bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlative Biomarker Analysis of Intrinsic Subtypes and Efficacy Across the MONALEESA Phase III Studies
Authors: Prat Aleix , Chaudhury Anwesha , Solovieff Nadia , Paré Laia , Martinez Débora , Chic Nuria , Martínez-Sáez Olga , Brasó-Maristany Fara , Lteif Agnes , Taran Tetiana , Babbar Naveen , Su Fei 
Published: March 2021

PURPOSE The prognostic and predictive value of intrinsic subtypes in hormone receptor–positive, human epidermal growth factor receptor 2–negative advanced breast cancer treated with endocrine therapy and ribociclib (RIB) is currently unknown. We evaluated the association of intrinsic subtypes with progression-free survival (PFS) in the MONALEESA trials. METHODS A retrospective and exploratory PAM50-based analysis of tumor samples from the phase III MONALEESA-2, MONALEESA-3, and MONALEESA-7 trials was undertaken. The prognostic relationship of PAM50-based subtypes with PFS and risk of disease progression by subtype and treatment were evaluated using a multivariable Cox proportional hazards model, adjusting for age, prior chemotherapy, performance status, visceral disease, bone-only metastases, histological grade, number of metastatic sites, prior endocrine therapy, and de novo metastatic disease. RESULTS Overall, 1,153 tumors from the RIB (n = 667) and placebo (n = 486) cohorts were robustly profiled. Subtype distribution was luminal A (LumA), 46.8%; luminal B (LumB), 24.0%; normal-like, 14.1%; HER2-enriched (HER2E), 12.6%; and basal-like, 2.4% and was generally consistent across treatment arms and trials. The associations between subtypes and PFS were statistically significant in both arms ( P < .001). The risks of disease progression for LumB, HER2E, and basal-like subtypes were 1.44, 2.32, and 3.87 times higher compared with those for LumA, respectively. All subtypes except basal-like demonstrated significant PFS benefit with RIB. HER2E (hazard ratio [HR], 0.40; P < .0001), LumB (HR, 0.52; P < .0001), LumA (HR, 0.63; P = .0007), and normal-like (HR, 0.47; P = .0005) subtypes derived benefit from RIB. Patients with basal-like subtype (n = 28) did not derive benefit from RIB (HR, 1.14; P = .78). CONCLUSION In this retrospective exploratory analysis of hormone receptor–positive and human epidermal growth factor receptor 2–negative advanced breast cancer, each intrinsic subtype exhibited a consistent PFS benefit with RIB, except for basal-like.
Cranial MRI Abnormalities and Long-term Follow-up of the Lesions in 770 Girls With Central Precocious Puberty
Authors: Helvacıoğlu Didem , Demircioğlu Turan Serap , Güran Tülay , Atay Zeynep , Dağçınar Adnan , Bezen Diğdem , Özturan Esin Karakılıç , Darendeliler Feyza , Yüksel Ayşegül , Dursun Fatma , Kılınç Suna , Semiz Serap , Abalı Saygın , Yıldız Metin , Önder Aşan , Bereket Abdullah 
Published: March 2021

Abstract

Context
Central precocious puberty (CPP) may arise from central nervous system (CNS) lesions in a few affected girls. Recently, the incidence of girls with CPP has increased mostly in 6-8 year olds, in whom the necessity of magnetic resonance imaging (MRI) is debated.

Objective
To investigate the frequency, long-term outcome and potential predictors of CNS lesions in a large cohort of girls with CPP.

Methods
A multicenter cohort of 770 Turkish girls with CPP who had systematic cranial MRI between 2005 and 2017. Age at puberty onset was &lt;6 years in 116 and 6-8 years in 654. CNS lesions were followed until final decision(6.2 ± 3.1 years). Potential predictors of CNS lesions were evaluated by univariate analyses.

Results
A total of 104/770 (13.5%) girls had abnormal brain MRI. Of these, 2.8% were previously known CNS lesions, 3.8% had newly detected and causally related CNS lesions, 3.1 % were possibly, related and 3.8% were incidental. Only 2 (0.25%) neoplastic lesions (1 low grade glioma and 1 meningioma) were identified; neither required intervention over follow-up of 6 and 3.5 years respectively. Age at breast development &lt;6 years (odds ratio [OR] 2.38; 95% CI 1.08-5.21) and the peak luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratio &gt;0.6 (OR 3.13; 95% CI 1.02-9.68) were significantly associated with CNS lesions. However, both patients with neoplastic lesions were &gt;6 years old.

Conclusion
Although age and LH/FSH ratio are significant predictors of CNS lesions, their predictive power is weak. Thus, systematic MRI seems to be the most efficient current approach to avoid missing an occult CNS lesion in girls with CPP, despite the low likelihood of finding a lesion requiring intervention.
Deletion of Intestinal SHP Impairs Short-term Response to Cholic Acid Challenge in Male Mice
Authors: Nguyen James T , Riessen Ryan , Zhang Tongyu , Kieffer Collin , Anakk Sayeepriyadarshini 
Published: March 2021

Abstract
Small heterodimer partner (SHP) is a crucial regulator of bile acid (BA) transport and synthesis; however, its intestine-specific role is not fully understood. Here, we report that male intestine-specific Shp knockout (IShpKO) mice exhibit higher intestinal BA but not hepatic or serum BA levels compared with the f/f Shp animals when challenged with an acute (5-day) 1% cholic acid (CA) diet. We also found that BA synthetic genes Cyp7a1 and Cyp8b1 are not repressed to the same extent in IShpKO compared with control mice post-CA challenge. Loss of intestinal SHP did not alter Fxrα messenger RNA (mRNA) but increased Asbt (BA ileal uptake transporter) and Ostα (BA ileal efflux transporter) expression even under chow-fed conditions. Surprisingly, the acute CA diet in IShpKO did not elicit the expected induction of Fgf15 but was able to maintain the suppression of Asbt, and Ostα/β mRNA levels. At the protein level, apical sodium-dependent bile acid transporter (ASBT) was downregulated, while organic solute transporter-α/β (OSTα/β) expression was induced and maintained regardless of diet. Examination of ileal histology in IShpKO mice challenged with acute CA diet revealed reduced villi length and goblet cell numbers. However, no difference in villi length, and the expression of BA regulator and transporter genes, was seen between f/f Shp and IShpKO animals after a chronic (14-day) CA diet, suggesting a potential adaptive response. We found the upregulation of the Pparα-Ugt axis after 14 days of CA diet may reduce the BA burden and compensate for the ileal SHP function. Thus, our study reveals that ileal SHP expression contributes to both overall intestinal structure and BA homeostasis.
State Policy and Mental Health Outcomes under COVID-19
Authors: Sances Michael W. , Campbell Andrea Louise 
Published: March 2021

Abstract
Context: The COVID-19 pandemic has caused enormous damage to physiological health and economic security, especially among racial and ethnic minorities. We examined downstream effects on mental health, how effects vary by race and ethnicity, and the role of existing state-level social policies in softening the pandemic's impact.
Methods: We analyze an online, multi-wave Census Bureau survey fielded to nearly a million respondents between late April and July 2020. The survey includes questions measuring psychological distress as well as indirect measures of experience with the pandemic. We combined these data with state-level measures of COVID-19 cases, lockdown orders, unemployment filings, and safety net policy.
Findings: We find significant mental stress among all respondents and a sizeable gap between nonwhite and white respondents. Adjusting for pandemic experiences eliminates this gap. The effect of losing work as a result of the pandemic is slightly offset by state policies such as unemployment benefit size and Medicaid expansion. The magnitude of these offsetting effects is similar across racial/ethnic groups.
Conclusions: The racialized impacts of the pandemic are exacerbated by inequalities in state policy exemplifying structural racism. If the least generous states matched the policies of the most generous, inequalities caused by the pandemic would be diminished.
Joint development recovery on resumption of embryonic movement following paralysis
Authors: Rolfe Rebecca A. , Scanlon O'Callaghan David , Murphy Paula 
Published: March 2021

ABSTRACTFetal activity in utero is a normal part of pregnancy and reduced or absent movement can lead to long-term skeletal defects, such as Fetal Akinesia Deformation Sequence, joint dysplasia and arthrogryposis. A variety of animal models with decreased or absent embryonic movements show a consistent set of developmental defects, providing insight into the aetiology of congenital skeletal abnormalities. At developing joints, defects include reduced joint interzones with frequent fusion of cartilaginous skeletal rudiments across the joint. At the spine, defects include shortening and a spectrum of curvature deformations. An important question, with relevance to possible therapeutic interventions for human conditions, is the capacity for recovery with resumption of movement following short-term immobilisation. Here, we use the well-established chick model to compare the effects of sustained immobilisation from embryonic day (E)4-10 to two different recovery scenarios: (1) natural recovery from E6 until E10 and (2) the addition of hyperactive movement stimulation during the recovery period. We demonstrate partial recovery of movement and partial recovery of joint development under both recovery conditions, but no improvement in spine defects. The joints examined (elbow, hip and knee) showed better recovery in hindlimb than forelimb, with hyperactive mobility leading to greater recovery in the knee and hip. The hip joint showed the best recovery with improved rudiment separation, tissue organisation and commencement of cavitation. This work demonstrates that movement post paralysis can partially recover specific aspects of joint development, which could inform therapeutic approaches to ameliorate the effects of human fetal immobility.This article has an associated First Person interview with the first author of the paper.
WNT-responsive SUMOylation of ZIC5 promotes murine neural crest cell development, having multiple effects on transcription
Authors: Ali Radiya G. , Bellchambers Helen M. , Warr Nicholas , Ahmed Jehangir N. , Barratt Kristen S. , Neill Kieran , Diamand Koula E. M. , Arkell Ruth M. 
Published: March 2021

ABSTRACT
Zinc finger of the cerebellum (Zic) proteins act as classic transcription factors to promote transcription of the Foxd3 gene during neural crest cell specification. Additionally, they can act as co-factors that bind proteins from the T-cell factor/lymphoid enhancing factor (TCF/LEF) family (TCFs) to repress WNT–β-catenin-dependent transcription without contacting DNA. Here, we show that ZIC activity at the neural plate border is influenced by WNT-dependent SUMOylation. In the presence of high canonical WNT activity, a lysine residue within the highly conserved zinc finger N-terminally conserved (ZF-NC) domain of ZIC5 is SUMOylated, which reduces formation of the ZIC–TCF co-repressor complex and shifts the balance towards transcription factor function. The modification is crucial in vivo, as a ZIC5 SUMO-incompetent mouse strain exhibits neural crest specification defects. This work reveals the function of the ZF-NC domain within ZIC, provides in vivo validation of target protein SUMOylation and demonstrates that WNT–β-catenin signalling directs transcription at non-TCF DNA-binding sites. Furthermore, it can explain how WNT signals convert a broad region of Zic ectodermal expression into a restricted region of neural crest cell specification.
Exposure to artificial light at night alters innate immune response in wild great tit nestlings
Authors: Ziegler Ann-Kathrin , Watson Hannah , Hegemann Arne , Meitern Richard , Canoine Virginie , Nilsson Jan-Åke , Isaksson Caroline 
Published: March 2021

ABSTRACT
The large-scale impact of urbanization on wildlife is rather well documented; however, the mechanisms underlying the effects of urban environments on animal physiology and behaviour are still poorly understood. Here, we focused on one major urban pollutant – artificial light at night (ALAN) – and its effects on the capacity to mount an innate immune response in wild great tit (Parus major) nestlings. Exposure to ALAN alters circadian rhythms of physiological processes, by disrupting the nocturnal production of the hormone melatonin. Nestlings were exposed to a light source emitting 3 lx for seven consecutive nights. Subsequently, nestlings were immune challenged with a lipopolysaccharide injection, and we measured haptoglobin and nitric oxide levels pre- and post-injection. Both haptoglobin and nitric oxide are important markers for innate immune function. We found that ALAN exposure altered the innate immune response, with nestlings exposed to ALAN having lower haptoglobin and higher nitric oxide levels after the immune challenge compared with dark-night nestlings. Unexpectedly, nitric oxide levels were overall lower after the immune challenge than before. These effects were probably mediated by melatonin, as ALAN-treated birds had on average 49% lower melatonin levels than the dark-night birds. ALAN exposure did not have any clear effects on nestling growth. This study provides a potential physiological mechanism underlying the documented differences in immune function between urban and rural birds observed in other studies. Moreover, it gives evidence that ALAN exposure affects nestling physiology, potentially causing long-term effects on physiology and behaviour, which ultimately can affect their fitness.
Tradição oral e tradução: a comunicação intercultural e as dificuldades para a tradução-versão dos provérbios entre o português brasileiro e o italiano
Authors: Arêas Alcebíades , Belizário Edvaldo Sampaio , Santos Maria Aparecida Cardoso 
Published: March 2021

Os provérbios fazem parte da cultura e do folclore de um povo e são passados de geração em geração, diretamente, por meio da palavra. Por fazerem parte da tradição oral de um povo, os provérbios transmitem conhecimento e ensinamento sobre os mais diversos aspectos da vida. Além disso, são fundamentais na consolidação de valores morais e princípios de convivência social, por conterem conselhos e admoestações visando a indicar modos para os homens conviverem e agirem de maneira cordial e respeitosa. Em outras palavras, provérbios, sentenças, aforismos e máximas, dentre outros, possuem grande valor didático-pedagógico, fixando-se na memória e atuando como um código de conduta. A forma concisa, a estrutura simples e a facilidade de compreensão das mensagens contidas nos provérbios permitem que suas fórmulas sejam memorizadas e transmitidas com grande facilidade entre povos e culturas de geração em geração. Uma característica importante das construções proverbiais é o seu caráter de universalidade, que não pode ser limitado por barreiras sociais, ideológicas ou geográficas. A capacidade de repetição e de atualização dos provérbios confere importância ao seu estudo, seja por enriquecer as pesquisas em tradução, seja por sinalizar a outros pesquisadores que existe muito a ser feito nesse campo. Neste artigo, além de retormarmos o conceito de provérbio, sua origem, suas variações e seu deslocamento semântico no tempo e no espaço, vamos apresentar uma proposta para traduzi-los no contexto linguístico-cultural das línguas portuguesa, variante brasileira, e italiana.
<strong><em>Stephanitis</em> (<em>Norba</em>) <em>syoitii</em> sp. nov. (Hemiptera: Heteroptera: Tingidae) from Taiwan, China</strong>
Authors: SOUMA JUN 
Published: March 2021

A new species of the subgenus Norba Horváth, 1912 of the lace bug genus Stephanitis Stål, 1873 (Hemiptera: Heteroptera: Tingidae), from Taiwan, China, is described under the name of S. (N.) syoitii sp. nov. This new species is different from other species of Stephanitis, mainly by the shape of its pronotum and hemelytron. Key words: lace bug, taxonomy, new species, eastern Asia
Influence of patient isolation due to colonization with multidrug-resistant organisms on functional recovery after spinal cord injury
Authors: Prang Peter , Schuld Christian , Rupp Ruediger , Hensel Cornelia , Weidner Norbert 
Published: March 2021

Study design
Chart reviews were combined with neurological and functional outcome data obtained from the prospective European Multicenter Study on Spinal Cord Injury (EMSCI, www.emsci.org).

Objectives
To determine if strict physical isolation of multidrug-resistant organisms (MDRO)-positive patients negatively affects neurological recovery and functional outcome in the first year after acute spinal cord injury (SCI).

Setting
SCI Center Heidelberg University Hospital.

Methods
Individuals with acute (< 6 weeks) traumatic or ischemic SCI were included. During primary comprehensive care, isolated MDRO-positive patients (n = 13) were compared with a MDRO-negative control group (n = 13) matched for functional (Spinal Cord Independence Measure–SCIM) and neurological impairment (motor scores based on the International Standards for Neurological Classification of Spinal Cord Injury—ISNCSCI) at an early stage up to 40 days after SCI. SCIM scores and motor scores were obtained at 12 weeks (intermediate stage) and 24 or 48 weeks (late stage) after SCI.

Results
Isolated MDRO-positive (median duration of hospitalization: 175 days, 39% of inpatient stay under isolation measures) and non-isolated MDRO-negative (median duration of hospitalization: 161 days) patients showed functional and neurological improvements, which were not statistically different between groups at the intermediate and late stage.

Conclusion
Prolonged isolation due to MDRO colonization for over a third of the inpatient comprehensive care period does not appear to impair neurological recovery and functional outcome within the first year after SCI.
Efficacy and Safety of Over-the-Counter Therapies for Chronic Constipation: An Updated Systematic Review
Authors: Rao Satish S.C. , Brenner Darren M. 
Published: March 2021

INTRODUCTION:
Constipation is commonly treated with over-the-counter (OTC) products whose efficacy and safety remain unclear. We performed a systematic review of OTC therapies for chronic constipation and provide evidence-based recommendations.

METHODS:
We searched PubMed and Embase for randomized controlled trials of ≥4-week duration that evaluated OTC preparations between 2004 and 2020. Studies were scored using the US Preventive Services Task Force criteria (0–5 scale) including randomization, blinding, and withdrawals. The strengths of evidence were adjudicated within each therapeutic category, and recommendations were graded (A, B, C, D, and I) based on the level of evidence (level I, good; II, fair; or III, poor).

RESULTS:
Of 1,297 studies identified, 41 met the inclusion criteria. There was good evidence (grade A recommendation) for the use of the osmotic laxative polyethylene glycol (PEG) and the stimulant senna; moderate evidence (grade B) for psyllium, SupraFiber, magnesium salts, stimulants (bisacodyl and sodium picosulfate), fruit-based laxatives (kiwi, mango, prunes, and ficus), and yogurt with galacto-oligosaccharide/prunes/linseed oil; and insufficient evidence (grade I) for polydextrose, inulin, and fructo-oligosaccharide. Diarrhea, nausea, bloating, and abdominal pain were common adverse events, but no serious adverse events were reported.

DISCUSSION:
The spectrum of OTC products has increased and quality of evidence has improved, but methodological issues including variability in study design, primary outcome measures, trial duration, and small sample sizes remain. We found good evidence to recommend polyethylene glycol or senna as first-line laxatives and moderate evidence supporting fiber supplements, fruits, stimulant laxatives, and magnesium-based products. For others, further validation with more rigorously designed studies is warranted.
Confidentiality and Conflicts of Interest: An Assessment of Twitter Posts in Gastrointestinal Endoscopy
Authors: Walradt Trent , Bilal Mohammad , Wadhwa Vaibhav , Chiang Austin L. , Berzin Tyler M. 
Published: March 2021

INTRODUCTION:
To evaluate compliance with confidentiality and conflicts of interest (COI) in tweets sharing gastrointestinal (GI) endoscopy videos/images.

Methods:
Physicians' tweets containing GI endoscopy videos/images were assessed for confidentiality and COI compliance.

Results:
Identifiable details in tweets included procedure date (17.9%), date of birth (0.8%), and patient's face visible (0.5%). Ninety-five tweets (10%) mentioned the name/brand of a medical device. Of the 19 posted by US physicians, 7 came from physicians who had received payments from the device manufacturer. None of these physicians disclosed relevant COI.

DISCUSSION:
GI endoscopy tweets describing clinical cases or procedures may insufficiently address issues of confidentiality and COI.
Persisting Villous Atrophy and Adherence in Celiac Disease: What Does the Patient Want? What Should a Clinician Advise?
Authors: Rej Anupam , Elli Luca , Sanders David Surendran 
Published: March 2021

Abstract
Adherence to a gluten-free diet in celiac disease remains challenging. Clinicians may view mucosal healing as crucial. From the patient's perspective, avoidance of an invasive upper endoscopy may be desirable. A fundamental misconception is that noninvasive tools including symptoms, serology, dietary adherence questionnaires, and novel gluten immunogenic peptides may detect ongoing villous atrophy rather than assess adherence. Duodenal biopsies are the only reliable method for assessment of mucosal healing—however, we as clinicians should provide patients with the uncertainties of this approach allowing them to make an informed decision on an individual basis.
Philosophy’s Workmate:Erōsand theErōticain Plato’sSymposium
Authors: Nally Edith Gwendolyn 
Published: March 2021

AbstractDiotima’s speech claims that philosophy ranks among theerōtica. The standard reading of this holds thaterōsmanifests in philosophical activity. This is puzzling. Eros has a reputation for overpowering the psyche, making reasoning impossible. The major interpretive discussion of this puzzle suggests that Diotima (and Plato by proxy) must therefore accept either non-rationalist philosophizing or rationalisterōs. This paper argues for an alternative. The “ancillary activities view” posits that theerōticado not manifesterōsbut are activities undertaken to achieve itstelos. On this view, love’s relationship to philosophy is as un-mysterious as wanting something and doing what it takes to get it.
The first diffusion of the Covid-19 outbreak in Northern Italy: an analysis based on a simplified version of the SIR model
Authors: Magnoni Mauro 
Published: March 2021

Abstract
In this paper an analysis of the first diffusion of the Covid-19 outbreak occurred in late February 2020 in Northern Italy is presented. In order to study the time evolution of the epidemic it was decided to analyze in particular as the most relevant variable the number of hospitalized people, considered as the less biased proxy of the real number of infected people. An approximate solution of the infected equation was found from a simplified version of the SIR model. This solution was used as a tool for the calculation of the basic reproduction number R
0 in the early phase of the epidemic for the most affected Northern Italian regions (Piedmont, Lombardy, Veneto and Emilia), giving values of R
0 ranging from 2.2 to 3.1. Finally, a theoretical formulation of the infection rate is proposed, introducing a new parameter, the infection length, characteristic of the disease.
Patterns of Forming Entrepreneurial Intention: Evidence in Vietnam
Authors: Khoi Nguyen Huu , Tuu Ho Huy , Olsen Svein Ottar , Le Angelina Nhat-Hanh 
Published: March 2021

Abstract
The purpose of this study is to explore the direct and interaction effects of entrepreneurial events (feasibility and desirability) and perceived risk (opportunity and threat) on entrepreneurial intention in a transitional economy – Vietnam. The testing results show that perceived desirability and perceived feasibility have direct and interactive effects on entrepreneur intention. Risk as both threat and as opportunity has direct and moderating effects on entrepreneurial intention.