bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-Term Risk of Subsequent Malignant Neoplasms Among Childhood and Adolescent Lymphoma Survivors (1975-2013): A Population-Based Predictive Nomogram
Authors: Liu Junqi , Zheng Qingzhu , Beeraka Narasimha M , Zhang Xiao , Li Tingxuan , Song Ruixia , Zhao Di , Fan Ruitai 
Published: May 2023

Abstract

Background
Studies are needed to assess risk factors pertinent to the incidence of secondary malignancies among childhood and adolescent lymphoma survivors. We aimed to identify risk factors pertinent to the incidence of secondary malignancies and subsequently establish a clinically practical predictive nomogram.

Methods
A total of 5561 patients who were diagnosed with primary lymphoma below the age of 20 years between 1975 and 2013 and survived for at least 5 years were identified. Standardized incidence ratio (SIR) and excess risk (ER) analysis were performed by sex, age, and year when primary lymphoma was diagnosed, sites and types of primary lymphoma, and therapy strategies. Univariable and multivariable logistic regression were used to identify independent risk factors for adolescent and childhood lymphoma-related secondary malignancies. Based on 5 factors (age, time from lymphoma diagnosis, gender, lymphoma type, and therapy), a nomogram for predicting the risk of a secondary malignancy for patients with childhood and adolescent primary lymphoma was established.

Results
Among 5561 lymphoma survivors, 424 developed a secondary malignancy. Females (SIR = 5.34, 95% CI, 4.73-5.99; ER = 50.58) exhibited a higher SIR and ER than males (SIR = 3.28, 95% CI, 2.76-3.87; ER = 15.53). Blacks were at a higher risk than Caucasians or others. Nodular lymphocyte-predominant Hodgkin lymphoma survivors exhibited typically high SIR (13.13, 95% CI, 6-24.92) and ER (54.79) among all lymphoma classifications. Lymphoma survivors who underwent radiotherapy, whether they received chemotherapy or not, had typically higher SIR and ER. Among all types of secondary malignancies, “bone and joint neoplasms” (SIR = 11.07, 95% CI, 5.52-19.81) and “soft tissue neoplasms” (SIR = 12.27, 95% CI, 7.59-18.76) presented significantly high SIR whereas “breast cancer” and “endocrine cancer” associated with higher ER. The median diagnosis age of secondary malignancies was 36 years old, and the median time interval between the diagnosis of two malignancies was 23 years. A nomogram was constructed to predict the risk of secondary malignancies in patients diagnosed with primary lymphoma before 20 years of age. After internal validation, the AUC and C-index of the nomogram are 0.804 and 0.804, respectively.

Conclusion and Relevance
The established nomogram provides a convenient and reliable tool for predicting the risk of a secondary malignancy among childhood and adolescent lymphoma survivors, concluding significant concern for lymphoma survivors with high-risk estimates.
MpDWF5A-Encoded Sterol Δ7-Reductase Is Essential for the Normal Growth and Development of Marchantia polymorpha
Authors: Hatada Miki , Akiyama Ryota , Yamagishi Moeko , Ishizaki Kimitsune , Mizutani Masaharu 
Published: May 2023

Abstract
Sterols are essential components of eukaryotic cell membranes. However, studies on sterol biosynthesis in bryophytes are limited. This study analyzed the sterol profiles in the bryophyte model plant Marchantia polymorpha L. The thalli contained typical phytosterols such as campesterol, sitosterol and stigmasterol. BLASTX analysis of the M. polymorpha genome against the Arabidopsis thaliana sterol biosynthetic genes confirmed the presence of all the enzymes responsible for sterol biosynthesis in M. polymorpha. We further focused on characterizing two genes, MpDWF5A and MpDWF5B, which showed high homology with A. thaliana DWF5, encoding Δ5,7-sterol Δ7-reductase (C7R). Functional analysis using a yeast expression system revealed that MpDWF5A converted 7-dehydrocholesterol to cholesterol, indicating that MpDWF5A is a C7R. Mpdwf5a-knockout (Mpdwf5a-ko) lines were constructed using CRISPR/Cas9-mediated genome editing. Gas chromatography–mass spectrometry analysis of Mpdwf5a-ko revealed that phytosterols such as campesterol, sitosterol and stigmasterol disappeared, and instead, the corresponding Δ7-type sterols accumulated. The thalli of Mpdwf5a-ko grew smaller than those of the wild type, and excessive formation of apical meristem in the thalli was observed. In addition, the gemma cups of the Mpdwf5a-ko were incomplete, and only a limited number of gemma formations were observed. Treatment with 1 µM of castasterone or 6-deoxocastasterone, a bioactive brassinosteroid (BR), partly restored some of these abnormal phenotypes, but far from complete recovery. These results indicate that MpDWF5A is essential for the normal growth and development of M. polymorpha and suggest that the dwarfism caused by the Mpdwf5a-ko defect is due to the deficiency of typical phytosterols and, in part, a BR-like compound derived from phytosterols.
FTSH PROTEASE 3 facilitates Complex I degradation through a direct interaction with the Complex I subunit PSST
Authors: Ghifari Abi S , Ivanova Aneta , Berkowitz Oliver , Whelan James , Murcha Monika W 
Published: May 2023

Abstract
Complex I (CI) (NADH dehydrogenase), the largest complex involved in mitochondrial oxidative phosphorylation, is composed of nuclear- and mitochondrial-encoded subunits. CI assembly occurs via the sequential addition of subdomains and modules. As CI is prone to oxidative damage, its subunits continually undergo proteolysis and turnover. We describe the mechanism by which CI abundance is regulated in a CI-deficient Arabidopsis thaliana mutant. Using a forward genetic approach, we determined that the CI Q-module domain subunit PSST interacts with FTSH PROTEASE 3 (FTSH3) to mediate the disassembly of the matrix arm domain for proteolysis and turnover as a means of protein quality control. We demonstrated the direct interaction of FTSH3 with PSST and identified the amino acid residues required for this interaction. The ATPase function of FTSH3, rather than its proteolytic activity, is required for this interaction, as its mutation was compensated for by a proteolytically inactive form of FTSH3. This study reveals the mechanistic process by which FTSH3 recognizes CI for degradation at amino acid resolution.
GmNAC039 and GmNAC018 activate the expression of cysteine protease genes to promote soybean nodule senescence
Authors: Yu Haixiang , Xiao Aifang , Wu Jiashan , Li Haoxing , Duan Yan , Chen Qingshan , Zhu Hui , Cao Yangrong 
Published: May 2023

Abstract
Root nodules are major sources of nitrogen for soybean (Glycine max (L.) Merr.) growth, development, production, and seed quality. Symbiotic nitrogen fixation is time-limited, as the root nodule senesces during the reproductive stage of plant development, specifically during seed development. Nodule senescence is characterized by the induction of senescence-related genes, such as papain-like cysteine proteases (CYPs), which ultimately leads to the degradation of both bacteroids and plant cells. However, how nodule senescence–related genes are activated in soybean is unknown. Here, we identified 2 paralogous NAC transcription factors, GmNAC039 and GmNAC018, as master regulators of nodule senescence. Overexpression of either gene induced soybean nodule senescence with increased cell death as detected using a TUNEL assay, whereas their knockout delayed senescence and increased nitrogenase activity. Transcriptome analysis and nCUT&Tag-qPCR assays revealed that GmNAC039 directly binds to the core motif CAC(A)A and activates the expression of 4 GmCYP genes (GmCYP35, GmCYP37, GmCYP39, and GmCYP45). Similar to GmNAC039 and GmNAC018, overexpression or knockout of GmCYP genes in nodules resulted in precocious or delayed senescence, respectively. These data provide essential insights into the regulatory mechanisms of nodule senescence, in which GmNAC039 and GmNAC018 directly activate the expression of GmCYP genes to promote nodule senescence.
Measures of Social and Occupational Function in Early Psychosis: A Systematic Review and Meta-analysis
Authors: Cowman Megan , Godfrey Emmet , Walsh Talissa , Frawley Emma , Fowler David , Alvarez-Jimenez Mario , O’Connor Karen , Wykes Til , Birchwood Max , Donohoe Gary 
Published: May 2023

Abstract
Deficits in social and occupational function are widely reported in psychosis, yet no one measure of function is currently agreed upon as a gold standard in psychosis research. The aim of this study was to carry out a systematic review and meta-analysis of functioning measures to determine what measures were associated with largest effect sizes when measuring between-group differences, changes over time, or response to treatment. Literature searches were conducted based on PsycINFO and PubMed to identify studies for inclusion. Cross-sectional and longitudinal observational and intervention studies of early psychosis (≤5 years since diagnosis) that included social and occupational functioning as an outcome measure were considered. A series of meta-analyses were conducted to determine effect size differences for between-group differences, changes over time, or response to treatment. Subgroup analyses and meta-regression were carried out to account for variability in study and participant characteristics. One hundred and sixteen studies were included, 46 studies provided data (N = 13 261) relevant to our meta-analysis. Smallest effect sizes for changes in function over time and in response to treatment were observed for global measures, while more specific measures of social and occupational function showed the largest effect sizes. Differences in effect sizes between functioning measures remained significant after variability in study and participant characteristics were accounted for. Findings suggest that more specific measures of social function are better able to detect changes in function over time and in response to treatment.
Negotiating Shanghai Mercy Hospital: Philanthropy, Business and Control of Madness in Republican China
Authors: Ma Jinping 
Published: May 2023

Summary
This study examines the initiation and administration of Mercy Hospital in Republican Shanghai. It explains the protracted negotiations that underpinned the collaboration between the Chinese founder Lu Bohong, the Shanghai Municipal Council (SMC) of the International Settlement and the Municipal Administration (FMA) of the French Concession. Despite mutual needs for a psychiatric hospital, the collaboration was undermined by disputes over funding shares and administrative direction. While Lu expected a symbolic modern philanthropy, the SMC and FMA saw it as an economic tool to relieve the responsibility of regulating refugees and the increasing mental patients. They repeatedly forced Lu to make concessions with financial instruments, but ended up non-cooperation, leading the patrons to compromise to keep their problem solver. However, after Lu’s murder and the subsequent dysfunction of the Chinese municipal government, the SMC and FMA could not help but take on this task to protect their settlements from the threat.
Longitudinal assessment of the sleep suicide link in Veterans: methods and study protocol
Authors: Primack Jennifer M , Quinn McKenzie J , Carskadon Mary A , Holman Caroline S , Nazem Sarra , Kelsey Madeline R , Fedorenko Erick J , McGeary Sarah , Brick Leslie A , McGeary John E 
Published: May 2023

Abstract
Although sleep disruption has emerged as a theoretically consistent and empirically supported suicide risk factor, the mechanistic pathways underlying the sleep–suicide link are less understood. This paper describes the methodology of a study intended to examine longitudinal mechanisms driving the link between sleep and suicide in Veterans at elevated suicide risk. Participants will be 140 Veterans hospitalized for suicide attempt or ideation with plan and intent or those identified through the Suicide Prevention Coordinator (SPC) office as being at acute risk. After study enrollment, actigraphy and ecological momentary assessment (EMA) data will be collected for 8 weeks, with follow-up assessments occurring at 2, 4, 6, 8, and 26 weeks. Participants respond to EMA questionnaires, derived from psychometrically validated assessments targeting emotional reactivity, emotion regulation, impulsivity, suicide risk, and sleep timing constructs, five times a day. First and last daily EMA target sleep parameters including sleep quantity, quality, timing, nightmares, and nocturnal awakenings. During follow-up assessments, participants will complete self-report assessments and interviews consistent with EMA constructs and the Iowa Gambling Task. The primary outcome for aim 1 is suicide ideation severity and for the primary outcome for aim 2 is suicide behavior. Findings from this study will improve our understanding of the dynamic interactions among sleep disturbance, emotion reactivity/regulation, and impulsivity to inform conceptual Veteran sleep–suicide mechanistic models. Improved models will be critical to optimizing the precision of suicide prevention efforts that aim to intervene and mitigate risk in Veteran populations, especially during a period of acute risk.
Employers’ Retirement Age Norms in European Comparison
Authors: Riekhoff Aart-Jan 
Published: May 2023

Abstract
Policies incentivizing longer working lives can remain ineffective if employers are not able and willing to employ an aging workforce. Depending on what employers consider appropriate age norms for work and retirement, they may be more willing to recruit and retain older workers. This study investigates how these retirement age norms differ across Europe and how they are related to country- and gender-specific pension policies and employment practices. The study uses data from the European Social Survey round 9 (collected in 2018) for 27 countries. Employers are identified as self-employed with personnel and managers who supervise others. The data include questions about the ages of when someone is too young to retire and when someone is too old to work. These items are combined and used in a set of multilevel interval regression models to analyze: (a) How employers’ retirement age norms differ from those of employees and (b) How employers’ retirement age norms vary across countries. The results indicate that, overall, employers have higher retirement age norms than employees, but that the difference narrows substantially once controlled for other factors. Employers’ retirement age norms are positively related to countries’ gender-specific statutory retirement ages and older-worker employment rates. In the case of statutory retirement ages, this association is stronger among employers than among various socioeconomic groups of employees.
Rapid high-resolution size distribution analysis for adeno-associated virus using high speed SV-AUC
Authors: Berkowitz Steven A. , Larson Nicholas , Bou-Assaf George , Laue Thomas 
Published: May 2023

AbstractWhen optimized, sedimentation velocity analytical ultracentrifugation (SV-AUC) provides the most-accurate, broadest-range, and highest-resolution size distribution analysis of any method. Generating simulated data for an adeno-associated virus (AAV) sample consisting of four species differing only in their DNA content and having closely spaced sedimentation coefficients, allows manipulation of the SV-AUC experimental protocol to optimize the size distribution resolution. In developing this high speed SV-AUC (hs-SV-AUC) protocol several experimental challenges must be overcome: 1) the need for rapid data acquisition, 2) avoiding optical artifacts from steep boundaries and 3) overcoming the increased potential for convection. A protocol, hs-SV-AUC, has been developed that uses high rotor speeds, interference detection and low temperatures to overcome these challenges. By confining data analysis to a limited radial-time window and using a very short run time (< 20 min after temperature equilibration), the need to match the sample and reference solvent composition and meniscus positions is relaxed, making interference detection is as simple to employ as absorbance detection. Experimental size distributions from the same AAV sample by hs-SV-AUC at 45K rpm and 10 °C versus low-speed SV-AUC at 15K rpm, and 10 °C illustrates the improved size distribution resolution offered by the hs-SV-AUC protocol.
A Robust Deep Learning Approach for Joint Nuclei Detection and Cell Classification in Pan-Cancer Histology Images
Authors: Walia Vidushi , Kotte Sujatha , Sivadasan Naveen , Sharma Hrishikesh , Joseph Thomas , Varma Binuja , Mukherjee Geetashree , Saipradeep V.G 
Published: May 2023

AbstractAdvanced image processing methods have shown promise in computational pathology, including the extraction of crucial microscopic features from histology images. Accurate detection and classification of cell nuclei from whole-slide images (WSI) play a crucial role in capturing the molecular and morphological landscape of the tissue sample. They enable widespread downstream applications, including cancer diagnosis, prognosis, and discovery of novel markers. Robust nuclei detection and classification are challenging due to the high intra-class variability and inter-class similarity of the microscopic morphological features. This is further compounded by the domain shift arising due to the variability in tissue types, staining protocols, and image acquisition. Motivated by the ability of the recent deep learning techniques to learn complex patterns in a biasfree manner, we develop a novel and robust deep learning model TransNuc, based on vision transformers, for simultaneous detection and classification of cell nuclei from H&E stained WSI. We benchmarked TransNuc on the comprehensive Open Pan-cancer Histology Dataset (PanNuke), sampled from over 20,000 WSI, comprising 19 different tissue types and five clinically important cell classes, namely, Neoplastic, Epithelial, Inflammatory, Connective, and Dead cells. TransNuc exhibited superior performance compared to the state-of-theart, including Hover-Net and Micro-Net. TransNuc was able to learn robust feature representations and thereby perform consistently better for the abundant classes such as neoplastic, and the under-represented classes such as dead cells. Similar performance gains were also obtained for epithelial and connective classes that have a significant inter-class morphological similarity.
Active density fluctuations in bacterial binary mixtures
Authors: Burriel Silvia Espada , Colin Remy 
Published: May 2023

AbstractIn wild environments, physical and biochemical interactions between intermixed motile and sessile microorganisms give rise to spatial organization that is key for the functioning and ecology of complex communities. However, how motility-driven physical interactions contribute to shaping multispecies communities remains little understood. To address this gap, we investigated model binary mixtures of motile and non-motileEscherichia colibacteria. We discovered a new type of non-equilibrium self-organization, wherein large-scale density fluctuations of non-motile bacteria emerge when mixed with motile ones under physiologically relevant conditions. Systematically exploring the phase diagram in microfluidics experiments and combining them with modeling and simulations, we uncovered the two-pronged physical mechanism of emergence: Circular swimming of motile cells close to surfaces generates recirculating hydrodynamic flows that advect non-motile cells, while sedimentation, by breaking the vertical symmetry, is essential for their local accumulation. This active self-organization behavior in mixed bacterial populations appears crucial for complex microbial community structuration.
Differences in gut metagenomes between dairy workers and community controls: a cross-sectional study
Authors: Trinh Pauline , Roberts Marilyn C. , Rabinowitz Peter M. , Willis Amy D. 
Published: May 2023

AbstractBackgroundAs a nexus of routine antibiotic use and zoonotic pathogen presence, the live-stock farming environment is a potential hotspot for the emergence of zoonotic diseases and antibiotic resistant bacteria. Livestock can further facilitate disease transmission by serving as intermediary hosts for pathogens as they undergo evolution prior to a spillover event. In light of this, we are interested in characterizing the microbiome and resistome of dairy workers, whose exposure to the livestock farming environment places them at risk for facilitating community transmission of antibiotic resistant genes and emerging zoonotic diseases.ResultsUsing shotgun sequencing, we investigated differences in the taxonomy, diversity and gene presence of the human gut microbiome of 10 dairy farm workers and 6 community controls, supplementing these samples with additional publicly available gut metagenomes. We observed greater abundance of tetracycline resistance genes and prevalence of cephamycin resistance genes in dairy workers’ metagenomes, and lower average gene diversity. We also found evidence of commensal organism association with plasmid-mediated tetracycline resistance genes in both dairy workers and community controls (includingFaecalibacterium prausnitzii, Ligilactobacillus animalis, andSimiaoa sunii). However, we did not find significant differences in the prevalence of resistance genes or virulence factors overall, nor differences in the taxonomic composition of dairy worker and community control metagenomes.ConclusionsThis study presents the first metagenomics analysis of United States dairy workers, providing insights into potential risks of exposure to antibiotics and pathogens in animal farming environments. Previous metagenomic studies of livestock workers in China and Europe have reported increased abundance and carriage of antibiotic resistance genes in livestock workers. While our investigation found no strong evidence for differences in the abundance or carriage of antibiotic resistance genes and virulence factors between dairy worker and community control gut metagenomes, we did observe patterns in the abundance of tetracycline resistance genes and the prevalence of cephamycin resistance genes that is consistent with previous work.
Epithelial-Mesenchymal Transition: An Organizing Principle of Mammalian Regeneration
Authors: Bedelbaeva Kamila , Cameron Benjamin , Latella Jack , Aslanukov Azamat , Gourevitch Dmitri , Davuluri Ramana , Heber-Katz Ellen 
Published: May 2023

ABSTRACTThe MRL mouse strain is one of the few examples of a mammal capable of healing appendage wounds by regeneration, a process that begins with the formation of a blastema, a structure containing de-differentiating mesenchymal cells. HIF-1α expression in the nascent MRL wound site blastema is one of the earliest identified events and is sufficient to initiate the complete regenerative program. However, HIF-1α regulates many cellular processes modulating the expression of hundreds of genes. A later signal event is the absence of a functional G1 checkpoint leading to G2 cell cycle arrest with increased cellular DNA but little cell division seen in the blastema. This lack of mitosis in MRL blastema cells is also a hallmark of regeneration in classical invertebrate and vertebrate regenerators such as the planaria, hydra, and newt. Here, we explore the cellular events occurring between HIF-1α upregulation and its regulation of the genes involved in G2 arrest (EVI-5, γH3, Wnt5a, and ROR2), and identify EMT (Twist, Slug) and chromatin remodeling (EZH-2 and H3K27me3) as key intermediary processes. The locus of these cellular events is highly regionalized within the blastema, occurring in the same cells as determined by double staining using immunohistochemistry and FACS analysis, and appear as EMT and chromatin remodeling followed by G2 arrest determined by kinetic expression studies.