bluuebunny/crossref_metadata_2025_split huggingface dataset:
Add-on effect of the Guizhi Fuling formula for management of reduced fertility potential in women with polycystic ovary syndrome: A systematic review and meta-analysis of randomized controlled trials
Authors: Rong Anna , Ta Na , E. Lihua , Meng Wenbin 
Published: April 2023

BackgroundGuizhi Fuling (GZFL) pill, a traditional Chinese herbal formula including Semen Persicae, Ramulus Cinnamomi, Poria, Radix Paeoniae Alba, and Cortex Moutan, has been widely applied in the management of gynecological diseases.ObjectiveTo evaluate the add-on effect of the GZFL formula for treating reduced fertility potential in women with polycystic ovary syndrome (PCOS) by conducting a systematic review and meta-analysis.MethodsTwo reviewers independently searched the PubMed, Embase, Cochrane Library, Wanfang, SinoMed, and CKNI databases until 09/11/2022. Eligible studies were randomized controlled trials (RCTs) of the GZFL formula plus Western medicine versus the Western medicine for treating PCOS. The primary endpoint was the ovulation, pregnancy, and miscarriage rate. The secondary endpoints included the serum follicle-stimulating hormone (FSH), total testosterone, luteinizing hormone (LH), estradiol, and homeostasis model assessment insulin resistance (HOMA-IR).ResultsThere were 16 RCTs with 1,385 patients identified. The GZFL formula plus Western medicine significantly improved the ovulation rate (risk ratios [RR] 1.24; 95% confidence intervals [CI] 1.15–1.34) and pregnancy rate (RR 1.53; 95% CI 1.38 to 1.69) than the Western medicine alone. Adjuvant treatment with the GZFL formula also significantly decreased the serum FSH (mean difference [MD] -0.48 U/l; 95% CI -0.80 to -0.15), total testosterone (standard mean difference [SMD] -1.07; 95% CI -1.71 to -0.44), LH level (MD -2.19 U/l; 95% CI -3.04 to -1.34), and HOMA-IR (MD -0.47; 95% CI -0.60 to -0.34). However, there was no significant difference in the miscarriage rate (RR 0.89; 95% CI 0.36–2.20) and serum estradiol level (SMD 0.34; 95% CI -0.25 to 0.94) between two groups.ConclusionsThe GZFL formula as adjuvant therapy can improve the ovulation and pregnancy rates in women with PCOS. Its beneficial effects may correlate with reducing FSH, total testosterone, and LH and ameliorating insulin resistance. However, more well-designed RCTs with larger samples and multicenter trials are required to confirm the current findings due to uncertainty of the evidence.Systematic review registrationPROSPERO identifier, CRD42022354530.
Deep learning radiomics model based on breast ultrasound video to predict HER2 expression status
Authors: Quan Meng-Yao , Huang Yun-Xia , Wang Chang-Yan , Zhang Qi , Chang Cai , Zhou Shi-Chong 
Published: April 2023

PurposeThe detection of human epidermal growth factor receptor 2 (HER2) expression status is essential to determining the chemotherapy regimen for breast cancer patients and to improving their prognosis. We developed a deep learning radiomics (DLR) model combining time-frequency domain features of ultrasound (US) video of breast lesions with clinical parameters for predicting HER2 expression status.Patients and MethodsData for this research was obtained from 807 breast cancer patients who visited from February 2019 to July 2020. Ultimately, 445 patients were included in the study. Pre-operative breast ultrasound examination videos were collected and split into a training set and a test set. Building a training set of DLR models combining time-frequency domain features and clinical features of ultrasound video of breast lesions based on the training set data to predict HER2 expression status. Test the performance of the model using test set data. The final models integrated with different classifiers are compared, and the best performing model is finally selected.ResultsThe best diagnostic performance in predicting HER2 expression status is provided by an Extreme Gradient Boosting (XGBoost)-based time-frequency domain feature classifier combined with a logistic regression (LR)-based clinical parameter classifier of clinical parameters combined DLR, particularly with a high specificity of 0.917. The area under the receiver operating characteristic curve (AUC) for the test cohort was 0.810.ConclusionOur study provides a non-invasive imaging biomarker to predict HER2 expression status in breast cancer patients.
Genetically predicted alterations in thyroid function are associated with the risk of benign prostatic disease
Authors: Huang Yan , Chen Cheng , Zhou Wanqing , Zhang Qian , Zhao Yanfei , He Dehao , Ye Zhi , Xia Pingping 
Published: April 2023

BackgroundBenign prostatic diseases (BPDs), such as benign prostate hyperplasia (BPH) and prostatitis, harm the quality of life of affected patients. However, observational studies exploring the association between thyroid function and BPDs have hitherto yielded inconsistent results. In this study, we explored whether there is a causal genetic association between them using Mendelian randomization (MR) analysis.MethodsWe used publicly available summary statistics from the Thyroidomics Consortium and 23andMe on thyrotropin (TSH; 54,288 participants), thyroxine [free tetraiodothyronine (FT4); 49,269 participants], subclinical hypothyroidism (3,440 cases and 49,983 controls), overt hypothyroidism (8,000 cases and 117,000 controls), and subclinical hyperthyroidism (1,840 cases and 49,983 controls) to screen for instrumental variables of thyroid function. Results for BPD such as prostatic hyperplasia (13,118 cases and 72,799 controls) and prostatitis (1,859 cases and 72,799 controls) were obtained from the FinnGen study. The causal relationship between thyroid function and BPD was primarily assessed using MR with an inverse variance weighted approach. In addition, sensitivity analyses were performed to test the robustness of the results.ResultsWe found that TSH [OR (95% CI) = 0.912(0.845-0.984), p =1.8 x 10-2], subclinical hypothyroidism [OR (95% CI) = 0.864(0.810-0.922), p =1.04 x 10-5], and overt hypothyroidism [OR (95% CI) = 0.885 (0.831-0. 944), p =2 x 10-4] had a significant effect on genetic susceptibility to BPH, unlike hyperthyroidism [OR (95% CI) = 1.049(0.990-1.111), p =1.05 x 10-1] and FT4 [OR (95% CI) = 0.979(0.857-1.119), p = 7.59 x 10-1] had no effect. We also found that TSH [OR (95% CI) =0.823(0.700-0.967), p = 1.8 x 10-2] and overt hypothyroidism [OR (95% CI) = 0.853(0.730-0.997), p = 4.6 x 10-2] significantly influenced the prostatitis, whereas FT4 levels [OR (95% CI) = 1.141(0.901-1.444), p = 2.75 x 10-1], subclinical hypothyroidism [OR (95% CI) =0. 897(0.784- 1.026), p = 1.12 x 10-1], and hyperthyroidism [OR (95% CI) = 1.069(0.947-1.206), p = 2.79 x 10-1] did not have a significant effect.ConclusionOverall, our study results suggest that hypothyroidism and TSH levels influence the risk of genetically predicted BPH and prostatitis, providing new insights into the causal relationship between thyroid function and BPD.
AVP deficiency (central diabetes insipidus) following immunization with anti-COVID-19 BNT162b2 Comirnaty vaccine in adolescents: A case report
Authors: Partenope Cristina , Pedranzini Quincy , Petri Antonella , Rabbone Ivana , Prodam Flavia , Bellone Simonetta 
Published: April 2023

IntroductionThe coronavirus disease 19 (COVID-19) pandemic has prompted the development of new vaccines to reduce the morbidity and mortality associated with this disease. Recognition and report of potential adverse effects of these novel vaccines (especially the urgent and life-threatening ones) is therefore essential.Case presentationA 16-year-old boy presented to the Paediatric Emergency Department with polyuria, polydipsia and weight loss over the last four months. His past medical history was unremarkable. Onset of symptoms was referred to be few days after first dose of anti-COVID-19 BNT162b2 Comirnaty vaccine and then worsened after the second dose. The physical exam was normal, without neurological abnormalities. Auxological parameters were within normal limits. Daily fluid balance monitoring confirmed polyuria and polydipsia. Biochemistry laboratory analysis and urine culture were normal. Serum osmolality was 297 mOsm/Kg H2O (285-305), whereas urine osmolality was 80 mOsm/Kg H2O (100-1100), suggesting diabetes insipidus. Anterior pituitary function was preserved. Since parents refused to give consent to water deprivation test, treatment with Desmopressin was administered and confirmed ex juvantibus diagnosis of AVP deficiency (or central diabetes insipidus). Brain MRI revealed pituitary stalk thickening (4 mm) with contrast enhancement, and loss of posterior pituitary bright spot on T1 weighted imaging. Those signs were consistent with neuroinfundibulohypophysitis. Immunoglobulin levels were normal. Low doses of oral Desmopressin were sufficient to control patient’s symptoms, normalizing serum and urinary osmolality values and daily fluid balance at discharge. Brain MRI after 2 months showed stable thicken pituitary stalk and still undetectable posterior pituitary. Due to persistence of polyuria and polydipsia, therapy with Desmopressin was adjusted by increasing dosage and number of daily administrations. Clinical and neuroradiological follow-up is still ongoing.ConclusionHypophysitis is a rare disorder characterized by lymphocytic, granulomatous, plasmacytic, or xanthomatous infiltration of the pituitary gland and stalk. Common manifestations are headache, hypopituitarism, and diabetes insipidus. To date, only time correlation between SARS-CoV-2 infection and development of hypophysitis and subsequent hypopituitarism has been reported. Further studies will be needed to deepen a possible causal link between anti-COVID-19 vaccine and AVP deficiency.
A global spatial-temporal land use regression model for nitrogen dioxide air pollution
Authors: Larkin Andrew , Anenberg Susan , Goldberg Daniel L. , Mohegh Arash , Brauer Michael , Hystad Perry 
Published: April 2023

Introduction: The World Health Organization (WHO) recently revised its health guidelines for Nitrogen dioxide (NO2) air pollution, reducing the annual mean NO2 level to 10 μg/m3 (5.3 ppb) and the 24-h mean to 25 μg/m3 (13.3 ppb). NO2 is a pollutant of global concern, but it is also a criteria air pollutant that varies spatiotemporally at fine resolutions due to its relatively short lifetime (~hours). Current models have limited ability to capture both temporal and spatial NO2 variation and none are available with global coverage. Land use regression (LUR) models that incorporate timevarying predictors (e.g., meteorology and satellite NO2 measures) and land use characteristics (e.g., road density, emission sources) have significant potential to address this need.Methods: We created a daily Land use regression model with 50 × 50 m2 spatial resolution using 5.7 million daily air monitor averages collected from 8,250 monitor locations.Results: In cross-validation, the model captured 47%, 59%, and 63% of daily, monthly, and annual global NO2 variation. Daily, monthly, and annual root mean square error were 6.8, 5.0, and 4.4 ppb and absolute bias were 46%, 30%, and 21%, respectively. The final model has 11 variables, including road density and built environments with fine (30 m or less) spatial resolution and meteorological and satellite data with daily temporal resolution. Major roads and satellite-based estimates of NO2 were consistently the strongest predictors of NO2 measurements in all regions.Discussion: Daily model estimates from 2005–2019 are available and can be used for global risk assessments and health studies, particularly in countries without NO2 monitoring.
Patient attitudes and preferences about expanded noninvasive prenatal testing
Authors: Dubois Marie-Line , Winters Patricia D. , Rodrigue Marc-André , Gekas Jean 
Published: April 2023

Introduction: Noninvasive prenatal testing (NIPT) using cell-free DNA (cfDNA) is typically carried out to screen for common fetal chromosomal anomalies, with the option to screen for a wider range of chromosomal changes (expanded NIPT) becoming increasingly available. However, little is known about pregnant patients’ attitudes and preferences regarding expanded NIPT.Methods: To address this gap, we surveyed general-risk patients having first-tier cfDNA screening at a private prenatal clinic on their expectations for expanded NIPT. Patients were asked questions regarding their current pregnancy and previous pregnancy history, their opinions on fetal DNA screenings during pregnancy and incidental findings, information and opinions on financial resources for NIPT, as well as socio-cultural questions to determine patient demographics.Results: Of the 200 survey participants, the majority were educated, self-reported as white, had a higher than average income, and reported no aneuploidy risk factors. When asked what information they would like to receive from cfDNA screening, the vast majority of participants wanted all information available that could have an immediate impact on fetal health (88%) or an immediate impact on infant health from birth (82%). Many participants also wanted information that could have a future impact on the child’s health or an immediate or future impact on the pregnant woman’s own health. Most participants wanted information about the sex of fetus (86%) and common trisomies (71%), with almost half of participants desiring information about rare autosomal aneuploidies and/or all genetic information that may affect the baby. In addition, participants were found to be comfortable screening for conditions that are well-known, influence care during pregnancy, and are treatable. Finally, while most respondents either had insurance coverage for NIPT or were able to afford NIPT out of pocket, the majority of our participants felt that expanded NIPT should be either free for everyone or for those considered high risk.Discussion: Our findings suggest that with appropriate pre-test counseling, pregnant patients may choose NIPT for an expanding list of conditions.
Identification of gut dysbiosis in axial spondyloarthritis patients and improvement of experimental ankylosing spondyloarthritis by microbiome-derived butyrate with immune-modulating function
Authors: Min Hong Ki , Na Hyun Sik , Jhun JooYeon , Lee Seon-Yeong , Choi Sun Shim , Park Go Eun , Lee Jeong Su , Um In Gyu , Lee Seung Yoon , Seo Hochan , Shin Tae-Seop , Kim Yoon-Keun , Lee Jennifer Jooha , Kwok Seung-Ki , Cho Mi-La , Park Sung-Hwan 
Published: April 2023

IntroductionDysbiosis is an environmental factor that affects the induction of axial spondyloarthritis (axSpA) pathogenesis. In the present study, we investigated differences in the gut microbiota of patients with axSpA and revealed an association between specific gut microbiota and their metabolites, and SpA pathogenesis.MethodUsing 16S rRNA sequencing data derived from feces samples of 33 axSpA patients and 20 healthy controls (HCs), we examined the compositions of their gut microbiomes.ResultsAs a result, axSpA patients were found to have decreased α-diversity compared to HCs, indicating that axSpA patients have less diverse microbiomes. In particular, at the species level, Bacteroides and Streptococcus were more abundant in axSpA patients than in HCs, whereas Faecalibacterium (F). prausnitzii, a butyrate-producing bacteria, was more abundant in HCs. Thus, we decided to investigate whether F. prausnitzii was associated with health conditions by inoculating F. prausnitzii (0.1, 1, and 10 μg/mL) or by administrating butyrate (0.5 mM) into CD4+ T cells derived from axSpA patients. The levels of IL-17A and IL-10 in the CD4+ T cell culture media were then measured. We also assessed osteoclast formation by administrating butyrate to the axSpA-derived peripheral blood mononuclear cells. The CD4+ IL-17A+ T cell differentiation, IL-17A levels were decreased, whereas IL-10 was increased by F. prausnitzii inoculation. Butyrate reduced CD4+ IL-17A+ T cell differentiation and osteoclastogenesis.DiscussionWe found that CD4+ IL-17A+ T cell polarization was reduced, when F. prausnitzii or butyrate were introduced into curdlan-induced SpA mice or CD4+ T cells of axSpA patient. Consistently, butyrate treatment was associated with the reduction of arthritis scores and inflammation levels in SpA mice. Taken together, we concluded that the reduced abundance of butyrate-producing microbes, particularly F. prausnitzii, may be associated with axSpA pathogenesis.
Haemagglutination inhibition and virus microneutralisation serology assays: use of harmonised protocols and biological standards in seasonal influenza serology testing and their impact on inter-laboratory variation and assay correlation: A FLUCOP collaborative study
Authors: Waldock Joanna , Remarque Edmond J. , Zheng Lingyi , Ho Sammy , Hoschler Katja , Neumann Britta , Sediri-Schön Hanna , Trombetta Claudia M. , Montomoli Emanuele , Marchi Serena , Lapini Giulia , Zhou Fan , Lartey Sarah L. , Cox Rebecca J. , Facchini Marzia , Castrucci Maria Rita , Friel Damien , Ollinger Thierry , Caillet Catherine , Music Nedzad , Palladino Giuseppe , Engelhardt Othmar G. ,   the FLUCOP consortium
Published: April 2023

IntroductionThe haemagglutination inhibition assay (HAI) and the virus microneutralisation assay (MN) are long-established methods for quantifying antibodies against influenza viruses. Despite their widespread use, both assays require standardisation to improve inter-laboratory agreement in testing. The FLUCOP consortium aims to develop a toolbox of standardised serology assays for seasonal influenza. Building upon previous collaborative studies to harmonise the HAI, in this study the FLUCOP consortium carried out a head-to-head comparison of harmonised HAI and MN protocols to better understand the relationship between HAI and MN titres, and the impact of assay harmonisation and standardisation on inter-laboratory variability and agreement between these methods.MethodsIn this paper, we present two large international collaborative studies testing harmonised HAI and MN protocols across 10 participating laboratories. In the first, we expanded on previously published work, carrying out HAI testing using egg and cell isolated and propagated wild-type (WT) viruses in addition to high-growth reassortants typically used influenza vaccines strains using HAI. In the second we tested two MN protocols: an overnight ELISA-based format and a 3-5 day format, using reassortant viruses and a WT H3N2 cell isolated virus. As serum panels tested in both studies included many overlapping samples, we were able to look at the correlation of HAI and MN titres across different methods and for different influenza subtypes.ResultsWe showed that the overnight ELISA and 3-5 day MN formats are not comparable, with titre ratios varying across the dynamic range of the assay. However, the ELISA MN and HAI are comparable, and a conversion factor could possibly be calculated. In both studies, the impact of normalising using a study standard was investigated, and we showed that for almost every strain and assay format tested, normalisation significantly reduced inter-laboratory variation, supporting the continued development of antibody standards for seasonal influenza viruses. Normalisation had no impact on the correlation between overnight ELISA and 3-5 day MN formats.
COVID-19 vaccination in patients with primary immunodeficiencies: an international survey on patient vaccine hesitancy and self-reported adverse events
Authors: Pergent Martine , Haerynck Filomeen , Hoste Levi , Gardulf Ann 
Published: April 2023

IntroductionThe Sars-CoV-2 pandemic caused great concern for this novel virus among patients with primary immunodeficiency (PID) or inborn errors of immunity (IEI) and their families. When COVID-19 vaccination program started, no data existed on adverse events (AEs) in this particular patient population, nor if patients felt hesitancy being vaccinated.ObjectivesTo explore i) reasons for COVID-19 vaccination hesitancy, ii) the number and symptoms of AEs and their severity, durability and management.MethodThe organisations International Patient Organisation for Primary Immunodeficiencies (IPOPI), European Society for Immunodeficiencies (ESID) and International Nursing Group for Immunodeficiencies (INGID) distributed a global self-administered online survey.ResultsThe survey was completed by 1317 patients (mean 47, range 12-100, years) from 40 countries. 41.7% of the patients denoted some hesitancy to COVID-19 vaccination, mainly having doubts about postvaccination protection related to their underlying PID and concerns about negative long-term effects. More women (22.6%) reported “very” or “pretty much” hesitancy compared to men (16.4%) (P&lt;0.05). The most common systemic AEs were fatigue, muscle/body pain and headache, usually the same day or the day after the vaccination and lasting for 1-2 days. 27.8% of the respondents reported severe systemic AEs after any dose of COVID-19 vaccine. Only a minority (7.8%) of these patients visited a health-care professional and 20 patients (1.5%) were hospitalized or seen at emergency room without specifying subsequent admission at the hospital. Significantly more local and systemic AEs were reported after the second dose. No differences regarding AEs were observed across different PID subgroups or vaccine types.ConclusionAt the time of the survey, almost half of the patients reported having felt hesitancy to COVID-19 vaccination highlighting the importance and need of developing joint international guidelines and education programs about COVID-19 vaccination. The types of AEs were comparable to healthy controls, but more frequent AEs were reported. Clinical studies and prospective, detailed registration of AEs related to COVID-19 vaccines in this patient population is of great importance. It is crucial to elucidate whether there is a coincidental or causal association between COVID-19 vaccine and some severe systemic AEs. Our data do not contradict that patients with PID can be advised to be vaccinated against COVID-19, in accordance with applicable national guidelines.