bluuebunny/crossref_metadata_2025 huggingface dataset:
Beyond the Insider-Outsider Divide: Heterogeneous Effects of Organizational Identity and Category Taken-for-Grantedness on Conformity
Authors: Paolella Lionel , Syakhroza Maima Aulia
Published: July 2020

Categories that become taken-for-granted tend to acquire rule-like standing. That is, people begin to strongly expect certain behaviors from entities that have claimed affiliation with them, and these expectations tend to induce conformity. However, conformity does not always ensue, and we lack an explanation of why the effects of category taken-for-grantedness might diverge. In this paper, we propose that the effects of increasing category taken-for-grantedness hinge upon an organization’s identity. We first argue that the relationship between organizational identity and the likelihood of conformity is U-shaped, with insiders and outsiders being more likely to conform relative to those with middling identities. We then propose that greater category taken-for-grantedness should reduce scrutiny for those whose identities mark them as more of insiders, subsequently making them less likely to conform. In contrast, outsiders become more likely to conform as taken-for-grantedness increases. We test our arguments in the empirical context of Islamic banking, using data on 118 Islamic banks worldwide between 2001 and 2014. We examine the likelihood that banks in the sector make what are known as zakat payments as a function of category taken-for-grantedness and the extent to which a bank’s identity is Islamic. We discuss implications for the literatures on categories and identity.
Selenium donors inhibits osteoclastogenesis through inhibiting IL-6 and plays a pivotal role in bone metastasis from breast cancer
Authors: Zhang Luyan , Wu Xifa , Feng Yong , Zheng Linlin , Jian Jinbo
Published: July 2020

Bone metastases are a frequent complication of breast cancer, and there has been little progress in the treatment of breast cancer patients with bone metastases. The cytotoxicity of selenium donors, including organic selenium and selenium nanoparticles (SeNPs), to cancer cells has been reported previously, but their relationship with bone metastases progression is not fully clear yet. In this study, multicenter clinical exploration was conducted to obtain dietary selenium intakes of breast cancer patients with or without bone metastasis, to study the relationship between selenium and breast cancer prognosis and bone metastasis. We found that dietary selenium intakes were significantly lower in breast cancer patients with bone metastasis, comparing with the non-bone metastasis cases. Selenium lower group of bone metastasis breast cancer patients had worse prognosis, whereas the daily selenium intakes could not predict the prognosis of breast cancer patients without bone metastasis. Subsequently, we study the regulatory role of selenium donors on bone metastasis at the cellular level, by challenging the cells with SeNPs. SeNPs showed potent cytotoxicity in breast cancer cells, no matter whether they were primary or bone-metastatic. SeNPs treated cancer cell inhibited the survival and differentiation of osteoclast progenitor cells. At the molecular level, we demonstrated that IL-6 partially mediated osteoclastogenesis suppression by SeNPs. These results provide a new way for biomarkers or drug development to treat and even prevent bone metastases of breast cancer by using selenium donors.
Urinary polycyclic aromatic hydrocarbons in relation to anthropometric measures and pubertal development in a cohort of Northern California girls
Authors: Dobraca Dina , Laurent Cecile A. , Greenspan Louise C. , Hiatt Robert A. , Sjödin Andreas , Kushi Lawrence H. , Windham Gayle C.
Published: July 2020

Background:

Polycyclic aromatic hydrocarbons (PAHs) are a class of ubiquitous, environmental chemicals that may have endocrine disrupting capabilities. We investigated whether childhood exposure to PAHs was associated with adiposity and pubertal timing in a longitudinal study of 404 girls enrolled in the Northern California site of the Breast Cancer and the Environment Research Program cohort.

Methods:

Baseline urinary samples from girls aged 6–8-years-old were assayed for 2-naphthol, fluorene metabolites, phenanthrene metabolites, 1-hydroxypyrene, and sum of PAH metabolites. Mixed-effects linear models were used to estimate how concentrations of PAH metabolites were related to changes in girl’s body mass index (BMI) and waist-to-height ratio from age 7 through 16 years old. Accelerated failure time models were used to estimate age of pubertal onset (Tanner stages 2 or higher for breast and pubic hair development).

Results:

Higher adiposity measurements among high tertiles of baseline PAH metabolites were evident at age 7 years old and increased thereafter (i.e., BMI for all PAH metabolites, waist-to-height ratio for fluorene and phenanthrene metabolites) or leveled off (i.e., waist-to-height ratio for 2-naphthol, 1-hydroxypyrene, sum of PAHs). Among girls overweight/obese at baseline, median age of breast development onset for high tertiles was 9.1–9.4 years old compared with 10–10.2 years old for low tertiles for all PAH metabolites; in contrast, found no association or slightly later onset of breast development for girls with normal weight at baseline.

Discussion:

These results suggest that exposure to specific PAHs during childhood may influence adiposity throughout adolescence and effect pubertal timing.
Long-term effects of latitude, ambient temperature, and ultraviolet radiation on the incidence of multiple sclerosis in two cohorts of US women
Authors: Lam Thao , VoPham Trang , Munger Kassandra L. , Laden Francine , Hart Jaime E.
Published: July 2020

Background:

Differences in multiple sclerosis (MS) risk by latitude have been observed worldwide; however, the exposures driving these associations are unknown. Ultraviolet radiation (UV) has been explored as a risk factor, and ambient temperature has been correlated with disease progression. However, no study has examined the impact of all three exposures. We examined the association between these exposures and incidence of MS within two nationwide prospective cohorts of women, the Nurses’ Health Study (NHS) and Nurses’ Health Study II (NHSII).

Methods:

Both cohorts were followed with biennial questionnaires to ascertain new diagnoses and risk factors. Time-varying exposures to latitude, cumulative average July temperature (°C), and cumulative average July erythemal UV (mW/m2) were predicted at each participant’s biennially updated residential addresses. Using Cox proportional hazards models adjusted for MS risk factors, we calculated hazard ratios (HR) and 95% confidence intervals (CIs) within each cohort and pooled via meta-analyses.

Results:

In multivariable models, there were suggestions that decreasing latitude (meta-analysis multivariable-adjusted HR = 0.72; 95% CI 0.55, 0.94 for women living <35.73° compared with those ≥42.15°, P-for-trend = 0.007) and increasing cumulative average July temperature (meta-analysis multivariable-adjusted HR = 0.81; 95% CI 0.72, 0.91 for each interquartile range increase [3.91°]) were associated with decreasing risk of MS. There was no evidence of heterogeneity between cohorts. We did not observe consistent associations with cumulative average UV.

Conclusion:

Our results suggest that adult exposures to decreasing latitude and increasing temperature, but not UV, were associated with reduced MS risk in these two cohorts of women. Studies of MS incidence may want to consider temperature as a risk factor.
Prevalence and Predictors of Obstructive Coronary Artery Disease in Nonlow-risk Acute Chest Pain Patients Who Rule Out for Myocardial Infarction in the High-sensitivity Troponin Era
Authors: Mahmoud Osama , Beer Dominik , Mahmaljy Hadi , Youniss Mohamed , Campoverde Edwin Hernandez , Elias Hadi , Stanton Matthew , Patel Maulin , Hashmi Insia , Young Katelyn , Kuppuraju Rajesh , Jacobs Steven , Alsaid Amro
Published: July 2020

Objectives:

The best management approach for chest pain patients who rule out for myocardial infarction (MI) in the high-sensitivity troponin (hsTn) era remains elusive. Patients, especially those with nonlow clinical risk scores, are often referred for inpatient ischemic testing to uncover obstructive coronary artery disease (CAD). Whether the prevalence of obstructive CAD in this cohort is high enough to justify routine testing is not known.

Methods:

We conducted a retrospective cohort analysis of 1517 emergency department chest pain patients who ruled out for MI by virtue of a stable high-sensitivity troponin T (hsTnT) levels (defined as <5 ng/L intermeasurements increase) and were admitted for inpatient testing.

Results:

Abnormal ischemia evaluation (including 5.9% with evidence of fixed wall motion or perfusion defects) was 11.9%. Of those undergoing invasive angiography (n = 292), significant coronary stenoses (≥70% or unstable lesions) and multivessel CAD occurred in 16.8% and 5.5%, respectively. In a multivariate logistic regression model, known CAD, prior MI, chest pain character, mildly elevated hsTnT, and left ventricular ejection fraction <40% were predictive of an abnormal ischemia evaluation result, whereas electrocardiography findings and the modified History, EKG, Age, Risk factors, and troponin (HEART) score were not. Of note, 30-day adverse cardiac events were strikingly low at 0.4% with no deaths despite an overwhelming majority (>90%) of patients scoring intermediate or high on the modified HEART score.

Conclusions:

A considerable percentage of acute chest pain patients who rule out for MI by hsTn had evidence of obstructive CAD, and the modified HEART score was not predictive of an abnormal ischemia evaluation.
FUNCTIONAL AND STRUCTURAL EFFECTS OF NONDAMAGING RETINAL LASER THERAPY FOR MACULAR TELANGIECTASIA TYPE 2
Authors: Lavinsky Daniel , Silva Monica Oliveira da , Chaves Anne E. , Schneider Wagner F. M. , Lavinsky Fabio , Palanker Daniel
Published: July 2020

Purpose:

Macular telangiectasia (MacTel) Type 2 is a progressing neurovascular disease of the macula, currently lacking effective treatment. This study assessed the effect of nondamaging retinal laser therapy (NRT) compared with sham.

Methods:

Twelve MacTel patients were enrolled in this double-masked, controlled, randomized clinical trial. For the nine patients with both eyes eligible, one eye was randomized to NRT or sham and the other received alternate treatment. For three patients with only one eye eligible, that eye was randomly assigned either NRT or sham. Ellipsoid zone disruption, best-corrected visual acuity, and macular automated perimetry at 12 months served as structural and functional measures.

Results:

Eleven eyes were randomized to sham and 10 to NRT. Baseline best-corrected visual acuity was 66 letters (20/50) for sham and 72 letters (20/40) for NRT (P = 0.245). Ellipsoid zone disruption area was 298 µm2 in sham and 368 µm2 in NRT (P = 0.391). At 12 months, ellipsoid zone disruption increased by 24% in sham and decreased by 34% in NRT (P < 0.001). Best-corrected visual acuity measures remained stable during follow-up compared with baseline. At 1 year, the mean macular sensitivity was 28 dB in the NRT group, compared with 26 dB in sham.

Conclusion:

Nondamaging retinal laser therapy was safe and well tolerated in patients with MacTel and resulted in structural and functional improvements, which could represent a protective effect of laser-induced hyperthermia. Longer follow-up and larger number of patients should help corroborate these effects.
RANIBIZUMAB WITH OR WITHOUT VERTEPORFIN PHOTODYNAMIC THERAPY FOR POLYPOIDAL CHOROIDAL VASCULOPATHY
Authors: Cheung Chui Ming Gemmy , Tan Colin S. , Patalauskaite Ramune , Margaron Philippe , Lai Timothy Y. Y.
Published: July 2020

Purpose:

To evaluate the demographic and imaging factors at baseline and Month 3 (M3) that predict visual or anatomical responses at Month 12 (M12) in the EVEREST-II study for polypoidal choroidal vasculopathy.

Methods:

Post-hoc analysis of 322 participants in the EVEREST-II study. Patient factors, best-corrected visual acuity (BCVA), treatment, and imaging parameters at baseline and M3 were evaluated with respect to outcomes at M12 using univariate and multivariable analysis.

Results:

Younger age (P < 0.001) and lower baseline BCVA (P < 0.001) were associated with higher BCVA gains at M12. Smaller baseline polypoidal lesion area was associated with higher BCVA gains at M12 only in the ranibizumab monotherapy arm (P = 0.008). Central subfield thickness at M3, area of branching vascular network at M3, BCVA at M3, and age were associated with change in BCVA from M3 at M12. Higher odds of fluid-free retina at M12 were associated with lower baseline central subfield thickness (P = 0.006), treatment with combination therapy (baseline and M3 models; P < 0.001), and absence of subretinal fluid at M3 (P < 0.001).

Conclusion:

Several imaging parameters at baseline and M3 can predict treatment outcome. The interaction between treatment arm and total polypoidal lesion area suggests this feature may assist selecting between initial ranibizumab monotherapy or combination therapy.
Recurrent c.776T>C mutation in CHST3 with four other novel mutations and a literature review
Authors: Duz Mehmet Bugrahan , Topak Ali
Published: July 2020

The chondrodysplasia with congenital joint dislocations,CHST3type, which was distinguished by predominantly contractures, marked vertebral changes, and normal facial appearance. Although, some clinical clues can be used for differential diagnosis, it is mostly too difficult to discriminate one type from another on basis of clinical findings only. Eight patients with multiple dislocations from five unrelated families were included in this study to elucidate molecular diagnoses. Clinical exome sequencing (CES) was performed on one patient from each family. Variable degree vertebral changes, pes equinovarus, and kyphoscoliosis accompanied multiple dislocations and short stature. In CES analyses, all mutations showed inCHST3. Previously reported c.776T>C homozygous mutations were detected in two families, compound heterozygous novel c.740G>C and c.881T>C mutations were found in one family, and homozygous novel c.564C>A and c.963G>A mutations were also determined in remaining two families, separately. BiallelicCHST3c.776T>C mutations are most frequent mutation inCHST3and have been reported predominantly in Turkish patients which may be remarkable for genotype-ethnicity correlation in chondrodysplasia with congenital joint dislocations,CHST3type. It is suggested that c.776T>C mutation can be accepted as a recurrent mutation inCHST3for Turkish patients who are suspected of having chondrodysplasia with congenital joint dislocations,CHST3type.
Assessing Cancer Patient Experience of Care in Outpatient Oncology Practices in the United States
Authors: Roth Lindsey , Tirodkar Manasi , Friedberg Mark , Smith-McLallen Aaron , Scholle Sarah Hudson
Published: July 2020

Introduction:

Cancer patients’ experience of care is an important component of quality that has not previously been used for comparing performance. We administered a new patient experience survey to cancer patients receiving outpatient chemotherapy treatment. We examined its measures for sensitivity to adjustment for case-mix and response tendency (level of general optimism/pessimism) and reliability for making performance comparisons between practices.

Methods:

We surveyed 2304 cancer patients who received chemotherapy at 23 medical oncology practices in Southeastern Pennsylvania, receiving 715 responses (response rate 31%; 14 practices had 10 or more responses). We aggregated patient responses to calculate practice-level scores on 5 predefined composites: Affective Communication, Shared Decision-Making, Patient Self-Management, Exchanging Information, and Access. We then ranked the practices on each composite before and after adjustment for standard case-mix variables and supplemental adjustment for response tendency (measured via the Life Orientation Test-Revised). We calculated the reliability of practice scores on each composite using hierarchical linear models and calculated minimum sample sizes necessary to achieve reliabilities exceeding 0.7.

Results:

After adjusting responses for case-mix and converting to a 0–100 scale, composite scores ranged from 77 for the Patient Self-Management composite to 92 for the Access composite. Adjustment for response tendency had an impact on practice rankings only for the Shared Decision-Making composite. The number of responses necessary to create reliable practice-level measurements ranged from 17 (Access composite) to 96 (Affective Communication composite).

Conclusions:

Patient experiences at oncology practices can be measured reliably using reasonable sample sizes. Standard case-mix adjustment is adequate for making comparisons on most composites.
Effects of the Recent Medicaid Expansions on Dental Preventive Services and Treatments
Authors: Lyu Wei , Shane Dan M. , Wehby George L.
Published: July 2020

Background:

Low-income adults in the United States have historically had poor access to dental services largely due to limited dental coverage.

Objective:

We examined the effects of recent Medicaid income-eligibility expansions under the Affordable Care Act on dental visits separately for preventive care and treatments.

Research Design:

We used restricted data from the 2011 to 2016 Medical Expenditure Panel Survey with state geocodes. The main analytical sample included nearly 21,000 individuals who were newly eligible for Medicaid. We employed a quasi-experimental difference-in-differences design to identify the impact of the state Medicaid expansions effective in 2014 on dental services use by the level of state Medicaid dental benefit for the newly eligible.

Results:

Expanding Medicaid in 2014 with extensive or limited dental coverage increased preventive dental visits and use of major dental treatments by over 5 percentage-points in 2014 and 2015. The increase in preventive visits continued in 2016 in expanding states with extensive coverage, while increase in major dental treatments continued in 2016 in expanding states with limited coverage. There is some but less consistent evidence of an increase in dental treatment with emergency-only coverage.

Conclusions:

Medicaid expansions with dental coverage beyond emergency-only services have increased access of the newly eligible low-income adults to dental treatments and preventive services, with extensive coverage showing continuing increase in preventive services use 3 years after the expansion. With limited coverage, there is some evidence of individuals needing to stretch treatments over a longer period. Providing comprehensive dental coverage can address unmet dental needs and improve oral health among low-income adults.
Diagnosis and management of pediatric metabolic bone diseases associated with skeletal fragility
Authors: Charoenngam Nipith , Cevik Muhammet B. , Holick Michael F.
Published: July 2020

Purpose of review

The goal of this review is to give an overview of diagnosis and up-to-date management of major pediatric metabolic bone diseases that are associated with bone fragility, including nutritional rickets, hypophosphatemic rickets, osteogenesis imperfecta, Ehlers--Danlos syndrome, Marfan's syndrome, hypophosphatasia, osteopetrosis and skeletal fluorosis.

Recent findings

During the past decade, a number of advanced treatment options have been introduced and shown to be an effective treatment in many metabolic bone disorders, such as burosumab for hypophosphatemic rickets and asfotase alfa for hypophosphatasia. On the other hand, other disorders, such as nutritional rickets and skeletal fluorosis continue to be underrecognized in many regions of the world. Genetic disorders of collagen-elastin, such as osteogenesis imperfecta, Ehlers--Danlos syndrome and Marfan's syndrome are also associated with skeletal fragility, which can be misdiagnosed as caused by non-accidental trauma/child abuse.

It is essential to provide early and accurate diagnosis and treatment for pediatric patients with metabolic bone disorders in order to maintain growth and development as well as prevent fractures and metabolic complications.
Pediatric mastocytosis
Authors: Hussain Sadaf H.
Published: July 2020

Purpose of review

The current article highlights recent developments in the field of pediatric cutaneous mastocytosis. Mastocytosis is a spectrum of conditions that range from fleetingly benign to aggressively malignant. Through recognizing the natural progression of disease, the role of biomarkers and mutational analysis, treatment and risk of triggers, physicians can confidently stage, counsel and manage patients with pediatric cutaneous mastocytosis.

Recent findings

Many lesions of cutaneous mastocytosis are chronic with some resolving around the mid-teenage years. KIT mutations are found in the majority of pediatric cutaneous mastocytosis but are not correlated with prognosis. Serum tryptase levels may be elevated in pediatric cutaneous mastocytosis patients without systemic mastocytosis. Pimecrolimus, omalizumab and tyrosine kinase inhibitors are effective treatment options. The low risk of NSAIDs and vaccinations has been characterized and epinephrine autoinjectors are rarely utilized in the pediatric cutaneous mastocytosis patient.

Pediatric cutaneous mastocytosis is a heterogeneous disease with good outcome overall. Organomegaly, elevated tryptase levels and the presence of KIT mutation in peripheral blood may aid in the decision to pursue bone marrow biopsy. The armamentarium of treatments has expanded and better understanding of the significance of triggers and vaccination safety allows the clinician to thoughtfully counsel and allay anxiety around pediatric cutaneous mastocytosis.
PIK3CA vascular overgrowth syndromes: an update
Authors: Hughes Meagan , Hao Michelle , Luu Minnelly
Published: July 2020

Purpose of review

Over the past decade many previously poorly understood vascular malformation disorders have been linked to somatic activating mutations in PIK3CA, which regulates cell survival and growth via activation of the mTOR1-AKT pathway. The goal of this article is to describe and provide an update on the clinical features, complications, and management strategies for the PIK3CA-related overgrowth spectrum (PROS).

Recent findings

PROS encompasses a heterogenous group of disorders with complications related to the tissues harboring the mutation. Vascular malformation syndromes, such as Klippel–Trenaunay syndrome and Congenital Lipomatous Overgrowth Vascular malformations Epidermal nevi and Skeletal abnormalities, have an increased risk of thromboembolic complications, which is accentuated postprocedurally. Asymmetric overgrowth, particularly of limbs, results in a high rate of orthopedic complications. Hypoglycemia screening in the neonatal period and ongoing monitoring for growth failure is recommended in megalencephaly capillary malformation due to its association with multiple endocrinopathies. Recently, sirolimus, an mTOR1 inhibitor, has shown promise in vascular anomalies and now PROS. PIK3CA direct inhibitor, Alpelisib (BYL719), was recently trialed with significant clinical benefit.

As the pathogenesis of these conditions is better elucidated and targeted treatments are developed, recognizing the clinical features, comorbidities, and evolving therapeutic landscape across the PROS spectrum becomes more crucial for optimization of care.
Hemangioma-related syndromes
Authors: Valdebran Manuel , Wine Lee Lara
Published: July 2020

Purpose of review

There is a growing understanding of complications and anomalies associated with infantile hemangiomas. The current review will discuss recent clinical advances in syndromes associated with segmental hemangiomas, including PHACE and LUMBAR syndrome. In addition, the importance of recognizing visceral hemangiomatosis is highlighted.

Recent findings

Ongoing longitudinal studies of PHACE and LUMBAR syndromes associated with segmental infantile hemangiomas have led to improved diagnosis and recommendations for screening for associated anomalies. Characterization of a growing spectrum of associated anomalies as well as better classification of at-risk patients will improve diagnosis and outcomes. In addition, visceral hemangiomatosis recognition and understanding of the potential association with consumptive hypothyroidism will improve initiation of appropriate screening.

Clinicians should be aware of infantile hemangiomas associated with potential syndromic complications and recognize the need to initiate appropriate work-up. Segmental hemangiomas of the head and neck region may indicate a risk of PHACE syndrome and associated developmental anomalies. Although LUMBAR syndrome is the association of lower body segmental hemangioma with developmental anomalies. Visceral hemangiomas most commonly affect the liver and may be associated with complications such as consumptive hypothyroidism and heart failure.
Brief Report: Switching From TDF to TAF in HIV/HBV-Coinfected Individuals With Renal Dysfunction—A Prospective Cohort Study
Authors: Surial Bernard , Béguelin Charles , Chave Jean-Philippe , Stöckle Marcel , Boillat-Blanco Noémie , Doco-Lecompte Thanh , Bernasconi Enos , Fehr Jan , Günthard Huldrych F. , Schmid Patrick , Walti Laura N. , Furrer Hansjakob , Rauch Andri , Wandeler Gilles ,   and the Swiss HIV Cohort Study
Published: July 2020

Background:

Whereas tenofovir disoproxil fumarate (TDF) can lead to renal adverse events, tenofovir alafenamide (TAF) has a more favorable renal safety profile. However, the impact of replacing TDF with TAF on renal function and liver parameters among HIV/hepatitis B virus (HBV)-coinfected individuals with renal dysfunction remains unclear.

Methods:

We included all participants from the Swiss HIV Cohort Study with an HIV/HBV coinfection who switched from TDF to TAF and had an estimated glomerular filtration rate (eGFR) <90 mL/min/1.73 m2 and a suppressed HIV viral load (<200 cp/mL). We assessed changes in eGFR, urine protein-to-creatinine ratio, and alanine aminotransferase (ALT) after 1 year using mixed-effect models with interrupted time series.

Results:

Among 106 participants (15.1% women, median age 53 years), eGFR was 60–89 mL/min/1.73 m2 in 84 (79.2%) and <60 mL/min/1.73 m2 in 22 (20.8%) individuals at the time of switch. One year after the switch from TDF to TAF, individuals with an eGFR between 60 and 89 mL/min/1.73 m2 experienced increases in eGFR of 3.2 mL/min/1.73 m2 (95% confidence interval [CI] 1.2 to 5.2), whereas those with an eGFR <60 mL/min/1.73 m2 experienced improvements of 6.2 mL/min/1.73 m2 (95% CI 2.4 to 10.0). Urine protein-to-creatinine ratio decreased overall (−6.3 mg/mmol, 95% CI −10.0 to −2.7), and ALT levels declined in patients with elevated baseline levels (−11.8 IU/L, 95% CI −17.3 to −6.4) 1 year after replacing TDF with TAF.

Conclusions:

Switching from TDF to TAF among HIV/HBV-coinfected individuals with renal impairment led to improvements in eGFR, a decline in proteinuria, and to ALT normalization in those with elevated ALT levels.
Recent advances in diagnosis and management of irritable bowel syndrome
Authors: Van den Houte Karen , Colomier Esther , Schol Jolien , Carbone Florencia , Tack Jan
Published: July 2020

Purpose of review

This review summarizes recent progress in the diagnosis and management of irritable bowel syndrome, with a focus on dietary and microbiota aspects.

Recent findings

From a pathophysiological point of view, IBS is a multifactorial condition with both peripheral (transit) as central (visceral hypersensitivity, anxiety, depression) contribution in a cumulative fashion to the symptom pattern and severity. More recently, the focus has shifted to diet and microbiota. The number of dietary options that can be used for IBS and the understanding of determinants of their efficacy is rapidly increasing. Several studies have confirmed the efficacy of the low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet. Sucrose-isomaltase deficiency has emerged as pathogenetic mechanisms in a subset of patients, who do not respond to low FODMAP diet but may respond to starch and sucrose elimination. Herbal remedies, probiotics and secretagogues have been the topic of additional treatment trials. The efficacy of fecal microbiota transplantation in IBS is variable across studies, but donor selection is emerging as a critical factor.

Irritable bowel syndrome has evolved into a disorder of interaction between dietary factors and gut microbiota, with impact on bowel symptoms as well as extra-intestinal, central, symptoms. Dietary adjustments and treatments targeting the gut microbiota are areas of active research and clinical progress.
Avian major histocompatibility complex copy number variation is associated with helminth richness
Authors: Minias Piotr , Gutiérrez Jorge S. , Dunn Peter O.
Published: July 2020

Genes of the major histocompatibility complex (MHC) play a key role in the adaptive immunity of vertebrates, as they encode receptors responsible for antigen recognition. Evolutionary history of the MHC proceeded through numerous gene duplications, which increase the spectrum of pathogens recognized by individuals. Although pathogen-mediated selection is believed to be a primary driver of MHC expansion over evolutionary times, empirical evidence for this association is virtually lacking. Here, we used an extensive dataset on MHC class II copy number variation in non-passerine birds to test for an evolutionary correlation with helminth parasite richness. As expected, our phylogenetically-informed modelling revealed a positive association between MHC copy number and total helminth richness, even after controlling for a broad spectrum of ecological and life-history traits. Thus, total helminth richness appears to be the most important correlate of MHC copy number, supporting a leading role of pathogen-mediated selection in the evolution of MHC in birds. Our results provide some of the first, although correlative, evidence linking parasitism to interspecific variation in MHC copy number among birds.
Renal carcinoma is associated with increased risk of coronavirus infections
Authors: Tripathi Satyendra C , Deshmukh Vishwajit , Creighton Chad J. , Patil Ashlesh
Published: July 2020

The current pandemic COVID-19 has affected most severely to the people with old age, or with comorbidities such as hypertension, diabetes mellitus, chronic kidney disease, COPD, and cancers. Cancer patients are twice more likely to contract the disease because of the malignancy or treatment-related immunosuppression; hence identification of the vulnerable population among these patients is essential. It is speculated that along with ACE2, other auxiliary proteins (DPP4, ANPEP, ENPEP, TMPRSS2) might facilitate the entry of coronaviruses in the host cells. We took a bioinformatics approach to analyze the gene and protein expression data of these coronavirus receptors in human normal and cancer tissues of multiple organs. Here, we demonstrated an extensive RNA and protein expression profiling analysis of these receptors across solid tumors and normal tissues. We found that among all, renal tumor and normal tissues exhibited increased levels of ACE2, DPP4, ANPEP, and ENPEP. Our results revealed that TMPRSS2 may not be the co-receptor for coronavirus in renal carcinoma patients. The receptors’ expression levels were variable in different tumor stage, molecular and immune subtypes of renal carcinoma. In clear cell renal cell carcinomas, coronavirus receptors were associated with high immune infiltration, markers of immunosuppression, and T cell exhaustion. Our study indicates that CoV receptors may play an important role in modulating the immune infiltrate and hence cellular immunity in renal carcinoma. As our current knowledge of pathogenic mechanisms will improve, it may help us in designing focused therapeutic approaches.
Associations between state-level healthcare access and COVID-19 case trajectories in the United States
Authors: Liu Shelley H. , Liu Bian , Norbury Agnes , Li Yan
Published: July 2020

Introduction

We conducted an ecological study to determine if state-level healthcare access is associated with trajectories of daily reported COVID-19 cases in the United States. Our focus is on trajectories of daily reported COVID-19 cases, rather than cumulative cases, as trajectories help us identify trends in how the pandemic naturally develops over time, and study the shapes of the curve in different states.

Methods

We analyzed data on daily reported confirmed and probable COVID-19 cases from January 21 to June 16, 2020 in 50 states, adjusted for the population size of each state. Cluster analysis for time-series data was used to split the states into clusters that have distinct trajectories of daily cases. Differences in socio-demographic characteristics and healthcare access between clusters were tested. Adjusted models were used to determine if healthcare access is associated with reporting a high trajectory of COVID-19 cases.

Results

Two clusters of states were identified. One cluster had a high trajectory of population- adjusted COVID-19 cases, and comprised of 19 states, including New York and New Jersey. The other cluster of states (n=31) had a low trajectory of population-adjusted COVID-19 cases.

There were significantly more Black residents (p=0.027) and more nursing facility residents (p=0.001) in states reporting high trajectory of COVID-19 cases. States reporting a high trajectory of COVID-19 cases also had fewer uninsured persons (p=0.005), fewer persons who reported having to forgo medical care due to cost (p=0.016), more registered physicians (p=0.002) and more nurses (p=0.03), higher health spending per capita (p=0.01), fewer residents in Health Professional Shortage Areas per 100,000 population (p=0.027), and higher adoption of Medicaid Expansion (p=0.05).

In adjusted models, a higher proportion of uninsured persons (OR: 0.51 [0.25-0.85]; p=0.032), higher proportion of patients who had to forgo medical care due to cost (OR: 0.55 [0.28-0.95]; p=0.048), and no adoption of Medicaid expansion (OR: 0.05 [0 – 0.59]; p=0.04), were associated with reporting a low trajectory of COVID-19 cases.

Conclusion

Our findings from adjusted models suggest that healthcare access can partially explain variations in COVID-19 case trajectories by state.
Combination Treatment Optimization Using a Pan-Cancer Pathway Model
Authors: Schmucker Robin , Farina Gabriele , Faeder James , Fröhlich Fabian , Saglam Ali Sinan , Sandholm Tuomas
Published: July 2020

The design of efficient combination therapies is a difficult key challenge in the treatment of complex diseases such as cancers. The large heterogeneity of cancers and the large number of available drugs renders exhaustivein vivoor evenin vitroinvestigation of possible treatments impractical. In recent years, sophisti-cated mechanistic, ordinary differential equation-based pathways models that can predict treatment responses at amolecularlevel have been developed. However, surprisingly little effort has been put into leveraging these models to find novel therapies. In this paper we use for the first time, to our knowledge, a large-scale state-of-the-art pan-cancer signaling pathway model to identify potentially novel combination therapies to treat individual cancer cell lines from various tissues (e.g., minimizing proliferation while keeping dosage low to avoid adverse side effects) and populations of cancer cell lines (e.g., minimizing the maximum or average proliferation across the cell lines while keeping dosage low). We also show how our method can be used to optimize the mixtures and dosages used insequentialtreatment plans—that is, optimized sequences of potentially different drug combinations—providing additional benefits. In order to solve the treatment optimization problems, we combine the Covariance Matrix Adaptation Evolution Strategy (CMA-ES) algorithm with a significantly more scalable sampling scheme for truncated Gaussian distributions, based on a Hamiltonian Monte-Carlo method. These optimization techniques are independent of the signaling pathway model, and can thus be used for other signaling pathway models also, provided that a suitable predictive model is available.
Calumenin contributes to epithelial-mesenchymal transition and predicts poor survival in glioma
Authors: Yang Ying , Wang Jin , Xu Shihai , Shi Fei , Shan Aijun
Published: July 2020

Calumenin (CALU) has been reported to be associated with invasiveness and metastasis in some malignancies. However, in glioma, the role of CALU remains unclear. In the current study, we aimed to unveil its role in glioma based on transcriptome level. Clinical and transcriptome data of 998 glioma patients, including 301 from CGGA mRNA microarray dataset and 697 from TCGA RNA sequencing dataset, were downloaded and analyzed. R language was used to perform statistical analyses and generate figures. In glioma, CALU expression seemed to be positively associated with WHO grade system, and was enriched in IDH wildtype, mesenchymal and classical subtype. Genes that tightly correlated with CALU were screened and annotated with Gene Ontology, and it turned out that, these genes were highly enriched in cell/biological adhesion, response to wounding, and extracellular matrix/structure organization, all of which were strongly correlated with the epithelial-mesenchymal transition (EMT) phenotype. Subsequent GSEA analysis further validated the profound involvement of CALU in EMT. To get further understanding of the association between EMT and CALU, GSVA analysis was performed to identify the EMT signaling pathways that CALU might involve. CALU expression was found to be positively correlated with TGFβ, PI3K/AKT, and hypoxia pathway. Furthermore, Pearson correlation indicated that CALU played synergistically with EMT key markers, including N-cadherin, vimentin, snail, slug and TWIST1, in both CGGA and TCGA dataset. Kaplan-Meier curves and Cox regression analyses showed that higher CALU predicted a worse survival for patients, and the prognostic value was independent of WHO grade and age. In conclusion, CALU was correlated with more malignant phenotypes in glioma. Moreover, CALU seemed to serve as a pro-EMT molecular target and could contribute to predict prognosis independently for glioma patients.
Predicting alcohol use from genome-wide polygenic scores, environmental factors, and their interactions in young adulthood
Authors: Kandaswamy Radhika , Allegrini Andrea , Nancarrow Alexandra F. , Cave Sophie Nicole , Plomin Robert , von Stumm Sophie
Published: July 2020

Alcohol use during emerging adulthood is associated with adverse life outcomes but its risk factors are not well known. Here, we predicted alcohol use in 3,153 young adults aged 22 years from (a) genome-wide polygenic scores (GPS) based on genome-wide association studies for the target phenotypes number of drinks per week and Alcohol Use Disorders Identification Test scores, (b) 30 environmental factors, and (c) their interactions (i.e., GxE effects). Data was collected from 1994 to 2018 as a part of the UK Twins Early Development Study. GPS accounted for up to 1.9% of the variance in alcohol use (i.e., Alcohol Use Disorders Identification Test score), while the 30 measures of environmental factors together accounted for 21.1%. The 30 GPS-environment interactions did not explain any additional variance and none of the interaction terms exceeded the significance threshold after correcting for multiple testing. Our findings suggest that GPS and environmental factors have primarily direct, additive effects rather than interacting systematically.
Multilevel community assembly of the tadpole gut microbiome
Authors: Correa Decio T. , Rodriguez David , Emer Carine , Saenz Daniel , Adams Cory K. , Schiesari Luis , Matz Mikhail , Leibold Mathew A.
Published: July 2020

The assembly of local communities is likely to reflect the effects of local environmental factors associated with filters that act at larger spatial scales. Dissecting these multiscale effects remains a timely challenge that is particularly important for host-associated microbiomes. We investigated the relative roles of local selection (due to host species identity) and regional effects (due to water body identity) on the community structure of bacteria in the gut of tadpoles from three biogeographic areas and used graph theory and metanetwork approaches to explore and illustrate the distribution of bacteria across different ponds. The pond of origin, which represents a regional species pool of bacteria, was in general more important in shaping the gut microbiome of tadpoles than host species identity. The resulting metanetworks are modular and indicate relatively few species of bacteria occurring in more than one pond. Thus, each pond represents a relatively distinct species pool of bacteria available for community assembly of the tadpole microbiomes. Our findings indicate that microbiome community assembly in amphibian larvae, as in many other communities, is a multiscale process with important regional effects that constrain how local (i.e. host-dependent) filters act to influence microbiome community composition.
DNNBrain: a unifying toolbox for mapping deep neural networks and brains
Authors: Chen Xiayu , Zhou Ming , Gong Zhengxin , Xu Wei , Liu Xingyu , Huang Taicheng , Zhen Zonglei , Liu Jia
Published: July 2020

Deep neural networks (DNNs) have attained human-level performance on dozens of challenging tasks through an end-to-end deep learning strategy. Deep learning gives rise to data representations with multiple levels of abstraction; however, it does not explicitly provide any insights into the internal operations of DNNs. Its success appeals to neuroscientists not only to apply DNNs to model biological neural systems, but also to adopt concepts and methods from cognitive neuroscience to understand the internal representations of DNNs. Although general deep learning frameworks such as PyTorch and TensorFlow could be used to allow such cross-disciplinary studies, the use of these frameworks typically requires high-level programming expertise and comprehensive mathematical knowledge. A toolbox specifically designed for cognitive neuroscientists to map DNNs and brains is urgently needed. Here, we present DNNBrain, a Python-based toolbox designed for exploring internal representations in both DNNs and the brain. By integrating DNN software packages and well-established brain imaging tools, DNNBrain provides application programming and command line interfaces for a variety of research scenarios, such as extracting DNN activation, probing DNN representations, mapping DNN representations onto the brain, and visualizing DNN representations. We expect that our toolbox will accelerate scientific research in applying DNNs to model biological neural systems and utilizing paradigms of cognitive neuroscience to unveil the black box of DNNs.
Enablingin vivoAnalysis Via Nanoparticle-mediated Intracellular Assay Probe Delivery: Using RAS as the Prototype
Authors: Chen Fengqian , Liu Qi , Hilliard Terrell , Wang Tingzeng , Dong Ziye , Li Wei , Liang Hongjun , Gao Weimin , Huang Leaf , Wang Degeng
Published: July 2020

Many experimental protocols must be executedin vitrodue to a lack of cell-permeable analysis probes. For instance, the cellular signaling moderator RAS proteins alternate between the active GTP-binding and the inactive GDP-binding states. Though many GTP analogs can serve as probes for RAS activity analysis, their cell impermeability rendersin vivoanalysis impossible. On the other hand, the lipid/calcium/phosphate (LCP) nanoparticle has enabled efficient intracellular delivery of a nucleotide analog as a chemotherapy agent. Thus, using RAS analysis and LCP nanoparticle as the prototype, we tackled the cell-impermeability issue via nanoparticle-mediated intracellular delivery of the analysis probe. Briefly, BODIPY-FT-GTP-γ-S, a GTP analog that becomes fluorescent only upon protein binding, was chosen as the analysis probe, so that GTP binding can be quantified by fluorescent activity. BODIPY-FT-GTP-γ-S-loaded LCP-nanoparticle was synthesized for efficient intracellular BODIPY-FT-GTP-γ-S delivery. Binding of the delivered BODIPY-FT-GTP-γ-S to the RAS proteins were consistent with previously reported observations; the RAS GTP binding activity was reduced in serum-starved cells; and a transient activation peak of the binding activity was observed upon subsequent serum reactivation of the cells. In a word, nanoparticle-mediated probe delivery enabled anin vivoRAS analysis method. The approach should be applicable to a wide variety of analysis protocols.
Rats and the COVID-19 pandemic: Early data on the global emergence of rats in response to social distancing
Authors: Parsons Michael H. , Kiyokawa Yasushi , Richardson Jonathan L. , Stryjek Rafal , Byers Kaylee A. , Himsworth Chelsea G. , Corrigan Robert M. , Deutsch Michael A , Ootaki Masato , Tanikawa Tsutomu , Parsons Faith E. , Munshi-South Jason
Published: July 2020

Following widespread closures of food-related businesses due to efforts to curtail the spread of SARS-CoV-2, public health authorities reported increased sightings of rats in close vicinity of people. Because rats vector a number of pathogens transmissible to people, changes in their behavior has consequences for human health risks. To determine the extent of how stay-at-home measures influenced patterns of rat sightings we: 1) examined the number of rat-related public service requests before and during the period of lockdown in New York City (NYC) and Tokyo, Japan; 2) examined reports made in proximity to closed food service establishments in NYC; and 3) surveyed pest control companies in the United States, Canada, Japan, and Poland. During the month following lockdown, the overall number of reports decreased by 30% in NYC, while increasing 24% in Tokyo. However, new hotspots of 311 calls were observed in proximity of closed food service establishments in NYC; and there was a consistent positive association between kernel density estimates of food service establishments and location of 311 calls (r = 0.33 to 0.45). Similarly, more reports were observed in the restaurant-dense eastern side of Tokyo. Changes in clientele for pest control companies varied geographically, with 37% of pest-management companies surveyed in North America reporting 50-100% of their post-lockdown rat-related requests coming from new clients. In Warsaw, where there are no clusters of restaurants in densely-populated areas, there were no changes. In Tokyo, there were no changes in clients. We conclude that changes in public service calls are region-specific and localized, with increases in rat sightings more likely near restaurant-dense regions. Pest control companies surveyed in North America either lost much of their business or shifted clientele from old to new locations. We discuss possible mitigation measures including ramping up pest control during re-opening of food-related establishments and the need for citywide rodent surveillance and disease monitoring.