bluuebunny/crossref_metadata_2025_split huggingface dataset:
Obtaining Textured Nickel Antimonide Films
Authors: Luzanov V. A. 
Published: March 2024

Abstract
It was shown for the first time that when nickel is deposited onto a heated gallium antimonide substrate, diffusion of antimony atoms from the substrate into the growing film occurs and a nickel antimonide film is formed, which has an axial texture with an axis perpendicular to the film plane along the (101) direction.
Preference and retention of daily and event-driven pre-exposure prophylaxis for HIV prevention: a prospective cohort in Can Tho city, Viet Nam
Authors: Nguyen Van Thi Thuy , Dat Vu Quoc , Truc Huynh Minh , Nguyen Anh Thu Pham , Linh Doan Thi Thuy , Johnson Cheryl , Baggaley Rachel Clare , Phan Huong Thi Thu 
Published: March 2024

ObjectivePre-exposure prophylaxis (PrEP) was introduced in Viet Nam in 2017, but data on oral PrEP preference and effective use beyond 3 months are limited. We aimed to evaluate PrEP preferences for PrEP, factors influencing uptake, choice and effective use, as well as barriers to PrEP.MethodsThis is a prospective cohort study in Can Tho, Viet Nam. Participants who were eligible for PrEP and provided informed consent were interviewed at baseline on demographic information, willingness to pay, reasons for choosing their PrEP regimen and the anticipated difficulties in taking PrEP and followed up at 3 months, 6 months and 12 months after PrEP initiation.FindingsBetween May 2020 and April 2021, 926 individuals at substantial risk for HIV initiated PrEP. Of whom 673 (72.7%) choose daily PrEP and 253 (27.3%) choose event-driven (ED)-PrEP. The majority of participants were men (92.7%) and only 6.8% were women and 0.5% were transgender women. Median participant age was 24 years (IQR 20–28) and 84.7% reported as exclusively same-sex relationship. The three most common reasons for choosing daily PrEP were effectiveness (24.3%) and unplanning for sex (22.9%). Those opting for ED-PrEP also cited effectiveness (22.7%), as well as convenience (18.0%) and easier effective use (12.0%). Only 7.8% of PrEP users indicated they were unwilling to pay for PrEP and 76.4% would be willing to pay if PrEP were less than US$15 per month. The proportion of user effectively using PrEP at 12 months was 43.1% and 99.2% in daily PrEP and ED-PrEP users, respectively.ConclusionsED-PrEP was preferred by more than a quarter of 23.5% of the participants and there was little concern about potential adverse events. High rates of effective use were reported by ED-PrEP users. Future research to inform implementation of PrEP in Viet Nam is needed to develop ways of measuring adherence to ED-PrEP more accurately and to understand and address difficulties in taking daily PrEP use.
Safeguarding in adolescent mental health research: navigating dilemmas and developing procedures
Authors: Randhawa Amie , Wood Grace , Michail Maria , Pallan Miranda , Patterson Paul , Goodyear Victoria 
Published: March 2024

Mental disorders are prevalent during adolescence. Self-harm and suicide are more common in adolescents with a probable mental disorder, with one in four reporting to have attempted self-harm. Research involving adolescents is, therefore, likely to include participants experiencing mental ill health, even if mental health is not the primary focus. Researchers should adopt procedures and principles that safeguard adolescent mental health in their research practice. Yet there are gaps between theory and practice of research with adolescents in relation to their mental health, and limited guidance is available.We discuss emerging safeguarding dilemmas and procedures in adolescent mental health research. Our experiences of safeguarding adolescent mental health are grounded in the UK National Institute for Health and Care Research-funded SMART Schools Study. Drawing from this secondary school-based study, we focus on how our research team encountered and addressed a high prevalence of participants (aged 12–13 and 14–15 years) reporting thoughts and behaviours related to self-harm or suicide (24% of participants). This included reviewing our existing risk mitigation processes and consulting with several committees including young people with lived experiences of mental health.We present the SMART Schools study safeguarding approach for adolescent mental health. This encompasses key safeguarding principles, study procedures and relevant justifications. We address school and university roles and responsibilities, pupil understanding, and efficient, effective and secure communication pathways. We embed guidance throughout this article for researchers working with adolescents in the context of mental health. Lastly, we present five key recommendations to safeguard the mental health of adolescents participating in research, including (1) appointing a safeguarding lead within the research team; (2) codesigning a bespoke study safeguarding approach; (3) adopting a responsive approach to mental health safeguarding; (4) being transparent about the study mental health safeguarding approach and (5) report the implementation and outcomes of safeguarding approaches.Trial registration numberISRCTN77948572.
Determining the distance patterns in the movements of future doctors in UK between 2002 and 2015: a retrospective cohort study
Authors: Hitchings Lucy , Fleet Ben , Smith Daniel Thomas , Read Jonathan M , Melville Colin , Sedda Luigi 
Published: March 2024

ObjectiveTo determine and identify distance patterns in the movements of medical students and junior doctors between their training locations.DesignA retrospective cohort study of UK medical students from 2002 to 2015 (UKMED data).SettingAll UK medical schools, foundations and specialty training organisation.ParticipantsAll UK medical students from 2002 to 2015, for a total of 97 932 participants.Outcome measuresIndividual movements and number of movements by county of students from family home to medical school training, from medical school to foundation training and from foundation to specialty training.MethodsLeslie matrix, principal components analysis, Gini coefficient, χ2test, generalised linear models and variable selection methods were employed to explore the different facets of students’ and junior doctors’ movements from the family home to medical school and for the full pathway (from family home to specialty training).ResultsThe majority of the movements between the different stages of the full pathway were restricted to a distance of up to 50 km; although the proportion of movements changed from year-to-year, with longer movements during 2007–2008. At the individual level, ethnicity, socioeconomic class of the parent(s) and the deprivation score of the family home region were found to be the most important factors associated with the length of the movements from the family home to medical school. Similar results were found when movements were aggregated at the county level, with the addition of factors such as gender and qualification at entry (to medical school) being statistically associated with the number of new entrant students moving between counties.ConclusionOur findings show that while future doctors do not move far from their family home or training location, this pattern is not homogeneous over time. Distances are influenced by demographics, socioeconomic status and deprivation. These results may contribute in designing interventions aimed at solving the chronic problems of maldistribution and underdoctoring in the UK.
Intensive glycaemic targets in overweight and obese individuals with gestational diabetes mellitus: clinical trial protocol for the iGDM study
Authors: Scifres Christina M , Battarbee Ashley N , Feghali Maisa N , Pierce Stephanie , Edwards Rodney K , Smith Emily M , Guise David , Bhamidipalli Sruthi , Daggy Joanne , Tuuli Methodius G 
Published: March 2024

IntroductionThe prevalence of both obesity and gestational diabetes mellitus (GDM) has increased, and each is associated with adverse perinatal outcomes including fetal overgrowth, neonatal morbidity, hypertensive disorders of pregnancy and caesarean delivery. Women with GDM who are also overweight or obese have higher rates of pregnancy complications when compared with normal-weight women with GDM, which may occur in part due to suboptimal glycaemic control. The current recommendations for glycaemic targets in pregnant women with diabetes are based on limited evidence and exceed the mean fasting (70.9±7.8 mg/dL) and 1-hour postprandial (108.9±12.9 mg/dL) glucose values in pregnant individuals without diabetes. Our prior work demonstrated that the use of intensive (fasting <90 mg/dL and 1-hour postprandial <120 mg/dL) compared with standard (fasting <95 mg/dL and 1-hour postprandial <140 mg/dL) glycaemic targets resulted in improved glycaemic control without increasing the risk for hypoglycaemia in pregnant individuals with GDM, but the impact of intensive glycaemic targets on perinatal outcomes is unknown.Methods and analysisThe Intensive Glycemic Targets in Overweight and Obese Women with Gestational Diabetes Mellitus: A Multicenter Randomized Trial (iGDM Trial) is a large, pragmatic randomised clinical trial designed to investigate the impact of intensive versus standard glycaemic targets on perinatal outcomes in women with GDM who are overweight and obese. During the 5-year project period, a multidisciplinary team of investigators from five medical centres representing regions of the USA with high rates of obesity will randomise 828 overweight and obese women with GDM to either intensive or standard glycaemic targets. We will test the central hypothesis that intensive glycaemic targets will result in lower rates of neonatal composite morbidity including large for gestational age birth weight, neonatal hypoglycaemia, respiratory distress syndrome and need for phototherapy when compared with standard glycaemic targets using the intention-to-treat approach to analysis.Ethics and disseminationThe Institutional Review Board (IRB) at Indiana University School of Medicine approved this study (IRB# 11435; initial approval date 25 August 2021). We will submit the results of the trial for publication in peer-reviewed journals and presentations at international scientific meetings.Trial registration numberNCT05124808.
Neutrino charge radius and electromagnetic dipole moments via scalar and vector leptoquarks
Authors: Bolaños-Carrera A. , Guiot-Lomelí M. , Tavares-Velasco G. 
Published: March 2024

AbstractThe one-loop contribution of scalar and vector leptoquarks (LQs) to the electromagnetic properties (NEPs) of massive Dirac neutrinos is presented via an effective Lagrangian approach. For the contribution of gauge LQs to the effective neutrino charge radius defined in Bernabeu et al. (Phys Rev Lett 89:101802, 2002. https://doi.org/10.1103/PhysRevLett.89.101802 [Erratum: Phys Rev Lett 89:229902 (2002)]), we considered a Yang–Mills scenario and used the background field method for the calculation. Analytical results for nonzero neutrino mass are presented, which can be useful to obtain the NEPs of heavy neutrinos, out of which approximate expressions are obtained for light neutrinos. For the numerical analysis we concentrate on the only renormalizable scalar and vector LQ representations that do not need extra symmetries to forbid tree-level proton decay. Constraints on the parameter space consistent with current experimental data are then discussed and it is found that the scalar $${\widetilde{R}}_2$$

R
~

2

and the vector $$U_1$$

U
1

representations could yield the largest LQ contributions to the NEPs: for LQ couplings to both left- and right handed neutrinos of the order of O(1) and a LQ mass of 1.5-2 TeV, the magnetic dipole moment (MDM) of a Dirac neutrino with a mass in the eV scale can be of the order of $$10^{-9}$$

10

-
9

–$$10^{-10}$$

10

-
10

$$\mu _B$$

μ
B

, whereas its neutrino electric dipole moment (EDM) can reach values as high as $$10^{-20}$$

10

-
20

–$$10^{-19}$$

10

-
19

ecm. On the other hand, the effective NCR can reach values up to $$10^{-35}$$

10

-
35

cm$$^2$$

2

even if LQs do not couple to right-handed neutrinos, in which case the EDM vanishes and the contribution to the MDM would be negligible.
Abstract A009: Addressing obesity’s impact on the PTEN mutant endometrium
Authors: Skalski Hilary J. , Harkins Shannon K. , Arendt Amelia R. , MacLachlan Madison , Becker Katelyn , Wegener Marc , Adams Marie , Hostetter Galen , Chandler Ronald L. 
Published: March 2024

Abstract
Obesity is a rising epidemic in the United States, with approximately 50% of adult women predicted to be obese by 2030. Obesity is a risk factor for endometrial hyperplasia (EH), which is characterized by the benign overgrowth of the endometrial epithelium and is considered a precursor lesion for endometrial cancer (EC). Somatic PTEN mutations are commonly observed in EH and EC, with PTEN loss being one of the earliest mutations observed in the progression to EC. Previous obesity work in our lab utilized high-fat diet (HFD)-induced obese WT mice and found that obesity affected different cell types within the endometrium, including non-tumor prone cells. Our preliminary findings suggest that 60% HFD prolongs the estrus stage of the estrus cycle in WT mice. The aims of this study are to determine the cell-specific effects of obesity on the endometrial epithelia carrying PTEN mutations. Female PTENfl/fl; Pax8Cre/+ mutant and Pax8Cre+/+ control mice on a C57BL/6J background were fed either a 60% HFD or it’s sucrose-matched control diet (CD) for a minimum of 22 weeks. Weekly mouse and food weights were collected. Mice were tested for glucose tolerance after being on diet for at least 4.5 months. Uterus and blood were collected at estrus stage. Uteri were processed for single-cell RNA seq. PTENfl/fl; Pax8Cre/+ mice on both the HFD and CD had a diminished weight gain compared to Pax8Cre+/+ mice on the same diet. HFD-treated mice exhibited hyperphagia, weighed significantly more than the CD mice, and demonstrated glucose intolerance. H&E staining of the adipose tissue and liver revealed adipocyte hypertrophy and fatty liver infiltration in HFD mice. IHC of PTENfl/fl; Pax8Cre/+ uteri confirmed epithelial-specific loss of PTEN and displayed endometrial hyperplasia. PTENfl/fl; Pax8Cre/+ uteri had an influx of Ly6G+ neutrophils invading the endometrial epithelium compared to the Pax8Cre+/+ mice. Strikingly in PTENfl/+; Pax8Cre/+ we observe clonal loss of PTEN immunoreactivity in a subset of endometrial glands with similar phenotypic features. We propose that obesity’s impact on non-tumor cell types within the endometrium will be shaped by early genetic mutations in tumor-prone epithelia.
Citation Format: Hilary J. Skalski, Shannon K. Harkins, Amelia R. Arendt, Madison MacLachlan, Katelyn Becker, Marc Wegener, Marie Adams, Galen Hostetter, Ronald L. Chandler. Addressing obesity’s impact on the PTEN mutant endometrium [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr A009.
Abstract B006: Mutant PPP2R1A induces the expression and secretion of IGFBP2 to promote uterine serous carcinoma metastasis
Authors: Haanen Terrance James , Boock Sophie , Taylor Sarah , O'Connor Caitlin , DiFeo Analisa , Narla Goutham 
Published: March 2024

Abstract
Uterine serous carcinoma (USC) tumors demonstrate a unique aggressiveness suggesting that the primary tumor is intrinsically equipped to disseminate, metastasize and initiate tumor formation at secondary sites. Yet the drivers and pathways regulating dissemination and metastasis in USC remain incompletely understood. Previous work by our group and others identified a mutational hotspot within PPP2R1A, which encodes the Aa scaffolding subunit of protein phosphatase 2A (PP2A), a heterotrimeric serine/threonine phosphatase and known tumor suppressor. Two recurrent mutations, P179R and S256F, occur exclusively within high-grade subtypes of uterine cancer at a rate of 30-40%. We previously published that the P179R mutant drives USC tumorigenesis through the inactivation of PP2A, and genetic correction of this mutant resulted in decreased primary and metastatic tumor formation. The underlying mechanisms for these observations, however, remain unclear. To study the mechanistic basis for these observations, we generated isogenic patient-derived USC cell lines expressing the Aa – P179R and S256F mutants. Expression of these mutants enhanced the tumor-initiating capacity (TIC), a hybrid epithelial to mesenchymal (EM) plasticity profile, and the secretion of tumor-promoting factors in vitro and in vivo. Molecular analysis of these cell lines and tumors demonstrated that these mutants drove increased NF-kb phosphorylation resulting in the upregulation and secretion of the EM cytokine, IGFBP2. We found that the Aa mutant phenotype was dependent on the IGFBP2 cytokine function in vitro and in vivo. Future experiments will focus on identifying which PP2A B regulatory subunits are responsible for regulating the onset of the NF-kb transcriptional program. Cellular reprogramming through the IGFBP2-induced NF-kb signaling pathway mediated by recurrent Aa mutants may explain the intrinsically aggressive nature of USC, through enhanced dissemination and metastasis.
Citation Format: Terrance James Haanen, Sophie Boock, Sarah Taylor, Caitlin O'Connor, Analisa DiFeo, Goutham Narla. Mutant PPP2R1A induces the expression and secretion of IGFBP2 to promote uterine serous carcinoma metastasis [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr B006.
Abstract B023: The role of ribosomal protein L22 in regulating the immune landscape in mismatch repair deficient endometrial cancers
Authors: Osborne Macy L. , Atkins Hannah , Gladden Andrew B. , Broaddus Russell R. 
Published: March 2024

Abstract
The purpose of this study is to identify novel mechanisms of immune evasion in mismatch repair deficient endometrial cancers. Despite having a hypermutated phenotype that is proposed to lead to the accumulation of many neoantigens for immune recognition, our group has found that mismatch repair deficient endometrial cancers characterized by MLH1 protein loss display large variations in the number of tumors infiltrating CD8+ T cells (TILs) across different tumors. To better understand how variations in TILs arise in mismatch repair deficient endometrial cancers, we utilized human endometrial cancer samples from the UNCseq cohort. Immunohistochemistry (IHC) was used to identify expression patterns in proteins of interest across mismatch repair deficient endometrial cancers. To determine how expression patterns of proteins of interest correlate with TILs in our patient samples, Definiens Tissue Studio was utilized to quantify immunofluorescent CD8+ TILs in our mismatch repair deficient endometrial cancer cohort. Although upregulation of programmed death ligand 1 (PD-L1) expression is often cited as an explanation for low TILs, analysis of human data by our group shows that PD-L1 expression does not correlate with TIL numbers in mismatch repair deficient endometrial cancers. Interestingly, The Cancer Genome Atlas (TCGA) data reported that ribosomal protein L22 (RPL22) is mutated in ~50% of mismatch repair deficient endometrial cancers. We analyzed RPL22 by IHC and found that it was lost in 52% of our human mismatch repair deficient endometrial cancer cohort. Loss of various ribosomal proteins can alter translation efficiency of proteins critical for promoting immunosurveillance and the immune response in cancer. In our cohort, mismatch repair deficient endometrial cancers that have lost expression of RPL22 have lower numbers of CD8+ TILs. Preliminary data also show that human endometrial cancer cell lines that do not express RPL22 also do not express beta-2-microglobulin (β2M), a component of the major histocompatibility complex I (MHC-I) molecules that is necessary for neoantigen presentation to CD8+ T cells. Thus, we hypothesize that RPL22 loss in mismatch repair deficient endometrial cancers results in decreased translation of β2M and CD8+ T cell evasion. Moving forward, we speculate that RPL22 could be utilized as a predictive biomarker for immunotherapy response in mismatch repair deficient endometrial cancers.
Citation Format: Macy L. Osborne, Hannah Atkins, Andrew B. Gladden, Russell R. Broaddus. The role of ribosomal protein L22 in regulating the immune landscape in mismatch repair deficient endometrial cancers [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr B023.
Abstract B028: Epithelial-specific loss of PIK3R1 in a murine model result in endometrial hyperplasia
Authors: Harkins Shannon K. , Skalski Hilary J. , Arendt Amelia , Pavliscak Laura , Wilson Mike R. , Chandler Ronald L. 
Published: March 2024

Abstract
Somatic mutations in the phosphatidylinositol 3-kinase (PI3K) pathway occur in 84% of endometrial carcinomas (EC) and up to 68% of endometrial hyperplasia (EH). Regulation of PI3K/Akt/mTOR signaling is integral for normal endometrial function and is governed by tumor suppressor genes PTEN and PIK3R1 and proto-oncogene PIK3CA. While the actions of PTEN and PIK3CA are in direct opposition as a phosphatase and kinase, respectively, PIK3R1 regulates PI3K/Akt/mTOR signaling in two distinct ways. As the regulatory subunit of the PI3K enzyme, PIK3R1 controls the catalytic activity of PIK3CA and augments PTEN activity. Mutations or alterations in PIK3R1 are present in 33% of EC and 9% of EH, the majority of which lead to loss of PIK3R1 protein (p85a). Both loss of PTEN and PIK3R1 lead to increased proliferation through PI3K/Akt/mTOR signaling, but the structural, functional, and mechanistic implications of PIK3R1 loss in the endometrial epithelium (EE) in vivo are largely unexplored. To further interrogate the changes in the endometrium resulting from PIK3R1 loss, we have created a murine model of endometrial epithelial-specific PIK3R1 loss driven by Pax8-Cre. Mice were estrus cycle staged and sacrificed in the diestrus phase to reduce confounding variables when assessing phenotypes between genotypes. PIK3R1 loss was confirmed by immunohistochemistry (IHC). Histology and immunostaining of control and PIK3R1 knockout (KO) mice were assessed by IHC and immunofluorescence. We found that PIK3R1 loss in the EE leads to EH distinct from what is observed with PTEN loss. In contrast to the EH with atypia seen In PTEN KO mice, the EH resulting from PIKR1 loss more closely resembles EH without atypia. The endometrium of PIK3R1 KO mice is characterized by thickened luminal epithelia with jagged edges and irregularities, mild glandular crowding, and occasional nuclear atypia. PIK3R1 KO mice also showed an increase in proliferation (Ki-67) and downstream PI3K signaling (phospho-S6) in the EE. Gene expression changes occurring within the EE from PIK3R1 KO and Cre-negative control mice were also assessed by RNA-seq. In vivo genomic analyses were compared to in vitro knockdown of PIK3R1 and publicly available patient data. We found that PIK3R1 loss leads to an increase in signaling through the PI3K/Akt/mTOR and MAPK pathways. Our data show that the effect of PIK3R1 loss is sufficient to cause EH and may have shared and distinct actions from PTEN.
Citation Format: Shannon K. Harkins, Hilary J. Skalski, Amelia Arendt, Laura Pavliscak, Mike R. Wilson, Ronald L. Chandler. Epithelial-specific loss of PIK3R1 in a murine model result in endometrial hyperplasia [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr B028.