bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computational pharmacogenotype extraction from clinical next-generation sequencing
Authors: Shugg Tyler , Ly Reynold C. , Osei Wilberforce , Rowe Elizabeth J. , Granfield Caitlin A. , Lynnes Ty C. , Medeiros Elizabeth B. , Hodge Jennelle C. , Breman Amy M. , Schneider Bryan P. , Sahinalp S. Cenk , Numanagić Ibrahim , Salisbury Benjamin A. , Bray Steven M. , Ratcliff Ryan , Skaar Todd C. 
Published: July 2023

BackgroundNext-generation sequencing (NGS), including whole genome sequencing (WGS) and whole exome sequencing (WES), is increasingly being used for clinic care. While NGS data have the potential to be repurposed to support clinical pharmacogenomics (PGx), current computational approaches have not been widely validated using clinical data. In this study, we assessed the accuracy of the Aldy computational method to extract PGx genotypes from WGS and WES data for 14 and 13 major pharmacogenes, respectively.MethodsGermline DNA was isolated from whole blood samples collected for 264 patients seen at our institutional molecular solid tumor board. DNA was used for panel-based genotyping within our institutional Clinical Laboratory Improvement Amendments- (CLIA-) certified PGx laboratory. DNA was also sent to other CLIA-certified commercial laboratories for clinical WGS or WES. Aldy v3.3 and v4.4 were used to extract PGx genotypes from these NGS data, and results were compared to the panel-based genotyping reference standard that contained 45 star allele-defining variants within CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, CYP4F2, DPYD, G6PD, NUDT15, SLCO1B1, TPMT, and VKORC1.ResultsMean WGS read depth was &gt;30x for all variant regions except for G6PD (average read depth was 29 reads), and mean WES read depth was &gt;30x for all variant regions. For 94 patients with WGS, Aldy v3.3 diplotype calls were concordant with those from the genotyping reference standard in 99.5% of cases when excluding diplotypes with additional major star alleles not tested by targeted genotyping, ambiguous phasing, and CYP2D6 hybrid alleles. Aldy v3.3 identified 15 additional clinically actionable star alleles not covered by genotyping within CYP2B6, CYP2C19, DPYD, SLCO1B1, and NUDT15. Within the WGS cohort, Aldy v4.4 diplotype calls were concordant with those from genotyping in 99.7% of cases. When excluding patients with CYP2D6 copy number variation, all Aldy v4.4 diplotype calls except for one CYP3A4 diplotype call were concordant with genotyping for 161 patients in the WES cohort.ConclusionAldy v3.3 and v4.4 called diplotypes for major pharmacogenes from clinical WES and WGS data with &gt;99% accuracy. These findings support the use of Aldy to repurpose clinical NGS data to inform clinical PGx.
Tightened social distancing measures and increased violence during the COVID-19 pandemic in South Korea
Authors: Kim Bookyoung , Son Kyung-Bok 
Published: July 2023

IntroductionIn 2020, the South Korean government introduced social distancing measures, varied by region, to address the pandemic. We captured variations in social distancing measures among regions in South Korea and investigated the association between the stringency of measures and the increased incidence of violence.MethodsIncidence reports from calls to violence hotlines, including school and domestic violence and sexual harassment, from 2016 to 2021 were retrieved. The regional per capita incidence rates for each violence hotlines were calculated. Difference-in-difference design with fixed effects was used to elucidate different trends in the incidence rate of violence between regions with stringent social distancing measures and regions with looser measures.ResultsSocial distancing measures led to a decreased incidence rate of school violence and an increased incidence rate of domestic violence and sexual harassment. Different trends in the incidence of violence were noted between regions with strict social distancing measures and regions with more lenient measures. Tightened measures caused surges in domestic violence and sexual harassment.ConclusionSocial distancing measures have been an inevitable mitigation strategy against virus transmission throughout the pandemic. However, women residing in tightened social distancing measures, in particular urban areas, need more support against domestic violence.
Serum alkaline phosphatase was independently associated with depression in patients with cerebrovascular disease
Authors: Tao Xi , Yang Chen , He Juan , Liu Qianrong , Wu Siyuan , Tang Wenjing , Wang Jia 
Published: July 2023

Background and purposeBlood markers have important value in the diagnosis of depressive disorders. Serum alkaline phosphatase (ALP) not only predicts stroke recurrence and poor functional prognosis in cerebrovascular disease (CVD) patients but also increases significantly in middle-aged women with depression. Thus, it has not been reported whether serum ALP is associated with the development of depression and/or vascular depression (VDe) in CVD patients.MethodsThis was a cross-sectional study of 353 CVD patients (stroke patients, n = 291; cerebral small vessel disease (CSVD) patients, n = 62). Baseline demographic information, fasting blood markers (such as blood counts, liver function, kidney function and lipids), and brain CT/MRI scans were collected. CVD patients were divided into non-depression, suspected vascular depression (SVD), and positive vascular depression (PVD) groups according to their Hamilton Rating Scale for Depression (HAMD) scores. Univariate analysis of baseline data, blood markers, and the prevalence of lesions (&gt; 1.5 cm) was performed. Subsequently, the diagnostic performance of the univariate and combined variables for SVD and PVD was analyzed using binary logistic regression. The diagnostic value of the multivariate model for VDe was analyzed by ordinal logistic regression.Results(1) Serum ALP (p = 0.003) and hypersensitive C-reactive protein (hs-CRP, p = 0.001) concentrations increased as HAMD scores increased, and the prevalence of brain atrophy (p = 0.016) and lesions in the basal ganglia (p = 0.001) and parietal (p = 0.001), temporal (p = 0.002), and frontal lobes (p = 0.003) also increased, whereas the concentrations of hemoglobin (Hb, p = 0.003), cholinesterase (ChE, p = 0.001), and high-density lipoprotein cholesterol (HDL-C, p = 0.005) declined. Among these variables, hs-CRP (r = 0.218, p &lt; 0.001) had a weak positively association with HAMD scores, and ChE (r = −0.226, p &lt; 0.001) had a weak negative association. (2) The combination of Hb, hs-CRP, ChE, ALP, and HDL-C improved diagnostic performance for VDe [AUC = 0.775, 95% CI (0.706, 0.844), p &lt; 0.001]. (3) Hb (OR = 0.986, p = 0.049), ChE (OR = 0.999, p = 0.020), ALP (OR = 1.017, p = 0.003), and basal ganglia lesions (OR = 2.197, p &lt; 0.001) were important factors impacting VDe development. After adjusting for Hb, hs-CRP, ChE, HDL-C, lesions in the above mentioned four locations, sex, age and the prevalence of CSVD and brain atrophy, ALP [OR = 1.016, 95% CI (1.005, 1.027), p = 0.004] was independently associated with VDe.ConclusionHb, hs-CRP, ChE, ALP, and HDL-C concentrations are potential blood markers of depression in CVD patients and, when combined, may improve diagnostic performance for VDe. Serum ALP was independently associated with VDe in patients with CVD.
Mentalization based treatment of youth on the psychotic spectrum: clinical profiles and outcomes for youth in the ECID
Authors: Dangerfield Mark , Brotnow Decker Line 
Published: July 2023

IntroductionEarly intervention may significantly improve the prognosis associated with psychotic disorders in adulthood.MethodsThe present study examined the acceptability and effectiveness of a standalone intensive, in-home, mentalization-based treatment (MBT) for extremely high-risk, non-help-seeking youth on the psychotic spectrum [Equipo Clínico de Intervención a Domicilio (ECID), Home Intervention Clinical Team].ResultsDespite previously being unable to participate in treatment, more than 90% of youth engaged and those on the psychotic spectrum demonstrated slightly higher engagement than the general high-risk group (95% and 85%, respectively, X1 = 4.218, p = 0.049). Generalized estimating equation (GEE) models revealed no main group effect on the likelihood of reengaging with school over the first 12 months of treatment (X1 = 1.015, p = 0.314) when controlling for the duration of school absenteeism at intake. Overall, the percentage of school engagement rose from 12 to 55 over this period, more than 40% of the total sample experienced clinically reliable change and an additional 50% appeared clinically stable. No statistically significant difference was observed between the groups in the average change in HoNOSCA total severity score (X1 = 0.249, p = 0.618) or the distribution of youth into categories of clinical change during the first year of treatment (X1 = 0.068, p = 0.795).DiscussionThe present findings suggest that a mentalization based intervention may be able to engage extremely high-risk youth in treatment and have clinically meaningful impact on symptom severity and functioning after 12 months.
A comparison of bioelectrical impedance analysis and air displacement plethysmography to assess body composition in children
Authors: Chen Fangfang , Wu Lijun , Chen Yiren , Wang Jing , Liu Junting , Huang Guimin , Hou Dongqing , Liao Zijun , Zhang Ting , Xie Xianghui , Liu Gongshu 
Published: July 2023

BackgroundAccurate assessment of body composition (BC) is important to investigate the development of childhood obesity. A bioelectrical impedance analysis (BIA) device is portable and inexpensive compared with air displacement plethysmography (ADP) for the assessment of BC and is widely used in children. However, studies of the effectiveness of BIA are few and present different results, especially in pediatric populations. The aim of this study was to evaluate the agreement between BIA and ADP for estimating BC.MethodsThe BC of 981 Chinese children (3–5 years) was measured using the BIA device (SeeHigher BAS-H, China) and ADP (BOD POD).ResultsOur results showed that BIA underestimated fat mass (FM) and overestimated fat-free mass (FFM) in normal weight children (P &lt; 0.05), but the opposite trend was shown in children with obesity (P &lt; 0.05). The agreement between FM and FFM measured by the two methods was strong (CCC &gt; 0.80). The linear regression equation of 5-year-old children was constructed.ConclusionThe SeeHigher BAS-H multi-frequency BIA device is a valid device to evaluate BC in Chinese preschool children compared with ADP (BOD POD), especially in 5-year-old children or children with obesity. Further research is needed to standardize the assessment of BC in children.
Serum acylcarnitines levels as a potential predictor for gestational diabetes: a systematic review and meta-analysis
Authors: Luo Hairong , Zhu Zanlei 
Published: July 2023

AimsGestational diabetes mellitus (GDM) stands as a prevalent obstetric complication bearing consequential health implications for both mother and child. While existing studies have probed the alterations in acylcarnitines during GDM, an updated systematic meta-analysis is needed to consolidate these findings. Hence, this study endeavours to furnish a comprehensive systematic review and meta-analysis delineating the association between acylcarnitines and GDM, aimed at bolstering diagnostic accuracy and preventive measures against GDM.MethodsTo extract pertinent studies for this meta-analysis, we meticulously scoured databases such as PubMed, Web of Science, Embase, and Cochrane Library up until May 2023. The inclusion criteria were studies contrasting plasma metabolomics between two cohorts: women diagnosed with GDM and normoglycemic pregnant women. Weighted mean differences (SMDs) and 95% confidence intervals (CIs) were calculated using random-effects models. The I2 index was employed to quantify heterogeneity amongst the studies. All meta-analyses were executed using Stata version 12.0.ResultsOur meta-analysis included eight studies encompassing 878 pregnant women. The analysis disclosed that relative to normoglycemic pregnant women, women with GDM exhibited significantly elevated levels of Short-Chain Acylcarnitines (SCAC) (SMD: 0.19, 95% CI: 0.02–0.36, I2 = 71.3%). No substantial difference was discerned in fasting total carnitine levels (SMD: 0.15, 95% CI: −0.16–0.31, I2 = 68.2%), medium-chain acylcarnitines (MCAC) (SMD: 0.08, 95% CI: −0.02–0.36, I2 = 79.0%), and long-chain acylcarnitines (LCAC) (SMD: 0.04, 95% CI: −0.06–0.15, I2 = 0%). Neither funnel plot assessment nor Egger’s regression and Begg’s rank correlation tests indicated any evidence of publication bias.ConclusionOur meta-analysis suggests that elevated levels of SCAC may heighten the risk of GDM onset. Given GDM’s deleterious impact on pregnant women and their offspring, these findings underscore the clinical imperative of managing this condition. Early surveillance of plasma metabolomic profiles, particularly serum acylcarnitine concentrations, may equip clinicians with a valuable tool for timely diagnosis and intervention in GDM.
Exposure to Dichlorvos pesticide alters the morphology of and lipid metabolism in the ventral prostate of rats
Authors: Quintino-Ottonicar Giovanna Galo , Silva Laura Ribeiro da , Maria Vinícius Luís Rocha da Silva , Pizzo Eleonora Malavolta , Santana Ana Clara Pacheco de , Lenharo Naíra Ruiz , Pinho Cristiane Figueiredo , Pereira Sergio 
Published: July 2023

Organophosphate pesticides are widely used in agriculture, leading to soil, water, and food contamination. Among these compounds is Dichlorvos [O,O-dimethyl O-(2,2-dichlorovinyl)phosphate, DDVP], which is listed as a highly toxic compound by the Environmental Protection Agency and World Health Organization. Exposure to DDVP can result in nervous, respiratory, hepatic, and reproductive abnormalities, in addition to endocrine disrupting, mutagenic, and carcinogenic effects. Little is known about the impacts of DDVP on the reprogramming of lipid metabolism, which is also associated with the development and progression of cancer, since the tumor cells need to recruit, capture, and use fatty acids to compose their building membranes. This study aimed to evaluate the influence of the pesticide DDVP on lipid metabolism in the prostate, after chemical induction by the carcinogen N-methyl-N-nitrosourea (MNU). For this, 32 Fischer rats aged 90 days were randomly divided into four experimental groups: Control, DDVP, MNU, and MNU + DDVP. The MNU and MNU + DDVP groups underwent chemical induction with MNU (15 mg/kg) and the DDVP and MNU + DDVP groups received a diet supplemented with DDVP (10 mg/kg). Histopathological analyses of the rat ventral prostate showed 100% incidence of epithelial hyperplasia in the MNU and MNU + DDVP groups. This finding was accompanied by an increase of the epithelial compartment in the MNU + DDVP group. Immunolocalization of important proteins linked to lipid metabolism has been established. In the MNU + DDVP group, Western blotting analyses pointed out an increased expression of the protein LIMP II (Lysosomal Integral Membrane Protein-II), which is correlated with the capture and distribution of lipids in tumor cells. Together, these results indicate that the association of a low dose of DDVP with MNU was able to promote alterations in the morphology and lipid metabolism of the rat ventral prostate, which may be related to tumor progression in this organ.
Investigation of Load Environment and Bending Load Capacities of Aged Prestressed Concrete Sleepers
Authors: Watanabe Tsutomu , Goto Keiichi , Minoura Shintaro 
Published: July 2023

In this study, field measurements of the bending moments of prestressed concrete (PC) sleepers installed on commercial lines were obtained, and numerical analyses to identify the effects of different parameters on their bending moments were conducted. The bending load capacities of aged PC sleepers collected from commercial lines via bending tests were also determined. According to the field measurement results of the wheel loads and bending moments of the PC sleepers, the measured values were smaller than the design values. In addition, neither the wheel load nor the bending moment depended on train speed. The numerical analysis results indicate that the positive bending moment at the rail seat section is unlikely to exceed the design decompression moment (DDM). However, the negative bending moment at the center section may exceed the DDM if center support is provided with a reduced spring constant under the rail (the “hanging” rail seat section). In addition, the bending moment increased with the rail surface roughness, so the rail should be kept smooth. Moreover, the results of the JIS E 1201 bending tests on the aged PC sleepers showed that the crack generation load and ultimate load decreased gradually with increases in age and passing tonnage. However, all samples satisfied the JIS standard values. Furthermore, the bending moments generated in the PC sleepers during train passage were considerably smaller than the crack generation load and ultimate load during the bending test. Thus, Japanese PC sleepers aged more than 50 years currently satisfy the standard flexural fracture values specified by the JIS, and safety is not immediately compromised.
Specific Features of Formation of Electron and Hole Trapping Centers in Irradiated CaSO4-Mn and BaSO4-Mn
Authors: Nurakhmetov Turlybek. N. , Alibay Temirulan. T. , Zhangylyssov Keleshek. B. , Daurenbekov Dulat. H. , Zhunusbekov Amangeldy. M. , Kainarbay Aset. Zh. , Sadykova Batsaiy. M. , Tolekov Doszhan. A. , Shamiyeva Raushan. K. 
Published: July 2023

Spectroscopic and thermoactivation methods were used to study the processes of accumulation of electron and hole trapping centers and energy transfer of electronic excitations to impurities in CaSO4-Mn and BaSO4-Mn. It is shown that electronic trapping centers are created during the excitation of an anionic complex as a result of charge transfer from O2−→SO42− to closely spaced anionic complexes SO42− in CaSO4 and BaSO4. In CaSO4 and BaSO4, energy transfer from the host to impurities occurs at the moment of charge transfer from the excited anionic complex to the combined radiative electronic state at 2.95–3.1 eV. This combined state is formed from electronic trapping centers Mn+-SO4− and SO43−-SO4−. It was found that the emerging combined radiative states at 2.95–3.1 eV of sulfates, which are formed as a result of charge transfer from the excited anionic complexes to the excited state of impurities, Tl+,Cu+,and Mn2+, occupy the same energy levels as the intrinsic electronic trapping center SO43− of the host at 2.95–3.17 eV. Experimental results show that during UV photon irradiation, anionic complexes are excited mainly near impurities in sulfates.
Using the Primary care Academic CollaboraTive to explore the characteristics and healthcare use of older housebound patients in England: protocol for a retrospective observational study and clinician survey (the CHiP study)
Authors: Winn Elizabeth , Kissane Madeleine , Merriel Samuel WD , Brain Thomas , Silverwood Victoria A , Whitehead Ishbel Orla , Howe Laura D , Payne Rupert A , Duncan Polly 
Published: July 2023

BackgroundOlder housebound people are an under-researched group for whom achieving good primary health care can be resource intensive.AimsTo describe the characteristics and healthcare use of older (≥65 years) housebound people; explore clinician views on delivery of care to housebound people; and assess the feasibility of using a new network of healthcare professionals to deliver high quality research.Design & settingRetrospective observational study of electronic GP records and clinician survey in England.MethodClinical members of a new UK research network called the Primary care Academic CollaboraTive (PACT) will collect the data. For part A, around 20 GP practices will be recruited and clinicians will identify 20 housebound and 20 non-housebound people, matched by age and gender (around 400 total in each group). Anonymised data will be collected on characteristics (age, gender, ethnicity, deprivation decile), long-term conditions, prescribed medicines, quality of healthcare (via Quality Outcomes Framework targets), and continuity of care. Reports with benchmarked practice-level data will be provided to practices to identify areas for quality improvement and to enhance engagement. For part B, 2–4 clinicians will be recruited from around 50 practices in England (around 150 clinicians) to complete a survey about delivery of healthcare for housebound people. For part C, data will be collected to assess the feasibility of using the PACT network to deliver primary care research.ConclusionOlder housebound people are a neglected group both in terms of research and clinical care. Understanding the characteristics and use of primary healthcare of housebound people will help identify how to improve their care.
Os anéis do poder nas adaptações seriadas do streaming, reconhecimento e percepção sensível
Authors: De Barros Laan Mendes , Fontaniello Bernardo 
Published: July 2023

Na sociedade em rede, o desenvolvimento de produtos midiáticos se vale das tendências mensuradas pelas empresas de mídia. É assim que as plataformas de streaming, como meio de produção, circulação e consumo de bens simbólicos, formatam séries audiovisuais com grande engajamento do público. Este artigo tensiona tais estratégias com a percepção sensível dos espectadores e fala da midiatização da sociedade e de experiências de reconhecimento a partir de séries de ficção adaptadas, que acionam disputas estéticas e políticas, como é o caso da questão de raça, aqui trazida em breve análise da série O senhor dos anéis: os anéis de poder.
Palavras-chave: plataformas de streaming; séries adaptadas; experiência estética; reconhecimento e alteridade
Pendidikan Moderasi Beragama Melalui Kajian Tafsir Ayat-Ayat Moderat di Rumah Belajar Serambi Jombang
Authors: Ramdhan Tri Wahyudi , Saifuddin Saifuddin , Arisandi Bustomi 
Published: July 2023

Kegiatan pengabdian ini berangkat dari teori umum bahwa kekerasan atas nama agama bermula dari satu pemahaman agama eksklusiv dan intoleran sudah sepatutnya mendapat perhatian, dan sebisa mungkin dibendung persebarannya.Berangkat dari sini, pengabdian bertujuan untuk memberikan penyuluhan dan pemahaman kesadaran beragama yang moderat, inklusif dan toleran melalui kajian tafsir ayat-ayat moderat di Rumah Belajar Serambi Jombang. Kegiatan ini menggunakan metode Participatory Action Research, melalui Kajian tafsir ayat-ayat moderat kepada 60 peserta,. Adapun materi pengabdian yang diberikan kepada masyarakat terkait dengan tema pengabdian Pendidikan moderasi beragama ini adalah penyampaian ayat-ayat pilihan khususnya yang terkait dengan nilai dan prinsip moderasi beragama. Hasil dari kegiatan ini bahwa pelaksanaan kegiatan ini terdiri dari tiga tahap yang setiap tahap meiliki tema pertama kajian tentang Non-Muslim dalam Al-Qur’an. Kedua tentang nilai-nilai kemanusiaan dalam Al-Qur’an. Ketiga tengan moderasi beragama dalam perspektif Al-Qur’an. Pengabdian kepada Masyarakat ini diharapkan memberikan manfaat dan dampak diantaranya pemahaman agama masyarakat yang cenderung kepada sikap moderat, karena sikap moderat dalam beragama sangat dianjurkan dan sikap ini dirujuk langsung dari sumber utama di dalam agama Islam, yaitu kitab suci Alquran.