bluuebunny/crossref_metadata_2025_split huggingface dataset:
How many nerve fibers innervate the human glans clitoris: a histomorphometric evaluation of the dorsal nerve of the clitoris
Authors: Uloko Maria , Isabey Erika P , Peters Blair R 
Published: January 2023

AbstractIntroductionIt is frequently quoted in mainstream media that the clitoris has “8000 nerve endings.” However, no study has yet quantified the number of nerve fibers (axons) innervating the human clitoris. The dorsal nerves of the clitoris (DNCs) are the primary source of sensation and somatic clitoral innervation. Therefore, reporting the number of axons in the DNCs is an important step in our understanding of clitoral innervation and sexual response with implications for many fields of medical practice. The purpose of this study is to quantify the mean number of axons in the human DNCs and to report the approximate mean number of nerve fibers that innervate the human glans clitoris.MethodsDNC samples were obtained from 7 transmasculine patients undergoing gender-affirming phalloplasty surgery. At the time of nerve coaptation, a small excess of the DNC (5 mm) was collected for analysis at the proximal level of the clitoral body, just distal of the emergence of the DNCs from underneath the pubic symphysis. Samples were placed into 3% glutaraldehyde fixative, postfixed in 1% osmium tetroxide, and serially dehydrated in ethanol and toluene. Samples were then embedded in araldite, sectioned on an ultramicrotome into 1-μm cross sections, and counterstained with 1% toluidine blue. Histomorphometric evaluation was performed at 1000x magnification with a Leitz Laborlux S microscope and image analysis software (Clemex Vision Professional) to obtain an axon counts. Descriptive statistics were performed to yield a mean and standard deviation of the number of axons in the DNCs. Assuming anatomic symmetry between bilateral DNCs, mean total number of somatic nerve fibers innervating the human glans clitoris was obtained by doubling the mean count of the DNCs.ResultsSeven sample DNCs were collected. Of those, 5 were analyzed as 2 did not have sufficient nerve tissue present. The mean number of nerve fibers in the human DNCs was 5140 (SD = 218.4). The mean number of myelinated nerve fibers innervating the human clitoris was 10,281 (SD = 436.8).ConclusionThis study is the first to report the number of axons in the human DNC, at a mean 5140. Given the bilateral nature of clitoral innervation and symmetry of anatomic structures, the approximate mean number of myelinated axons that innervate the human glans clitoris is 10,280. When the uncaptured unmyelinated fibers and contributions from the cavernosal innervation are accounted for, it is clear that far Moree than 8000 axons innervate the human clitoris.
Nearest-neighbor parameters for the prediction of RNA duplex stability in diverse in vitro and cellular-like crowding conditions
Authors: Ghosh Saptarshi , Takahashi Shuntaro , Banerjee Dipanwita , Ohyama Tatsuya , Endoh Tamaki , Tateishi-Karimata Hisae , Sugimoto Naoki 
Published: January 2023

Abstract
RNA performs various spatiotemporal functions in living cells. As the solution environments significantly affect the stability of RNA duplexes, a stability prediction of the RNA duplexes in diverse crowded conditions is required to understand and modulate gene expression in heterogeneously crowded intracellular conditions. Herein, we determined the nearest-neighbor (NN) parameters for RNA duplex formation when subjected to crowding conditions with an ionic concentration relevant to that found in cells. Determination of the individual contributions of excluded volume effect and water activity to each of the NN parameters in crowded environments enabled prediction of the thermodynamic parameters and their melting temperatures for plenty of tested RNA duplex formation in vitro and in cell with significant accuracy. The parameters reported herein will help predicting RNA duplex stability in different crowded environments, which will lead to an improved understanding of the stability-function relationship for RNAs in various cellular organelles with different molecular environments.
SPRTN-dependent DPC degradation precedes repair of damaged DNA: a proof of concept revealed by the STAR assay
Authors: Glumac Mateo , Polović Mirjana , Batel Anja , Gelemanović Andrea , Maček Boris , Velić Ana , Marinović-Terzić Ivana 
Published: January 2023

AbstractDNA-protein crosslinks (DPCs), formed by the covalent conjugation of proteins to DNA, are toxic lesions that interfere with DNA metabolic processing and transcription. The development of an accurate biochemical assay for DPC isolation is a priority for the mechanistic understanding of their repair. Here, we propose the STAR assay for the direct quantification of DPCs, sensitive to physiologically relevant treatment conditions. Implementing the STAR assay revealed the formation of small cross-linked peptides on DNA, created by the proteolytic degradation of DPCs by SPRTN. The initial proteolytic degradation of DPCs is required for the downstream activation of DNA repair, which is mediated through the phosphorylation of H2Ax. This leads to the accumulation of DNA repair factors on chromatin and the subsequent complete removal of the cross-linked peptides. These results confirmed that the repair of DPCs is a two-step process, starting with proteolytic resection by SPRTN, followed by the repair of the underlying damage to the DNA.
An intellectual disability-related MED23 mutation dysregulates gene expression by altering chromatin conformation and enhancer activities
Authors: Yang Yenan , Li Chonghui , Chen Ziyin , Zhang Yiyang , Tian Qing , Sun Meiling , Zhang Shuai , Yu Miao , Wang Gang 
Published: January 2023

AbstractTranscriptional Mediator controls diverse gene programs for various developmental and pathological processes. The human Mediator MED23/R617Q mutation was reported in a familial intellectual disability (ID) disorder, although the underlying mechanisms remain poorly understood. Constructed by gene editing, the Med23/R617Q knock-in mutant mice exhibited embryonic lethality due to the largely reduced Med23/R617Q protein level, but the R617Q mutation in HEK293T cells didn’t change its expression and incorporation into Mediator Complex. RNA-seq revealed that MED23/R617Q mutation disturbed gene expression, related to neural development, learning and memory. Specifically, R617Q mutation reduced the MED23-dependent activities of ELK1 and E1A, but in contrast, upregulated the MAPK/ELK1-driven early immediate genes (IEGs) JUN and FOS. ChIP-seq and Hi-C revealed that the MED23 R617Q mutation reprogramed a subset of enhancers and local chromatin interactions, which correlated well with the corresponding gene expression. Importantly, the enhancers and chromatin interactions surrounding IEGs were unchanged by the R617Q mutation, but DACH1, an upstream repressor of IEGs, showed reduced enhancer-promoter interactions and decreased expression in mutant cells, thus relieving its inhibition to the intellectual-related IEGs. Overall, unraveling the MED23-DACH1-IEG axis provides a mechanistic explanation for the effects of the MED23/R617Q mutation on gene dysregulation and inherited ID.
Interaction of human HelQ with DNA polymerase delta halts DNA synthesis and stimulates DNA single-strand annealing
Authors: He Liu , Lever Rebecca , Cubbon Andrew , Tehseen Muhammad , Jenkins Tabitha , Nottingham Alice O , Horton Anya , Betts Hannah , Fisher Martin , Hamdan Samir M , Soultanas Panos , Bolt Edward L 
Published: January 2023

AbstractDNA strand breaks are repaired by DNA synthesis from an exposed DNA end paired with a homologous DNA template. DNA polymerase delta (Pol δ) catalyses DNA synthesis in multiple eukaryotic DNA break repair pathways but triggers genome instability unless its activity is restrained. We show that human HelQ halts DNA synthesis by isolated Pol δ and Pol δ-PCNA-RPA holoenzyme. Using novel HelQ mutant proteins we identify that inhibition of Pol δ is independent of DNA binding, and maps to a 70 amino acid intrinsically disordered region of HelQ. Pol δ and its POLD3 subunit robustly stimulated DNA single-strand annealing by HelQ, and POLD3 and HelQ interact physically via the intrinsically disordered HelQ region. This data, and inability of HelQ to inhibit DNA synthesis by the POLD1 catalytic subunit of Pol δ, reveal a mechanism for limiting DNA synthesis and promoting DNA strand annealing during human DNA break repair, which centres on POLD3.
Application of microfluidic chip electrophoresis for high-throughput nucleic acid fluorescence fragment analysis assays
Authors: Sun Yali , Lu Zhi-xiang , Miller Michael , Perroud Thomas , Tong Yanhong 
Published: January 2023

Abstract
Nucleic acid fragment analysis via separation and detection are routine operations in molecular biology. However, analysis of small single-stranded nucleic acid fragments (&lt;100nt) is challenging and mainly limited to labor-intensive polyacrylamide gel electrophoresis or high-cost capillary electrophoresis methods. Here we report an alternative method, a microfluidic chip electrophoresis system that provides a size resolution of 5nt and a detection time of one minute per sample of fluorescence-labeled DNA/RNA fragments. The feasibility of this system was evaluated by quantifying CRISPR-Cas9 cleavage efficiency and the detection resolution was evaluated by analyzing ssDNA/RNA adenylation and phosphorylation. We employed this system to study the RNA capping efficiency and double-stranded DNA unwinding efficiency in isothermal amplification as two examples for assay design and evaluation. The microfluidic chip electrophoresis system provides a rapid, sensitive, and high-throughput fluorescence fragment analysis (FFA), and can be applied for enzyme characterization, reaction optimization, and product quality control in various molecular biology processes.
The Scottish COVID Cancer Immunity Prevalence Study: A Longitudinal Study of SARS-CoV-2 Immune Response in Patients Receiving Anti–Cancer Treatment
Authors: Purshouse Karin , Thomson John P , Vallet Mahéva , Alexander Lorna , Bonisteel Isaac , Brennan Maree , Cameron David A , Figueroa Jonine D , Furrie Elizabeth , Haig Pamela , Heck Mattea , McCaughan Hugh , Mitchell Paul , McVicars Heather , Primrose Lorraine , Silva Ines , Templeton Kate , Wilson Natalie , Hall Peter S 
Published: January 2023

AbstractBackgroundCancer and anti-cancer treatment (ACT) may be risk factors for severe SARS-CoV-2 infection and limited vaccine efficacy. Long–term longitudinal studies are needed to evaluate these risks. The Scottish COVID cancer immunity prevalence (SCCAMP) study characterizes the incidence and outcomes of SARS-CoV-2 infection and vaccination in patients with solid tumors undergoing ACT. This preliminary analysis includes 766 patients recruited since May 2020.MethodsPatients with solid-organ cancers attending secondary care for active ACT consented to the collection of routine electronic health record data and serial blood samples over 12 months. Blood samples were tested for total SARS-CoV-2 antibody.ResultsA total of 766 participants were recruited between May 28, 2020 and October 31, 2021. Most received cytotoxic chemotherapy (79%). Among the participants, 48 (6.3%) were tested positive for SARS-CoV-2 by PCR. Infection rates were unaffected by ACT, largely aligning with the local population. Mortality proportion was not higher with a recent positive SARS-CoV-2 PCR (10.4% vs 10.6%). Multivariate analysis revealed lower infection rates in vaccinated patients regardless of chemotherapy (HR 0.307 [95% CI, 0.144-0.6548]) or immunotherapy (HR 0.314 [95% CI, 0.041-2.367]) treatment. A total of 96.3% of patients successfully raised SARS-CoV-2 antibodies after &gt;2 vaccines. This was independent of the treatment type.ConclusionThis is the largest on-going longitudinal real-world dataset of patients undergoing ACT during the early stages of the COVID-19 pandemic. This preliminary analysis demonstrates that patients with solid tumors undergoing ACT have high protection from SARS-CoV-2 infection following COVID-19 vaccination. The SCCAMP study will evaluate long–term COVID-19 antibody trends, focusing on specific ACTs and patient subgroups.
Neuroimaging the effects of smartphone (over-)use on brain function and structure—a review on the current state of MRI-based findings and a roadmap for future research
Authors: Montag Christian , Becker Benjamin 
Published: January 2023

AbstractThe smartphone represents a transformative device that dramatically changed our daily lives, including how we communicate, work, entertain ourselves, and navigate through unknown territory. Given its ubiquitous availability and impact on nearly every aspect of our lives, debates on the potential impact of smartphone (over-)use on the brain and whether smartphone use can be “addictive” have increased over the last years. Several studies have used magnetic resonance imaging to characterize associations between individual differences in excessive smartphone use and variations in brain structure or function. Therefore, it is an opportune time to summarize and critically reflect on the available studies. Following this overview, we present a roadmap for future research to improve our understanding of how excessive smartphone use can affect the brain, mental health, and cognitive and affective functions.
Stalled Racial Progress and Japanese Trade in the 1970s and 1980s
Authors: Batistich Mary Kate , Bond Timothy N 
Published: January 2023

AbstractWe assess the impact of a rapid rise in Japanese import competition on the growth in racial earnings and employment gaps during the 1970s and 80s. Using commuting zone level variation in exposure, we find Japanese competition led to a decrease in manufacturing employment and labour force participation for blacks. This was driven by a shift in demand for skill in manufacturing. The difference in effects between the 10th percentile most and least exposed commuting zone was equivalent to 36–46% of the relative rise in black non-labour force participation, and 78–96% of the relative decline in black median male earnings.
The Triad of Childhood-Onset Schizophrenia, Autism Spectrum Disorder, and Catatonia: A Case Report
Authors: Leslie Alison C , O’Sullivan Michael 
Published: January 2023

AbstractChildhood-onset schizophrenia (COS) is a rare and severe form of schizophrenia with an estimated prevalence of 1/10,000. Schizophrenia and Autism spectrum disorder (ASD) have shared phenotypic features and shared genetic etiology. There is growing research surrounding the co-occurrence of psychomotor syndromes like catatonia with neurodevelopmental disorders like ASD or psychiatric disorders like schizophrenia. In 2013, Shorter and Wachtel described a phenomenon of the ‘Iron Triangle’ where COS, ASD, and catatonia often co-occur. The Iron Triangle theory is based on observation of historical case literature, which showed that all three diagnoses in the Iron Triangle were routinely assigned to children and adolescents. The pattern of this “Iron Triangle” suggests there may be a single underlying pathology resulting in a unique mixed form of catatonia, autism, and psychosis. We describe the case of a boy with sequential development of COS, ASD, and catatonia who also has syndromic facial and musculoskeletal features. This case highlights overlapping diagnostic features of these three disorders and can help us better understand how “hidden” features of catatonia may occur in patients with COS or ASD but go unrecognized, because they are grouped as features under autism/schizophrenia rather than a distinct diagnosis of catatonia. Further study is warranted to elucidate if this phenotypic pattern constitutes a new single diagnosis that is not well understood, an endophenotype of schizophrenia, or if this is the result of phenomenological overlap between catatonia, ASD, and COS.
Early-life nutrition interacts with developmental genes to shape the brain and sleep behavior inDrosophila melanogaster
Authors: Olivares Gonzalo H , Núñez-Villegas Franco , Candia Noemi , Oróstica Karen , González-Ramírez M Constanza , Vega-Macaya Franco , Zúñiga Nolberto , Molina Cristian , Oliva Carlos , Mackay Trudy F C , Verdugo Ricardo A , Olguín Patricio 
Published: January 2023

AbstractThe mechanisms by which the genotype interacts with nutrition during development to contribute to the variation of complex behaviors and brain morphology of adults are not well understood. Here we use the Drosophila Genetic Reference Panel to identify genes and pathways underlying these interactions in sleep behavior and mushroom body morphology. We show that early-life nutritional restriction effects on sleep behavior and brain morphology depends on the genotype. We mapped genes associated with sleep sensitivity to early-life nutrition, which were enriched for protein-protein interactions responsible for translation, endocytosis regulation, ubiquitination, lipid metabolism, and neural development. By manipulating the expression of candidate genes in the mushroom bodies (MBs) and all neurons, we confirm that genes regulating neural development, translation and insulin signaling contribute to the variable response of sleep and brain morphology to early-life nutrition. We show that the interaction between differential expression of candidate genes with nutritional restriction in early life resides in the MBs or other neurons and that these effects are sex-specific. Natural variations in genes that control the systemic response to nutrition and brain development and function interact with early-life nutrition in different types of neurons to contribute to the variation of brain morphology and adult sleep behavior.
Unrelated Donor Cord Blood Transplantation in Children: Lessons Learned Over 3 Decades
Authors: Kurtzberg Joanne , Troy Jesse D , Page Kristin M , El Ayoubi Hanadi Rafii , Volt Fernanda , Maria Scigliuolo Graziana , Cappelli Barbara , Rocha Vanderson , Ruggeri Annalisa , Gluckman Eliane 
Published: January 2023

Abstract
Four decades ago, Broxmeyer et al. demonstrated that umbilical cord blood (CB) contained hematopoietic stem cells (HSC) and hypothesized that CB could be used as a source of donor HSC for rescue of myeloablated bone marrow. In 1988, Gluckman et al. reported the first successful matched sibling cord blood transplant (CBT) in a child with Fanconi Anemia. In 1991, Rubinstein et al. established an unrelated donor CB bank, and in 1993, the first unrelated CBT used a unit from this bank. Since that time, &gt;40 000 CBTs have been performed worldwide. Early outcomes of CBT were mixed and demonstrated the importance of cell dose from the CB donor. We hypothesized that improvements in CB banking and transplantation favorably impacted outcomes of CBT today and performed a retrospective study combining data from Eurocord and Duke University in 4834 children transplanted with a single unrelated CB unit (CBU) from 1993 to 2019. Changes in standard transplant outcomes (overall survival [OS], disease free survival [DFS], acute and chronic graft-versus-host disease [GvHD], treatment related mortality [TRM], and relapse) over 3 time periods (1: &lt;2005; 2: 2005 to &lt;2010; and 3: &gt;2010 to 2019) were studied. Increased cell dose and degree of HLA matching were observed over time. OS, times to engraftment, and DFS improved over time. The incidence of TRM and GvHD decreased while the incidence of relapse remained unchanged. Relative contributions of cell dose and HLA matching to transplant outcomes were also assessed and showed that HLA matching was more important than cell dose in this pediatric cohort.
Effectiveness of Remdesivir Treatment Protocols Among Patients Hospitalized with COVID-19: A Target Trial Emulation
Authors: Breskin Alexander , Wiener Catherine , Adimora Adaora A. , Brown Robert S. , Landis Charles , Reddy K. Rajender , Verna Elizabeth C. , Crawford Julie M. , Mospan Andrea , Fried Michael W. , Brookhart M. Alan 
Published: January 2023

Background:
Remdesivir is recommended for certain hospitalized patients with COVID-19. However, these recommendations are based on evidence from small randomized trials, early observational studies, or expert opinion. Further investigation is needed to better inform treatment guidelines with regard to the effectiveness of remdesivir among these patients.

Methods:
We emulated a randomized target trial using chargemaster data from 333 US hospitals from 1 May 2020 to 31 December 2021. We compared three treatment protocols: remdesivir within 2 days of hospital admission, no remdesivir within the first 2 days of admission, and no remdesivir ever. We used baseline comorbidities recorded from encounters up to 12 months before admission and identified the use of in-hospital medications, procedures, and oxygen supplementation from charges. We estimated the cumulative incidence of mortality or mechanical ventilation/extracorporeal membrane oxygenation with an inverse probability of censoring weighted estimator. We conducted analyses in the total population as well as in subgroups stratified by level of oxygen supplementation.

Results:
A total of 274,319 adult patients met the eligibility criteria for the study. Thirty-day in-hospital mortality risk differences for patients adhering to the early remdesivir protocol were −3.1% (95% confidence interval = −3.5%, −2.7%) compared to no early remdesivir and −3.7% (95% confidence interval −4.2%, −3.2%) compared to never remdesivir, with the strongest effect in patients needing high-flow oxygen. For mechanical ventilation/extracorporeal membrane oxygenation, risk differences were minimal.

Conclusions:
We estimate that, among hospitalized patients with COVID-19, remdesivir treatment within 2 days of admission reduced 30-day in-hospital mortality, particularly for patients receiving supplemental oxygen on the day of admission.
A Summary of Chinese Guidelines on Diagnosis and Management of Hyperglycemia in Pregnancy (2022)
Authors:   Maternal-Fetal Medicine Committee, Chinese Society of Obstetrics and Gynecology, Chinese Medical Association; Chinese Society of Perinatal Medicine, Chinese Medical Association; Professional Committee of Gestational Diabetes Mellitus, Chinese Maternal and Child Health Association, Wang Chen , Juan Juan , Yang Huixia 
Published: January 2023

Abstract
Hyperglycemia is one of the most common complications women encounter during pregnancy, and is associated with a higher incidence of short- and long-term health risks for both the mother and offspring. In 2022, the Maternal-Fetal Medicine Committee of the Chinese Society of Obstetrics and Gynecology, Chinese Medicine Association, worked with the Chinese Society of Perinatal Medicine and the Professional Committee of Gestational Diabetes Mellitus of the Chinese Maternal and Child Health Association to update the Guidelines for the diagnosis and management of hyperglycemia in pregnancy in China. The aim was to further standardize the management of hyperglycemia in pregnancy from the aspects of screening, diagnosis, monitoring, treatment, and prevention of gestational diabetes mellitus, and consequently to further improve the health of mother and child.