bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utility of whole genome sequencing in assessing risk and clinically relevant outcomes for pulmonary fibrosis
Authors: Zhang David , Newton Chad A. , Wang Binhan , Povysil Gundula , Noth Imre , Martinez Fernando J. , Raghu Ganesh , Goldstein David , Garcia Christine Kim 
Published: August 2022

BackgroundWhole genome sequencing (WGS) can detect variants and estimate telomere length. The clinical utility of WGS in estimating risk, progression and survival of pulmonary fibrosis patients is unknown.MethodsIn this observational cohort study, we performed WGS on 949 patients with idiopathic pulmonary fibrosis or familial pulmonary fibrosis to determine rare and common variant genotypes, estimate telomere length and assess the association of genomic factors with clinical outcomes.ResultsWGS estimates of telomere length correlated with quantitative PCR (R=0.65) and Southern blot (R=0.71) measurements. Rare deleterious qualifying variants were found in 14% of the total cohort, with a five-fold increase in those with a family history of diseaseversusthose without (25%versus5%). Most rare qualifying variants (85%) were found in telomere-related genes and were associated with shorter telomere lengths. Rare qualifying variants had a greater effect on telomere length than a polygenic risk score calculated using 20 common variants previously associated with telomere length. The common variant polygenic risk score predicted telomere length only in sporadic disease. Reduced transplant-free survival was associated with rare qualifying variants, shorter quantitative PCR-measured telomere lengths and absence of theMUC5Bpromoter (rs35705950) single nucleotide polymorphism, but not with WGS-estimated telomere length or the common variant polygenic risk score. Disease progression was associated with both measures of telomere length (quantitative PCR measured and WGS estimated), rare qualifying variants and the common variant polygenic risk score.ConclusionAs a single test, WGS can inform pulmonary fibrosis genetic-mediated risk, evaluate the functional effect of telomere-related variants by estimating telomere length, and prognosticate clinically relevant disease outcomes.
Destructive inflammatory reaction after an autologous retinal pigment epithelium and choroid transplantation: no detection of an auto-immune response
Authors: van Romunde Saskia H. M. , Vergouwen Daphne P. C. , Iacovello Daniela , Roelen Dave L. , Verdijk Robert M. , ten Berge Josianne C. E. M. , Pertile Grazia , Schreurs Marco W. J. , van Meurs Jan C. 
Published: August 2022

Abstract
Purpose
Five patients who underwent uncomplicated retinal pigment epithelium (RPE)-choroid transplantation for neovascular age-related macular degeneration developed a destructive inflammatory reaction causing subretinal fluid accumulation and extensive RPE atrophy in the graft. We hypothesized that this inflammation could be caused by an auto-immune response against the graft, resulting in circulating auto-antibodies. The aim of our study was to examine a potential autoimmune origin, which would allow a more targeted therapy approach.

Methods
Five above-mentioned patients and four control groups of five patients each were included: 1) after uncomplicated RPE-choroid transplantation, 2) after full macular translocation, 3) treated with anti-vascular endothelial growth factor, and 4) healthy controls. Histopathology of rejected graft tissue was performed using standard procedures. Presence of RPE-choroid autoantibodies in serum was examined by indirect immunofluorescence and Western blot, and human leukocyte antigen (HLA) typing was performed.

Results
Histopathological examination of an explanted graft showed infiltration of T-lymphocytes and macrophages in the choroid and RPE, and an increased number of B-cell lymphocytes were found in the choroid. Indirect immunofluorescence showed weak RPE-choroid autoantibody immunoreactivity in three patients of different groups. Western blot did not show specific RPE-choroid autoantibody immunoreactivity and no difference of HLA genotypes between the groups was found.

Conclusions
Although local mononuclear inflammatory cell infiltration and a high number of B-lymphocytes were observed in an explanted graft, we did not detect serological evidence of an autoimmune origin of the postoperative inflammation using direct immunofluorescence and Western Blot. Alternatively, the graft failure may have been caused by local innate inflammation, triggered by breakdown of tolerance. Based on our current findings of this small study group, we have no rationale to pursue therapies targeted towards autoreactive graft failure. More research is needed to confirm our findings.
Semen parameters are seriously affected in acephalic spermatozoa syndrome
Authors: Ying Li-juan , Yu Lin , Yang Tingting , Wu Ying-bi , Xu Jin-yan , Jia Ye-lin , Zheng Yan , Li Fuping 
Published: August 2022

Abstract
Background
Previous studies have reported that some patients with headless spermatozoa have poor semen quality, but there has been no published systematic analysis of semen quality in patients with different proportions of headless spermatozoa in semen. We aimed to explore the association of acephalic spermatozoa syndrome and semen quality in men with distinct proportions of headless spermatozoa.

Material and methods
Semen parameter values in patients for whom headless spermatozoa were found in the ejaculates was studied and compared to that of 413 age-matched prenatal examination patients. All semen samples were analyzed following the same methodology in a single laboratory.

Results
All semen parameter values except semen volume were negatively (P < 0.05) correlated with the proportion of headless spermatozoa. The semen samples were divided into four groups on the basis of the proportion of headless spermatozoa (PHS) as follows: 0 < PHS ≤ 5% (n = 172, Group A1); 5 < PHS ≤ 10% (n = 76, Group A2); 10 < PHS ≤ 20% (n = 71, Group B); and PHS > 20% (n = 71, Group C). In Group A1, only one semen parameter value (progressive motility) was lower than those of the control group, but in Group A2, this increased to five (sperm vitality, normal sperm morphology, sperm motility, VCL (curvilinear velocity) and ALH (amplitude of lateral head displacement)). Worse still, all semen parameter values were significantly lower in Group B and Group C than in the control group (P < 0.05).

Conclusions
Semen samples containing headless spermatozoa tend to have lower quality than samples without headless spermatozoa. Increases in the proportion of headless spermatozoa in semen are associated with decreased semen quality. We suggest that headless spermatozoa should be seriously assessed and accurately counted in semen analysis, especially for ejaculate in which the proportion of headless spermatozoa exceeds 5%.
Tick range expansion to higher elevations: does Borrelia burgdorferi sensu lato facilitate the colonisation of marginal habitats?
Authors: Lemoine Mélissa , Cornetti Luca , Reeh Kevin , Tschirren Barbara 
Published: August 2022

AbstractBackgroundParasites can alter host and vector phenotype and thereby affect ecological processes in natural populations. Laboratory studies have suggested thatBorrelia burgdorferisensu lato, the causative agent of human Lyme borreliosis, may induce physiological and behavioural alterations in its main tick vector in Europe,Ixodes ricinus, which increase the tick’s mobility and survival under challenging conditions. These phenotypic alterations may allowI. ricinusto colonise marginal habitats (‘facilitation hypothesis’), thereby fuelling the ongoing range expansion ofI. ricinustowards higher elevations and latitudes induced by climate change. To explore the potential for such an effect under natural conditions, we studied the prevalence ofB. burgdorferis.l. in questingI. ricinusand its variation with elevation in the Swiss Alps.ResultsWe screened forB. burgdorferis.l. infection in questing nymphs ofI. ricinus(N = 411) from 15 sites between 528 and 1774 m.a.s.l to test ifB. burgdorferis.l. prevalence is higher at high elevations (i.e. in marginal habitats). Opposite of what is predicted under the facilitation hypothesis, we found thatB. burgdorferis.l. prevalence inI. ricinusnymphs decreased with increasing elevation and thatBorreliaprevalence was 12.6% lower inI. ricinusnymphs collected at the range margin compared to nymphs in the core range. But there was no association betweenBorreliaprevalence and elevation within the core range ofI. ricinus. Therefore the observed pattern was more consistent with a sudden decrease inBorreliaprevalence above a certain elevation, rather than a gradual decline with increasing elevation across the entire tick range.ConclusionsIn conclusion, we found no evidence thatB. burgdorferis.l.-induced alterations ofI. ricinusphenotype observed in laboratory studies facilitate the colonisation of marginal habitats in the wild. Rather, ticks in marginal habitats are substantially less likely to harbour the pathogen. These findings have implications for a better understanding of eco-evolutionary processes in natural host-parasite systems, as well as the assessment of Lyme borreliosis risk in regions whereI. ricinusis newly emerging.
Integrated metabolomics and transcriptomic analysis of the flavonoid regulatory networks in Sorghum bicolor seeds
Authors: Zhou Yaxing , Lv Jingbo , Yu Zhonghao , Wang Zhenguo , Li Yan , Li Mo , Deng Zhilan , Xu Qingquan , Cui Fengjuan , Zhou Wei 
Published: August 2022

Abstract
Background
The objective of this study was to reveal the flavonoid biosynthesis pathway in white (Z6), red (Z27) and black (HC4) seeds of the sweet sorghum (Sorghum bicolor) using metabolomics and transcriptomics, to identify different flavonoid metabolites, and to analyze the differentially expressed genes involved in flavonoid biosynthesis.

Results
We analyzed the metabolomics and transcriptomics data of sweet sorghum seeds. Six hundred and fifty-one metabolites including 171 flavonoids were identified in three samples. Integrated analysis of transcriptomics and metabolomics showed that 8 chalcone synthase genes (gene19114, gene19115, gene19116, gene19117, gene19118, gene19120, gene19122 and gene19123) involved in flavonoid biosynthesis, were identified and play central role in change of color. Six flavanone including homoeriodictyol, naringin, prunin, naringenin, hesperetin and pinocembrin were main reason for the color difference.

Conclusions
Our results provide valuable information on the flavonoid metabolites and the candidate genes involved in the flavonoid biosynthesis pathway in sweet sorghum seeds.
Effects of artificial honey and epigallocatechin-3-gallate on streptococcus pyogenes
Authors: Jiang Xiaoge , Lin An , Li Shijia , Shi Yangyang , Zhou Fangjie , Felix Gomez Grace Gomez , Gregory Richard L. , Zhang Chaoliang , Chen Song , Huang Ruijie 
Published: August 2022

Abstract
Background
Streptococcus pyogenes is an important global human pathogen that causes pharyngitis, and antibacterial therapy has become an important part of the overall therapy for pharyngitis. As natural derivatives, honey and green tea are often recommended for patients with pharyngitis in traditional Chinese medicine without experimental theoretical basis on wether the combined effect of honey and green tea on pharyngitis is better than they alone. The aims of this study were to explore the effects of artificial honey (AH) and epigallocatechin-3-gallate (EGCG) on S. pyogenes and elucidate the possible mechanisms, which were investigated using MIC (the minimum inhibitory concentration), FIC (fractional inhibitory concentration) index, growth pattern, biofilm formation and RT-qPCR.

Results
The MIC of AH on S. pyogenes was 12.5% (v/v) and the MIC of EGCG was 1250 μg/ml. The FIC index of AH and EGCG was 0.5. The planktonic cell growth, growth pattern and biofilm formation assays showed that AH and EGCG mixture had stronger inhibitory effect on S. pyogenes than they alone. RT-qPCR confirmed that the expression of hasA and luxS gene were inhibited by AH and EGCG mixture.

Conclusions
AH and EGCG mixture can inhibit the planktonic cell growth, biofilm formation and some virulence genes expression of S. pyogenes, better than they alone. The combination of honey and green tea have the potential to treat pharyngitis as natural derivatives, avoiding drug resistance and double infection.
Quantifying the burden of lipid anomalies among adolescents in India
Authors: Kirti Kirti , Singh Shri Kant 
Published: August 2022

Abstract
Background
The present study’s aim is to quantify the burden of lipid abnormalities (excessive non-high-density lipoprotein (non-HDL) cholesterol and low-density lipoprotein (LDL) cholesterol) among Indian adolescents. Which has emerged as a significant covariate of coronary heart disease (CHD).

Methods
The present study aims to unearth the prevalence of any lipid anomalies, their level, and types of lipid profiles among adolescents in India using the Comprehensive National Nutrition Survey 2016–18 i.e., cross-sectional data. Descriptive and bivariate statistical analyses have been used to check the associations and significant differences between groups of individuals suffering from any type of lipid abnormalities.

Results
A total of 35,830 adolescents aged between 10 and 19 years (mean age:14.36 yrs.; SD = 2.81 for males and 14.39 yrs.; SD = 2.78 for females) were included. Roughly 77 percent of the adolescents are suffering from any lipid anomalies. Their mean lipid levels are 140.6 (SD = 32.9), 84.1 (SD = 24.8), 47.3 (SD = 10.7), and 95.3 (SD = 50.0) for total cholesterol, LDL, HDL, and triglycerides, respectively. A higher proportion of adolescents suffered from lipid anomalies among those who were overweight or obese (89%, 95% CI 85, 92) and pre-diabetics (81%, 95% CI 78, 83) compared to each of their counterparts. Furthermore, a considerable proportion of samples with vitamin A (70%, 95% CI 68, 73), D (81%, 95% CI 79, 82), and B12 deficits (73%,95% CI 72, 75), as well as zinc (77%, 95% CI 76, 77), folate (76%, 95% CI 74, 77), and iron deficits (75%,95% CI 73, 77), were suffering from any lipid anomalies. Of individuals who consume an unhealthy diet, 77% (95% CI 76, 78) of them were suffering from any lipid anomalies than others.

Conclusions
The study contends that preventing the increasing burden of lipid abnormalities among Indian adolescents is essential. Vitamin and mineral deficiencies and unhealthy dietary habits are significantly associated with high LDL and non-HDL levels. In the longer run, this might cause the early onset of hypertension, diabetes, and CHDs. Hence, appropriate interventions are needed to curtail these early onsets by primarily focusing on adolescents.
Cognitive biases encountered by physicians in the emergency room
Authors: Kunitomo Kotaro , Harada Taku , Watari Takashi 
Published: August 2022

Abstract
Background
Diagnostic errors constitute an important medical safety problem that needs improvement, and their frequency and severity are high in emergency room settings. Previous studies have suggested that diagnostic errors occur in 0.6-12% of first-time patients in the emergency room and that one or more cognitive factors are involved in 96% of these cases. This study aimed to identify the types of cognitive biases experienced by physicians in emergency rooms in Japan.

Methods
We conducted a questionnaire survey using Nikkei Medical Online (Internet) from January 21 to January 31, 2019. Of the 159,519 physicians registered with Nikkei Medical Online when the survey was administered, those who volunteered their most memorable diagnostic error cases in the emergency room participated in the study. EZR was used for the statistical analyses.

Results
A total of 387 physicians were included. The most common cognitive biases were overconfidence (22.5%), confirmation (21.2%), availability (12.4%), and anchoring (11.4%). Of the error cases, the top five most common initial diagnoses were upper gastrointestinal disease (22.7%), trauma (14.7%), cardiovascular disease (10.9%), respiratory disease (7.5%), and primary headache (6.5%). The corresponding final diagnoses for these errors were intestinal obstruction or peritonitis (27.3%), overlooked traumas (47.4%), other cardiovascular diseases (66.7%), cardiovascular disease (41.4%), and stroke (80%), respectively.

Conclusions
A comparison of the initial and final diagnoses of cases with diagnostic errors shows that there were more cases with diagnostic errors caused by overlooking another disease in the same organ or a disease in a closely related organ.
Age- and sex-based changes in spike protein antibody status after SARS-CoV-2 vaccination and effect of past-infection in healthcare workers in Osaka
Authors: Hoshida Shiro , Koeda Nobuyuki , Hattori Hideki , Tanaka Masahiro , Tanaka Ichiro , Fukui Hiroyuki , Fujita Junya , Sasaki Yo , Tamura Shigeyuki 
Published: August 2022

Abstract
Objective
We aimed to compare the changes in SARS-CoV-2 spike protein antibody titres based on age group and sex using paired blood sampling after vaccination in association with the presence of nucleocapsid protein antibody.

Methods
All participants were healthcare workers at Yao Municipal Hospital in Osaka who voluntarily provided peripheral blood samples (n = 636, men/women 151/485, mean age 45 years). We investigated the serial changes in SARS-CoV-2 spike protein antibody titres at 1 and 7 months after the second vaccination regarding their relationship with sex and age group. At 7 months, we also examined anti-nucleocapsid assays. Antibody titres were shown as logarithmic values and the differences were assessed using a paired or unpaired student’s t-test as appropriate.

Results
Among participants younger than 30 years, the antibody titres of spike protein were significantly higher in women one (p = 0.005) and seven (p = 0.038) months after vaccination. However, among those aged 30–49 years, the antibody titres were not different between the sexes at either follow-up time point. In contrast, among those aged 50–59 years, between-sex differences in antibody titres were observed only at 7 months, which was associated with a significant reduction in men. A significant negative correlation was observed between the antibody titres for spike protein at both time points in participants with positive nucleocapsid protein antibody at 7 months (r = − 0.467, p = 0.043), although a significant positive correlation was observed in those with negative results (r = 0.645, p < 0.001),

Conclusions
Between-sex differences in SARS-CoV-2 spike protein antibody titres by paired blood sampling at different time points after vaccination depended on age group. The presence of nucleocapsid protein antibody was associated with changes in spike protein antibody titres after vaccination.
Characteristics of people with epilepsy in three Eastern African countries – a pooled analysis
Authors: Stelzle Dominik , Kaducu Joyce , Schmidt Veronika , Welte Tamara M. , Ngowi Bernard J. , Matuja William , Escheu Gabrielle , Hauke Peter , Richter Vivien , Ovuga Emilio , Pfausler Bettina , Schmutzhard Erich , Amos Action , Harrison Wendy , Keller Luise , Winkler Andrea S. 
Published: August 2022

Abstract
Background
Epilepsy is one of the most common neurological disorders worldwide. Yet, its treatment gap is large in some areas and especially in sub-Saharan Africa data on clinical, radiological and semiological characteristics, as well as on treatment of persons with epilepsy (PWE) are still scarce.

Methods
We pooled data from four cross-sectional studies on epilepsy in eastern Africa. Two studies from Malawi and Uganda were community-based; two studies in Tanzania (urban Dar es Salaam and rural Haydom) were hospital-based. Clinical characteristics of PWE were assessed by the same questionnaire. Additionally, data on treatment were collected and computed tomography (CT) scans were performed.

Results
Overall, 1179 PWE were included in our analysis (581 (49.3%) female, median age 22 years (IQR 15–32 years)). Up to 25% of the patients had focal onset seizures. Those showed a higher rate of remarkable CT scan findings, with especially post-ischaemic and neurocysticercosis-associated lesions, compared to PWE with generalized onset seizures (35.1% vs. 20%). The majority of the patients experienced tonic–clonic seizures (70–85%). Only 67–78% of PWE received anti-seizure medication (ASM) treatment in the community-based studies, mostly monotherapy with phenobarbital, phenytoin or carbamazepine. Yet, underdosage was frequent and a large proportion of PWE received alternative non-ASM treatment consisting of herbal treatment (up to 83%) and/or scarification (up to 20%).

Conclusions
Epilepsy is common in sub-Saharan Africa, often caused by neurocysticercosis or ischaemic strokes. PWE suffer from high seizure rates and subsequent injuries, as well as from socio-economic consequences due to insufficient ASM treatment. This pooled analysis illustrates the need for structural programmes for adequate identification, education, assessment and treatment of PWE in sub-Saharan Africa.
Fetal adverse effects following NSAID or metamizole exposure in the 2nd and 3rd trimester: an evaluation of the German Embryotox cohort
Authors: Dathe Katarina , Frank Johanna , Padberg Stephanie , Hultzsch Stefanie , Beck Evelin , Schaefer Christof 
Published: August 2022

Abstract
Background
Non-steroidal anti-inflammatory drugs (NSAID) are frequently used to treat pain, fever and inflammatory conditions. Due to evidenced fetotoxicity, treatment with NSAID and metamizole should be avoided in the 3rd trimester of pregnancy. There is an ongoing debate on fetotoxic risk of 2nd trimester use which is why we have conducted this study.

Methods
In this observational cohort study outcome of pregnancies with NSAID and/or metamizole exposure in the 2nd and/or 3rd trimester (study cohort n = 1092) was compared with pregnancies exposed to NSAID and/or metamizole in the 1st trimester only (comparison cohort, n = 1154). The WHO-UMC system was used to assess causality between study medication and study endpoints. Prenatal study endpoints were constriction of ductus arteriosus Botalli, oligohydramnios, late spontaneous abortion (SAB) or stillbirth. Postnatal study endpoints were patent ductus arteriosus (PDA), anomalies of the right heart ventricle, primary pulmonary hypertension (PPHT), and neonatal impairment of kidney function.

Results
Ductus arteriosus constriction was diagnosed in 5/1092 (0.5%) in the study cohort versus 0/1154 pregnancies in the comparison cohort. In one fetus, ductus arteriosus constriction and oligohydramnios occurred already in the late 2nd trimester after long-term NSAID exposure. Oligohydramnios was diagnosed in 41/1092 (3.8%) in the study cohort versus 29/1154 (2.5%) cases in the comparison cohort [RR, 1.5 (95% CI 0.9–2.4)]. Limited to 2nd trimester, oligohydramnios occurred in 8/904 (0.9%) versus 2/1154 (0.2%) pregnancies [RR, 5.1 (95% CI 1.1–24.0)]. At least in four of the 2nd trimester exposed pregnancies NSAID exposure lasted several weeks. Late SAB or stillbirth occurred in 14/1092 (1.3%) versus 17/1154 (1.5%). Postnatal cardiovascular or renal pathology did not differ between the cohorts.

Conclusions
NSAID use in the 2nd trimester limited to a few days does not appear to pose a relevant risk. Use for longer periods in the advanced 2nd trimester, however, may cause oligohydramnios and ductus arteriosus constriction similar to effects observed after 3rd trimester use.