bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring P2X7 receptor antagonism as a therapeutic target for neuroprotection in an hiPSC motor neuron model
Authors: Johns Alexandra E , Taga Arens , Charalampopoulou Andriana , Gross Sarah K , Rust Khalil , McCray Brett A , Sullivan Jeremy M , Maragakis Nicholas J 
Published: September 2024

Abstract
ATP is present in negligible concentrations in the interstitium of healthy tissues but accumulates to significantly higher concentrations in an inflammatory microenvironment. ATP binds to 2 categories of purine receptors on the surface of cells, the ionotropic P2X receptors and metabotropic P2Y receptors. Included in the family of ionotropic purine receptors is P2X7 (P2X7R), a non-specific cation channel with unique functional and structural properties that suggest it has distinct roles in pathological conditions marked by increased extracellular ATP. The role of P2X7R has previously been explored in microglia and astrocytes within the context of neuroinflammation, however the presence of P2X7R on human motor neurons and its potential role in neurodegenerative diseases has not been the focus of the current literature. We leveraged the use of human iPSC-derived spinal motor neurons (hiPSC-MN) as well as human and rodent tissue to demonstrate the expression of P2X7R on motor neurons. We extend this observation to demonstrate that these receptors are functionally active on hiPSC-MN and that ATP can directly induce death via P2X7R activation in a dose dependent manner. Finally, using a highly specific P2X7R blocker, we demonstrate how modulation of P2X7R activation on motor neurons is neuroprotective and could provide a unique pharmacologic target for ATP-induced MN death that is distinct from the role of ATP as a modulator of neuroinflammation.
The Global Burden of Disease Due to Benign Gynecological Conditions: A Call to Action
Authors: Wijeratne Dileep , Gibson Joanna F. E. , Fiander Alison , Rafii-Tabar Elizabeth , Thakar Ranee 
Published: September 2024

(Abstracted from Int J Gynecol Obstet 2024;164:1151–1159)
Benign gynecological conditions (BGCs) are responsible for a significant burden of unrecognized morbidity, preventable suffering, and poor quality of life for women and girls, particularly in low- and middle-income countries (LMICs). The consequences of BGCs extend beyond immediate symptoms, with menstrual disorders, for example, being strongly associated with girls’ absenteeism from school.
Optimizing peripheral I.V. access outcomes – Part 2
Authors: Nickel Barb 
Published: September 2024

Abstract:
Peripheral I.V. access failure is a source of patient discomfort and dissatisfaction with a significant financial impact on healthcare. This article reviews the benefits and the risks of peripheral I.V. catheter (PIVC) utilization, infusate characteristics and their impact on peripheral vasculature, PIVC site assessment and management, and PIVC research priorities. Part 1 of this series was published in Nursing's September 2024 issue.
Unusual Maternal and Fetal Findings With Cell-Free DNA Screening
Authors: Santoli Carmen M. A. , Anastasio Mary Katherine , Sparks Teresa N. , Dotters-Katz Sarah K. , Kuller Jeffrey A. 
Published: September 2024

ABSTRACT

Importance
With advances in prenatal cell-free DNA (cfDNA) technology, the information available with cfDNA continues to expand beyond the common fetal aneuploidies such as trisomies 21, 18, and 13. Due to the admixture of maternal and fetal/placental DNA, prenatal cfDNA remains a screening test with the possibility of false-positive and false-negative results.

Objective
This review aims to summarize unusual incidental maternal and fetal genomic abnormalities detectable by cfDNA and to provide anticipatory guidance regarding management.

Evidence Acquisition
Of 140 articles identified with keywords such as “incidental” and “discordant” cfDNA, 55 original research articles, review articles, case series, and societal guidelines were reviewed.

Results
Prenatal cfDNA may incidentally identify a spectrum of maternal genomic abnormalities such as malignancy, mosaicism, and copy number variants. When discordant with fetal diagnosis, these cases require additional investigation with maternal genetic testing and follow-up evaluation. Such incidental fetal/placental abnormalities may include rare autosomal trisomies, uniparental disomy, and triploidy. Further evaluation of fetal/placental abnormalities can be pursued with a combination of ultrasound and prenatal diagnosis with chorionic villous sampling and/or amniocentesis. Societal guidelines do not currently recommend cfDNA screening for rare autosomal trisomies, microdeletions, or copy number variants, and some experts suggest that sex chromosome screening should be opted in after counseling.

Conclusions
Knowledge about possible incidental findings with prenatal cfDNA is needed to inform pretest and posttest counseling with appropriate follow-up evaluation.

Relevance
As cfDNA technology has advanced to include genome-wide findings, it is important for clinicians, genetic counselors, and societal guidelines to acknowledge the spectrum of possible results outside of the traditional and sex chromosome aneuploidies.

Target Audience
Obstetricians and gynecologists, family physicians

Learning Objectives
After completing this activity, the learner will be better able to describe maternal and fetal/placental abnormalities detectable by cfDNA that are outside of the traditional aneuploidies; discuss pretest and posttest counseling and follow-up recommendations; and explain societal guidelines regarding the recommended scope of prenatal cfDNA screening.
Pembrolizumab or Placebo With Chemoradiotherapy Followed by Pembrolizumab or Placebo for Newly Diagnosed, High-Risk, Locally Advanced Cervical Cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): A Randomized, Double-Blind, Phase 3 Clinical Trial
Authors: Lorusso Domenica , Xiang Yang , Hasegawa Kosei , Scambia Giovanni , Leiva Manuel , Ramos-Elias Pier , Acevedo Alejandro , Sukhin Vladyslav , Cloven Noelle , Pereira de Santana Gomes Andrea J. , Mejía Fernando Contreras , Reiss Ari , Ayhan Ali , Lee Jung-Yun , Saevets Valeriya , Zagouri Flora , Gilbert Lucy , Sehouli Jalid , Tharavichitkul Ekkasit , Lindemann Kristina , Lazzari Roberta , Chang Chih-Long , Lampé Rudolf , Zhu Hong , Oaknin Ana , Christiaens Melissa , Polterauer Stephan , Usami Tomoka , Li Kan , Yamada Karin , Toker Sarper , Keefe Stephen M. , Pignata Sandro , Duska Linda R. ,   on behalf of the ENGOT-cx11/GOG-3047/KEYNOTE-A18 Investigators
Published: September 2024

(Abstracted from Lancet 2024;403:1341–1350)
Prognosis for locally advanced cervical cancer is poor, with 5-year progression-free survival (PFS) and overall survival ranging from 47% to 80%. For the past several decades, treatment has included external beam radiotherapy with concurrent chemotherapy followed by brachytherapy, and novel therapeutic options are needed.
Sustained nerve growth factor-induced C-nociceptor sensitization to electrical sinusoidal stimulation in humans
Authors: Solinski Hans Jürgen , Schmelz Martin , Rukwied Roman 
Published: September 2024

Abstract

Introduction:
Injection of recombinant human nerve growth factor (rhNGF) evokes acute heat and prolonged “polymodal” (mechanosensitive [CM]) and “silent” (mechanoinsensitive [CMi]) C-nociceptor sensitization. Both nociceptor classes can be activated differentially using slowly depolarizing electrical sinusoidal stimuli.

Objectives:
To explore the temporal profile of nociceptor sensitization to heat and mechanical and electrical stimuli in humans after rhNGF.

Methods:
Recombinant human nerve growth factor (1 µg) and NaCl (0.9%) was injected into human forearm skin (n = 9, 50 µL/injection). Pain ratings (numeric rating scale) to transcutaneous electrical stimuli (1 ms 20 Hz rectangular pulses, 500-ms half-period sine wave [1 Hz] and 4 Hz sine wave pulses [2.5 and 60 seconds]) were assessed at days 3, 21, and 49 after injection, in addition to heat pain thresholds (HPTs, 9 × 9 mm thermode) and mechanical impact pain (4 and 8 m/second).

Results:
Suprathreshold sinusoidal stimulation for specific CM (1 Hz) and combined CM and CMi (4 Hz) activation resulted in enhanced pain from day 3 post rhNGF and lasted throughout 7 weeks. These temporal dynamics contrasted minimum HPTs at day 3 (normalized by day 49) or mechanical impact pain (developing slowly until day 21 before declining depending on stimulus intensity). Correlation analyses of electrical pain indicated diverging kinetics when assessed for CM with or without concomitant CMi activation at days 3 and 21, which converged 7 weeks post rhNGF.

Conclusions:
Exceptionally long sensitization of CM and CMi nociceptors by rhNGF, uncovered by suprathreshold electrical sinusoidal stimulation, indicates a signal transduction–independent long-lasting hyperexcitability of C-nociceptors that clinically may contribute to rhNGF-maintained chronic inflammatory pain.
Towards explaining the fertility gap in farmed Pekin ducks
Authors: Beyts Cammy H , Wright Jonathan , Araya-Ajoy Yimen , Watson Kellie 
Published: September 2024

AbstractMaximising reproductive success is crucial to animal production systems, particularly in meeting global demands for animal products and improving commercially important traits. However, while social interactions and mating strategies are known to influence reproductive success in wild populations, their consideration in agricultural systems remains limited. Using an interdisciplinary framework that combines concepts from behavioural ecology and quantitative genetics in an animal breeding context, we investigated the role of sperm limitation and polygynous mating strategies (female polyandry, male monopolisation of females and male polygamy) in limiting female reproductive success in farmed Pekin ducks (Anas platyrthynchos domestica). We assessed the impact of these behaviours on chick production and quantified their genetic and environmental (co)variance. Our results revealed that the number of dam mates positively influenced chick production in female ducks. However, contrary to our expectation, skew in chick paternity (our measure of male monopolisation) was associated with increased female chick production, challenging the hypothesis that male monopolisation limits the sperm available to females and reduces their reproductive success. We found no evidence that male polygamy led to decreased female chick production. Genetic analysis revealed that female mate number and reproductive skew exhibit genetic variance, providing opportunities for targeted selection to enhance chick production. However, there was a negative genetic association between female polyandry and skew in chick paternity, suggesting a trade-off between these traits that would need to be considered in future selection programmes. Our findings highlight how concepts from behavioural ecology can be incorporated into breeding programmes, providing new opportunities to develop effective and sustainable breeding strategies.
A mosaic of whole-body representations in human motor cortex
Authors: Deo Darrel R. , Okorokova Elizaveta V. , Pritchard Anna L. , Hahn Nick V. , Card Nicholas S. , Nason-Tomaszewski Samuel R. , Jude Justin , Hosman Thomas , Choi Eun Young , Qiu Deqiang , Meng Yuguang , Wairagkar Maitreyee , Nicolas Claire , Kamdar Foram B. , Iacobacci Carrina , Acosta Alexander , Hochberg Leigh R. , Cash Sydney S. , Williams Ziv M. , Rubin Daniel B. , Brandman David M. , Stavisky Sergey D. , AuYong Nicholas , Pandarinath Chethan , Downey John E. , Bensmaia Sliman J. , Henderson Jaimie M. , Willett Francis R. 
Published: September 2024

SummaryUnderstanding how the body is represented in motor cortex is key to understanding how the brain controls movement. The precentral gyrus (PCG) has long been thought to contain largely distinct regions for the arm, leg and face (represented by the “motor homunculus”). However, mounting evidence has begun to reveal a more intermixed, interrelated and broadly tuned motor map. Here, we revisit the motor homunculus using microelectrode array recordings from 20 arrays that broadly sample PCG across 8 individuals, creating a comprehensive map of human motor cortex at single neuron resolution. We found whole-body representations throughout all sampled points of PCG, contradicting traditional leg/arm/face boundaries. We also found two speech-preferential areas with a broadly tuned, orofacial-dominant area in between them, previously unaccounted for by the homunculus. Throughout PCG, movement representations of the four limbs were interlinked, with homologous movements of different limbs (e.g., toe curl and hand close) having correlated representations. Our findings indicate that, while the classic homunculus aligns with each area’s preferred body region at a coarse level, at a finer scale, PCG may be better described as a mosaic of functional zones, each with its own whole-body representation.
Pan-Cancer Genetic Analysis of Mitochondrial DNA Repair Gene Set
Authors: Dong Angela , Rasteh Ayana Meegol , Liu Hengrui 
Published: September 2024

AbstractBackgroundThe mitochondrial DNA repair has gained attention for its potential impact on pan-cancer genetic analysis. This study investigates the clinical relevance of mitochondrial DNA repair genes: PARP1, DNA 2, PRIMPOL, TP53, MGME1.MethodsUsing multi-omics profiling data and Gene Set Cancer Analysis (GSCA) with normalized SEM mRNA expression, this research analyzes differential expression, gene mutation, and drug correlation.ResultsTP53 was the most commonly mutated mitochondrial-related gene in cancer, with UCS and OV having the highest mutation rates. CPG mutations linked to lowest survival rates. Breast cancer, with various subtypes, was potentially influenced by mitochondrial DNA repair genes. ACC was shown to be high in gene survival analysis. BRCA, USC, LUCS, COAD, and OV showed CNV levels impacting survival. A negative gene expression-methylation correlation was observed and was weakest in KIRC. Mitochondrial DNA repair genes were linked to Cell cycle_A activation. A weak correlation was found between immune infiltration and mitochondrial genes. Few drug compounds were shown to be affected by mitochondrial-related genes.ConclusionUnderstanding mitochondrial-related genes could redefine cancer diagnosis, and prognosis, and serve as therapeutic biomarkers, potentially altering cancer cell behavior and treatment outcomes.
The L1CAM SAX-7 is an antagonistic modulator of Erk Signaling
Authors: Moseley-Alldredge Melinda , Aragón Caroline , Vargus Marcus , Alley Divya , Somia Nirali , Chen Lihsia 
Published: September 2024

AbstractL1CAMs are immunoglobulin superfamily cell adhesion molecules that ensure proper nervous system development and function. In addition to being associated with the autism and schizophrenia spectrum disorders, mutations in the L1CAM family of genes also underlie distinct developmental syndromes with neurological conditions, such as intellectual disability, spastic paraplegia, hypotonia and congenital hydrocephalus. Studies in both vertebrate and invertebrate model organisms have established conserved neurodevelopmental roles for L1CAMs; these include axon guidance, dendrite morphogenesis, synaptogenesis, and maintenance of neural architecture, among others. InCaenorhabditis elegans, L1CAMs, encoded by thesax-7gene, are required for coordinated locomotion. We previously uncovered a genetic interaction betweensax-7and components of synaptic vesicle cycle, revealing a non-developmental role forsax-7in regulating synaptic activity. More recently, we determined thatsax-7also genetically interacts with extracellular signal-related kinase (ERK) signaling in controlling coordinated locomotion.C. elegansERK, encoded by thempk-1gene, is a serine/threonine protein kinase belonging to the mitogen-activated protein kinase (MAPK) family that governs multiple aspects of animal development and cellular homeostasis. Here, we show this genetic interaction betweensax-7andmpk-1occurs not only in cholinergic neurons for coordinated locomotion, but also extends outside the nervous system, revealing novel roles for SAX-7/L1CAM in non-neuronal processes, including vulval development. Our genetic findings in both the nervous system and developing vulva are consistent with SAX-7/L1CAM acting as an antagonistic modulator of ERK signaling.
Age-related alterations in functional and structural networks in the brain in macaque monkeys
Authors: Ouchi Kazuya , Yamamoto Shinya , Obara Makoto , Sugase-Miyamoto Yasuko , Tsurugizawa Tomokazu 
Published: September 2024

AbstractResting-state networks (RSNs) have been used as biomarkers of brain diseases and cognitive performance. However, age-related changes in the RSNs of macaques, a representative animal model, are still not fully understood. In this study, we measured the RSNs in macaques aged 3–20 years and investigated the age-related changes from both functional and structural perspectives. The proportion of structural connectivity in the RSNs significantly decreased, whereas functional connectivity showed an increasing trend with age. Additionally, the amplitude of low-frequency fluctuations tended to increase with age, indicating that resting-state neural activity may be more active in the RSNs may increase with age. These results indicate that structural and functional alterations in typical RSNs are age-dependent and can be a marker of aging in the brain.
Global and compartmentalized serotonergic control of sensorimotor integration underlying motor adaptation
Authors: Haruvi Ravid , Barbara Rani , Shainer Inbal , Rosenberg Ayelet , Moshe Lihi , Malamud Dorel , Toledano Jonathan , Braun Dotan , Baier Herwig , Kawashima Takashi 
Published: September 2024

AbstractThe vertebrate serotonergic system plays a critical role in modulating adaptive behavior. Yet, it has been challenging to unravel the downstream targets and the effects of serotonin on ongoing neural dynamics due to its widespread innervation and the complex nature of receptor signaling. Here, we show that the serotonergic system controls brain-wide neural dynamics in a spatially dualistic manner, global and compartmentalized, during motor adaptation behavior in zebrafish. Larval zebrafish adapt the vigor of tail motions depending on environmental drag force during visual pursuit behavior in a serotonin-dependent manner. Whole-brain imaging of serotonin release and systematic spatial mapping of serotonin receptors showed highly compartmentalized patterns that span multiple brain areas. Interestingly, whole-brain neural activity imaging combined with the perturbation of tph2+ raphe serotonin neurons revealed dualistic modulation of neural activity depending on behavioral encoding: global suppression of locomotor networks and the compartmentalized enhancement of midbrain sensory networks, both of which synergistically enabled motor adaptation. The compartmentalized modulation resulted from local serotonin release and receptor expression, while the global effect was due to modulation of a key network hub that broadcasts behavioral state signals. Our results reveal how the serotonergic system interacts with brain-wide neural dynamics through its parallel interactions and provide a conceptual framework for understanding the neural mechanisms of widespread serotonergic behavioral control.
A Hopfield network model of neuromodulatory arousal state
Authors: Osman Mohammed Abdal Monium , Fox Kai , Stern Joshua Isaac 
Published: September 2024

AbstractNeural circuits display both input-driven activity that is necessary for the real-time control of behavior and internally generated activity that is necessary for memory, planning, and other cognitive processes. A key mediator between these intrinsic and evoked dynamics is arousal, an internal state variable that determines an animal’s level of engagement with its environment. It has been hypothesized that arousal state acts through neuromodulatory gain control mechanisms that suppress recurrent connectivity and amplify bottom-up input. In this paper, we instantiate this longstanding idea in a continuous Hopfield network embellished with a gain parameter that mimics arousal state by suppressing recurrent interactions between the network’s units. We show that dynamics capturing some essential effects of arousal state at the neural and cognitive levels emerge in this simple model as a single parameter—recurrent gain—is varied. Using the model’s formal connections to the Boltzmann machine and the Ising model, we offer functional interpretations of arousal state rooted in Bayesian inference and statistical physics. Finally, we liken the dynamics of neuromodulator release to an annealing schedule that facilitates adaptive behavior in ever-changing environments. In summary, we present a minimal neural network model of arousal state that exhibits rich but analytically tractable emergent behavior and reveals conceptually clarifying parallels between arousal state and seemingly unrelated phenomena.
Effectiveness of Ghana’s COVID-19 policy responses and lessons learnt for the future: A multi-methods evaluation
Authors: Crankson Shirley , Pokhrel Subhash , Anokye Nana 
Published: September 2024

AbstractGhana implemented various mitigating policies in response to the COVID-19 outbreak. This study examined the effectiveness of these policies to contribute to the ongoing discussions on proactive and pre-emptive interventions for similar future outbreaks.A mix of qualitative and quantitative methods were used for the analysis. Data were drawn from multiple sources, including peer-reviewed and grey literature, and academic experts from Ghanaian universities. The data from the literature informed a questionnaire that was sent to independent academic experts to explore their opinions on whether the policies met their intended objectives. The experts’ opinions were collected on a 5-point Likert scale and from an open-ended question using an online data collection platform, Qualtrics. The data were evaluated using narrative synthesis, descriptive statistics and thematic analysis.We identified and evaluated eight key COVID-19 policy responses in Ghana: (1) partial lockdown of epicentres; (2) COVID-19 public awareness campaigns; (3) ban on public gatherings; (4) COVID-19 vaccination; (5) border closures; (6) entry border COVID-19 screening; (7) incentives for healthcare workers (HCWs); and (8) the Ghana Alleviation and Revitalisation of Enterprises Support (GCARES). Two policies - the COVID-19 awareness campaigns and border closure - effectively improved public awareness of COVID-19 and helped to reduce COVID-19 case importation (median score ≥4).Ghana’s COVID-19 public awareness campaigns and border closure policies could serve as a valuable model for informing proactive interventions to address future infectious disease outbreaks.