bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mlh1-Pms1 ATPase activity is regulated distinctly by self-generated nicks and strand discrimination signals in mismatch repair
Authors: Piscitelli Jonathan M , Witte Scott J , Sakinejad Yasmine S , Manhart Carol M 
Published: December 2024

Abstract
In eukaryotic post-replicative mismatch repair, MutS homolog complexes detect mismatches and in the major eukaryotic pathway, recruit Mlh1-Pms1/MLH1-PMS2 (yeast/human) complexes, which nick the newly replicated DNA strand upon activation by the replication processivity clamp, PCNA. This incision enables mismatch removal and DNA repair. Beyond its endonuclease role, Mlh1-Pms1/MLH1-PMS2 also has ATPase activity, which genetic studies suggest is essential for mismatch repair, although its precise regulatory role on DNA remains unclear. Here, we use an ATP-binding and hydrolysis-deficient yeast Mlh1-Pms1 variant to show that ATP hydrolysis promotes disengagement from Mlh1-Pms1-generated nicks, with hydrolysis in the Mlh1 subunit driving this activity. Our data suggest that the ATPase-deficient variant becomes trapped on its own endonuclease product, suggesting a mechanistic explanation for observations in genetic experiments. Additionally, we observed that Mlh1-Pms1 selectively protects DNA from exonuclease degradation at pre-existing nicks, which may act as strand discrimination signals in mismatch repair. Together, our findings suggest that Mlh1-Pms1 exhibits distinct behaviors on its own endonuclease products versus substrates with pre-existing nicks, supporting two distinct modes of action during DNA mismatch repair.
Modeling heterogeneity in the progression of chronic kidney disease
Authors: Butz Elena , Schultheiss Ulla T , Sekula Peggy 
Published: December 2024

Abstract
Cohort studies with comprehensive follow-up periods that track patients with chronic kidney disease (CKD) and gather extensive health data are important for understanding the diverse progression patterns of CKD. This review explores the potential of emerging analytical techniques that can be applied in addition to conventional analysis approaches to enhance CKD research, by offering more detailed insights into disease progression.
To maximize the insights available from CKD cohort data with extended follow-up, we examined two advanced approaches: analysis of disease trajectories and of recurrent events. The analysis of trajectories examines the timing and relationships between events, uncovering progression patterns and identifying key events that could signal future outcomes. In contrast, the application of recurrent event analysis facilitates the examination of repeated occurrences of significant events, thereby providing a more nuanced understanding of the evolution of risk over time.
Using data from the German Chronic Kidney Disease study, this review illustrates how these approaches can enhance conventional analyses. The application of these supplementary methodologies to CKD research has the potential to facilitate a transition towards a more personalized approach to patient care. The insights gained may inform the development of tailored treatment strategies and contribute to enhanced overall patient outcomes.
SHORT AND CROOKED AWN, encoding the epigenetic regulator EMF1, promotes barley awn development
Authors: Nakamura Koki , Kikuchi Yuichi , Shiraga Mizuho , Kotake Toshihisa , Hyodo Kiwamu , Taketa Shin , Ikeda Yoko 
Published: December 2024

Abstract
The awn is a bristle-like extension from the tip of the lemma in grasses. In barley, the predominant cultivars possess long awns that contribute to grain yield and quality through photosynthesis. In addition, various awn morphological mutants are available in barley, rendering it a useful cereal crop to investigate the mechanims of awn development. Here, we identified the gene causative of the short and crooked awn (sca) mutant, which exhibits a short and curved awn phenotype. Intercrossing experiments revealed that the sca mutant induced in the Japanese cultivar (cv.) “Akashinriki” is allelic to the independently isolated moderately short-awn mutant breviaristatum-a (ari-a). Map-based cloning and sequencing revealed that SCA encodes the Polycomb group–associated protein EMBRYONIC FLOWER 1. We found that SCA affects awn development through the promotion of cell proliferation, elongation, and cell wall synthesis. RNA sequencing of cv. Bowman backcross-derived near-isogenic lines of sca and ari-a6 alleles showed that SCA is directly or indirectly involved in promoting the expression of genes related to awn development. Additionally, SCA represses various transcription factors essential for floral organ development and plant architecture, such as MADS-box and Knotted1-like homeobox genes. Notably, the repression of the C-class MADS-box gene HvMADS58 by SCA in awns is associated with the accumulation of the repressive histone modification H3K27me3. These findings highlight the potential role of SCA-mediated gene regulation, including histone modification, as a novel pathway in barley awn development.
A linker histone acts as a transcription factor to orchestrate malic acid accumulation in apple in response to sorbitol
Authors: Hu Da-Gang , Zhang Mengxia , Li Chunlong , Zhao Ting-Ting , Du Lian-Da , Sun Quan , Wang Chu-Kun , Meng Dong , Sun Cui-Hui , Fei Zhangjun , Dandekar Abhaya M , Cheng Lailiang 
Published: December 2024

Abstract
High carbohydrate availability promotes malic acid accumulation in fleshy fruits, but the underlying mechanism is not known. Here, we show that antisense repression of ALDOSE-6-PHOSPHATE REDUCTASE in apple (Malus domestica) decreases the concentrations of sorbitol and malate and the transcript levels of several genes involved in vacuolar malate transport, including the aluminum-activated malate transporter (ALMT) gene MdALMT9 (Ma1), the P-ATPase gene MdPH5, the MYB transcription factor gene MdMYB73, and the cold-induced basic helix-loop-helix transcription factor gene MdCIbHLH1, in fruit and leaves. We identified a linker histone H1 variant, MdH1.1, which complements the Arabidopsis (Arabidopsis thaliana) H1 deficient mutant and functions as a transcription factor. MdH1.1 activates MdMYB73, MdCIbHLH1, and MdPH5 expression by directly binding to their promoters. MdMYB73, in return, binds to the promoter of MdH1.1 to enhance its transcription. This MdH1.1-MdMYB73 feedback loop responds to sorbitol, regulating Ma1 expression. Antisense suppression of either MdH1.1 or MdMYB73 expression significantly decreases whereas overexpression increases Ma1 expression and malate accumulation. These findings demonstrate that MdH1.1, in addition to being an architectural protein for chromatin structure, operates as a transcription factor orchestrating malic acid accumulation in response to sorbitol, revealing how sugar signaling modulates vacuolar malate transport via a linker histone in plants.
The brassinosteroid signaling-related ILI–OsAIF–OsbHLH92 transcription factor module antagonistically controls leaf angle and grain size in rice
Authors: Lu Mingmin , Liu Mingqian , Luo Qin , He Yubing , Tian Yanan , Zhan Huadong 
Published: December 2024

Abstract
Atypical basic helix–loop–helix (bHLH) transcription factors, which lack the basic region for DNA binding, are important elements of brassinosteroid (BR) signaling. Recently, our systematic characterization of the rice (Oryza sativa) INCREASED LEAF INCLINATION (ILI) subfamily of atypical bHLHs revealed their indispensable roles in BR-mediated growth and development. Here, we reported the isolation of two additional rice ILI-interacting atypical bHLHs, ATBS1-INTERACTING FACTOR 1 (OsAIF1)/OsbHLH176 and OsAIF2/OsbHLH178. Genetic and cytological analyses of the OsAIFs knockout mutants and overexpression lines revealed that OsAIF1 and OsAIF2 negatively regulate rice leaf inclination and grain size in a synergistic and redundant manner. Compared to the wild-type, osaif knockout mutants exhibited hypersensitivity to BR, while OsAIF1 and OsAIF2 overexpression lines showed greatly reduced sensitivity or complete insensitivity to BR, indicating that these two OsAIFs act as major negative regulators of rice BR signaling. As ILI-interacting negative atypical HLHs, OsAIF1 and OsAIF2 genetically counteracted the positive ILI subfamily of atypical HLHs. Moreover, OsAIF1 and OsAIF2 physically interacted with and antagonized OsbHLH92, a positive regulator of BR signaling, thereby modulating rice development and gene transcription. These findings suggested that the atypical HLHs (ILIs and OsAIF1/OsAIF2) and the bHLH (OsbHLH92) transcription factors form a triantagonistic cascade in rice, counteracting each other to fine-tune leaf angle and grain size through BR signaling. Our results provide insights into the mechanisms balancing BR signaling and growth in rice.
Effectiveness of pharmacological therapies for fibromyalgia syndrome in adults: an overview of Cochrane Reviews
Authors: Moore Andrew , Bidonde Julia , Fisher Emma , Häuser Winfried , Bell Rae Frances , Perrot Serge , Makri Souzi , Straube Sebastian 
Published: December 2024

Abstract

Objectives
To summarize and evaluate Cochrane reviews of pharmacological therapies for adults with fibromyalgia syndrome (FMS) pain.

Methods
Systematic search of Cochrane Database of Systematic Reviews to May 2024. Generic quality assessment used AMSTAR-2 criteria, validity checks of potentially critical factors in evaluation of analgesic efficacy and assessment of susceptibility of results to publication bias. Pain outcomes were participant-reported pain relief of ≥30% or ≥50%, or PGIC much or very much improved.

Results
Twenty-one reviews (87 trials, 17 631 patients) were included. All rated moderate (15) or high-quality (6) using AMSTAR-2 and at least seven of eight critical pain criteria were met by 13 of 21 reviews. Diagnosis of FMS used recognized criteria. Seven reviews found no trials (carbamazepine, clonazepam, lamotrigine, phenytoin, oxycodone, topiramate or valproate), seven had limited and inadequate data (antipsychotics, cannabinoids, combination therapy, gabapentin, lacosamide, monoamine oxidase inhibitors, NSAIDs) and two were subject to publication bias (amitriptyline, SSRI). Mirtazapine had moderate evidence of no effect. Duloxetine, milnacipran and pregabalin had moderate/good evidence of substantial pain relief for 4–12 weeks in around 1 in 10 adults with moderate or severe FMS pain, without evidence of efficacy beyond six months. Serious adverse events were no more common than with placebo. There was no evidence about who might benefit or experience adverse events. There was no substantial efficacy evidence for other medicines.

Conclusions
Duloxetine, milnacipran and pregabalin had good evidence that about 1 person in 10 with moderate or severe pain experienced pain intensity reduction by at least 50%.
Changes in iPSC-Astrocyte morphology reflect Alzheimer’s disease patient clinical markers
Authors: Rowland Helen A , Miller Georgina , Liu Qiang , Li Shuhan , Sharp Nicola R , Ng Bryan , Wei Tina , Arunasalam Kanisa , Koychev Ivan , Hedegaard Anne , Ribe Elena M , Chan Dennis , Chessell Tharani , Kocagoncu Ece , Lawson Jennifer , Malhotra Paresh , Ridha Basil H , Rowe James B , Thomas Alan J , Zamboni Giovanna , Zetterberg Henrik , Cader M Zameel , Wade-Martins Richard , Lovestone Simon , Nevado-Holgado Alejo , Kormilitzin Andrey , Buckley Noel J 
Published: December 2024

Abstract
Human induced pluripotent stem cells (iPSCs) provide powerful cellular models of Alzheimer’s disease (AD) and offer many advantages over non-human models, including the potential to reflect variation in individual-specific pathophysiology and clinical symptoms. Previous studies have demonstrated that iPSC-neurons from individuals with Alzheimer’s disease (AD) reflect clinical markers, including β-amyloid (Aβ) levels and synaptic vulnerability. However, despite neuronal loss being a key hallmark of AD pathology, many risk genes are predominantly expressed in glia, highlighting them as potential therapeutic targets. In this work iPSC-derived astrocytes were generated from a cohort of individuals with high versus low levels of the inflammatory marker YKL-40, in their cerebrospinal fluid (CSF). iPSC-derived astrocytes were treated with exogenous Aβ oligomers and high content imaging demonstrated a correlation between astrocytes that underwent the greatest morphology change from patients with low levels of CSF-YKL-40 and more protective APOE genotypes. This finding was subsequently verified using similarity learning as an unbiased approach. This study shows that iPSC-derived astrocytes from AD patients reflect key aspects of the pathophysiological phenotype of those same patients, thereby offering a novel means of modelling AD, stratifying AD patients and conducting therapeutic screens.
Fine particulate matter and nonaccidental and cause-specific mortality: Do associations vary by exposure assessment method?
Authors: Klompmaker Jochem O. , James Peter , Kaufman Joel D. , Schwartz Joel , Yanosky Jeff D. , Hart Jaime E. , Laden Francine 
Published: December 2024

Background:
There is considerable heterogeneity in fine particulate matter (PM2.5)–mortality associations between studies, potentially due to differences in exposure assessment methods. Our aim was to evaluate associations of PM2.5 predicted from different models with nonaccidental and cause-specific mortality.

Methods:
We followed 107,906 participants of the Nurses’ Health Study cohort from 2001 to 2016. PM2.5 concentrations were estimated from spatiotemporal models developed by researchers at the University of Washington (UW), Pennsylvania State University (PSU), and Harvard TH Chan School of Public Health (HSPH). We calculated 12-month moving average concentrations and we used time-varying Cox proportional hazard ratios (HRs).

Results:
There were 30,242 nonaccidental deaths in 1,435,098 person-years. We observed high correlations and similar temporal trends between the PM2.5 predictions. We found no associations of UW, PSU, or HSPH PM2.5 with nonaccidental mortality, but suggestive positive associations with cancer, cardiovascular, and respiratory disease mortality. There were small differences in HRs between the PM2.5 predictions. All three predictions showed the strongest associations with cancer mortality: HRs (95% confidence interval, expressed per 5 µg/m3 increase) were 1.06 (1.01, 1.12) for UW, 1.08 (1.03, 1.13) for PSU, and 1.05 (1.00, 1.10) for HSPH. In a subset restricted to participants who were always exposed to PM2.5 below 12 µg/m3, we observed positive associations with nonaccidental mortality.

Conclusion:
We found that differences between PM2.5 exposure assessment methods could lead to minor differences in strengths of associations between PM2.5 and cause-specific mortality in a population of US female nurses.
Clinical Characteristics of Patients With Symptomatic Nasolacrimal Duct Stenosis
Authors: Rose Geoffrey E. , Vahdani Kaveh 
Published: December 2024

Purpose:
To characterize symptoms and signs for patients with tearing eye(s) and ipsilateral nasolacrimal duct stenosis (NLDS), as defined by delayed fluorescein disappearance test and ocular reflux of saline during gentle irrigation of a patent drainage system.

Methods:
Retrospective case-note review of a consistent grading of 4 symptoms and 7 signs, together with estimates of the degree of fluid reflux and nasal fluid passage on gentle saline syringing. Characteristics, including gender differences, were compared for unilateral or bilateral symptoms. A side-to-side comparison was performed in unilateral cases, and assessed for concordance of signs and/or symptoms.

Results:
The average age of presentation was 62.4 years in 386 patients (37% male), with a third having unilateral symptoms. Systemic atopy (22%) and chronic nasal disease (27%) were frequent. Patients with unilateral symptoms were significantly younger (males 9.5, females 5.5 years; p < 0.000001) and had shorter symptom duration (p = 0.0025). Three-quarters of asymptomatic sides had objective evidence of nasolacrimal duct stenosis, and there was significant side-to-side concordance for 7/9 clinical signs. Among 640 symptomatic systems, many of the presenting (subjective) symptoms and/or objective signs showed a significant direct or inverse correlation.

Conclusion:
The lack of laterality- or gender bias for symptoms and signs suggests that patients with nasolacrimal duct stenosis might seek treatment for the epiphora per se, rather than for issues with ocular dominance or visual requirements. The close correlation between subjective symptom-severity and objective estimates of signs suggests that thorough clinical assessment can be very reliable, and that several factors probably contribute to symptoms in these patients.
Characteristics of Patients Hospitalized With Methamphetamine-Associated Heart Failure
Authors: Hiatt Shirin O. , Camacho S. Albert , Lee Christopher S. , Dieckmann Nathan F. , Mitchell Jayne , Robles Yasmine , Shalen Evan F. , Habecker Beth A. , Denfeld Quin E. 
Published: December 2024

Background
Methamphetamine-associated heart failure (MethHF) carries devastating individual and societal consequences; however, our understanding of this condition is limited.

Objective
The objective of this study is to compare the sociodemographic and clinical characteristics of patients hospitalized with MethHF with patients hospitalized with heart failure (HF) not associated with methamphetamine (non-MethHF).

Methods
This was an analysis of screening data from MethHF patients who screened out of the Biological and Physiological Mechanisms of Symptom Clusters in Heart Failure study and a subset of non-MethHF patients enrolled in the study. Descriptive and comparative statistics were used.

Results
Patients hospitalized with MethHF (n = 99), compared with non-MethHF (n = 87), were significantly younger, more often male, more likely from urban areas, and had higher rates of prior emergency room usage. Patients with MethHF also had more nonischemic etiologies and reduced ejection fraction. Nearly a third of patients with MethHF also had a new diagnosis of HF.

Conclusions
There are a few notable differences in sociodemographic and clinical characteristics between patients hospitalized with MethHF versus non-MethHF.
Comparison of oral zinc supplement and placebo effect in improving the T-cells regeneration in patients undergoing autologous hematopoietic stem cell transplantation: Clinical trial study
Authors: Nikoonezhad Maryam , Zavaran Hosseini Ahmad , Hajifathali Abbas , Parkhideh Sayeh , Shadnoush Mahdi , Shakiba Yadollah , Zahedi Hoda 
Published: December 2024

Background:
Immune reconstitution is a significant factor in the success of “hematopoietic stem cell transplantation” (HSCT). Delaying the immune reconstitution increases the risk of infections and relapse after transplantation. T-cell recovery after HSCT is mainly thymus-dependent, and thymic atrophy is associated with various clinical conditions that correlate with HSCT outcomes. Thymus rejuvenation can improve immune reconstitution after transplantation.
Zinc (Zn) plays a pivotal role in thymus rejuvenation. Zn deficiency can lead to thymic atrophy, which increases susceptibility to infections. Zn supplementation restores the immune system by increasing thymus output and T-cell repertoire production.
We designed this protocol to investigate the effect of oral Zn supplementation on T-cell recovery in patients undergoing HSCT.

Methods:
Forty eligible candidates for autologous-HSCT will be selected. They will be randomly divided into Zn and placebo groups. Subsequently, they will receive 3 Zn or placebo tablets for the first 30 days post-HSCT (+1 to +30), followed by 1 pill or placebo for days (+31 to +90). The copy numbers of “recent thymic emigrants” T cells and “T cell Receptor Excision Circles” (TREC) will be assessed before and after the intervention in peripheral blood mononuclear cells (PBMCs). All patients will be followed up 365 days post-HSCT for relapse and infection.

Conclusion:
This clinical trial is the first to determine the efficiency of “Zn gluconate” as daily Supplementation in T cell recovery post-HSCT.
If successful, an available and inexpensive drug will improve immune system reconstruction after HSCT, reduce the risk of infection, particularly viral infections, and increase patient survival.
Research on the correlation between inflammatory bowel disease and depression: A bibliometric analysis
Authors: Liu Pengliang , Zhang Yongchuang , Huang Huang , Li Yucheng 
Published: December 2024

Background:
The aim of this study was to conduct a bibliometric analysis of published studies on the relationship between inflammatory bowel disease (IBD) and depression. The study also aims to identify the major researchers, institutions, and countries and regions in this field to identify current research hotspots.

Methods:
The Web of Science Core Database in the Science Citation Index Expanded database was selected as the data source and was searched to obtain relevant literature on IBD and depression. Bibliometric analysis of relevant publications was performed by utilizing VOSviewer, CiteSpace, bibliometrix, and Microsoft Excel 2019.

Results:
A total of 393 papers were included from January 1, 2014, to December 25, 2023, showing a general upward trend in the number of publications. There were 48 countries and 743 institutions, of which the United States had the largest number of publications. There were 2250 authors involved in research in the field, with clear collaborations between authors. There were currently 163 journals that have published research on this topic, with IBDs being the most cited journal. IBD and depression-related studies are gradually gaining attention from researchers, and the research direction is gradually expanding to epidemiology, gut microbiota, and other related topics.

Conclusion:
This study comprehensively summarizes the research trends and developments of IBD and depression through bibliometrics. This information points out the research frontiers and hot directions in recent years, which will serve as a reference for researchers in this field.