bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic impairment of folate metabolism regulates cortical interneurons and social behavior
Authors: Sadigurschi Noa , Scrift Gilad , Hirrlinger Johannes , Golan Hava M. 
Published: June 2023

IntroductionThe implications of folate deficiency in neuropsychiatric disorders were demonstrated in numerous studies. Genetic deficiency in a key folate metabolism enzyme, MTHFR, is an example of the interaction between genetic and environmental risk factors: the maternal MTHFR deficiency governs in-utero nutrient availability, and the embryo’s Mthfr genotype influences its ability to metabolize folates. Here, we explore how the maternal and offspring Mthfr genotypes affect cortical interneuron densities and distributions, mouse social outcome, and the relation of the different interneuron patterns to cortical excitability.MethodsTwo experiments were conducted to examine the effects of maternal and offspring Mthfr-KO heterozygosity. Mice were tested for direct social interactions (DSIs), repetitive behavior and cortical laminar distribution of interneuron populations expressing glutamate-decarboxylase-65, parvalbumin and somatostatin. Susceptibility to seizure was tested by exposure to pentylenetetrazole (PTZ).ResultsMaternal Mthfr+/− genotype was associated with suppressed social activities and reduced interneuron densities in all layers of the retrosplenial cortex (RSC). Somatostatin density and the somatostatin/parvalbumin ratio in the RSC and frontal cortex positively correlated with social behavior in the mice. An interaction between maternal and offspring Mthfr genotypes resulted in higher susceptibility of wild-type offspring to PTZ induced seizure.DiscussionMaternal folate metabolism was shown to be critical to interneuron ontogenesis. Our results demonstrate that interneurons have a specific susceptibility to folate deficiency that may mediate folate’s involvement in neuropsychiatric disease. The relations between cortical somatostatin interneuron patterns and social behavior highlight this subpopulation of interneurons as a target for further research.
Functional roles of two novel P450 genes in the adaptability of Conogethes punctiferalis to three commonly used pesticides
Authors: Yuan Xingxing , Li Han , Guo Xianru , Jiang He , Zhang Qi , Zhang Lijuan , Wang Gaoping , Li Weizheng , Zhao Man 
Published: June 2023

Introduction: Insect cytochrome P450 (CYP450) genes play important roles in the detoxification and metabolism of xenobiotics, such as plant allelochemicals, mycotoxins and pesticides. The polyphagous Conogethes punctiferalis is a serious economic pest of fruit trees and agricultural crops, and it shows high adaptability to different living environments.Methods: The two novel P450 genes CYP6CV1 and CYP6AB51 were identified and characterized. Quantitative real-time PCR (qRT-PCR) technology was used to study the expression patterns of the two target genes in different larval developmental stages and tissues of C. punctiferalis. Furthermore, RNA interference (RNAi) technology was used to study the potential functions of the two P450 genes by treating RNAi-silenced larvae with three commonly used pesticides.Results: The CYP6CV1 and CYP6AB51 genes were expressed throughout various C. punctiferalis larval stages and in different tissues. Their expression levels increased along with larval development, and expression levels of the two target genes in the midgut were significantly higher than in other tissues. The toxicity bioassay results showed that the LC50 values of chlorantraniliprole, emamectin benzoate and lambda-cyhalothrin on C. punctiferalis larvae were 0.2028 μg/g, 0.0683 μg/g and 0.6110 mg/L, respectively. After treating with different concentrations of chlorantraniliprole, emamectin benzoate and lambda-cyhalothrin (LC10, LC30, LC50), independently, the relative expressions of the two genes CYP6CV1 and CYP6AB51 were significantly induced. After the dsRNA injection, the expression profiles of the two CYP genes were reduced 72.91% and 70.94%, respectively, and the mortality rates of the larvae significantly increased when treated with the three insecticides independently at LC10 values.Discussion: In the summary, after interfering with the CYP6CV1 and CYP6AB51 in C. punctiferalis, respectively, the sensitivity of C. punctiferalis to chlorantraniliprole, emamectin benzoate and lambda-cyhalothrin was significantly increased, indicating that the two CYP6 genes were responsible for the adaptability of C. punctiferalis to the three chemical insecticides in C. punctiferalis. The results from this study demonstrated that CYP6CV1 and CYP6AB51 in C. punctiferalis play crucial roles in the detoxification of chlorantraniliprole, emamectin benzoate and lambda-cyhalothrin.
Discovering compassion in medical training: a qualitative study with curriculum leaders, educators, and learners
Authors: Lane Charles B. , Brauer Erin , Mascaro Jennifer S. 
Published: June 2023

BackgroundCompassion is considered a fundamental human capacity instrumental to the creation of medicine and for patient-centered practice and innovations in healthcare. However, instead of nurturing and cultivating institutional compassion, many healthcare providers cite the health system itself as a direct barrier to standard care. The trend of compassion depletion begins with medical students and is often attributed to the culture of undergraduate medical training, where students experience an increased risk of depression, substance use, and suicidality.ObjectivesThis qualitative study aims to develop a more comprehensive understanding of compassion as it relates to undergraduate medical education. We used focus groups with key stakeholders in medical education to characterize beliefs about the nature of compassion and to identify perceived barriers and facilitators to compassion within their daily responsibilities as educators and students.MethodsResearchers conducted a series of virtual (Zoom) focus groups with stakeholders: Students (N = 14), Small Group Advisors (N = 11), and Medical Curriculum Leaders (N = 4). Transcripts were thematically analyzed using MAXQDA software.ResultsStudy participants described compassion as being more than empathy, demanding action, and capable of being cultivated. Stakeholders identified self-care, life experiences, and role models as facilitators. The consistently identified barriers to compassion were time constraints, culture, and burnout. Both medical students and those training them agreed on a general definition of compassion and that there are ways to cultivate more of it in their daily professional lives. They also agreed that undergraduate medical education – and the healthcare culture at large – does not deliberately foster compassion and may be directly contributing to its degradation by the content and pedagogies emphasized, the high rates of burnout and futility, and the overwhelming time constraints.DiscussionIntentional instruction in and cultivation of compassion during undergraduate medical education could provide a critical first step for undergirding the professional culture of healthcare with more resilience and warm-hearted concern. Our finding that medical students and those training them agree about what compassion is and that there are specific and actionable ways to cultivate more of it in their professional lives highlights key changes that will promote a more compassionate training environment conducive to the experience and expression of compassion.
Right inferior frontal gyrus theta-burst stimulation reduces smoking behaviors and strengthens fronto-striatal-limbic resting-state functional connectivity: a randomized crossover trial
Authors: Upton Spencer , Brown Alexander A. , Golzy Mojgan , Garland Eric L. , Froeliger Brett 
Published: June 2023

IntroductionFunctional and anatomical irregularities in the right inferior frontal gyrus (rIFG), a ventrolateral prefrontal region that mediates top-down inhibitory control over prepotent behavioral responding, are implicated in the ongoing maintenance of nicotine dependence (ND). However, there is little research on the effects of neuromodulation of the rIFG on smoking behavior, inhibitory control, and resting-state functional connectivity (rsFC) among individuals with ND.MethodsIn this double-blind, crossover, theta-burst stimulation (TBS) study, adults with ND (N = 31; female: n = 15) completed a baseline session and were then randomized to two counterbalanced sessions of functionally neuronavigated TBS to the rIFG: continuous TBS (cTBS) on 1 day and intermittent TBS (iTBS) on another. Differences in cigarette cravings, smoking, and fronto-striatal-limbic rsFC were assessed.ResultsRelative to baseline, cTBS significantly reduced appetitive and withdrawal cravings immediately after treatment. The effects of cTBS on withdrawal craving persisted for 24 h, as well as produced a reduction in smoking. Furthermore, cTBS significantly strengthened rsFC between the rIFG pars opercularis and subcallosal cingulate (fronto-striatal circuit), and between the rIFG pars opercularis and the right posterior parahippocampal gyrus (fronto-limbic circuit). At post-24 h, cTBS-induced increase in fronto-striatal rsFC was significantly associated with less appetitive craving, while the increase in fronto-limbic rsFC was significantly associated with less withdrawal craving and smoking.DiscussionThese findings warrant further investigation into the potential value of rIFG cTBS to attenuate smoking behavior among individuals with ND.
Binocular rivalry in autistic and socially anxious adults
Authors: Kamhout Sarah , Olivier Joshua M. , Morris Jarom , Brimhall Hayden R. , Black Braeden L. , Gabrielsen Terisa P. , South Mikle , Lundwall Rebecca A. , Nielsen Jared A. 
Published: June 2023

BackgroundSocial anxiousness is a pervasive symptom in both social anxiety disorder and autism spectrum conditions. Binocular rivalry, which occurs when different images are presented to each eye, has been used to explore how visual and cognitive processing differs across various clinical diagnoses. Previous studies have separately explored whether individuals with autism or anxiety experience binocular rivalry in ways that are different from neurotypical individuals.MethodsWe applied rivalry paradigms that are similar to those used in previous studies of autism and general anxiety to individuals experiencing symptoms of social anxiousness at clinical or subclinical levels. We also incorporated rivalrous stimuli featuring neutral and emotional facial valances to explore potential overlap of social processing components in social anxiety and autism.ResultsWe hypothesized that higher levels of social anxiousness would increase binocular rivalry switch rates and that higher levels of autistic traits would decrease switch rates. However, stimulus condition did not affect switch rates in either diagnostic group, and switch rate was not significantly predictive of dimensional measures of either autism or social anxiety.DiscussionThis may suggest a common mechanism for atypical visual cognition styles previously associated with social anxiety and autism. Alternatively, differences in switch rates may only emerge at higher trait levels than reported by the participants in our studies. Furthermore, these findings may be influenced by sex differences in our unique sample.
White matter microstructural perturbations after total sleep deprivation in depression
Authors: Taraku Brandon , Zavaliangos-Petropulu Artemis , Loureiro Joana R. , Al-Sharif Noor B. , Kubicki Antoni , Joshi Shantanu H. , Woods Roger P. , Espinoza Randall , Narr Katherine L. , Sahib Ashish K. 
Published: June 2023

BackgroundTotal sleep deprivation (TSD) transiently reverses depressive symptoms in a majority of patients with depression. How TSD modulates diffusion tensor imaging (DTI) measures of white matter (WM) microstructure, which may be linked with TSD’s rapid antidepressant effects, remains uncharacterized.MethodsPatients with depression (N = 48, mean age = 33, 26 women) completed diffusion-weighted imaging and Hamilton Depression Rating (HDRS) and rumination scales before and after &gt;24 h of TSD. Healthy controls (HC) (N = 53, 23 women) completed the same assessments at baseline, and after receiving TSD in a subset of HCs (N = 15). Tract based spatial statistics (TBSS) investigated voxelwise changes in fractional anisotropy (FA) across major WM pathways pre-to-post TSD in patients and HCs and between patients and HCs at baseline. Post hoc analyses tested for TSD effects for other diffusion metrics, and the relationships between change in diffusion measures with change in mood and rumination symptoms.ResultsSignificant improvements in mood and rumination occurred in patients with depression (both p &lt; 0.001), but not in HCs following TSD. Patients showed significant (p &lt; 0.05, corrected) decreases in FA values in multiple WM tracts, including the body of the corpus callosum and anterior corona radiata post-TSD. Significant voxel-level changes in FA were not observed in HCs who received TSD (p &gt; 0.05). However, differential effects of TSD between HCs and patients were found in the superior corona radiata, frontal WM and the posterior thalamic radiation (p &lt; 0.05, corrected). A significant (p &lt; 0.05) association between change in FA and axial diffusivity within the right superior corona radiata and improvement in rumination was found post-TSD in patients.ConclusionTotal sleep deprivation leads to rapid microstructural changes in WM pathways in patients with depression that are distinct from WM changes associated with TSD observed in HCs. WM tracts including the superior corona radiata and posterior thalamic radiation could be potential biomarkers of the rapid therapeutic effects of TSD. Changes in superior corona radiata FA, in particular, may relate to improvements in maladaptive rumination.
Mapping the disparities in intimate partner violence prevalence and determinants across Sub-Saharan Africa
Authors: Mossie Tilahun B. , Mekonnen Fenta Haile , Tadesse Meseret , Tadele Animut 
Published: June 2023

ObjectiveThis study aimed to map disparities in prevalence and associated factors across countries in Sub-Saharan Africa.MethodsWe used National Demographic and Health Survey (DHS) data from 26 countries in the region with 114,340 participants. Women and girls in the reproductive age group of 15 to 49 years were included in the study. To map disparities across countries and their provinces, we employed the kriging interpolation technique. We used STATA for data management.ResultThe prevalence of physical, emotional and sexual IPV in Sub-Saharan Africa was 30.58, 30.22, and 12.6% respectively, and at least one form of IPV was 42.62%. Disparities were observed across the countries and provinces in each country. Younger age, secondary-level education and above, moderate participation in decision-making, not working out of home, not afraid of the spouse, rich (wealth index), not having a child, high maternal literacy, and rural residence relatively decreased the odds of IPV. The husbands’ lower education, alcohol consumption, and high controlling behavior increased the probability of IPV.ConclusionThe prevalence of Intimate Partner Violence in Sub-Saharan Africa is the highest in the world, a signal that the global agenda to end all forms of violence against women will be difficult to achieve. There is a large gap across countries and provinces in each country. Area-specific intervention packages that focus on modifiable factors should be strengthened.
Therapeutic Drug Monitoring of Mycophenolic Acid Identifies Kidney Transplant Recipients Responsive to Two SARS-CoV-2 mRNA Vaccine Doses
Authors: von Moos Seraina , Rho Elena , Dammann Maria , Kokkonen Sanna Marjaana , Mueller Thomas F. , Schachtner Thomas 
Published: June 2023

Immune-responsiveness to SARS-CoV-2 mRNA vaccination is reduced in kidney transplant recipients (KTRs). Previous reports point to a role of mycophenolic acid (MPA). Our observational cohort study included all KTRs at University Hospital Zurich receiving two SARS-CoV-2 mRNA vaccine doses more than 6 months post-transplantation, who were assessed by measuring anti-spike immunoglobulin G (IgG). We applied principles of therapeutic drug monitoring (TDM) to correlate MPA exposure and lymphocyte counts with SARS-CoV-2 IgG. MPA trough levels differ largely among KTRs with a median of 3.1 mg/L (range 0.7–9.5 mg/L). 34 of 84 KTRs (40%) developed positive SARS-CoV-2 IgG after two vaccine doses. KTRs who developed positive SARS-CoV-2 IgG showed significantly higher eGFR (p &lt; 0.001), lower MPA trough levels (p &lt; 0.001) and higher CD19+ lymphocytes (p &lt; 0.001). MPA trough levels &lt;2.5 mg/l and CD19+ lymphocytes &gt;40/μl identify KTRs with seroconversion. Upon logistic regression, MPA trough levels &lt;2.5 mg/L were associated with a 7-fold (CI 95%: 1.589–29.934) and ciclosporin use with a 6-fold (CI 95%: 1.148–30.853) increase in the odds of seroconversion. Our study indicates that immune-responsiveness to SARS-CoV-2 mRNA vaccines correlates with MPA exposure measured by MPA trough level but argues against a class effect of MPA. TDM-guided MPA dosing may be a strategy to increase seroconversion rate.
Investigation of the Seasonal Variation in Fat Patterning of Ellisras Rural Children and Adolescents, in the Limpopo Province, South Africa
Authors: Mulaudzi Lusani , Mkhatshwa Thandiwe N. , Makhubedu Mankopodi M. , Matshipi Moloko , Lebelo Sogolo L. , Monyeki Kotsedi D. 
Published: June 2023

An increase in childhood obesity has become a global concern since childhood obesity often leads to adulthood obesity. This study aimed to investigate whether there is seasonal variation in fat patterning, and whether fat patterning is associated with seasons among the Ellisras population aged 5–15 years. A total of 1986 children and adolescents (1034 boys and 952 girls) aged 5–15 enrolled in this cross-sectional study. Skinfold measurements were obtained using standard procedures. Obesity prevalence was determined using frequency analysis. The correlation between obesity and two seasons was tested using multinomial regression analysis. The results showed that girls aged 11–15 years had significantly (p ≤ 0.03) larger median fat variables (triceps, biceps, and suprailiac) in spring compared to autumn. The prevalence of obesity ranged from 3–11% with boys being more obese (4–11%) than girls (3–7%) aged 5–15. Regression analysis showed a negative significant (p ≤ 0.001) correlation between autumn and obesity by the subscapular/(subscapular+triceps) (SST) ratio, both unadjusted −2.991 (95%CI −3.233:−2.803) and adjusted −2.897 (95% CI −4.331:−1.629). The findings of the study showed that there was seasonal variation in fat patterning among boys and girls in the Ellisras population and that fat patterning is associated with seasons.
Exploring why European primary care physicians sometimes do not think of, or act on, a possible cancer diagnosis. A qualitative study
Authors: Hajdarevic Senada , Högberg Cecilia , Marzo-Castillejo Mercè , Siliņa Vija , Sawicka-Powierza Jolanta , Esteva Magadalena , Koskela Tuomas , Petek Davorina , Contreras-Martos Sara , Mangione Marcello , Ožvačić Adžić Zlata , Asenova Radost , Gašparović Babić Svjetlana , Brekke Mette , Buczkowski Krzysztof , Buono Nicola , Çifçili Saliha Serap , Dinant Geert-Jan , Doorn Babette , Hoffman Robert D , Kuodza George , Murchie Peter , Pilv Liina , Puia Aida , Rapalavicius Aurimas , Smyrnakis Emmanouil , Weltermann Birgitta , Harris Michael 
Published: June 2023

BackgroundWhile primary care physicians (PCPs) play a key role in cancer detection, they can find cancer diagnosis challenging, and some patients have considerable delays between presentation and onward referral.AimTo explore European PCPs’ experiences and views on cases where they considered that they had been slow to think of, or act on, a possible cancer diagnosis.Design & settingA multicentre European qualitative study, based on an online survey with open-ended questions, asking PCPs for their narratives about cases when they had missed a diagnosis of cancer.MethodUsing maximum variation sampling, PCPs in 23 European countries were asked to describe what happened in a case where they were slow to think of a cancer diagnosis, and for their views on why it happened. Thematic analysis was used to analyse the data.ResultsA total of 158 PCPs completed the questionnaire. The main themes were as follows: patients’ descriptions did not suggest cancer; distracting factors reduced PCPs’ cancer suspicions; patients’ hesitancy delayed the diagnosis; system factors not facilitating timely diagnosis; PCPs felt that they had acted wrongly; and problems with communicating adequately.ConclusionThe study identified six overarching themes that need to be addressed. Doing so should reduce morbidity and mortality in the small proportion of patients who have a significant, avoidable delay in their cancer diagnosis. The ‘Swiss cheese’ model of accident causation showed how the themes related to each other.
ANALISIS KARAKTERISTIK STRUKTUR MATERIAL SWING ARM TERHADAP RESPON GETARAN ACAK PADA SEPEDA MOTOR HONDA SUPRA X 125R MENGGUNAKAN METODE ELEMEN HINGGA
Authors: Winarno Ilham , Marliana Eka 
Published: June 2023

Penelitian ini dilakukan dengan tujuan untuk mengetahui karakteristik material swing arm pada sepeda motor Honda Supra X 125R dalam kondisi pembebanan dinamis. Analisa dinamika dilakukan untuk mengetahui nilai frekuensi natural dan displacement maksimum dalam modal analysis. Metode yang digunakan dalam penelitian ini adalah simulasi FEM dengan membuat pemodelan 3D menggunakan software Autodesk Inventor. Selanjutnya model disimulasikan menggunakan software Ansys Workbench. Hasil simulasi FEM menunjukkan material mild steel yang paling dominan memiliki respon paling baik adalah jenis SS400, dengan nilai equivalent stress (von mises) maksimum sebesar 16,601 MPa dan displacement maksimumnya sebesar 2,9109e–002 mm. Hasil modal analysis menunjukkan material SS400 memiliki respon yang paling dominan, dengan rata-rata frekuensi natural paling tinggi untuk mode shapes 2, 4 dan 5, serta memiliki nilai displacement paling kecil untuk mode shapes 1, 3, dan 4.
DESAIN OPTIMAL TERAS SMALL MODULAR MOLTEN SALT REACTOR (SM-MSR) SEBAGAI SISTROPULSI KAPAL PERANG EM P
Authors: Prabudi Cahyo Ridho , Aritonang Sovian , Setiadipura Topan 
Published: June 2023

Sebagai salah satu upaya untuk peningkatan daya tahan kapal perang dapat dilakukan dengan menggunakan sistem propulsi nuklir sebagai sumber tenaga penggerak. Penggunaan energy nuklir sebagai sitem penggerak memiliki nilai efektifitas yang tinggi jika dibandingkan dengan minyak alam. Salah satu contoh model reaktor yang dapat digunakan pada kapal perang yaitu Molten Salt Reactor (MSR). MSR yang ada saat ini masih berukuran sangat besar. Oleh karena itu dalam penelitian ini akan dilakukan desain optimal teras Small Modular Molten Salt Reactor (SM-MSR) yang diseuaikan dengan luas permukaan kapal perang. Dari simulasi dan optimasi yang dilakukan dengan software MCNP dengan parameter yang menjadi acuan adalah kritikalitas. Diperoleh komposisi material bahan bakar yang optimal adalah dengan 1% Li dan 2% U-235 dengan geometri desain optimal memiliki jari-jari pin cell core 0.8 cm, jari-jari pin cell blanket 2.6 cm dan tinggi core 160 cm. Desain awal SM-MSR pada penelitian ini memiliki koefisien reaktivitas void yang negative.