bluuebunny/crossref_metadata_2025_split huggingface dataset:
Favorable prostate-specific antigen levels correlate with a worse prognosis in high-grade prostate cancer: a population-based analysis
Authors: Liu Zenan , Hong Peng , He Jide , Li Ziang , Wu Jialong , Qiu Lei , Zhao Zhenkun , Lu Jian 
Published: June 2024

Background:
To compare the association between prostate-specific antigen (PSA) levels and prostate cancer-specific mortality (PCSM) and the effectiveness of local treatment in patients with high-grade and low-grade prostate cancer (PCa).

Methods:
This retrospective cohort study enrolled patients diagnosed with clinically localized PCa (cT1-4N0M0) from January 2010 to December 2020 in the Surveillance, Epidemiology, and End Results (SEER) database. Fine-Gray competing risk regression analysis was conducted to generate cumulative incidence plots and estimate the hazard ratio (HR) and 95% CI of PCSM. Multivariable restricted cubic spline analysis was used to examine the nonlinear associations of continuous values of PSA levels with PCSM. Inverse probability of treatment weighting was employed to minimize imbalances in baseline characteristics between different local treatment cohorts.

Results:
A total of 392 083 eligible patients were included in the study, including 327 659 low-grade (Gleason score [GS]≤7) PCa and 64424 high-grade (GS≥8) PCa. In multivariate Fine-Gray competing risk regression analysis, using PSA levels of 4.1–10.0 ng/ml as the reference, the adjusted HR among high-grade patients with PSA levels ≤2.5 ng/ml, 2.6–4.0 ng/ml, 10.1–20.0 ng/ml and >20.0 ng/ml were 1.988 (95% CI: 1.677–2.358), 1.411 (95% CI: 1.194–1.668), 1.472 (95% CI: 1.351–1.603), and 2.506 (95% CI: 2.318–2.709), respectively. Among low-grade PCa, the adjusted HR were 0.985 (95% CI: 0.800–1.213), 0.727 (95% CI: 0.602–0.877), 1.844 (95% CI: 1.679–2.026), and 3.574 (95% CI: 3.220–3.966), respectively. Multivariable-adjusted restricted cubic spline analysis showed a U/J-shaped distribution relationship between PSA levels and PCSM in high-grade PCa, while there was a positive association between PSA levels and PCSM in low-grade PCa. As for local treatment effectiveness, radiation therapy (RT) provided better control of PCSM compared to radical prostatectomy (RP) and RP+RT in high-grade PCa, while RP provided better control of PCSM compared to RT and RP+RT in low-grade PCa.

Conclusion:
Low PSA level (≤2.5 ng/ml) is significantly associated with a very high-risk of PCSM in high-grade localized PCa but not in low-grade localized PCa. High-grade localized PCa patients benefit more from RT in terms of PCSM control, while low-grade localized PCa patients benefit more from RP. High-grade localized PCa with low PSA level may be a unique subgroup that could benefit from novel risk stratification strategies in PCa, which requires further studies to investigate the potential of developing novel therapeutic strategies, prognostic tools, and clinical management approaches.
Climate change, microplastics, and male infertility
Authors: Daniels Danesha , Berger Eberhardt Alexandra 
Published: June 2024

Purpose of review
Semen quality is on the decline. While the etiology is unknown, recent literature suggests there may be a relationship between climate change, environmental toxins and male fertility. This review relays new information regarding associations between our environment and male infertility.

Recent Findings
Several recent studies have documented a negative association between heat stress and spermatogenesis, which suggests that climate change may be a factor in declining in sperm counts. The influence of particle pollution on spermatogenesis has also been recently investigated, with studies demonstrating a negative association. Another possible factor are microplastics, which have been posited to reduce sperm production. Recent animal studies have shown that microplastic exposure alters both adult sperm production and prenatal male genital development. The relationship between endocrine disrupting chemicals and male fertility remains an area of active study, with recent animal and human studies suggesting an association between these chemicals and male fertility.

Summary
The etiology of the decline in male fertility over the past decades is yet unknown. However, changes in our environment as seen with climate change and exposure to pollutants and endocrine disrupting chemicals are proposed mechanisms for this decline. Further studies are needed to investigate this association further.
Integrating Nurse-Led Interventions in Ophthalmology Care
Authors: Zhang Yufen , Cao Naiyue 
Published: June 2024

Background:
Nurse-led interventions in ophthalmology care can enhance the overall patient experience while optimizing health care system efficiency.

Purpose:
The purpose of this study was to investigate the impact of nurse-led interventions in ophthalmology care.

Methods:
A comprehensive search was conducted across multiple databases for articles published from 2000 to 2023. Randomized controlled trials, quasi-experimental, and observational studies were included. Quality assessments were performed using the Cochrane Risk of Bias tool or Newcastle-Ottawa Scale, based on study design.

Results:
Nineteen studies were included. Nurse-led interventions positively impacted patient outcomes, improved efficiency and resource utilization, enhanced patient satisfaction and adherence, maintained safety and efficacy, and demonstrated notable diagnostic accuracy. Included studies originated from different countries and employed diverse methodologies, offering a global perspective on nurse-led interventions in ophthalmology care.

Conclusion:
The findings advocate for the integration of nurse-led strategies in routine practice to realize equitable, efficient, and patient-centered eye care.
A Comprehensive Clinicopathologic and Molecular Reappraisal of GLI1-altered Mesenchymal Tumors with Pooled Outcome Analysis Showing Poor Survival in GLI1- amplified Versus GLI1-rearranged Tumors
Authors: Saoud Carla , Agaimy Abbas , Dermawan Josephine K. , Chen Jie-Fu , Rosenblum Marc K. , Dickson Brendan C. , Dashti Nooshin , Michal Michael , Kosemehmetoglu Kemal , Din Nasir Ud , Albritton Karen , Agaram Narasimhan P. , Antonescu Cristina R. 
Published: June 2024

GLI1-altered mesenchymal tumor is a recently described distinct pathologic entity with an established risk of malignancy, being defined molecularly by either GLI1 gene fusions or amplifications. The clinicopathologic overlap of tumors driven by the 2 seemingly distinct mechanisms of GLI1 activation is still emerging. Herein, we report the largest series of molecularly confirmed GLI1-altered mesenchymal neoplasms to date, including 23 GLI1-amplified and 15 GLI1-rearranged new cases, and perform a comparative clinicopathologic, genomic, and survival investigation. GLI1-rearranged tumors occurred in younger patients (42 vs. 52 y) and were larger compared with GLI1-amplified tumors (5.6 cm vs. 1.5 cm, respectively). Histologic features were overall similar between the 2 groups, showing a multinodular pattern and a nested architecture of epithelioid, and less commonly spindle cells, surrounded by a rich capillary network. A distinct whorling pattern was noted among 3 GLI1-amplified tumors. Scattered pleomorphic giant cells were rarely seen in both groups. The immunoprofile showed consistent expression of CD56, with variable S100, CD10 and SMA expression. Genomically, both groups had overall low mutation burdens, with rare TP53 mutations seen only in GLI1-amplified tumors. GLI1-amplified mesenchymal tumors exhibit mostly a single amplicon at the 12q13-15 locus, compared with dedifferentiated liposarcoma, which showed a 2-peak amplification centered around CDK4 (12q14.1) and MDM2 (12q15). GLI1-amplified tumors had a significantly higher GLI1 mRNA expression compared with GLI1-rearranged tumors. Survival pooled analysis of current and published cases (n=83) showed a worse overall survival in GLI1-amplified patients, with 16% succumbing to disease compared with 1.7% in the GLI1-rearranged group. Despite comparable progression rates, GLI1-amplified tumors had a shorter median progression-free survival compared with GLI1-rearranged tumors (25 mo vs. 77 mo). Univariate analysis showed that traditional histologic predictors of malignancy (mitotic count ≥4/10 high-power fields, presence of necrosis, and tumor size ≥5 cm) are associated with worse prognosis among GLI1-altered mesenchymal tumors.
Incidental 68Ga-PSMA Uptake in the Benign Enchondroma—A Rare Finding on 68Ga-PSMA PET/CT
Authors: Singh Parneet , Kandula Keerthana Kiran , Patel Ranjan Kumar , Parida Girish Kumar , Agrawal Kanhaiyalal 
Published: June 2024

Abstract

68Ga-PSMA (prostate-specific membrane antigen)-HBED-CC (N,N′-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N′-diacetic acid) PET/CT is the new advancement in oncological imaging. However, false-positive uptake can be seen in benign lesions on 68Ga-PSMA PET/CT. We describe a rare case of intense 68Ga-PSMA uptake in an enchondroma confirmed on MRI.
Amygdala-predominant α-synuclein pathology exacerbates hippocampal neuron loss in Alzheimer’s disease
Authors: Gawor Klara , Tomé Sandra , Vandenberghe Rik , Van Damme Philip , Vandenbulcke Mathieu , Otto Markus , von Arnim Christine A.F. , Ghebremedhin Estifanos , Ronisz Alicja , Ospitalieri Simona , Blaschko Matthew , Thal Dietmar R. 
Published: June 2024

AbstractMisfolded α-synuclein (αSyn) protein accumulates in 43-63% of individuals with symptomatic Alzheimer’s disease (AD). Two main patterns of co-morbid αSyn pathology have been identified: caudo-rostral and amygdala-predominant, with the latter being more common in AD. αSyn pathology has been shown to interact with DNA-binding protein 43 (TDP-43) and abnormally phosphorylated Tau protein (pTau). These proteins tend to accumulate in the amygdala, yet the specific role of amygdala-predominant αSyn pathology in the progression of AD and hippocampal degeneration remains unclear.In this cross-sectional study, we analyzed 291 autopsy brains from both demented and non-demented elderly individuals neuropathologically. Neuronal density in the CA1 region of the hippocampus was assessed using hematoxylin-stained sections for all cases. We semi-quantitatively evaluated αSyn pathology severity in six brain regions and stratified the cases into the two spreading patterns. In 99 AD cases, we assessed limbic-predominant age-related TDP-43 neuropathological changes (LATE-NC), CA1 pTau density, and cerebral amyloid angiopathy (CAA). Structural equation modeling analysis was conducted based on the assessed pathological parameters in AD patients.We identified an association between the amygdala-predominant αSyn pathology pattern and decreased neuronal density in the CA1 region. AD patients with an amygdala-predominant αSyn pattern exhibited the most severe pTDP-43 pathology among all groups, while those with the caudo-rostral pattern had the lowest severity of AD-related pathological changes including CAA type 1. Our model revealed that the relationship between αSyn pathology and CA1 neuron loss is mediated through pTau and LATE-NC.Our results indicate that amygdala-predominant αSyn pathology, in contrast to αSyn pathology with a caudo-rostral pattern, significantly contributes to hippocampal neuron loss, potentially by accelerating TDP-43 and pTau pathologies. This finding, along with observed neuropathological differences between AD patients with these two αSyn spreading patterns, underscores the need for precise stratification of patients. The stratification should consider not only the molecular and morphological identity of co-pathologies but also the distribution pattern of the respective co-pathologies.
Recent neo-X and Y sex chromosomes in an ant cricket
Authors: Mérel Vincent , Vogel Simon , Lavanchy Guillaume , Dumas Zoé , Labédan Marjorie , Stalling Thomas , Schwander Tanja 
Published: June 2024

AbstractIn eukaryotes with separate sexes, sex determination often involves heteromorphic sex chromosomes which have diverged as a consequence of recombination suppression. In species with very old heteromorphic sex chromosomes, mechanisms such as dosage compensation and meiotic sex chromosome inactivation adjust for the fact that sex chromosomes occur as a single copy in the heterogametic sex. However, how such mechanisms evolve remains largely unknown because species with young sex chromosomes characterised by recent recombination suppression remain understudied. We discovered such young neo-sex chromosomes in the ant cricketMyrmecophilus myrmecophilus, which displays a neo-XY system. We generated a chromosomal-level assembly of the female genome and compared it to male genomic data and identified four evolutionary strata on the X, with varying degrees of Y chromosome degeneration. Phylogenetic studies and genomic comparisons with closely related species revealed two cases of taxonomic synonymies and that theMyrmecophilusneo-sex chromosomes likely evolved approximately 7 million years ago from an X-autosome fusion. The X strata subsequently emerged as a consequence of two localised events of recombination suppression. Ant crickets thus represent a promising new model for studying the early stages of sex chromosome degeneration and the establishment of processes such as dosage compensation or meiotic sex chromosome inactivation.
Fokker-Planck diffusion maps of multiple single cell microglial transcriptomes reveals radial differentiation into substates associated with Alzheimer’s pathology
Authors: Baumgartner Andrew , Robinson Max , Golde Todd , Jaydev Suman , Huang Sui , Hadlock Jennifer , Funk Cory 
Published: June 2024

AbstractThe identification of microglia subtypes is important for understanding the role of innate immunity in neu-rodegenerative diseases. Current methods of unsupervised cell type identification assume a small noise-to-signal ratio of transcriptome measurements that would produce well-separated cell clusters. However, identification of subtypes is obscured by gene expression noise, diminishing the distances in transcriptome space between distinct cell types and blurring boundaries. Here we use Fokker-Planck (FP) diffusion maps to model cellular differentiation as a stochastic process whereby cells settle into local minima, corresponding to cell subtypes, in a potential landscape constructed from transcriptome data using a nearest neighbor graph approach. By applying critical transition fields, we identify individual cells on the verge of transitioning between subtypes, revealing microglial cells in inactivated, homeostatic state before radially transitioning into various specialized subtypes. Specifically, we show that cells from Alzheimer’s disease patients are enriched in a microglia subtype associated to antigen presentation and T-cell recruitment.
Glacier retreat decreases plant-pollinator network robustness over space-time
Authors: Conti Matteo , Cerretti Pierfilippo , Ferrari Andrea , Gabrieli Paolo , Paone Francesco , Polidori Carlo , Losapio Gianalberto 
Published: June 2024

AbstractGlaciers are retreating worldwide at an ever-increasing rate, exposing new ice-free areas to ecological succession. This process leads to changes in biodiversity and potentially to species interactions. However, we still have a limited understanding of how glacier retreat influences species interaction networks, particularly the structure and robustness of mutualistic networks. After reconstructing plant-pollinator networks along a glacier foreland, we address the effects of glacier retreat on pollination network structure and robustness. Our results show that the prevalence of different network motifs changes over space-time. With glacier retreat, pollination networks shift from being highly connected with specialist interactions to loosely connected with generalist interactions. Furthermore, network robustness decreased with glacier retreat. Despite the turnover of plant species, we find that structural roles played by different plant species stay constant over space-time. Our findings suggest that glacier retreat pushes pollination networks towards a loss of specialist interactions and low robustness, leading to increased fragility in the long term. Monitoring network motifs may provide valuable insights into the ability of novel pollination networks to withstand disturbances and preserve functionality in the face of glacier extinction.
Pregnancy History and Estradiol Influence Spatial Memory, Hippocampal Plasticity, and Inflammation in Middle-aged Rats
Authors: Puri Tanvi A. , Lieblich Stephanie E. , Ibrahim Muna , Galea Liisa A. M. 
Published: June 2024

AbstractPregnancy and motherhood (parity) can have long-term effects on cognition and brain aging in both humans and rodents. Estrogens are related to cognitive function and neuroplasticity. Estrogens can improve cognition in postmenopausal women, but the evidence is mixed, in part due to differences in hormone therapy dose and composition. In addition, past pregnancy influences brain aging and cognition, with earlier age of first pregnancy being associated with poorer outcomes with aging. However, few studies have examined specific features of pregnancy history such as the age of first pregnancy or the possible mechanisms underlying these changes. We examined whether maternal age at first pregnancy and estradiol treatment differentially affected hippocampal neuroplasticity, inflammation, activation, and cognition in middle-age. Thirteen-month-old rats (who were nulliparous (never mothered) or previously primiparous (had a litter) at 3 months or 7 months) received daily injections of estradiol (or sesame oil vehicle) for sixteen days and were tested on the Morris Water Maze. An older age of first pregnancy was associated with impaired spatial memory but improved performance on reversal training, and increased new neurons in the ventral hippocampus compared to the other groups. Estradiol decreased total activation and percent activation of new neurons in the dorsal hippocampus, regardless of parity history. Estradiol also decreased the production of anti-inflammatory cytokines based on age of first pregnancy. This work suggests that estradiol affects neuroplasticity and neuroinflammation in middle age, and that pregnancy history can have long lasting effects on hippocampus structure and function.
Differential Gene Expression in MRI-classified Glioblastoma
Authors: Rhodes Christopher T. , Wang Yufeng , Lin Chin-Hsing Annie 
Published: June 2024

ABSTRACTPrevious characterization of the genome and transcriptome of glioblastoma (GBM) has revealed molecular alterations that potentially drive GBM pathogenesis and heterogeneity1-6. These open-resources are evolving, such as The Cancer Genome Atlas (TCGA) and The Cancer Imaging Atlas (TCIA) at the National Institute of Health comprising a large cohort of molecular and MRI data. Yet, no report deciphers the link between molecular signatures and MRI-classified GBM. The necessity to re-form molecular and imaging data motivated our computational approach to integrate TCIA and TCGA datasets derived from GBM. We uncovered common and distinct molecular signatures across GBM patients and specific to tumor locations, respectively. Despite heterogeneity in GBM, the top 12 genes from our analysis highlights that the dysregulation of a subset of neurotransmitter receptor or transporter and synaptic activity is common across GBM patients. The coherent layer of imaging and molecular information would help us stratify precision neuro-oncology and treatment options in ways that are not possible through MRI or genomic data alone. Our findings provide molecular targets in the disrupted neurocircuit of GBM, suggesting imbalanced excitation and inhibition. Given the fact that GBM patients exhibit similar symptoms resembling patients with neurodegenerative diseases and seizures, our results supported the hypothesis-GBM in the context of neurological disorders beyond a solely cancerous disease.
Causal Cortical and Thalamic Connections in the Human Brain
Authors: Lyu Dian , Stiger James , Lusk Zoe , Buch Vivek , Parvizi Josef 
Published: June 2024

AbstractThe brain’s functional architecture is intricately shaped by causal connections between its cortical and subcortical structures. Here, we studied 27 participants with 4864 electrodes implanted across the anterior, mediodorsal, and pulvinar thalamic regions, and the cortex. Using data from electrical stimulation procedures and a data-driven approach informed by neurophysiological standards, we dissociated three unique spectral patterns generated by the perturbation of a given brain area. Among these, a novel waveform emerged, marked by delayed-onset slow oscillations in both ipsilateral and contralateral cortices following thalamic stimulations, suggesting a mechanism by which a thalamic site can influence bilateral cortical activity. Moreover, cortical stimulations evoked earlier signals in the thalamus than in other connected cortical areas suggesting that the thalamus receives a copy of signals before they are exchanged across the cortex. Our causal connectivity data can be used to inform biologically-inspired computational models of the functional architecture of the brain.
Coexistence despite competition: Vegetation structural complexity shapes bryophyte diversity over succession
Authors: Hanusch Maximilian 
Published: June 2024

AbstractVascular plants and bryophytes are key components driving the development of diverse ecosystems following glacial retreat. Unravelling biotic interaction mechanisms between both groups is crucial for understanding the generation of biodiversity under natural conditions. Focusing on a 170-year primary succession gradient in the Austrian Alps, this study examines mechanisms of competitive interaction between vascular plants and bryophytes during the initial phases of ecosystem establishment. Using data on vegetation structural complexity derived from multispectral 3D-scans of vegetation, the local habitat’s substrate diversity, and vascular plant and bryophyte taxonomic composition, this study provides a mechanistic understanding of plant-plant interactions within a natural ecosystem. Vascular plants dominate the vertical niche through complex growth structures, which negatively affect bryophyte diversity. A pattern that is uniquely detectable by estimates of vegetation structural complexity. Path analysis confirms that vegetation structural complexity drives competition through a reduction of realized niche sizes of bryophyte communities, a concept introduced here as ecological dispersion. This study demonstrates the advantages of 3D-laser-scanning approaches in capturing the complexity of vegetation structure and its impacts on ecosystem dynamics. The findings underscore the importance of vegetation structural complexity in the establishment and maintenance of natural ecosystems and underscore the potential of 3D-laser-scanning methods in future studies to inform biodiversity conservation and restoration approaches in similar environments.