bluuebunny/crossref_metadata_2025_split huggingface dataset:
Do Public Works Programs Have Sustained Impacts? A Review of Experimental Studies from LMICs
Authors: Bagga Aanchal , Holmlund Marcus , Khan Nausheen , Mani Subha , Mvukiyehe Eric , Premand Patrick 
Published: December 2024

Abstract
Many low- and middle-income countries (LMICs) have introduced public works programs that offer temporary cash-for-work opportunities to poor individuals. We review experimental evidence on the impacts of public works programs on participants over the short and medium run, providing new insights on whether they have sustained impacts. Our findings show that public works mainly increase employment and earnings during the program. Short-term positive effects tend to fade in the medium run, except in a few cases in which large impacts on savings or investments in self-employment activities are also observed. We find evidence of improvements in psychological well-being and women's empowerment in some cases, but not systematically, and with limitations in measurement. In some contexts, public works programs also improve market wages, affecting both participants and non-participants. We conclude by outlining directions for future research.
Molecular profiling unveils pyroptosis markers in preterm birth
Authors: Li Xiaoyun , Huang Zhulan , Bai Jiangtao , Che Aiwen , Zhou Jinhua , Yang Hongmei 
Published: December 2024

AbstractThrough a comprehensive examination of pyroptosis‐related differential expressed genes (PRDEGs), this work investigates the molecular complexities of spontaneous preterm birth (SPTB), also known as premature delivery, before the due date. Through the process of merging and correcting batch effects in the GSE120480 and GSE73714 datasets, we were able to identify 36 PRDEGs that exhibited significant expression differentiation in SPTB. Through functional enrichment and pathway analysis, their importance in amino acid transport and cytokine receptor interaction has been highlighted. Among the genes that have emerged as crucial, CEBPA, APOA1, and CEP55 have been identified. The relevance of these molecules was demonstrated using experimental knockdowns, which also suggested that they could be used as molecular biomarkers and therapeutic targets for SPTB.
Excess shed mesothelin disrupts pancreatic cancer cell clustering to impair peritoneal colonization
Authors: Ewa Theressa , Panchwagh Neel , Tai Chin‐Hsien , Avula Leela Rani , Joseph Sarah , Rudloff Michael W. , Malik Nargis , Zhang Xianyu , Alewine Christine 
Published: December 2024

AbstractPeritoneum is the second most common site of metastasis in patients with pancreatic ductal adenocarcinoma (PDAC). Peritoneal colonization is impaired in PDAC cells with knockout (KO) of the cancer surface antigen mesothelin (MSLN) or by introducing Y318A mutation in MSLN to prevent binding to mucin‐16 (MUC‐16). MSLN has a membrane‐bound form but is also shed to release soluble MSLN (sMSLN). Their individual roles in peritoneal metastasis are unknown. Here, a C‐terminal truncated MSLN mutant (∆591) incapable of cell membrane insertion but proficient in secretion was engineered. Expression of ∆591 MSLN failed to rescue peritoneal metastasis in MSLN KO cells and inhibited peritoneal colonization when overexpressed in WT PDAC cells. Exposing PDAC cells to conditioned medium (CM) containing excess sMSLN impaired cancer cell clustering in vitro and in peritoneal fluid in vivo, while CM containing only Y318A sMSLN did not. These data demonstrate that interaction of membrane‐bound MSLN with MUC‐16 promotes cell clustering that is critical for efficient peritoneal metastasis. However, peritoneal colonization by MSLN KO cells was rescued by expression of ∆591 mutant MSLN bearing Y318A mutation, suggesting that sMSLN also has a MUC‐16‐independent role in peritoneal spread. Alterations in inflammatory signaling pathways occurred following KO cell exposure to CM containing sMSLN, and CM from cancer cells with intact peritoneal metastasis provoked increased KO cell secretion of IL‐1α. While excess sMSLN inhibits cell clustering and peritoneal colonization, sMSLN may also promote PDAC peritoneal metastasis independent of MUC‐16.
Role of LIPIN 1 in regulating metabolic homeostasis in the retinal pigment epithelium
Authors: Usoltseva Anna S. , Litwin Christopher , Lee Michael , Hill Colton , Cai Jiyang , Chen Yan 
Published: December 2024

AbstractDysregulated lipid metabolism, characterized by the accumulation of lipid deposits on Bruch's membrane and in drusen, is considered a key pathogenic event in age‐related macular degeneration (AMD). The imbalance of lipid production, usage, and transport in local tissues, particularly in the retinal pigment epithelium (RPE), is increasingly recognized as crucial in AMD development. However, the molecular mechanisms governing lipid metabolism in the RPE remain elusive. LIPIN1, a multifunctional protein acting as both a modulator of transcription factors and a phosphatidate phosphatase (PAP1), is known to play important regulatory roles in lipid metabolism and related biological functions, such as inflammatory responses. While deficits in LIPIN1 have been linked to multiple diseases, its specific roles in the retina and RPE remain unclear. In this study, we investigated LIPIN1 in RPE integrity and function using a tissue‐specific knockout animal model. The clinical and histological examinations revealed age‐dependent degeneration in the RPE and the retina, along with impaired lipid metabolism. Bulk RNA sequencing indicated a disturbance in lipid metabolic pathways. Moreover, these animals exhibited inflammatory markers reminiscent of human AMD features, including deposition of IgG and C3d on Bruch's membrane. Collectively, our findings indicate that LIPIN1 is a critical component of the complex regulatory network of lipid homeostasis in the RPE. Disruption of LIPIN1‐mediated regulation impaired lipid balance and contributed to AMD‐related pathogenic changes.
Disulfidoptosis‐related molecular subtypes and prognostic model for optimizing drug therapy in metastatic osteosarcoma patients
Authors: Wang Xiaoping , Xie Chao , Lin Lijun 
Published: December 2024

AbstractDisulfidotosis is a newly identified form of cell death associated with tumor response, patient outcomes, and cancer progression. This study aims to identify disulfidptosis‐related genes (DiRGs) and their role in osteosarcoma (OS) to predict prognosis and optimize drug therapy for better patient survival. Gene expression matrices and clinical information on OS were obtained from the TARGET and GEO databases. Unsupervised clustering analysis identified two DiRG molecular subgroups with significantly different intratumoral heterogeneity and tumor microenvironment cell infiltrating characteristics in OS. A robust disulfidptosis‐related prognostic model using five DiRGs was developed, demonstrating excellent predictive and prognostic power in OS with AUC values of 0.69, 0.78, and 0.85 for 1‐, 3‐, and 5‐year periods, respectively. Investigations into the impact of disulfidoptosis on immune status in OS patients across different risk subgroups revealed that a low immune score and compromised immune status were associated with an unfavorable prognosis for OS patients. INF2 and MEGF10 genes are highly reliable predictors of metastasis among the hub DiRG genes. The validation results indicate a robust correlation between the expression of INF2 and MEGF10 and the severity of malignancy and metastasis in OS. Six drugs targeting osteosarcoma metastasis were identified, with INF2‐BP‐1‐102 and MEGF10‐AS703569 showing the best docking scores, indicating their potential to treat OS metastasis effectively. These findings provide valuable insight into improving treatment for OS patients.
Exploring Burnout and Leadership Mitigation Plans in Academic Nursing Environments
Authors: Saylor Jennifer , Evans Jennifer , Goodolf Dawn , Martin Nia M. , Martinez-Hollingsworth Adrienne 
Published: December 2024

Background:
Staff burnout in higher education may affect nursing department functionality. There is limited literature regarding staff burnout and its manifestations in nursing colleges and schools.

Purpose:
This study evaluated academic nurse leaders’ perceptions of burnout and mitigation strategies in colleges and schools of nursing.

Methods:
A descriptive, cross-sectional survey examined burnout and mitigation strategies among associate deans, business officers, and members of the Organizational Leadership Network (n = 105).

Results:
Among academic leaders, 57.14% noted that staff burnout was either a notable or a major challenge. Resignations (56.86%) and difficulties in backfilling staff positions (54.90%) were the 2 most common manifestations of staff burnout. However, only a small percentage had an active burnout mitigation strategy for faculty (13.33%) and staff (6.67%).

Conclusion:
There is a disconnect between acknowledging burnout as a pressing concern and implementing effective mitigation strategies. By creating a supportive work environment and encouraging professional development, leaders can significantly reduce burnout and enhance overall employee well-being.
Undergraduate Nursing Students’ Perceptions of Geriatric Care and Nursing Curriculum
Authors: Consolo Victoria , Clark Stephanie B. , Lippe Megan P. 
Published: December 2024

Background:
The geriatric population in the United States is growing rapidly with an expected increase of 22% by 2040. Nursing students, however, consistently report negative attitudes toward caring for geriatric patients.

Purpose:
The purpose was to assess undergraduate nursing student perceptions of care for the geriatric population, how their nursing curriculum influenced these perceptions, and any perceived curricular changes, didactic or clinical, that could potentially improve students’ preparedness and desire to seek a career in geriatric nursing.

Methods:
Using a convergent parallel mixed methods approach, senior prelicensure nursing students completed a Likert-scale survey with additional open-ended questions to assess perceptions of geriatric care and how the current nursing curriculum relates to those perceptions.

Results:
Quantitative data identified that most students believed the didactic curriculum prepared them for geriatric care but did not increase their desire to work with geriatric patients. Qualitative data identified negative stereotypes and clinical experiences and revealed a lack of desire for geriatric care.

Conclusions:
Lack of desire for geriatric care was the norm for participants. Geriatric care should be more heavily weighted in academics, and educators should develop innovative methods that increase the desire of prelicensure students to commit to care for the geriatric population.
Mpox vaccine communication among sexually active men who have sex with men
Authors: Abara Winston E. , Carpino Tom , Atkins Kaitlyn , Hannah Marissa , Edwards O. Winslow , Renfro Kaytlin J. , Baral Stefan , Sanchez Travis , Learner Emily R. , Galloway Eboni , Lansky Amy 
Published: December 2024

Abstract
We assessed mpox vaccine communication and sexual behavior among U.S. MSM during the 2022 mpox outbreak. Less than 40% of respondents asked a new male sex partner about their mpox vaccination status. Mpox vaccine communication was positively associated with condomless anal sex and group sex. Mpox vaccine communication is low but may inform and sexual behaviors among MSM.
Hi-C Calibration by Chemically Induced Chromosomal Interactions
Authors: Li Yi , Zou Fan , Bai Lu 
Published: December 2024

AbstractThe genome-wide chromosome conformation capture method, Hi-C, has greatly advanced our understanding of genome organization. However, its quantitative properties, including sensitivity, bias, and linearity, remain challenging to assess. Measuring these propertiesin vivois difficult due to the heterogenous and dynamic nature of chromosomal interactions. Here, using Chemically Induced Chromosomal Interaction (CICI) method, we create stable intra- and inter-chromosomal interactions in G1-phase budding yeast across a broad range of contact frequencies. Hi-C analysis of these engineered cell populations demonstrates that static intra-chromosomal loops do not generate Topologically Associated Domains (TADs) and only promote 3D proximity within ∼50kb flanking regions. At moderate sequencing depth, Hi-C is sensitive enough to detect interactions occurring in 5-10% of cells. It also shows no inherent bias toward intra-versus inter-chromosomal interactions. Furthermore, we observe a linear relationship between Hi-C signal intensity and contact frequency. These findings illuminate the intrinsic properties of the Hi-C assay and provide a robust framework for its calibration.
The sodium-glucose cotransporter 2 inhibitor tofogliflozin induces vasodilation by activating Kv channels, the SERCA pump, and the sGC/cGMP pathway
Authors: Zhuang Wenwen , Park Minju , Jeong Junsu , Kim Hye Ryung , Jang YeEun , Seo Mi Seon , An Jin Ryeol , Park Hongzoo , Jung Won-Kyo , Choi Il-Whan , Park Won Sun 
Published: December 2024

AbstractOBJECTIVETofogliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor widely used to treat T2DM, but it also exhibits cardio-protective effects. This study investigated the vasodilatory action of tofogliflozin using rabbit femoral artery rings pre-contracted with phenylephrine.APPROACH AND RESULTSThe femoral artery quickly separated from the rabbit and fix it to the organ bath chamber. Subsequently, administer an inhibitor that modulates vascular tension in the rings or remove the endothelium to assess its impact on vasodilation. The results showed the concentration-dependent induction of vasodilation by tofogliflozin, a response that remained unchanged following endothelial removal, pretreatment with the nitric oxide synthase (NOS) inhibitor L-NAME, or the inhibition of low- and intermediate-conductance Ca2+-activated K+channels (SKCaand IKCa) using apamin in combination with TRAM-34. Furthermore, pretreatment with the voltage-dependent K+(Kv) channel inhibitor 4-AP reduced the vasodilatory effects of tofogliflozin whereas pretreatment with the ATP-sensitive K+(KATP) channel inhibitor glibenclamide or the large-conductance Ca2+-activated K+(BKCa) channel inhibitor paxilline did not. Notably, our findings indicated that Kv7.X, rather than Kv1.5 or Kv2.1, is the primary Kv subtype involved in tofogliflozin-induced vasodilation. The vasodilatory effects of tofogliflozin were also significantly inhibited in femoral arterial rings pretreated with the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) pump inhibitors thapsigargin and cyclopiazonic acid (CPA). Tofogliflozin-induced vasodilation was unaltered in arterial rings exposed to the adenylyl cyclase inhibitor SQ 22536, the protein kinase A (PKA) inhibitor KT 5720, and the protein kinase G (PKG) inhibitor KT 582 whereas it was effectively reduced by the soluble guanylyl cyclase (sGC) inhibitor ODQ.CONCLUSIONSThese findings suggest that tofogliflozin-induced vasodilation is mediated by the activation of the SERCA pump, the sGC/cGMP pathway, and Kv channels, but not the PKA signaling pathway, other K+channels, or endothelium-dependent mechanisms.
Systematic design of multiplex methylation-specific qPCR for cancer related biomarkers
Authors: Wang Joy , Lee Michelle Yiru , Lin Brian Boyuan , Wu Annie X. 
Published: December 2024

AbstractAnalysis of circulating cell-free DNA (cfDNA) methylation abnormalities has emerged as a powerful strategy for detecting various diseases, particularly cancers. This study demonstrates a process for developing a multiplex methylation-specific qPCR assay for cancer biomarker detection.AbstractAnalysis of circulating cell-free DNA (cfDNA) methylation abnormalities has emerged as a promising strategy for detecting various diseases, including cancer. While single-biomarker approaches may lack sensitivity, comprehensive next-generation sequencing (NGS) can be cumbersome and expensive. Multiplex methylation qPCR assays offer a practical intermediate solution by providing accurate, accessible, and affordable methylation biomarker detection. In this study, we demonstrated a process for developing a multiplex methylation-specific qPCR assay using colorectal cancer (CRC) methylation biomarkers as a case study. Starting with a set of CRC methylation biomarkers, we developed the Multiplex Methylation-specific qPCR (MMqPCR) algorithm to scan differentially methylated regions (DMRs) for methylation-specific PCR primer and probe design. We then established a systematic process to eliminate assay cross-reactions, reduce background noise, and assess multiplex compatibility. Using a low concentration of hypermethylated DNA (0.1%) in a digital analysis, we demonstrated a 95.8% detection rate with the multiplex strategy, significantly outperforming the singleplex approach (47.9%). The multiplex qPCR development principles and automated primer design algorithm presented here provide valuable tools for developing disease screening, detection or monitoring methods based on methylation analysis.
Unveiling the evolutionary history of European vipers and their venoms from a multi-omic approach
Authors: Talavera Adrián , Palmada-Flores Marc , Martínez-Freiría Fernando , Mochales-Riaño Gabriel , Burriel-Carranza Bernat , Estarellas Maria , Fernández-Guiberteau Daniel , Camina Álvaro , Ursenbacher Sylvain , Vörös Judit , Halpern Bálint , Pla Davinia , Calvete Juan José , Mikheyev Alexander S. , Marquès-Bonet Tomàs , Carranza Salvador 
Published: December 2024

AbstractSnake genomes attract significant attention from multiple disciplines, including medicine, drug bioprospection, and evolutionary biology, due to the unique features found in snakes, especially, the evolution of venom. However, genomic research within the family Viperidae has mostly focused to date on the subfamily Crotalinae, while overlooking Viperinae, the Old World vipers. Among Viperinae, European vipers (Vipera) have been the subject of extensive research because of their venoms, phylogeographic, and ecological diversification. Nevertheless, venom research in this group has been conducted using mostly proteomes alone, while phylogeography and systematics in the genus have relied on biased information from mitochondrial phylogenies. Here, we generated chromosome-level genome assemblies for threeViperaspecies and whole-genome sequencing data for 94 samples representing 15Viperataxa. This comprehensive dataset has enabled us to disentangle the phylogenomic relationships of this genus, affected by mito-nuclear discordance and pervaded by ancestral introgression. Population-level analyses in the Iberian Peninsula, where the three oldest lineages withinViperameet, revealed signals of recent adaptive introgression between ecologically dissimilar species, whereas chromosomal rearrangements isolate species occupying similar niches. Finally, using transcriptomic and proteomic data, we characterized theViperatoxin-encoding genes, in which opposing selective forces were unveiled as common drivers of the evolution of venom as an integrated phenotype.
A role for fibroblast and mural cell subsets in models of neuropathic pain
Authors: Villa-Hernandez Sara , Walker Julia Vlachaki , Hore Zoe , Fedele Laura , Zebochin Irene , Li Yuening , Davis Harvey , Kanda Takashi , Shimizu Fumitaka , Taams Leonie , Denk Franziska 
Published: December 2024

AbstractNeuropathic pain is a particularly intractable type of chronic pain that can result from physical nerve damage due to surgery or entrapment. Here, we present data which suggest that a particular subclass of fibroblast and mural cells may be implicated in the sensory neuron dysfunction that is characteristic of this pain state.In a mouse model of traumatic painful neuropathy, we used RNA sequencing, cell sorting and nerve tissue clearing to study mesenchymal lineage cells. We show that Pdgfrb+ fibroblasts and mural cells are increased in number for at least two months post-nerve damage and express high levels of known and putative pro-algesic mediators, which are further upregulated in neuropathy.We go on to demonstrate that a human nerve pericyte line releases a selection of these pro-algesic mediators at protein level. Moreover, conditioned media from stimulated human pericytes induces intra-cellular changes in human induced pluripotent stem cell derived sensory neurons; these changes (phosphorylation of the transcription factor STAT3) have been previously linked to sensory neuron activation.In summary, our data indicate that mesenchymal cell abnormalities should be considered when developing novel strategies to tackle neuropathic pain.
The mammalian protein MTCH1 can function as an insertase
Authors: Dimogkioka Anna Roza , Elias Anni , Rapaport Doron 
Published: December 2024

AbstractThe outer mitochondrial membrane (OMM) hosts a variety of proteins such as import machineries, enzymes, fission/fusion factors, and pore proteins. InSaccharomyces cerevisiae, the MIM complex, consisting of Mim1 and Mim2, mediates the insertion of α-helical proteins into the OMM. Until recently, it was unclear which proteins serve this function in higher eukaryotes. Recent studies identified MTCH2 as the insertase of α-helical proteins into the OMM in mammals. MTCH1 is a paralogue of MTCH2 but its general function and contribution to the biogenesis process are not clear. To better characterize MTCH1, we explored whether MTCH1 or MTCH2 could functionally replace Mim1/Mim2 in yeast. Expression of MTCH1 and MTCH2 in yeast cells lacking Mim1, Mim2, or both revealed that MTCH1, but not MTCH2, could compensate the growth defects upon deleting the MIM complex. Furthermore, MTCH1 could restore the biogenesis of MIM substrates, TOM complex stability, and morphology of mitochondria. These findings indicate that MTCH1 by itself has insertase activity and is a functional homologue of the MIM complex, despite the absence of any evolutionary relation between the mammalian and yeast insertases.
Further varieties of ancient endogenous retrovirus in human DNA
Authors: Frith Martin C. 
Published: December 2024

SummaryA retrovirus inserts its genome into the DNA of a cell, occasionally a germ-line cell that gives rise to descendants of the host organism: it is then called an endogenous retrovirus (ERV). The human genome contains relics from many kinds of ancient ERV. Some relics contributed new genes and regulatory elements.This study finds further kinds of ancient ERV, in the thoroughly-studied human genome version hg38: ERV-Hako, ERV-Saru, ERV-Hou, ERV-Han, and ERV-Goku. It also finds many relics of ERV-V, previously known from just two copies on chromosome 19 with placental genes. It finds a type of ERV flanked by MER41E long terminal repeats (LTRs), with surprisingly little similarity to the known MER41 ERV. ERV-Hako has subtypes that contain sequence from host genesSUSD6andSPHKAP: theSUSD6variant was transferred between catarrhine and platyrrhine primates. A retrovirus uses tRNA to prime reverse transcription: Hako is the only human ERV relic that used tRNA-Trp (tryptophan, symbol W), and HERV-W is misnamed because it used tRNA-Arg, based on the Genomic tRNA Database. One ERV-Saru LTR is the previously-described enhancer ofAIM2in innate immunity. This study contributes to understanding primate ERV history, but also shows that related ERVs can have drastic differences, challenging the goal of clearly annotating all ERV relics in genomes.