bluuebunny/crossref_metadata_2025_split huggingface dataset:
Specifying cellular context of transcription factor regulons for exploring context-specific gene regulation programs
Authors: Minaeva Mariia , Domingo Júlia , Rentzsch Philipp , Lappalainen Tuuli 
Published: January 2025

Abstract
Understanding the role of transcription and transcription factors (TFs) in cellular identity and disease, such as cancer, is essential. However, comprehensive data resources for cell line-specific TF-to-target gene annotations are currently limited. To address this, we employed a straightforward method to define regulons that capture the cell-specific aspects of TF binding and transcript expression levels. By integrating cellular transcriptome and TF binding data, we generated regulons for 40 common cell lines comprising both proximal and distal cell line-specific regulatory events. Through systematic benchmarking involving TF knockout experiments, we demonstrated performance on par with state-of-the-art methods, with our method being easily applicable to other cell types of interest. We present case studies using three cancer single-cell datasets to showcase the utility of these cell-type-specific regulons in exploring transcriptional dysregulation. In summary, this study provides a valuable pipeline and a resource for systematically exploring cell line-specific transcriptional regulations, emphasizing the utility of network analysis in deciphering disease mechanisms.
vClean: assessing virus sequence contamination in viral genomes
Authors: Wagatsuma Ryota , Nishikawa Yohei , Hosokawa Masahito , Takeyama Haruko 
Published: January 2025

Abstract
Recent advancements in viral metagenomics and single-virus genomics have improved our ability to obtain the draft genomes of environmental viruses. However, these methods can introduce virus sequence contaminations into viral genomes when short, fragmented partial sequences are present in the assembled contigs. These contaminations can lead to incorrect analyses; however, practical detection tools are lacking. In this study, we introduce vClean, a novel automated tool that detects contaminations in viral genomes. By applying machine learning to the nucleotide sequence features and gene patterns of the input viral genome, vClean could identify contaminations. Specifically, for tailed double-stranded DNA phages, we attempted accurate predictions by defining single-copy-like genes and counting their duplications. We evaluated the performance of vClean using simulated datasets derived from complete reference genomes, achieving a binary accuracy of 0.932. When vClean was applied to 4693 genomes of medium or higher quality derived from public ocean metagenomic data, 1604 genomes (34.2%) were identified as contaminated. We also demonstrated that vClean can detect contamination in single-virus genome data obtained from river water. vClean provides a new benchmark for quality control of environmental viral genomes and has the potential to become an essential tool for environmental viral genome analysis.
ProPr54 web server: predicting σ54 promoters and regulon with a hybrid convolutional and recurrent deep neural network
Authors: Achterberg Tristan , de Jong Anne 
Published: January 2025

Abstract
σ54 serves as an unconventional sigma factor with a distinct mechanism of transcription initiation, which depends on the involvement of a transcription activator. This unique sigma factor σ54 is indispensable for orchestrating the transcription of genes crucial to nitrogen regulation, flagella biosynthesis, motility, chemotaxis and various other essential cellular processes. Currently, no comprehensive tools are available to determine σ54 promoters and regulon in bacterial genomes. Here, we report a σ54 promoter prediction method ProPr54, based on a convolutional neural network trained on a set of 446 validated σ54 binding sites derived from 33 bacterial species. Model performance was tested and compared with respect to bacterial intergenic regions, demonstrating robust applicability. ProPr54 exhibits high performance when tested on various bacterial species, highly surpassing other available σ54 regulon identification methods. Furthermore, analysis on bacterial genomes, which have no experimentally validated σ54 binding sites, demonstrates the generalization of the model. ProPr54 is the first reliable insilico method for predicting σ54 binding sites, making it a valuable tool to support experimental studies on σ54. In conclusion, ProPr54 offers a reliable, broadly applicable tool for predicting σ54 promoters and regulon genes in bacterial genome sequences. A web server is freely accessible at http://propr54.molgenrug.nl.
PSAURON: a tool for assessing protein annotation across a broad range of species
Authors: Sommer Markus J , Zimin Aleksey V , Salzberg Steven L 
Published: January 2025

Abstract
Evaluating the accuracy of protein-coding sequences in genome annotations is a challenging problem for which there is no broadly applicable solution. In this manuscript, we introduce PSAURON (Protein Sequence Assessment Using a Reference ORF Network), a novel software tool developed to help assess the quality of protein-coding gene annotations. Utilizing a machine learning model trained on a diverse dataset from over 1000 plant and animal genomes, PSAURON assigns a score to coding DNA or protein sequence that reflects the likelihood that the sequence is a genuine protein-coding region. PSAURON scores can be used for genome-wide protein annotation assessment as well as the rapid identification of potentially spurious annotated proteins. Validation against established benchmarks demonstrates PSAURON’s effectiveness and correlation with recognized measures of protein quality, highlighting its potential use as a widely applicable method to evaluate precision in gene annotation. PSAURON is open source and freely available at https://github.com/salzberg-lab/PSAURON.
Collaborative governance in politicized times: the battle over asylum policies in Italian cities
Authors: Bazurli Raffaele , Campomori Francesca 
Published: January 2025

Abstract
Collaborative governance has gained momentum for its promise to deliver social inclusion, with municipalities viewed as ideal spaces for its success. However, little research critically examines the political conditions under which this is the case. This article theorizes why and how collaborative local governance succeeds or fails in today’s divided democracies. It argues that politicization manifests in three dimensions of local governance—among stakeholders, across government levels, and in the framing of policy target groups. These dynamics often incentivize the exclusion of marginalized populations. For collaboration to succeed, it must be anchored in an ideologically cohesive network of stakeholders, with civil society organizations acting as political advocates for disadvantaged groups. Drawing on fieldwork conducted in 2018–2022, we compare asylum policies in two Italian cities: Bologna and Venice. Despite rising far-right politics nationally, Bologna’s collaborative governance persisted thanks to the sustained commitment of local officials and civil society actors, all sharing ideological and strategic motivations in promoting refugee rights. In contrast, anti-migrant politics has increasingly informed the policy agenda of Venice elected officials. The politicization of immigration offered them powerful incentives to wipe out long-established collaborations and to frame refugees as undeserving policy targets, leading to their exclusion from public services. These findings extend to other geographical contexts and policy sectors, calling for a more political understanding of collaborative local governance.
Who’s to blame for the Brazilian nuclear program never coming of age?
Authors: Nicolini Gabriel João Paulo , Belém Lopes Dawisson 
Published: January 2025

Abstract
The article examines Brazil’s attempt to establish a national nuclear industry during its military regime (1964–85), focusing on the 1975 nuclear agreement with West Germany. Based on extensive document analysis and interviews, this study reveals that despite the agreement’s goal of reducing dependence on US technology, it reinforced Brazil’s reliance on foreign sources and highlighted flaws in its Science and Technology strategy. The technocratic elite, or “nucleocracy,” prioritized rapid development over nurturing domestic research, sidelining academic and industrial stakeholders. The article employs the National Innovation Systems framework, particularly the triple helix model, to demonstrate how insufficient collaboration between academia, industry, and government hindered the establishment of a self-sufficient nuclear sector. The findings underscore that international scientific collaborations, while intended to foster technological autonomy, can paradoxically entrench dependence when domestic capacity-building is neglected.
Signaling via retinoic acid receptors mediates decidual angiogenesis in mice and human stromal cell decidualization
Authors: Zhao Qingshi , Samuels Cherie‐Ann , Timmins Patrick , Massri Noura , Chemerinski Anat , Wu Tracy , Loia Rachel , Cheung Emma K. , Zhang Xusheng , Arora Ripla , Babwah Andy V. , Douglas Nataki C. 
Published: January 2025

AbstractAt the maternal‐fetal interface, tightly regulated levels of retinoic acid (RA), the physiologically active metabolite of vitamin A, are required for embryo implantation and pregnancy success. Herein, we utilize mouse models, primary human cells, and pharmacological tools to demonstrate how depletion of RA signaling via RA receptor (RAR) disrupts implantation and progression of early pregnancy. To inhibit RAR signaling during early pregnancy, BMS493, an inverse pan‐RAR agonist that prevents RA‐induced differentiation, was administered to pregnant mice during the peri‐implantation period. Attenuation of RA/RAR signaling prior to embryo implantation results in implantation failure, whereas attenuation of RA/RAR signaling after embryo implantation disrupts the post‐implantation decidual vasculature and results in pregnancy failure by mid‐gestation. To inhibit RAR signaling during human endometrial stromal cell (HESC) decidualization, primary HESCs and decidualized primary HESCs were transfected with silencing RNA specific for human RARA. Inhibition of RA/RARA signaling prevents initiation of HESC decidualization, but not maintenance of the decidualized HESC phenotype. These data show that RA/RAR signaling is required for maintenance of the decidual vasculature that supports early pregnancy in mice, and distinct RAR signaling is required for initiation, but not maintenance of primary HESC decidualization in vitro.
Mechanical Failure of the Stryker T2 Alpha Retrograde Femoral Nail
Authors: Lopas Luke A. , Soni Chirag , Natoli Roman M. , Jang Yohan , Milburn Mason , McKinley Todd O. , Mullis Brian , Szatkowski Jan P. 
Published: January 2025

OBJECTIVE:
To evaluate mechanical failure rates of retrograde femoral nails in the treatment of distal femur fractures.

METHODS:

Design: Retrospective chart review.

Setting:
Urban Academic Level 1 Trauma Center.

Patient Selection Criteria:
Included were adult patients who sustained a distal femur fracture (AO/OTA 33) who were treated with a retrograde intramedullary nail from August 2021 through September 2022.

Outcome Measures and Comparisons:
The primary outcome was the rate of mechanical failure of the intramedullary nail defined as deformation and/or breakage of the intramedullary nail. The rate of mechanical failure was compared amongst retrograde femoral nails used at the same institution during the same time period.

RESULTS:
One hundred and twenty distal femur fractures were identified (77 native distal femur, 43 periprosthetic) that were treated with a retrograde intramedullary nail. Average patient age was 67 years (SD 15.1, range 18-96 years). Eighty-three (69.2%) of patients were female. Four mechanical nail failures (deformation and/or breakage of the intramedullary nail) were observed within six months of surgery, two in patients with native distal femur fractures, and two in patients with periprosthetic distal femur fractures. All failures occurred among forty-nine fractures treated with a newly released retrograde femoral nail, the T2 Alpha Retrograde Femoral Nail (Stryker, Mahwah, NJ). This represents an 8.2% mechanical failure rate of distal femur fractures treated with this new nail compared to no failures observed with any other nail (p=0.03).

CONCLUSIONS:
Mechanical nail failures, within six months of surgery for distal femur fracture, of a new retrograde femoral nail were observed to be higher than seen with other nails. Further evaluation is needed to determine if this experience represents factors related to patient, injury, or surgical characteristics, an anomaly, or a safety signal.

Level Of Evidence:
Therapeutic Level III. See instructions for authors for a complete description of levels of evidence.
Inpatient Multimodal Pain Regimens Do Not Impact Hospital Length of Stay or Long-term Postoperative Opioid Use Following 1 and 2-Level Lumbar Fusion
Authors: Carter Michael , Narayanan Rajkishen , Toci Gregory , Lee Yunsoo , Fras Sebastian , Hammelef Emma , Mumtaz Shiraz , Garayo Tasha , Kurd Mark , Kaye Ian David , Canseco Jose , Hilibrand Alan , Vaccaro Alexander , Kepler Christopher , Schroeder Gregory 
Published: January 2025

Study Design:
Retrospective cohort study.

Objective:
To determine hospital length of stay (LOS) and long-term opioid consumption among patients who received inpatient multimodal analgesia following lumbar spine surgery, as opposed to those who received opioids alone.

Summary of Background Data:
Opioids have long been the historical choice for managing postoperative pain. The use of multimodal analgesia has become more commonplace in recent years as it is thought to achieve similar levels of pain control while simultaneously diminishing opioid consumption and decreasing LOS.

Materials and Methods:
Patients who underwent 1 or 2-level lumbar fusion from 2018 to 2019 were included. Patients who received opioids on an as-needed basis were propensity-matched to a cohort who received multimodal analgesia based on demographics, surgical approach, and levels fused. LOS was collected for each patient. One year preoperative to 2 postoperative opioid use was obtained from the Pennsylvania Prescription Drug Monitoring Program and included total prescriptions and total morphine milligram equivalents (MMEs). A subanalysis was also performed comparing preoperative, perioperative, and postoperative tramadol consumption during this time frame.

Results:
A total of 69 patients received an opioid-only pain regimen, while 207 patients received multimodal analgesia. Patients receiving a multimodal pain regimen consumed a higher daily tramadol MME but a comparable total in-hospital MME to patients in the opioid-only cohort. No statistically significant differences existed between cohorts with regards to LOS, preoperative, perioperative, and postoperative opioid consumption, though multimodal patients consumed more tramadol from 0 to 30 days postoperatively.

Conclusions:
Patients who received a multimodal pain regimen consumed comparable quantities of opioids to those who received opioids alone and did not have a longer LOS following 1 and 2-level lumbar fusion.
Efficacy and Safety of 730-nm Picosecond Laser for the Treatment of Acquired Bilateral Nevus of Ota-like Macules
Authors: Han Rui , Sun Yifang , Su Mingshan 
Published: January 2025

BACKGROUND
The effectiveness and safety of 730-nm picosecond laser for treating acquired bilateral nevus of Ota-like macules remain uncertain.

OBJECTIVE
This study aims to evaluate the potential benefits and risks of using the 730-nm picosecond laser for ABNOM removal.

METHODS
This is a retrospective review of patients who were presented to the clinic between January 2020 and January 2024 for the treatment of ABNOM with 730-nm picosecond laser alone. The efficacy of the laser was assessed based on the Quartile Improvement Scale, using high-resolution photographs evaluated by blinded dermatologists.

RESULTS
A total of 72 Chinese participants with Fitzpatrick skin types III to IV were included in the study. The overall effective rate of the treatment was 75%, achieved after an average of 2.42 ± 0.75 sessions. A subgroup analysis of 41 patients who completed 3 treatment sessions showed statistically significant differences in outcomes across the sessions. The mean improvement scores for sessions 1, 2, and 3 were 1.63 ± 1.04, 2.66 ± 1.22, and 3.29 ± 1.17, respectively (p < .01). No cases of hypopigmentation were observed. The incidence of postinflammatory hyperpigmentation was 5.56%.

CONCLUSION
The 730-nm picosecond laser is a safe and effective treatment for ABNOM in Chinese patients.
Sleep as a possible mediator in the association of mental health parameters with cardiovascular health indices in women: exploratory analyses from the Heart SCORE Study
Authors: Fonkoue Ida T. , Silva Milena , Racette Susan B. , Safo Sandra E. , de las Fuentes Lisa , Lowe Dawn , Ebong Imo A. , Buysse Daniel , Reis Steven E. , Saeed Anum 
Published: January 2025

Abstract

Objective
This exploratory study aimed to determine the possible role of sleep in the relationships of depression and anxiety, with early surrogate markers of subclinical atherosclerosis, such as brachial artery (BA) diameter and carotid intima media thickness (CIMT) in women.

Methods
We included 1,075 self-reported postmenopausal women, 45 to 75 years from the Heart Strategies Concentrating on Risk Evaluation Study. Exposure variables were depression and anxiety assessed using the Center for Epidemiologic Studies Depression Scale and the State-Trait Anxiety Inventory, respectively. Outcome variables were BA diameter and CIMT measured using ultrasonography. The mediator, sleep, was assessed with the Pittsburgh Sleep Symptom Questionnaire–Insomnia. Ordinary least squares regression was used for mediation analyses.

Results
Of the 1,075 participants, 56.3% were White and 43.7% were Black. Our analyses revealed significant associations of depression and anxiety with sleep (P < 0.001 for all). After adjusting for confounders, depression was associated with max CIMT (R2 = 0.15, P = 0.004), but not BA diameter (R2 = 0.09, P = 0.083). Although the mediating role of sleep in the association between anxiety and BA diameter was not statistically significant [proportion mediated (CI); 0.41 (−2.77, 4.06); P = 0.219], we observed differential results within each racial group. Sleep appeared to partially mediate the association of anxiety with BA diameter in White [0.21 (0.54, 0.80); P = 0.044] women only.

Conclusions
We found preliminary indications that sleep might mediate the association of anxiety with BA diameter in White women but does not appear to serve as a mediator in all the other relationships we examined.
A randomized controlled trial to evaluate a novel dual laser therapy for vulvar lichen sclerosus: exploratory study assessing the impact of menopausal status
Authors: Zivanovic Irena , Gamper Marianne , Fesslmeier Debra , Bischofberger Helena , Viereck Volker 
Published: January 2025

Abstract

Objective
A randomized controlled trial showed that Neodymium:YAG/Erbium:YAG laser therapy was safe and significantly improved clinical outcomes and subjective symptoms of vulvar lichen sclerosus (LS). Most improvements were similar to those after the recommended first-line therapy with topical steroid. In this exploratory study, we wanted to analyze the impact of menopausal status on perception and treatment outcome.

Methods
Sixty-six women with clinical lichen sclerosus were assigned to the laser or the steroid arm (2:1). Participants of the laser arm received four laser treatments with a follow-up of 6 months after treatment initiation. Clinical objective (LS score) and subjective outcomes (vulvovaginal symptoms questionnaire [VSQ], symptom visual analogue scale [VAS] score, patient satisfaction) were evaluated.

Results
Nineteen of the 66 study participants were premenopausal, 47 postmenopausal. At baseline, premenopausal women were significantly younger (39.4 vs 67.4 yr, P < 0.001), only a few applied local estrogen (16% vs 74%, P < 0.001), and their VSQ score was higher (9.58 vs 7.32, P = 0.015) indicating more severe vulvovaginal symptoms. Laser therapy objectively led to similar clinical improvements for pre- and postmenopausal women (−2.62 vs −2.23, P = 0.437), but subjectively to a significantly higher improvement of the VSQ score in postmenopausal women (−4.13 vs −1.08, P = 0.005). Postmenopausal women were more satisfied with laser therapy than premenopausal women (71% vs 46%, P = 0.002).

Conclusion
Compared to premenopausal women, postmenopausal women experienced a lower subjective burden of the disease and a better subjective improvement after laser therapy. Perceptions and expectations are age-dependent and should be considered when treating women with lichen sclerosus.
Prevalence of urinary tract infections in women with vulvovaginal atrophy and the impact of vaginal prasterone on the rate of urinary tract infections
Authors: Rubin Rachel , Sanaee May , Yee Alyssa , Moyneur Erick , Dea Katherine , Dury Alain Y. 
Published: January 2025

Abstract

Objective
The aims of this study were to assess the prevalence of urinary tract infections (UTI) in women newly diagnosed with vulvovaginal atrophy (VVA) versus women without VVA and to evaluate the potential of vaginal prasterone to be used in postmenopausal VVA women with UTI as prophylaxis to reduce the future UTI risk. As a first subgroup analysis, women using aromatase inhibitors, medications that stop the production of estrogen were analyzed. As a second subgroup analysis, we looked at women with diabetes to investigate whether the same prophylaxis approach should be considered.

Methods
This observational retrospective inception cohort study was conducted using the Integrated Dataverse open-source claims database with data from February 2015 through January 2020.

Results
A total of 22,245 women treated with prasterone for a minimum of 12 weeks were matched to women without any prescribed VVA-related treatment. Overall, women treated with prasterone have a significantly lower UTI prevalence compared to those untreated (6.58% vs 12.3%; P < 0.0001). The highest difference in UTI prevalence among the prasterone treated and untreated women was observed in those aged 65‐74 (7.15% vs 16.2%; P < 0.0001). Among aromatase inhibitor users and women with diabetes, those treated with prasterone have a significantly lower UTI prevalence (4.90% vs 9.79%; P < 0.01 and 14.59% vs 20.48%; P < 0.0001, respectively).

Conclusions
This study suggests that intravaginal prasterone may be a good candidate for prophylaxis in postmenopausal women with UTI to reduce future UTI risk, including for women taking aromatase inhibitors and women with diabetes. This study is based on real-world evidence and warrants further investigation in a clinical setting.