bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cleavage-stage or blastocyst-stage embryo biopsy has no impact on growth and health in children up to 2 years of age
Authors: Belva Florence , Kondowe Fiskani , De Vos Anick , Keymolen Kathelijn , Buysse Andrea , Hes Frederik , Berckmoes Veerle , Verdyck Pieter , Verpoest Willem , De Rycke Martine 
Published: September 2023

Abstract
Background
Studies show conflicting results on neonatal outcomes following embryo biopsy for PGT, primarily due to small sample sizes and/or heterogeneity in the timing of embryo biopsy (day 3; EBD3 or day 5/6; EBD5) and type of embryo transfer. Even fewer data exist on the impact on children’s health beyond the neonatal period. This study aimed to explore outcomes in children born after EBD3 or EBD5 followed by fresh (FRESH) or frozen-thawed embryo transfer (FET).

Methods
This single-centre cohort study compared birth data of 630 children after EBD3, of 222 EBD5 and of 1532 after non-biopsied embryo transfers performed between 2014 and 2018. Follow-up data on growth were available for 426, 131 and 662 children, respectively.

Results
Embryo biopsy, either at EBD3 or EBD5 in FET and FRESH cycles did not negatively affect anthropometry at birth, infancy or childhood compared to outcomes in non-biopsied FET and FRESH cycles.
While there was no adverse effect of the timing of embryo biopsy (EBD3 versus EBD5), children born after EBD3 followed by FET had larger sizes at birth, but not thereafter, than children born after EBD3 followed by FRESH.
Reassuringly, weight and height gain, proportions of major congenital malformations, developmental problems, hospital admissions and surgical interventions were similar between comparison groups.

Conclusion
Our study indicated that neither EBD3 nor EBD5 followed by FRESH or FET had a negative impact on anthropometry and on health outcomes up to 2 years of age.
The application of HER2 and CD47 CAR-macrophage in ovarian cancer
Authors: Chen Yizhao , Zhu Xiangling , Liu Hanze , Wang Cunzhi , Chen Yu , Wang Huihui , Fang Yilong , Wu Xuming , Xu Yuting , Li Chunhua , Lv Xinyue , Huang Jinghua , Han Xintong , Li Ruilin , Hong Wenming , Yu Zhiying , Wei Wei , Tu Jiajie 
Published: September 2023

Abstract
Background
The chimeric antigen receptor (CAR)-T therapy has a limited therapeutic effect on solid tumors owing to the limited CAR-T cell infiltration into solid tumors and the inactivation of CAR-T cells by the immunosuppressive tumor microenvironment. Macrophage is an important component of the innate and adaptive immunity, and its unique phagocytic function has been explored to construct CAR macrophages (CAR-Ms) against solid tumors. This study aimed to investigate the therapeutic application of CAR-Ms in ovarian cancer.

Methods
In this study, we constructed novel CAR structures, which consisted of humanized anti-HER2 or CD47 scFv, CD8 hinge region and transmembrane domains, as well as the 4-1BB and CD3ζ intracellular domains. We examined the phagocytosis of HER2 CAR-M and CD47 CAR-M on ovarian cancer cells and the promotion of adaptive immunity. Two syngeneic tumor models were used to estimate the in vivo antitumor activity of HER2 CAR-M and CD47 CAR-M.

Results
We constructed CAR-Ms targeting HER2 and CD47 and verified their phagocytic ability to ovarian cancer cells in vivo and in vitro. The constructed CAR-Ms showed antigen-specific phagocytosis of ovarian cancer cells in vitro and could activate CD8+ cytotoxic T lymphocyte (CTL) to secrete various anti-tumor factors. For the in vivo model, mice with human-like immune systems were used. We found that CAR-Ms enhanced CD8+ T cell activation, affected tumor-associated macrophage (TAM) phenotype, and led to tumor regression.

Conclusions
We demonstrated the inhibition effect of our constructed novel HER2 CAR-M and CD47 CAR-M on target antigen-positive ovarian cancer in vitro and in vivo, and preliminarily verified that this inhibitory effect is due to phagocytosis, promotion of adaptive immunity and effect on tumor microenvironment.
Knowledge and awareness of policies and programmes to reduce adolescent pregnancy in Ghana: a qualitative study among key stakeholders
Authors: Ahinkorah Bright Opoku , Kang Melissa , Perry Lin , Brooks Fiona 
Published: September 2023

Abstract
Introduction
Adolescent sexual and reproductive health continues to be a major public health issue in low-and middle-income countries. While many countries have policies aimed at reducing adolescent pregnancy, evidence of their impact is unclear. This study sought to explore the knowledge and awareness of policies and programmes aimed at reducing adolescent pregnancy among health and education professionals and grassroot workers in Ghana.

Methods
We employed a cross-sectional, qualitative study design involving semi-structured interviews with 30 key informants (health and education professionals and grassroot workers) in the Central Region of Ghana. We also conducted a desktop review of policies aimed at reducing adolescent pregnancy in Ghana. We used content analysis to analyse the data.

Results
Eight of the 30 participants demonstrated awareness of policies aimed at reducing adolescent pregnancy but only two could elaborate on this. By contrast, 19 of the 30 participants were aware of relevant programmes and provided detailed description of their implementation and activities carried out under each programme. Despite participants’ low policy awareness and knowledge, their descriptions of the activities carried out under each programme aligned with the strategies and activities of the policies mentioned, as evident from the desktop review of the policies.

Conclusion
Greater engagement of stakeholders in future policy development should increase policy awareness. Dissemination of policy content through community-based media channels and in local languages should promote and facilitate stakeholder engagement, which in turn should increase effective policy implementation with subsequent reduction of adolescent pregnancy.
Psychiatric burden in a cohort of adults with Niemann Pick type C disease: from psychotic symptoms to frontal lobe behavioral disorders
Authors: Morin A. , Carle G. , Ponchel A. , Fernández-Eulate G. , Nadjar Y. 
Published: September 2023

Abstract
Objectives
To describe Niemann-Pick type C (NP-C) behavioral symptoms (focusing on psychotic symptoms) and its relation to frontal lobe functioning.

Methods
We retrospectively reviewed medical charts of NP-C-patients followed in the Lysosomal Diseases reference center in Paris Pitié-Salpêtrière. We collected demographic data, psychiatric clinical manifestations, psychometric scales, and extended neuropsychological data including executive and behavioral frontal lobe functions evaluations.

Results
Nineteen patients were included in the study with ten of them having experienced at least one acute psychotic episode, being inaugural for six of them. Most of the patients suffered from behavioral (15/17) and cognitive disorders (18/19) (including executive dysfunction (11/12), apathy (13/17), impaired social cognition (11/13) and stereotyped behaviors (5/10). For five patients, quality of life was significantly impaired by these abnormal behaviors. Concerning frontal neuropsychological evaluation, Facial emotion recognition was by far the most performed neuropsychological test (n = 8) and the score was always abnormal. It is noteworthy that psychotic symptoms were often drug resistant (8/9) and that Miglustat was associated with a better control of psychotic symptoms.

Conclusions
We report a high frequency of psychiatric symptoms in NP-C encompassing acute psychotic manifestations, often presenting early in the course of the disease with atypical features. We also report disabling behavioral manifestations related to frontal dysfunction.
Sintilimab treatment for chronic active Epstein–Barr virus infection and Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis in children
Authors: Chen Ruyue , Lin Qiang , Zhu Yun , Shen Yunyan , Xu Qinying , Tang Hanyun , Cui Ningxun , Jiang Lu , Dai Xiaomei , Chen Weiqing , Li Xiaozhong 
Published: September 2023

Abstract
Background
Chronic active Epstein–Barr virus infection (CAEBV) and Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) are rare but life-threatening progressive diseases triggered by EBV infection. Glucocorticoid/immunosuppressants treatment is temporarily effective; however, most patients relapse and/or progress. Hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy; however, there are risks of transplantation-associated complications. Currently there is no standard treatment for CAEBV and EBV-HLH. Programmed death protein 1 (PD-1) inhibitors have achieved a high response in many EBV-related diseases. Sintilimab (a recombinant human IgG4 monoclonal antibody against PD-1) disrupts the interaction between PD-1 and its ligand, leading to T cell reinvigoration.

Methods
A retrospective analysis was performed on three children with CAEBV or EBV-HLH in the Children’s Hospital of Soochow University between 12 December 2020 and 28 November 2022. The efficacy of sintilimab was evaluated.

Results
Three patients, including two males and one female, were analyzed. Among them, two children were diagnosed with CAEBV with intermittent fever for more than four years, and one child was diagnosed with EBV-HLH. After sintilimab treatment and a mean follow-up of 17.1 months (range 10.0–23.3 months), patients 1 and 3 achieved a complete clinical response and patient 2 achieved a partial clinical response. All three children showed a > 50% decrease in EBV-DNA load in both blood and plasma. EBV-DNA copies in sorted T, B, and NK cells were also markedly decreased after sintilimab treatment.

Conclusion
Our data supported the efficacy of PD-1 targeted therapy in certain patients with CAEBV and EBV-HLH, and suggested that sintilimab could provide a cure for these diseases, without HSCT. More prospective studies and longer follow-up are needed to confirm these conclusions.
Understanding the interface between European wild boar (Sus scrofa) and domestic pigs (Sus scrofa domesticus) in Sweden through a questionnaire study
Authors: Ernholm Linda , Ståhl Karl , Neimanis Aleksija , Widgren Stefan , Sternberg-Lewerin Susanna 
Published: September 2023

Abstract
Background
In recent years, the wildlife/livestock interface has attracted increased attention due to disease transmission between wild and domestic animal populations. The ongoing spread of African swine fever (ASF) in European wild boar (Sus scrofa) emphasize the need for further understanding of the wildlife/livestock interface to prevent disease spill-over between the wild and domestic populations. Although wild boar may also act as a potential source for other infectious disease agents, ASF is currently the most severe threat from wild boar to domestic pigs. To gather information on the wild boar situation at commercial pig producing farms in Sweden, a digital questionnaire survey was distributed through the animal health services.

Results
Most pigs produced for commercial purposes in Sweden are raised without outdoor access. Of the 211 responding pig producers, 80% saw wild boar or signs of wild boar activity in the vicinity of their farm at least once during the year. Observations were significantly correlated with geographical region, but there was no correlation between farm characteristics (farm size, main type of production, outdoor access) and observed wild boar presence or proximity. However, a reported higher frequency of wild boar observations was positively correlated with the observations being made in closer proximity to the farm.
Hunting and strategic baiting were the most common mitigation strategies used to keep wild boar at bay. Of the 14 farms raising pigs with outdoor access, 12 responded that these pigs could be raised solely indoors if needed.
Pigs with outdoor access are required to be fenced in, but double fencing in these outdoor pig enclosures was not practiced by all. A perimeter fence surrounding any type of pig farm was very rare. More than half of the producers that grew crops with intended use for pigs reported crop damage by wild boar.

Conclusion
This study shows that although pigs raised for commercial purposes in Sweden are, to a large extent, kept indoors the potential for indirect contact with wild boar exists and must be considered. Variable local situations regarding wild boar abundance may require an adaptive approach regarding biosecurity efforts.
New ways to cope with depression—study protocol for a randomized controlled mixed methods trial of bouldering psychotherapy (BPT) and mental model therapy (MMT)
Authors: Kind Leona , Luttenberger Katharina , Leßmann Vivien , Dorscht Lisa , Mühle Christiane , Müller Christian P. , Siegmann Eva-Maria , Schneider Sophia , Kornhuber Johannes 
Published: September 2023

Abstract
Background
Due to the growing gap between the demand and supply of therapeutic services for people suffering from depression, with this study, we are investigating the effectiveness and factors of influence of new approaches in group treatments for depression. Two previous studies have already identified bouldering psychotherapy (BPT) as an effective option. It combines psychotherapeutic interventions with action- and body-oriented bouldering exercises. Mental model therapy (MMT) is a new cognitive-behavioral approach for treating depression. It focuses on identifying cognitive distortions, biases in decision making, and false assumptions and aims to correct and replace them with useful mental models. We aim to investigate the effectiveness of the interventions compared with a control group (CG) and to assess the factors of influence in a mixed methods approach.

Methods
The study is being conducted as a randomized controlled intervention trial. Adult participants with unipolar depression are being randomized into three groups (BPT, MMT, or CG), and the first two groups are undergoing a 10-week treatment phase. CG follows their individual standard treatment as usual. A priori power analysis revealed that about 120 people should be included to capture a moderate effect. The primary outcome of the study is depression rated with the Montgomery and Asberg Depression Rating Scale (MADRS) before (t0), directly after (t1), and 12 months after the intervention phase (t2). Data are being collected via questionnaires, computer-assisted video interviews, and physical examinations. The primary hypotheses will be statistically analyzed by mixed model ANOVAs to compare the three groups over time. For secondary outcomes, further multivariate methods (e.g., mixed model ANOVAs and regression analyses) will be conducted. Qualitative data will be evaluated on the basis of the qualitative thematic analysis.

Discussion
This study is investigating psychological and physical effects of BPT and MMT and its factors of influence on outpatients suffering from depression compared with a CG in a highly naturalistic design. The study could therefore provide insight into the modes of action of group therapy for depression and help to establish new short-term group treatments. Methodological limitations of the study might be the clinical heterogeneity of the sample and confounding effects due to simultaneous individual psychotherapy.

Trial registration
ISRCTN, ISRCTN12347878. Registered 28 March 2022,
https://www.isrctn.com/ISRCTN12347878.
Prospective identification of variables as outcomes for treatment (PIVOT): study protocol for a randomised, placebo-controlled trial of hydroxyurea for Ghanaian children and adults with haemoglobin SC disease
Authors: Smart Luke R. , Segbefia Catherine I. , Latham Teresa S. , Stuber Susan E. , Amissah-Arthur Kwesi N. , Dzefi-Tettey Klenam , Lane Adam C. , Dei-Adomakoh Yvonne A. , Ware Russell E. 
Published: September 2023

Abstract
Background
Haemoglobin SC (HbSC) is a common form of sickle cell disease (SCD), especially among individuals of West African ancestry. Persons with HbSC disease suffer from the same clinical complications and reduced quality of life that affect those with sickle cell anaemia (HbSS/Sβ0). Retrospective anecdotal data suggest short-term safety and benefits of hydroxyurea for treating HbSC, yet rigorous prospective data are lacking regarding optimal dosing, clinical and laboratory effects, long-term safety and benefits, and appropriate endpoints to monitor. Prospective Investigation of Variables as Outcomes for Treatment (PIVOT) was designed with three aims: (1) to measure the toxicities of hydroxyurea treatment on laboratory parameters, (2) to assess the effects of hydroxyurea treatment on sickle-related clinical and laboratory parameters, and (3) to identify study endpoints suitable for a future definitive phase III trial of hydroxyurea treatment of HbSC disease.

Methods
PIVOT is a randomised, placebo-controlled, double blind clinical trial of hydroxyurea. Approximately 120 children and 120 adults ages 5–50 years with HbSC disease will be enrolled, screened for 2 months, and then randomised 1:1 to once-daily oral hydroxyurea or placebo. Study treatment will be prescribed initially at 20 ± 5 mg/kg/day with an opportunity to escalate the dose twice over the first 6 months. After 12 months of blinded study treatment, all participants will be offered open-label hydroxyurea for up to 4 years. Safety outcomes include treatment-related cytopenias, whole blood viscosity, and adverse events. Efficacy outcomes include a variety of laboratory and clinical parameters over the first 12 months of randomised treatment, including changes in haemoglobin and fetal haemoglobin, intracranial arterial velocities measured by transcranial Doppler ultrasound, cerebral oxygenation using near infrared spectrometry, spleen volume and kidney size by ultrasound, proteinuria, and retinal imaging. Exploratory outcomes include functional erythrocyte analyses with ektacytometry for red blood cell deformability and point-of-sickling, patient-reported outcomes using the PROMIS questionnaire, and 6-min walk test.

Discussion
For children and adults with HbSC disease, PIVOT will determine the safety of hydroxyurea and identify measurable changes in laboratory and clinical parameters, suitable for future prospective testing in a definitive multi-centre phase III clinical trial.

Trial registration
PACTR, PACTR202108893981080. Registered 24 August 2021, https://pactr.samrc.ac.za
Daytime sleepiness in Chinese professional, semi professional and students soccer players in the Shanghai lockdown
Authors: You Songhui , Cicchella Antonio 
Published: September 2023

Abstract
Purpose
April-May 2021 Shanghai city was under strict lockdown. Soccer players suffered from the restrictions, being unable to train and have a social life. The aim of this study was to compare differences in daytime sleepiness between genders and qualification levels in a cohort university Chinese soccer player under 0 Covid policy restrictions in the urban area of Shanghai.

Methods
491 questionnaires of Epworth Sleepiness Scales (ESS) were compiled online by male and female Soccer Students (SS), Semi-Professional players (SP) and Professional Players (PP) during the ongoing restriction measures post Shanghai lockdown. ANOVA was performed for players levels and gender.

Results
Significant differences were found between the 3 levels and between males and females. PP showed a very low score in the ESS (5,97) well below the threshold of 8 for daytime sleepiness, while SS and SP showed an ESS score above the threshold. Female showed higher scores in comparison to males. Differences between males and females reflect the confinement conditions in the ESS items, showing more difference in the item of ESS which are related with indoor situations.

Conclusions
This study shows the first data on sleepiness in Chinese soccer players of different level of qualification immediately post lockdown condition. Professional male’s players sleepiness was lower, than females, SS and SP after the exceptional lockdown measures. The reasons can reside in the more ordered lifestyle of PP in comparison to SS and SP, which mitigated the effects of the lockdown. Our results suggest that measures to improve sleep in females’ soccer player should be adopted if these exceptional conditions will happen again.
Haemonchus contortus HcL6 promoted the Th9 immune response in goat PBMCs by activating the STAT6/PU.1/NF-κB pathway
Authors: Liang Meng , Zhang Yang , Wang Mingyue , Wen Zhaohai , Chen Cheng , Bu Yongqian , Lu Mingmin , Song Xiaokai , Xu Lixin , Li Xiangrui , Yan Ruofeng 
Published: September 2023

AbstractTh9 cells play a crucial role in parasite immunity. The development of Th9 cells is facilitated by several cytokines. Key transcription factors, such as STAT6, STAT5, and PU.1, are known to enhance IL-9 expression during the Th9 immune response. NF-κB-mediated transduction pathways participate in the induction of IL-9. In a previous study, we unveiled a unique ribosomal protein derived from Haemonchus contortus excretory-secretory proteins (HcESPs) that interact with host Th9 cells. In the present study, the effects of the Haemonchus contortus ribosomal protein L6 domain DE-containing protein (HcL6) on IL-9 secretion, Th9 differentiation, and IL-9 transcription were assessed by employing ELISA, flow cytometry, and qPCR methodologies. The observations revealed the transcriptional upregulation of several key genes within the Th9 immune response pathway. Moreover, silencing STAT6, PU.1, and NF-κB was found to attenuate the Th9 immune response. In this study, we unveiled the Th9 immune response-inducing capabilities of HcL6 and elucidated some of its underlying mechanisms. These findings suggest that HcL6 is an immunostimulatory antigen capable of inducing the Th9 immune response. These insights could prove instrumental in identifying potential candidate antigens for the development of immunoprophylactic strategies against H. contortus infections.
Hepatitis B reactivation in cancer patients receiving immune checkpoint inhibitors: a systematic review and meta-analysis
Authors: Xia Zhengzheng , Zhang Jianyu , Chen Wenjun , Zhou Haiyan , Du Di , Zhu Kongcai , Chen Hui , Meng Jun , Yang Jun 
Published: September 2023

Abstract
Background
Immunotherapy shows promise as a treatment option for various cancers. However, there is growing concern over potential complications from hepatitis B virus (HBV) reactivation after checkpoint blockade immunotherapy. Although most of the previous clinical trials on immune checkpoint inhibitors (ICIs) excluded patients with HBV, a few case reports and retrospective studies of HBV reactivation have been published. The aim of this study is to assess the risk of hepatitis B virus reactivation (HBVr) in patients receiving ICIs for advanced cancer.

Methods
English and Chinese language literature published prior to April 30, 2023, was searched in PubMed, EMBASE, Web of Science, Cochrane, SinoMed, CNKI and Wanfang Data for studies reporting HBVr rates in cancer patients treated with ICIs. A pooled risk estimate was calculated for HBVr rates with 95% confidence intervals (CI).

Results
Data from 34 studies including 7126 patients were retrieved and analyzed. The pooled HBVr rate in cancer patients treated with ICIs was 1.3% (I2 = 90.44%, 95% CI: 0.2–2.9%, P < 0.001). Subgroup analysis revealed that patients diagnosed with hepatocellular carcinoma (HCC), HBV carriers, and patients from Asian regions or in developing countries have a higher rate of HBVr.

Conclusions
Our meta-analysis demonstrated a low risk of HBVr in patients treated with ICIs for advanced cancer. ICI treatment may be safely used in patients with existing HBV infection or chronic hepatitis B, accompanied by regular monitoring and appropriate antiviral prophylaxis if necessary.

Graphical Abstract