bluuebunny/crossref_metadata_2025_split huggingface dataset:
A 2 and 5-Year Longitudinal Analysis of 671 Consecutive Patients Diagnosed with Unilateral Vestibular Schwannoma
Authors: Tan Neil C.-W. , Macfarlane Robert , Donnelly Neil , Mannion Richard , Tysome James R. , Jefferies Sarah , Bance Manohar , Axon Patrick R. 
Published: June 2022

Objective
To analyse the 2 and 5-year outcomes of a cohort of patients with newly diagnosed vestibular schwannoma patients.

Study Design
Longitudinal cohort study.

Setting
Tertiary skull base referral unit.

Patients
Six hundred and seventy-one consecutive patients referred to the Cambridge Skull Base Unit between 2005 and 2010.

Main Outcome Measures
1) Treatment outcomes, 2) hearing preservation, 3) facial nerve function, and 4) gross tumor control.

Results
At initial diagnosis, 440/671(65.6%) of patients entered a watch, wait and rescan (WWR) pathway, 208/671 (31%) underwent primary microsurgical excision and 23/671 (3.4%) primary radiotherapy. Of patients who entered WWR, 144/440 (32.7%) exhibited tumor growth necessitating secondary intervention at a mean of 22.7 months; 67.4% had radiotherapy and 32.6% surgery. Radiotherapy was successful at achieving tumor control in 95% of cases. Primary surgery via the translabyrinthine route was performed in the majority of cases allowing for a radiologically clear surgical resection in 93% of cases.

Conclusion
The Cambridge philosophy of treating the newly diagnosed vestibular schwannoma aims at preserving functional status where possible. In patients with small tumors it is recommended that they are placed on to a WWR pathway, of which 67.3% will not exhibit any growth by 5 years. If small tumors grow more than 2 mm by serial scanning, radiotherapy offers a high rate of tumor control. In patients with larger tumors more than 20 mm we would advocate microsurgical excision by the translabyrinthine route which offers excellent functional outcomes and gross tumor control.
Association of adverse childhood experiences with subsequent kidney disease among middle-aged and older adults in China: A national analysis
Authors: Shi Wenming , Huang Yonggang , Jin Changbo 
Published: June 2022

AbstractObjectiveFew studies have been performed to address the impacts of adverse childhood experiences (ACEs) on kidney function in later life. We aimed to investigate the association between ACEs with subsequent kidney disease among middle-aged and older adults.MethodsThis national population-based study used data from the China Health and Retirement Longitudinal Study (CHARLS) 2015 and the life history survey in 2014. A total of 10102 participants aged ≥ 45 years from China were included. A wide range of 11 ACE indicators including childhood hunger, child’s poor health, physical abuse, emotional neglect, loneliness, peer bullying, domestic violence, household mental illness, household substance abuse, parental death, and incarcerated household member were measured by validated questionnaires. The cumulative number of ACEs was summed and and classified into four subgroups: ≤ 1, 2, 3 and ≥ 4. Glomerular filtration rate (eGFR) was estimated by serum cystatin C concentration and chronic kidney disease (CKD) was defined as eGFR < 60 ml/min/1.73m2. Multiple regression models were used to explore the relationship between accumulated ACEs and individual ACE indicator with subsequent kidney function.FindingsOf the 10102 participants, 46.8% were males, and 16.0% reported exposure to four or more ACEs. Compared those with ≤ 1 ACE, participants who experienced four or more ACEs have a higher risk of decreased eGFR (β= -1.169, 95%CI: -2.113 to -0.225) and CKD (adjusted odds ratio, aOR=1.35, 1.04-1.75), after controlling for confounders. Exposure to specific ACE indicators of childhood poor health, physical abuse and household mental illness presented significant associations with reduced eGFR. The effects were more evident in men aged ≥ 60 years, with lower education or worse financial status.ConclusionsOur study suggests that higher ACEs exposure increased the risk of subsequent kidney disease. The findings provide implications for mitigating the adverse effects of early-life stress and promoting kidney health by reducing ACEs.
A Population-Based Study of Plasma Metabolomic Profiles of Persistent Tinnitus Identifies Candidate Biomarkers
Authors: Zeleznik Oana A. , Welling D. Bradley , Stankovic Konstantina , Frueh Lisa , Balasubramanian Raji , Curhan Gary C. , Curhan Sharon G. 
Published: June 2022

AbstractTinnitus, the perception of sound without the corresponding external stimulus, currently affects 15% of the US population. There is a critical need to unravel the heterogeneous etiologies underlying tinnitus and identify tailored treatment targets. Metabolomic studies have elucidated biological pathways underlying several neurodegenerative disorders and could identify metabolic perturbations that influence tinnitus development. We conducted the first large-scale metabolomic study to identify novel tinnitus biomarkers. We cross-sectionally evaluated plasma metabolite profiles and persistent tinnitus among 6477 women (488 with daily tinnitus ≥5 minutes and 5989 controls). A broad array of 466 metabolites was measured using liquid-chromatography mass spectrometry. Logistic regression was used to estimate odds ratios (OR, per 1 SD increase in metabolite values) and 95% confidence intervals (CI) for each individual metabolite while Metabolite Set Enrichment Analysis (MSEA) was used to identify metabolite classes enriched for associations with tinnitus; all models were adjusted for multiple comparisons. Compared with controls, homocitrulline (OR(95%CI)=1.32(1.16-1.50), C38:6 phosphatidylethanolamine (PE; 1.24(1.12-1.38)), C52:6 triglyceride (TAG; 1.22(1.10-1.36)), C36:4 PE (1.22(1.1-1.35)), C40:6 PE (1.22(1.09-1.35)), and C56:7 TAG (1.21(1.09-1.34)) were positively associated, whereas alpha-keto-beta-methylvalerate (0.68(0.56-0.82)) and levulinate (0.60(0.46-0.79)) were inversely associated with tinnitus (adjusted-p<0.05). Among metabolite classes, TAGs, PEs, and diglycerides (DAGs) were positively associated, while phosphatidylcholine (PC) plasmalogens, lysophosphatidylcholines (LPC), and cholesteryl esters were inversely associated with tinnitus (false discovery rate <0.05). This study identified novel plasma metabolites and metabolite classes that were significantly associated with persistent tinnitus. These findings extend our current understanding of tinnitus and could inform investigations of therapeutic targets for this challenging disorder.
Gender and COVID-19 Vaccine disparities in Cameroon
Authors: Amani Adidja , Mossus Tatiana , Lekeumo Cheuyem Fabrice Zobel , Bilounga Chanceline , Mikamb Pamela , Atchou Jonas Basseguin , Minyem Ngombi Aude Perine , Nangmo Armanda , Kamga Yannick , Bediang Georges , Kamgno Joseph , Bissek Anne-Cécile Zoung-Kanyi 
Published: June 2022

AbstractSix months following the national launch of COVID-19 vaccination in Cameroon, only 1.1% of the target population was fully vaccinated with women representing less than one-third of the vaccinated population regardless of their age, profession or comorbidities. Hence, the aim of this study was to understand the low COVID-19 vaccination rate of women in order to enhance vaccine uptake. A cross-sectional study was conducted between July and October 2021 through an online survey. Also, a retrospective analysis of the Cameroon Ministry of Public Health (MINSANTE) database of the pandemic (COVID-19), for the period of March 2020 to October 2021 was equally carried out. Our sample consisted of 249 responders aged between 18 and 50 years enrolled in the 10 regions of Cameroon, with 142 (57%) who were female. We assessed factors related to having been vaccinated against Covid-19 and predictors to Covid-19 vaccination among non-vaccinated people. Concerning Covid-19 vaccination, 39.2% were not vaccinated. Non-vaccination was statistically associated with being female, being a healthcare worker, fear of adverse effects, and not believing in the vaccine. In the qualitative analysis, women identified themselves as being anti-COVID vaccine for several reasons, including doubts about the quality or safety of the vaccine; the perception that anti-COVID-19 vaccines are presented as being an obligation; including the multitude of vaccines on the market, the believe that there are “more local” effective alternatives to the vaccine. The implementation of the gender approach to COVID vaccination is a condition for the effectiveness and sustainability of actions.
Defining suspected child maltreatment using International Classification of Diseases codes: A scoping literature review
Authors: Liu Yuerong , Terrell Lindsay , Joyce Brianna , Black Julia , Kaplan Samantha J. , Gifford Elizabeth J. 
Published: June 2022

AbstractBackgroundAdministrative medical and claims records are increasingly used to study prevalence of and outcomes for children exposed to child maltreatment. However, suspicion of child maltreatment is often under-documented in medical records using International Classification of Diseases (ICD) codes. Although researchers have developed strategies to more broadly capture the injuries, illnesses, and circumstances that are suggestive of maltreatment, there is no consensus on which codes to use for this purpose.ObjectiveTo systematically examine the types of research being conducted with ICD codes related to suspected maltreatment, summarize the methods used to identify the codes, and propose future direction.MethodsWe searched five electronic databases for studies that reported ICD codes suggestive of child maltreatment in any medical setting, included participants aged 0-18 years, and published in a peer-reviewed journal in English. Two reviewers independently screened the titles, abstracts, and the full texts. Data were synthesized in a qualitative manner.ResultsThirty-seven studies met inclusion criteria. Most studies focused on determining the incidence or trends of maltreatment-related injuries or illnesses. Studies varied greatly in the codes used to identify suspected maltreatment. Only four articles reported on the validation of selected codes. ICD codes for transport accidents were the most frequently excluded co-occurring codes. Studies frequently relied on two seminal studies and two national-level guidelines.ConclusionsSubstantial heterogeneity existed in the ICD codes and methods used to identify suspected maltreatment. The age range for codes, excluded co-occurring codes, and validation of codes are areas future research should address. This review may reduce costs for future researchers so that they could choose optimal measures of suspected maltreatment from our summarized list of codes without reinventing the wheel. Our review provides a basis for the development of recommended guidelines in establishing uniform codes for suspected maltreatment that could promote public health surveillance and allow for more efficient and uniform policy or program evaluation.
Comparing the XGBoost machine learning algorithm to polygenic scoring for the prediction of intelligence based on genotype data
Authors: Fahey Laura , Morris Derek W. , Ó Broin Pilib 
Published: June 2022

AbstractA polygenic score (PGS) is a linear combination of effects from a GWAS that represents and can be used to predict genetic predisposition to a particular phenotype. A key limitation of the PGS method is that it assumes additive and independent SNP effects, when it is known that epistasis (gene interactions) can contribute to complex traits. Machine learning methods can potentially overcome this limitation by virtue of their ability to capture nonlinear interactions in high dimensional data. Intelligence is a complex trait for which PGS prediction currently explains up to 5.2% of the variance, a relatively small proportion of the heritability estimate of 50% obtained from twin studies. Here, we use gradient boosting, a machine learning technique based on an ensemble of weak prediction models, to predict intelligence from genotype data. We found that while gradient boosting did not outperform the PGS method in predicting intelligence based on SNP data, it was capable of achieving similar predictive performance with less than a quarter of the SNPs with the top SNPs identified as being important for predictive performance being biologically meaningful. These results indicate that ML methods may be useful in interpreting the biological meaning underpinning SNP-phenotype associations due to the smaller number of SNPs required in the ML model as opposed to the standard PGS method based on GWAS.
Cancer type-specific prioritization strategy for targetable dependencies developed from the DepMap profile of head and neck cancer
Authors: Cao Austin C. , Sannigrahi Malay K. , Rajagopalan Pavithra , Brody Robert M. , Raghav Lovely , Gimotty Phyllis A. , Basu Devraj 
Published: June 2022

ABSTRACTObjectivesThe DepMap genome-wide loss of function CRISPR screens offer new insight into gene dependencies in HPV(-) head and neck squamous cell carcinoma (HNSCC) cell lines. We aimed to leverage this data to guide preclinical studies by cataloging novel targetable dependencies that are predicted to offer a useful therapeutic window. We also aimed to identify targets potentially representing synthetic lethalities by testing for associations between genetic alterations and gene dependency profile.MethodsDepMap was queried for gene probability and effect scores in cell lines from 87 tumors, including 63 HPV(-) HNSCCs plus 24 esophageal squamous cell carcinomas (ESCCs), which have comparable etiology, tissue or origin, and genetic profile to HNSCC. A probability score of ≥ 0.5 was used as the threshold for essentiality. Essential genes were selected for analysis by 4 criteria: (1) presence in ≥10% cell lines, (2) lack of common essential designation by DepMap, (3) lack of predicted dependency in normal cell lineages, and (4) designation as druggable by the Drug-Gene Interaction Database.ResultsThe 143 genes meeting selection criteria had a median gene effect score of 0.56. Selection criteria captured targets of standard therapeutic agents of HNSCC includingTYMS(5-FU), tubulin genes (taxanes),EGFR(cetuximab), plus additional known oncogenes likePIK3CAandERBB3. Functional classification analysis showed enrichment of tyrosine kinases, serine/threonine kinases, RNA-binding proteins, and mitochondrial carriers. 90% of the 143 dependencies were not known oncogenes in the OncoKB Database. 10% of targets had inhibitors previously used in a non-HNSCC phase II trial, including 8 that have not yet been tested in cancer. The 13 genes with median gene effect scores greater than of PIK3CA and not well-studied in HNSCC were assigned highest priority, includingDHRSX, MBTPS1, TDP2, FARS2, TMX2, RAB35, CFLAR, GPX4, SLC2A1, TP63, PKN2, MAP3K11,andTIPARP. A novel association was found betweenNOTCH1mutation and increasedTAP1dependency.ConclusionsThe DepMap CRISPR screens capture well-studied targets in HNSCC as well as numerous genes without known roles in HNSCC or malignancy in general. Several of these targets have well-developed inhibitors that provide resources to guide preclinical studies. Association of some of the dependencies with known molecular subgroups in HNSCC may enhance use of cell line models to guide personalization of therapy.
Genome-wide SNP genotyping as a simple and practical tool to accelerate the development of inbred lines in outbred tree species: an example in cacao (Theobroma cacao L.)
Authors: Lopes Uilson Vanderlei , Pires Jose Luis , Gramacho Karina Peres , Grattapaglia Dario 
Published: June 2022

AbstractCacao is a globally important crop with a long history of domestication and selective breeding. Despite the increased use of elite clones by cacao farmers, worldwide plantations are established mainly using hybrid progeny material derived from heterozygous parents, therefore displaying high tree-to-tree variability. The deliberate development of hybrids from advanced inbred lines produced by successive generations of self-pollination has not yet been fully considered in cacao breeding. This is largely due to the self-incompatibility of the species, the long generation cycles (3-5 years) and the extensive trial areas needed to accomplish the endeavor. We propose a simple and accessible approach to develop inbred lines based on accelerating the buildup of homozygosity based on regular selfing assisted by genome-wide SNP genotyping. In this study we genotyped 90 clones from the Brazilian CEPEC’s germplasm collection and 49 inbred offspring of six S1 or S2 cacao families derived from self-pollinating clones CCN-51, PS-13.19, TSH-1188 and SIAL-169. A set of 3,380 SNPs distributed across the cacao genome were interrogated on the EMBRAPA multi-species 65k Infinium chip. The 90 cacao clones showed considerable variation in genome-wide SNP homozygosity (mean 0.727± 0.182) and 19 of them with homozygosity >90%. By assessing the increase in homozygosity across two generations of self-pollinations, SNP data revealed the wide variability in homozygosity within and between S1 and S2 families. Even in small families (<10 sibs), individuals were identified with up to ∼1.5 standard deviations above the family mean homozygosity. From baseline homozygosities of 0.476 and 0.454, offspring with homozygosities of 0.862 and 0.879 were recovered for clones TSH-1188 and CCN-51 respectively, in only two generations of selfing (81-93% increase). SNP marker assisted monitoring and selection of inbred individuals can be a practical tool to optimize and accelerate the development of inbred lines of outbred species. This approach will allow a faster and more accurate exploitation of hybrid strategies in cacao breeding programs and potentially in other perennial fruit and forest trees.
Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs
Authors: Donner Jonas , Freyer Jamie , Davison Stephen , Anderson Heidi , Blades Matthew , Honkanen Leena , Inman Laura , Brookhart-Knox Casey A. , Louviere Annette , Forman Oliver P , Foran Rebecca Chodroff 
Published: June 2022

AbstractHundreds of genetic variants linked to Mendelian disease have been characterized in dogs to date, and commercial screening is being offered for most of them worldwide. There typically remains a paucity of information regarding the broader population frequency of newly discovered variants, as well as uncertainty regarding their functional and clinical impact on additional genomic ancestry backgrounds beyond the discovery breed. Panel screening of disease variants, commercially offered as direct-to-consumer genetic testing, provides an opportunity to establish large-scale cohorts with both genotype and phenotype data available to address open questions related to variant prevalence and relevance. In this study, we screened the largest canine cohort examined in a single study to date (1,054,293 representative dogs from our existing cohort of more than three million dogs; a total of 811,628 mixed breed dogs and 242,665 purebreds from more than 150 countries and territories) for 250 genetic disease-associated variants to understand their prevalence and distribution in the general population. Electronic medical records from veterinary clinics were available for 43.5% of the genotyped dogs, enabling follow up on the clinical impact of variants. We provide detailed frequencies for all tested variants across breeds and find that 57% of dogs carry at least one copy of a studied Mendelian disease-linked variant. We provide evidence of full penetrance for 10 variants, and at minimum plausible evidence for the clinical significance of 22 variants, on a wide variety of breed backgrounds. We further show that a reduction in genome-wide heterozygosity is associated with an increased Mendelian disease load and assess genome-wide heterozygosity levels in over 100 breeds. The accumulated knowledge represents a resource to guide discussions on disease variant presence and genetic test relevance by breed.
Multi-scale modelling of shear stress on the syncytiotrophoblast: Could maternal blood flow impact placental function across gestation?
Authors: Lee Tet Chuan , Moulvi Ali , James Joanna L. , Clark Alys R. 
Published: June 2022

AbstractThe surface of the placenta is lined by a single multinucleated cell, the syncytiotrophoblast, which forms a functional barrier between maternal and fetal blood in pregnancy. The placenta plays a critical role in healthy fetal development and over the course of pregnancy forms a complex branching tree-like structure which bathes in maternal blood and serves a vital exchange function. It has been suggested that the structure of the placenta may evolve, in part, under the influence of the shear stress exerted by maternal blood flow over its surface, with the syncytiotrophoblast having a role in mechanosensing. However, data describing the mechano-sensitive nature of this cell, particularly in early gestation, is lacking. In this study we show that the syncytiotrophoblast expresses six proteins that have been related to shear sensing, and this expression is higher in the first trimester than at term. This suggests shear on the sycytiotrophoblast as an important factor influencing placental morphogenesis early in pregnancy. We then predict shear stress felt by the syncytiotrophoblast in first trimester and term placental tissue using a combination of porous medium modelling and explicit simulations of blood flow in realistic geometries derived from microCT imaging. Our models predict that typical shear stress on first-trimester tissue is higher than at term, supporting the feasibility of this mechanical stimulus as an important driver of healthy placental development.
Tocilizumab versus baricitinib in hospitalized patients with severe COVID-19: an open label, randomized controlled trial
Authors: Karampitsakos Theodoros , Papaioannou Ourania , Tsiri Panagiota , Katsaras Matthaios , Katsimpris Andreas , Kalogeropoulos Andreas P. , Malakounidou Elli , Zarkadi Eirini , Tsirikos Georgios , Georgiopoulou Vasiliki , Sotiropoulou Vasilina , Koulousousa Electra , Chourpiliadi Charikleia , Matsioulas Apostolos , Lagadinou Maria , Sampsonas Fotios , Akinosoglou Karolina , Marangos Markos , Tzouvelekis Argyris 
Published: June 2022

AbstractBackgroundTocilizumab and baricitinib have proven efficacy in COVID-19. There were no randomized-controlled trials comparing these compounds in patients with COVID-19.Materials/Patients and MethodsIn this open label, randomized controlled trial, we assigned 251 patients with COVID-19 and PaO2/FiO2<200 to receive either tocilizumab (n=126) or baricitinib (n=125) plus standard of care. To determine whether baricitinib was non-inferior to tocilizumab, we assessed if the upper boundary of the two-sided 95% confidence interval of the hazard ratio did not exceed 1.50. The primary outcome was mechanical ventilation or death by day 28. Secondary outcomes included time to hospital discharge by day 28 and change in WHO progression scale at day 10.ResultsBaricitinib was non-inferior to tocilizumab for the primary composite outcome of mechanical ventilation or death by day 28 (HR 0.83, 95% CI: 0.56 to 1.21, p=0.001 for non-inferiority). Baricitinib was non-inferior to tocilizumab for the time to hospital discharge within 28 days (discharged alive-tocilizumab: 52.4% vs baricitinib: 58.4%; HR 0.85, (95% CI: 0.61 to 1.18), p<0.001 for non-inferiority). There was no significant difference between baricitinib and tocilizumab arm in the change in WHO scale at day 10 [0.0 (95% CI: 0.0 to 0.0) vs 0.0 (95% CI: 0.0 to 1.0), p=0.83].ConclusionBaricitinib was non-inferior to tocilizumab with regards to the composite outcome of mechanical ventilation or death by day 28 and the time to discharge by day 28 in patients with severe COVID-19. Cost-effectiveness should be taken into account to avoid a dramatic upswing in health system budgets.