bluuebunny/crossref_metadata_2025_split huggingface dataset:
TORREY, a Phase 2 study to evaluate the efficacy and safety of inhaled seralutinib for the treatment of pulmonary arterial hypertension
Authors: Frantz Robert P. , Benza Raymond L. , Channick Richard N. , Chin Kelly , Howard Luke S. , McLaughlin Vallerie V. , Sitbon Olivier , Zamanian Roham T. , Hemnes Anna R. , Cravets Matt , Bruey Jean‐Marie , Roscigno Robert , Mottola David , Elman Erin , Zisman Lawrence S. , Ghofrani Hossein‐Ardeschir 
Published: October 2021

Aberrant kinase signaling that involves platelet‐derived growth factor receptor (PDGFR) α/β, colony stimulating factor 1 receptor (CSF1R), and stem cell factor receptor (c‐KIT) pathways may be responsible for vascular remodeling in pulmonary arterial hypertension. Targeting these specific pathways may potentially reverse the pathological inflammation, cellular proliferation, and fibrosis associated with pulmonary arterial hypertension progression. Seralutinib (formerly known as GB002) is a novel, potent, clinical stage inhibitor of PDGFRα/β, CSF1R, and c‐KIT delivered via inhalation that is being developed for patients with pulmonary arterial hypertension. Here, we report on an ongoing Phase 2 randomized, double‐blind, placebo‐controlled trial (NCT04456998) evaluating the efficacy and safety of seralutinib in subjects with World Health Organization Group 1 Pulmonary Hypertension who are classified as Functional Class II or III. A total of 80 subjects will be enrolled and randomized to receive either study drug or placebo for 24 weeks followed by an optional 72‐week open‐label extension study. The primary endpoint is the change from baseline to Week 24 in pulmonary vascular resistance by right heart catheterization. The secondary endpoint is the change in distance from baseline to Week 24 achieved in the 6‐min walk test. A computerized tomography sub‐study will examine the effect of seralutinib on pulmonary vascular remodelling. A separate heart rate monitoring sub‐study will examine the effect of seralutinib on cardiac effort during the 6‐min walk test.
The midterm effect of exercise capacity and quality of life in adult patients who underwent hybrid transthoracic device closure of ventricular septal defects
Authors: Chen Qiang , Yang Rong , Lei Yu-Qing , Sun Kai-Peng , Cao Hua 
Published: October 2021

Abstract
Objective
To investigate the midterm effect of exercise capacity and quality of life (QoL) of adult patients who underwent transthoracic device closure of ventricular septal defects (VSDs) and explore the gap in the quality of life and cardiopulmonary function between those patients and healthy people.

Methods
From January 2010 to January 2015, 58 adult patients who underwent transthoracic device closure of VSD and 60 healthy people matched for age and sex were selected and analyzed. Echocardiography and exercise capacity tests were performed, and the MOS 36-item short-form health survey (SF-36) was used to investigate the changes in QoL.

Results
Fifty-five patients completed the study. At the 1-year and 5-year follow-ups, the patients’ left ventricular end-systolic and end-diastolic diameters were smaller than those preoperatively, but the difference was not statistically significant. In the QoL survey, the patients’ scores after treatment showed a trend of improvement, and the improvement effect was not transient. After VSD closure, the difference in QoL between the patients and the control group was significantly reduced. However, in the exercise capacity test, the patients’ results were still worse than those of the controls.

Conclusion
Transthoracic device closure of VSDs is significant in improving adult patients’ QoL at the midterm follow-up, reflected in their physical and psychological fields. However, they are still unable to achieve normal levels of peak exercise ability. Therefore, further exploration and interventions are worth considering.
Disease duration of progression is helpful in identifying isolated bulbar palsy of amyotrophic lateral sclerosis
Authors: Zhang Huagang , Chen Lu , Tian Jinzhou , Fan Dongsheng 
Published: October 2021

Abstract
Background
Compared with typical bulbar onset amyotrophic lateral sclerosis (ALS), isolated bulbar palsy (IBP), an often under-understood variant of ALS, is characterized by symptoms confined to bulbar region for extended periods and relative preservation of limb and ventilation function. To find a cutoff value of disease duration that can distinguish IBP from typical bulbar onset ALS well, the association of survival with disease progression in bulbar onset ALS patients was analyzed.

Methods
Clinical data of bulbar onset ALS patients were collected from January 2009 to December 2013. The duration from bulbar onset to first significant limb involvement was analyzed by a cutoff point analysis with maximally selected log-rank statistics and dichotomized to categorize patient outcomes. The patients were divided into two groups, the IBP and typical bulbar onset ALS groups, according to the cutoff value. Clinical features were compared.

Results
115 bulbar onset ALS patients were recruited, and the duration from bulbar onset to first significant limb involvement was associated with survival (P < 0.001). The cutoff duration was 20 months. 19 patients were identified as IBP and 96 patients as typical bulbar onset ALS using 20 months as the cutoff duration. Female was more common, limb weakness was less frequent and pure upper motor neuron (UMN) bulbar signs were more frequent in the IBP group than in the typical bulbar onset ALS group (P = 0.047; P = 0.004; P = 0.031). The median survival time of the IBP group was significantly longer than that of the typical bulbar onset ALS group (64 months and 26 months, respectively; P < 0.001).

Conclusions
A cutoff duration of 20 months from bulbar onset to first significant limb involvement may be used to specifically distinguish IBP from typical bulbar onset ALS. IBP was characterized by female predominance, relative preservation of limb function, more pure UMN bulbar signs and a relatively benign prognosis.
Successful repeated uterine artery embolization in postpartum hemorrhage with disseminated intravascular coagulation: a case report and literature review
Authors: Sugai Shunya , Nonaka Taro , Tamegai Kana , Sato Tatsuhiko , Haino Kazufumi , Enomoto Takayuki , Nishijima Koji 
Published: October 2021

Abstract
Background
Postpartum hemorrhage (PPH) is a potentially fatal condition requiring urgent and appropriate intervention. Uterine artery embolization (UAE) has a high hemostatic capacity for PPH, but it may fail. Disseminated intravascular coagulation (DIC) has been reported as a risk factor associated with the failure of UAE.

Case presentation
A 37-year-old primigravida with dichorionic diamniotic twins and placenta previa underwent cesarean section. The blood loss during surgery was 4950 mL. Hemostasis was achieved using an intrauterine balloon tamponade device. However, she lost a further 2400 mL of blood 5 h after surgery. We embolized both uterine arteries using gelatin sponges and confirmed hemostasis. She was suffering from DIC and received ample blood transfusions. However, a further 1300 mL of blood was lost 18 h after surgery and we performed repeated UAE, with complete recanalization of the uterine arteries on both sides and re-embolization with gelatin sponges. Her DIC was treated successfully by blood transfusions at this time, and she showed no further bleeding after the repeated UAE.

Conclusions
DIC is a risk factor for the failure of UAE. Repeated UAE may be effective after sufficient improvement of the hematological status in patients with PPH and DIC.
Antiangiogenic antibody BD0801 combined with immune checkpoint inhibitors achieves synergistic antitumor activity and affects the tumor microenvironment
Authors: Xue Liting , Gao Xingyuan , Zhang Haoyu , Tang Jianxing , Wang Qian , Li Feng , Li Xinxin , Yu Xiaohong , Lu Zhihong , Huang Yue , Tang Renhong , Yang Wenqing 
Published: October 2021

Abstract
Background
Signaling through VEGF/VEGFR induces cancer angiogenesis and affects immune cells. An increasing number of studies have recently focused on combining anti-VEGF/VEGFR agents and immune checkpoint inhibitors (ICIs) to treat cancer in preclinical and clinical settings. BD0801 is a humanized rabbit anti-VEGF monoclonal antibody in the clinical development stage.

Methods
In this study, the anti-cancer activities of BD0801 and its potential synergistic anti-tumor effects when combined with different immunotherapies were assessed by using in vitro assays and in vivo tumor models. Ex vivo studies were conducted to reveal the possible mechanisms of actions (MOA) underlying the tumor microenvironment modification.

Results
BD0801 showed more potent antitumor activity than bevacizumab, reflected by stronger blockade of VEGF/VEGFR binding and enhanced inhibitory effects on human umbilical vein endothelial cells (HUVECs). BD0801 exhibited dose-dependent tumor growth inhibitory activities in xenograft and murine syngeneic tumor models. Notably, combining BD0801 with either anti-PD-1 or anti-PD-L1 antibodies showed synergistic antitumor efficacy in both lung and colorectal cancer mouse models. Furthermore, the mechanistic studies suggested that the MOA of the antitumor synergy involves improved tumor vasculature normalization and enhanced T-cell mediated immunity, including increased tumor infiltration of CD8+ and CD4+ T cells and reduced double-positive CD8+PD-1+ T cells.

Conclusions
These data provide a solid rationale for combining antiangiogenic agents with immunotherapy for cancer treatment and support further clinical development of BD0801 in combination with ICIs.
Social and environmental risk factors for unintentional suffocation among infants in China: a descriptive analysis
Authors: Yu Xue , Miao Lei , Zhu Jun , Liang Juan , Dai Li , Li Xiaohong , Li Qi , Rao Rui , Yuan Chunhua , Wang Yanping , He Chunhua , Kang Leni 
Published: October 2021

AbstractBackgroundThis retrospective study aimed to determine the epidemiological features of deaths caused by unintentional suffocation among infants in China.MethodsThe data used in this study were obtained from China’s Under 5 Child Mortality Surveillance System (U5CMSS) from October 1, 2015, to September 30, 2016. A total of 377 children under 1 year of age who died from unintentional suffocation were included in the survey. Primary caregivers were interviewed individually using the Unintentional Suffocation Mortality among Children under 5 Questionnaire. EpiData was used to establish the database, and the results were analysed using SPSS 22.0.ResultsMost (85.9%) unintentional infant suffocations occurred in rural areas, and 67.5% occurred in infants 0 to 3 months old. Among the primary caregivers of the infants, most (82.7%) had a junior middle school education or below, and 83.1% of them lacked unintentional suffocation first aid skills. Of the 377 unintentional suffocated-infant deaths, the causes of death were accidental suffocation and strangulation in bed (ASSB) (193, 51.2%), inhalation suffocation (154, 40.8%), other unintentional suffocation (6, 1.6%), and unknown (24, 6.4%). Among the infant deaths due to ASSB, overlaying (88.6%) was the most frequently reported circumstance. A total of 93.8% of cases reported occurred during co-sleeping/bed sharing with parents, and in 72.8% of the cases, the infants were covered with the same quilt as their parents. In our study, most inhalation suffocation deaths (88.3%) involved liquid food (such as breast milk and formula milk). A total of 80.5% of infant deaths reportedly occurred after eating; in 28.2% of those cases, the infants were held upright and patted by their caregivers, and 57.2% of them were laid down to sleep immediately after eating.ConclusionsTo reduce the occurrence of unintentional suffocation, local government should strengthen knowledge and awareness of unintentional suffocation prevention and safety among parents and caregivers. Additionally, health care providers should educate parents and caregivers about safety issues of unintentional suffocation, and relevant policies should be introduced to provide environments and activities that reduce the risk of suffocation, such as promoting the Safe to Sleep Campaign. It is important to enhance the focus on infant unintentional suffocation as a health issue.
A psychometric assessment of a network social capital scale among sexual minority men and gender minority individuals
Authors: Zarwell Meagan , Walsh Jennifer L. , Quinn Katherine G. , Kaniuka Andréa , Patton Alexandra , Robinson William T. , Cramer Robert J. 
Published: October 2021

AbstractBackgroundSocial capital, the potential for individuals to access resources through group memberships, is linked to a constellation of health outcomes. We modified a previously evaluated Constructed Family Social Capital Scale for gay, bisexual and other men who have sex with men who belong to constructed families to create a new measure of social capital within sexual minority men and gender minority individuals’ social networks.MethodsParticipants were recruited from a Pride festival in Milwaukee, Wisconsin in 2018 to complete a cross-sectional survey. This analysis is restricted to 383 participants who identified as sexual minority men or gender minority individuals and completed nine items measuring social capital within their social networks. We conducted exploratory and confirmatory factor analyses to assess factor structure. Internal consistency was measured using Cronbach’salpha.ResultsReliability was high, indicating the scale’s utility to assess Network Social Capital among sexual minority men and gender minority individuals. A single-factor solution with high factor loadings was found for the nine-item scale.ConclusionsThis study extended the psychometric properties of a preliminary social capital instrument modified from a prior study in a different population and context. The modified measure has implications for use among sexual minority men and gender minority individuals to measure social capital within social networks. Previous studies suggest that interventions to enhance social capital among sexual minority men and gender minority individuals may be beneficial for HIV prevention interventions. This tool may be relevant for the evaluation of social capital interventions within networks of sexual minority men and gender minority individuals.
Targeting strategies for oxaliplatin-induced peripheral neuropathy: clinical syndrome, molecular basis, and drug development
Authors: Yang Yang , Zhao Bing , Gao Xuejiao , Sun Jinbing , Ye Juan , Li Jun , Cao Peng 
Published: October 2021

AbstractOxaliplatin (OHP)-induced peripheral neurotoxicity (OIPN) is a severe clinical problem and potentially permanent side effect of cancer treatment. For the management of OIPN, accurate diagnosis and understanding of significant risk factors including genetic vulnerability are essential to improve knowledge regarding the prevalence and incidence of OIPN as well as enhance strategies for the prevention and treatment of OIPN. The molecular mechanisms underlying OIPN are complex, with multi-targets and various cells causing neuropathy. Furthermore, mechanisms of OIPN can reinforce each other, and combination therapies may be required for effective management. However, despite intense investigation in preclinical and clinical studies, no preventive therapies have shown significant clinical efficacy, and the established treatment for painful OIPN is limited. Duloxetine is the only agent currently recommended by the American Society of Clinical Oncology. The present article summarizes the most recent advances in the field of studies on OIPN, the overview of the clinical syndrome, molecular basis, therapy development, and outlook of future drug candidates. Importantly, closer links between clinical pain management teams and oncology will advance the effectiveness of OIPN treatment, and the continued close collaboration between preclinical and clinical research will facilitate the development of novel prevention and treatments for OIPN.
Surfaceome CRISPR screen identifies OLFML3 as a rhinovirus-inducible IFN antagonist
Authors: Mei Hong , Zha Zhao , Wang Wei , Xie Yusang , Huang Yuege , Li Wenping , Wei Dong , Zhang Xinxin , Qu Jieming , Liu Jia 
Published: October 2021

Abstract
Background
Rhinoviruses (RVs) cause more than half of common colds and, in some cases, more severe diseases. Functional genomics analyses of RVs using siRNA or genome-wide CRISPR screen uncovered a limited set of host factors, few of which have proven clinical relevance.

Results
Herein, we systematically compare genome-wide CRISPR screen and surface protein-focused CRISPR screen, referred to as surfaceome CRISPR screen, for their efficiencies in identifying RV host factors. We find that surfaceome screen outperforms the genome-wide screen in the success rate of hit identification. Importantly, using the surfaceome screen, we identify olfactomedin-like 3 (OLFML3) as a novel host factor of RV serotypes A and B, including a clinical isolate. We find that OLFML3 is a RV-inducible suppressor of the innate immune response and that OLFML3 antagonizes type I interferon (IFN) signaling in a SOCS3-dependent manner.

Conclusion
Our study suggests that RV-induced OLFML3 expression is an important mechanism for RV to hijack the immune system and underscores surfaceome CRISPR screen in identifying viral host factors.
Differential regulation of transposable elements (TEs) during the murine submandibular gland development
Authors: Valdebenito-Maturana Braulio , Torres Francisca , Carrasco Mónica , Tapia Juan Carlos 
Published: October 2021

AbstractThe submandibular gland (SG) is a relatively simple organ formed by three cell types: acinar, myoepithelial, and an intricate network of duct-forming epithelial cells, that together fulfills several physiological functions from assisting food digestion to acting as an immune barrier against pathogens. Successful SG organogenesis is the product of highly controlled and orchestrated genetic and transcriptional programs. Mounting evidence links Transposable Elements (TEs), originally thought to be selfish genetic elements, to different aspects of gene regulation in mammalian development and disease. To our knowledge, the role of TEs during murine SG organogenesis has not been studied. Using novel bioinformatic tools and publicly available RNA-Seq datasets, our results indicate that a significant number of genic and intergenic TEs are differentially expressed during the SG development. Furthermore, changes in expression of specific TEs correlated with that of genes involved in cellular division and differentiation, critical aspects for SG maturation. Altogether, we propose that TEs modulate gene networks that operate during SG development.
Performance of the plasma Aβ42/Aβ40 ratio, measured with a novel HPLC-MS/MS method, as a biomarker of amyloid PET status in a DPUK-KOREAN cohort
Authors: Jang Hyemin , Kim Ji Sun , Lee Hye Joo , Kim Chi-Hun , Na Duk L. , Kim Hee Jin , Allué José Antonio , Sarasa Leticia , Castillo Sergio , Pesini Pedro , Gallacher John , Seo Sang Won ,   on behalf of DPUK
Published: October 2021

Abstract
Background
We assessed the feasibility of plasma Aβ42/Aβ40 determined using a novel liquid chromatography-mass spectrometry method (LC-MS) as a useful biomarker of PET status in a Korean cohort from the DPUK Study.

Methods
A total of 580 participants belonging to six groups, Alzheimer’s disease dementia (ADD, n = 134), amnestic mild cognitive impairment (aMCI, n = 212), old controls (OC, n = 149), young controls (YC, n = 15), subcortical vascular cognitive impairment (SVCI, n = 58), and cerebral amyloid angiopathy (CAA, n = 12), were included in this study. Plasma Aβ40 and Aβ42 were quantitated using a new antibody-free, LC-MS, which drastically reduced the sample preparation time and cost. We performed receiver operating characteristic (ROC) analysis to develop the cutoff of Aβ42/Aβ40 and investigated its performance predicting centiloid-based PET positivity (PET+).

Results
Plasma Aβ42/Aβ40 were lower for PET+ individuals in ADD, aMCI, OC, and SVCI (p < 0.001), but not in CAA (p = 0.133). In the group of YC, OC, aMCI, and ADD groups, plasma Aβ42/Aβ40 predicted PET+ with an area under the ROC curve (AUC) of 0.814 at a cutoff of 0.2576. When adding age, APOE4, and diagnosis, the AUC significantly improved to 0.912.

Conclusion
Plasma Aβ42/Aβ40, as measured by this novel LC-MS method, showed good discriminating performance based on PET positivity.
Metastatic choriocarcinoma in a young woman presenting as thyroid storm: a case report
Authors: Saleem Muhammad , Sethi Sher M. , Ali Abrar , Kiran Zareen 
Published: October 2021

Abstract
Background
Thyroid storm is an endocrine emergency and life-threatening condition discovered in 1926. There is no specific laboratory parameter that can differentiate or distinguish between thyroid storm and primary hyperthyroidism. Diagnosis is made on a clinical scoring system, including the Burch–Wartofsky point scale and Japanese Thyroid Association scoring system. The management is early diagnosis, immediate initiation of anti-thyroid medications, intensive care monitoring, and prevention of multiorgan failure.

Case presentation
A 30-year-old Pakistani female presented with complaint of headache, vomiting, and generalized weakness for 3 weeks. She had an episode of seizure-like activity at home, and so was rushed to the emergency department. A detailed thyroid examination revealed a soft, nontender gland with no enlargement or bruit and no exophthalmos. Her thyroid-stimulating hormone was extremely low, with high free triiodothyronine and thyroxine. Thyroglobulin was 425 ng/ml (normal reference range ≤ 55 ng/ml), and thyroid-stimulating hormone receptor antibody was 0.87 IU/L (normal reference range 0–1.75 IU/L). She had high levels of beta-human chorionic gonadotropin hormone on initial presentation. Transvaginal ultrasound showed no intrauterine pregnancy, but an echogenic focus was found adherent to the right ovary with no vascularity. With the chief complaint of headache, she underwent magnetic resonance imaging of the brain that showed multiple scattered hemorrhagic lesions in supratentorial and infratentorial brain parenchyma that were highly suspicious for metastases. Computed tomography scan of the chest, abdomen, and pelvis revealed multiple neoplastic lesions in the lung, liver, spleen, and kidneys. A Tru-Cut liver biopsy showed linear cores of liver tissue with metastatic carcinoma with morphological features consistent with choriocarcinoma. Our patient scored 65 on the Burch–Wartofsky point scale. As per the Japanese Thyroid Association scoring system, our patient met the criteria for a “definite thyroid storm.” She had initiated propranolol to achieve adequate control of her heart rate and dexamethasone. Carbimazole was started to control her thyroid function. Her thyroid function after 2 weeks of treatment showed significant improvement. Methotrexate and etoposide were given for choriocarcinoma. She made a good recovery and was discharged home. She will undergo rehabilitation along with ongoing chemotherapy (methotrexate and etoposide weekly till beta-human chorionic gonadotropin levels normalize). Unless her source of beta-human chorionic gonadotropin is carefully under control, she will continue to take anti-thyroid medications.

Conclusion
Choriocarcinoma is not only associated with hyperthyroidism but can induce thyroid storm. Beta-human chorionic gonadotropin is directly associated with promoting thyroid dysfunction. Patients with gestational trophoblastic disease should be under close surveillance to prevent thyroid storms.