bluuebunny/crossref_metadata_2025_split huggingface dataset:
Current understanding of the role of DNA methylation in pituitary neuroendocrine tumors
Authors: Peterson Racheal , Cote David J , Zada Gabriel 
Published: January 2025

Abstract
Pituitary neuroendocrine tumors (PitNETs) are unusual among neoplasms in that sporadic tumors are not typically associated with genetic mutations. Instead, epigenetics, a non-mutational process by which gene expression is modified via a variety of mechanisms, may be a driving factor in PitNET growth and behavior. DNA methylation is one of the most well understood forms of epigenetic modification. Research on DNA methylation profiles of PitNETs has identified a large number of genes silenced or upregulated by DNA methylation, particularly when methylated at CpG islands of gene promoter regions. Global patterns of DNA methylation may provide valuable insight into origins of pituitary adenoma subtypes, assist with PitNet diagnostics and have been found to correspond to the current WHO classification of PitNETs based on transcription factor lineage. Analysis of differentially methylated regions of individual genes may have prognostic value as well as guide research toward nonsurgical therapeutic strategies. Pituitary epigenetics and DNA methylation analysis are rapidly growing areas of interest with the potential to shape the future of pituitary tumor diagnostics and treatment.
Mass Equidistribution for Poincaré Series of Large Index
Authors: Kimmel Noam 
Published: January 2025

Abstract
Let $P_{k,m}$ denote the Poincaré series of weight k and index m for the full modular group $\mathrm{SL}_2(\mathbb{Z})$, and let $\{P_{k,m}\}$ be a sequence of Poincaré series for which m(k) satisfies $m(k) / k \rightarrow\infty$ and $m(k) \ll k^{\frac{3}{2} - \epsilon}$. We prove that the L2 mass of such a sequence equidistributes on $\mathrm{SL}_2(\mathbb{Z}) \backslash \mathbb{H}$ with respect to the hyperbolic measure as k goes to infinity. As a consequence, we deduce that the zeros of such a sequence $\{P_{k,m}\}$ become uniformly distributed in $\mathrm{SL}_2(\mathbb{Z}) \backslash \mathbb{H}$ with respect to the hyperbolic measure.
National Analysis of Over 48,000 Veterans With HIV Demonstrates CD4/CD8 Ratio as a Risk Marker for Anal Intraepithelial Lesions and Anal Cancer
Authors: Hewitt Austin , Freeman Matthew J. , Leverson Glen , Bailey Howard H. , Carchman Evie , Striker Rob , Sanger Cristina B. 
Published: January 2025

BACKGROUND:
Anal squamous intraepithelial lesions are identifiable and treatable precancerous lesions that lack defined risk factors determining screening necessity.

OBJECTIVE:
Assess the prevalence and risk factors associated with low- and high-grade anal squamous intraepithelial lesions and anal squamous cell carcinoma.

DESIGN:
Retrospective cohort analysis of veterans with HIV between 1999-2023.

SETTINGS:
National multicenter study of the Department of Veterans Affairs.

PATIENTS:
Veterans with HIV who had >1 year of follow-up and no anal squamous intraepithelial lesions or anal cancer diagnosis prior to the study period.

MAIN OUTCOMES AND MEASURES:
Primary outcomes include the prevalence, disease-free survival rates, and hazard ratios associated with risk factors for developing anal squamous intraepithelial lesions and/or anal cancer.

RESULTS:
48,368 patients were analyzed. The average age of patients at study initiation was 47.8 years with a mean follow-up of 12.3 years. 7,572 (16%) patients had at least one anal cytopathology or histopathology result. Prevalence of anal disease was recorded for low-grade disease (n = 1,513, 3.1%), high-grade disease (n = 1,484, 3.1%), and cancer (n = 664, 1.4%). Mean times to first incident low-grade disease, high-grade disease, and cancer were 8.5 (SD = 6.0), 9.1 (SD = 6.0), and 9.7 (SD = 6.2) years, respectively. 5-year, 10-year, and 20-year disease-free survival rates for development of low-grade disease, high-grade disease, or cancer were 97.5%, 94.5%, and 88.4%, respectively. Cox regression modeling demonstrated CD4/CD8 ratios <0.5 were associated with increased risk of anal cancer (HR: 3.93, 95% CI: 3.33-4.63, p < 0.001).

LIMITATIONS:
Retrospective study that focuses almost exclusively on male U.S. veterans. Results might not apply to non-male, non-U.S. populations.

CONCLUSIONS:
National analysis of over 48,000 veterans with HIV demonstrates 16% had anal cytopathology or histopathology results with an anal cancer prevalence of 1.4%. CD4/CD8 ratios <0.5 correlate strongly with severity of anal disease and can help identify patients at highest risk for anal cancer to prioritize screening efforts. See Video Abstract.
Injury Patterns in Academy-Level Male Youth Soccer Players: A 3-Season Prospective Cohort Study
Authors: Munro Thomas M. , Noe McKenna C. , Margherio Shannon R. , Lee Brian R. , Harvey Brian S. 
Published: January 2025

Objective:
To report injury epidemiology in youth male academy-level athletes in the United States.

Design:
An observational study on injury occurrences and playing time over the 2019 to 2020, 2020 to 2021, and 2021 to 2022 soccer seasons.

Setting:
Data collected from a single midwestern soccer academy in the United States in partnership with a tertiary care level I pediatric heath institution.

Patients:
All male youth athletes to have enrolled and participated in the developmental academy during any of the 3 studied seasons.

Interventions:
None. This was an observational study.

Main Outcome Measures:
Injury rate (incidence per 1000 playing hours), type, location, mechanism (noncontact vs contact), severity, and mode of play (match vs training) in which the injury was sustained.

Results:
Overall rate of injury was 3.64 per 1000 h exposure. Injuries of moderate severity (8-28 days of missed playing time) were most common. When stratified by team, injury rates were highest in the U15 (5.15/1000 h) and lowest in the U12 (0.87/1000 h). Most injuries involved muscles of the lower extremities.

Conclusions:
Among male youth academy-level soccer athletes in the United States, older players tended to sustain injuries at a higher rate than younger. The lower extremity was the most common injury location, and muscle injuries and most common type. Concussions remain common in this population, accounting for nearly a 10th of all athletic injuries.

Clinical Relevance:
Injury epidemiology data from this study add to the growing worldwide pool of data from youth, male, academy-level soccer athletes that will augment development of injury prevention interventions.
High job stress evaluated using the Brief Job Stress Questionnaire as an independent risk factor for hypertension among a Japanese male occupational population
Authors: Sekizuka Hiromitsu , Kato Hirohisa , Ishii Toshiya , Nagumo Satoko 
Published: January 2025

Objective
Stress and working environments are risk factors for hypertension. A new occupational health policy called the Stress Check Program was started in Japan in 2015. Therefore, we clarified whether the presence or absence of high job stress (HJS) as determined using the Brief Job Stress Questionnaire (BJSQ) is related to the comorbidity of hypertension.

Methods
The results of a single year’s BJSQ and medical examinations were investigated for 18 629 active Japanese male office workers who were 30–59 years old. The presence or absence of HJS was assessed using the BJSQ and investigated using a personal computer in a medical interview. Furthermore, the relationships between HJS and hypertension comorbidity were analyzed.

Results
The mean age of the subjects was 43.8 ± 10.3 years old, and the proportion of subjects with HJS was 10%. After adjustment for age and lifestyle habits, HJS was associated with a risk of hypertension comorbidity (odds ratio, 1.18; 95% confidence interval, 1.02–1.36; P = 0.022). HJS was a significant hypertensive comorbidity factor.

Conclusion
HJS measured using the BJSQ independently contributed to hypertension comorbidity among male office workers.
Risk Factors for Wound Complications After Obstetric Anal Sphincter Injury
Authors: Meckes Nicole A. , Toal Coralee T. , Wang Li , Giugale Lauren E. 
Published: January 2025

Importance
Wound complications after obstetric anal sphincter injury (OASI) can amplify morbidity and affect quality of life.

Objective
The objective of this study was to evaluate for characteristics associated with wound complications after OASI.

Study Design
This was a retrospective cohort study of patients with an OASI who were evaluated in a postpartum pelvic floor healing clinic between November 1, 2020, and May 16, 2023. Our primary outcome was to identify factors associated with wound complications (wound infection or breakdown, antibiotic treatment, or surgical intervention). We hypothesized that operative vaginal delivery would be associated with wound complications and that peripartum antibiotics would be protective. Statistical analyses included t tests, chi-square test, Fisher exact test, and multivariable logistic regression.

Results
Of 332 patients with an OASI, 74 (22.3%) experienced a wound complication. There were 31 (9.3%) wound infections and 62 (18.7%) wound breakdowns; 50 (15.1%) patients received additional antibiotics, and 20 (6.0%) underwent additional surgical intervention. On univariate analysis, those with wound complications were older (31.9 vs 30.6 years, P = 0.01) and more likely to have had an episiotomy (23.0% vs 12.5%, P = 0.03). On multivariable logistic regression, older maternal age was associated with wound complication (odds ratio, 1.1, 95% CI, 1.01–1.13, P = 0.03), and peripartum antibiotics were associated with decreased odds of wound complication (odds ratio, 0.57, 95% CI, 0.33–0.97, P = 0.04). Patients with wound complications were more likely to undergo in-office procedures (P < 0.001) and report postpartum pain (P < 0.001), urinary incontinence (P = 0.02), fecal urgency (P = 0.02), and other symptoms (P = 0.04).

Conclusions
Older maternal age was associated with wound complications after OASI, while peripartum antibiotics were protective. Patients with wound complications were more likely to report symptoms of pelvic floor disorders.
The evolution of heteromorphic sex chromosomes in plants
Authors: Carey Sarah B. , Bentz Philip C. , Lovell John T. , Akozbek Laramie M. , Havill Joshua S. , Padgitt-Cobb Lillian , Lynch Ryan C. , Allsing Nicholas , Osmanski Austin , Easterling Katherine A. , Orozco Leonardo R. , Hale Haley , McCoy Hannah , Meharg Zachary , McKay John , Grimwood Jane , Vergara Daniela , Guerrero Rafael F. , Kane Nolan C. , Michael Todd P. , Muehlbauer Gary J. , Harkess Alex 
Published: January 2025

SUMMARY
Ancient heteromorphic sex chromosomes are common in mammals, but not in
plants. Sex chromosomes in the plant family Cannabaceae, which includes species
like hops and hemp, were identified a century ago because of their obviously
heteromorphic XYs. However, we know very little about their structure, nor their
role in the development of the economically, medicinally, and culturally
important flowers. Here we assembled genomes, with phased sex chromosomes, for
three XY male hops (Humulussp.), two XY
maleCannabis, and two
monoeciousCannabisindividuals. Most of the
non-recombining regions evolved prior to the divergence
betweenCannabisandHumulusaround
47 MYA supporting this sex chromosome origin is among the oldest known in
flowering plants. The Y chromosomes are highly-degenerate, with very few genes
remaining, and show substantial rearrangements, while the X also shows faster
rates of molecular evolution. The Cannabaceae sex chromosomes contain critical
genes for flower development and the production of key compounds like bitter
acids and cannabinoids, which are important traits for the plants. The sex
chromosomes thus have played a vital role in the domestication and breeding of
these species, and more generally, the Cannabaceae family.
Memory-Phenotype Ly49+ CD8 T emerging from the thymus develop into two
subsets with distinct immune functions
Authors: Laubreton Daphné , Grau Morgan , Malassigne Victor , Prieux Margaux , Tomkowiak Martine , Vocanson Marc , Walzer Thierry , Marvel Jacqueline 
Published: January 2025

Abstract
Ly49+ CD8 T cells are memory-phenotype (MP) cells expressing Ly49 family
inhibitory receptors, that control autoimmune diseases development through the
regulation of follicular CD4 T cells. During viral infection, their number
increases, suggesting an involvement in antiviral responses. These cells do not
derive from naive cells and are thought to develop in the thymus. This study
identified two subsets of Ly49+ CD8 T cells, based on CD8β expression, in mice
and humans. Lineage tracing and reliance on the transcription factor Zeb1
indicate a thymic origin via agonist selection. scRNAseq analysis revealed that
a small fraction of CD8αβ-Ly49+ cells acquired an effector profile during
vaccinia virus infection. Moreover, the majority of Ly49+ CD8 T cells seems to
respond to cytokine-driven bystander signals.In
vitro, these signals promoted the expression of effector molecules
such as IFNγ and granzyme B, as well as the homing chemokine receptor CXCR5,
potentially driving their recruitment to germinal centers.

Summary
This study shows that Ly49+ CD8 T cells comprises two subsets that
develop in the thymus through agonist selection. In viral infection, both
subsets respond to bystander stimuli that could drive their regulatory
activity. Furthermore, some CD8αβ-expressing Ly49+ cells exert TCR-mediated
antiviral response.
Highly dynamic supernumerary mini-chromosomes in aMagnaporthe
oryzaestrain
Authors: Lin Guifang , Zheng Huakun , Koo Dal-Hoe , Wang Zonghua , Cook David , Valent Barbara , Liu Sanzhen 
Published: January 2025

Abstract
Magnaporthe oryzae(syn.Pyricularia
oryzae), the causative agent of devastating crop diseases,
exhibits remarkable genomic plasticity that contributes to its adaptability and
pathogenicity.
IndividualM.oryzaestrains
may contain supernumerary mini-chromosomes, which are dispensable and highly
repetitive. Here, we explored the stability of two mini-chromosomes of
aLoliumstrain isolated in the US, TF05-1, in
which one mini-chromosome contains sequences nearly identical to the
mini-chromosome of the wheat isolate B71 from Bolivia. The discordance of their
phylogenetic relationships based on genomic polymorphisms in core chromosomes
and polymorphisms in mini-chromosomes indicated horizontal transfer of the
mini-chromosome. Karyotyping analysis and genome sequencing analysis found
variation in numbers and sizes of mini-chromosomes among asexual monoconidial
progeny of TF05-1. Rearrangement within mini-chromosomes occurred frequently in
the TF05-1 progeny. We characterized an intrachromosomal rearrangement
presumably mediated by a palindrome repeat. The rearrangement resulted in a
300-kb deletion and a 900-kb duplication. The susceptibility to structural
variation in mini-chromosomes may be associated with repetitive features and the
high activity of transposable elements in mini-chromosomes, in which many intact
retrotransposons were recently inserted, largely unmethylated, and likely have
yet to be silenced by fungal genome defense mechanisms such as repeat-induced
point mutation.
Unprecedented female mutation bias in aye-ayes
Authors: Wang Richard J. , Peña-García Yadira , Muthuswamy Raveendran , Harris R. Alan , Nguyen Thuy-Trang , Gingras Marie-Claude , Wu Yifan , Perez Lesette , Yoder Anne D. , Simmons Joe H. , Rogers Jeffrey , Hahn Matthew W. 
Published: January 2025

Abstract
Every mammal studied to date has been found to have a male mutation bias:
male parents transmit morede novomutations to
offspring than female parents, contributing increasingly more mutations with
age. Although male-biased mutation has been studied for more than 75 years, its
causes are still debated. One obstacle to understanding this pattern is its near
universality—without variation in mutation bias, it is difficult to find an
underlying cause. Here, we present new data on multiple pedigrees from two
primate species: aye-ayes (Daubentonia
madagascarensis), a member of the strepsirrhine primates, and
olive baboons (Papio anubis). In stark contrast to
the pattern found across mammals, we find a much larger effect of maternal age
than paternal age on mutation rates in the aye-aye. In addition, older aye-aye
mothers transmit substantially more mutations than older fathers. We carry out
both computational and experimental validation of our results, contrasting them
with results from baboons and other primates using the same methodologies.
Further, we analyze a set of DNA repair and replication genes to identify
candidate mutations that may be responsible for the change in mutation bias
observed in aye-ayes. Our results demonstrate that mutation bias is not an
immutable trait, but rather one that can evolve between closely related species.
Further work on aye-ayes (and possibly other lemuriform primates) should help to
explain the molecular basis for sex-biased mutation.
Small molecule targeting of FBXO21 mediated p85α ubiquitylation in acute
myeloid leukemia
Authors: Dobish Kasidy K. , Vishwakarma Suchita , Peters Hendrik C. , Winship C. Bea , Alvarado Danielle , Hyde R. Katherine , Natarajan Amarnath , Buckley Shannon M. 
Published: January 2025

ABSTRACT

PI3K inhibitors
PI3K inhibitors that target the catalytic sub-unit p110 are used in
cancer therapy to inhibit overactive PI3K signaling pathway. However, their
clinical use is limited by severe adverse effects and development of
resistance, highlighting the need for further research on regulation of the
PI3K pathway. We have identified that FBXO21 ubiquitinates regulatory PI3K
subunit p85α, and silencing of FBXO21 inhibits canonical PI3K signaling. To
target FBXO21, we developed a small molecule designed to interfere with
substrate:ligase interaction. Our novel small molecule effectively blocks
p85α ubiquitination leading to decreased PI3K pathway activation and cell
death in acute myeloid leukemia (AML). Moreover, our studies demonstrate
selectivity for AML cells over healthy counterparts, and elimination of
AMLin vivo, emphasizing FBXO21’s potential as
a promising therapeutic target for AML. Targeting substrate:ligase
interactions provide new avenues for drug discovery that may enhance the
efficacy of current therapies and benefits for improving patient
outcomes.

STATEMENT OF SIGNIFICANCE
Our studies highlight the potential of the ubiquitin E3 ligase FBXO21 as
an alternative therapeutic target for the PI3K signaling pathway, not only
in AML but in cancers with aberrant PI3K signaling.
Forest habitat and forest dominated landscapes are associated with bumblebee
species with visual traits related to light sensitivity
Authors: Bartholomée Océane , Tichit Pierre , Åström Jens , Smith Henrik G. , Åström Sandra , Sydenham Markus A. K. , Baird Emily 
Published: January 2025

Abstract
While functional traits like body size have been extensively linked to
species distributions, the influence of sensory traits on species’ responses to
environmental changes remains underexplored. Particularly, the relationship
between light sensitivity and niche segregation across different distributional
extents – local habitat conditions and across entire landscapes – remains
unclear. In this study, we examined bumblebee communities monitored across
Norway on grassland and forest habitats within landscapes varying in forest
cover within 1 km radii. We investigated whether the eye parameter – a visual
trait measuring the trade-off between light sensitivity (high values) and visual
resolution (low values) – was associated with local habitat types and the forest
cover at the landscape scale. Additionally, we combined bumblebee-plant
interactions with a plant trait, to determine if bumblebee light sensitivity
correlated with the shade tolerance of the plants they foraged on. Our findings
showed that bumblebee species with high eye parameters were more common and
abundant in forest habitats and areas with greater forest cover, while species
with low eye parameters showed the opposite trend. This pattern was also
reflected at the community level, as indicated by the community-weighted mean of
the eye parameter which increased with forest cover and was higher in forest
habitats. Furthermore, bumblebees with higher eye parameters tended to forage on
plants with greater shade tolerance.
These results suggest that visual adaptations for light sensitivity
contribute to shaping bumblebee species distributions across different scales.
Overall, our study underscores the importance of pollinator vision in
understanding species niches, in relation to habitat use and foraging behaviour.
By relating pollinator visual abilities to plant niches for the first time, this
study provides an important basis for future modelling of plant-pollinator
interactions and targeted conservation measures for both plants and pollinators
in forested landscapes.
A Locus Control Region Generates Distinct Active Placental Lactogen And
Inactive Growth Hormone Gene Domains In Term Placenta That Are Disrupted With
Obesity
Authors: Jin Yan , McNicol Ian , Cattini Peter A. 
Published: January 2025

Abstract
A Placental villi include an outer layer of syncytiotrophoblasts (STBs) and
an inner layer of cytotrophoblasts (CTBs) that fuse to generate STBs in
pregnancy. While activation of the single locus containing the human (h)
placental lactogen (hPL) genes
(hPL-A/CSH1andhPL-B/CSH2)
begins in the CTBs, their expression in STBs requires further epigenetic
modifications as well as interactions between locus control region (LCR) and
gene regulatory sequences. No transcription factor that limits or facilitates
hPL LCR/gene interactions for locus activation is reported but the
paternally-expressed gene 3 (PEG3/PW1) transcription factor is a candidate. PEG3
is expressed by villous CTBs but not STBs, and putative PEG3 sites were
identified in the hPL LCR and promoter sequences. Furthermore, dysregulation of
both hPL and PEG3 gene expression have been linked to peripartum depression.
Using CTB-like JEG-3 cells, we show PEG3 binding to hypersensitive sites (HS
III-V) within the LCR, and that hPL transcript levels increase with PEG-3
knockdown. In term placenta, PEG3 binding at placenta-specific HS IV was
increased with maternal obesity, where a decrease in hPL RNA levels is seen,
while PEG3 binding was reduced in women with obesity who develop insulin-treated
gestationaldiabetes mellitus(O/GDM+Ins), where
increased hPL gene expression is observed. Chromatin conformation capture
revealed distinct hPL gene domain interactions that are modified with maternal
obesity but largely reversed in O/GDM+Ins, correlating with PEG3 binding. Thus,
decreased PEG3 binding may be required for hPL domain generation and expression
during CTB to STB transition.