bluuebunny/crossref_metadata_2025_split huggingface dataset:
The implementation of embedded researchers in policy, public services, and commercial settings: a systematic evidence and gap map
Authors: Kneale Dylan , Stansfield Claire , Goldman Rebecca , Lester Sarah , Edwards Rachael C. , Thomas James 
Published: April 2024

Abstract
Background
Embedding researchers into policy and other settings may enhance research capacity within organisations to enable them to become more research active. We aimed to generate an evidence map on evaluations of embedded researcher interventions to (i) identify where systematic reviews and primary research are needed and (ii) develop conceptual understandings of ‘embedded researchers’. We define ‘embedded researchers’ through a set of principles that incorporate elements such as the aim of activities, the types of relationships and learning involved, and the affiliations and identities adopted.

Methods
We included studies published across all sectors, searching fourteen databases, other web sources and two journals for evaluations published between 1991 and spring 2021. Data were extracted using a coding tool developed for this study. We identified new typologies of embedded researcher interventions through undertaking Latent Class Analysis.

Results
The map describes 229 evaluations spanning a variety of contexts. Our set of principles allowed us to move beyond a narrow focus on embedded researchers in name alone, towards consideration of the wide range of roles, activities, identities, and affiliations related to embedded researchers. We identified 108 different allied terms describing an embedded researcher. Embedded researcher activity spanned a continuum across lines of physical, cultural, institutional, and procedural embeddedness (from weaker to more intense forms of embeddedness) and took a range of forms that bridge or blur boundaries between academia and policy/practice.

Conclusions
We developed a broad map of international embedded researcher activity in a wide range of sectors. The map suggests that embedded researcher interventions occupy a broader suite of models than previously acknowledged and our findings also offer insight on the type and nature of this literature. Given the clear policy interest in this area, a better understanding of the processes involved with becoming embedded within an organisation is needed. Further work is also necessary to address the challenges of evaluating the work of embedded researchers, including consideration for which outcome measures are most appropriate, to better understand their influence.
Genetic Susceptibility, Mendelian Randomization, and Nomogram Model Construction of Gestational Diabetes Mellitus
Authors: Liang Qiulian , Li Ming , Huang Gongchen , Li Ruiqi , Qin Linyuan , Zhong Ping , Xing Xuekun , Yu Xiangyuan 
Published: April 2024

Abstract

Context
Gestational diabetes mellitus (GDM) is a pregnancy-complicated disease that poses a risk to maternal and infant health. However, the etiology of the disease has been not yet elucidated.

Objective
To detect the genetic susceptibility and construct a nomogram model with significantly associated polymorphisms and key clinical indicators for early prediction of GDM.

Methods
Eleven functional single nucleotide polymorphisms (SNPs) screened by genome-wide association study were genotyped in 554 GDM cases and 641 healthy controls. Functional analysis of GDM positively associated SNPs, multivariate mendelian randomization (MVMR), and a GDM early predictive nomogram model construction were performed.

Result
rs1965211, rs3760675, and rs7814359 were significantly associated with genetic susceptibility to GDM after adjusting age and prepregnancy body mass index (pre-BMI). It seems that GDM-associated SNPs have effects on regulating target gene transcription factor binding, posttranscriptional splicing, and translation product structure. Besides, rs3760675 can be expression quantitative trait loci and increase the XAB2 mRNA expression level (P = .047). The MVMR analysis showed that the increase of clinical variables of BMI, hemoglobin A1c (HbA1c), and fasting plasma glucose (FPG) had significant causal effects on GDM (BMI-ORMVMR = 1.52, HbA1c-ORMVMR = 1.32, FPG-ORMVMR = 1.78), P &lt; .05. A nomogram model constructed with pre-BMI, FPG, HbA1c, and genotypes of rs1965211, rs3760675, and rs7814359 showed an area under the receiver operating characteristic curve of 0.824.

Conclusion
Functional polymorphisms can change women's susceptibility to GDM and the predictive nomogram model based on genetic and environmental factors can effectively distinguish individuals with different GDM risks in early stages of pregnancy.
Regulation of the Function of T Follicular Helper Cells and B Cells in Type 1 Diabetes Mellitus by the OX40/OX40L Axis
Authors: Du Xuan , Zhu Yan , Lu Wen , Fu Nannan , Wang Qin , Shi Bimin 
Published: April 2024

Abstract

Objective/Main Outcome
To study the expression of OX40 on T follicular helper (Tfh) cells and the ligand OX40L on antigen-presenting cells (APCs) in peripheral blood of patients with type 1 diabetes mellitus (T1DM) and the role of OX40 signaling in promoting Tfh cells to assist B-cell differentiation.

Design
Cross-sectional study.

Setting
Endocrinology department of a university hospital.

Participants
Twenty-five patients with T1DM and 35 with newly diagnosed type 2 diabetes mellitus (T2DM) from January 2021 to December 2021 (39 males, 21 females; mean age: 31.0 ± 4.5, range: 19-46 years).

Interventions
None.

Methods
The peripheral blood proportion of CD4+CD25−CD127+CXCR5+PD1+ Tfh cells in patients with T1DM or T2DM and the OX40L expression in CD14+ monocytes and CD19+ B cells were analyzed by flow cytometry. The OX40 signal effect on Tfh-cell function was analyzed by coincubating B cells with Tfh cells under different conditions. Flow cytometry detected the ratio of CD19−CD138+ plasmacytes.

Results
The Tfh cells ratio and intracellular IL-21 expression in peripheral blood was significantly higher in patients with T1DM than with T2DM, and the OX40 expression in peripheral Tfh cells and OX40L expression in APC were significantly higher in T1DM. After adding OX40L protein, the CD19−CD138+-plasmacytes percentage was significantly increased and higher in T1DM. Blocking of anti-OX40L monoclonal antibodies significantly reduced the plasmacytes ratio.

Conclusion
The peripheral Tfh cells proportion increased and the OX40 expression in peripheral Tfh cells was upregulated in patients with T1DM vs patients with T2DM. OX40/OX40L signaling enhanced the Tfh-cell function to assist B-cell differentiation, which may contribute to the pathogenesis of T1DM.
Characterization of 35 Novel NR5A1/SF-1 Variants Identified in Individuals With Atypical Sexual Development: The SF1next Study
Authors: Naamneh Elzenaty Rawda , Martinez de Lapiscina Idoia , Kouri Chrysanthi , Sauter Kay-Sara , Sommer Grit , Castaño Luis , Flück Christa E 
Published: April 2024

Abstract

Context
Steroidogenic factor 1 (NR5A1/SF-1) is a nuclear receptor that regulates sex development, steroidogenesis, and reproduction. Genetic variants in NR5A1/SF-1 are common among differences of sex development (DSD) and associate with a wide range of phenotypes, but their pathogenic mechanisms remain unclear.

Objective
Novel, likely disease-causing NR5A1/SF-1 variants from the SF1next cohort of individuals with DSD were characterized to elucidate their pathogenic effect.

Methods
Different in silico tools were used to predict the impact of novel NR5A1/SF-1 variants on protein function. An extensive literature review was conducted to compare and select the best functional studies for testing the pathogenic effect of the variants in a classic cell culture model. The missense NR5A1/SF-1 variants were tested on the promoter luciferase reporter vector -152CYP11A1_pGL3 in HEK293T cells and assessed for their cytoplasmic/nuclear localization by Western blot.

Results
Thirty-five novel NR5A1/SF-1 variants were identified in the SF1next cohort. Seventeen missense NR5A1/SF-1 variants were functionally tested. Transactivation assays showed reduced activity for 40% of the variants located in the DNA binding domain and variable activity for variants located elsewhere. Translocation assessment revealed 3 variants (3/17) with affected nuclear translocation. No clear genotype-phenotype, structure-function correlation was found.

Conclusion
Genetic analyses and functional assays do not explain the observed wide phenotype of individuals with these novel NR5A1/SF-1 variants. In 9 individuals, additional likely disease-causing variants in other genes were found, strengthening the hypothesis that the broad phenotype of DSD associated with NR5A1/SF-1 variants may be caused by an oligogenic mechanism.
Association of Acylcarnitines With Maternal Cardiometabolic Risk Factors Is Defined by Chain Length: The S-PRESTO Study
Authors: Chen Li , Goh Xue Ping , Bendt Anne K , Tan Karen Mei-Ling , Leow Melvin Khee-Shing , Tan Kok Hian , Chan Jerry Kok Yen , Chan Shiao-Yng , Chong Yap Seng , Gluckman Peter D , Eriksson Johan G , Wenk Markus R , Mir Sartaj Ahmad 
Published: April 2024

Abstract

Context
Due to the essential role of carnitine as an intermediary in amino acid, carbohydrate, and lipid metabolism, a detailed characterization of circulating and urinary carnitine concentrations will aid in elucidating the molecular basis of impaired maternal metabolic flexibility and facilitating timely intervention for expectant mothers.

Objective
To investigate the association of maternal plasma and urinary free carnitine and acylcarnitines with cardiometabolic risk factors.

Methods
Liquid chromatography tandem mass spectrometry–based quantification of free carnitine and acylcarnitines (C2-C18) was performed on 765 plasma and 702 urine samples collected at preconception, 26 to 28 weeks’ pregnancy, and 3 months postpartum in the Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO) cohort study.

Results
Plasma concentrations of free carnitine and acylcarnitines decreased coupled with increased renal clearance in pregnancy compared with preconception and postpartum. Renal clearance of carnitine increased with an increase in prepregnancy body mass index (ppBMI) and gestational weight gain. Plasma short-chain acylcarnitines were positively associated with ppBMI, irrespective of the physiological state, while medium- and long-chain acylcarnitines were negatively associated with ppBMI at preconception and postpartum but showed a positive association in pregnancy. Similarly, plasma short-chain acylcarnitines were positively associated with Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) whereas medium- and long-chain acylcarnitines were negatively associated with HOMA-IR at preconception and in pregnancy. Mothers who developed gestational diabetes mellitus during pregnancy had ∼10% higher plasma propionylcarnitine concentration and ∼18% higher urine tiglylcarnitine concentration than mothers with normal glucose metabolism at preconception.

Conclusion
This study provides the metabolic and physiological basis of maternal carnitine homeostasis, which can be used in assessment of maternal cardiometabolic health at preconception to improve pregnancy outcomes.
Clinicopathological and Molecular Profile of Sellar Neurocytoma
Authors: Liu Yulou , Guo Jing , Cheng Jianhua , Fang Qiuyue , Wang Dawei , Xie Weiyan , Li Chuzhong 
Published: April 2024

Abstract

Objective
To investigate the clinical features, imaging characteristics, and molecular profile of sellar neurocytoma (SN).

Methods
Clinical, imaging, and pathological features of 11 cases of SN were retrospectively analyzed. Electron microscopy was performed in 5 cases. Molecular features were detected in tumor tissue by RNA sequencing, quantitative polymerase chain reaction, and immunohistochemistry.

Results
The clinical features of SN patients showed a high incidence of hyponatremia (73%, 8/11), and the tumors tended to invade the lateral side of the saddle area from preoperative imaging analysis. The tumors had positive NeuN, synaptophysin, neurofilament, somatostatin receptor 2 (SSTR2) immunohistochemistry staining. Tumor transcriptomic analysis suggested a new LMCD1-AS1:GRM7-AS1 fusion gene event and increased expression of 10 hypothalamus-secreted hormones in SN. Fifteen differentially expressed genes were verified for quantitative polymerase chain reaction verification. SSTR2 has been verified by immunohistochemistry.

Conclusion
Hyponatremia is the dominant clinical features of SN. Preoperative imaging suggests that growth toward the dorsal region is the imaging feature of SN. SSTR2 expression and LMCD1-AS1:GRM7-AS1 fusion gene event expected to become a new molecular marker for SN. Somatostatin receptor ligand therapy may be a potential therapy for SN.
Dietary n-3 Fatty Acids Intake and All-Cause and Cardiovascular Mortality in Patients With Prediabetes and Diabetes
Authors: Che Jinhang , He Na , Kuang Xue , Zheng Caiyin , Zhou Ruoyu , Zhan Xiaodan , Liu Zengzhang 
Published: April 2024

Abstract

Context
While the association between n-3 polyunsaturated fatty acids (PUFAs) and cardiovascular (CV) events has been thoroughly examined, there is still a scarcity of research regarding their effect on the long-term prognosis in diabetic patients.

Objective
We aimed to explore the effects of n-3 PUFA on all-cause and cardiovascular mortality in patients with pre-diabetes and diabetes.

Method
Herein, a total of 16 539 eligible individuals were enrolled from the National Health and Nutrition Examination Survey (NHANES) 2003 to 2018, and categorized into T1, T2, and T3 based on the tertiles of n-3 PUFA. The Cox proportional risk regression models, Kaplan-Meier curve, and subgroup analysis were conducted to evaluate the association between n-3 PUFA and mortality. Restricted cubic spline (RCS) curves graphically demonstrated the dose-response relationship. Additionally, weighted quantile sum (WQS) models were adopted to measure the mixed and individual effects of n-3 PUFA on mortality.

Results
Following a median follow-up period of 8.42 years, 3010 individuals died, with 989 deaths attributed to CV diseases. Significantly lower risk of all-cause (T2: 0.81 [0.71-0.92], T3: 0.77 [0.64-0.94]) and CV (T2: 0.75 [0.61-0.93]) mortality was observed after adjusting for multivariables compared to the reference (T1). Meanwhile, the RCS curve revealed a negative nonlinear association between n-3 PUFA and mortality. None of the interactions in any subgroup analysis were statistically significant except for BMI (P for interaction = .049). Finally, the WQS analysis demonstrated alpha-linolenic acid (ALA) and docosapentaenoic acid (DPA) as the main contributors to n-3 PUFAs’ benefits against mortality.

Conclusion
Increased dietary intake of n-3 PUFAs, particularly ALA and DPA, was associated with a reduced risk of all-cause and CV mortality among Americans with prediabetes and diabetes.
Plasma Proteomics of Diabetic Kidney Disease Among Asians With Younger-Onset Type 2 Diabetes
Authors: Gurung Resham Lal , Zheng Huili , Koh Hiromi Wai Ling , M Yiamunaa , Liu Jian-Jun , Liu Sylvia , Chan Clara , Ang Keven , Tan Clara Si Hua , Sobota Radoslaw Mikolaj , Subramaniam Tavintharan , Sum Chee Fang , Lim Su Chi 
Published: April 2024

Abstract

Context
Patients with younger onset of type 2 diabetes (YT2D) have increased risk for kidney failure compared to those with late onset. However, the mechanism of diabetic kidney disease (DKD) progression in this high-risk group is poorly understood.

Objective
This work aimed to identify novel biomarkers and potential causal proteins associated with DKD progression in patients with YT2D.

Methods
Among YT2D (T2D onset age &lt;40 years), 144 DKD progressors (cases) were matched for T2D onset age, sex, and ethnicity with 292 nonprogressors (controls) and divided into discovery and validation sets. DKD progression was defined as decline of estimated glomerular filtration rate (eGFR) of 3 mL/min/1.73 m2 or greater or 40% decline in eGFR from baseline. A total of 1472 plasma proteins were measured through a multiplex immunoassay that uses a proximity extension assay technology. Multivariable logistic regression was used to identify proteins associated with DKD progression. Mendelian randomization (MR) was used to evaluate causal relationship between plasma proteins and DKD progression.

Results
Forty-two plasma proteins were associated with DKD progression, independent of traditional cardiorenal risk factors, baseline eGFR, and urine albumin-to-creatinine ratio. The proteins identified were related to inflammatory and remodeling biological processes. Our findings suggest angiogenin as one of the top signals (odds ratio = 5.29; 95% CI, 2.39-11.73; P = 4.03 × 10−5). Furthermore, genetically determined plasma angiogenin level was associated with increased odds of DKD progression.

Conclusion
Large-scale proteomic analysis identified novel proteomic biomarkers for DKD progression in YT2D. Genetic evidence suggest a causal role of plasma angiogenin in DKD progression.
Impact of Ghrelin on Islet Size in Nonpregnant and Pregnant Female Mice
Authors: Gupta Deepali , Burstein Avi W , Shankar Kripa , Varshney Salil , Singh Omprakash , Osborne-Lawrence Sherri , Richard Corine P , Zigman Jeffrey M 
Published: April 2024

Abstract
Reducing ghrelin by ghrelin gene knockout (GKO), ghrelin-cell ablation, or high-fat diet feeding increases islet size and β-cell mass in male mice. Here we determined if reducing ghrelin also enlarges islets in females and if pregnancy-associated changes in islet size are related to reduced ghrelin. Islet size and β-cell mass were larger (P = .057 for β-cell mass) in female GKO mice. Pregnancy was associated with reduced ghrelin and increased liver-expressed antimicrobial peptide-2 (LEAP2; a ghrelin receptor antagonist) in wild-type mice. Ghrelin deletion and pregnancy each increased islet size (by ∼19.9-30.2% and ∼34.9-46.4%, respectively), percentage of large islets (&gt;25 µm2×103, by ∼21.8-42% and ∼21.2-41.2%, respectively), and β-cell mass (by ∼15.7-23.8% and ∼65.2-76.8%, respectively). Neither islet cross-sectional area, β-cell cross-sectional area, nor β-cell mass correlated with plasma ghrelin, although all positively correlated with LEAP2 (P = .081 for islet cross-sectional area). In ad lib-fed mice, there was an effect of pregnancy, but not ghrelin deletion, to change (raise) plasma insulin without impacting blood glucose. Similarly, there was an effect of pregnancy, but not ghrelin deletion, to change (lower) blood glucose area under the curve during a glucose tolerance test. Thus, genetic deletion of ghrelin increases islet size and β-cell cross-sectional area in female mice, similar to males. Yet, despite pregnancy-associated reductions in ghrelin, other factors appear to govern islet enlargement and changes to insulin sensitivity and glucose tolerance in the setting of pregnancy. In the case of islet size and β-cell mass, one of those factors may be the pregnancy-associated increase in LEAP2.
Comparison of In-Hospital Mortality and Neurosurgical Intervention Between Intracranial Gunshot Wounds Arising From Long Guns and Handguns: A Propensity Score Matched Study
Authors: Jiang Sam H. , Marotta Dario , Molina Neves Teresa , Bhaskara Mounika , Mehta Ankit I. 
Published: April 2024

BACKGROUND AND OBJECTIVES:
Patients with intracranial gunshot wounds (IC-GSWs) often present with severe neurological injuries requiring prompt neurological evaluation. Neurosurgical intervention is reserved for those with reasonable chances of survival. Handguns and long guns, such as shotguns and rifles, have differing mechanisms of injury which may influence surgical candidacy and outcomes. This study aims to compare rates and types of neurosurgical intervention and inpatient outcomes in patients with IC-GSWs handguns and long guns.

METHODS:
The National Trauma Data Bank was retrospectively queried for patients with IC-GSWs from 2017 to 2019. Patients with long gun IC-GSWs were propensity score matched with those with handgun IC-GSWs based on patient demographics, comorbidities, insurance status, injury extent and severity, and hospital trauma level. Group differences were compared using Student's t-tests and Pearson's χ2 tests, and multivariable logistic regression was used to identify predictors of in-hospital mortality.

RESULTS:
Overall, patients in the long gun group were more likely to undergo neurosurgical intervention (21% vs 17%, P = .02). Following propensity score matching, the long gun group had lower rates of in-hospital mortality (35% vs 43%, P < .01), lower rates of cardiac arrest (5% vs 8%, P = .02), and lower rates of reoperation (0% vs 2%, P = .02) than the handgun group. In multivariable regression, independent predictors of survival included long gun IC-GSWs (odds ratio [OR] 0.65, CI 0.52-0.83), neurosurgical foreign body removal (OR 0.44, CI 0.33-0.58), intracranial debridement (OR 0.47, 0.33-0.67), and craniectomy (OR 0.46, CI 0.34-0.63).

CONCLUSION:
Patients with IC-GSWs present to the hospital with severe neurological injury. Neurosurgical intervention was independently associated with decreased mortality. After matching, patients with long gun IC-GSWs experienced lower in-hospital mortality rates compared with those from handguns. This study suggests that patients suffering from long gun IC-GSW may respond particularly well to neurosurgical intervention and firearm type should be considered when determining neurosurgical candidacy.
The Crossing Motor Ulnar Nerve Branch at Elbow
Authors: Majid Sonia S. , Patel Neel T. , Mrowczynski Oliver D. , Goldman Evan , Rizk Elias B. , Harbaugh Kimberly S. 
Published: April 2024

BACKGROUND AND OBJECTIVES:
Cubital tunnel syndrome is the second most common nerve entrapment, and understanding the anatomy is crucial for the success of the nerve release. During ulnar nerve release for cubital tunnel syndrome, a motor branch is frequently encountered crossing anteriorly over the ulnar nerve from its medial/ulnar side proximally to the lateral/radial side distally. Little has been noted about this crossing branch in the literature. In this anatomic study, we sought to characterize this branch further and discuss its potential significance in cubital tunnel release.

METHODS:
We performed a cadaveric dissection of 48 elbow specimens as if performing a cubital tunnel release. We assessed for the presence of the crossing motor branch of the ulnar nerve and measured the distance from the medial epicondyle to the branch takeoff and to its target of innervation.

RESULTS:
Of our 48 specimens, 34 (71%) were noted to have a crossing motor branch at the area of compression by the deep flexor carpi ulnaris muscle fascia (common aponeurosis). On average, the distance from the medial epicondyle to the branch origin from the ulnar nerve was 18.2 mm and to the target muscle innervation was 28.4 mm.

CONCLUSION:
Identifying this branch is important for performing a cubital tunnel release, and awareness of this anatomy during ulnar nerve decompression procedures may help avoid injury to this motor branch.