bluuebunny/crossref_metadata_2025_split huggingface dataset:
FishmiRNA: An Evolutionarily Supported MicroRNA Annotation and Expression Database for Ray-Finned Fishes
Authors: Desvignes Thomas , Bardou Philippe , Montfort Jérôme , Sydes Jason , Guyomar Cervin , George Simon , Postlethwait John H , Bobe Julien 
Published: January 2022

Abstract
MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression involved in countless biological processes and are widely studied across metazoans. Although miRNA research continues to grow, the large community of fish miRNA researchers lacks exhaustive resources consistent among species. To fill this gap, we developed FishmiRNA, an evolutionarily supported miRNA annotation and expression database for ray-finned fishes: www.fishmirna.org. The self-explanatory database contains detailed, manually curated miRNA annotations with orthology relationships rigorously established by sequence similarity and conserved syntenies, and expression data provided for each detected mature miRNA. In just few clicks, users can download the annotation and expression database in several convenient formats either in its entirety or a subset. Simple filters and Blast search options also permit the simultaneous exploration and visual comparison of expression data for up to any ten mature miRNAs across species and organs. FishmiRNA was specifically designed for ease of use to reach a wide audience.
Dissecting the genotype-phenotype correlation of COL4A5 gene mutation and its response to renin-angiotensin-aldosterone system blockers in Chinese male patients with Alport syndrome
Authors: Di Hongling , Zhang Jiahui , Gao Erzhi , Zheng Chunxia , Huang Xianghua , Wang Qing , Yu Xiaomin , Liu Zhihong 
Published: January 2022

ABSTRACT

Background
Alport syndrome (AS) is an inherited type IV collagen–related disorder with an irreversible tendency to progress to end-stage renal disease (ESRD). X-linked AS (XLAS) is caused by mutations in the COL4A5 gene. The aim of this study was to investigate the effects of underlying mutations on clinical manifestations and the response to therapy in XLAS.

Methods
We conducted a retrospective cohort study of 187 Chinese male patients with XLAS confirmed by pathological examination and genetic analysis. The Kaplan–Meier method and Cox proportional hazards model were used to assess the age and risk of progression to ESRD under different genotypes and treatment conditions.

Results
A strong relationship between transcript type and renal outcome was observed, with the median age of ESRD onset being 22 years for truncating mutations and 39 years for non-truncating mutations. The response of affected patients to renin–angiotensin–aldosterone system (RAAS) blockers was genotype-associated. This therapy delayed the onset of ESRD by 16 years in patients with non-truncating mutations and 3 years in patients with truncating mutations. The efficacy of RAAS blockers functioned in a time-dependent manner, with a 7% reduction in the risk of progression to ESRD per each 6-month increase in treatment duration [hazard ratio 0.93 (95% confidence interval 0.89–0.96); P &lt; 0.001].

Conclusions
Clinical features and response to RAAS blockers were observed to be strongly correlated with the genotypes of male XLAS patients. Genotyping of COL4A5 gene mutations is essential and is a useful tool to assess the prognosis of AS patients.
RtNet: a deep hybrid neural network for the identification of acute rejection and chronic allograft nephropathy after renal transplantation using multiparametric MRI
Authors: Zhi Rui , Zhang Xiao-Dong , Hou Ying , Jiang Ke-Wen , Li Qiao , Zhang Jing , Zhang Yu-Dong 
Published: January 2022

ABSTRACT

Background
Reliable diagnosis of the cause of renal allograft dysfunction is of clinical importance. The aim of this study is to develop a hybrid deep-learning approach for determining acute rejection (AR), chronic allograft nephropathy (CAN) and renal function in kidney-allografted patients by multimodality integration.

Methods
Clinical and magnetic resonance imaging (MRI) data of 252 kidney-allografted patients who underwent post-transplantation MRI between December 2014 and November 2019 were retrospectively collected. An end-to-end convolutional neural network, namely RtNet, was designed to discriminate between AR, CAN and stable renal allograft recipient (SR), and secondarily, to predict the impaired renal graft function [estimated glomerular filtration rate (eGFR) ≤50 mL/min/1.73 m2]. Specially, clinical variables and MRI radiomics features were integrated into the RtNet, resulting in a hybrid network (RtNet+). The performance of the conventional radiomics model RtRad, RtNet and RtNet+ was compared to test the effect of multimodality interaction.

Results
Out of 252 patients, AR, CAN and SR was diagnosed in 20/252 (7.9%), 92/252 (36.5%) and 140/252 (55.6%) patients, respectively. Of all MRI sequences, T2-weighted imaging and diffusion-weighted imaging with stretched exponential analysis showed better performance than other sequences. On pairwise comparison of resulting prediction models, RtNet+ produced significantly higher macro-area-under-curve (macro-AUC) (0.733 versus 0.745; P = 0.047) than RtNet in discriminating between AR, CAN and SR. RtNet+ performed similarly to the RtNet (macro-AUC, 0.762 versus 0.756; P &gt; 0.05) in discriminating between eGFR ≤50 mL/min/1.73 m2 and &gt;50 mL/min/1.73 m2. With decision curve analysis, adding RtRad and RtNet to clinical variables resulted in more net benefits in diagnostic performance.

Conclusions
Our study revealed that the proposed RtNet+ model owned a stable performance in revealing the cause of renal allograft dysfunction, and thus might offer important references for individualized diagnostics and treatment strategy.
Integrating morphologic and molecular histopathological features through whole slide image registration and deep learning
Authors: Faust Kevin , Lee Michael K , Dent Anglin , Fiala Clare , Portante Alessia , Rabindranath Madhumitha , Alsafwani Noor , Gao Andrew , Djuric Ugljesa , Diamandis Phedias 
Published: January 2022

Abstract

Background
Modern molecular pathology workflows in neuro-oncology heavily rely on the integration of morphologic and immunohistochemical patterns for analysis, classification, and prognostication. However, despite the recent emergence of digital pathology platforms and artificial intelligence-driven computational image analysis tools, automating the integration of histomorphologic information found across these multiple studies is challenged by large files sizes of whole slide images (WSIs) and shifts/rotations in tissue sections introduced during slide preparation.

Methods
To address this, we develop a workflow that couples different computer vision tools including scale-invariant feature transform (SIFT) and deep learning to efficiently align and integrate histopathological information found across multiple independent studies. We highlight the utility and automation potential of this workflow in the molecular subclassification and discovery of previously unappreciated spatial patterns in diffuse gliomas.

Results
First, we show how a SIFT-driven computer vision workflow was effective at automated WSI alignment in a cohort of 107 randomly selected surgical neuropathology cases (97/107 (91%) showing appropriate matches, AUC = 0.96). This alignment allows our AI-driven diagnostic workflow to not only differentiate different brain tumor types, but also integrate and carry out molecular subclassification of diffuse gliomas using relevant immunohistochemical biomarkers (IDH1-R132H, ATRX). To highlight the discovery potential of this workflow, we also examined spatial distributions of tumors showing heterogenous expression of the proliferation marker MIB1 and Olig2. This analysis helped uncover an interesting and unappreciated association of Olig2 positive and proliferative areas in some gliomas (r = 0.62).

Conclusion
This efficient neuropathologist-inspired workflow provides a generalizable approach to help automate a variety of advanced immunohistochemically compatible diagnostic and discovery exercises in surgical neuropathology and neuro-oncology.
Nicotine Content in Swedish-Type Snus Sold in Norway From 2005 to 2020
Authors: Vedøy Tord Finne , Lund Karl Erik 
Published: January 2022

Abstract

Introduction
Use of snus (moist smokeless tobacco) is widespread in Scandinavia and increasingly popular in the U.S. Snus products vary in terms of product design, portion size, and nicotine content. The aim of this study was to examine variations in the nicotine content in snus sold on the Norwegian market from 2005 to 2020.

Methods
We calculated the nicotine content in dry snus in milligram per gram (mg/g) and milligram per serving (mg/s), weighted by the products’ market share from data on nicotine content, water content, and portion size (both for portion and loose snus) for the ten most sold snus products from each of the three largest manufacturers in 2005, 2010, 2015, and 2020.

Results
In all snus products combined, the nicotine content per gram snus (mg/g) increased from 16.3 to 24.1, while nicotine per serving (mg/s) was stable around 13.0. In portion snus, the nicotine content increased for both mg/g and mg/s, most notably from 2005 to 2010. In loose snus, mg/g decreased marginally, while mg/s was stable throughout the period.

Conclusions
In a period with increasing snus use, the nicotine content in snus increased per gram snus, but not per serving. The stability in nicotine per serving is likely due to a decreasing market share of loose snus which accounted for 54% of the snus products in 2005 and 5% in 2020, and which traditionally has a high content of nicotine per serving.

Implications
Use of snus is popular in Scandinavia, most notably in Sweden and Norway, but also increasingly common in Finland, especially among young adults. There are no prior market-based studies of variations in the nicotine content in Swedish snus over time. We found that the average amount of nicotine per gram snus sold on the Norwegian market increased in the period 2005 to 2020, most notably from 2005 to 2010, while the amount of nicotine per serving was stable in the same period, primarily due to a decreasing share of loose snus.
Effects of Marijuana Use on Smokers Switching to E-Cigarettes in a Randomized Clinical Trial
Authors: Rice Myra , Nollen Nicole L , Ahluwalia Jasjit S , Benowitz Neal , Woodcock Anna , Pulvers Kim 
Published: January 2022

Abstract

Introduction
Co-use of tobacco and marijuana is common, and research suggests that marijuana use may be a barrier to smoking cessation. Research to date has not evaluated how marijuana use affects e-cigarette switching behaviors and related outcomes in a harm reduction trial.

Aims and Methods
This secondary analysis includes African American (48%) and Latinx (52%) adult smokers randomized to the e-cigarette group (N = 114) of a harm reduction clinical trial from 2018 to 2019. Participants were provided JUUL e-cigarettes and encouraged to make an exclusive switch for 6 weeks. Our primary outcome was cigarettes smoked per week. Secondary health outcomes were e-cigarette substitution (calculated by measuring e-cigarette pod use), expired carbon monoxide (CO), and respiratory symptoms. Marijuana products were recorded at three timepoints and coded for combustion.

Results
Marijuana use during the study (n = 52, 46%) was not associated with week 6 cigarettes smoked or e-cigarette substitution, and combustible marijuana use was not associated with week 6 respiratory symptoms (ps &gt; .05). After controlling for cigarettes smoked at week 6, combustible marijuana use was significantly associated with a 4.4 ppm increase in CO compared with no use of marijuana (p = .001).

Conclusions
Marijuana use was not a barrier to switching to e-cigarettes in this 6-week trial. Marijuana use contributed to elevated CO, reflecting greater exposure to toxic combustion products, beyond the effects of cigarette smoking. Marijuana co-use may increase risk of adverse health outcomes and may be a confounding factor when using CO as an endpoint to bioverify exclusive e-cigarette use.

Implications
This is the first known study to examine the effects of marijuana use on smokers switching to e-cigarettes. Marijuana use was not a barrier to cigarette reduction in a 6-week randomized clinical trial. Marijuana use uniquely contributed to higher carbon monoxide among cigarette smokers, indicating greater exposure to toxic combustion products, which could increase risk of adverse health outcomes. Furthermore, combustible marijuana use may be a confounding factor when CO is used as an endpoint to bioverify exclusive e-cigarette use.
BBX17 Interacts with CO and Negatively Regulates Flowering Time in Arabidopsis thaliana
Authors: Xu Xiaorui , Xu Jingya , Yuan Chen , Chen Qianqian , Liu Qinggang , Wang Xuming , Qin Cheng 
Published: January 2022

Abstract
Floral transition, the change from vegetative growth to reproductive development, is dramatic in flowering plants. Here, we show that one subgroup III member of the B-box (BBX) family, BBX17, is a repressor of floral transition under long-day conditions. BBX17 contains a B-box domain and a CCT domain. Although the phenotype of the BBX17 loss-of-function plants was comparable to that of wild-type plants, BBX17-overexpression plants displayed a delayed-flowering phenotype under long-day conditions. The delayed-flowering phenotype was not the result of an altered CONSTANS (CO) expression level but rather the repression of the FLOWERING LOCUS T (FT) expression level. BBX17 physically associated with CO and repressed its ability to control FT expression. Furthermore, the BBX17 protein degraded in the dark, but irradiating seedlings with white, blue, red or far-red light stabilized the BBX17 level. We also proved that the degradation of BBX17 was via 26S proteasome and requires COP1. Thus, BBX17 acts as a key factor in the CO–FT regulatory system to control Arabidopsis thaliana flowering.
Low temperature inhibits anthocyanin accumulation in strawberry fruit by activating FvMAPK3-induced phosphorylation of FvMYB10 and degradation of Chalcone Synthase 1
Authors: Mao Wenwen , Han Yu , Chen Yating , Sun Mingzhu , Feng Qianqian , Li Li , Liu Liping , Zhang Kaikai , Wei Lingzhi , Han Zhenhai , Li Bingbing 
Published: January 2022

Abstract
Low temperature causes poor coloration of strawberry (Fragaria sp.) fruits, thus greatly reducing their commercial value. Strawberry fruits accumulate anthocyanins during ripening, but how low temperature modulates anthocyanin accumulation in plants remains largely unknown. We identified MITOGEN-ACTIVATED PROTEIN KINASE3 (FvMAPK3) as an important negative regulator of anthocyanin accumulation that mediates the poor coloration of strawberry fruits in response to low temperature. FvMAPK3 activity was itself induced by low temperature, leading to the repression of anthocyanin accumulation via two mechanisms. Activated FvMAPK3 acted as the downstream target of MAPK KINASE4 (FvMKK4) and SUCROSE NONFERMENTING1-RELATED KINASE2.6 (FvSnRK2.6) to phosphorylate the transcription factor FvMYB10 and reduce its transcriptional activity. In parallel, FvMAPK3 phosphorylated CHALCONE SYNTHASE1 (FvCHS1) to enhance its proteasome-mediated degradation. These results not only provide an important reference to elucidate the molecular mechanisms underlying low-temperature-mediated repression of anthocyanin accumulation in plants, but also offer valuable candidate genes for generating strawberry varieties with high tolerance to low temperature and good fruit quality.
A cascade of bHLH-regulated pathways programs maize anther development
Authors: Nan Guo-Ling , Teng Chong , Fernandes John , O'Connor Lily , Meyers Blake C , Walbot Virginia 
Published: January 2022

AbstractThe spatiotemporal development of somatic tissues of the anther lobe is necessary for successful fertile pollen production. This process is mediated by many transcription factors acting through complex, multi-layered networks. Here, our analysis of functional knockout mutants of interacting basic helix–loop–helix genes Ms23, Ms32, basic helix–loop–helix 122 (bHLH122), and bHLH51 in maize (Zea mays) established that male fertility requires all four genes, expressed sequentially in the tapetum (TP). Not only do they regulate each other, but also they encode proteins that form heterodimers that act collaboratively to guide many cellular processes at specific developmental stages. MS23 is confirmed to be the master factor, as the ms23 mutant showed the earliest developmental defect, cytologically visible in the TP, with the most drastic alterations in premeiotic gene expression observed in ms23 anthers. Notably, the male-sterile ms23, ms32, and bhlh122-1 mutants lack 24-nt phased secondary small interfering RNAs (phasiRNAs) and the precursor transcripts from the corresponding 24-PHAS loci, while the bhlh51-1 mutant has wild-type levels of both precursors and small RNA products. Multiple lines of evidence suggest that 24-nt phasiRNA biogenesis primarily occurs downstream of MS23 and MS32, both of which directly activate Dcl5 and are required for most 24-PHAS transcription, with bHLH122 playing a distinct role in 24-PHAS transcription.
The Mediating Effect of Perceived Injustice and Pain Catastrophizing in the Relationship of Pain on Fatigue and Sleep in Breast Cancer Survivors: A Cross-Sectional Study
Authors: Lahousse Astrid , Ivakhnov Sergei , Nijs, PhD Jo , Beckwée, PhD David , Cools, PhD Wilfried , Fernández de las Peñas, PhD César , Roose Eva , Leysen, PhD Laurence 
Published: January 2022

AbstractObjectiveMultidimensional aspects of pain have raised awareness about cognitive appraisals, such as perceived injustice (PI) and pain catastrophizing (PC). It has been demonstrated that they play an important role in patients’ pain experience. However, the mediating effect of these appraisals has not been investigated in breast cancer survivors (BCS), nor have they been related to fatigue and sleep.MethodsCross-sectional data from 128 BCS were analysed by structural path analysis with the aim to examine the mediating effect of PI and PC in the relationship of pain on fatigue and sleep.ResultsThe indirect mediating effects of PI on fatigue (CSI*PI = 0.21; P &lt; .01 and VAS*PI = 1.19; P &lt; .01) and sleep (CSI*PI = 0.31; P &lt; .01 and VAS*PI = 1.74; P &lt; .01) were found significant for both pain measures (Central Sensitization Inventory [CSI] and Visual Analogue Scale [VAS]). PC, on the other hand, only mediated the relationship between pain measured by VAS and fatigue (VAS*PC = 0.80; P = .03). Positive associations were found, indicating that higher pain levels are positively correlated with PI and PC, which go hand in hand with higher levels of fatigue and sleep problems.ConclusionsPI is an important mediator in the relationship of pain on fatigue and sleep, while PC is a mediator on fatigue after cancer treatment. These findings highlight that both appraisals are understudied and open new perspectives regarding treatment strategies in BCS.
Evaluation of the radon adsorption efficiency of activated carbon fiber using tetrafluoromethane
Authors: Kotsar Y , Nakano Y , Takeuchi Y , Miuchi K 
Published: January 2022

Abstract
The radioactive noble gas radon-222 (222Rn) is one of the most significant background sources in various types of rare event experiments, such as direct dark matter searches, neutrinoless double-beta decay searches, and neutrino experiments. Previously, a method to measure $\rm {}^{222}Rn$ concentration in purified air, argon, and xenon gases at a level of $\rm 1 \, mBq/m^{3}$ was established. Since other detector media are used in these experiments, there is a potential need to expand the study for other types of gases. In this paper the performance of an 80 liter $\rm {}^{222}Rn$ detector filled with tetrafluoromethane ($\rm CF_4$) gas, which is used for a direct dark matter search experiment, NEWAGE, was measured. The calibration factor of the detector for the $\rm CF_4$ gas was measured and its dependence on the absolute humidity was investigated. We also employed activated carbon fiber to evaluate its 222Rn adsorption efficiency in CF4, which was found to be $82.7\pm 0.1(\text{stat.})\pm 2.3(\text{syst.})\%$ at 0.10 MPa. For pressures lower than atmospheric pressure, we found that adsorption efficiency rises with lower pressure, and it is equal to $93.7\pm 0.3(\text{stat.})\pm 3.9(\text{syst.})\%$ at 0.03 MPa.
Degree of Safety Against Falls Provided by 4 Different Prosthetic Knee Types in People With Transfemoral Amputation: A Retrospective Observational Study
Authors: Palumbo Pierpaolo , Randi Pericle , Moscato Serena , Davalli Angelo , Chiari Lorenzo 
Published: January 2022

Abstract

Objective
People with transfemoral amputation have balance and mobility problems and are at high risk of falling. An adequate prosthetic prescription is essential to maximize their functional levels and enhance their quality of life. This study aimed to evaluate the degree of safety against falls offered by different prosthetic knees.

Methods
A retrospective study was conducted using data from a center for prosthetic fitting and rehabilitation. Eligible individuals were adults with unilateral transfemoral amputation or knee disarticulation. The prosthetic knee models were grouped into 4 categories: locked knees, articulating mechanical knees (AMKs), fluid-controlled knees (FK), and microprocessor-controlled knees (MPK). The outcome was the number of falls experienced during inpatient rehabilitation while wearing the prosthesis. Association analyses were performed with mixed-effect Poisson models. Propensity score weighting was used to adjust causal estimates for participant confounding factors.

Results
Data on 1486 hospitalizations of 815 individuals were analyzed. Most hospitalizations (77.4%) were related to individuals with amputation due to trauma. After propensity score weighting, the knee category was significantly associated with falls. People with FK had the highest rate of falling (incidence rate = 2.81 falls per 1000 patient days, 95% CI = 1.96 to 4.02). FK significantly increased the risk of falling compared with MPK (incidence rate ratio [IRRFK-MPK] = 2.44, 95% CI = 1.20 to 4.96). No other comparison among knee categories was significant.

Conclusions
Fluid-controlled prosthetic knees expose inpatients with transfemoral amputation to higher incidence of falling than MPK during rehabilitation training.

Impact
These findings can guide clinicians in the selection of safe prostheses and reduction of falls in people with transfemoral amputation during inpatient rehabilitation.