bluuebunny/crossref_metadata_2025 huggingface dataset:
Research Consent Models Used in Prospective Studies of Neurologically Deceased Organ Donors: A Systematic Review
Authors: D’Aragon Frederick , Burns Karen E. A. , Yaworski Amanda , Lucas Amanda , Arseneau Erika , Belley-Cote Emilie , Dhanani Sonny , Frenette Anne-Julie , Lamontagne François , Lauzier François , Akhtar Aemal , Oczkowski Simon , Rochwerg Bram , Meade Maureen O.
Published: February 2020

Research to inform the care of neurologically deceased organ donors is complicated by a lack of standards for research consent. In this systematic review, we aim to describe current practices of soliciting consent for participation in prospective studies of neurologically deceased donors, including the frequency and justification for these various models of consent. Among the 74 studies included, 14 did not report on any regulatory review, and 13 did not report on the study consent procedures. Of the remaining 47 studies, 24 utilized a waiver of research consent. The most common justification for a waiver of research consent related to the fact that neurologically deceased donors are not considered human subjects. In conclusion, among studies of neurologically deceased donors, research consent models vary and are inconsistently reported. Consensus and standardization in the application of research consent models will help to advance this emerging field of research.
Dose–Response of TLD-100 in the Dose Range Useful for Hypofractionated Radiotherapy
Authors: Liuzzi Raffaele , Piccolo Consiglia , D’Avino Vittoria , Clemente Stefania , Oliviero Caterina , Cella Laura , Pugliese Mariagabriella
Published: February 2020

Purpose:

The aim of the study was to exploit the feasibility of thermoluminescent dosimeters (TLDs) in radiation therapy techniques in which high dose per fraction is involved.

Methods:

Dose–response of TLD-100 (LiF: Mg, Ti) was investigated in both 6-MV photon and 6-MeV electron beams. The element correction factor (ECF) generation method was applied to check the variability of the TLDs response. Two batches of 50 TLDs were divided into groups and exposed in the dose range 0 to 30 Gy. Regression analysis was performed with both linear and quadratic models. For each irradiation beam, the calibration curves were obtained in 3 dose range 0 to 8 Gy, 0 to 10 Gy, and 0 to 30 Gy. The best-fitting model was assessed by the Akaike Information Criterion test.

Results:

The ECF process resulted a useful tool to reduce the coefficients of variation from original values higher than 5% to about 3.5%, for all the batches exposed. The results confirm the linearity of dose–response curve below the dose level of 10 Gy for photon and electron beam and the supralinear trend above.

Conclusion:

The TLDs are suitable dosimeters for dose monitoring and verification in radiation treatment involving dose up to 30 Gy in a single fraction.
The doctor wellbeing toolkit
Authors: Castronovo Grace
Published: February 2020

Doctors suffer with high levels of stress, anxiety and depression; they are at increased risk of suicide when compared with the general population and other professional groups. Several high-profile deaths of junior doctors have led to a renewed focus on the wellbeing of doctors. In this article, we will review some of the facts underlying burnout in the National Health Service and provide a toolkit for doctors to assess their own wellbeing and learn simple strategies to enable them to live a more balanced and fulfilled life through self-care.
Management of gastrointestinal symptoms in palliative care
Authors: Kumar Monica
Published: February 2020

The management of symptoms related to the gastrointestinal tract is an ongoing challenge in the care of patients with advanced malignancy. Clinical symptoms are often detrimental to a patient’s quality of life. The goal of palliative medicine includes care of the mind, body, and spirit. Symptom management and improving quality of life for patients and their families is paramount. As the population ages, this results in more complex health needs and the need for a multidisciplinary team approach. This article will outline a general and systematic approach to managing gastrointestinal symptoms in palliative care; it will emphasise the importance of holistic medicine in improving a patient’s quality of life.
Real‐world experience using combination therapy with riociguat and risk assessment using REVEAL Lite 2.0 in patients with pulmonary arterial hypertension
Authors: Sahay Sandeep , Rahaghi Franck
Published: February 2020

Pulmonary arterial hypertension is a progressive disease that can lead to right‐sided ventricular failure and premature death. Tailoring therapy to individual patient’s needs, along with regular risk assessment, is integral for optimal outcomes in patients with pulmonary arterial hypertension. Results from the AMBITION trial support the use of upfront combination of tadalafil and ambrisentan. In a recent analysis of risk assessment in pulmonary arterial hypertension, abridged versions of the REVEAL 2.0 risk score were shown to be comparable to the full tools. In this report, we present a case series of the use of riociguat in upfront combination or sequentially, and the impact on risk scores as determined by the abridged REVEAL Lite 2.0 approach.
Barriers in Adopting Healthy Body Weight Among Malaysian Population: A Cross-Sectional Study of Body Weight Perception and Misperception Versus Actual Body Weight
Authors: Wan Abdul Hamed Wan Nurhafizah , Abd Aziz Noor Azah
Published: February 2020

Perception of body weight has been recognized as an important barrier in the adoption of healthy lifestyles. Several factors affect perception of body weight, but the outcomes have been varied. This study aimed to study the perception and misperception of body weight and its association with the measured body mass index. A clinic-based cross-sectional study was done in the clinic using systematic sampling. Data were collected by using a self-administered questionnaire consisting of the sociodemographic profile, body weight perception question adopted from Weight Management Questionnaire and Youth Risk Behavior Surveillance System (YRBSS) 1991-2017. The prevalence of body weight misperception in the sample population was 58.6%. Most of the respondents were overweight (33.9%) and obese (33.9%). Respondents aged 25 years and older were 2.98 times more likely to have misperception compared with other age groups (95% CI: 1.21-3.19, P = .006). Divorced respondents were 4.70 times more likely to have body misperception compared with married respondents (95% CI 1.44-15.32, P = 0.01). This study showed that misperception of body weight could be influenced by reversible factors and measured body mass index. Hence, the rectification of these misperceptions is important in the clinical setting especially in these vulnerable groups of respondents.
Military, Civilian, or Both: David Ben-Gurion’s Perception of National Security After the War of Independence
Authors: Fried Yoram
Published: February 2020

Over the years, attempts to define the notion of national security in terms of what it means and what it represents have ranged from a classical, purely military definition, to a broader multidimensional concept encompassing a range of different features. Studies on Israel’s national security concept have tended to emphasize the formative role played by David Ben-Gurion, Israel’s first prime minister and defense minister. These works have focused on the military aspects of the national security concept, based on arguments concerning the perceived threat of wartime engagements with Arab armies. This article argues that Ben-Gurion’s national security concept was essentially a civilian perspective with military features that responded to the four types of threats, local, regional, international, and Jewish, facing the State of Israel at the time, most of which were not military.
Visualizing Age, Period, and Cohort Patterns of Substance Use in the U.S. Opioid Crisis
Authors: Verdery Ashton M. , England Kira , Chapman Alexander , Luo Liying , McLean Katherine , Monnat Shannon
Published: February 2020

Descriptions of the contemporary U.S. opioid crisis emphasize several “waves” of overdose deaths. However, a focus on trends in overdose deaths may obscure important sociological dynamics. The authors provide heatmap visualizations of estimated annual rates of past-year substance use, rather than overdose deaths, for prescription pain relievers and heroin. These visualizations are based on weighted analyses of self-reports, cross-classified by age and period, collected as part of the National Survey on Drug Use and Health from 2002 to 2017. Whereas descriptions of the U.S. opioid crisis tend to focus on period dynamics, these visualizations indicate that cohort patterns of drug use are also evident in addition to well-known age variation. A substantive focus on cohort patterns highlights the possibility that cohorts of people who use drugs may remain at risk for overdose in the years to come. These findings suggest that policies aimed only at restricting opioid availability may have limited effects.
Megakaryocyte migration defects due to nonmuscle myosin IIA mutations underlie thrombocytopenia in MYH9-related disease
Authors: Pal Kasturi , Nowak Roberta , Billington Neil , Liu Rong , Ghosh Arit , Sellers James R. , Fowler Velia M.
Published: February 2020

Megakaryocytes (MKs), the precursor cells for platelets, migrate from the endosteal niche of the bone marrow (BM) toward the vasculature, extending proplatelets into sinusoids, where circulating blood progressively fragments them into platelets. Nonmuscle myosin IIA (NMIIA) heavy chain gene (MYH9) mutations cause macrothrombocytopenia characterized by fewer platelets with larger sizes leading to clotting disorders termed myosin-9–related disorders (MYH9-RDs). MYH9-RD patient MKs have proplatelets with thicker and fewer branches that produce fewer and larger proplatelets, which is phenocopied in mouse Myh9-RD models. Defective proplatelet formation is considered to be the principal mechanism underlying the macrothrombocytopenia phenotype. However, MYH9-RD patient MKs may have other defects, as NMII interactions with actin filaments regulate physiological processes such as chemotaxis, cell migration, and adhesion. How MYH9-RD mutations affect MK migration and adhesion in BM or NMIIA activity and assembly prior to proplatelet production remain unanswered. NMIIA is the only NMII isoform expressed in mature MKs, permitting exploration of these questions without complicating effects of other NMII isoforms. Using mouse models of MYH9-RD (NMIIAR702C+/−GFP+/−, NMIIAD1424N+/−, and NMIIAE1841K+/−) and in vitro assays, we investigated MK distribution in BM, chemotaxis toward stromal-derived factor 1, NMIIA activity, and bipolar filament assembly. Results indicate that different MYH9-RD mutations suppressed MK migration in the BM without compromising bipolar filament formation but led to divergent adhesion phenotypes and NMIIA contractile activities depending on the mutation. We conclude that MYH9-RD mutations impair MK chemotaxis by multiple mechanisms to disrupt migration toward the vasculature, impairing proplatelet release and causing macrothrombocytopenia.
Discovery and characterization of targetable NTRK point mutations in hematologic neoplasms
Authors: Joshi Sunil K. , Qian Kristin , Bisson William H. , Watanabe-Smith Kevin , Huang Ariane , Bottomly Daniel , Traer Elie , Tyner Jeffrey W. , McWeeney Shannon K. , Davare Monika A. , Druker Brian J. , Tognon Cristina E.
Published: February 2020

Much of what is known about the neurotrophic receptor tyrosine kinase (NTRK) genes in cancer was revealed through identification and characterization of activating Trk fusions across many tumor types. A resurgence of interest in these receptors has emerged owing to the realization that they are promising therapeutic targets. The remarkable efficacy of pan-Trk inhibitors larotrectinib and entrectinib in clinical trials led to their accelerated, tissue-agnostic US Food and Drug Administration (FDA) approval for adult and pediatric patients with Trk-driven solid tumors. Despite our enhanced understanding of Trk biology in solid tumors, the importance of Trk signaling in hematological malignancies is underexplored and warrants further investigation. Herein, we describe mutations in NTRK2 and NTRK3 identified via deep sequencing of 185 patients with hematological malignancies. Ten patients contained a point mutation in NTRK2 or NTRK3; among these, we identified 9 unique point mutations. Of these 9 mutations, 4 were oncogenic (NTRK2A203T, NTRK2R458G, NTRK3E176D, and NTRK3L449F), determined via cytokine-independent cellular assays. Our data demonstrate that these mutations have transformative potential to promote downstream survival signaling and leukemogenesis. Specifically, the 3 mutations located within extracellular (ie, NTRK2A203T and NTRK3E176D) and transmembrane (ie, NTRK3L449F) domains increased receptor dimerization and cell-surface abundance. The fourth mutation, NTRK2R458G, residing in the juxtamembrane domain, activates TrkB via noncanonical mechanisms that may involve altered interactions between the mutant receptor and lipids in the surrounding environment. Importantly, these 4 activating mutations can be clinically targeted using entrectinib. Our findings contribute to ongoing efforts to define the mutational landscape driving hematological malignancies and underscore the utility of FDA-approved Trk inhibitors for patients with aggressive Trk-driven leukemias.
ESR/ERS statement paper on lung cancer screening
Authors: Kauczor Hans-Ulrich , Baird Anne-Marie , Blum Torsten Gerriet , Bonomo Lorenzo , Bostantzoglou Clementine , Burghuber Otto , Čepická Blanka , Comanescu Alina , Couraud Sébastien , Devaraj Anand , Jespersen Vagn , Morozov Sergey , Nardi Agmon Inbar , Peled Nir , Powell Pippa , Prosch Helmut , Ravara Sofia , Rawlinson Janette , Revel Marie-Pierre , Silva Mario , Snoeckx Annemiek , van Ginneken Bram , van Meerbeeck Jan P. , Vardavas Constantine , von Stackelberg Oyunbileg , Gaga Mina
Published: February 2020

In Europe, lung cancer ranks third among the most common cancers, remaining the biggest killer. Since the publication of the first European Society of Radiology and European Respiratory Society joint white paper on lung cancer screening (LCS) in 2015, many new findings have been published and discussions have increased considerably. Thus, this updated expert opinion represents a narrative, non-systematic review of the evidence from LCS trials and description of the current practice of LCS as well as aspects that have not received adequate attention until now. Reaching out to the potential participants (persons at high risk), optimal communication and shared decision-making will be key starting points. Furthermore, standards for infrastructure, pathways and quality assurance are pivotal, including promoting tobacco cessation, benefits and harms, overdiagnosis, quality, minimum radiation exposure, definition of management of positive screen results and incidental findings linked to respective actions as well as cost-effectiveness. This requires a multidisciplinary team with experts from pulmonology and radiology as well as thoracic oncologists, thoracic surgeons, pathologists, family doctors, patient representatives and others. The ESR and ERS agree that Europe's health systems need to adapt to allow citizens to benefit from organised pathways, rather than unsupervised initiatives, to allow early diagnosis of lung cancer and reduce the mortality rate. Now is the time to set up and conduct demonstration programmes focusing, among other points, on methodology, standardisation, tobacco cessation, education on healthy lifestyle, cost-effectiveness and a central registry.
Comprehensive Evaluation and Analysis of the Mechanism of Cold Tolerance Based on the Transcriptome of Weedy Rice Seedlings
Authors: Han Bing , Ma Xiaoding , Cui Di , Wang Yanjie , Geng Leiyue , Cao Guilan , Zhang Hui , Han Longzhi
Published: February 2020

In this study, the cold-tolerance capacity of 133 varieties of weedy rice was evaluated based on the comprehensive evaluation index D, with Kongyu 131 used as a cold-tolerant control. A total of 39.8% of the 133 varieties were considered ‘strong’, indicating that weedy rice populations indeed have relatively strong cold-tolerance capacity as a whole, and the robust cold-tolerant varieties WR29 and WR157 were identified. Regression analysis showed that the metrics including the nitrogen recovery index, superoxide dismutase (SOD) content and malondialdehyde (MDA) content correlated significantly (P < 0.05) with cold tolerance and could be used as indicators of cold tolerance. On the basis of a transcriptome analysis of WR157, a robust cold-tolerant variety identified in this study, a total of 4645 putative DEGs were identified in treated groups compared to the control groups, with 2123 upregulated DEGs and 2522 downregulated DEGs. All upregulated DEGs were enriched on 1388 terms, all downregulated DEGs were enriched on 1566 terms; 911 of the 2123 upregulated DEGs fell into 98 KEGG categories and 1103 of the 2522 downregulated DEGs were in 115 categories. Further analysis showed that GO:0019740 and GO:0006808 are involved in nitrogen utilization; GO:0009269 and GO:0009414 are related to the stress response; and GO:0016491 and GO:0016614 are related to oxidoreductase activity.

Background

Weedy rice (Oryza) is a related pest species of cultivated rice (Oryza sativa L.) that has strong abiotic stress resistance; however, the comprehensive mechanism governing its cold tolerance is poorly understood.

Conclusion

Our comprehensive evaluation based on five morphological indices and nine physiological indicators revealed outstanding levels of cold-tolerance capacity among weedy rice varieties from different regions and revealed some terms related to cold tolerance via transcriptome analysis. Our results underscored the reliable evaluation methods for additional cold tolerance studies and revealed several genes related to cold tolerance, which will help researchers breed cultivated rice varieties to increase their cold-tolerance capacity. These traits have the ability to increase seedling survival rate and growth, as well as future yields.
iSeqQC: a tool for expression-based quality control in RNA sequencing
Authors: Kumar Gaurav , Ertel Adam , Feldman George , Kupper Joan , Fortina Paolo
Published: February 2020

Background

Quality Control in any high-throughput sequencing technology is a critical step, which if overlooked can compromise an experiment and the resulting conclusions. A number of methods exist to identify biases during sequencing or alignment, yet not many tools exist to interpret biases due to outliers.

Results

Hence, we developed iSeqQC, an expression-based QC tool that detects outliers either produced due to variable laboratory conditions or due to dissimilarity within a phenotypic group. iSeqQC implements various statistical approaches including unsupervised clustering, agglomerative hierarchical clustering and correlation coefficients to provide insight into outliers. It can be utilized through command-line (Github: https://github.com/gkumar09/iSeqQC) or web-interface (http://cancerwebpa.jefferson.edu/iSeqQC). A local shiny installation can also be obtained from github (https://github.com/gkumar09/iSeqQC).

Conclusion

iSeqQC is a fast, light-weight, expression-based QC tool that detects outliers by implementing various statistical approaches.
Population-specific, recent positive directional selection suggests adaptation of human male reproductive genes to different environmental conditions
Authors: Schaschl Helmut , Wallner Bernard
Published: February 2020

Background

Recent human transcriptomic analyses revealed a very large number of testis-enriched genes, many of which are involved in spermatogenesis. This comprehensive transcriptomic data lead us to the question whether positive selection was a decisive force influencing the evolution and variability of testis-enriched genes in humans. We used two methodological approaches to detect different levels of positive selection, namely episodic positive diversifying selection (i.e., past selection) in the human lineage within primate phylogeny, potentially driven by sperm competition, and recent positive directional selection in contemporary human populations, which would indicate adaptation to different environments.

Results

In the human lineage (after correction for multiple testing) we found that only the geneTULP2, for which no functional data are yet available, is subject to episodic positive diversifying selection. Using less stringent statistical criteria (uncorrectedp-values), also the geneSPATA16, which has a pivotal role in male fertility and for which episodes of adaptive evolution have been suggested, also displays a putative signal of diversifying selection in the human branch. At the same time, we found evidence for recent positive directional selection acting on several human testis-enriched genes (MORC1,SLC9B1,ROPN1L,DMRT1,PLCZ1,RNF17,FAM71DandWBP2NL) that play important roles in human spermatogenesis and fertilization. Most of these genes are population-specifically under positive selection.

Conclusion

Episodic diversifying selection, possibly driven by sperm competition, was not an important force driving the evolution of testis-enriched genes in the human lineage. Population-specific, recent positive directional selection suggests an adaptation of male reproductive genes to different environmental conditions. Positive selection acts on eQTLS and sQTLs, indicating selective effects on important gene regulatory functions. In particular, the transcriptional diversity regulated by sQTLs in testis-enriched genes may be important for spermatocytes to respond to environmental and physiological stress.
Molecular bases for drought tolerance in common vetch: designing new molecular breeding tools
Authors: De la Rosa Lucía , Zambrana Encarnación , Ramirez-Parra Elena
Published: February 2020

Background

Common vetch (Vicia sativa L.) is a forage grain legume of high protein content and high nitrogen fixation, relevant in sustainable agriculture systems. Drought is the main limiting factor of this crop yield. Genetic resources collections are essential to provide genetic variability for breeding. The analysis of drought associated parameters has allowed us to identify drought tolerant and sensitive ecotypes in a vetch core collection.

Results

To understand the mechanisms involved in drought response we analysed transcriptomic differences between tolerant and sensitive accessions. Polymorphic variants (SNPs and SSRs) in these differential expressed genes (DEGs) have also been analysed for the design of drought-associated markers. A total of 1332 transcripts were commonly deregulated in both genotypes under drought. To know the drought adaptive response, we also analysed DEGs between accessions. A total of 2646 transcripts are DEG between sensitive and tolerant ecotypes, in watered and drought conditions, including important genes involved in redox homeostasis, cell wall modifications and stress-response. The integration of this functional and genetic information will contribute to understand the molecular mechanisms of drought response and the adaptive mechanisms of drought tolerance in common vetch. The identification of polymorphic variants in these DEGs has also been screened for the design of drought-associated markers that could be used in future breeding program strategies.

Conclusions

Our studies shed light for the first time in common vetch about the genes and pathways associated with drought tolerance. In addition, we identify over 100 potential drought associated polymorphism, as SNPs or SSRs, which are differently present in drought and tolerant genotypes. The use of these molecular markers for trait prediction would enable the development of genomic tools for future engineering strategies by screening of germplasm crop collections for traits related with crop drought resilience, adaptability or yield in vetch.
Recurrent epileptic seizures following cardiac catheterization with iodixanol: a case report
Authors: Lei Pingping , He Weiping , Shi Quan , Sun Meiying , Sun Zhigang
Published: February 2020

Background

Contrast-induced encephalopathy (CIE) is a rare complication of cardiac catheterization; clinical manifestations include cortical blindness, seizures and focal neurological deficits. In general, recurrent epileptic seizures following cardiac catheterization with iodixanol occur more rarely than do other complications.

Case presentation

Here, we report a case of a 76-year-old male patient who experienced unstable angina for nearly 10 months and was admitted to our hospital. Repeat cardiac catheterization was performed using iodixanol. At approximately 20 h after the first cardiac catheterization, his upper limbs began to exhibit slight trembling; the patient was conscious and could not control these movements. A total of 6 episodes occurred before the second cardiac catheterization was performed, with each episode lasting approximately 2 s. These symptoms were not treated. At approximately 2 h after the second cardiac catheterization, the symptoms became more severe, and the frequency of the episodes increased significantly; the symptoms had fully subsided at 6 h after the second operation. An electroencephalogram (EEG) demonstrated diffuse slowing with epileptiform abnormalities. Paroxysmal spike-wave and slow wave discharges were observed in the bilateral areas, and the abnormalities were marked in the frontal areas. These observations led us to conclude that the patient was experiencing epileptic seizures. During 6 months of monthly clinical follow-up visits after discharge, no abnormalities of the nervous system were found by cardiologists or neurologists, and the patient’s EEG was normal. No antiepileptic drugs were administered throughout this process.

Conclusions

CIE, especially recurrent epileptic seizures, is a rare but often reversible complication of cardiac catheterization with iodixanol. Its symptoms can be mild and therefore are easily ignored by physicians. Early CIE detection may be achieved by EEG. Repeated exposure to contrast agents carries the risk of recurrent epileptic seizures.
Pattern of vitreo-retinal diseases at the national referral hospital in Bhutan: a retrospective, hospital-based study
Authors: Rai Bhim B. , Morley Michael G. , Bernstein Paul S. , Maddess Ted
Published: February 2020

Background

Knowing the pattern and presentation of the diseases is critical for management strategies. To inform eye-care policy we quantified the pattern of vitreo-retinal (VR) diseases presenting at the national referral hospital in Bhutan.

Methods

We reviewed all new patients over three years from the retinal clinic of the Jigme Dorji Wangchuck National Referral Hospital. Demographic data, presenting complaints and duration, treatment history, associated systemic diseases, diagnostic procedures performed, and final diagnoses were quantified. Comparisons of the expected and observed frequency of gender used Chi-squared tests. We applied a sampling with replacement based bootstrap analysis (10,000 cycles) to estimate the population means and the standard errors of the means and standard error of the 10th, 25th, 50th, 75th and 90th percentiles of the ages of the males and females within 20-year cohorts. We then applied t-tests employing the estimated means and standard errors. The 2913 subjects insured that the bootstrap estimates were statistically conservative.

Results

The 2913 new cases were aged 47.2 ± 21.8 years. 1544 (53.0%) were males. Housewives (953, 32.7%) and farmers (648, 22.2%) were the commonest occupations. Poor vision (41.9%), screening for diabetic and hypertensive retinopathy (13.1%), referral (9.7%), sudden vision loss (9.3%), and trauma (8.0%) were the commonest presenting symptoms. Coexistent diabetes and hypertension were the most common associated systemic diseases. Haematological tests (blood sugar, HbA1c and lipid profile, 31.8%), OCT (27.4%), refraction (9.9%), B-scan (8.7%), fundus photography (8.0%) were the most commonly performed diagnostic tests. Hypertensive retinopathy (18.9%) was the commonest VR disease, followed by refractive errors referred for retinal evaluation (16.7%), diabetic retinopathy with macular oedema (15.8%), and AMD (11.0%). Retinal detachment was more prevalent in females (83 vs. 41, p = 0.007). Rare vision-threatening diseases like seasonal hyper-acute pan-uveitis also presented.

Conclusions

The developing VR service in Bhutan is challenged by the spectrum of diseases, limited human resources (e.g. one retinal surgeon during the study), and accessibility to tertiary eye-care services, all amidst difficult terrain. Sustained effort and robust coordination among the eye-care professionals, government and non-governmental organisations are critical for optimising VR services, especially as rates of diseases such as diabetes and hypertension grow.
Association between alcohol consumption and osteoarthritis prevalence in Korea as assessed by the alcohol use disorders identification test (AUDIT): a cross-sectional study
Authors: Kang Ah. Hyun , Kim Me-riong , Shin Joon-Shik , Lee Jinho , Lee Yoon Jae , Park Yeoncheol , Nam Dongwoo , Kim Eun-Jung , Ha In-Hyuk
Published: February 2020

Background

Osteoarthritis (OA) holds significance as a highly prevalent disorder in elderly populations. Various studies have been conducted on the association between alcohol consumption and OA, but the results have often been conflicting. The aim of this study was to investigate the relationship between alcohol consumption and OA in a large-scale sample representative of the Korean population.

Methods

Among the 25,534 participants surveyed in the fifth Korean National Health and Nutrition Examination Survey (2010–2012), 7165 individuals aged ≥50 who responded to drinking-related items were analyzed. The Alcohol Use Disorders Identification Test (AUDIT) grade was calculated, and radiologic examination analysis included the Kellgren-Lawrence (KL) grade of the lumbar spine, hip, and knee joints. Logistic regression analysis was performed to evaluate the association between AUDIT grades and OA through estimation of odds ratios (ORs).

Results

In crude analyses, OA (KL grade ≥ 2) of the lumbar spine and knee was more prevalent towards Zone I, but following adjustment, knee OA prevalence significantly increased in Zone III and IV compared to Zone I (Zone III: OR 1.464, 95% confidence interval (CI) 1.027–2.088; Zone IV: OR 1.543, 95% CI 1.028–2.317, respectively). Meanwhile, adjusted hip and lumbar OA values showed positive associations towards Zone IV, but did not reach statistical significance. Additional analyses of the association between alcohol consumption and pain severity of knee OA patients were nonsignificant.

Conclusions

These results imply that radiological knee OA, rather than symptomatic knee OA, is associated with alcohol consumption.
EPI immunization coverage, timeliness and dropout rate among children in a West Cameroon health district: a cross sectional study
Authors: Ateudjieu Jérôme , Yakum Martin Ndinakie , Goura André Pascal , Tembei Ayok Maureen , Ingrid Douanla Koutio , Bita’a Landry Beyala , Kenfack Bruno , Amada Lapia , Tadzong Isaac , Bissek Anne Cecile
Published: February 2020

Background

Monitoring of the expanded program on immunization’s performance is not only limited to routine periodic reports but equally includes surveys. Based on unpublished national EPI surveillance data from the past 5 years in Cameroon, the Foumban health district has reported a high number of vaccine preventable disease suspected cases. Contradictory information on the immunization coverage in this district exists from both administrative data and published literature. As a result, the objective of this study was to estimate the immunization coverage and dropout rate in age group 12–23 months and timeliness in age group 0–59 months among children in Foumban Health District (Cameroon), in 2018.

Method

This was a descriptive cross-sectional study targeting randomly selected children aged 0–59 months from Foumban health district. Data were collected by trained and supervised surveyors using a pretested questionnaire to describe the immunization coverage, timeliness and dropout rate in eighty clusters of about thirty buildings selected by stratified random sampling in July 2018.

Results

In total, 80 clusters covering 2121 buildings were selected and all were reached (100%). A total of 1549 (81.2%) households accepted to participate in the survey and 1430 children aged 0–59 months including 294 (20.6%) aged 12–23 months were enrolled into the study. Of these 1430 children, 427 [29.9 (27.4–32.2)%] aged 0–59 months were vaccinated with evidence. In the age group 12–23 months, the immunization coverage with evidence of BCG, DPT-Hi + Hb 3 and measles/rubella were 28.6(23.4–33.9)%, 22.8 (18.1–27.6)% and 14.3 (10.3–18.1)% respectively. Within age group 0–59 months; the proportion of children who missed their vaccination appointments increased from 23.3 to 31.7% for the vaccine planned at birth (BCG) and last vaccine planned (Measles/Rubella) for the EPI program respectively. In age group 12–23 months; the specific (DPT-Hi + Hb1–3) and general (BCG-Measles/Rubella) dropout rates of vaccination with evidence were 14.1 and 50.0% respectively.

Conclusion

Documented immunization coverage, dropout rate and timeliness in Foumban Health district are lower than that targeted by the Cameroon EPI. Competent health authorities have to take necessary actions to ensure the implementation of national guidelines with regards to children access to immunization. Also, studies have to be conducted to identify determinants of low immunization coverage and delays in immunization schedules as well as high dropout rates.
The use of complementary and alternative medicine in a multi-ethnic Asian population: results from the 2016 Singapore Mental Health Study
Authors: Seet Vanessa , Abdin Edimansyah , Vaingankar Janhavi A. , Shahwan Shazana , Chang Sherilyn , Lee Bernard , Chong Siow Ann , Subramaniam Mythily
Published: February 2020

Background

This study seeks to investigate factors associated with using complementary and alternative medicine (CAM) for a mental illness among the three major ethnic groups (Chinese, Indians and Malays) in the general population of Singapore.

Methods

Data from the 2016 Singapore Mental Health Study was used; responses from the “Services” section of the Composite International Diagnostic Interview version 3.0 (CIDI 3.0) administered during face-to-face household interviews with participants were analyzed to establish prevalence of CAM use among Singaporeans. Additionally, sociodemographic variables of interest were selected for sub-group regression analyses to yield correlates of CAM use among the three ethnic groups.

Results

6.4% of Singaporeans used at least one form of CAM in the past 12 months for their mental illness. Malays reported using CAM the most, followed by Indians and Chinese. Sociodemographic variables such as education and employment were differently associated with CAM use among the ethnicities. Across all three ethnic groups, CAM users were more likely to report poorer mental health-related quality of life.

Conclusion

Despite the significant differences in CAM use among Chinese, Malays and Indians, those who had a mental illness were significantly more likely to use CAM regardless of ethnicity. This highlights the need for communication between CAM practitioners and conventional mental healthcare providers for early referral when appropriate which would lead to improved healthcare delivery and better clinical outcomes.
Till death do us part: the effect of marital status on health care utilization and costs at end-of-life. A register study on all colorectal cancer decedents in Norway between 2009 and 2013
Authors: Bjørnelv Gudrun Maria Waaler , Edwin Bjørn , Fretland Åsmund Avdem , Deb Partha , Aas Eline
Published: February 2020

Background

Economic analyses of end-of-life care often focus on single aspects of care in selected cohorts leading to limited knowledge on the total level of care required to patients at their end-of-life. We aim at describing the living situation and full range of health care provided to patients at their end-of-life, including how informal care affects formal health care provision, using the case of colorectal cancer.

Methods

All colorectal cancer decedents between 2009 and 2013 in Norway (n = 7695) were linked to six national registers. The registers included information on decedents’ living situation (days at home, in short- or long-term institution or in the hospital), their total health care utilization and costs in the secondary, primary and home- and community-based care setting. The effect of informal care was assessed through marital status (never married, currently married, or previously married) using regression analyses (negative binominal, two-part models and generalized linear models), controlling for age, gender, comorbidities, education, income, time since diagnosis and year of death.

Results

The average patient spent four months at home, while he or she spent 27 days in long-term institutions, 16 days in short-term institutions, and 21 days in the hospital. Of the total costs (~NOK 400,000), 58, 3 and 39% were from secondary carers (hospitals), primary carers (general practitioners and emergency rooms) and home- and community-based carers (home care and nursing homes), respectively. Compared to the never married, married patients spent 30 more days at home and utilized less home- and community-based care, but more health care services at the secondary and primary health care level. Their total healthcare costs were significantly lower (−NOK 65,621) than the never married. We found similar, but weaker, patterns for those who had been married previously.

Conclusion

End-of-life care is primarily provided in the secondary and home-and community-based care level, and informal caregivers have a substantial influence on formal end-of-life care provision. Excluding aspects of care such as home and community-based care or informal care in economic analyses of end-of-life care provides a biased picture of the total resources required, and might lead to inefficient resource allocations.
Enhancement of bleomycin production in Streptomyces verticillus through global metabolic regulation of N-acetylglucosamine and assisted metabolic profiling analysis
Authors: Chen Hong , Cui Jiaqi , Wang Pan , Wang Xin , Wen Jianping
Published: February 2020

Background

Bleomycin is a broad-spectrum glycopeptide antitumor antibiotic produced by Streptomyces verticillus. Clinically, the mixture of bleomycin A2 and bleomycin B2 is widely used in combination with other drugs for the treatment of various cancers. As a secondary metabolite, the biosynthesis of bleomycin is precisely controlled by the complex extra-/intracellular regulation mechanisms, it is imperative to investigate the global metabolic and regulatory system involved in bleomycin biosynthesis for increasing bleomycin production.

Results

N-acetylglucosamine (GlcNAc), the vital signaling molecule controlling the onset of development and antibiotic synthesis in Streptomyces, was found to increase the yields of bleomycins significantly in chemically defined medium. To mine the gene information relevant to GlcNAc metabolism, the DNA sequences of dasR-dasA-dasBCD-nagB and nagKA in S. verticillus were determined by chromosome walking. From the results of Real time fluorescence quantitative PCR (RT-qPCR) and electrophoretic mobility shift assays (EMSAs), the repression of the expression of nagB and nagKA by the global regulator DasR was released under induction with GlcNAc. The relief of blmT expression repression by BlmR was the main reason for increased bleomycin production. DasR, however, could not directly affect the expression of the pathway-specific repressor BlmR in the bleomycins gene cluster. With at the beginning of bleomycin synthesis, the supply of the specific precursor GDP-mannose played the key role in bleomycin production. Genetic engineering of the GDP-mannose synthesis pathway indicated that phosphomannose isomerase (ManA) and phosphomannomutase (ManB) were key enzymes for bleomycins synthesis. Here, the blmT, manA and manB co-expression strain OBlmT/ManAB was constructed. Based on GlcNAc regulation and assisted metabolic profiling analysis, the yields of bleomycin A2 and B2 were ultimately increased to 61.79 and 36.9 mg/L, respectively.

Conclusions

Under GlcNAc induction, the elevated production of bleomycins was mainly associated with the alleviation of the inhibition of BlmT, so blmT and specific precursor synthesis pathways were genetically engineered for bleomycins production improvement. Combination with subsequent metabolomics analysis not only effectively increased the bleomycin yield, but also extended the utilization of chitin-derived substrates in microbial-based antibiotic production.
Hsa_circ_0011385 accelerates the progression of thyroid cancer by targeting miR-361-3p
Authors: Xia Fada , Chen Yong , Jiang Bo , Bai Ning , Li Xinying
Published: February 2020

Background

Thyroid cancer is an endocrine malignancy that is growing in incidence worldwide. Despite progress in diagnostics and treatment of thyroid cancer, prognosis remains poor. Emerging research has shown that circular RNAs (circRNAs) have crucial regulatory roles in cancers. However, the possible functions and mechanisms of hsa_circ_0011385 remain undetermined.

Materials and methods

Expression levels of hsa_circ_0011385 and miR-361-3p were evaluated by qRT-PCR assay. The interaction between hsa_circ_0011385 and miR-361-3p was verified by dual-luciferase reporter assay. Effects of hsa_circ_0011385 or miR-361-3p on cell viability, proliferation, cell cycle, apoptosis, migration and invasion were confirmed by cell counting kit-8 (CCK-8), carboxyfluoresceinsuccinimidyl ester (CFSE), flow cytometry, and Transwell assays in vitro. The effect of hsa_circ_0011385 on thyroid cancer progression was also determined by in vivo tumor formation assay. Target genes of miR-361-3p were predicted by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and the expression of apoptosis- and metastasis-related proteins were assessed by Western blot assay.

Results

Hsa_circ_0011385 upregulated in thyroid cancer; hsa_circ_0011385 knockdown inhibited thyroid cancer cell proliferation, migration and invasion, and promoted cell cycle arrest and apoptosis. In addition, hsa_circ_0011385 could negatively regulate miR-361-3p by functioning as a sponge. Hsa_circ_0011385 promoted thyroid cancer cell proliferation, migration and invasion and suppressed cell cycle arrest and apoptosis by targeting miR-361-3p in vitro. We also found that hsa_circ_0011385 knockdown dramatically inhibited thyroid cancer growth in vivo. Furthermore, hsa_circ_0011385 regulated expression of apoptosis and metastasis-related proteins in thyroid cancer.

Conclusions

Hsa_circ_0011385facilitated thyroid cancer cell proliferation, invasion and migration, and inhibited thyroid cancer cell cycle arrest and apoptosis by targeting miR-361-3p, suggesting that the hsa_circ_0011385/miR-361-3p axis might be a promising therapeutic target for thyroid cancer.
The gender-related variability in the pharmacokinetics and antiplasmodial activity of naphthoquine in rodents
Authors: Xie Yuewu , Liu Huixiang , Sun Yanhong , Xing Jie
Published: February 2020

Background

Naphthoquine (NQ) is a suitable partner anti-malarial for the artemisinin-based combination therapy (ACT), which is recommended to be taken orally as a single-dose regimen. The metabolism of NQ was mainly mediated by CYP2D6, which is well-known to show gender-specific differences in its expression. In spite of its clinical use, there is limited information on the pharmacokinetics of NQ, and no data are available for females. In this study, the effect of gender on the pharmacokinetics and antiplasmodial efficacy of NQ in rodents was evaluated. The underlying factors leading to the potential gender difference, i.e., plasma protein binding and metabolic clearance, were also evaluated.

Methods

The pharmacokinetic profiles of NQ were investigated in healthy male or female rats after a single oral administration of NQ. The antiplasmodial efficacy of NQ was studied in male or female mice infected withPlasmodium yoelii. The recrudescence and survival time of infected mice were also recorded after drug treatment. Plasma protein binding of NQ was determined in pooled plasma collected from male or female mice, rat or human. In vitro metabolism experiments were performed in the liver microsomes of male or female mice, rat or human.

Results

The results showed that the gender of rats did not affect NQ exposure (AUC0–tand Cmax) significantly (P > 0.05). However, a significant (P < 0.05) longer t1/2was found for NQ in male rats (192.1 ± 47.7), compared with female rats (143.9 ± 27.1). Slightly higher but not significant (P > 0.05) antiplasmodial activity was found for NQ in male mice (ED90, 1.10 mg/kg) infected withP. yoelii, compared with female mice (ED90, 1.67 mg/kg). The binding rates of NQ to plasma protein were similar in males and females. There was no metabolic difference for NQ in male and female mice, rat or human liver microsomes.

Conclusions

These results indicated that the pharmacokinetic profiles of NQ were similar between male and female rats, except for a longer t1/2in male rats. The difference was not associated with plasma protein binding or hepatic metabolic clearance. Equivalent antiplasmodial activity was found for NQ in male and female mice infected withP. yoelii. This study will be helpful for the rational design of clinical trials for NQ.
Tumor retractor: a simple and novel instrument for brain tumor surgery
Authors: Lim Jaejoon , Sung Kyoung Su , Hwang So Jung , Chun Duk-Hee , Cho Kyung Gi
Published: February 2020

Background

It is important to secure a surgical space during brain tumor surgery. One of the commonly used methods is to retract the brain. We hypothesized that the tumor can be retracted and that the normal brain tissue retraction can be minimized during surgery, and thus, the degree of collateral damage caused by brain retraction would be reduced.

Methods

The tumor retractor had a 90°, hard, and sharp tip for fixation of the tumor. The distal part of the retractor has a malleable and thin blade structure. By adjusting the angle of the distal malleable part of the tumor retractor, the operator can make the retracting angle additionally. Retractors with thin blade can be used in a conventional self-retraction system. To pull and hold the tumor constantly, the tumor retractor is held by a self-retraction system. The surgical technique using a tumor retractor is as follows: The first step is to fix the retractor to the tumor. The second step is to pull the retractor in the operator’s desired direction by applying force. After the tumor is pulled by adjusting the degree of force and angle, the surgical arm should be held in place to maintain the tumor retracted state.

Results

The tumor retractor was used to minimize the brain retraction, pulling the tumor in the opposite direction from the surrounding brain tissue. In clinical cases, we can apply the tumor retractor with good surgical outcomes.

Conclusions

A tumor retractor can be used to pull a tumor and minimize the brain retraction.