bluuebunny/crossref_metadata_2025 huggingface dataset:
Norms for Zung’s Self-rating Anxiety Scale
Authors: Dunstan Debra A. , Scott Ned
Published: February 2020

Background

Zung’s Self-rating Anxiety Scale (SAS) is a norm-referenced scale which enjoys widespread use a screener for anxiety disorders. However, recent research (Dunstan DA and Scott N, Depress Res Treat 2018:9250972, 2018) has questioned whether the existing cut-off for identifying the presence of a disorder might be lower than ideal.

Method

The current study explored this issue by examining sensitivity and specificity figures against diagnoses made on the basis of the Patient Health Questionnaire (PHQ) in clinical and community samples. The community sample consisted of 210 participants recruited to be representative of the Australian adult population. The clinical sample consisted of a further 141 adults receiving treatment from a mental health professional for some form of anxiety disorder.

Results

Mathematical formulas, including Youden’s Index and the Receiver Operating Characteristics Curve, applied to positive PHQ diagnoses (presence of a disorder) from the clinical sample and negative PHQ diagnoses (absence of a disorder) from the community sample suggested that the ideal cut-off point lies between the current and original points recommended by Zung.

Conclusions

Consideration of prevalence rates and of the potential costs of false negative and false positive diagnoses, suggests that, while the current cut-off of 36 might be appropriate in the context of clinical screening, the original raw score cut-off of 40 would be most appropriate when the SAS is used in research.
Machine learning analysis of exome trios to contrast the genomic architecture of autism and schizophrenia
Authors: Sardaar Sameer , Qi Bill , Dionne-Laporte Alexandre , Rouleau Guy. A. , Rabbany Reihaneh , Trakadis Yannis J.
Published: February 2020

Background

Machine learning (ML) algorithms and methods offer great tools to analyze large complex genomic datasets. Our goal was to compare the genomic architecture of schizophrenia (SCZ) and autism spectrum disorder (ASD) using ML.

Methods

In this paper, we used regularized gradient boosted machines to analyze whole-exome sequencing (WES) data from individuals SCZ and ASD in order to identify important distinguishing genetic features. We further demonstrated a method of gene clustering to highlight which subsets of genes identified by the ML algorithm are mutated concurrently in affected individuals and are central to each disease (i.e., ASD vs. SCZ “hub” genes).

Results

In summary, after correcting for population structure, we found that SCZ and ASD cases could be successfully separated based on genetic information, with 86–88% accuracy on the testing dataset. Through bioinformatic analysis, we explored if combinations of genes concurrently mutated in patients with the same condition (“hub” genes) belong to specific pathways. Several themes were found to be associated with ASD, including calcium ion transmembrane transport, immune system/inflammation, synapse organization, and retinoid metabolic process. Moreover, ion transmembrane transport, neurotransmitter transport, and microtubule/cytoskeleton processes were highlighted for SCZ.

Conclusions

Our manuscript introduces a novel comparative approach for studying the genetic architecture of genetically related diseases with complex inheritance and highlights genetic similarities and differences between ASD and SCZ.
Psychometric properties and factor structure of the Korean version of the screen for child anxiety related emotional disorders (SCARED)
Authors: Shin Jiyoon , Kim Kyoung Min , Lee Kyung Hwa , Hong Soon-Beom , Lee Jung , Choi Chi-Hyun , Han Ji Youn , Kim Seong Hae , Suh Da Eun , Cho Soo-Churl , Kim Jae-Won
Published: February 2020

Background

The aim of this study was to examine the psychometric properties of the Korean version of Screen for Child Anxiety Related Emotional Disorders (SCARED) on a sample of Korean youths and to examine the cross-cultural differences in adolescents’ anxiety.

Methods

Our study included 147 adolescents (ages 12–17, 92 girls), 93 with major depressive disorder and 54 as controls. Participants were evaluated using the Kiddie-Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL), SCARED, Child Behavior Checklist (CBCL), Disruptive Behavioral Disorder Scale (DBD) and Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS). Pearson’s r and Cronbach’s α values of the SCARED were calculated, and exploratory factor analysis was conducted.

Results

The Korean SCARED scores were correlated with the total anxiety scores of K-SADS-PL (r = 0.74) and the CBCL anxious/depressed subscale scores (r = 0.35). Results showed a five-factor structure with good internal consistency, in which some items were loaded on different factors compared to previous studies.

Conclusions

The Korean SCARED demonstrated promising psychometric properties, and could be a valid scale for screening anxiety symptoms in primary care. The fact that different items comprised the factors may reflect the cultural difference between United States and Korea in experiencing anxiety.
Sleep quality and nocturnal pain in patients with femoroacetabular impingement and acetabular dysplasia
Authors: Reddy Nisha , Martinez J. Riley , Mulligan Edward , Nakonezny Paul , Wells Joel
Published: February 2020

Background

Femoroacetabular impingement (FAI) syndrome and acetabular dysplasia (AD) are common pathologies that lead to pain in the young adult hip. Nocturnal pain in these patients is often reported, yet little is known regarding the effect of these hip pathologies on overall sleep quality. The purpose of this study was to evaluate sleep quality in patients with AD and FAI syndrome.

Methods

This cross-sectional study consisted of 115 patients who complained of hip pain secondary to either FAI syndrome or AD. One hundred fifteen patients with hip pain secondary to FAI syndrome and AD were assessed using the Hip Outcome Score (HOS), Modified Harris Hip Score (mHHS), and then Hip disability and Osteoarthritis Outcome Score (HOOS). Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Multiple linear regression, with adaptive LASSO variable selection, was used to assess factors associated with sleep quality.

Results

Of the 115 patients, 62 had a diagnosis of FAI syndrome and 53 with AD. The mean age was 34.55 ± 11.66 (age range: 14 to 58 years), 76.52% had an ASA classification of 1 (ASA range: 1 to 3), and all Tonnis grades were either 0 or 1. The mean PSQI global score for all patients was 8.46 ± 4.35 (PSQI range: 0 to 21), indicating poor sleep quality. The adaptive LASSO-penalized least squares multiple linear regression revealed that HOOS Pain, SF-12 Role Emotional, and SF-12 Mental Health significantly predicted Sleep Quality (Adjusted R2 = 0.4041). Sleep quality improved as pain, emotional problems, and mental health improved.

Conclusion

Patients with symptomatic FAI syndrome and AD have poor sleep quality. Worsening pain from a patient’s hip pathology is associated with poor sleep, even prior to the onset of osteoarthrosis of the hip. Patients presenting with hip pain from FAI syndrome and AD should be screened for sleep disturbance and may benefit from a multidisciplinary treatment approach.
Herbal medicine from the perspective of type II diabetic patients and physicians: what is the relationship?
Authors: Alqathama Aljawharah , Alluhiabi Ghadeer , Baghdadi Halah , Aljahani Lujain , Khan Ola , Jabal Sara , Makkawi Shorooq , Alhomoud Farah
Published: February 2020

Background

Diabetes mellitus (DM) is a major public health problem and one of the most challenging diseases worldwide. According to the World Health Organization (WHO), the Kingdom of Saudi Arabia (KSA) has the second highest rate of diabetes in the Middle East and seventh highest globally. Some diabetic patients may prefer to use alternative approaches such as herbal remedies to control their blood glucose level and this study aims to assess the prevalence of herbal usage and to evaluate users’ and doctors’ knowledge, attitudes and beliefs about herbal medicine as well as the patient/doctor relationship in this regard.

Method

A cross-sectional survey was conducted in several hospitals and medical centres in Makkah, KSA, between January and March 2019. Around 289 type II diabetic patients and 105 doctors were interviewed.

Results

We found that 68% of the participants were frequent consumers of herbal remedies, especially cinnamon, ginger and fenugreek. Patients’ knowledge of herbal usage was mainly gleaned from family and friends as well as social media, and we found that many (71.4%) did not bother to consult or inform their doctors about their choice to self-medicate with herbs. Patients had no concerns regarding the efficacy and safety of herbal usage use in diabetes, as around half of the participants believe that herbal medicine is effective (54%) and safe (46%) for treating symptoms of diabetes. Two-thirds of the doctors (66%) routinely ask patients whether they use herbs for their condition. Although 25% of the doctors took a positive view of herbal medicine in relation to diabetes, others expressed concerns with the rise in herb use and want to see more attention paid to safety aspects.

Conclusion

The study concludes that herbal remedies are commonly used by diabetic patients and that a gap exists in the relationship between patients and doctors concerning the disclosure of herbal remedy use and views on its safety.
MEX3A knockdown inhibits the development of pancreatic ductal adenocarcinoma
Authors: Wang Xing , Shan Yu-Qiang , Tan Qing-Quan , Tan Chun-Lu , Zhang Hao , Liu Jin-Heng , Ke Neng-Wen , Chen Yong-Hua , Liu Xu-Bao
Published: February 2020

Background

Pancreatic ductal adenocarcinoma (PDA) is one of the most serious causes of death in the world due to its high mortality and inefficacy treatments. MEX3A was first identified in nematodes and was associated with tumor formation and may promote cell proliferation and tumor metastasis. So far, nothing is known about the relationship between MEX3A and PDA.

Methods

In this study, the expression level of MEX3A in PDA tissues was measured by immunohistochemistry. The qRT-PCR and western blot were used to identify the constructed MEX3A knockdown cell lines, which was further used to construct mouse xenotransplantation models. Cell proliferation, colony formation, cell apoptosis and migration were detected by MTT, colony formation, flow cytometry and Transwell.

Results

This study showed that MEX3A expression is significantly upregulated in PDA and associated with tumor grade. Loss-of-function studies showed that downregulation of MEX3A could inhibit cell growth in vitro and in vivo. Moreover, it was demonstrated that knockdown of MEX3A in PDA cells promotes apoptosis by regulating apoptosis-related factors, and inhibits migration through influencing EMT. At the same time, the regulation of PDA progression by MEX3A involves changes in downstream signaling pathways including Akt, p-Akt, PIK3CA, CDK6 and MAPK9.

Conclusions

We proposed that MEX3A is associated with the prognosis and progression of PDA,which can be used as a potential therapeutic target.
Use of thiazide diuretics for the prevention of recurrent kidney calculi: a systematic review and meta-analysis
Authors: Li Dan-feng , Gao Yu-lu , Liu Hong-chao , Huang Xiao-chen , Zhu Rui-fang , Zhu Chang-tai
Published: February 2020

Background

Thiazide diuretics reduce the risk of recurrent kidney calculi in patients with kidney calculi or hypercalciuria. However, whether thiazide diuretics can definitely prevent recurrent kidney calculi remains unclear. We aimed to evaluate the effect and safety of thiazide diuretics on recurrent kidney calculi.

Methods

The PubMed, Cochrane Library, and EMBASE databases were systematically searched using the keywords thiazide diuretics and kidney calculi to identify randomized controlled trials (RCTs). The primary outcome was the incidence of recurrent kidney calculi, and the secondary outcome was the 24-h urinary calcium level. The pooled risk ratio (RR), risk difference (RD), standardized mean difference (SMD), and 95% confidence interval (CI) were calculated. The evidence quality was graded using the GRADE criteria, and recommendations for recurrent kidney calculus prevention using thiazide diuretics were reassessed.

Results

Eight RCTs involving 571 patients were included. The pooled RR for the incidence of kidney calculi in the thiazide diuretic groups was 0.44 (95% CI 0.33–0.58, P < 0.0001) compared to that in the placebo and untreated groups; the pooled RD was − 0.23 (95% CI − 0.30 to − 0.16, P < 0.0001). The pooled SMD for the 24-h urinary calcium level was − 18.59 (95% CI − 25.11 to − 12.08, P < 0.0001). The thiazide diuretic groups had a high incidence of adverse reactions and low tolerance. The evidence quality for decrease in kidney calculus incidence using thiazide diuretics was low, while that for the 24-h urinary calcium level decrease among those with recurrent kidney calculi was moderate, and that for the decrease in kidney calculus incidence using short-acting and long-acting thiazide diuretics was low. The overall strength of recommendation for prevention of recurrent renal calculi using thiazide diuretics was not recommended. The subgroup and sensitivity analysis findings were robust.

Conclusions

Long-term use of thiazide diuretics reduces the incidence of recurrent renal calculi and 24-h urinary calcium level. However, the benefits are insufficient, and the evidence quality is low. Considering the adverse effects, poor patient compliance, and economic burden of long-term medication, their use in preventing recurrent kidney calculi is not recommended.
Episodes of violence suffered by migrants transiting through Libya: a cross-sectional study in “Médecins du Monde’s” reception and healthcare centre in Seine-Saint-Denis, France
Authors: Reques L. , Aranda-Fernandez E. , Rolland C. , Grippon A. , Fallet N. , Reboul C. , Godard N. , Luhmann N.
Published: February 2020

Introduction

The Central Mediterranean Route, passing through Libya, is one of the most dangerous for migrants. Episodes of violence have been documented but have not been accurately quantified. The objective of the study was to estimate the prevalence of episodes of violence suffered in Libya by migrants consulting the Médecins du Monde reception and healthcare centre in Seine-Saint-Denis (Ile-de-France).

Methodology

A monocentric cross-sectional study was conducted from February to May 2019 including migrants over the age of 18 years who had passed through Libya and arrived in Europe from 2017. The presence of emotional distress was considered as exclusion criterion. The proportion, frequency and factors associated to physical, deprivation and sexual violence in Libya were estimated through a bespoke questionnaire, as well as healthcare access in Libya and psychosocial support needs.

Results

Ninety eight people were recruited and 72 were interviewed (17 refused to participate and 9 were excluded). 76.4% were men, with a mean age of 31.9 years, 76.4% had low educational level, 66.7% came from Ivory Coast and 59.7% had left their country for security reasons. The median length of stay in Libya was 180 days. The overall proportion of participants having suffered from violence was 96.4% among men and 88.2% among women. The prevalence of physical, deprivation and sexual violence for men and women were 94.2, 81.7 and 18% and 80.0, 86.7 and 53.3%, respectively. Access to healthcare in Libya was 2.8 and 63.9% of participants were oriented to psychosocial support after the interview.

Conclusions

The vast majority of migrants reported having been victims of violence during their transit through Libya. Women were at particular risk of sexual violence. Access to health care in Libya was almost non-existent. Psychosocial support for this population is urgent.
Novel CDKL5 mutations were found in patients in China: retrospective investigation in cases of CDKL5-related disorders
Authors: Yan Yumei , He Dake , Wu Jing , Hou Ruolin , Sun Kun , Li Ling
Published: February 2020

Objective

CDKL5-related disorders (CDD) is an epileptic encephalopathy resulted of gene mutations of CDKL5. This study aimed to explore the development process of CDD and to expand its mutation spectrum.

Methods

Clinic datawas collected about three infantile epileptic encephalopathy cases diagnosed at Xinhua Hospital Affiliated to Shanghai Jiaotong University, School of Medicine. Next generation sequencing technology was used to find three de novo mutations of CDKL5. We searched published literatures about CDKL5 in pubmed and made an analysis about our clinic data and the related literatures.

Results

The three patients were all girls. Their average onset age of seizures was around 2 months, and all of them have intractable epileptic seizures, severe intellectual disability, and hypotension. Among them, two presented infantile spasm and high arrhythmia in EEG, and the other manifested clonic seizure and broad epileptiform discharge in EEG. Extracerebral space widening in cranial MRIs was demonstrated in two cases. Visual evoked potential was abnormal in two cases. Seizures were resistant to all kinds of antiepileptic drugs (AEDs). Gene tests showed three de novo mutations of CDKL5: one was a truncated mutation (c.2254A > T,P.R752X, stop279), which was pathogenic according to the ACMG guide, the other two were missense mutations (c.377G > T,p.Cys126Phe) and a frameshift mutation (c.362-362insG(p.Ala122GlyfsTer7), which were likely pathogenic according to the ACMG.

Conclusions

All three de novo mutations are first reported. Based on the combined related literature and the manifestations observed, we diagnosed the three children as CDKL5-related disorders, and concluded that the de novo CDKL5 mutations are the reason for their epilepsy.
Impact of protocolized diuresis for de-resuscitation in the intensive care unit
Authors: Bissell Brittany D. , Laine Melanie E. , Thompson Bastin Melissa L. , Flannery Alexander H. , Kelly Andrew , Riser Jeremy , Neyra Javier A. , Potter Jordan , Morris Peter E.
Published: February 2020

Objective

Administration of diuretics has been shown to assist fluid management and improve clinical outcomes in the critically ill post-shock resolution. Current guidelines have not yet included standardization or guidance for diuretic-based de-resuscitation in critically ill patients. This study aimed to evaluate the impact of a multi-disciplinary protocol for diuresis-guided de-resuscitation in the critically ill.

Methods

This was a pre-post single-center pilot study within the medical intensive care unit (ICU) of a large academic medical center. Adult patients admitted to the Medical ICU receiving mechanical ventilation with either (1) clinical signs of volume overload via chest radiography or physical exam or (2) any cumulative fluid balance ≥ 0 mL since hospital admission were eligible for inclusion. Patients received diuresis per clinician discretion for a 2-year period (historical control) followed by a diuresis protocol for 1 year (intervention). Patients within the intervention group were matched in a 1:3 ratio with those from the historical cohort who met the study inclusion and exclusion criteria.

Results

A total of 364 patients were included, 91 in the protocol group and 273 receiving standard care. Protocolized diuresis was associated with a significant decrease in 72-h post-shock cumulative fluid balance [median, IQR − 2257 (− 5676–920) mL vs 265 (− 2283–3025) mL; p < 0.0001]. In-hospital mortality in the intervention group was lower compared to the historical group (5.5% vs 16.1%; p = 0.008) and higher ICU-free days (p = 0.03). However, no statistically significant difference was found in ventilator-free days, and increased rates of hypernatremia and hypokalemia were demonstrated.

Conclusions

This study showed that a protocol for diuresis for de-resuscitation can significantly improve 72-h post-shock fluid balance with potential benefit on clinical outcomes.
Scaling up Quality Improvement for Surgical Teams (QIST) – avoiding surgical site infection and anaemia at the time of surgery: protocol for a cluster randomised controlled trial
Authors: Scrimshire Ashley B , Booth Alison , Fairhurst Caroline , Reed Mike , Tadd Win , Laverty Annie , Corbacho Belen , Torgerson David , McDaid Catriona
Published: February 2020

Background

Measures shown to improve outcomes for patients often fail to be adopted into routine practice in the NHS. The Institute for Health Improvement Breakthrough Series Collaborative (BSC) model is designed to support implementation at scale. This trial aims to assess the effectiveness and cost-effectiveness of quality improvement collaboratives (QICs) based on the BSC method for introducing service improvements at scale in the NHS.

Methods

Forty Trusts will be randomised (1:1) to introduce one of two protocols already shown to improve outcomes in patients undergoing elective total hip and knee replacement surgery.

The intervention is improvement collaboratives based on the BSC model, a learning system that brings together a large number of teams to seek improvement focussed on a proven intervention. Collaboratives aim to deliver at scale, maximise local engagement and leadership and are designed to build capacity, enable learning and prepare for sustainability. Collaboratives involve Learning Sessions, Action Periods, and a summative congress.

Trusts will be supported to introduce either: decolonisation for Methicillin Sensitive Staphylococcus aureus (MSSA) to reduce post-operative infection (QIST: Infection), or an anaemia optimisation programme to reduce peri-operative blood transfusions (QIST: Anaemia). Trusts will continue with their usual practice for whichever protocol they are not introducing. Anonymised data related to both infection and anaemia outcomes for patients undergoing hip or knee arthroplasty at all sites will mean that the two groups act as controls for each other.

The primary outcome for the QIST: Infection collaborative is deep MSSA surgical site infection within 90 days of surgery, and for the QIST: Anaemia collaborative is blood transfusion within 7 days of surgery. Patient-level secondary outcomes include length of hospital stay and readmission, which will also inform the economic costings. Qualitative interviews will evaluate the support provided to teams.

Discussion

The scale of this trial brings considerable challenges and potential barriers to delivery. Anticipated challenges relate to recruiting and sustaining up to 40 organisations, each with its own culture and context. This complex project with multiple stakeholders across a large geographical area will be managed by experienced senior-level project leaders with a proven track record in advanced project management. The team should ensure effective project governance and communications.

Trial registration

ISRCTN, ISRCTN11085475. Prospectively registered on 15 February 2018.
Large-scale kinetic metabolic models of Pseudomonas putida KT2440 for consistent design of metabolic engineering strategies
Authors: Tokic Milenko , Hatzimanikatis Vassily , Miskovic Ljubisa
Published: February 2020

Background

Pseudomonas putidais a promising candidate for the industrial production of biofuels and biochemicals because of its high tolerance to toxic compounds and its ability to grow on a wide variety of substrates. Engineering this organism for improved performances and predicting metabolic responses upon genetic perturbations requires reliable descriptions of its metabolism in the form of stoichiometric and kinetic models.

Results

In this work, we developed kinetic models ofP. putidato predict the metabolic phenotypes and design metabolic engineering interventions for the production of biochemicals. The developed kinetic models contain 775 reactions and 245 metabolites. Furthermore, we introduce here a novel set of constraints within thermodynamics-based flux analysis that allow for considering concentrations of metabolites that exist in several compartments as separate entities. We started by a gap-filling and thermodynamic curation of iJN1411, the genome-scale model ofP. putidaKT2440. We then systematically reduced the curated iJN1411 model, and we created three core stoichiometric models of different complexity that describe the central carbon metabolism ofP. putida. Using the medium complexity core model as a scaffold, we generated populations of large-scale kinetic models for two studies. In the first study, the developed kinetic models successfully captured the experimentally observed metabolic responses to several single-gene knockouts of a wild-type strain ofP. putidaKT2440 growing on glucose. In the second study, we used the developed models to propose metabolic engineering interventions for improved robustness of this organism to the stress condition of increased ATP demand.

Conclusions

The study demonstrates the potential and predictive capabilities of the kinetic models that allow for rational design and optimization of recombinantP. putidastrains for improved production of biofuels and biochemicals. The curated genome-scale model ofP. putidatogether with the developed large-scale stoichiometric and kinetic models represents a significant resource for researchers in industry and academia.
Whole-cell biocatalysis for hydrogen storage and syngas conversion to formate using a thermophilic acetogen
Authors: Schwarz Fabian M. , Müller Volker
Published: February 2020

Background

In times of global climate change, the conversion and capturing of inorganic CO2 have gained increased attention because of its great potential as sustainable feedstock in the production of biofuels and biochemicals. CO2 is not only the substrate for the production of value-added chemicals in CO2-based bioprocesses, it can also be directly hydrated to formic acid, a so-called liquid organic hydrogen carrier (LOHC), by chemical and biological catalysts. Recently, a new group of enzymes were discovered in the two acetogenic bacteria Acetobacterium woodii and Thermoanaerobacter kivui which catalyze the direct hydrogenation of CO2 to formic acid with exceptional high rates, the hydrogen-dependent CO2 reductases (HDCRs). Since these enzymes are promising biocatalysts for the capturing of CO2 and the storage of molecular hydrogen in form of formic acid, we designed a whole-cell approach for T. kivui to take advantage of using whole cells from a thermophilic organism as H2/CO2 storage platform. Additionally, T. kivui cells were used as microbial cell factories for the production of formic acid from syngas.

Results

This study demonstrates the efficient whole-cell biocatalysis for the conversion of H2 + CO2 to formic acid in the presence of bicarbonate by T. kivui. Interestingly, the addition of KHCO3 not only stimulated formate formation dramatically but it also completely abolished unwanted side product formation (acetate) under these conditions and bicarbonate was shown to inhibit the membrane-bound ATP synthase. Cell suspensions reached specific formate production rates of 234 mmol gprotein−1 h−1 (152 mmol gCDW−1 h−1), the highest rates ever reported in closed-batch conditions. The volumetric formate production rate was 270 mmol L−1 h−1 at 4 mg mL−1. Additionally, this study is the first demonstration that syngas can be converted exclusively to formate using an acetogenic bacterium and high titers up to 130 mM of formate were reached.

Conclusions

The thermophilic acetogenic bacterium T. kivui is an efficient biocatalyst which makes this organism a promising candidate for future biotechnological applications in hydrogen storage, CO2 capturing and syngas conversion to formate.
A reference profile-free deconvolution method to infer cancer cell-intrinsic subtypes and tumor-type-specific stromal profiles
Authors: Wang Li , Sebra Robert P. , Sfakianos John P. , Allette Kimaada , Wang Wenhui , Yoo Seungyeul , Bhardwaj Nina , Schadt Eric E. , Yao Xin , Galsky Matthew D. , Zhu Jun
Published: February 2020

Background

Patient stratification based on molecular subtypes is an important strategy for cancer precision medicine. Deriving clinically informative cancer molecular subtypes from transcriptomic data generated on whole tumor tissue samples is a non-trivial task, especially given the various non-cancer cellular elements intertwined with cancer cells in the tumor microenvironment.

Methods

We developed a computational deconvolution method, DeClust, that stratifies patients into subtypes based on cancer cell-intrinsic signals identified by distinguishing cancer-type-specific signals from non-cancer signals in bulk tumor transcriptomic data. DeClust differs from most existing methods by directly incorporating molecular subtyping of solid tumors into the deconvolution process and outputting molecular subtype-specific tumor reference profiles for the cohort rather than individual tumor profiles. In addition, DeClust does not require reference expression profiles or signature matrices as inputs and estimates cancer-type-specific microenvironment signals from bulk tumor transcriptomic data.

Results

DeClust was evaluated on both simulated data and 13 solid tumor datasets from The Cancer Genome Atlas (TCGA). DeClust performed among the best, relative to existing methods, for estimation of cellular composition. Compared to molecular subtypes reported by TCGA or other similar approaches, the subtypes generated by DeClust had higher correlations with cancer-intrinsic genomic alterations (e.g., somatic mutations and copy number variations) and lower correlations with tumor purity. While DeClust-identified subtypes were not more significantly associated with survival in general, DeClust identified a poor prognosis subtype of clear cell renal cancer, papillary renal cancer, and lung adenocarcinoma, all of which were characterized by CDKN2A deletions. As a reference profile-free deconvolution method, the tumor-type-specific stromal profiles and cancer cell-intrinsic subtypes generated by DeClust were supported by single-cell RNA sequencing data.

Conclusions

DeClust is a useful tool for cancer cell-intrinsic molecular subtyping of solid tumors. DeClust subtypes, together with the tumor-type-specific stromal profiles generated by this pan-cancer study, may lead to mechanistic and clinical insights across multiple tumor types.
Billing I-AIM: a novel framework for ultrasound billing
Authors: Hughes Daralee , Corrado Michelle M. , Mynatt Irene , Prats Michael , Royall Nelson A. , Boulger Creagh , Bahner David P.
Published: February 2020

Background

Point-of-care ultrasound (POCUS) has an ever-growing footprint in medicine. With this growth POCUS billing and reimbursement has become an area gaining quite a bit of attention as a means of funding and sustaining quality and education programs. Standardization across providers is needed to improve the financial viability of POCUS.

Results

We created an institutional collaborative which developed a framework to identify critical POCUS billing and reimbursement checkpoints. The framework, Billing I-AIM, provides a feasible structure to enhance provider-based reimbursement and perform quality improvement efforts across variable POCUS environments.

Conclusions

POCUS billing using the Billing I-AIM technique allows administrative oversight, quality assurance, and educational functions as well. A discussion of the framework and respective application is provided.
Transcriptome differences in adipose stromal cells derived from pre- and postmenopausal women
Authors: Xie Yun , Fang Bin , Liu Wenhui , Li Guangshuai , Huang Ru-Lin , Zhang Lu , He Jiahao , Zhou Shuangbai , Liu Kai , Li Qingfeng
Published: February 2020

Background

As the population ages, an increasing number of postmenopausal women are donors of adipose stromal cells (ASCs) and may benefit from autologous ASC-related treatments. However, the effect of menopausal status on ASCs has not been investigated.

Methods

RNA sequencing data were downloaded, and differentially expressed genes (DEGs) were identified. Hierarchical clustering, Gene Ontology, and pathway analyses were applied to the DEGs. Two gene coexpression network analysis approaches were applied to the DEGs to provide a holistic view and preserve gene interactions. Hub genes of the gene coexpression network were identified, and their expression profiles were examined with clinical samples. ASCs from pre- and postmenopausal women were co-cultured with monocytes and T cells to determine their immunoregulatory role.

Results

In total, 2299 DEGs were identified and presented distinct expression profiles between pre- and postmenopausal women. Gene Ontology and pathway analyses revealed some fertility-, sex hormone-, immune-, aging-, and angiogenesis-related terms and pathways. Gene coexpression networks were constructed, and the top hub genes, including TIE1, ANGPT2, RNASE1, PLVAP, CA2, and MPZL2, were consistent between the two approaches. Expression profiles of hub genes from the RNA sequencing data and clinical samples were consistent. ASCs from postmenopausal women elicit M1 polarization, while their counterparts facilitate CD3/4+ T cell proliferation.

Conclusions

The present study reveals the transcriptome differences in ASCs derived from pre- and postmenopausal women and provides holistic views by preserving gene interactions via gene coexpression network analysis. The top hub genes identified by this study could serve as potential targets to enhance the therapeutic potential of ASCs.
Impulsive quantum $(p,q)$-difference equations
Authors: Nuntigrangjana Thana , Putjuso Sasitorn , Ntouyas Sotiris K. , Tariboon Jessada
Published: February 2020

In this paper we study quantum $(p,q)$(p,q)-difference equations with impulse and initial or boundary conditions. We consider first order impulsive $(p,q)$(p,q)-difference boundary value problems and second order impulsive $(p,q)$(p,q)-difference initial value problems. Existence and uniqueness results are proved via Banach’s fixed point theorem.
Government expenditure on human capital and growth in Namibia: a time series analysis
Authors: Shafuda Christopher P. P. , De Utpal Kumar
Published: February 2020

An attempt is made in this paper to examine the impacts of government spending on human capital on human development indicators like healthcare outcomes, education achievements and increase in national income in Namibia using time series data from 1980 to 2015. The analysis reveals a significant long-run inverse relationship of government spending on healthcare with fertility rate, infant mortality rate and under-5 mortality rate. However, no co-integration is observed between government spending on healthcare and life-expectancy or adult mortality rate. Also, the findings reveal a significant long-run positive relationship of government spending on education with literacy rate, net primary and gross tertiary enrolment rate. Whereas, no co-integration between government spending on education and gross enrolment rate at primary and secondary level is observed. The vector auto-regression analysis revealed significant impacts of expenditure on healthcare and education on the GDP growth in the long run through improved human resources. The results are thus in favour of continuation of expansionary government expenditure policy to achieve faster economic growth in Namibia. However, drastic changes should be adopted to improve basic education and primary healthcare in the country.
The coMforT study of a trauma-informed mindfulness intervention for women who have experienced domestic violence and abuse: a protocol for an intervention refinement and individually randomized parallel feasibility trial
Authors: Pitt Katherine , Feder Gene S , Gregory Alison , Hawcroft Claire , Kessler David , Malpass Alice , Millband Sarah , Morris Richard , Zammit Stan , Lewis Natalia V
Published: February 2020

Background

Domestic violence and abuse (DVA) is common and destructive to health. Post-traumatic stress disorder (PTSD) is a major mental health consequence of DVA. People who have experienced DVA have specific needs, arising from the repeated and complex nature of the trauma. The National Institute for Health and Care Excellence recommends more research on the effectiveness of psychological interventions for people who have experienced DVA. There is growing evidence that mindfulness-based interventions may help trauma symptoms.

Methods

Intervention refinement and randomized controlled feasibility trial. A prototype trauma-informed mindfulness-based cognitive therapy (TI-MBCT) intervention will be co-produced following qualitative interviews and consensus exercise with stakeholders. Participants in the feasibility trial will be recruited from DVA agencies in two geographical regions and randomized to receive either TI-MBCT or usual care (self-referral to the Improving Access to Psychological Therapies (IAPT) service). TI-MBCT will be delivered as a group-based eight-week program. It will not be possible to blind the participants or the assessors to the study allocation. The following factors will inform the feasibility of progressing to a fully powered trial: recruitment, retention, intervention fidelity, and the acceptability of the intervention and trial design to participants. We will also test the feasibility of measuring the following participant outcomes before and 6 months post-randomization: PTSD, dissociative symptoms, depression, anxiety, DVA re-victimization, self-compassion, and mother-reported child health. Process evaluation and economic analysis will be embedded within the feasibility trial.

Discussion

This study will lead to the development of a TI-MBCT intervention for DVA survivors with PTSD and inform the feasibility and design of a fully powered randomized controlled trial (RCT). The full trial will aim to determine the effectiveness and cost-effectiveness of a TI-MBCT intervention in improving the clinically important symptoms of PTSD in DVA survivors.

Trial registration

ISRCTN, ISRCTN64458065, Registered 11 January 2019.
The impact of anti-tobacco legislation on birth weight in Peru
Authors: Mallma Patricia , Carcamo Cesar , Kaufman Jay S.
Published: February 2020

Background

Tobacco exposure remains a significant issue for public health, especially for pregnant women. It increases the risk for premature labor, low birth weight and small for gestational age (SGA), among other effects. To reduce these risks, many countries have enacted public policies to curb tobacco exposure. Peru enacted anti-tobacco laws that forbid smoking in public places, require prevention text and images in products and publicity, along with restriction of sales to adults. We evaluated the effect of the implementation of this law on newborn outcomes: birth weight, prematurity and SGA.

Methods

This was a quasi-experimental study that utilized data from the Peruvian Live Birth Registry. Children born to mothers from urban areas were the intervention group, while children born to mothers from rural areas were considered the control group. Only singletons with information on birth weight and gestational age, born to mothers aged 12 to 49 years were included in the study. In addition, newborns with birth weights greater than + 4 standard deviations (SD) or less than − 4 SD from the gestational age-specific mean were excluded. To measure the effect of legislation on birth weight we performed a difference in differences analysis.

Results

A total of 2,029,975 births were included in the analysis. After adjusting for characteristics of the mother and the child, and contextual variables, the anti-tobacco law in Peru reduced the incidence of prematurity by 30 cases per 10,000 live births (95% CI: 19 to 42).

Conclusions

The reform had negligible effects on overall birth weights and on the incidence of SGA. This modest result suggests the need for a more aggressive fight against tobacco, prohibiting all types of advertising and promotion of tobacco products, among others measures.
MR diffusion versus MR perfusion in patients with ovarian tumors; how far could we get?
Authors: El Ameen Nadia F. , Eissawy Mohamed G. , Mohsen Laila Adel M. S. , Nada Omnia Mokhtar , Beshreda Gerges M.
Published: February 2020

Background

Ovarian tumors are one of the prevalent gynecological tumors. They are the fifth commonest tumor in women. The therapeutic strategy depends on whether the tumor is benign, borderline or malignant. They always cause nonspecific symptoms at early stages and diagnosed at advanced stages. We tried to test and compare the sensitivity and accuracy of diffusion-weighted imaging (DWI) and MR perfusion in the diagnosis of ovarian tumors among fifty patients with ovarian masses who collected after meeting the inclusion criteria depending on grayscale sonographic findings after the approval of the ethical committee of our institution. The sensitivity and accuracy of the techniques were compared.

Results

The surgical and pathological reports of our patients proved a non-tumorous lesion in three patients. They also proved benign ovarian tumors in 18/47 (38.3%) patients, borderline tumors in 4/47 (8.5%) patients and malignant ovarian tumors in 25/47 (53.2%) patients. According to conventional MRI, ovarian tumors could be diagnosed with sensitivity 92%, specificity 61.11%, PPV 76.7%, NPV 84.6% and accuracy 79.1%. DWI and MR perfusion showed the same results where they showed sensitivity 98%, specificity 83%, PPV 90%, NPV 98% and accuracy 93% with ADC cut-off value 1 × 10−3 mm2/s.

Conclusion

Diffusion-weighted imaging and MR perfusion are useful in the diagnosis of ovarian tumors with approximately the same sensitivity and positive impact on operative management.
Characterization of Instructor and Student Behaviors in CURE and Non-CURE Learning Environments: Impacts on Student Motivation, Science Identity Development, and Perceptions of the Laboratory Experience
Authors: Esparza David , Wagler Amy E. , Olimpo Jeffrey T.
Published: February 2020

Course-based undergraduate research experiences (CUREs) serve to increase student access to authentic scientific opportunities. Current evidence within the literature indicates that engagement in CUREs promotes students’ science identity development, science self-efficacy, motivation, and ability to “think like a scientist.” Despite the importance of these findings, few studies have examined the behaviors and interactions occurring within CURE and non-CURE settings and the impact of those behaviors on said student outcomes. To address these concerns, we conducted a mixed-methods study to explore student and instructor behaviors in four CURE and four non-CURE introductory biology laboratory sections. Representative video data were collected in each section and coded using the Laboratory Observation Protocol for Undergraduate STEM. In addition, pre/postsemester affective survey data were obtained from CURE and non-CURE participants. Results indicated that CURE students and instructors engaged in more interactive behaviors (e.g., one-on-one dialogue, questioning) than their non-CURE counterparts, a finding confirmed by analyzing behavioral patterns via construction of partial correlation networks. Multiple regression analyses further revealed that both student and instructor interactive behaviors and enrollment in a CURE were strong predictors of pre/postsemester shifts in student motivation, science identity development, collaboration, and perceived opportunities to make relevant scientific discoveries.
Outcomes in Black and White Patients With Metastatic Renal Cell Carcinoma Treated With First-Line Tyrosine Kinase Inhibitors: Insights From Two Large Cohorts
Authors: Bossé Dominick , Xie Wanling , Lin Xun , Simantov Ronit , Lalani Aly-Khan A. , Graham Jeffrey , Wells J. Connor , Donskov Frede , Rini Brian , Beuselinck Benoit , Alva Ajjai , Hansen Aaron , Wood Lori , Soulières Denis , Kollmannsberger Christian , Patenaude Francois , Heng Daniel Y.C. , Choueiri Toni K. , McKay Rana R.
Published: February 2020

PURPOSE

To investigate whether black race is an independent predictor of overall survival (OS) in metastatic renal cell carcinoma (mRCC).

METHODS

We performed a retrospective 2-cohort (International Metastatic Renal Cell Carcinoma Database Consortium [IMDC] and trial-database) study of patients with mRCC treated with first-line tyrosine kinase inhibitors (TKIs). Unmatched (UM) and matched (M) analyses accounting for imbalances in region, year of treatment, age, and sex between races were performed. Cox models adjusting for histology, number of metastatic sites, nephrectomy, and IMDC risk compared time to treatment failure (TTF; IMDC cohort), progression-free survival (PFS; trial-database cohort), and OS.

RESULTS

The IMDC cohort included 73 black versus 3,381 (UM) and 1,236 (M) white patients. The trial-database cohort included 21 black versus 1,040 (UM) and 431 (M) white patients. Median OS for black versus white patients was 18.5 versus 25.8 months in the IMDC group and 21.0 versus 25.6 months in the trial-database group. Differences in OS were not significant in multivariable analysis in the IMDC group (hazard ratio [HR]M, 1.0; 95% CI, 0.7 to 1.5; HRUM, 1.1; 95% CI, 0.8 to 1.4) and trial-database (HRM, 1.5; 95% CI, 0.8 to 2.7; HRUM, 1.4; 95% CI, 0.8 to 2.6) cohorts. TTF for black patients was shorter in the UM IMDC cohort (HRUM, 1.4; 95% CI, 1.1 to 1.8; P = .003), but not in the M analysis. PFS was shorter for black patients in both analyses in the trial-database cohort (HRM, 2.3; 95% CI, 1.4 to 3.9; P = .002; HRUM, 2.3; 95% CI, 1.4 to 3.9; P = .002).

CONCLUSION

Black patients had more IMDC risk factors and worse outcomes with TKIs versus white patients. Race was not an independent predictor of OS. Strategies to understand biologic determinants of outcomes for minority patients are needed to optimize care.
Maternal Glucocorticoid Metabolism Across Pregnancy: A Potential Mechanism Underlying Fetal Glucocorticoid Exposure
Authors: Stoye David Q , Andrew Ruth , Grobman William A , Adam Emma K , Wadhwa Pathik D , Buss Claudia , Entringer Sonja , Miller Gregory E , Boardman James P , Seckl Jonathan R , Keenan-Devlin Lauren S , Borders Ann E B , Reynolds Rebecca M
Published: February 2020

Context

Across pregnancy, maternal serum cortisol levels increase up to 3-fold. It is not known whether maternal peripheral cortisol metabolism and clearance change across pregnancy or influence fetal cortisol exposure and development.

Objectives

The primary study objective was to compare maternal urinary glucocorticoid metabolites, as markers of cortisol metabolism and clearance, between the second and third trimester of pregnancy. Secondary objectives were to test associations of total maternal urinary glucocorticoid excretion, with maternal serum cortisol levels and offspring birth weight z score.

Design, Participants, and Setting

A total of 151 women with singleton pregnancies, recruited from prenatal clinic at the Pittsburgh site of the Measurement of Maternal Stress (MOMS) study, had 24-hour urine collections during both the second and third trimesters.

Results

Between the second and third trimester, total urinary glucocorticoid excretion increased (ratio of geometric means [RGM] 1.37, 95% CI 1.22-1.52, P < .001), and there was an increase in calculated 5β-reductase compared to 5α-reductase activity (RGM 3.41, 95% CI 3.04-3.83, P < .001). During the third trimester total urinary glucocorticoid excretion and serum cortisol were negatively correlated (r = –0.179, P = .029). Mean total urinary glucocorticoid excretion across both trimesters and offspring birth weight z score were positively associated (β = 0.314, P = .001).

Conclusions

The estimated activity of maternal enzymes responsible for cortisol metabolism change between the second and third trimester of pregnancy. Additionally, maternal peripheral metabolism and clearance of cortisol may serve as a novel mechanism affecting fetal cortisol exposure and growth.