bluuebunny/crossref_metadata_2025_split huggingface dataset:
Williams syndrome: on the role of intellectual abilities in anxiety
Authors: Willfors Charlotte , Riby Deborah M. , van der Poll Marcus , Ekholm Katja , Avdic Björlin Hanna , Kleberg Johan Lundin , Nordgren Ann 
Published: November 2021

AbstractBackgroundIndividuals with Williams syndrome (WS) have an elevated risk for anxiety disorders throughout the life span, making it a research priority to identify the individual factors associated with anxiety. Most of the existing literature is based on questionnaire data and suggests that impaired executive functions (EF) increase the risk for anxiety in WS. The aim of this study was to use direct measures by trained clinicians to investigate the effects of general intelligence, inhibition, sustained attention, and working memory on anxiety in WS, to further elucidate potential underlying mechanisms.MethodTwenty-four individuals with WS participated in the study (mean age: 29 years, range: 9–53 years), together with at least one of their parents. The MINI international neuropsychiatric interview for DSM-5 was completed to establish clinical diagnosis of anxiety, and the Clinical Global Impression Scale – Severity was used for an expert rating of symptom severity. Intellectual abilities were measured using the Wechsler scales, and attention and inhibition using the Conner’s Continuous Performance Test. In addition, a parent-report questionnaire measuring EF, learning and memory was collected.ResultsIn contrast to the apriori hypothesis, there was no significant association between anxiety and core elements of EF such as working memory, sustained attention, and inhibition (i.e. the process of restraining one’s impulses or behaviour). Using ordinal logistic regression analyses, we showed that decreasing intelligence quotient (IQ) and age are associated with elevated anxiety. We confirmed these results in between-groups analyses (anxiety disorder vs no current anxiety disorder), and low IQ was associated with higher risk of having an anxiety diagnosis. In addition, Bayesian statistics gave substantial evidence for no significant association between anxiety and inhibition.ConclusionBy using direct measures of psychological pathology and functioning, the current results provide a deeper characterisation of the WS phenotype and provide novel insights into the potential mechanisms underpinning anxiety.
STAT5 is activated in macrophages by breast cancer cell-derived factors and regulates macrophage function in the tumor microenvironment
Authors: Jesser Emily A. , Brady Nicholas J. , Huggins Danielle N. , Witschen Patrice M. , O’Connor Christine H. , Schwertfeger Kathryn L. 
Published: November 2021

AbstractBackgroundIn breast cancer, complex interactions between tumor cells and cells within the surrounding stroma, such as macrophages, are critical for tumor growth, progression, and therapeutic response. Recent studies have highlighted the complex nature and heterogeneous populations of macrophages associated with both tumor-promoting and tumor-inhibiting phenotypes. Defining the pathways that drive macrophage function is important for understanding their complex phenotypes within the tumor microenvironment. Signal transducer and activator of transcription (STAT) transcription factors, such as STAT5, are key regulators of immune cell function. The studies described here investigate the functional contributions of STAT5 to tumor-associated macrophage function in breast cancer.MethodsInitial studies were performed using a panel of human breast cancer and mouse mammary tumor cell lines to determine the ability of tumor cell-derived factors to induce STAT5 activation in macrophages. Further studies used these models to identify soluble factors that activate STAT5 in macrophages. To delineate STAT5-specific contributions to macrophage function, a conditional model of myeloid STAT5 deletion was used for in vitro,RNA-sequencing, and in vivo studies. The effects of STAT5 deletion in macrophages on tumor cell migration and metastasis were evaluated using in vitro co-culture migration assays and an in vivo tumor cell-macrophage co-injection model.ResultsWe demonstrate here that STAT5 is robustly activated in macrophages by tumor cell-derived factors and that GM-CSF is a key cytokine stimulating this pathway. The analysis of RNA-seq studies reveals that STAT5 promotes expression of immune stimulatory genes in macrophages and that loss of STAT5 in macrophages results in increased expression of tissue remodeling factors. Finally, we demonstrate that loss of STAT5 in macrophages promotes tumor cell migration in vitro and mammary tumor metastasis in vivo.ConclusionsBreast cancer cells produce soluble factors, such as GM-CSF, that activate the STAT5 pathway in macrophages and drive expression of inflammatory factors. STAT5 deletion in myeloid cells enhances metastasis, suggesting that STAT5 activation in tumor-associated macrophages protects against tumor progression. Understanding mechanisms that drive macrophage function in the tumor microenvironment will ultimately lead to new approaches that suppress tumor-promoting functions while enhancing their anti-tumor functions.
Comprehensive characterization of single-cell full-length isoforms in human and mouse with long-read sequencing
Authors: Tian Luyi , Jabbari Jafar S. , Thijssen Rachel , Gouil Quentin , Amarasinghe Shanika L. , Voogd Oliver , Kariyawasam Hasaru , Du Mei R. M. , Schuster Jakob , Wang Changqing , Su Shian , Dong Xueyi , Law Charity W. , Lucattini Alexis , Prawer Yair David Joseph , Collar-Fernández Coralina , Chung Jin D. , Naim Timur , Chan Audrey , Ly Chi Hai , Lynch Gordon S. , Ryall James G. , Anttila Casey J. A. , Peng Hongke , Anderson Mary Ann , Flensburg Christoffer , Majewski Ian , Roberts Andrew W. , Huang David C. S. , Clark Michael B. , Ritchie Matthew E. 
Published: November 2021

AbstractA modified Chromium 10x droplet-based protocol that subsamples cells for both short-read and long-read (nanopore) sequencing together with a new computational pipeline (FLAMES) is developed to enable isoform discovery, splicing analysis, and mutation detection in single cells. We identify thousands of unannotated isoforms and find conserved functional modules that are enriched for alternative transcript usage in different cell types and species, including ribosome biogenesis and mRNA splicing. Analysis at the transcript level allows data integration with scATAC-seq on individual promoters, improved correlation with protein expression data, and linked mutations known to confer drug resistance to transcriptome heterogeneity.
Rab32 uses its effector reticulon 3L to trigger autophagic degradation of mitochondria-associated membrane (MAM) proteins
Authors: Herrera-Cruz Maria Sol , Yap Megan C. , Tahbaz Nasser , Phillips Keelie , Thomas Laurel , Thomas Gary , Simmen Thomas 
Published: November 2021

Abstract
Background
Rab32 is a small GTPase associated with multiple organelles but is particularly enriched at the endoplasmic reticulum (ER). Here, it controls targeting to mitochondria-ER contacts (MERCs), thus influencing composition of the mitochondria-associated membrane (MAM). Moreover, Rab32 regulates mitochondrial membrane dynamics via its effector dynamin-related protein 1 (Drp1). Rab32 has also been reported to induce autophagy, an essential pathway targeting intracellular components for their degradation. However, no autophagy-specific effectors have been identified for Rab32. Similarly, the identity of the intracellular membrane targeted by this small GTPase and the type of autophagy it induces are not known yet.

Results
To investigate the target of autophagic degradation mediated by Rab32, we tested a large panel of organellar proteins. We found that a subset of MERC proteins, including the thioredoxin-related transmembrane protein TMX1, are specifically targeted for degradation in a Rab32-dependent manner. We also identified the long isoform of reticulon-3 (RTN3L), a known ER-phagy receptor, as a Rab32 effector.

Conclusions
Rab32 promotes degradation of mitochondrial-proximal ER membranes through autophagy with the help of RTN3L. We propose to call this type of selective autophagy “MAM-phagy”.
Much ado about something: a response to “COVID-19: underpowered randomised trials, or no randomised trials?”
Authors: Haber Noah A. , Wieten Sarah E. , Smith Emily R. , Nunan David 
Published: November 2021

AbstractNon-pharmaceutical interventions (NPI) for infectious diseases such as COVID-19 are particularly challenging given the complexities of what is both practical and ethical to randomize. We are often faced with the difficult decision between having weak trials or not having a trial at all. In a recent article, Dr. Atle Fretheim argues that statistically underpowered studies are still valuable, particularly in conjunction with other similar studies in meta-analysis in the context of the DANMASK-19 trial, asking “Surely, some trial evidence must be better than no trial evidence?” However, informative trials are not always feasible, and feasible trials are not always informative. In some cases, even a well-conducted but weakly designed and/or underpowered trial such as DANMASK-19 may be uninformative or worse, both individually and in a body of literature. Meta-analysis, for example, can only resolve issues of statistical power if there is a reasonable expectation of compatible well-designed trials. Uninformative designs may also invite misinformation. Here, we make the case that—when considering informativeness, ethics, and opportunity costs in addition to statistical power—“nothing” is often the better choice.
Efficacy of Bushen Huatan Decoction combined with Baduanjin in the treatment of polycystic ovary syndrome with insulin resistance (IR-PCOS), kidney deficiency and phlegm dampness: study protocol for a randomized controlled trial
Authors: Qian Haiqing , Xu Wenting , Cui Lijuan , Wang Rong , Wang Jiahui , Tang Mengyu , Wei Minggang , Wang Lihong 
Published: November 2021

Abstract
Background
Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease in women. Insulin resistance (IR) has emerged as a central contributor to the pathogenesis of this disease. According to traditional Chinese medicine (TCM), kidney deficiency is the main syndrome of PCOS. The deficiency of the kidney cannot vaporize water-dampness, and the retention of water-dampness accumulates into phlegm dampness stagnation, resulting in visceral dysfunction and metabolic disorder. TCM involving syndrome differentiation and treatment is widely used to adjust women’s menstrual cycles. Our patented formula Bushen Huatan Decoction (BSHTD) has been proven to be effective in the clinical treatment of IR-PCOS. Baduanjin also plays an important role in improving metabolic syndrome through lifestyle intervention. This study investigates the clinical efficacy of Bushen Huatan Decoction combined with Baduanjin in IR-PCOS, to form a specific TCM-behaviour intervention plan in the treatment of IR-PCOS.

Methods/design
This is a randomized controlled trial involving 190 participants diagnosed with IR-PCOS. All participants will be randomly allocated into 5 groups: group A will receive metformin; group B, BSHTD; group C, Baduanjin; group D, BSHTD combined with metformin; and group E, BSHTD combined with Baduanjin. One course of treatment lasts 3 months, a total of two courses. The primary outcomes are changes in the homeostatic model assessment of insulin resistance (HOMA-IR) and improvements in the oral glucose tolerance test (OGTT) and insulin-releasing test (INS). The secondary outcomes are improvements in the menstrual cycle, ovulation rate, clinical pregnancy rate, basic serum sex hormone levels, free androgen index (FAI), Ferriman-Gallwey scores, body mass index (BMI) and TCM syndrome scores. The related observation indexes will be collected at baseline, during the process of treatment and at the 6-month follow-up. Simultaneously, close monitoring of possible adverse events will be performed throughout the trial process.

Discussion
This trial will investigate the efficacy of the comprehensive intervention program of Bushen Huatan Decoction combined with Baduanjin on the adjustment of the menstrual cycle, improvement of insulin resistance and correction of glucose metabolism disorder in IR-PCOS patients. It is expected to form an alternative treatment of TCM-behaviour intervention therapy for IR-PCOS and promote the Chinese fitness Qigong Baduanjin in the application of lifestyle diseases.

Trial registration
Chinese Clinical Trial Registry ChiCTR2100043415. Registered on 15 February 2021.
Aedes albopictus life table: environment, food, and age dependence survivorship and reproduction in a tropical area
Authors: Cui Guzhen , Zhong Saifeng , Zheng Tuquan , Li Zhangrui , Zhang Xu , Li Chuang , Hemming-Schroeder Elizabeth , Zhou Guofa , Li Yiji 
Published: November 2021

Abstract
Background
Environmental conditions affect the biology of mosquito vectors. Aedes albopictus is a major vector of many important diseases including dengue, Zika, and chikungunya in China. Understanding the development, fecundity, and survivorship of Ae. albopictus mosquitoes in different environmental conditions is beneficial for the implementation of effective vector control measures.

Methods
Aedes albopictus larval and adult life-table experiments were conducted under natural conditions in indoor, half-shaded, and fully shaded settings, simulating the three major habitat types in Hainan Province, a tropical island in the South China Sea. Temperature, humidity, and light intensity were recorded daily. Larval rearing used habitat water and tap water, with and without additional artificial food. Development time, survivorship, pupation rate, and adult emergence rates were monitored. Adult mosquito survivorship and fecundity were monitored daily and reproductive rates were determined, and age-dependent survivorship and reproduction were analyzed.

Results
The pupation time and male and female emergence times were significantly shorter in indoor conditions than in shaded and half-shaded conditions for both tap water with added food and habitat water with added food groups. For habitat water with added food, the shaded environment had the lowest pupation rate among the settings. For tap water with added food group, the shaded environment had the lowest pupation rate. The mean survival time of females was 27.3 ± 0.8 days in the indoor condition, which was significantly longer than that in the half-shaded (18.4 ± 0.6 days) and shaded (13.8 ± 1.2 days) conditions. Adult mortality was age-dependent, and the rate of change in mortality with age was not significantly different among different environmental conditions. The mean net replacement rate (R0) of female mosquitoes showed no significant difference among the three conditions, whereas the per capita intrinsic growth rate (r) in the shaded condition was 42.0% and 20.4% higher than that in the indoor and half-shaded conditions, respectively. Female daily egg mass was also age-dependent in all the settings, decaying exponentially with age.

Conclusions
Our results imply that half-shaded conditions are likely the best natural condition for adult emergence and female reproduction, and food supply is crucial for larval development and pupation. The results provide new avenues for integrated mosquito management in indoor and outdoor areas, especially in half-shaded areas.

Graphical Abstract
Urine transferrin as an early endothelial dysfunction marker in type 2 diabetic patients without nephropathy: a case control study
Authors: Sánchez-Hidalgo José Juan , Suárez-Cuenca Juan Antonio , Lozano-Nuevo José Juan , García-López Víctor Hugo , Leal-Gutiérrez María Graciela , León-Angel Sein Antonio , Ramírez-Villa María Leslye , Rodea-Rubio Martha Elena , González-Hernández José Enrique , Canela-Mayoral José Antonio , Murillo-Heredia Eduardo , Vera-Gómez Eduardo , Hernández-Patricio Alejandro , Zamora-Alemán Carlos Ramiro , Domínguez-Pérez Gabriela Alexandra , Gutiérrez-Buendia Juan Ariel , Mondragón-Terán Paul 
Published: November 2021

Abstract
Background
Albumin, along with other proteins, is abnormally eliminated via the urine during early stages of diabetic nephropathy. Moreover, endothelial dysfunction (ED) accompanying early diabetic nephropathy may develop even before microalbuminuria is detectable. Transferrin has a molecular weight comparable to albumin, whereas transferrinuria and microalbuminuria in a 24-h urine sample may comparably reflect early diabetic nephropathy. Whereas transferrin metabolism is related with ED during very early diabetic nephropathy has not been elucidated yet. This case–control study aimed to evaluate the relation between ED and urine transferrin, even before early diabetic nephropathy is present.

Methods
Patients were enrolled from two study sites in Mexico City: Ticomán General Hospital (healthy controls); and a Specialized Clinic for the Management of the Diabetic Patient (cases). All patients provided written informed consent. The primary endpoint was the correlation between urinary transferrin concentration and ED measured in type 2 diabetic patients without albuminuria. ED was evaluated by ultrasonographic validated measurements, which included carotid intima-media thickness (CIMT) and flow mediated dilation (FMD). Plasma biomarkers included glycated hemoglobin, creatinine, cholesterol and triglycerides, as well as urine albumin, transferrin and evidence of urinary tract infection.

Results
Sixty patients with type 2 Diabetes Mellitus (t2DM; n = 30) or without t2DM (n = 30), both negative for microalbuminuria, were recruited. The group with t2DM were older, with higher values of HbA1c and higher ED. This group also showed significant differences in urine transferrin and urine/plasma transferrin ratio, as compared with healthy controls (14.4 vs. 18.7 mg/mL, p = 0.04, and 74.2 vs. 49.5; p = 0.01; respectively). Moreover, urine transferrin correlated with higher CIMT values (r = 0.37, p = 0.04), being particularly significant for t2DM population. CIMT also correlated with time from t2DM diagnosis (r = 0.48, p < 0.001) and HbA1c (r = 0.48; p < 0.001).

Conclusion
Urine transferrin correlated with subclinical atherogenesis in patients with t2DM without renal failure, suggesting its potential to identify cardiovascular risk in patients at very early nephropathy stage without microalbuminuria.
Breast may not always be best: moderation of effects of postnatal depression by breastfeeding and infant sex
Authors: Braithwaite Elizabeth C. , Sharp Helen , Pickles Andrew , Hill Jonathan , Wright Nicola 
Published: November 2021

Abstract
Background
There is good evidence that female infants are particularly vulnerable to poor emotional outcomes following in utero glucocorticoid exposure. It is currently unclear whether such effects might persist into the postnatal period for breastfed infants, as maternal cortisol is expressed in breastmilk and is influenced by maternal psychological distress. We pre-registered hypotheses that maternal postnatal depression would be associated with infant negative emotionality, and that this effect would be moderated by breastfeeding status and infant sex.

Methods
We analysed data from the Wirral Child Health and Development Study (WCHADS), a prospective epidemiological study starting in pregnancy. Nine weeks after birth mothers self-reported depressive symptoms and breastfeeding status, and reported infant negative emotionality using the distress to limits subscale of the infant behaviour questionnaire (IBQ-R) when their infant was aged 9 weeks and 14 months. Maximum likelihood estimations made use of data from 857 mother-infant pairs.

Results
At 9 weeks of age, maternal postnatal depressive symptoms were positively associated with infant distress to limits; however, this effect was not moderated by infant sex or breastfeeding. At age 14 months, the association between postnatal depression symptoms and distress to limits was greatest in the breastfed females, whereas the association was smaller, but still significant, in the non-breastfed females. For males, the association was non-significant in both the breastfed and non-breastfed groups. A test of sex difference between breastfed males and females was significant.

Conclusions
We provide evidence that effects of maternal postnatal depression on child emotional outcomes are moderated by breastfeeding status and differ by infant sex. Female vulnerability to elevated maternal breastmilk glucocorticoids may, at least in part, explain these effects.
Topology optimization subject to additive manufacturing constraints
Authors: Ebeling-Rump Moritz , Hömberg Dietmar , Lasarzik Robert , Petzold Thomas 
Published: November 2021

AbstractIn topology optimization the goal is to find the ideal material distribution in a domain subject to external forces. The structure is optimal if it has the highest possible stiffness. A volume constraint ensures filigree structures, which are regulated via a Ginzburg–Landau term. During 3D printing overhangs lead to instabilities. As a remedy an additive manufacturing constraint is added to the cost functional. First order optimality conditions are derived using a formal Lagrangian approach. With an Allen-Cahn interface propagation the optimization problem is solved iteratively. At a low computational cost the additive manufacturing constraint brings about support structures, which can be fine tuned according to demands and increase stability during the printing process.
Factors influencing access and utilization of health services among older people during the COVID − 19 pandemic: a scoping review
Authors: Bastani Peivand , Mohammadpour Mohammadtaghi , Samadbeik Mahnaz , Bastani Misagh , Rossi-Fedele Giampiero , Balasubramanian Madhan 
Published: November 2021

AbstractBackgroundAccess to healthcare and service utilization are both considered essential factors for improving the general health and wellbeing of older people, especially at the time of COVID-19 pandemic. The aim of the study is to explore factors affecting healthcare access and health service utilization for older people during the pandemic.MethodsPubMed, Web of Science, Scopus and Embase were systematically searched for relevant articles. Access, utilization, health, elderly and COVID-19 were used as keywords in the search strategy. A total of 4308 articles were identified through the initial database search; 50 articles were included in the review as passing the eligibility criteria. The searches were conducted up to August 2021. Data extraction was performed, and evidence was descriptively illustrated. Thematic analysis was used to explore factors influencing the elderly’s access and utilization of healthcare services, using Max QDA10, a qualitative analysis software.ResultsAmong articles included in the review (n = 50), a majority of the studies were from the United States (36%), followed by India (8%). According to the main healthcare services, a large number of articles (18%) were related to mental health services, followed by digital health services (16%). Factors were identified at an individual, provider and systems level. Seven main themes emerged from the thematic analysis, as determinants of elderly’s access and utilization of healthcare services during COVID-19 pandemic. These included: access to non-COVID related services, access to COVID-related services, literacy and education, accommodation challenges, perceived attitudes of aging, and policies and structures, and social determinants.ConclusionMental health and digital health services were identified as major issues influencing or contributing to or influencing older people’s health during the COVID-19 pandemic. We also argue on the importance of a rounded view, as attention to a range of factors is vital for policy decisions towards sustainable care and equitable interventions for improving the health of older people.