time (169.48±25.96 vs. 153.10±23.00 min; P=0.004) and aortic clamp time (110.80±17.37 vs. 101.00±14.38 min; P=0.005). The duration of the intensive care unit stay and the overall postoperative length of stay were not different between the two groups (P=0.734 and P=0.472, respectively). The postoperative systolic pulmonary artery pressure differed between the two groups [38.00±8.45 (MIMVS); 33.65±7.34 (MIMVS + TAP), P=0.022]. Conclusions Our study showed that totally endoscopic mitral valve surgery with concomitant TAP is just as safe and effective as isolated totally endoscopic mitral valve surgery, even with a long surgery duration. Our study also suggested that totally endoscopic mitral valve surgery with concomitant TAP can improve tricuspid function in patients.
Expression of Organic Anion Transporting Polypeptides in an H-Ras 12V Transgenic Mouse Model of Spontaneous Hepatocellular Carcinoma

Purpose Expression of organic anion transporting polypeptides (OATPs) 1B1/1B3 in hepatocellular carcinoma (HCC) induces a paradoxical enhancement of gadoxetic acid on liver magnetic resonance imaging (MRI). We examined the expression profile of OATPs with regard to tumor differentiation in a genetically modified H-Ras 12V mouse model of spontaneous HCC that undergoes multistep hepatocarcinogenesis with minimal inter-individual variation. Materials and Methods Tumor nodules were harvested from transgenic H-Ras 12V mice. Hematoxylin and eosin-stained slides were examined for tumor differentiation and high-grade pathological components (tumor necrosis, thickened trabeculae, or vascular invasion). Immunohistochemistry of OATP 1B1/1B3 was performed, and OATP expression was assessed. Results We examined well-differentiated HCCs (n=59) in which high-grade pathological components were absent (n=49) or present (n=10). Among the well-differentiated HCCs without high-grade pathological components (n=49), OATP expression was negative, weak positive, and moderate positive in 23, 17, and nine cases, respectively. Among the well-differentiated HCCs with high-grade pathological components (n=10), OATP expression was negative, weak positive, and moderate positive in one, two, and seven cases, respectively. The ratio of positive OATP 1B1/1B3 expressing tumors was higher in HCCs with high-grade pathological components than in those without high-grade pathological components (p=0.004). Conclusion Our findings support those of previous clinical studies that have reported the frequent appearance of gadoxetic acid-enhanced MRI in moderately differentiated HCC.
Machine Learning‐Reinforced Noninvasive Biosensors for Healthcare

The emergence and development of noninvasive biosensors largely facilitate the collection of physiological signals and the processing of health‐related data. The utilization of appropriate machine learning algorithms improves the accuracy and efficiency of biosensors. Machine learning‐reinforced biosensors are started to use in clinical practice, health monitoring, and food safety, bringing a digital revolution in healthcare. Herein, the recent advances in machine learning‐reinforced noninvasive biosensors applied in healthcare are summarized. First, different types of noninvasive biosensors and physiological signals collected are categorized and summarized. Then machine learning algorithms adopted in subsequent data processing are introduced and their practical applications in biosensors are reviewed. Finally, the challenges faced by machine learning‐reinforced biosensors are raised, including data privacy and adaptive learning capability, and their prospects in real‐time monitoring, out‐of‐clinic diagnosis, and onsite food safety detection are proposed.
Food availability and long-term predation risk interactively affect antipredator response.

Food availability and temporal variation in predation risk are both important determinants of the magnitude of antipredator responses, but their effects have rarely been examined simultaneously, particularly in wild prey. Here, we determine how food availability and long-term predation risk affect antipredator responses to acute predation risk by monitoring the foraging response of free-ranging snowshoe hares (Lepus americanus) to an encounter with a Canada lynx (Lynx canadensis) in Yukon, Canada, over 4 winters (from 2015-2016 to 2018-2019). We examined how this response was influenced by natural variation in long-term predation risk (two-month mortality rate of hares) while providing some individuals with supplemental food. On average, snowshoe hares reduced foraging time up to 10 hours after coming into close proximity (≤ 75 m) with lynx, and reduced foraging time an average of 15.28 ± 7.08 minutes per lynx encounter. Hares tended to respond more strongly when the distance to lynx was shorter. More importantly, the magnitude of hares' antipredator response to a lynx encounter was affected by the interaction between food-supplementation and long-term predation risk. Food-supplemented hares reduced foraging time more than control hares after a lynx encounter under low long-term risk, but decreased the magnitude of the response as long-term risk increased. In contrast, control hares increased the magnitude of their response as long-term risk increased. Our findings show that food availability and long-term predation risk interactively drive the magnitude of reactive antipredator response to acute predation risk. Determining the factors driving the magnitude of antipredator responses would contribute to a better understanding of the indirect effects of predators on prey populations.
Substrate usage determines carbon flux via the citrate cycle in Helicobacter pylori

Helicobacter pylori displays a worldwide infection rate of about 50%. The Gram‐negative bacterium is the main reason for gastric cancer and other severe diseases. Despite considerable knowledge about the metabolic inventory of H. pylori, carbon fluxes through the citrate cycle (TCA cycle) remained enigmatic. In this study, different 13C‐labeled substrates were supplied as carbon sources to H. pylori during microaerophilic growth in a complex medium. After growth, 13C‐excess and 13C‐distribution were determined in multiple metabolites using GC–MS analysis. [U‐13C6]Glucose was efficiently converted into glyceraldehyde but only less into TCA cycle‐related metabolites. In contrast, [U‐13C5]glutamate, [U‐13C4]succinate, and [U‐13C4]aspartate were incorporated at high levels into intermediates of the TCA cycle. The comparative analysis of the 13C‐distributions indicated an adaptive TCA cycle fully operating in the closed oxidative direction with rapid equilibrium fluxes between oxaloacetate—succinate and α‐ketoglutarate—citrate. 13C‐Profiles of the four‐carbon intermediates in the TCA cycle, especially of malate, together with the observation of an isocitrate lyase activity by in vitro assays, suggested carbon fluxes via a glyoxylate bypass. In conjunction with the lack of enzymes for anaplerotic CO2 fixation, the glyoxylate bypass could be relevant to fill up the TCA cycle with carbon atoms derived from acetyl‐CoA.
Tuning the Fluorescence and the Intramolecular Charge Transfer of Phenothiazine Dipolar and Quadrupolar Derivatives by Oxygen Functionalization

A series of new naphthalimide and phenothiazine-based push–pull systems (NPI-PTZ1–5), in which we structurally modulate the oxidation state of the sulfur atom in the thiazine ring, i.e., S(II), S(IV), and S(VI), was designed and synthesized by the Pd-catalyzed Sonogashira cross-coupling reaction. The effect of the sulfur oxidation state on the spectral, photophysical, and electrochemical properties was investigated. The steady-state absorption and emission results show that oxygen functionalization greatly improves the optical (absorption coefficient and fluorescence efficiency) and nonlinear optical (hyperpolarizability) features. The cyclic voltammetry experiments and the quantum mechanical calculations suggest that phenothiazine is a stronger electron donor unit relative to phenothiazine-5-oxide and phenothiazine-5,5-dioxide, while the naphthalimide is a strong electron acceptor in all cases. The advanced ultrafast spectroscopic measurements, transient absorption, and broadband fluorescence up conversion give insight into the mechanism of photoinduced intramolecular charge transfer. A planar intramolecular charge transfer (PICT) and highly fluorescent excited state are populated for the oxygen-functionalized molecules NPI-PTZ2,3 and NPI-PTZ5; on the other hand, a twisted intramolecular charge transfer (TICT) state is produced upon photoexcitation of the oxygen-free derivatives NPI-PTZ1 and NPI-PTZ4, with the fluorescence being thus significantly quenched. These results prove oxygen functionalization as a new effective synthetic strategy to tailor the photophysics of phenothiazine-based organic materials for different optoelectronic applications. While oxygen-functionalized compounds are highly fluorescent and promising active materials for current-to-light conversion in organic light-emitting diode devices, oxygen-free systems show very efficient photoinduced ICT and may be employed for light-to-current conversion in organic photovoltaics.
Comparing the pelvis of Tibetan and Chinese Han women in rural areas of China: two population-based studies using coarsened exact matching

Abstract This study aims to investigate the difference of pelvic size and shape between Tibetan and Chinese Han women. Data on pelvic dimension measures including interspinous diameter (IS), intercrestal diameter (IC), external conjugate (EC) and transverse outlet (TO) were acquired from two population-based studies amongst Tibetan women in Lhasa, and Chinese Han women in Shaanxi province in China. After coarsened exact matching, there was no statistical difference between any characteristics amongst Tibetan and Chinese Han women (p>.05). The generalised estimating equation models showed Tibetan women had significantly lower IS and IC means than Chinese Han women (IS: 24.39 cm vs. 24.77 cm, p<.001; IC: 26.35 cm vs. 26.93 cm, p<.001) but statistically higher in TO mean (9.12 cm vs. 9.03 cm, p<.001). This study showed Tibetan women have smaller pelvis compared to Chinese Han women. This should offer a useful literature on the comparison of pelvis between Tibetan and Chinese Han women although the difference is small. Impact Statement What is already known on this subject? Previous studies in China indicated different populations have different dimensions of pelvis, with the pelvis of Uighur women being bigger than Chinese Han women, and that of Zhuang and Tu women being smaller than Chinese Han women. Little research reports the specific size of Tibetan women’s pelvis. Living at high altitude, the Tibetan population have differentiated demographics and show local adaptions, such as unelevated haemoglobin, and significant catch-up growth for infants compared with Chinese Han infants. Therefore, there is a strong rationale for better understanding pelvic characteristics amongst this population. What the results of this study add? This study showed Tibetan women have smaller pelvises compared to Chinese Han women. Tibetan women have a smaller interspinous diameter and intercrestal diameter than Chinese Han women, which leads to relatively narrow hip. What the implications are of these findings for clinical practice and/or further research? This study provides useful comparative information on pelvic features between Tibetan and Chinese Han women although the findings of differences were small. In addition, during the formulation of women’s health policy, the results of this study can provide data to support the selection of appropriate indicators of obstetrics and gynaecology for different populations of pregnant women during antenatal care and delivery.
CHD4 regulates platinum sensitivity through MDR1 expression in ovarian cancer: A potential role of CHD4 inhibition as a combination therapy with platinum agents

Platinum sensitivity is an important prognostic factor in patients with ovarian cancer. Chromodomain-helicase-DNA-binding protein 4 (CHD4) is a core member of the nucleosome remodeling and deacetylase complex, which functions as a chromatin remodeler. Emerging evidence indicates that CHD4 could be a potential therapeutic target for cancer therapy. The purpose of this study was to clarify the role of CHD4 in ovarian cancer and investigate its therapeutic potential focusing on platinum sensitivity. In an analysis of the Cancer Genome Atlas ovarian cancer dataset, CHD4 gene amplification was associated with worse overall survival. CHD4 mRNA expression was significantly higher in platinum-resistant samples in a subsequent clinical sample analysis, suggesting that CHD4 overexpression conferred platinum resistance to ovarian cancer cells, resulting in poor patient survival. In concordance with these findings, CHD4 knockdown enhanced the induction of apoptosis mediated by cisplatin in ovarian cancer cells TOV21G and increased cisplatin sensitivity in multiple ovarian cancer cells derived from different subtypes. However, CHD4 knockdown did not affect the expression of RAD51 or p21, the known targets of CHD4 in other cancer types that can modulate platinum sensitivity. Knockdown and overexpression assays revealed that CHD4 positively regulated the expression of multi-drug transporter MDR1 and its coding protein p-glycoprotein. In addition, a first-in-class CHD4/SMARCA5 inhibitor ED2-AD101 showed synergistic interactions with cisplatin. Our findings suggest that CHD4 mediates platinum sensitivity by modulating MDR1 expression in ovarian cancer. Further, CHD4 suppression has a potential to be a novel therapeutic strategy in combination with platinum agents.
An Easy, Cost‐Effective, and Scalable Method to Deplete Human Ribosomal RNA for RNA‐seq

RNA sequencing (RNA‐seq) is a powerful and increasingly prevalent method to characterize and quantify the transcriptome. Ribosomes are extremely abundant, however, and approximately 80% of total RNA is ribosomal RNA (rRNA). Therefore, to detect and quantify less abundant yet biologically important transcripts such as messenger RNA (mRNA) and long noncoding RNAs (lncRNA), it is essential to minimize the rRNA being sequenced. Although commercial methods exist to deplete rRNA from total RNA samples before sequencing, they are expensive and require specific amounts of input RNA, and the most commonly used kit is no longer available as a stand‐alone product. Here, we present an optimized rRNA depletion protocol using RNase H and DNA oligonucleotides complementary to human rRNA transcripts. This protocol includes guidelines for DNA oligo preparation, RNA:DNA hybridization, RNase H cleavage and RNA cleanup, and benchmarking of rRNA depletion. The method is flexible because the user can include additional complementary DNA oligos directed against any abundant transcript in their particular system. Furthermore, the performance of this rRNA depletion approach is comparable to or better than that of commercial kits, at a fraction of the cost and across a wide range of input RNA amounts. © 2021 Wiley Periodicals LLC.
Draft Genome Sequence of Klebsiella pneumoniae subsp. pneumoniae CCI2, Isolated from Leaf Soil

Klebsiella pneumoniae subsp. pneumoniae CCI2 was isolated from leaf soil collected in Hiroshima Prefecture, Japan. The draft genome sequence comprises 78 contigs and contains 5,075,115 bp with a G+C content of 57.7%. ABSTRACT Klebsiella pneumoniae subsp. pneumoniae CCI2 was isolated from leaf soil collected in Hiroshima Prefecture, Japan. The draft genome sequence comprises 78 contigs and contains 5,075,115 bp with a G+C content of 57.7%.
Comparing the acute effects of shiftwork on mothers and fathers

Abstract Background Shift work may impact women more negatively than men due to the increased burden of coping with demanding work schedules while also undertaking more of the domestic chores, including childcare. Aims To examine whether the combination of shift working and caring for children affects the sleep, fatigue and work–family conflict experienced by women more than it affects men. Methods Using data from a survey of the Swedish working population, mixed linear regression models examined work schedule (daywork, shift work with nights, shift work without nights), gender and presence of children <13 years at home as predictors of sleep insufficiency, sleep disturbance, fatigue and work–family conflict, over up to three successive measurement occasions. Adjustments were made for age, education, full/part-time working and baseline year. Results In fully adjusted models (N = 8938), shift work was associated with insufficient sleep (P < 0.01), disturbed sleep (P < 0.01), fatigue (P < 0.05) and work–family conflict (P < 0.001). Interactions in the analyses of sleep disturbance (P < 0.001) and work–family interference (P < 0.05) indicated that among participants with no children, females reported more disturbed sleep and more work–family conflict than their male counterparts, irrespective of schedule; while among participants with children, female dayworkers reported more disturbed sleep than their male counterparts, and females working shifts without nights reported more work–family interference. Conclusions Having young children did not exacerbate negative effects of shift work, in either men or women. This may reflect high levels of gender equality and childcare provision in Sweden.
Development and validation of a prognostic score for long‐term transplant‐free survival in autoimmune hepatitis type 1

Abstract Background No prognostic score is currently available for long‐term survival in autoimmune hepatitis (AIH) patients. Objective The aim of this study was to develop and validate such a prognostic score for AIH patients at diagnosis. Methods The prognostic score was developed using uni‐ & multivariate Cox regression in a 4‐center Dutch cohort and validated in an independent 6‐center Belgian cohort. Results In the derivation cohort of 396 patients 19 liver transplantations (LTs) and 51 deaths occurred (median follow‐up 118 months; interquartile range 60–202 months). In multivariate analysis age (hazard ratio [HR] 1.045; p < 0.001), non‐caucasian ethnicity (HR 1.897; p = 0.045), cirrhosis (HR 3.266; p < 0.001) and alanine aminotransferase level (HR 0.725; p = 0.003) were significant independent predictors for mortality or LT (C‐statistic 0.827; 95% CI 0.790–0.864). In the validation cohort of 408 patients death or LT occurred in 78 patients during a median follow‐up of 74 months (interquartile range: 25–142 months). Predicted 5‐year event rate did not differ from observed event rate (high risk group 21.5% vs. 15.7% (95% CI: 6.3%–24.2%); moderate risk group 5.8% versus 4.3% (95% CI: 0.0%–9.1%); low risk group 1.9% versus 5.4% (95% CI: 0.0%–11.4%); C‐statistic 0.744 [95% CI 0.644–0.844]). Conclusions A Dutch‐Belgian prognostic score for long‐term transplant‐free survival in AIH patients at diagnosis was developed and validated.