bluuebunny/crossref_metadata_2025 huggingface dataset:
The Arabidopsis eATP receptor, DORN1 and CNGC19 channel act in tandem to regulate plant defense upon Spodoptera litura herbivory
Authors: Kundu Pritha , Kumari Misha , Meena Mukesh Kumar , Mishra Shruti , Vadassery Jyothilakshmi
Published: January 2025

Plants deploy cellular Ca2+ elevation as a signal for environmental stress signaling. Extracellular ATP (eATP) is released into the extracellular matrix when cells are wounded. DOES NOT RESPOND TO NUCLEOTIDES 1 (DORN1), a key legume-type lectin receptor, senses and binds eATP and activates Ca2+ signaling. No evidence directly links calcium-mediated eATP signaling to resistance against insect herbivores. Here, we report upregulation of DORN1 transcripts upon wounding and Spodoptera litura feeding in Arabidopsis. Loss-of-function of DORN1 resulted in increased S. litura feeding compared to that on wildtype. Plant immunity is compromised in dorn1 mutants as they show reduced S. litura oral secretion mediated Ca2+ elevation, jasmonic acid accumulation, and expression of jasmonate responsive genes. The herbivory-induced calcium channel, CYCLIC NUCLEOTIDE GATED CHANNEL 19 (CNGC19), co-expresses with DORN1. We found that eATP-induced Ca2+ elevation requires functional CNGC19. Loss-of-function of DORN1 and CNGC19 highly increased the susceptibility to S. litura, mediated by reduced accumulation of jasmonates. We also demonstrate a plausible interaction of CNGC19 with DORN1. The data implicate the role of damage-released eATP and its receptor DORN1 in herbivory-induced defense signaling. DORN1 together with the Ca2+ channel CNGC19 generate the eATP-induced Ca2+ elevation, leading to the activation of immune signaling.
AGN feedback in isolated galaxies with a SMUGGLE multiphase ISM
Authors: Sivasankaran Aneesh , Blecha Laura , Torrey Paul , Kelley Luke Zoltan , Bhowmick Aklant , Vogelsberger Mark , Hernquist Lars , Marinacci Federico , Sales Laura V
Published: January 2025

Feedback from active galactic nuclei (AGNs) can strongly impact the host galaxies by driving high-velocity winds that impart substantial energy and momentum to the interstellar medium (ISM). In this work, we study the impact of these winds in isolated galaxies using high-resolution hydrodynamics simulations. Our simulations use the explicit ISM and stellar evolution model called Stars and MUltiphase Gas in GaLaxiEs. Additionally, using a super-Lagrangian refinement scheme, we resolve AGN feedback coupling to the ISM at $\sim$10–100 pc scales. We find that AGN feedback efficiently regulates the growth of supermassive black holes. However, its effect on star formation and outflows depends strongly on the relative strengths of AGN versus local stellar feedback and the geometrical structure of the gas disc. When the energy injected by AGN is subdominant to that of stellar feedback, there are no significant changes in the star formation rates or mass outflow rates of the host galaxy. Conversely, when the energy budget is dominated by the AGN, we see a significant decline in the star formation rates accompanied by an increase in outflows. Galaxies with thin gas discs like the Milky Way allow feedback to escape easily into the polar directions without doing much work on the ISM. In contrast, galaxies with thick and diffuse gas discs confine the initial expansion of the feedback bubble within the disc, resulting in more work done on the ISM. Phase space analysis indicates that outflows primarily comprise hot and diffuse gas, with a lack of cold and dense gas.
Pro-cumulin addition in a biphasic in vitro oocyte maturation system modulates human oocyte and cumulus cell transcriptomes
Authors: Cava-Cami Berta , Galvao Antonio , Van Ranst Heidi , Stocker William A , Harrison Craig A , Smitz Johan , De Vos Michel , Kelsey Gavin , Anckaert Ellen
Published: January 2025

Biphasic IVM can be offered as a patient-friendly alternative to conventional ovarian stimulation in IVF patients predicted to be hyper-responsive to ovarian stimulation. However, cumulative live birth rates after IVM per cycle are lower than after conventional ovarian stimulation for IVF. In different animal species, supplementation of IVM media with oocyte-secreted factors (OSFs) improves oocyte developmental competence through the expression of pro-ovulatory genes in cumulus cells. Whether the addition of OSFs in human biphasic IVM culture impacts the transcriptome of oocytes and cumulus cells retrieved from small antral follicles in minimally stimulated non-hCG-triggered IVM cycles remains to be elucidated. To answer this, human cumulus–oocyte complexes (COCs) that were fully surrounded by cumulus cells or partially denuded at the time of retrieval were cultured in a biphasic IVM system either without or with the addition of pro-cumulin, a GDF9:BMP15 heterodimer. Oocytes and their accompanying cumulus cells were collected separately, and single-cell RNA-seq libraries were generated. The transcriptomic profile of cumulus cells revealed that pro-cumulin upregulated the expression of genes involved in cumulus cell expansion and proliferation while downregulating steroidogenesis, luteinization, and apoptosis pathways. Moreover, pro-cumulin modulated the immature oocyte transcriptome during the pre-maturation step, including regulating translation, apoptosis, and mitochondria remodeling pathways in the growing germinal vesicle oocytes. The addition of pro-cumulin also restored the transcriptomic profile of matured metaphase II oocytes that were partially denuded at collection. These results suggest that cumulus cell and oocyte transcriptome regulation by pro-cumulin may increase the number of developmentally competent oocytes after biphasic IVM treatment. Future studies should assess the effects of pro-cumulin addition in human biphasic IVM at the proteomic level and the embryological outcomes, particularly its potential to enhance outcomes of oocytes that are partially denuded at COC collection.
AAV vector transduction restriction and attenuated toxicity in hESCs via a rationally designed inverted terminal repeat
Authors: Song Liujiang , Hasegawa Tomoko , Brown Nolan J , Bower Jacquelyn J , Samulski Richard J , Hirsch Matthew L
Published: January 2025

Adeno-associated virus (AAV) inverted terminal repeats (ITRs) induce p53-dependent apoptosis in human embryonic stem cells (hESCs). To interrogate this phenomenon, a synthetic ITR (SynITR), harboring substitutions in putative p53 binding sites was generated and evaluated for vector production and gene delivery. Replication of SynITR flanked transgenic genome was similar compared to wild type (wt) ITR, with a modest increase in vector titers. Packaged in the AAV2 capsid, wtITR and SynITR vectors demonstrated similar transduction efficiencies of human cells without toxicity. Following AAV2-wtITR vector infection of hESCs, rapid apoptosis was observed as reported. In contrast, infection by AAV2 vectors packaged with SynITRs attenuated the wtITR-induced hESC toxicity. While hESC particle entry and the abundance of double stranded circular episomes was similar for the ITR contexts, reporter expression was inhibited from transduced SynITR genomes. Mechanistically, infection of hESCs induced γH2AX in an ITR-independent manner, however, canonical activation of p53α was uncoupled using AAV-SynITR. Further investigations in hESCs revealed additional novel findings: (i) p53β is uniquely and constitutively active and (ii) AAV vector infection, independent of the ITR sequence, induces activation of p53ψ. The data herein reveal an ITR-dependent AAV vector transduction restriction specific to hESCs and manipulation of the DNA damage response via ITR engineering.
Transcription near arrested DNA replication forks triggers ribosomal DNA copy number changes
Authors: Sasaki Mariko , Kobayashi Takehiko
Published: January 2025

DNA copy number changes via chromosomal rearrangements or the production of extrachromosomal circular DNA. Here, we demonstrate that the histone deacetylase Sir2 maintains the copy number of budding yeast ribosomal RNA gene [ribosomal DNA (rDNA)] by suppressing end resection of DNA double-strand breaks (DSBs) formed upon DNA replication fork arrest in the rDNA and their subsequent homologous recombination (HR)-mediated rDNA copy number changes during DSB repair. Sir2 represses transcription from the regulatory promoter E-pro located near the fork arresting site. When Sir2 is absent, this transcription is stimulated but terminated by arrested replication forks. This transcription–replication collision induces DSB formation, DSB end resection and the Mre11-Rad50-Xrs2 complex-dependent DSB repair that is prone to chromosomal rDNA copy number changes and the production of extrachromosomal rDNA circles. Therefore, repression of transcription near arrested replication forks is critical for the maintenance of rDNA stability by directing DSB repair into the HR-independent, rearrangement-free pathway.
Methyl-dependent auto-regulation of the DNA N6-adenine methyltransferase AMT1 in the unicellular eukaryote Tetrahymena thermophila
Authors: Duan Lili , Li Haicheng , Ju Aili , Zhang Zhe , Niu Junhua , Zhang Yumiao , Diao Jinghan , Liu Yongqiang , Song Ni , Ma Honggang , Kataoka Kensuke , Gao Shan , Wang Yuanyuan
Published: January 2025

DNA N6-methyladenine (6mA) is a potential epigenetic mark involved in gene transcription in eukaryotes, yet the regulatory mechanism governing its methyltransferase (MTase) activity remains obscure. Here, we exploited the 6mA MTase AMT1 to elucidate its auto-regulation in the unicellular eukaryote Tetrahymena thermophila. The detailed endogenous localization of AMT1 in vegetative and sexual stages revealed a correlation between the 6mA reestablishment in the new MAC and the occurrence of zygotically expressed AMT1. Catalytically inactive AMT1 reduced 6mA level on the AMT1 gene and its expression, suggesting that AMT1 modulated its own transcription via 6mA. Furthermore, AMT1-dependent 6mA regulated the transcription of its target genes, thereby affecting cell fitness. Our findings unveil a positive feedback loop of transcriptional activation on the AMT1 gene and highlight the crucial role of AMT1-dependent 6mA in gene transcription.
Fam170a deficiency causes male infertility by impairing histone-to-protamine exchange during mouse spermiogenesis
Authors: Cheng Jinmei , Gu Yimin , Wang Yueming , Xun Junjie , Wang Guishuan , Wang Yu , Wang Jianyu , Li Yinchuan , Sun Fei
Published: January 2025

Chromatin remodeling, which involves the histone-to-protamine exchange process during spermiogenesis, is crucial for sperm nuclear condensation and male fertility. However, the key regulators and underlying molecular mechanisms involved in this process remain largely unexplored. In this study, we discovered that deficiency in the family with sequence similarity 170 member A (Fam170a) led to abnormal sperm nuclear morphology and male infertility in mice, mirroring the observation of very low Fam170a transcription levels in sperm of infertile men with teratozoospermia. Further investigation revealed that Fam170a plays a significant role in the histone-to-protamine chromatin remodeling process. This was evidenced by the earlier core histone removal, accelerated translation and degradation of transition proteins, and reduced protamine incorporation during spermiogenesis in Fam170a-deleted mice. Mechanistically, we found that Fam170a interacts with chromatin remodeling-associated proteins and regulates the transcription of genes related to chromatin remodeling. Notably, Fam170a directly interacts with the deubiquitinating enzyme Usp7 and facilitates its nuclear translocation in elongating sperm, enhancing the deubiquitinating activity of Usp7 on testis-specific histone H2A and H2B variants. Collectively, our findings identify Fam170a as a previously unrecognized key regulator of sperm chromatin remodeling and suggest that histone deubiquitination may play an essential role in the histone-to-protamine exchange process.
Oxidative damage within alternative DNA structures results in aberrant mutagenic processing
Authors: Zewail-Foote Maha , del Mundo Imee M A , Klattenhoff Alex W , Vasquez Karen M
Published: January 2025

Genetic instability is a hallmark of cancer, and mutation hotspots in human cancer genomes co-localize with alternative DNA structure-forming sequences (e.g. H-DNA), implicating them in cancer etiology. H-DNA has been shown to stimulate genetic instability in mammals. Here, we demonstrate a new paradigm of genetic instability, where a cancer-associated H-DNA-forming sequence accumulates more oxidative lesions than B-DNA under conditions of oxidative stress (OS), often found in tumor microenvironments. We show that OS results in destabilization of the H-DNA structure and attenuates the fold increase in H-DNA-induced mutations over control B-DNA in mammalian cells. Furthermore, the mutation spectra revealed that the damaged H-DNA-containing region was processed differently compared to H-DNA in the absence of oxidative damage in mammalian cells. The oxidatively modified H-DNA elicits differential recruitment of DNA repair proteins from both the base excision repair and nucleotide excision repair mechanisms. Altogether, these results suggest a new model of genetic instability whereby H-DNA-forming regions are hotspots for DNA damage in oxidative microenvironments, resulting in its altered mutagenic processing. Our findings provide valuable insights into the role of OS in DNA structure-induced genetic instability and may establish H-DNA-forming sequences as promising genomic biomarkers and potential therapeutic targets for genetic diseases.
Effect of Haemodiafiltration Versus Haemodialysis on Vascular Access Patency when Starting Haemodialysis
Authors: Yoshida Mahoko , Maeoka Yujiro , Takahashi Akira , Ishiuchi Naoki , Osaki Yosuke , Sasaki Kensuke , Masaki Takao
Published: January 2025

Background

Haemodiafiltration (HDF) therapy improves the prognosis by reducing inflammation and oxidative stress, and improving endothelial function. These factors contribute to vascular access (VA) stenosis, one of the most common complications in patients on haemodialysis (HD) or HDF. This study aimed to assess the efficacy of HDF on VA patency.

Methods

This multicentre, prospective, observational study with post-hoc analysis included 612 patients among 643 who underwent VA procedures and started dialysis between April 2012 and March 2021. Five hundred and sixteen patients were on HD from starting dialysis, while 96 switched to HDF after starting dialysis. One-to-one propensity score matching was performed to compare the 24-month patency rates of VA between groups by Kaplan–Meier and log-rank tests, and a Cox proportional hazard regression analysis was used to identify factors affecting patency rates.

Results

There were 87 patients in each group. The 24-month primary patency rates were 74.2% for HDF and 47.7% for HD (P < 0.001). A multivariate Cox proportional hazards analysis showed that a history of cardiovascular disease (hazard ratio [HR] 2.29; 95% confidence interval [CI] 1.21–4.34, P = 0.01) and higher haemoglobin A1c values (HR 1.37; 95% CI 1.00–1.82, P = 0.04) were associated with poor 24-month primary patency. However, HDF (HR 0.30; 95% CI 0.16–0.56, P < 0.001) and use of statins (HR 0.50; 95% CI 0.27–0.94, P = 0.03) were associated with better patency. A stratified analysis showed that HRs for loss of VA patency were lower in patients with HDF than in those with HD in the subgroups of ≥ 65 years, male sex, radiocephalic arteriovenous fistula, a history of diabetes mellitus or cardiovascular disease, haemoglobin concentrations <10 g/dL, and albumin concentrations < 3.5 g/dL.

Conclusions

HDF potentially improves VA patency rates compared with HD, even in patients with cardiovascular disease or diabetes, commonly associated with poor patency.
Porous covalent organic framework liquid for boosting CO2 adsorption and catalysis via dynamically expanding effect
Authors: Chen Zi-Ao , Zou Lei , Cao Rong , Huang Yuan-Biao
Published: January 2025

The features of intrinsic porosity and fluidity endow porous liquids (PLs) unique properties and performances but the preparation of PLs remains challenging due to the difficulty in liquefying and keeping porous features at the same time. Herein, we develop a stepwise surface functionalization and ion exchange strategy to achieve a rare example of flexible covalent organic framework (COF) based porous liquid (COF-PLs). By coating the outer surface of the judiciously selected three-dimensional flexible COF-301 with an imidazolium salt corona, followed by liquefaction using the anion canopy potassium poly(ethylene glycol) sulfonate (PEGS) via electrostatic interactions to obtain the flexible porous liquid COF-301-PL. Theoretical calculations and CO2 adsorption experiments reveal that the cavities of COF-301-PL undergo dynamic adjustments in response to changes in CO2 pressure. The dynamic expansion effect not only can provide additional gas adsorption capacity (7.04 mmol/g at 40 bar) but also facilitate the mass transfer of gas molecules during the catalytic process. Consequently, COF-301-PL exhibits superior catalytic efficiency for the conversion of CO2 into cyclic carbonate by a factor of 24 and 17 compared to those of PEGS and COF-301 solid counterpart, respectively. The optimization of substrate adsorption and mass transfer conditions consequently improves the overall efficiency of catalytic reactions. This work offers a new perspective on the preparation of PLs and their large potential application for gas adsorption and catalysis.
Osteogenic Effects of Bioactive Compounds Found in Fruits on Mesenchymal Stem Cells: A Review
Authors: Sodré Lia Igel , Gall Maria Eduarda Cordebello , Elias Monique de Barros , Oliveira Luana Oeby de , Lobo Francine Albernaz Teixeira Fonseca , Carias Rosana Bizon Vieira , Teodoro Anderson Junger
Published: January 2025

Phytochemicals, which are bioactive compounds contained in fruits, vegetables, and teas, have a positive effect on human health by having anti-inflammatory, antioxidant, and anticarcinogenic effects. Several studies have highlighted the ability of bioactive compounds to activate key cellular enzymes associated with important signaling pathways related to cell division and proliferation, as well as their role in inflammatory and immunological responses. Some phytochemicals are associated with increased proliferation, differentiation, and expression of markers related to osteogenesis, bone formation, and mineralization by activating various signaling pathways. The objective of this study was to clarify which bioactive compounds present in fruits have osteogenic effects on mesenchymal stem cells and the possible associated mechanisms. A literature search was conducted in the LILACS, MEDLINE, and PubMed databases for pertinent articles published between 2014 and 2024. This review included 34 articles that report the osteogenic effects of various bioactive compounds found in different fruits. All the articles reported that phytochemicals play a role in enhancing the regenerative properties of mesenchymal cells, such as proliferation, osteogenic differentiation, secretion of angiogenic factors, and extracellular matrix formation. This review highlights the potential of these phytochemicals in the prevention and treatment of bone diseases. However, more studies are recommended to identify and quantify the therapeutic dose of phytochemicals, investigate their mechanisms in humans, and ensure their safety and effectiveness for health, particularly for bone health.
Effects of Probiotics and Diet Management in Patients With Irritable Bowel Syndrome: A Systematic Review and Network Meta-analysis
Authors: Lei Yupeng , Sun Xuemei , Ruan Tiechao , Lu Wenting , Deng Bixin , Zhou Ruixi , Mu Dezhi
Published: January 2025

Context

The efficacy of probiotics and diet management in irritable bowel syndrome (IBS) is controversial, and their relative effectiveness remains unclear.

Objective

This study aimed to evaluate the effects of probiotics, diet management, and their combination on IBS.

Data Sources

PubMed, Embase, Cochrane, and Web of Science were searched from inception to July 10, 2023, for relevant studies, including symptom relief, IBS–symptom severity score (-SSS), and IBS–quality of life measure (-QOL).

Data Extraction

Two investigators independently performed the data extraction and quality assessment.

Data Analysis

A network meta-analysis was performed using a frequentist approach and a random-effects model to estimate the relative risk (RR) and 95% CI.

Results

Forty-four articles were eligible for this study. In relieving IBS symptoms, compared with a sham diet, a low–fermentable oligosaccharide, disaccharide, monosaccharide, and polyols (low-FODMAP) diet (RR: 3.22; 95% CI: 1.70–6.26) and low-FODMAP diet combined with probiotics (RR: 17.79; 95% CI: 3.27–112.54) significantly relieved IBS symptoms. The control group showed significantly lower effectiveness than the probiotics group (RR: 0.47; 95% CI: 0.32–0.69). According to the surface under the cumulative rank curve (SUCRA), a low-FODMAP diet combined with probiotics (80.4%) had the best effect in relieving IBS symptoms, followed by a low-FODMAP diet (70.8%), probiotics (65.1%), and a gluten-free diet (54.3%). In reducing the total IBS-SSS, the low-FODMAP diet (90.5%) was the most effective, followed by the low-FODMAP diet combined with probiotics (76.6%), probiotics alone (62.3%), and gluten-free diet (28.3%). In reducing total IBS-QOL, probiotics (72.1%) ranked first, followed by gluten-free (57.0%) and low-FODMAP (56.9%) diets. Probiotics (34.9%) were associated with the lowest risk of adverse effects.

Conclusion

A low-FODMAP diet combined with probiotics is most effective in relieving IBS symptoms. A low-FODMAP diet is the most recommended diet for alleviating IBS severity, and probiotics were associated with improving the QOL of patients with IBS, with the fewest adverse events.

Systematic Review Registration

PROSPERO registration no. CRD42024499113.
Better not to vote to restore democracy? Boycotting the 2023 national referendum as a manifestation of (anti)party identification: The case of Poles voting abroad
Authors: Musiał-Karg Magdalena , Kapsa Izabela
Published: January 2025

This article explores the attitudes of Poles living abroad who decided not to participate in the national referendum, even though they voted in simultaneously held parliamentary elections. Their abstention is viewed as a manifestation of their (anti) party identification. The ruling right-wing populist party had hoped that raising fears about immigrants, the retirement age, and the sale of Polish assets would boost support for the referendum and—consequently—parliamentary elections. However, this strategy backfired by mobilizing the party’s opponents, who boycotted the referendum in protest. Through quantitative analysis, we explore how the 2023 referendum deepened societal divisions fueled by polarization. We investigate the connection between voters’ decisions and their party affiliations. Using data from a sample of 1087 individuals, our analysis shows significant correlations between party identification and referendum abstention. The findings suggest that strong party allegiance can drive strategic nonparticipation, often as a form of protest or civil disobedience against opposing political forces.
Safety and health care utilization following COVID-19 vaccination (BNT162b2) among children and youth with juvenile idiopathic arthritis and inflammatory bowel disease: A population-based study
Authors: Lee Jennifer J Y , Bernatsky Sasha , Benchimol Eric I , Kwong Jeffrey C , Li Qing , Yeung Rae S M , Widdifield Jessica
Published: January 2025

Objectives

To evaluate among Ontario children and youth (<16 years old) with juvenile idiopathic arthritis (JIA) or inflammatory bowel disease (IBD), whether COVID-19 vaccines (Monovalent BNT162b2) were associated with adverse events of special interest (AESI) or health care utilization.

Methods

Using health administrative databases, all children/youth with JIA or IBD who received at least one vaccine were identified from November 2020 to December 2021 with follow-up until August 31, 2022. Self-controlled case series analyses were used to determine the relative incidence rates (RIR) of events in any 3-week period [AESI, Emergency Department (ED) visits, hospitalizations] and in any 1-month period [specialist visits] post-vaccine compared to control periods.

Results

We studied 1629 JIA and 1050 IBD patients. In the JIA cohort, the median age at vaccination was 12.0 years [Interquartile range (IQR): 10.0 to 14.0], and the median disease duration was 4.3 years (IQR: 2.0 to 7.5). By December 2021, 67.1% (n = 1093) received two doses and 24.1% (n = 393) received three doses. In the IBD cohort, the median age at vaccination was 13.0 (IQR: 11.0 to 14.0) with a median disease duration of 2.4 years (IQR: 1.1 to 4.8). Fifty-four percent (n = 565) received two doses and 36.3% (n = 381) received three doses. During risk periods, AESI was rarely reported. Relative to control periods, JIA and IBD patients demonstrated similar rates of hospitalizations [JIA: RIR: 0.76 (95% confidence interval [CI]: 0.25 to 2.33), IBD: RIR: 0.64 (95% CI: 0.29 to 1.41)], ED visits [JIA: RIR: 1.11 (95% CI: 0.77 to 1.59), IBD: RIR: 0.93 (95% CI: 0.61 to 1.43)], and specialist visits [JIA: RIR: 1.06 (95% CI: 0.89 to 1.26), IBD: RIR: 0.56 (95% CI: 0.22 to 1.43)].

Conclusions

Overall, this study demonstrates the safety of the BNT162b2 vaccine in children/youths with JIA and IBD, with no associated increase in AESI or health care use.
Development of START, a novel multimedia-based symptom appraisal tool for autoimmune rheumatic diseases
Authors: Xiang Ling , Low Andrea H L , Leung Ying Ying , Fong Warren , Lau Tang Ching , Koh Dow Rhoon , Yoon Sungwon , Thumboo Julian
Published: January 2025

Objectives

To facilitate earlier diagnosis of autoimmune rheumatic diseases (ARDs), we aimed to (i) develop Symptom Testing for Autoimmune RheumaTic diseases (START), a novel multimedia-based symptom appraisal tool for ARDs and (ii) pilot test START among established ARD cases and non-ARD controls.

Methods

We developed START using a social cognitive theory–based theoretical framework and consensus-based lists of ARDs and manifestations from our previous work. START was revised through reviews by an expert panel of rheumatologists and cognitive debriefing interviews (CDIs) with patients newly referred for assessment of ARDs. We pilot tested START to evaluate its sensitivity, specificity and test–retest reliability in detecting patients with known ARDs.

Results

Of the 59 manifestations of ARDs identified from our previous work, 33 reached expert consensus for content validity, 26 were removed because they were non-specific or late features of ARDs. Similar manifestations were grouped, resulting in 19 items. The phrasing and formatting of items in START were revised based on findings from the CDIs with 36 patients and expert panel review. Visual illustrations such as photos and drawings were included to improve comprehension of items in START, using an online platform for implementation. Pilot testing in 145 patients with ARDs, 133 patients with non-ARDs and 155 healthy controls found that the sensitivity, specificity and test–retest reliability in detecting patients with any ARDs were 86.2%, 80.9% and 0.789, respectively.

Conclusion

A novel multimedia-based symptom appraisal tool for ARDs was developed, which addresses the limitations of existing tools and exhibited promising sensitivity and specificity in detecting patients with known ARDs.
Imaging tests as predictors of progression to rheumatoid arthritis in clinically suspect arthralgia: a systematic review and meta-analysis
Authors: Gupta Ankita , Anis Sulaiman , de Pablo Paola
Published: January 2025

Objectives

To determine and compare the diagnostic accuracy of imaging tests for the prediction of RA progression in people with inflammatory joint pain or clinically suspect arthralgia (CSA).

Methods

We searched MEDLINE, Embase and Web of Science from 1987 to March 2024. Studies evaluating any imaging tests in participants with inflammatory joint pain or CSA without clinical synovitis were eligible. Reference standards included RA classification criteria, methotrexate initiation or development of inflammatory arthritis (IA). Two authors independently extracted data and assessed validity according to QUADAS-2. We estimated summary sensitivities and specificities for each imaging characteristic and fitted bivariate and hierarchical SROC models for meta-analysis where possible.

Results

We found 39 eligible studies including 42 cohorts, of which 12 evaluated MRI (n = 2782; 19% with RA/IA), 26 evaluated ultrasound (US) (n = 6805; 25% with RA/IA) and 10 evaluated other imaging tests (n = 3362; 20% with RA/IA). Summary sensitivity and specificity for US Power Doppler ≥1 in at least one joint were 37% (95%CI 18%–60%) and 90% (95%CI 82%–94%), respectively (seven studies). Summary sensitivity and specificity for MRI synovitis in at least one joint were 45% (95%CI 29%–62%) and 84% (95%CI 66%–94%), respectively (four studies). Lack of consensus regarding positive threshold definitions limited meta-analysis for other imaging features.

Conclusion

Evidence for MRI or US in predicting RA/IA in people with CSA is heterogeneous and of variable quality. Further studies with larger sample sizes, longer follow-up times and uniform imaging test scoring are warranted to determine whether imaging characteristics, in combination with clinical information, can predict RA in this population.

Systematic review registration

PROSPERO: https://www.crd.york.ac.uk/prospero, CRD42024501243
Predictive value of insulin resistance metabolic score for cardiovascular disease in Chinese arthritis patients: a prospective cohort study
Authors: Ke Wen-kai , Xu Ling-ling , Luo Ni
Published: January 2025

Objectives

Although patients with arthritis have significantly increased cardiovascular disease (CVD) risk, effective prediction tools remain limited. This study aimed to evaluate the predictive value of the Metabolic Score for Insulin Resistance (METS-IR) for CVD events among Chinese patients with arthritis.

Methods

Using data from the China Health and Retirement Longitudinal Study (CHARLS), we conducted a 7-year prospective cohort study (2011–2018) involving 1,059 patients with arthritis. The primary exposure was baseline METS-IR, and the primary outcome was incident CVD. Multivariate Cox regression models were used to analyze the association between METS-IR and CVD risk, adjusting for demographic characteristics and lifestyle factors.

Results

After adjusting for confounding factors, each quartile increase in METS-IR was associated with a 36% increased risk of CVD (HR = 1.36,95%CI : 1.14–1.61, p< 0.001). Compared with the lowest quartile, the highest quartile showed a 63% increased risk (HR = 1.63,95%CI : 1.12–2.37, p< 0.05), demonstrating a significant dose-response relationship (p for trend < 0.05).

Conclusion

METS-IR serves as an effective tool for predicting CVD risk among Chinese patients with arthritis, providing new strategies for early risk identification and prevention.
Efficacy and safety of first-line targeted synthetic DMARDs in rheumatoid arthritis patients with chronic kidney disease
Authors: Yoshimura Yusuke , Yamanouchi Masayuki , Koizumi Ryo , Mizuno Hiroki , Oba Yuki , Kurihara Shigekazu , Suwabe Tatsuya , Tsunoda Susumu , Kishioka Ayumi , Takeuchi Toshihiro , Tanimizu Hikaru , Kamido Hisashi , Yoshimoto Masatoshi , Sugimoto Hisashi , Ikuma Daisuke , Tanaka Kiho , Inoue Noriko , Sekine Akinari , Hasegawa Eiko , Wada Takehiko , Ubara Yoshifumi , Sawa Naoki
Published: January 2025

Objectives

To evaluate the efficacy and safety of first-line targeted synthetic disease-modifying anti-rheumatic drugs (tsDMARDs) in patients with rheumatoid arthritis (RA) and chronic kidney disease (CKD).

Methods

This retrospective cohort study included 216 patients with RA prescribed their first tsDMARDs at two hospitals between 2013 and 2022. Dose reduction and contraindication guidelines for tsDMARDs according to kidney function were followed. The patients were categorised by kidney function and tsDMARD modality. The primary outcome was the 24-month drug retention rate, and the secondary outcomes were changes in the Disease Activity Score 28-C-reactive protein (DAS28-CRP) level, prednisolone dosage, and reasons for discontinuation.

Results

The 24-month drug retention rates according to the estimated glomerular filtration rate (eGFR) (≥60, 30–60, or < 30 mL/min/1.73 m2) were as follows: all tsDMARDs (46.0, 44.1, 47.1%), tofacitinib (55.9, 53.3, 66.7%), baricitinib (64.2, 42.0%), and peficitinib (36.4, 44.1, 40.0%). Even in groups with lower kidney function, the drug retention rate was maintained (adjusted hazard ratio was 1.14 (95% confidence interval, 0.81–1.62), p= 0.45). Patients had a decreased DAS28-CRP (p< 0.01) and a reduced prednisolone dosage (p< 0.01) over the six-month period following tsDMARD initiation. The incidence of herpes zoster and deep vein thrombosis (DVT) was higher in the group with an eGFR <30 mL/min/1.73 m2, but not statistically significant.

Conclusions

tsDMARDs have demonstrated efficacy and safety in patients with RA and CKD; however, clinicians should consider the potential for herpes zoster and DVT in patients with eGFR <30 mL/min/1.73 m2.
Sick Houses: Towards a Transnational History of Housing Hygiene Surveys, 1889–1913
Authors: Strunz Stephan
Published: January 2025

Between 1889 and 1913, housing took centre stage in hygiene enquiries. Countless surveys across Europe sought to identify specific housing problems as health hazards. This paper explores the art of housing hygiene surveys in Belgium, France and Germany. Scrutinising surveys from Berlin, Liège and Paris, I characterise two contesting survey methods. On one hand, large-scale statistical surveys such as the sanitary register of houses in Paris aimed to establish robust epidemiological evidence on the connection between structural elements (like lighting and ventilation) and tuberculosis. On the other hand, monographic surveys adopted more idiosyncratic approaches, probing the relationship of housing and health from architectural, economic, hygienic and social angles, without insisting on a single vector of explanation. Although the era of monographic housing surveys was short-lived, it illuminates the complexity of housing as an epistemic object, which even today proves challenging to assess from a public health standpoint.
Efficient and Rapid Generation of Neural Stem Cells by Direct Conversion Fibroblasts with Single microRNAs
Authors: Li Yuanyuan , Sun Jing , Xu Tingting , Dai Bo , Wang Yuesi
Published: January 2025

Neural stem cells (NSCs) have great potentials in the application of neurodegenerative disease therapy, drug screening, and disease modeling. However, current approaches for induced NSCs (iNSCs) generation from somatic cells are still slow and inefficient. Here we establish a rapid and efficient method of iNSCs generation from human and mouse fibroblasts by single microRNAs (miR-302a). These iNSCs exhibited morphological, molecular and functional properties resembling those of adult human and mouse NSCs, and human iNSCs can be expanded for more than 20 passages in vitro. Furthermore, miR-302a alone was demonstrated to be sufficient to reprogram both human and mouse fibroblasts into iNSCs. Our results showed that direct conversion of autologous fibroblasts with miR-302a into iNSCs, which provides a rapid and efficient strategy to generate iNSCs for both basic research and clinical applications.
Potential of accelerometers to remotely early detect bovine ephemeral fever in cattle using pattern mining
Authors: Trieu Ly Ly , Bailey Derek W , Cao Huiping , Son Tran Cao , Macor Justin , Trotter Mark G , O’Connor Lauren , Tobin Colin T
Published: January 2025

Bovine Ephemeral Fever (BEF), caused by an arthropod-borne rhabdovirus, is widespread in tropical and subtropical regions. It affects cattle with symptoms of fever, lameness, inappetence and in some situations can result in mortality. The goal of this study is to determine if accelerometer data can be used to identify the behavior patterns that occur when cattle become ill from BEF. Eight heifers in a separate experiment were monitored with 3-axis accelerometers sensors. Movement variation (MV) was calculated from accelerometer data (25 Hz) using 1-min epochs and then averaged hourly. Two different approaches, cosine similarity (CS) and deviation from previous behavioral patterns, were developed to autonomously detect patterns and recognize the onset of sickness in cattle using accelerometer data. Analyses show that one heifer had behavioral changes one day before the manager observed BEF, and another heifer had behavioral changes on the same day the manager observed BEF. The other six heifers did not display any BEF symptoms. To validate the efficacy of our analytical approaches, we employed them on a separate commercial herd of 73 cows where 4 of the 27 monitored cows were observed with BEF symptoms. Predictions were either on the day or even the day prior to the manager’s observation and diagnosis. There were likely no false positives in the first or second trials using the deviation algorithm with sum_deviation formula, but there were several false positives with the other algorithms. These case studies demonstrate the potential of accelerometer data to autonomously detect disease onset, in some cases before it was apparent to the human observer. However, more research is needed to minimize false positives that may occur from other similar diseases, abnormal weather events or cyclical changes in behavior such as estrus is required.
A systematic review on health risks of water pollutants: classification, effects and innovative solutions for conservation
Authors: Shekhar Chander , Khosya Reetu , Sharma Arvind Kumar , Thakur Kushal , Mahajan Danish , Kumar Rakesh , Kumar Sunil , Sharma Amit Kumar
Published: January 2025

In this developing era, increased anthropogenic activities result in the contamination of natural resources. Different kinds of pollutants threaten the water quality being crucial for the existence of life. There are different sources and routes through which different kinds of pollutants cause health consequences. This systematic review consists of the classification of water pollutants and a particular focus on toxicological studies on aquatic life, soil, plants and humans with a comparative account of conservation technologies. In this study, various databases like Scopus, Science Direct, Google Scholar, Research Gate and Web of Science were used to find the most relevant and recent literature till September 2024. Studies were selected based on their focus on classes of water pollutants, routes, their cumulative effects and remediation technologies. This review successfully managed to classify the different water pollutants and found a significant association between their exposure and disorders shown by aquatic life and human health. There is a number of evidence of neurological disorders, reproductive and endocrine disruptions. However, the effect can also be seen in both aquatic as well as terrestrial ecosystems. Long-term exposure to water pollutants presents significant health risks and indicates degrading quality of drinking water and aquatic life. This review provides insight into the emergence of pollutants in water and the need for strong preventive policies. It also suggests the necessity of developing cost-effective and advanced conservation technologies for the availability of safe water.
Bridge employment in middle vs. late life for men and women: gendered social roles or life structures?
Authors: Aksaray Gorkem , Marcus Justin
Published: January 2025

Utilizing longitudinal data from a stratified random sample of 15,433 retirees from Turkey, a country with uniquely large variation in postretirement work years, our study is the first to examine the phenomenology of middle vs. late life in postretirement work and demographic intersectionality in retirement. Synthesizing theory in the vocational psychology of retirement with industrial sociology of the life course, the social forces approach we advocate helps shed light on whether documented sex differences in bridge employment participation are caused by social bias or life structure. Results suggest that family and work contexts affecting the gender gap in bridge employment participation may be explained by differing communal and work factors inherent at the intersection of sex and age, and that life stage interacts with social and work opportunity structures very differently for men and women. Yet a nuanced look also points to some trends suggesting a social bias explanation.
The appendicular osteology of the Early Jurassic theropod Piatnitzkysaurus floresi and its implications on the morphological disparity of non-coelurosaurian tetanurans
Authors: Pradelli Luciano A , Pol Diego , Ezcurra Martín D
Published: January 2025

Piatnitzkysaurus floresi is a theropod dinosaur from the Cañadón Asfalto Formation (Chubut Province, Argentina) and one of the few Early Jurassic tetanurans known worldwide. This species is known from two specimens and plays a key role in our understanding of the early evolution of tetanuran theropods. Nevertheless, the published information about its postcranium is limited to the original description of the 1980s and drawings in a few views. Here, we redescribe in detail the appendicular skeleton of Piatnitzkaysaurus and integrate new information into new phylogenetic and morphological disparity analyses focused on non-coelurosaurian tetanurans. Our results agree with recent studies that place Piatnitzkysauridae (including Condorraptor, Marshosaurus, Piatnitzkysaurus, and Xuanhanosaurus) as the earliest diverging group of Allosauroidea and within a monophyletic Carnosauria (Allosauroidea + Megalosauroidea). Morphological disparity analyses of the appendicular skeleton of non-coelurosaurian tetanurans show that the Jurassic species occupy a different morphospace from the Cretaceous species. Condorraptor and Piatnitzkysaurus are found within the morphospace occupied by the Middle Jurassic species from the Northern Hemisphere, which indicates the presence of similar body plans for the non-coelurosaurian tetanurans during the Early–Middle Jurassic worldwide. The new information about Piatnitzkysaurus improves our knowledge about the evolution of early tetanurans.
Potassium channel‐mediated NO‐induced vasodilation during maturation: Dominance of Kv7 channels
Authors: Shvetsova Anastasia A. , Gaynullina Dina K. , Winkler Peter , Wohlfart Paulus , Schubert Rudolf
Published: January 2025

Maturation represents a process characterized by adaptive changes, particularly in the circulatory system. However, it is not known whether, in neonates, potassium channels contribute to NO‐induced vasorelaxation at all and, if so, which potassium channels these are. Therefore, this study tested the hypothesis that potassium channels mediate NO‐induced vasorelaxation in newborn rats. Young (10‐ to 15‐day‐old) and adult (2‐ to 3‐month‐old) male rats were studied using real‐time PCR, isometric myography, and the sharp microelectrode technique on saphenous arteries. We observed prominent mRNA expression of several distinct isoforms of potassium channel families known to potentially mediate SNP‐induced vasodilation. Further, in both adult and young rats, SNP can relax vessels independently of potassium channels. A solely potassium channel‐independent anticontractile effect of SNP was observed also when either Kir6, or Kir2, or Kv2 channels, respectively, were available in both adult and young rats. However, when Kv1 channels were available, a Kv1 channel‐dependent component contributed to the anticontractile effect of SNP in young rats. When BKCa channels were available, a BKCa channel‐dependent component contributed to the anticontractile effect of SNP in adult rats. A considerable Kv7 channel‐dependent component contributed to the anticontractile effect of SNP in both adult and young rats. Thus, the data of the present study show for the first time that potassium channels, even multiple ones, contribute to SNP‐induced vasorelaxation in newborn rats and that the potassium channels involved in SNP‐induced vasorelaxation change from Kv1/Kv7 channels to BKCa/Kv7 channels during postnatal development.
Effect modification in settings with “truncation by death”
Authors: Gonçalves Bronner P. , Suzuki Etsuji
Published: January 2025

Epidemiologic studies recruiting individuals with higher-than-population-average mortality can be affected by “truncation by death”, whereby the outcome of interest (e.g. quality of life) is considered not to be defined for individuals who die before the end of follow-up. Here, we use the potential outcomes framework and principal stratification to derive conditions under which the survivor average causal effect, an estimand defined for the “always-survivors” stratum, is modified by a variable that represents a possible common cause of survival and the outcome of interest, and by a variable that only affects survival. Further, we show that this principal effect can be expressed as a weighted average of this treatment effect for individuals with each level of these variables, and that these weights depend not only on the relative frequencies of the levels in the total population, but also in the “always-survivors” principal stratum. We also discuss the implications of this work for the transportability of the survivor average causal effect.
Estimating prevalence of opioid misuse in North Carolina counties from 2016-2021: An integrated abundance model approach
Authors: Kline David M. , White Brian N. , Lancaster Kathryn E. , Egan Kathleen L. , Murphy Eva , Miller William C. , Hepler Staci A.
Published: January 2025

Background:

The overdose epidemic remains largely driven by opioids, but county-level prevalence of opioid misuse is unknown. Without this information, public health and policy responses are limited by a lack of knowledge on the scope of the problem.

Methods:

Using an integrated abundance model, we estimate annual county-level prevalence of opioid misuse for counties in North Carolina from 2016 to 2021. The model integrates county-level observed counts of illicit opioid overdose deaths, people receiving prescriptions for buprenorphine, and people served by treatment programs. It also incorporates state-level survey estimates of misuse prevalence. County-level social and environmental covariates are also accounted for in the model. Data are integrated through a Bayesian hierarchical model to estimate posterior distributions of the parameters.

Results:

In general, the estimated prevalence of misuse was decreasing over the study period. Estimated prevalence was above average in the western and southeastern parts of the state. We also estimated that the proportion of people who misuse opioids who fatally overdosed increased sharply over the study period as the median estimated proportion in 2021 was more than 8 times greater than 2016. The proportion of people who misuse opioids who received buprenorphine and were served by treatment programs increased over the study period.

Conclusions:

Estimates from our integrated abundance model fill an important gap in public health knowledge about the local prevalence of people who misuse opioids and can be used to inform an adequate and equitable allocation of resources to communities across the state.