Miracle-dz/UniFAR-FTUs huggingface dataset:
Plant clock modifications for adapting flowering time to local environments

Abstract During and after the domestication of crops from ancestral wild plants, humans selected cultivars that could change their flowering time in response to seasonal daylength. Continuous selection of this trait eventually allowed the introduction of crops into higher or lower latitudes and different climates from the original regions where domestication initiated. In the past two decades, numerous studies have found the causal genes or alleles that change flowering time and have assisted in adapting crop species such as barley (Hordeum vulgare), wheat (Triticum aestivum L.), rice (Oryza sativa L.), pea (Pisum sativum L.), maize (Zea mays spp. mays), and soybean (Glycine max (L.) Merr. ) to new environments. This updated review summarizes the genes or alleles that contributed to crop adaptation in different climatic areas. Many of these genes are putative orthologs of Arabidopsis (Arabidopsis thaliana) core clock genes. We also discuss how knowledge of the clock’s molecular functioning can facilitate molecular breeding in the future.
Reproducibility and postacquisition correction methods for quantitative magnetic resonance imaging of the anterior cruciate ligament (ACL)

Quantitative magnetic resonance imaging has been used to evaluate the structural integrity of knee joint structures. However, variations in acquisition parameters between scanners pose significant challenges. Understanding the effect of small differences in acquisition parameters for quantitative sequences is vital to the validity of cross‐institutional studies, and for the harmonization of large, heterogeneous datasets to train machine learning models. The study objective was to assess the reproducibility of T2* relaxometry and the constructive interference in steady‐state sequence (CISS) across scanners, with minimal hardware‐necessitated changes to acquisition parameters. It was hypothesized that there would be no significant differences between scanners in anterior cruciate ligament T2* relaxation times and CISS signal intensities (SI). Secondarily, it was hypothesized that differences could be corrected by rescaling the SI distribution to harmonize between scanners. Seven volunteers were scanned on 3T Prisma and Tim Trio scanners (Siemens). Three correction methods were evaluated for T2*: inverse echo time scaling, z‐scoring, and Nyúl histogram matching. For CISS, scans were normalized to cortical bone, scaled by the background noise ratio, and log‐transformed. Before correction, significant mean differences of 6.0 ± 3.2 ms (71.8%; p = 0.02) and 0.49 ± 0.15 units (40.7%; p = 0.02) for T2* and CISS across scanners were observed, respectively. After rescaling, T2* differences decreased to 2.6 ± 2.7 ms (23.9%; p = 0.03), 1.3 ± 2.5 ms (10.9%; p = 0.13), and 1.27 ± 3.0 ms (19.6%; p = 0.40) for inverse echo time, z‐scoring, and Nyúl, respectively, while CISS decreased to 0.01 ± 0.11 units (4.0%; p = 0.87). These findings suggest that small acquisition parameter differences may lead to large changes in T2* and SI values that must be reconciled to compare data across magnets.
Bayesian inference of ancestral recombination graphs

We present a novel algorithm, implemented in the software ARGinfer, for probabilistic inference of the Ancestral Recombination Graph under the Coalescent with Recombination. Our Markov Chain Monte Carlo algorithm takes advantage of the Succinct Tree Sequence data structure that has allowed great advances in simulation and point estimation, but not yet probabilistic inference. Unlike previous methods, which employ the Sequentially Markov Coalescent approximation, ARGinfer uses the Coalescent with Recombination, allowing more accurate inference of key evolutionary parameters. We show using simulations that ARGinfer can accurately estimate many properties of the evolutionary history of the sample, including the topology and branch lengths of the genealogical tree at each sequence site, and the times and locations of mutation and recombination events. ARGinfer approximates posterior probability distributions for these and other quantities, providing interpretable assessments of uncertainty that we show to be well calibrated. ARGinfer is currently limited to tens of DNA sequences of several hundreds of kilobases, but has scope for further computational improvements to increase its applicability.
Brolucizumab for the treatment of diabetic macular edema.

PURPOSE OF REVIEW To review the available data supporting the use of brolucizumab in the treatment of diabetic macular edema (DME). RECENT FINDINGS Brolucizumab is a humanized single- chain variable antibody fragment (scFv), the smallest functional subunit of an antibody approved for intravitreal use. Three phase III studies demonstrate that at 52 weeks, brolucizumab has statistically superior anatomical outcomes of reducing retinal thickness (54.0-57.5% of brolucizumab treated eyes achieved central subfield thickness <280 μm compared to 40.1-41.4% of aflibercept treated eyes) and retinal fluid (present in 54.2-60.3% of brolucizumab treated eyes compared to 72.9-78.2% of aflibercept treated eyes). Brolucizumab also demonstrated a prolonged durability up to 16 weeks, thus reducing treatment burden. The visual outcomes appear noninferior to current anti-VEGF agents with an increased risk for intraocular inflammatory events (0.3-4.7% compared to 0.6-1.7%). SUMMARY Results from recent phase III trials showing the efficacy and safety of brolucizumab presents an additional therapeutic option in the DME treatment landscape. It can reduce treatment burden in DME with increased inter-treatment intervals while conferring efficacy in both functional and anatomical outcomes. Caution should be taken regarding the risks of intraocular inflammation, retinal vasculitis, and retinal vascular occlusion.
Structures, functions, and inhibitors of LUBAC and its related diseases

Ubiquitination is a reversible posttranslational modification in which ubiquitin is covalently attached to substrates at catalysis by E1, E2, and E3 enzymes. As the only E3 ligase for assembling linear ubiquitin chains in animals, the LUBAC complex exerts an essential role in the wide variety of cellular activities. Recent advances in the LUBAC complex, including structure, physiology, and correlation with malignant diseases, have enabled the discovery of potent inhibitors to treat immune‐related diseases and cancer brought by LUBAC complex dysfunction. In this review, we summarize the current progress on the structures, physiologic functions, inhibitors of LUBAC, and its potential role in immune diseases, tumors, and other diseases, providing the theoretical basis for therapy of related diseases targeting the LUBAC complex.
HPV AND DNA METHYLATION TESTING IN URINE FOR CERVICAL INTRAEPITHELIAL NEOPLASIA AND CERVICAL CANCER DETECTION.

BACKGROUND Biomarker detection in urine offers a potential solution to increase effectiveness of cervical cancer screening programs by attracting non-responders. In this prospective study, the presence of high-risk human papillomavirus (hrHPV DNA) and the performance of DNA methylation analysis was determined for the detection of cervical cancer and high-grade cervical intraepithelial neoplasia (CIN2/3) in urine, and compared to paired cervicovaginal self-samples and clinician-taken cervical scrapes. METHODS A total of 587 samples were included from 113 women with cervical cancer, 92 women with CIN2/3, and 64 controls. Samples were tested for hrHPV DNA and five methylation markers. Univariate and multivariate logistic regression and leave-one-out cross-validation were used to determine the methylation marker performance for CIN3 and cervical cancer (CIN3+) detection in urine. Agreement between samples was determined using Cohen's kappa statistics and the Spearman correlation coefficients. RESULTS HrHPV presence was high in all sample types, 79% to 92%. Methylation levels of all markers in urine significantly increased with increasing severity of disease. The optimal marker panel (ASCL1/LHX8) resulted in an AUC of 0.84 for CIN3+ detection in urine, corresponding to an 86% sensitivity at a 70% predefined specificity. At this threshold 96%(109/113) of cervical cancers, 68%(46/64) of CIN3 and 58%(14/24) of CIN2 were detected. Between paired samples, a strong agreement for HPV16/18 genotyping and a fair to strong correlation for methylation was found. CONCLUSION HrHPV DNA and DNA methylation testing in urine offers a promising solution to detect cervical cancer and CIN2/3 lesions, especially for women currently unreached by conventional screening methods.
The technical landscape for patient-centered CDS: progress, gaps, and challenges

Abstract Supporting healthcare decision-making that is patient-centered and evidence-based requires investments in the development of tools and techniques for dissemination of patient-centered outcomes research findings via methods such as clinical decision support (CDS). This article explores the technical landscape for patient-centered CDS (PC CDS) and the gaps in making PC CDS more shareable, standards-based, and publicly available, with the goal of improving patient care and clinical outcomes. This landscape assessment used: (1) a technical expert panel; (2) a literature review; and (3) interviews with 18 CDS stakeholders. We identified 7 salient technical considerations that span 5 phases of PC CDS development. While progress has been made in the technical landscape, the field must advance standards for translating clinical guidelines into PC CDS, the standardization of CDS insertion points into the clinical workflow, and processes to capture, standardize, and integrate patient-generated health data.
Formation Mechanism of a Nano‐Ring of Bismuth Cations and Mono‐Lacunary Keggin‐Type Phosphomolybdate

Abstract A new hetero‐bimetallic polyoxometalate (POM) nano‐ring was synthesized in a one‐pot procedure. The structure consists of tetrameric units containing four bismuth‐substituted monolacunary Keggin anions including distorted [BiO8] cubes. The nano‐ring is formed via self‐assembly from metal precursors in aqueous acidic medium. The compound (NH4)16[(BiPMo11O39)4] ⋅ 22 H2O; (P4Bi4Mo44) was characterized by single‐crystal X‐ray diffraction, extended X‐ray absorption fine structure spectroscopy (EXAFS), Raman spectroscopy, matrix‐assisted laser desorption/ionisation‐time of flight mass spectrometry (MALDI‐TOF), and thermogravimetry/differential scanning calorimetry mass spectrometry (TG‐DSC‐MS). The formation of the nano‐ring in solution was studied by time‐resolved in situ small‐ and wide‐angle X‐ray scattering (SAXS/WAXS) and in situ EXAFS measurements at the Mo−K and the Bi−L3 edge indicating a two‐step process consisting of condensation of Mo‐anions and formation of Bi−Mo‐units followed by a rapid self‐assembly to yield the final tetrameric ring structure.
Awareness of and willingness to use oral HIV self-test kits among Kenyan young adults living in informal urban settlements: a cross-sectional survey

ABSTRACT Self-administered HIV testing may be a promising strategy to improve testing in hard-to-reach young adults, provided they are aware of and willing to use oral HIV self-testing (HIVST). This study examined awareness of and willingness to use oral HIVST among 350 high-risk young adults, aged 18–22, living in Kenya’s informal urban settlements. Bivariate and multivariate logistic regressions were used to examine differences in HIVST awareness and willingness by demographic and sexual risk factors. Findings showed that most participants were male (56%) and less than 20 years old (60%). Awareness of oral HIVST was low (19%). However, most participants (75%) were willing to use an oral HIV self-test in the future and ask their sex partner(s) to self-test before having sex (77%). Women (OR = 1.80, 95%CI:1.11, 2.92), older participants (aged 20+) (OR = 2.57, 95% CI:1.48, 4.46), and more educated participants (OR = 2.25, 95%CI:1.36, 3.70) were more willing to use HIVST as compared to men, teen-aged, and less educated participants, respectively. Young adults who reported recent engagement in high-risk sexual behaviors, such as unprotected sex, sex while high or drunk, or sex exchange, were significantly less likely to be willing to use an oral HIV self-test kit (OR = 0.34, 95%CI:0.13,0.86). Those with the highest monthly income (OR = 0.47, 95%CI: 0.25, 0.89) were also less willing to use HIVST. More community- and peer-based efforts are needed to highlight the range of benefits of HIVST (i.e., social, clinical, and structural) to appeal to various youth demographics, in addition to addressing concerns relating to HIVST.
Exploring Practice Patterns of Pediatric Telerehabilitation During COVID-19: A Survey Study

Background and Objective: Sudden transition to telerehabilitation during the coronavirus disease 2019 (COVID-19) pandemic was challenging for pediatric therapists, including physical therapists and occupational therapists, due to lack of prior experience and knowledge. The primary goal of the current study was to survey the pediatric therapists regarding the practice trends and specific challenges/strengths of delivering telerehabilitation during the pandemic. Materials and Methods: An electronic survey was developed by the research term and validated through cognitive interviews with three pediatric therapists. A total of 107 therapists completed the survey. Descriptive statistics were used to summarize the trends for the survey questions. Results: The majority of therapists (92.5%) reported no prior experience with telerehabilitation. When comparing telerehabilitation with standard-of-care, the therapists reported similar session durations and frequencies, but greater caregiver-initiated cancellations of telerehabilitation sessions. Furthermore, a greater percentage of therapists modified the intervention activities compared with assessments, which impacted therapists' perceptions about quality of telerehabilitation as a greater percentage of therapists expressed confidence in treating children compared with assessing children virtually. One of the commonly reported telerehabilitation challenges was reduced virtual engagement of children, and strength was better assessment of home environment. Lastly, a greater percentage of therapists relied on consultations and fewer therapists used empirical evidence to guide their delivery of virtual care. Conclusions: Telerehabilitation is a cost-effective health care model that offers remote accessibility and flexible scheduling. However, several limitations in the current pediatric telerehabilitation model, including lack of teleassessments and empirical evidence, could limit post-COVID use of telerehabilitation.
Reducing ischemic kidney injury through application of a synchronization modulation electric field to maintain Na+/K+-ATPase functions

Renal ischemia-reperfusion injury is an important contributor to the development of delayed graft function after transplantation, which is associated with higher rejection rates and poorer long-term outcomes. One of the earliest impairments during ischemia is Na+/K+-ATPase (Na/K pump) dysfunction due to insufficient ATP supply, resulting in subsequent cellular damage. Therefore, strategies that preserve ATP or maintain Na/K pump function may limit the extent of renal injury during ischemia-reperfusion. Here, we applied a synchronization modulation electric field to activate Na/K pumps, thereby maintaining cellular functions under ATP-insufficient conditions. We tested the effectiveness of this technique in two models of ischemic renal injury: an in situ renal ischemia-reperfusion injury model (predominantly warm ischemia) and a kidney transplantation model (predominantly cold ischemia). Application of the synchronization modulation electric field to a renal ischemia-reperfusion injury mouse model preserved Na/K pump activity, thereby reducing kidney injury, as reflected by 40% lower plasma creatinine (1.17 ± 0.03 mg/dl) in the electric field–treated group as compared to the untreated control group (1.89 ± 0.06 mg/dl). In a mouse kidney transplantation model, renal graft function was improved by more than 50% with the application of the synchronization modulation electric field according to glomerular filtration rate measurements (85.40 ± 12.18 μl/min in the untreated group versus 142.80 ± 11.65 μl/min in the electric field–treated group). This technique for preserving Na/K pump function may have therapeutic potential not only for ischemic kidney injury but also for other diseases associated with Na/K pump dysfunction due to inadequate ATP supply. Description Kidney injury can be reduced by electrically fueling Na+/K+-ATPases during renal ischemia without overall ATP consumption. Electrically inhibiting ischemic damage Organ ischemia can lead to insufficient ATP supplies, resulting in Na+/K+-ATPase dysfunction and cell damage. Here, Chen and colleagues applied a synchronization modulation electric field to rodent kidneys to maintain Na+/K+-ATPase function during ischemia. The technique first synchronizes the Na+/K+-ATPases and then applies electric energy to run the pumps, producing an ATP molecule with each pumping cycle. The pumping rates can be modulated either up or down and then maintained at the target rate. In mouse models of warm and cold ischemia, the technique decreased kidney injury and improved function, and application of the technique to human kidneys during cold storage decreased histological evidence of injury, suggesting that the approach might be useful in minimizing allograft dysfunction.
A possible role for VPS13-family proteins in bulk lipid transfer, membrane expansion and organelle biogenesis

ABSTRACT At organelle–organelle contact sites, proteins have long been known to facilitate the rapid movement of lipids. Classically, this lipid transport involves the extraction of single lipids into a hydrophobic pocket on a lipid transport protein. Recently, a new class of lipid transporter has been described with physical characteristics that suggest these proteins are likely to function differently. They possess long hydrophobic tracts that can bind many lipids at once and physically span the entire gulf between membranes at contact sites, suggesting that they may act as bridges to facilitate bulk lipid flow. Here, we review what has been learned regarding the structure and function of this class of lipid transporters, whose best characterized members are VPS13 and ATG2 proteins, and their apparent coordination with other lipid-mobilizing proteins on organelle membranes. We also discuss the prevailing hypothesis in the field, that this type of lipid transport may facilitate membrane expansion through the bulk delivery of lipids, as well as other emerging hypotheses and questions surrounding these novel lipid transport proteins.
Habitual Green Kiwifruit Consumption Is Associated with a Reduction in Upper Gastrointestinal Symptoms: A Systematic Scoping Review

ABSTRACT Kiwifruit have known positive effects on digestion. During clinical intervention trials using kiwifruit to improve constipation, upper gastrointestinal (GI) symptoms such as abdominal discomfort and pain, indigestion, and reflux were also alleviated. We aimed to evaluate the evidence for upper GI symptom relief by kiwifruit in clinical trials on participants with functional constipation (FC), irritable bowel syndrome with constipation (IBS-C), and healthy participants, and to elucidate which symptoms may be relieved and whether a difference exists between the effects of gold and green kiwifruit. We executed a systematic scoping review of 3 electronic databases from 1947 through January 2021 to identify clinical trials that reported effects of green or gold kiwifruit or kiwifruit compounds on upper GI symptoms as secondary outcomes in healthy participants or participants with FC or IBS-C. Studies were divided into those using the Gastrointestinal Symptom Rating Scale (GSRS) and those using alternative measurement tools. GSRS outcomes were pooled and statistically analyzed; non-GSRS outcomes were summarized. We identified 12 clinical trials with a total of 661 participants (124 controls, 537 receiving intervention) providing evidence for symptom relief of upper GI symptoms by kiwifruit intake. Only 5 of the 12 clinical trials used the GSRS to assess upper GI symptom relief. We found good evidence that green kiwifruit may reduce abdominal discomfort and pain, and some evidence that kiwifruit consumption may attenuate indigestion. Pooled GSRS outcome analysis indicates an average reduction of –0.85 (95% CI: –1.1, –0.57; Z = 6.1) in abdominal pain scores and –0.33 (95% CI: –0.52, –0.15; Z = –3.5) in indigestion scores with habitual kiwifruit consumption. While the number of studies reporting on upper GI symptom relief with a comparable measurement is limited, there is consistent evidence for the efficacy of kiwifruit on upper GI symptom relief. More research to strengthen the evidence is recommended.
Off‐pump versus on‐pump coronary artery bypass grafting for octogenarians: A meta‐analysis involving 146 372 patients

There is an ongoing debate concerning the optimal surgical option of myocardial revascularization for octogenarians. The current meta‐analysis aimed to compare clinical outcomes following off‐pump coronary artery bypass grafting (OPCABG) or conventional coronary artery bypass grafting (CCABG) in octogenarians. PubMed, Cochrane, Web of Science, and EMBASE databases were searched to identify eligible studies from inception to March 2021. The analysis was performed using STATA 15.1. A literature search yielded 18 retrospective studies involving 146 372 patients (OPCABG = 44 522 vs. CCABG = 101 850). Pooled analysis showed a strong trend toward reducing mortality risk in the OPCABG group (odds ratio: 0.75, 95% confidence interval: 0.56–1.00, p = .05). However, it did not reach statistical significance. The sensitive analysis demonstrated that OPCABG was less likely to cause death than CCABG. There were comparable data in myocardial infarction, renal failure, deep sternal wound infection, and hospital stays between the two groups, although the incidence of stroke, atrial fibrillation, prolonged ventilation, and reoperation for bleeding was significantly lower in the OPCAGB group. OPCABG may be an effective surgical strategy for myocardial revascularization, especially in reducing the incidence of postoperative stroke, atrial fibrillation, prolonged ventilation, and reoperation for bleeding.