bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical presentations and treatment outcomes of Hashimoto encephalopathy at Siriraj Hospital – Thailand’s largest national tertiary referral center
Authors: Dumrikarnlert Chaisak , Thakolwiboon Smathorn , Senanarong Vorapun
Published: September 2023

Background

Hashimoto encephalopathy has multiple clinical presentations, and other than the presence of thyroid antibody, laboratory and imaging investigations are all non-specific. Data specific to the clinical presentations and treatment outcomes of patients with Hashimoto encephalopathy in Thailand remain scarce.

Objectives

To retrospectively investigate the clinical presentations and treatment outcomes of patients with Hashimoto encephalopathy at Siriraj Hospital.

Methods

Patients who presented with acute encephalopathy at our center during July 2012-March 2017 were evaluated for eligibility. The inclusion criteria were positive anti-thyroperoxidase (anti-TPO) or anti-thyroglobulin (anti-Tg) in serum with negative neuronal antibody in serum or cerebral spinal fluid (CSF). Clinical presentations, symptom duration, laboratory results of thyroid status and thyroid autoantibody, CSF study, and clinical outcomes were collected.

Results

Of the 204 patients who presented with encephalopathy, 31 (15.2%) were positive for the anti-TPO or anti-Tg antibody. Of those, 13 patients met the diagnostic criteria for Hashimoto encephalopathy. Clinical presentations included cognitive impairment (76.9%), clouding of consciousness (46.2%), and behavior change (30.8%). The neuropsychiatric presentations were visual hallucination (30.8%), auditory hallucination (15.4%), delusion (7.7%), and mood disturbance (23.1%). Other clinical presentations included seizure (38.5%), abnormal movement (23.1%), sleep disturbance (38.5%), ataxia (46.2%), stroke-like episode (15.4%), and fever (15.4%). Most patients (76.9%) had onset within < 3 months. Regarding outcomes, 1 patient who did not receive corticosteroid died from status epilepticus and septic shock. Among the 12 patients who received corticosteroid, 9 (75%) had marked improvement, 1 (8.3%) had slight improvement, and 2 (16.6%) had no clinical improvement. Seven patients (53.9%) had normal thyroid function, 4 patients (30.8%) had subclinical hypothyroidism, and 2 patients (15.4%) had subclinical hyperthyroidism.

Conclusions

The results of this study revealed cognitive impairment, neuropsychiatric symptoms, seizure, ataxia, and sleep disturbance to be common manifestations of Hashimoto encephalopathy. This condition should always be considered in individuals with subacute onset of unexplained cognitive impairment or cerebellar ataxia. Laboratory and neuroimaging investigations were all found to be nonspecific in Hashimoto encephalopathy. Most patients responded well to treatment, so clinical suspicion and early diagnosis and treatment will lead to improved patient outcomes.
Investigating the impact of diameters and thread designs on the Biomechanics of short implants placed in D4 bone: a 3D finite element analysis
Authors: Alqahtani Ali Robaian , Desai Shrikar R. , Patel Jignesh R. , Alqhtani Nasser Raqe , Alqahtani Abdullah Saad , Heboyan Artak , Fernandes Gustavo V. O. , Mustafa Mohammed , Karobari Mohamed Isaqali
Published: September 2023

Background

Dental implants emerge as a dependable and efficacious alternative for patients experiencing partial or complete tooth loss. The stability of these implants is influenced by surface topography and macro-level design. In cases where the height of the maxillary posterior region is diminished, employing short implants can prove advantageous. With the aim of examining the distribution of von Mises stress, strain, and micromovement in D4 bone quality surrounding platform-switched short implants, measuring 6 mm in length and featuring diameters ranging from 4 to 6 mm, as well as different thread designs, an in-depth finite element analysis was conducted under immediate loading conditions.

Methodology

A 3D finite element model was constructed to simulate maxillary molar crowns, incorporating an implant with a length of 6 mm and varying diameters and thread designs. The diameters utilized were 4/3.6 mm, 5/4 mm, and 6/4.8 mm, while the thread designs included buttress, square, and triangle patterns. Each model underwent analysis with a 100 N force applied in two directions: vertical and oblique, relative to the long axis of the implant. Stress, strain, and micromovement in the peri-implant region were recorded, employing the Ansys Workbench R v.18.1 software for modelling and analysis.

Results

When comparing all three diameters, the wide diameter (6 mm threads) exhibited the lowest values of peri-implant von Mises stresses (3.3 MPa and 35.1 MPa), strains (194 Ɛ and 484 Ɛ), and micromovements (0.7 μm and 1.3 Ɛ) subjected to axial and non-axial loading of a 100 N force. Notably, square microthreads yielded the most favorable stress parameters among the different thread shapes, manifesting the minimum values of stress, strains, and micromovements in their vicinity.

Conclusion

For the treatment of atrophic ridges or in scenarios necessitating extensive surgical preparation of the implant site, a combination of short implants, wide diameters, and platform switching can be employed. In situations with reduced bone height and the requirement for an implant-supported prosthesis to replace a missing permanent maxillary molar, the utilization of wide-diameter platform-switched short implants measuring 6 mm in length, featuring a square thread design, should be taken into consideration.
Application of PBL combined with traditional teaching in the Immunochemistry course
Authors: Song Pingping , Shen Xiangchun
Published: September 2023

Background

The problem-based learning (PBL) model has been widely carried out in many fields of medical colleges and universities. Immunochemistry as a cross-disciplinary science plays a vital role in preventing the occurrence of diseases and bridging the development of Life Science and Medicine. But now the Immunochemistry course still lacks the teaching practice in PBL. To explore the significance of PBL applied in the Immunochemistry course, the effect of the PBL model on the learning of undergraduates majoring in Chemicobiology was systematically evaluated.

Methods

The teaching objects were the undergraduates majoring in Chemicobiology from Guizhou Medical University. The PBL model was applied in the Immunochemistry course. 62 undergraduates in Grade 2018 were set as the control group and adopted the traditional expository model. 93 undergraduates in Grades 2019–2020 were separately set as the experimental groups, which adopted the PBL model based on traditional lecture-based learning. In the PBL model, six cases related to course contents were designed for the students to complete. The final exams of the undergraduates in Grades 2018–2020 were analyzed by the score ranges (< 60 points, 60–69 points, 70–79 points, and ≥ 80 points) and nonparametric test. Finally, the questionnaire survey about the teaching evaluation was performed in Grades 2019–2020.

Results

In Grades 2019 and 2020, the excellent rates (≥ 80 points), pass rates (≥ 60 points), fail rates (< 60 points), and average scores of the undergraduates were separately about 29%, 91.11% and 93.75%, 6.25%, and 8.89%, and 72.55 and 74.45 points. But in Grade 2018, the excellent rate, pass rate, failure rate, and average score of the undergraduates were separately 9.68%, 59.68%, 40.32%, and 62.55 points. By the statistical analysis, it was found that the excellent rates (χ2 = 8.317,P < 0.005) and pass rates (χ2 = 24.52,P < 0.0001) in Grades 2018–2020 were different, of which Grade 2020were the highest (29.17%, 93.75%) and Grade 2018 was the lowest (9.68%, 59.68%). The average score, excellent rate, and pass rate in Grade 2018 had significant differences with Grade 2019 (P < 0.0001,P < 0.0167) and Grade 2020 (P < 0.001,P < 0.0167). The questionnaire survey also showed that the student’s learning interests, independent problem-solving ability, knowledge structure system, and scientific thought and teamwork awareness were enhanced. In Grades 2019 and 2020, the ICC (95% CI) of criterion validity and inter-rater reliability were separately 0.42/0.34 and 0.81/0.80 (P < 0.0001).

Conclusion

The combination of PBL and traditional expository models played positive roles in the student’s learning in the Immunochemistry course.
Induced pluripotent stem cells: ex vivo models for human diseases due to mitochondrial DNA mutations
Authors: Chen Chao , Guan Min-Xin
Published: September 2023

Mitochondria are essential organelles for cellular metabolism and physiology in eukaryotic cells. Human mitochondria have their own genome (mtDNA), which is maternally inherited with 37 genes, encoding 13 polypeptides for oxidative phosphorylation, and 22 tRNAs and 2 rRNAs for translation. mtDNA mutations are associated with a wide spectrum of degenerative and neuromuscular diseases. However, the pathophysiology of mitochondrial diseases, especially for threshold effect and tissue specificity, is not well understood and there is no effective treatment for these disorders. Especially, the lack of appropriate cell and animal disease models has been significant obstacles for deep elucidating the pathophysiology of maternally transmitted diseases and developing the effective therapy approach. The use of human induced pluripotent stem cells (iPSCs) derived from patients to obtain terminally differentiated specific lineages such as inner ear hair cells is a revolutionary approach to deeply understand pathogenic mechanisms and develop the therapeutic interventions of mitochondrial disorders. Here, we review the recent advances in patients-derived iPSCs as ex vivo models for mitochondrial diseases. Those patients-derived iPSCs have been differentiated into specific targeting cells such as retinal ganglion cells and eventually organoid for the disease modeling. These disease models have advanced our understanding of the pathophysiology of maternally inherited diseases and stepped toward therapeutic interventions for these diseases.
A novel near-infrared EGFR targeting probe for metastatic lymph node imaging in preclinical mouse models
Authors: Xie Diya , Li Yunlong , Shi Jiahong , Zhu Yao Ping , Wang Yiqing , Butch Christopher J. , Wang Zhiyong
Published: September 2023

For the treatment of patients with oral squamous cell carcinoma (OSCC), the imaging of cervical lymph nodes and the evaluation of metastastic progression are of great significance. In recent years, the development of new non-radioactive lymph node tracers has been an area of intense research. Here, we report the synthesis, good biocompatibility, and in vivo evaluation of a new small molecule near-infrared (NIR) fluorescence probe by the conjugation of Lapatinib to S0456 (LP-S). We show that like Lapatinib, LP-S binds to the epidermal growth factor receptor (EGFR) resulting in high quality fluorescence imaging of metastatic lymph nodes in OSCC mouse models. After local injection of LP-S into the tumor, the lymphatic drainage pathway and lymph nodes can be clearly identified by NIR fluorescence imaging. Further, the LP-S probe shows higher contrast and longer retention in metastatic lymph nodes, allowing them to be differentiated from normal lymph nodes, and affording a new choice for fluorescence-guided surgery.

Graphical abstract
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

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

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

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

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

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

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

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

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

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

Th9 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

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
Investigating the factor structure and measurement invariance of the eating disorder examination questionnaire (EDE-Q) among cisgender gay men and lesbian women from the United States
Authors: Compte Emilio J. , McGuire F. Hunter , Brown Tiffany A. , Lavender Jason M. , Murray Stuart B. , Capriotti Matthew R. , Flentje Annesa , Lubensky Micah E. , Lunn Mitchell R. , Obedin-Maliver Juno , Nagata Jason M.
Published: September 2023

Background

Although the Eating Disorder Examination-Questionnaire (EDE-Q) is one of the most widely used self-report assessments of eating disorder symptoms, evidence indicates potential limitations with its original factor structure and associated psychometric properties in a variety of populations, including sexual minority populations. The aims of the current investigation were to explore several previously published EDE-Q factor structures and to examine internal consistency and measurement invariance of the best-fitting EDE-Q model in a large community sample of cisgender gay men and cisgender lesbian women.

Methods

Data were drawn from 1624 adults (1060 cisgender gay men, 564 cisgender lesbian women) who participated in The PRIDE Study, a large-scale longitudinal cohort study of sexual and gender minorities from the United States. A series of confirmatory factor analyses (CFAs) were conducted to explore the fit of eight proposed EDE-Q models; internal consistency (Cronbach’s alphas, Omega coefficients) and measurement invariance (multi-group CFA) were subsequently evaluated.

Results

A brief seven-item, three-factor (dietary restraint, shape/weight overvaluation, body dissatisfaction) model of the EDE-Q from Grilo et al. (Obes Surg. 23:657–662, 2013), consistently evidenced the best fit across cisgender gay men and lesbian women. The internal consistencies of the three subscales were adequate in both groups, and measurement invariance across the groups was supported.

Conclusions

Taken together, these findings support the use of the seven-item, three-factor version of the EDE-Q for assessing eating disorder symptomatology in cisgender gay men and lesbian women. Future studies can confirm the current findings in focused examinations of the seven-item, three-factor EDE-Q in diverse sexual minority samples across race, ethnicity, socioeconomic status, and age ranges.
Refractory esophageal anastomotic stricture after esophageal atresia surgery improved with retrograde balloon dilatation through gastrostomy followed by laparoscopic fundoplication: a case report
Authors: Nakagawa Yoichi , Uchida Hiroo , Hinoki Akinari , Shirota Chiyoe , Sumida Wataru , Makita Satoshi , Yokota Kazuki , Amano Hizuru , Yasui Akihiro , Kato Daiki , Gohda Yousuke , Maeda Takuya
Published: September 2023

Background

An esophageal anastomotic stricture (EAS) after an esophageal atresia surgery occurs in approximately 4–60% of the cases, and its first-line therapy includes balloon dilatation. Oral balloon dilatation cannot be performed in some EAS cases; conversely, even if dilatation is possible, these strictures recur in some cases, necessitating a surgical procedure for repairing the stenosis. However, these procedures are invasive and have short- and long-term complications. If an EAS recurs repeatedly after multiple balloon dilations, gastroesophageal reflux disease (GERD) may be the underlying cause. A fundoplication procedure may be effective for treating a refractory EAS, as in the present case.

Case presentation

A neonatal patient with type D esophageal atresia underwent thoracoscopic esophago-esophageal anastomosis at the age of 1 day, and her postoperative course was uneventful. Thereafter, the patient underwent gastrostomy for poor oral intake at the age of 3 months. After gastrostomy, the patient presented with a complete obstructive EAS. Balloon dilatation via the oral route was attempted; however, a guidewire could not be inserted into the EAS site. Hence, retrograde balloon dilatation via gastrostomy was performed successfully. However, the EAS recurred easily thereafter, and laparoscopic anti-reflux surgery was performed to prevent GERD. The anti-reflux surgery cured the otherwise refractory EAS and prevented its recurrence.

Conclusions

Retrograde balloon dilatation is another treatment option for an EAS. When an EAS recurs soon after dilatation, the patient must be evaluated for GERD; if severe GERD is observed, an appropriate anti-reflux surgery is required before dilating the EAS.
A convergent alternating projections onto convex sets method for data reconstruction
Authors: Sun Yimin , Hirsch Quentin
Published: September 2023

The alternating projections onto convex sets (POCS) method is one of the well-known data reconstruction methods in the seismic field. We first review the POCS theory in mathematics and then point out that many POCS methods reported in the literature have overlooked the convergence condition, which is a fundamental and important aspect in POCS. We further develop a convergent POCS (CP) method that uses an existing POCS method as the algorithm framework and adds a convergence condition before a convex set is updated, and we mathematically prove the convergence of this proposed CP method. Several examples are used to demonstrate the success of the CP method. The CP method is a reconstruction scheme robust to variations in the input data and the thresholding schedule.
Benchmarking of the Cervical Cancer Care Cascade and Survival Outcomes After Radiation Treatment in a Low- and Middle-Income Country Setting
Authors: Grover Surbhi , MacDuffie Emily , Nsingo Memory , Lei Xiudong , Mehta Priyanka , Davey Sonya , Urusaro Sandra , Chiyapo Sebathu , Vuylsteke Peter , Monare Barati , Bazzett-Matabele Lisa , Ralefala Tlotlo , Luckett Rebecca , Ramogola-Masire Doreen , Smith Grace L.
Published: September 2023

Delays in care for patients with cervical cancer in Botswana can be benchmarked using a multidisciplinary clinic model.
HIV and Early Treatment Outcomes Among Women With Cervical Cancer Treated With Concurrent Chemoradiation in Tanzania
Authors: Mrema Alita Steven , Ngoma Mamsau , Josiah Chacha , Lugina Emmanuel , Mvungi Nanzoke , Paul Magreth , Mkuchika Evelyne , Nundu Emmanuel , Iddy Salama Khamisi , Rugengamanzi Eulade , Vuhahula Yokobeth Mtambo , Kiwanga Faraja Christopher , Wood Charles , Mwaiselage Julius
Published: September 2023

PURPOSE

Cervical cancer (CC) is the leading malignancy in Tanzania. Low-income countries are faced with double epidemics of HIV and CC. This study aimed to investigate how HIV and cancer stage at diagnosis affect early treatment outcomes among women with CC treated with concurrent chemoradiation in Tanzania in the highly active antiretroviral therapy era.

MATERIALS AND METHODS

This was a prospective cohort study of patients newly diagnosed with CC at the Ocean Road Cancer Institute from November 2019 to January 2020. The tumor response was assessed using RECIST 3 months post-treatment. The tumor response was categorized as a complete or partial response according to the ultrasound and pelvic examination findings. The univariate and multivariate logistic regression explained the relationship between several covariates (age, stage, HIV status, equivalent dose in 2 Gy fractions, chemotherapy cycles, and treatment time) and treatment response.

RESULTS

A total of 102 patients with CC were included in this study at baseline. After adjusting for other covariates, only completion of treatment within 56 days (odds ratio [OR], 9.23; 95% CI, 1.53 to 55.85; P = .016) and receiving at least three cycles of cisplatin (OR, 5.6; 95% CI, 1.47 to 21.34; P = .012) were significantly associated with complete tumor response. HIV status was not significantly associated with complete tumor response (OR, 1.534; 95% CI, 0.424 to 5.545; P = .5144).

CONCLUSION

Early treatment response was independent of HIV status. With wide coverage of anitretroviral therapy, patients with HIV can receive radical treatment and have the same early outcomes as their HIV-negative counterparts.
Loss of Chromosome 3q Is a Prognostic Marker in Fusion-Negative Rhabdomyosarcoma
Authors: Dehner Carina A. , Bell Robert C. , Cao Yang , He Kevin , Chrisinger John S.A. , Armstrong Amy E. , Yohe Marielle , Shern Jack , Hirbe Angela C.
Published: September 2023

We show that loss of chr3q is associated with worse outcomes in fusion-negative (FN)-RMS compared with fusion-positive (FP)-RMS, suggesting that this chromosomal abnormality could be a prognostic marker for (FN) RMS.
Erratum: On the derivation of the generalized Langevin equation and the flucutation-dissipation theorem
Authors: Vroylandt Hadrien
Published: September 2023

Original article:
EPL, 140 (2022) 62003.
Lydia Davis’s Grammatical Examples
Authors: Boorman Lola
Published: September 2023

Critics have always struggled to situate the work of short story writer and translator Lydia Davis within wider trends in postwar and contemporary literature. Paying particular attention to a group of Davis’s “grammar stories,” this essay reads Davis’s fiction as Wittgensteinian “grammatical investigations” that attempt to work against what Toril Moi has described as the “generalized doubt” that characterized the theoretical and aesthetic “skepticism” of postmodernism. Davis’s commitment to this process situates her work within post-postmodern debates about doubt and belief, but reframes these concerns about communication, both aesthetic and social, as problems of grammar. The essay examines how her grammatical investigations resist poststructuralist interpretations of language that dominated the work of her postmodern contemporaries, especially (her ex-partner) Paul Auster, in the 1980s and 1990s. It goes on to explore the gendered labor involved in these kinds of grammatical investigation, labor that is often excluded from the institutional mainstream but crucial in devising “therapies” for problems of linguistic skepticism.
Supporting the translation of multiscale research in rare disease
Authors: Hooper Kirsty M. , Hmeljak Julija
Published: September 2023

Summary: In anticipation of our upcoming Special Issue, ‘Translating Multiscale Research in Rare Disease’, we celebrate the strides taken in rare disease research that are improving patient diagnosis, prognosis and treatment.
Characterisation of TbSmee1 suggests endocytosis allows surface-bound cargo to enter the trypanosome flagellar pocket
Authors: Schichler Daja , Konle Antonia , Spath Eva-Maria , Riegler Sina , Klein Alexandra , Seleznev Anna , Jung Sisco , Wuppermann Timothy , Wetterich Noah , Borges Alyssa , Meyer-Natus Elisabeth , Havlicek Katharina , Pérez Cabrera Sonia , Niedermüller Korbinian , Sajko Sara , Dohn Maximilian , Malzer Xenia , Riemer Emily , Tumurbaatar Tuguldur , Djinovic-Carugo Kristina , Dong Gang , Janzen Christian J. , Morriswood Brooke
Published: September 2023

All endocytosis and exocytosis in the African trypanosome Trypanosoma brucei occurs at a single subdomain of the plasma membrane. This subdomain, the flagellar pocket, is a small vase-shaped invagination containing the root of the single flagellum of the cell. Several cytoskeleton-associated multiprotein complexes are coiled around the neck of the flagellar pocket on its cytoplasmic face. One of these, the hook complex, was proposed to affect macromolecule entry into the flagellar pocket lumen. In previous work, knockdown of T. brucei (Tb)MORN1, a hook complex component, resulted in larger cargo being unable to enter the flagellar pocket. In this study, the hook complex component TbSmee1 was characterised in bloodstream form T. brucei and found to be essential for cell viability. TbSmee1 knockdown resulted in flagellar pocket enlargement and impaired access to the flagellar pocket membrane by surface-bound cargo, similar to depletion of TbMORN1. Unexpectedly, inhibition of endocytosis by knockdown of clathrin phenocopied TbSmee1 knockdown, suggesting that endocytic activity itself is a prerequisite for the entry of surface-bound cargo into the flagellar pocket.