bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined use of gap-PCR and next-generation sequencing improves thalassaemia carrier screening among premarital adults in China
Authors: Zhao Jianghong , Li Jia , Lai Qiaohong , Yu Yanping
Published: January 2020

Aims

Thalassaemia is one of the most common genetics disorders in the world, especially in southern China. The aim of the present study was to investigate the feasibility of combining the gap-PCR and next-generation sequencing (NGS) for thalassaemia carrier screening in the Chinese population.

Methods

Blood samples were obtained from 944 prepregnancy couples; thalassaemia carrier screening was performed by using a routine haematological method and a combination of gap-PCR and NGS method.

Results

We found that the α thalassaemia carrier rate was 11% (207/1888); the β thalassaemia carrier rate was 3.7% (70/1888); the composite α thalassaemia and β thalassaemia carrier rate was 0.4% (8/1888). We also identified seven novel mutations, includingHBA1: c.412A>G, −50 (G>A),HBB: c.*+129T>A,HBB: c.-64G>C,HBB: c.-180G>C,HBB: c.*+5G>A andHBB: c.-113A>G. By comparing the combined gap-PCR and NGS method, the MCV+MCH and HbA2 detection strategy showed a lower sensitivity of 61.05% (105/172) and a higher missed diagnosis ratio of 38.95% (67/172) for α thalassaemia mutations. The sensitivity was improved with the MCV+MCH and HbA2 detection screen when compared with MCV+MCH detection for β thalassaemia (98.51% vs 85.90%).

Conclusions

Our study suggests the combined gap-PCR and NGS method is a cost-effective method for the thalassaemia carrier screening, particularly for the α thalassaemia mutation carriers.
Late cardiac adverse events in patients with cancer treated with immune checkpoint inhibitors
Authors: Dolladille Charles , Ederhy Stephane , Allouche Stéphane , Dupas Querntin , Gervais Radj , Madelaine Jeannick , Sassier Marion , Plane Anne-Flore , Comoz Francois , Cohen Ariel Aron , Thuny Franck Roland , Cautela Jennifer , Alexandre Joachim
Published: January 2020

Background

Immune checkpoint inhibitor (ICI)-associated early cardiac adverse events (CAEs), mostly acute and fulminant myocarditis, have been well characterized and mainly occur during the first 90 days after ICI therapy initiation. ICI-associated late CAEs (occurring after the first 90 days of treatment) have not yet been described.

Methods

First, we compared characteristics of a cohort involving early (defined as a CAE time to onset (TTO) of <90 days after ICI therapy initiation) and late (defined as a CAE TTO of ≥90 days after ICI therapy initiation) ICI-associated CAE consecutive cases who were referred to three French cardio-oncology units. Second, ICI-associated CAE cases were searched in VigiBase, the WHO global individual case safety report database, and early and late ICI-associated CAEs were compared.

Results

In the cohort study, compared with early CAE cases (n=19, median TTO of 14 days), late ICI-associated CAE cases (n=19, median TTO of 304 days) exhibited significantly more left ventricular systolic dysfunction (LVSD) and heart failure (HF) and less frequent supraventricular arrhythmias. In VigiBase, compared with early cases (n=437, 73.3%, median TTO 21 days), the late ICI-associated CAE reports (n=159, 26.7%, median TTO 178 days) had significantly more frequent HF (21.1% vs 31.4%, respectively, p=0.01). Early and late ICI-associated CAE cases had similarly high mortality rates (40.0% vs 44.4% in the cohort and 30.0% vs 27.0% in VigiBase, respectively).

Conclusions

Late CAEs could occur with ICI therapy and were mainly revealed to be HF with LVSD.

Trial registration numbers

NCT03678337,NCT03882580, andNCT03492528.
Centralized pain and pain catastrophizing mediate the association between lifetime abuse history and self-reported pain medication side effects
Authors: Pierce Jennifer , Hassett Afton L , Schneiderhan Jill R , Divers Jude , Brummett Chad M , Goesling Jenna
Published: January 2020

Background

Self-reported side effects of pain medication are important determinants of treatment course that can affect patient adherence, medication discontinuation and physician decisions. Yet, few studies have investigated patient-level predictors of self-reported pain medication side effects. The present study sought to fill this gap by exploring the impact of physical or sexual abuse history on self-reported pain medication side effects and considered a mediation model in which those effects are transmitted through a centralized pain phenotype and pain catastrophizing.

Methods

We conducted a cross-sectional analysis of 3118 patients presenting to a tertiary-care, outpatient pain clinic.

Results

Approximately 15% of the sample (n=479) reported a lifetime history of abuse. Patients with a lifetime history of abuse, particularly abuse that occurred in both childhood and adulthood, reported more pain medication side effects compared with patients reporting no abuse history. Furthermore, path analysis showed that a centralized pain phenotype and pain catastrophizing mediated the association between lifetime abuse history and the sum of pain medication side effects.

Conclusions

This suggests that individuals who experience abuse may develop a heightened physiological sensitivity to stimuli, as well as a tendency to interpret stimuli negatively, exaggerate the impact of aversive stimuli and undermine their ability to cope with the stressor. This study highlights the need for physicians to understand patient-level predictors of medication tolerance and to consider a history of abuse and trauma in decisions regarding treatment and medication management.
Cultural connectedness as a determinant of physical activity among Indigenous adults in Saskatchewan
Authors: Ironside Avery , Ferguson Leah J. , Katapally Tarun R. , Foulds Heather J.A.
Published: January 2020

Cultural connectedness has been associated with increased self-esteem and mental health among Indigenous Peoples. Physical activity is an important contributor to health, although the importance of culture as a determinant of physical activity for Indigenous Peoples in Canada is unclear. The purpose of this study is to evaluate differences in cultural connectedness between Indigenous adults in Canada achieving high and low physical activity levels. Questionnaires evaluated cultural connectedness and physical activity. Indigenous adults were classified into high and low physical activity groups at the specific group mean and as meeting or not meeting musculoskeletal activity guidelines of twice per week. First Nations and specifically Cree/Nehiyaw First Nations adults who were more physically active reported greater identity, spirituality, traditions, exploration, commitment, affirmation/belonging, and overall cultural connectedness. Cultural connectedness elements of commitment, exploration, identity, affirmation/belonging, traditions, spirituality, and overall cultural connectedness were not different between high and low physical activity Métis adults. Musculoskeletal activity was not associated with any elements of cultural connectedness among any Indigenous identity. Cultural connectedness is a protective factor for physical activity among First Nations and Cree/Nehiyaw First Nations adults, but not among Métis adults in Canada.

Novelty Musculoskeletal activity was not associated with cultural connectedness. Cultural connectedness is a protective factor of physical activity for First Nations adults. Moving away from one’s home community was associated with lower cultural connectedness for Indigenous Peoples.
The Pseudoomphalina kalchbrenneri complex in North America
Authors: Voitk Andrus , Saar Irja , Lebeuf Renée , Kennedy Peter
Published: January 2020

Pseudoomphalina kalchbrenneri is a Eurasian species. In North America the Pso. kalchbrenneri complex is represented by Pseudoomphalina anticostica sp. nov. and Pso. compressipes in the east and Pso. intermedia in the west. Pseudoomphalina farinacea and Pso. felleoides are later synonyms for Pso. compressipes. The somewhat similar Pseudolaccaria pachyphylla occupies a temperate band through Eurasia, confirmed by sequencing in both eastern and western North America. It differs from species of the Pso. kalchbrenneri complex by smaller size, finely granular pileus, non-decurrent gills, and lack of hymenial cystidia. All species of the Pso. kalchbrenneri complex are uncommon, and macroscopically similar. Pseudoomphalina kalchbrenneri and Pso. intermedia can be identified by their distribution (Europe and western North America, respectively) and lack of cystidia. The cystidiate eastern North American Pso. anticostica and Pso. compressipes can be differentiated by the smaller spores of the latter. Pseudoomphalina cokeri is the most ancestral species on the Pseudoomphalina lineage, while Clitocybe thujana and Agaricus apertus (Clitocybe/Clitocybula aperta) fall outside Pseudoomphalina and Pseudolaccaria. We add 21 new sequences to GenBank, including six types (Agaricus compressipes, Clitocybe felleoides, C. farinacea, C. intermedia, C. thujana, Agaricus apertus), and one new species (Pso. anticostica).
A nanostructured bifunctional acid–base catalyst resin formed by lyotropic liquid crystal monomers
Authors: Dwulet Gregory E. , Coscia Benjamin J. , Shirts Michael R. , Gin Douglas L.
Published: January 2020

An ordered, nanoporous polymer resin was prepared from the self-assembly of lyotropic liquid crystal monomers and employed as a heterogeneous, bifunctional catalyst. This material contains antagonistic acid and base sites in the periodic nanopores and efficiently catalyzes a model tandem reaction (i.e., the deacetalization–nitroaldol reaction between benzaldehyde dimethyl acetal and nitromethane to yield β-nitrostyrene) with excellent product selectivity. This lyotropic liquid crystal-based solid catalyst represents one of the few examples of polymeric tandem catalysts synthesized by a “bottom-up” strategy that imparts control over the stoichiometry of acidic and basic monomers and is the only reported example of a lyotropic liquid crystal-based polymer that contains mutually incompatible catalytic groups. Furthermore, this heterogeneous catalyst is highly active, exhibiting a turnover frequency for this tandem test reaction that exceeds other reported catalytic polymeric materials.
Resolving singularities in relativistic spacetimes
Authors: Konkowski Deborah A. , Weninger Drew M. , Helliwell Thomas M.
Published: January 2020

The definitions of classical and quantum singularities are reviewed. While it is known that some classical timelike and null singularities in static and conformally static spacetimes are resolved by a quantum probe, here it is shown that the ring singularity in the stationary overspinning Kerr spacetime remains singular.
Casimir and non-Newtonian force experiment (CANNEX): Review, status, and outlook
Authors: Sedmik René I. P.
Published: January 2020

Many theoretical approaches aiming to explain dark matter or dark energy predict variations of Newton’s law of gravity at sub-millimeter separations. In this low-energy domain, force metrology provides an alternative to astronomical observations and high-energy experiments in the search for new physics. The Casimir And Non-Newtonian force EXperiment (CANNEX) has been designed from the ground up to allow for metrological force measurements between truly parallel macroscopic flat plates in the separation range 3–30 micrometer. Benefiting from this geometry, the experiment could potentially reach sensitivities of [Formula: see text]nN/m2 for pressures and [Formula: see text]mN/m3 for pressure gradients. Achieving such precision would enable us to test a variety of non-Newtonian interactions and to unambiguously detect thermal Casimir forces at large separation. In this paper, we review the experimental setup together with proposed improvements, and give an outlook on potential measurements that will be performed once the setup has been rebuilt at its new location in Vienna.
Stability of charged Kiselev thin-shell wormholes
Authors: Sharif Muhammad , Javed Faisal
Published: January 2020

This work is devoted to exploring the stability of thin-shell wormholes developed from two equivalent copies of charged quintessence (charged Kiselev) black holes by using Visser cut and paste approach. The characteristics of the surface matter of the shell are determined by using Israel formalism. We examine the stability of thin-shell by assuming a barotropic equation of state for the surface matter of the wormhole throat. We conclude that wormhole becomes stable in the presence of both charge and Kiselev parameter otherwise, it shows an unstable behavior.
Congruence classes and extensions of rings with an application to braces
Authors: Brzeziński Tomasz , Rybołowicz Bernard
Published: January 2020

Two observations in support of the thesis that trusses are inherent in ring theory are made. First, it is shown that every equivalence class of a congruence relation on a ring or, equivalently, any element of the quotient of a ring [Formula: see text] by an ideal [Formula: see text] is a paragon in the truss [Formula: see text] associated to [Formula: see text]. Second, an extension of a truss by a one-sided module is described. Even if the extended truss is associated to a ring, the resulting object is a truss, never a ring, unless the module is trivial. On the other hand, if the extended truss is associated to a brace, the resulting truss is also associated to a brace, irrespective of the module used.
MAIT Cells in Health and Disease
Authors: Provine Nicholas M. , Klenerman Paul
Published: January 2020

Mucosal-associated invariant T (MAIT) cells have been attracting increasing attention over the last few years as a potent unconventional T cell subset. Three factors largely account for this emerging interest. Firstly, these cells are abundant in humans, both in circulation and especially in some tissues such as the liver. Secondly is the discovery of a ligand that has uncovered their microbial targets, and also allowed for the development of tools to accurately track the cells in both humans and mice. Finally, it appears that the cells not only have a diverse range of functions but also are sensitive to a range of inflammatory triggers that can enhance or even bypass T cell receptor–mediated signals—substantially broadening their likely impact in health and disease. In this review we discuss how MAIT cells display antimicrobial, homeostatic, and amplifier roles in vivo, and how this may lead to protection and potentially pathology.
Siglecs as Immune Cell Checkpoints in Disease
Authors: Duan Shiteng , Paulson James C.
Published: January 2020

Sialic acid–binding immunoglobulin-type lectins (Siglecs) are expressed on the majority of white blood cells of the immune system and play critical roles in immune cell signaling. Through recognition of sialic acid–containing glycans as ligands, they help the immune system distinguish between self and nonself. Because of their restricted cell type expression and roles as checkpoints in immune cell responses in human diseases such as cancer, asthma, allergy, neurodegeneration, and autoimmune diseases they have gained attention as targets for therapeutic interventions. In this review we describe the Siglec family, its roles in regulation of immune cell signaling, current efforts to define its roles in disease processes, and approaches to target Siglecs for treatment of human disease.
Precision Management of Advanced Non–Small Cell Lung Cancer
Authors: Yang Ching-Yao , Yang James Chih-Hsin , Yang Pan-Chyr
Published: January 2020

The rapid evolution of treatment for advanced lung cancer is a story of how scientists have struggled to move from nonselective cytotoxic chemotherapy to personalized precision medicine. In this century, extraordinary advances have been made in the management of advanced and metastatic non–small cell lung cancer, especially in the development of small molecules targeting specific tyrosine kinase receptors and immune checkpoint inhibitors. These developments have led to a significant improvement in survival for lung cancer patients with metastatic disease. Now, the core guidelines to treat non–small cell lung cancer are based on the identification of targetable driver mutations and immune checkpoints. Continued investigations of newly identified druggable genetic alterations, explorations of biomarkers of immune checkpoint inhibitors, development of next-generation immunotherapy, and optimization of combination therapy are necessary to provide better treatment outcomes for lung cancer patients in the future.
Broadly Neutralizing Antibodies for HIV Prevention
Authors: Karuna Shelly T. , Corey Lawrence
Published: January 2020

In the last decade, over a dozen potent broadly neutralizing antibodies (bnAbs) to several HIV envelope protein epitopes have been identified, and their in vitro neutralization profiles have been defined. Many have demonstrated prevention efficacy in preclinical trials and favorable safety and pharmacokinetic profiles in early human clinical trials. The first human prevention efficacy trials using 10 sequential, every-two-month administrations of a single anti-HIV bnAb are anticipated to conclude in 2020. Combinations of complementary bnAbs and multi-specific bnAbs exhibit improved breadth and potency over most individual antibodies and are entering advanced clinical development. Genetic engineering of the Fc regions has markedly improved bnAb half-life, increased mucosal tissue concentrations of antibodies (especially in the genital tract), and enhanced immunomodulatory and Fc effector functionality, all of which improve antibodies' preventative and therapeutic potential. Human-derived monoclonal antibodies are likely to enter the realm of primary care prevention and therapy for viral infections in the near future.
Sacral nerve stimulation increases gastric accommodation in rats: a spinal afferent and vagal efferent pathway
Authors: Ye Feng , Liu Yi , Li Shiying , Zhang Sujuan , Foreman Robert D. , Chen Jiande DZ
Published: January 2020

Impaired gastric accommodation (GA) has been frequently reported in various gastrointestinal diseases. No standard treatment strategy is available for treating impaired GA. We explored the possible effect of sacral nerve stimulation (SNS) on GA and discovered a spinal afferent and vagal efferent mechanism in rats. Sprague-Dawley rats (450–500 g) with a chronically implanted gastric cannula and ECG electrodes were studied in a series of sessions to study: 1) the effects of SNS with different parameters on gastric tone, compliance, and accommodation using a barostat device; two sets of parameters were tested as follows: parameter 1) 5 Hz, 500 µs, 10 s on 90 s off; 90% motor threshold and parameter 2) same as parameter 1 but 25 Hz; 2) the involvement of spinal afferent pathway via detecting c-fos immunoreactive (IR) cells in the nucleus of the solitary tract (NTS) of the brain; 3) the involvement of vagal efferent activity via the spectral analysis of heart rate variability derived from the ECG; and 4) the nitrergic mechanism, Nω-nitro-l-arginine methyl ester (l-NAME), a nitric oxide synthase (NOS) inhibitor, was given before SNS at 5 Hz. Compared with sham-SNS: 1) SNS at 5 Hz inhibited gastric tone and increased gastric compliance and GA. No difference was noted between the stimulation frequencies of 5 and 25 Hz. 2) SNS increased the expression of c-fos in the NTS. 3) SNS increased cardiac vagal efferent activity and decreased the sympathovagal ratio. 4) l-NAME blocked the relaxation effect of SNS. In conclusion, SNS with certain parameters relaxes gastric fundus and improves gastric accommodation mediated via a spinal afferent and vagal efferent pathway.

NEW & NOTEWORTHY Currently, there is no adequate medical therapy for impaired gastric accommodation, since medications that relax the fundus often impair antral peristalsis and thus further delay gastric emptying that is commonly seen in patients with functional dyspepsia or gastroparesis. The advantage of the potential sacral nerve stimulation therapy is that it improves gastric accommodation by enhancing vagal activity, and the enhanced vagal activity would lead to enhanced antral peristalsis rather than inhibiting it.
Safety and Efficacy Evaluation of Traditional Chinese Medicine (Qingre‐Lishi‐Yishen Formula) Based on Treatment of Regular Glucocorticoid Combined with Cyclophosphamide Pulse in Children Suffered from Moderately Severe Henoch–Schonlein Purpura Nephritis with Nephrotic Proteinuria
Authors: Fan Lirong , Yan Huimin , Zhen Xiaofang , Wu Xiaoming , Hao Jing , Hou Linyi , Han Lei
Published: January 2020

Objective. At present, the most appropriate management of Henoch–Schonlein purpura nephritis (HSPN) with nephrotic‐range proteinuria still remains controversial; thus, the purpose of this study is to evaluate safety and efficacy of traditional Chinese medicine (TCM), Qingre‐Lishi‐Yishen Formula (QLYF), integrated with regular oral glucocorticoid and cyclophosphamide intravenous pulse therapeutic regimen in children suffered from moderately severe HSPN with nephrotic proteinuria. Methods. From 1 January 2012, to 1 January 2016, totally 150 hospitalized children suffered from HSPN with nephrotic proteinuria were included. All were treated with glucocorticoid and cyclophosphamide, and 100 of them were treated with integrative traditional Chinese decoction QLYF. Patients were followed up for 2 years. Rate of adverse event occurrence, short‐term clinical effects, long‐term clinical effects, and TCM therapeutic evaluation were all compared. Results. Total adverse event rate was lower in the QLYF group (χ2 = 5.357, p = 0.022); rates of respiratory infection, urinary infection, poor appetite, hepatotoxity, cardiotoxicity, and neutropenia were all decreased in patients who received QLYF (p < 0.05), and no cases of hepatic and renal toxicities related to the herbal medicine were observed in the QLYF group. For short‐term clinical efficacy evaluation, lower levels of 24 hour proteinuria (p < 0.05) and urine blood cell count (p < 0.05) were found in the QLYF group. For long‐term efficacy evaluation, better clinical control rate effective rate, lower recurrence rate (p < 0.05), and fewer TCM syndrome score (p < 0.05) were found in the QLYF group. Conclusion. Compared with merely using regular oral glucocorticoid plus cyclophosphamide pulse therapeutic regimen, the therapeutic regimen that integrates QLYF with the abovementioned western medicine might be a safe means to decrease the occurrence rate of adverse events and improve short‐term and long‐term clinical effects in children who suffered from moderately severe HSPN with nephrotic proteinuria.
Optimization of Extraction Conditions of Phytochemical Compounds and Anti‐Gout Activity of Euphorbia hirta L. (Ara Tanah) Using Response Surface Methodology and Liquid Chromatography‐Mass Spectrometry (LC‐MS) Analysis
Authors: Abu Bakar Fazleen Izzany , Abu Bakar Mohd Fadzelly , Abdullah Norazlin , Endrini Susi , Fatmawati Sri
Published: January 2020

Gout is a common disease affected most of the people due to the elevation of uric acid in the blood. Flavonoid and phenolic compounds are reported to exert the anti‐gout activity of medicinal plants. Hence, this study aimed at optimizing the extraction conditions of phenolic and flavonoid compounds as well as the anti‐gout (xanthine oxidase inhibitory activity) in vitro of Euphorbia hirta using response surface methodology (RSM). The plant part used was the whole plant excluding roots. The effects of three independent variables (extraction time, X1; extraction temperature, X2; and solid‐to‐liquid ratio, X3) on three response variables (total flavonoid content, Y1; total phenolic content, Y2; and xanthine oxidase inhibitory activity, Y3) were determined using central composite design (CCD) while phytochemical profiling of the extracts was determined by liquid chromatography‐mass spectrometry (LC‐MS). Quadratic models produced a satisfactory fitting of the experimental data with regard to total flavonoid content (r2 = 0.9407, p < 0.0001), total phenolic content (r2 = 0.9383, p < 0.0001), and xanthine oxidase inhibitory activity (r2 = 0.9794, p < 0.0001). The best extraction conditions observed for total flavonoid content, total phenolic content, and xanthine oxidase inhibitory activity were at a temperature of 79.07°C for 17.42 min with solid‐to‐liquid ratio of 1 : 20 g/ml. The optimum values for total flavonoid, total phenolic, and xanthine oxidase inhibitory activity were 67.56 mg RE/g, 155.21 mg GAE/g, and 91.42%, respectively. The main phytochemical compounds in the optimized E. hirta extract are neochlorogenic acid, quercetin‐3β‐D‐glucoside, syringic acid, caffeic acid, ellagic acid, astragalin, afzelin, and quercetin. As conclusion, this study clearly demonstrated the best conditions to obtain higher xanthine oxidase inhibitory activity and phytochemical compounds which can be further used for the development of anti‐gout agents.
Prognostic Factors for Overall Survival of Patients with Prostate Cancer in Kyadondo County, Uganda
Authors: Yahaya James Joseph , Okecha Tonny , Odida Michael , Wabinga Henry
Published: January 2020

Background.Prostate cancer is the second most common cancer among men globally. A few studies that have been done in Uganda on survival of patients with prostate cancer indicate that, the overall survival of patients with prostate cancer in Uganda is poor. The aim of this study was to determine the 3-year overall survival rate of a cohort of patients with prostate cancer residing in Kyadondo County who were diagnosed from 2012 to 2014. The secondary objective was to correlate the overall survival with the clinicopathological prognostic factors.Materials and Methods.This was a retrospective cohort study which involved 136 patients who were diagnosed histologically with prostate cancer at the department of pathology between 2012 and 2014. The cases were registered at the Kampala cancer registry and followed up to 31stDecember 2017. Data analysis was done using STATA version 12.0. The Kaplan-Meir curves were used for analysis of the 3-year overall survival rate. Hazard ratio (HR) and Log-rank test at 95% confidence interval under Cox-regression model were used to evaluate the effect of the covariates on the 3-year overall survival rate.p<0.05was considered statistically significant.Results.More than half of the cases, 55.9% (n=76) had Gleason score >8. Most of the patients, 67.7% (n=92) had advanced disease at diagnosis. The 3-year overall survival rate was 67.6% with median survival of 36.5 months and range of 0–65 months. Clinical stage of the patients (HR = 1.65,p=0.039), Gleason score (HR = 1.88,p=0.008), and lymphovascular invasion (HR = 0.37,p=0.002) were the independent predictors of the 3-year overall survival rate in this study.Conclusion.The 3-year overall survival of prostate cancer patients in Uganda is poor. Most of the patients with are diagnosed with advanced clinical stages (stage III and IV). The Gleason score, clinical stage and lymphovascular invasion can powerfully predict independently the overall survival of patients with prostate cancer. This implies that the Gleason score, clinical stage and lymphovascular invasion may be used to predict the overall survival of patients with prostate cancer even prior prostatectomy.
Kanglaite Injection Combined with Chemotherapy versus Chemotherapy Alone for the Improvement of Clinical Efficacy and Immune Function in Patients with Advanced Non‐Small‐Cell Lung Cancer: A Systematic Review and Meta‐Analysis
Authors: Wen Jianxia , Yang Tao , Wang Jian , Ma Xiao , Tong Yuling , Zhao Yanling
Published: January 2020

Recent advances have shown that immune checkpoint inhibitors are emerging as promising therapeutic targets to improve the quality of life in cancer patients. This meta‐analysis was conducted to evaluate the influence of Kanglaite injection (KLTi) combined with chemotherapy versus chemotherapy alone on clinical efficacy, immune function, and safety for the treatment of advanced non‐small‐cell lung cancer (NSCLC). Several electronic databases, including PubMed, Web of Science, Wan‐Fang, VMIS, EMBASE, Cochrane Library, CNKI, CBM, and MEDLINE, as well as grey literatures, were comprehensively searched from January 2000 to November 2019. Randomized controlled trials (RCTs) reporting outcomes of clinical efficacy and immune function were collected according to their inclusion and exclusion criteria. Cochrane Reviewers’ Handbook 5.2 was applied to assess the risk of bias of included trials. STATA 13.0 and Review Manager 5.3 software were used for meta‐analysis. Twenty‐five RCTs comprising 2151 patients meeting the inclusion criteria were identified. Meta‐analysis showed that compared with chemotherapy alone, KLTi plus the same chemotherapy significantly improved clinical efficacy, including complete response, partial response, stable disease, and progressive disease, as well as immune function, including CD3+, CD4+, CD8+, and CD4+/CD8+. There was a significant reduction in nausea and vomiting, thrombocytopenia, and leukopenia in combination treatments. However, the outcomes were limited because of the low quality and small sample size of the included studies. In conclusion, this work might provide beneficial evidence of KLTi combined with chemotherapy for improving clinical efficacy and immune function, as well as reducing the incidence of adverse events in advanced NSCLC patients. KLTi might be a beneficial therapeutic method for the treatment of advanced NSCLC. Due to the quality of the data, more rigorous and well‐designed RCTs are needed to confirm these findings.
Seroprevalence of Human Betaretrovirus Surface Protein Antibodies in Patients with Breast Cancer and Liver Disease
Authors: Zhang Guangzhi , Bashiri Kiandokht , Kneteman Mark , Cave Kevan , Hong Youngkee , Mackey John R. , Alter Harvey J. , Mason Andrew L.
Published: January 2020

Mouse mammary tumor virus (MMTV) is a betaretrovirus that plays a causal role in the development of breast cancer and lymphoma in mice. Closely related sequences that share 91–99% nucleotide identity with MMTV have been repeatedly found in humans with neoplastic and inflammatory diseases. Evidence for infection with a betaretrovirus has been found in patients with breast cancer and primary biliary cholangitis and referred to as the human mammary tumor virus and the human betaretrovirus (HBRV), respectively. Using the gold standard technique of demonstrating retroviral infection, HBRV proviral integrations have been detected in cholangiocytes, lymph nodes, and liver of patients with primary biliary cholangitis. However, the scientific biomedical community has not embraced the hypothesis that MMTV like betaretroviruses may infect humans because reports of viral detection have been inconsistent and robust diagnostic assays are lacking. Specifically, prior serological assays using MMTV proteins have produced divergent results in human disease. Accordingly, a partial HBRV surface (Su) construct was transfected into HEK293 to create an ELISA. The secreted HBRV gp52 Su protein was then used to screen for serological responses in patients with breast cancer and liver disease. A greater proportion of breast cancer patients (n = 98) were found to have serological reactivity to HBRV Su as compared to age- and sex-matched control subjects (10.2% versus 2.0%, P=0.017, OR = 5.6 [1.25–26.3]). Similarly, the frequency of HBRV Su reactivity was higher in patients with primary biliary cholangitis (n  =  156) as compared to blood donors (11.5% vs. 3.1%, P=0.0024, OR = 4.09 [1.66–10.1]). While the sensitivity of the HBRV Su ELISA was limited, the assay was highly specific for serologic detection in patients with breast cancer or primary biliary cholangitis, respectively (98.0% [93.1%–99.7%] and 97.0% [93.4%–98.6%]). Additional assays will be required to link immune response to betaretrovirus infection and either breast cancer or primary biliary cholangitis.
Antihyperglycemic Effects and Mode of Actions of Musa paradisiaca Leaf and Fruit Peel Hydroethanolic Extracts in Nicotinamide/Streptozotocin‐Induced Diabetic Rats
Authors: Abdel Aziz Sarah M. , Ahmed Osama M. , Abd EL-Twab Sanaa M. , Al-Muzafar Hessah Mohammed , Amin Kamal Adel , Abdel-Gabbar Mohamed
Published: January 2020

The present study aimed to evaluate the antihyperglycemic effects of Musa paradisiaca (M. paradisiaca) leaf and fruit peel hydroethanolic extracts and to suggest their probable mode of actions in nicotinamide (NA)/streptozotocin (STZ)‐induced diabetic rats. The leaf and fruit peel hydroethanolic extracts were analyzed by GC‐MS that indicated the presence of phytol, octadecatrienoic acid, hexadecanoic acid, and octadecadienoic acid as major components in the leaf extract and vitamin E, octadecenamide, β‐sitosterol, and stigmasterol as major phytochemicals in the fruit peel extract. Diabetes mellitus was induced by a single intraperitoneal injection of STZ (60 mg/kg body weight) dissolved in citrate buffer (pH 4.5), 15 minutes after intraperitoneal injection of NA (120 mg/kg body weight). The NA/STZ‐induced diabetic rats were, respectively, treated with M. paradisiaca leaf and fruit peel hydroethanolic extracts at a dose of 100 mg/kg body weight/day by oral administration for 28 days. The treatment of NA/STZ‐induced diabetic rats with leaf and fruit peel extracts significantly improved the impaired oral glucose tolerance and significantly increased the lowered serum insulin and C‐peptide levels. The HOMA‐IR (as the index of insulin resistance) and QUICKI (as a marker for insulin sensitivity), as well as HOMA‐β cell function were significantly alleviated as a result of treatment of diabetic rats with leaf and fruit peel extracts. In association, the elevated serum‐free fatty acids, TNF‐α, and IL‐6 levels were significantly decreased. In addition, the suppressed adipose tissue PPARγ, GLUT4, adiponectin, and insulin receptor β‐subunit mRNA expressions were upregulated while the elevated adipose tissue resistin expression was downregulated in diabetic rats as a result of treatment with the leaf and peel extract. Based on these results, it can be concluded that M. paradisiaca leaf and fruit peel hydroethanolic extracts have antihyperglycemic effects which may be mediated via their insulinotropic and insulin‐sensitizing effects.
Elliptic Flow of Identified Particles in Pb–Pb Collisions at sNN=5.02 TeV
Authors: Wang Er-Qin , Ma Yin-Qun , Gao Li-Na , Fan San-Hong
Published: January 2020

In this paper, by using a Tsallis-Pareto-type function and the multisource thermal model, the elliptic flow coefficients of particles π±, K±, p+p¯, Λ+Λ¯, and KS0 produced in Pb–Pb collisions at the center-of-mass energy of sNN=5.02TeV are investigated. In the process of collisional evolution, because of geometric structure, pressure gradient, and thermal diffusion effects, deformation and translation occurred in the isotropic emission source, leading to anisotropy in the azimuth distribution of the final-state particles. Based on these dynamic factors, the dependence of elliptic flow on transverse momentum is described as well.
Vaping Is Not Safe: A Case of Acute Eosinophilic Pneumonia following Cannabis Vapor Inhalation
Authors: Antwi-Amoabeng Daniel , Islam Raheel
Published: January 2020

There is a well-established association between inhalational exposures and acute eosinophilic pneumonia (AEP). The most reported exposure is cigarette smoking. Here, we present a case of progressive shortness of breath and nonproductive cough in a college student with no significant medical history, approximately 10 days after inhaling cannabis aerosols on two separate occasions. He was started on empiric antibiotics and bronchodilators without improvement. He was diagnosed with AEP based on peripheral eosinophilia and high-resolution CT image results. He made rapid recovery on intravenous glucocorticoids. Vaping has gained popularity among young adults mainly due to the perception that it is a safe alternative to smoking. This case shows that there may be a false sense of security with vaping. Vaping poses a yet-to-be quantified public health threat, which requires further studies.
Optimization of Energy Consumption in Net-Zero Energy Buildings with Increasing Thermal Comfort of Occupants
Authors: Mahdavi Adeli Mohsen , Farahat Said , Sarhaddi Faramarz
Published: January 2020

Residential and commercial buildings consume approximately 60% of the world’s electricity. It is almost impossible to provide a general definition of thermal comfort, because the feeling of thermal comfort is affected by varying preferences and specific traits of the population living in different climate zones. Considering that no studies have been conducted on thermal satisfaction of net-zero energy buildings prior to this date, one of the objectives of the present study is to draw a comparison between the thermal parameters for evaluation of thermal comfort of a net-zero energy building occupants. In so doing, the given building for this study is first optimized for the target parameters of thermal comfort and energy consumption, and, hence, a net-zero energy building is formed. Subsequent to obtaining the acceptable thermal comfort range, the computational analyses required to determine the temperature for thermal comfort are carried out using the Computational Fluid Dynamics (CFD) model. The findings of this study demonstrate that to reach net-zero energy buildings, solar energy alone is not able to supply the energy consumption of buildings and other types of energy should also be used. Furthermore, it is observed that optimum thermal comfort is achieved in moderate seasons.
Socioeconomic Status in Relation to Risks of Major Gastrointestinal Cancers in Chinese Adults: A Prospective Study of 0.5 Million People
Authors: Pang Yuanjie , Kartsonaki Christiana , Guo Yu , Chen Yiping , Yang Ling , Bian Zheng , Bragg Fiona , Millwood Iona Y. , Lv Jun , Yu Canqing , Chen Junshi , Li Liming , Holmes Michael V. , Chen Zhengming
Published: January 2020

Background:

Low socioeconomic status (SES) is associated with higher risk of certain gastrointestinal (e.g., colorectal, pancreatic, and liver) cancers in Western populations. Evidence is very limited in China, where correlates and determinants of SES differ from those in the West.

Methods:

The prospective China Kadoorie Biobank recruited 512,715 adults (59% women, mean age 51 years) from 10 (5 urban, 5 rural) regions. During 10 years of follow-up, 27,940 incident cancers (including 3,061 colorectal, 805 pancreatic, and 2,904 liver) were recorded among 510,131 participants without prior cancer at baseline. Cox regression was used to estimate adjusted HRs for specific cancers associated with area-level (e.g., per capita gross domestic product, disposable income) and individual-level (e.g., education, household income) SES.

Results:

Area-level SES and household income showed positive associations with incident colorectal and pancreatic cancers and inverse associations with liver cancer (Ptrend < 0.05). Education showed no association with colorectal cancer but inverse associations with pancreatic and liver cancers, with adjusted HRs comparing university to no formal schooling being 1.05 [95% confidence interval (CI), 0.85–1.29], 0.49 (95% CI, 0.28–0.85), and 0.61 (95% CI, 0.47–0.81), respectively. Potential risk factors (e.g., smoking, alcohol) partly explained the inverse associations of education with pancreatic and liver cancers (17.6% and 60.4%), respectively.

Conclusions:

Among Chinese adults, the associations of SES with gastrointestinal cancers differed by cancer type and SES indicator. Potential risk factors partially explained the inverse associations of education with pancreatic and liver cancers.

Impact:

The different associations between SES with gastrointestinal cancers may inform cancer prevention strategies.
Mortality prognostic factors associated with SAPS 3 and APACHE II in elderly patients admitted in intensive care unit
Authors: Lucena Marcus Vinícius Ferraz De , Santos-Veloso Marcelo Antônio Oliveira , Xavier Geylson Rodrigo dos Santos , Ferreira Inácio Borges , Moraes Felipe de Castro , Lucena Renata Amorim De , Lucena Letícia Amorim De , Markman Filho Brivaldo , Lima Sandro Gonçalves De
Published: January 2020

Study design: a descriptive, prospective cohort study. Objectives: identify the risk factors associated with SAPS 3 and APACHE II score to improve mortality prediction in elderly admitted in the intensive care unit (ICU). Methodology: a cohort study with 174 elderly patients admitted in ICU from July 2016 to June 2017. The primary independent variables analyzed were: presence of stress hyperglycemia, the need for invasive mechanical ventilation (IMV), acute renal failure, level of consciousness and use of vasopressors. The outcomes studied were death and hospital discharge. Results: ICU and hospital mortality were 17.8% and 29.8%, respectively. The multivariate analysis of factors associated with hospital death not contemplated in the obtaining of SAPS 3 demonstrated that IMV, Chronic Obstructive Pulmonary Disease (COPD) and Mean Arterial Pressure (MAP) <70 mmHg improved the prediction of mortality. The Hosmer-Lemeshow test (p=0.472) and area under ROC curve=0.80 (CI95%:0.731-0.872) confirmed, respectively, an appropriate calibration and acceptable-to-excellent discriminatory power for this model. IMV and COPD were also factors associated with the APACHE II score in prediction of mortality with appropriated calibration (p=0.471) and acceptable-to-excellent discriminatory power (area under ROC curve=0.80 [CI95%:0.730-0.868]). Conclusion: IMV, COPD, and MAP <70 mmHg were associated with SAPS3 and APACHE II to predict mortality in elderly admitted to ICU.
Pulsed Field Ablation Versus Radiofrequency Ablation
Authors: Koruth Jacob S. , Kuroki Kenji , Kawamura Iwanari , Brose Richard , Viswanathan Raju , Buck Eric D. , Donskoy Elina , Neuzil Petr , Dukkipati Srinivas R. , Reddy Vivek Y.
Published: January 2020

Background:

Pulsed field ablation (PFA) can be myocardium selective, potentially sparing the esophagus during left atrial ablation. In an in vivo porcine esophageal injury model, we compared the effects of newer biphasic PFA with radiofrequency ablation (RFA).

Methods:

In 10 animals, under general anesthesia, the lower esophagus was deflected toward the inferior vena cava using an esophageal deviation balloon, and ablation was performed from within the inferior vena cava at areas of esophageal contact. Four discrete esophageal sites were targeted in each animal: 6 animals received 8 PFA applications/site (2 kV, multispline catheter), and 4 animals received 6 clusters of irrigated RFA applications (30 W×30 seconds, 3.5 mm catheter). All animals were survived to 25 days, sacrificed, and the esophagus submitted for pathological examination, including 10 discrete histological sections/esophagus.

Results:

The animals weight increased by 13.7±6.2% and 6.8±6.3% (
P
=0.343) in the PFA and RFA cohorts, respectively. No PFA animals (0 of 6, 0%) developed abnormal in-life observations, but 1 of 4 RFA animals (25%) developed fever and dyspnea. On necropsy, no PFA animals (0 of 6, 0%) demonstrated esophageal lesions. In contrast, esophageal injury occurred in all RFA animals (4 of 4, 100%;
P
=0.005): a mean of 1.5 mucosal lesions/animal (length, −21.8±8.9 mm; width, −4.9±1.4 mm) were observed, including one esophago-pulmonary fistula and deep esophageal ulcers in the other animals. Histological examination demonstrated tissue necrosis surrounded by acute and chronic inflammation and fibrosis. The necrotic RFA lesions involved multiple esophageal tissue layers with evidence of arteriolar medial thickening and fibrosis of periesophageal nerves. Abscess formation and full-thickness esophageal wall disruptions were seen in areas of perforation/fistula.

Conclusions:

In this novel porcine model of esophageal injury, biphasic PFA induced no chronic histopathologic esophageal changes, while RFA demonstrated a spectrum of esophageal lesions including fistula and deep esophageal ulcers and abscesses.
Orthostatic Hypotension, Cardiovascular Outcomes, and Adverse Events
Authors: Juraschek Stephen P. , Taylor Addison A. , Wright Jackson T. , Evans Gregory W , Miller Edgar R. , Plante Timothy B. , Cushman William C. , Gure Tanya R. , Haley William E. , Moinuddin Imran , Nord John , Oparil Suzanne , Pedley Carolyn , Roumie Christianne L. , Whittle Jeff , Wiggers Alan , Finucane Ciarán , Anne Kenny Rose , Appel Lawrence J. , Townsend Raymond R. ,   for the SPRINT Research Group
Published: January 2020

Orthostatic hypotension (OH) is frequently observed with hypertension treatment, but its contribution to adverse outcomes is unknown. The SPRINT (Systolic Blood Pressure Intervention Trial) was a randomized trial of adults, age ≥50 years at high risk for cardiovascular disease with a seated systolic blood pressure (BP) of 130 to 180 mm Hg and a standing systolic BP ≥110 mm Hg. Participants were randomized to a systolic BP treatment goal of either <120 or <140 mm Hg. OH was defined as a drop in systolic BP ≥20 or diastolic BP ≥10 mm Hg 1 minute after standing from a seated position. We used Cox models to examine the association of OH with cardiovascular disease or adverse study events by randomized BP goal. During the follow-up period (median 3years), there were 1170 (5.7%) instances of OH among those assigned a standard BP goal and 1057 (5.0%) among those assigned the intensive BP goal. OH was not associated with higher risk of cardiovascular disease events (primary outcome: hazard ratio 1.06 [95% CI, 0.78–1.44]). Moreover, OH was not associated with syncope, electrolyte abnormalities, injurious falls, or acute renal failure. OH was associated with hypotension-related hospitalizations or emergency department visits (hazard ratio, 1.77 [95% CI, 1.11–2.82]) and bradycardia (hazard ratio, 1.94 [95% CI, 1.19–3.15]), but these associations did not differ by BP treatment goal. OH was not associated with a higher risk of cardiovascular disease events, and BP treatment goal had no effect on OH’s association with hypotension and bradycardia. Symptomless OH during hypertension treatment should not be viewed as a reason to down-titrate therapy even in the setting of a lower BP goal.

Clinical Trial Registration

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT01206062.
Long-range temporal correlations in scale-free neuromorphic networks
Authors: Shirai Shota , Acharya Susant Kumar , Bose Saurabh Kumar , Mallinson Joshua Brian , Galli Edoardo , Pike Matthew D. , Arnold Matthew D. , Brown Simon Anthony
Published: January 2020

Biological neuronal networks are the computing engines of the mammalian brain. These networks exhibit structural characteristics such as hierarchical architectures, small-world attributes, and scale-free topologies, providing the basis for the emergence of rich temporal characteristics such as scale-free dynamics and long-range temporal correlations. Devices that have both the topological and the temporal features of a neuronal network would be a significant step toward constructing a neuromorphic system that can emulate the computational ability and energy efficiency of the human brain. Here we use numerical simulations to show that percolating networks of nanoparticles exhibit structural properties that are reminiscent of biological neuronal networks, and then show experimentally that stimulation of percolating networks by an external voltage stimulus produces temporal dynamics that are self-similar, follow power-law scaling, and exhibit long-range temporal correlations. These results are expected to have important implications for the development of neuromorphic devices, especially for those based on the concept of reservoir computing.