bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and associated factors for burnout among attending general surgeons: a national cross-sectional survey
Authors: Celik Suleyman Utku , Aslan Alperen , Coskun Eylul , Coban Beyza Nur , Haner Zeynep , Kart Selin , Skaik Mahmoud N. I. , Kocer Merve Didem , Ozkan Bahar Busra , Akyol Cihangir
Published: January 2021

Background

Burnout resulting from long-term and unmanaged workplace stress is high among healthcare professionals, especially surgeons, and affects both individuals and the quality of patient care. The objective of this study was to determine the prevalence and associated factors for burnout among attending general surgeons and to identify possible preventive strategies.

Methods

A national cross-sectional survey using a 35-item questionnaire was conducted among members of the Turkish Surgical Society. The survey evaluated demographics, professional and practice characteristics, social participation, and burnout as well as interventions to deal with burnout. Burnout was defined as a high score on the emotional exhaustion (EE) and/or depersonalization (DP) subscales. Surgeons with high scores on both the EE and DP and a low score on personal accomplishment (PA) were considered to have severe burnout.

Results

Six hundred fifteen general surgeons completed the survey. The median EE, DP, and PA scores were 34 (IQR, 20–43), 9 (IQR, 4–16), and 36 (IQR, 30–42), respectively. Overall, the prevalence of burnout and severe burnout were 69.1 and 22.0%, respectively. On multivariable analysis, factors independently associated with burnout were working in a training and research hospital (OR = 3.34;P < 0.001) or state hospital (OR = 2.77;P = 0.001), working ≥ 60 h per week (OR = 1.57;P = 0.046), and less frequent participation in social activities (OR = 3.65;P < 0.001).

Conclusions

Burnout is an important problem among general surgeons with impacts and consequences for professionals, patients, and society. Considering that burnout is a preventable condition, systematic efforts to identify at-risk populations and to develop strategies to address burnout in surgeons are needed.
Assessing the contextual effect of community in the utilization of postnatal care services in Ghana
Authors: Dankwah Emmanuel , Feng Cindy , Kirychuck Shelley , Zeng Wu , Lepnurm Rein , Farag Marwa
Published: January 2021

Background

Inequalities in the use of postnatal care services (PNC) in Ghana have been linked to poor maternal and neonatal health outcomes. This has ignited a genuine concern that PNC interventions with a focus on influencing solely individual-level risk factors do not achieve the desired results. This study aimed to examine the community-level effect on the utilization of postnatal care services. Specifically, the research explored clusters of non-utilization of PNC services as well as the effect of community-level factors on the utilization of PNC services, with the aim of informing equity-oriented policies and initiatives.

Methods

The 2014 Ghana Demographic and Health Survey GDHS dataset was used in this study. Two statistical methods were used to analyze the data; spatial scan statistics were used to identify hotspots of non-use of PNC services and second two-level mixed logistic regression modeling was used to determine community-level factors associated with PNC services usage.

Results

This study found non-use of PNC services to be especially concentrated among communities in the Northern region of Ghana. Also, the analyses revealed that community poverty level, as well as community secondary or higher education level, were significantly associated with the utilization of PNC services, independent of individual-level factors. In fact, this study identified that a woman dwelling in a community with a higher concentration of poor women is less likely to utilize of PNC services than those living in communities with a lower concentration of poor women (Adjusted odds ratio (AOR) = 0.60, 95%CI: 0.44–0.81). Finally, 24.0% of the heterogeneity in PNC services utilization was attributable to unobserved community variability.

Conclusion

The findings of this study indicate that community-level factors have an influence on women’s health-seeking behavior. Community-level factors should be taken into consideration for planning and resource allocation purposes to reduce maternal health inequities. Also, high-risk communities of non-use of obstetric services were identified in this study which highlights the need to formulate community-specific strategies that can substantially shift post-natal use in a direction leading to universal coverage.
Patient-controlled admission contracts: a longitudinal study of patient evaluations
Authors: Nyttingnes Olav , Šaltytė Benth Jūratė , Ruud Torleif
Published: January 2021

Background

Mental health professionals usually decide patients’ access to inpatient care to ensure care based on need and potential benefit. The purpose of the current study is to investigate how patients evaluate admissions under a contract of Patient-Controlled Admissions (PCA), where the patient could initiate 5 day stays at a community mental health center at their own discretion.

Methods

Patients with a PCA contract in 2011 and 2012 were invited to participate in the study. Staff first recorded clinical baseline values for patients. Towards the end of each PCA stay, staff conducted a structured discharge interview of the admission with the patient. A structured follow-up interview evaluating the PCA arrangement 2 years after inclusion was also performed. We report frequencies from data on PCA requests, PCA admissions and the 2 year evaluation interview, and we used multiple regression models to explore predictors of perceived helpfulness and improvement from the PCA admissions.

Results

The included patients (n = 74) made 628 requests for PCAs during the 2 years after inclusion, and 507 PCAs took place. The five-day limit could not be upheld in 7.5% of PCAs. Patients rated PCAs as helping considerably (33.1%), a good deal (30.4%) or somewhat (21.1%), and reported feeling considerably (15.2%), a good deal (26.2%) or somewhat (36.3%) better during the admission. Significant predictors of helpfulness and feeling better were socializing more during the stay and reporting higher motivation to get away from a difficult situation or getting to the ward safety and calmness. A diagnosis of schizophrenia spectrum or bipolar disorder and more services from mental health specialist care also predicted feeling better during the PCA. In the two-year follow-up interview, 90% rated themselves as very or quite satisfied, and more than 90% would recommend PCAs to others.

Conclusions

The PCA arrangement was feasible and was frequently utilized by patients. Patients were satisfied with PCAs and the PCA arrangement. These short stays seemed particularly helpful for patients with a more severe diagnosis. Strong patient satisfaction gives reasons for testing and implementing increased patient influence on the mental health admission procedures in the form of PCAs.
Economic evaluation of alternative testing regimes and settings to detect undiagnosed HIV in Australia
Authors: Williams Owain D. , Dean Judith A. , Crothers Anna , Gilks Charles F. , Gow Jeff
Published: January 2021

Background

The study aimed to estimate the comparative costs per positive diagnosis of previously undetected HIV in three testing regimes: conventional; parallel and point of care (POC) testing. The regimes are analysed in six testing settings in Australia where infection is concentrated but with low prevalence.

Methods

A cost model was developed to highlight the trade-offs between test and economic efficiency from a provider perspective. First, an estimate of the number of tests needed to find a true (previously undiagnosed) positive diagnosis was made. Second, estimates of the average cost per positive diagnosis in whole of population (WoP) and men who have sex with men (MSM) was made, then third, aggregated to the total cost for diagnosis of all undetected infections.

Results

Parallel testing is as effective as conventional testing, but more economically efficient. POC testing provide two significant advantages over conventional testing: they screen out negatives effectively at comparatively lower cost and, with confirmatory testing of reactive results, there is no loss in efficiency. The average and total costs per detection in WoP are prohibitive, except for Home Self Testing. The diagnosis in MSM is cost effective in all settings, but especially using Home Self Testing when the individual assumes the cost of testing.

Conclusions

This study illustrates the trade-offs between economic and test efficiency and their interactions with population(s) prevalence. The efficient testing regimes and settings are presently under or not funded in Australia. Home Self Testing has the potential to dramatically increase testing rates at very little cost.
A multilevel study of patient-centered care perceptions in mental health teams
Authors: Durand François , Fleury Marie-Josée
Published: January 2021

Background

The successful combination of interprofessional collaboration in multidisciplinary teams with patient-centered care is necessary when it comes to delivering complex mental health services. Yet collaboration is challenging and patient-centered care is intricate to manage. This study examines correlates of patient-centered care such as team adaptivity and proactivity, collaboration, belief in interprofessional collaboration and informational role self-efficacy in multidisciplinary mental health teams.

Method

A cross-sectional multilevel survey design was used, based on self-administered bilingual validated questionnaires. Participants (N=314) were mental health professionals and managers working in public primary care or specialized mental health services, in inpatient or outpatient settings.

Results

This study showed that belief in interprofessional collaboration’s relationship with patient-centered perceptions is increased in teams with high collaboration. Collaboration is also found as a mediator, representing a process by which team adaptive and proactive behaviors are transformed into positive patient-centered perceptions.

Conclusions

Our results were in line with recent studies on team processes establishing that collaboration is a key component in multilevel examinations of predictors of patient-centered care. In terms of practice, our study showed that multidisciplinary teams should know that working hard on collaboration is an answer to the complexity of patient-centered care. Collaboration is related to the teams’ ability to respond to its challenges. It is also related to individuals’ beliefs central to the delivery of interprofessional care.
Prevalence of anthelmintic resistance of gastrointestinal nematodes in Polish goat herds assessed by the larval development test
Authors: Mickiewicz Marcin , Czopowicz Michał , Moroz Agata , Potărniche Adrian-Valentin , Szaluś-Jordanow Olga , Spinu Marina , Górski Paweł , Markowska-Daniel Iwona , Várady Marián , Kaba Jarosław
Published: January 2021

Background

Helminthic infections, in particular those caused by gastrointestinal nematodes (GIN), are found worldwide and are among the most economically important diseases of goats. Anthelmintic resistance (AR) in GIN of goats is currently present worldwide, and single- or multidrug resistant species are widespread. The aim of this study was to determine the prevalence of AR to benzimidazoles (BZ), macrocyclic lactones (ML) and imidazothiazoles represented by levamisole (LEV) in the Polish goat herds by using an in vitro larval development test, which is useful especially in large-scale epidemiological surveys.

Results

This cross-sectional study was conducted from September 2018 to June 2019 and enrolled 42 dairy goat herds scattered over the entire country. The most commonly used anthelmintic class in goat herds in Poland were BZ (92%), followed by ML (85%) and LEV (13%). BZ-resistant GIN populations were found in 37 herds (88%, CI 95%: 75 to 95%), ML-resistant GIN populations in 40 herds (95%, CI 95, 84 to 99%), and LEV-resistant GIN populations in 5 herds (12%, CI 95%: 5 to 25%). Multidrug resistance involving all three anthelmintic classes was found in 5 herds (12%, CI 95, 5 to 25%). Based on the morphological features of stage 3 larvae the main resistant GIN turned out to beHaemonchus contortusandTrichostrongylusspp. The use of BZ and frequency of anthelmintic treatments were significantly related to the presence of AR to BZ in Polish goat herds.

Conclusions

This cross-sectional study demonstrates the existence of AR to BZ, ML and LEV on Polish goat farms. Resistance to BZ and ML is widespread, while AR to LEV is currently at a low level. A considerable proportion of herds harbours multidrug resistant GIN, which requires further consideration. An effective anthelmintic treatment strategy, reasonable preventive measures and better understanding of the resistance-related management practices by farmers and veterinarians may delay further development of AR.
Sputum ACE2, TMPRSS2 and FURIN gene expression in severe neutrophilic asthma
Authors:   U-BIOPRED Consortium, Kermani Nazanin Zounemat , Song Woo-Jung , Badi Yusef , Versi Ali , Guo Yike , Sun Kai , Bhavsar Pank , Howarth Peter , Dahlen Sven-Erik , Sterk Peter J. , Djukanovic Ratko , Adcock Ian M. , Chung Kian Fan
Published: January 2021

Background

Patients with severe asthma may have a greater risk of dying from COVID-19 disease. Angiotensin converting enzyme-2 (ACE2) and the enzyme proteases, transmembrane protease serine 2 (TMPRSS2) and FURIN, are needed for viral attachment and invasion into host cells.

Methods

We examined microarray mRNA expression of ACE2, TMPRSS2 and FURIN in sputum, bronchial brushing and bronchial biopsies of the European U-BIOPRED cohort. Clinical parameters and molecular phenotypes, including asthma severity, sputum inflammatory cells, lung functions, oral corticosteroid (OCS) use, and transcriptomic-associated clusters, were examined in relation to gene expression levels.

Results

ACE2 levels were significantly increased in sputum of severe asthma compared to mild-moderate asthma. In multivariate analyses, sputum ACE2 levels were positively associated with OCS use and male gender. Sputum FURIN levels were significantly related to neutrophils (%) and the presence of severe asthma. In bronchial brushing samples, TMPRSS2 levels were positively associated with male gender and body mass index, whereas FURIN levels with male gender and blood neutrophils. In bronchial biopsies, TMPRSS2 levels were positively related to blood neutrophils. The neutrophilic molecular phenotype characterised by high inflammasome activation expressed significantly higher FURIN levels in sputum than the eosinophilic Type 2-high or the pauci-granulocytic oxidative phosphorylation phenotypes.

Conclusion

Levels of ACE2 and FURIN may differ by clinical or molecular phenotypes of asthma. Sputum FURIN expression levels were strongly associated with neutrophilic inflammation and with inflammasome activation. This might indicate the potential for a greater morbidity and mortality outcome from SARS-CoV-2 infection in neutrophilic severe asthma.
Comprehensive elaboration of glycemic variability in diabetic macrovascular and microvascular complications
Authors: Sun Bao , Luo Zhiying , Zhou Jiecan
Published: January 2021

Diabetes mellitus is the major risk factor for the development of macrovascular and microvascular complications. It is increasingly recognized that glycemic variability (GV), referring to oscillations in blood glucose levels and representing either short-term or long-term GV, is involved in the pathogenesis of diabetic complications and has emerged as a possible independent risk factor for them. In this review, we summarize the metrics and measurement of GV in clinical practice, as well as comprehensively elaborate the role and related mechanisms of GV in diabetic macrovascular and microvascular complications, aiming to provide the mechanism-based therapeutic strategies for clinicians to manage diabetes mellitus.
Effects of liraglutide on diastolic function parameters in patients with type 2 diabetes and coronary artery disease: a randomized crossover study
Authors: Kumarathurai Preman , Sajadieh Ahmad , Anholm Christian , Kristiansen Ole P. , Haugaard Steen B. , Nielsen Olav W.
Published: January 2021

Background

Diastolic dysfunction is highly prevalent in patients with type 2 diabetes mellitus (T2DM) and is associated with overweight, glucose dysregulation and coronary artery disease (CAD). The GLP-1 receptor agonist, liraglutide, has shown to induce weight loss and improve metabolic factors, thus modulating factors associated with diastolic dysfunction. We have previously reported the effects of liraglutide on systolic function, and in this current study we explore the effects of liraglutide on diastolic function parameters in patients with stable CAD, preserved left ventricular ejection fraction (LVEF), and newly diagnosed T2DM.

Methods

Thirty subjects were randomized to liraglutide or placebo intervention for 12 + 12-weeks in this double-blind cross-over study. 2D-echocardiography using tissue velocity imaging was used for assessment of diastolic function parameters. Early diastolic filling velocity (E), late atrial filling velocity (A), E-wave deceleration time (EDT) and E/A ratio was assessed from the pulse wave (PW)-Doppler velocity recording of the mitral inflow. Peak early diastolic annular velocities (e′) was measured from color tissue doppler images.

Results

Liraglutide, when compared to placebo, induced a significant reduction in average e′ and lateral e′ velocities (– 0.57 cm/s [– 1.05 to − 0.08] and –0.74 cm/s [–1.32 to –0.15], respectively). Adjusted for the concomitant increase in HR (+ 6.16 bpm [0.79 to 11.54], the changes were not significant. No significant changes in other diastolic function parameters were observed.

Conclusions

Liraglutide therapy did not improve any diastolic function parameters in subjects with T2DM, CAD, and preserved LVEF. Instead, a deterioration in e’ was observed, which was associated to an increase in heart rate induced by liraglutide therapy.

Trial registrationClinical Trial Registration:http://www.clinicaltrials.gov(unique identifier: NCT01595789) (first submitted May 8, 2012)
Dual SGLT-1 and SGLT-2 inhibition improves left atrial dysfunction in HFpEF
Authors: Bode David , Semmler Lukas , Wakula Paulina , Hegemann Niklas , Primessnig Uwe , Beindorff Nicola , Powell David , Dahmen Raphael , Ruetten Hartmut , Oeing Christian , Alogna Alessio , Messroghli Daniel , Pieske Burkert M. , Heinzel Frank R. , Hohendanner Felix
Published: January 2021

Background

Sodium–glucose linked transporter type 2 (SGLT-2) inhibition has been shown to reduce cardiovascular mortality in heart failure independently of glycemic control and prevents the onset of atrial arrhythmias, a common co-morbidity in heart failure with preserved ejection fraction (HFpEF). The mechanism behind these effects is not fully understood, and it remains unclear if they could be further enhanced by additional SGLT-1 inhibition. We investigated the effects of chronic treatment with the dual SGLT-1&2 inhibitor sotagliflozin on left atrial (LA) remodeling and cellular arrhythmogenesis (i.e. atrial cardiomyopathy) in a metabolic syndrome-related rat model of HFpEF.

Methods

17 week-old ZSF-1 obese rats, a metabolic syndrome-related model of HFpEF, and wild type rats (Wistar Kyoto), were fed 30 mg/kg/d sotagliflozin for 6 weeks. At 23 weeks, LA were imaged in-vivo by echocardiography. In-vitro, Ca2+ transients (CaT; electrically stimulated, caffeine-induced) and spontaneous Ca2+ release were recorded by ratiometric microscopy using Ca2+-sensitive fluorescent dyes (Fura-2) during various experimental protocols. Mitochondrial structure (dye: Mitotracker), Ca2+ buffer capacity (dye: Rhod-2), mitochondrial depolarization (dye: TMRE) and production of reactive oxygen species (dye: H2DCF) were visualized by confocal microscopy. Statistical analysis was performed with 2-way analysis of variance followed by post-hoc Bonferroni and student’s t-test, as applicable.

Results

Sotagliflozin ameliorated LA enlargement in HFpEF in-vivo. In-vitro, LA cardiomyocytes in HFpEF showed an increased incidence and amplitude of arrhythmic spontaneous Ca2+ release events (SCaEs). Sotagliflozin significantly reduced the magnitude of SCaEs, while their frequency was unaffected. Sotagliflozin lowered diastolic [Ca2+] of CaT at baseline and in response to glucose influx, possibly related to a ~ 50% increase of sodium sodium–calcium exchanger (NCX) forward-mode activity. Sotagliflozin prevented mitochondrial swelling and enhanced mitochondrial Ca2+ buffer capacity in HFpEF. Sotagliflozin improved mitochondrial fission and reactive oxygen species (ROS) production during glucose starvation and averted Ca2+ accumulation upon glycolytic inhibition.

Conclusion

The SGLT-1&2 inhibitor sotagliflozin ameliorated LA remodeling in metabolic HFpEF. It also improved distinct features of Ca2+-mediated cellular arrhythmogenesis in-vitro (i.e. magnitude of SCaEs, mitochondrial Ca2+ buffer capacity, diastolic Ca2+ accumulation, NCX activity). The safety and efficacy of combined SGLT-1&2 inhibition for the treatment and/or prevention of atrial cardiomyopathy associated arrhythmias should be further evaluated in clinical trials.
The damage and tolerance mechanisms of Phaffia rhodozyma mutant strain MK19 grown at 28 °C
Authors: Miao Li-Li , Chi Shuang , Hou Ting-Ting , Liu Zhi-Pei , Li Ying
Published: January 2021

Background

Phaffia rhodozyma has many desirable properties for astaxanthin production, including rapid heterotrophic metabolism and high cell densities in fermenter culture. The low optimal temperature range (17–21 °C) for cell growth and astaxanthin synthesis in this species presents an obstacle to efficient industrial-scale astaxanthin production. The inhibition mechanism of cell growth at > 21 °C in P. rhodozyma have not been investigated.

Results

MK19, a mutant P. rhodozyma strain grows well at moderate temperatures, its cell growth was also inhibited at 28 °C, but such inhibition was mitigated, and low biomass 6 g/L was obtained after 100 h culture. Transcriptome analysis indicated that low biomass at 28 °C resulted from strong suppression of DNA and RNA synthesis in MK19. Growth inhibition at 28 °C was due to cell membrane damage with a characteristic of low mRNA content of fatty acid (f.a.) pathway transcripts (acc, fas1, fas2), and consequent low f.a. content. Thinning of cell wall and low mannose content (leading to loss of cell wall integrity) also contributed to reduced cell growth at 28 °C in MK19. Levels of astaxanthin and ergosterol, two end-products of isoprenoid biosynthesis (a shunt pathway of f.a. biosynthesis), reached 2000 µg/g and 7500 µg/g respectively; ~2-fold higher than levels at 21 or 25 °C. Abundance of ergosterol, an important cell membrane component, compensated for lack of f.a., making possible the biomass production of 6 g/L for MK19 at 28 °C.

Conclusions

Inhibition of growth of P. rhodozyma at 28 °C results from blocking of DNA, RNA, f.a., and cell wall biosynthesis. In MK19, abundant ergosterol made possible biomass production 6 g/L at 28 °C. Significant accumulation of astaxanthin and ergosterol indicated an active MVA pathway in MK19 at 28 °C. Strengthening of the MVA pathway can be a feasible metabolic engineering approach for enhancement of astaxanthin synthesis in P. rhodozyma. The present findings provide useful mechanistic insights regarding adaptation of P. rhodozyma to 28 °C, and improved understanding of feasible metabolic engineering techniques for industrial scale astaxanthin production by this economically important yeast species.
Whole genome sequencing and metabolomics analyses reveal the biosynthesis of nerol in a multi-stress-tolerant Meyerozyma guilliermondii GXDK6
Authors: Mo Xueyan , Cai Xinghua , Hui Qinyan , Sun Huijie , Yu Ran , Bu Ru , Yan Bing , Ou Qian , Li Quanwen , He Sheng , Jiang Chengjian
Published: January 2021

Background

Nerol (C10H18O), an acyclic monoterpene, naturally presents in plant essential oils, and is used widely in food, cosmetics and pharmaceuticals as the valuable fragrance. Meanwhile, chemical synthesis is the only strategy for large-scale production of nerol, and the disadvantages of chemical synthesis greatly limit the production and its application. These defects drive the interests of researchers shift to the production of nerol by eco-friendly methods known as biosynthesis methods. However, the main technical bottleneck restricting the biosynthesis of nerol is the lacking of corresponding natural aroma-producing microorganisms.

Results

In this study, a novel multi-stress-tolerant probiotics Meyerozymaguilliermondii GXDK6 with aroma-producing properties was identified by whole genome sequencing and metabolomics technology. GXDK6 showed a broad pH tolerance in the range of 2.5–10.0. The species also showed salt tolerance with up to 12% NaCl and up to 18% of KCl or MgCl2. GXDK6 exhibited heavy-metal Mn2+ tolerance of up to 5494 ppm. GXDK6 could also ferment with a total of 21 kinds of single organic matter as the carbon source, and produce abundant aromatic metabolites. Results from the gas chromatography–mass spectrometry indicated the production of 8–14 types of aromatic metabolites (isopentanol, nerol, geraniol, phenylethanol, isobutanol, etc.) when GXDK6 was fermented up to 72 h with glucose, sucrose, fructose, or xylose as the single carbon source. Among them, nerol was found to be a novel aromatic metabolite from GXDK6 fermentation, and its biosynthesis mechanism had also been further revealed.

Conclusion

A novel aroma-producing M. guilliermondii GXDK6 was identified successfully by whole genome sequencing and metabolomics technology. GXDK6 showed high multi-stress-tolerant properties with acid–base, salty, and heavy-metal environments. The aroma-producing mechanism of nerol in GXDK6 had also been revealed. These findings indicated the aroma-producing M. guilliermondii GXDK6 with multi-stress-tolerant properties has great potential value in the fermentation industry.
YAP manipulates proliferation via PTEN/AKT/mTOR-mediated autophagy in lung adenocarcinomas
Authors: Xu Wei , Zhang Mingjiong , Li Yue , Wang Yu , Wang Kai , Chen Qiaoyu , Zhang Runjie , Song Weiwei , Huang Qiqing , Zhao Weihong , Wu Jianqing
Published: January 2021

Background

Autophagy is a double-edged sword during the initiation and progression of multiple tumors. The Hippo pathway effector YAP has been proved to be involved in autophagy processes. The present study aimed to investigate how YAP regulates cell proliferation via autophagy in lung adenocarcinomas (LUAD).

Methods

Data of LUAD chip GSE43458 was obtained from Gene Expression Omnibus (GEO). RT-qPCR and Western blot were performed to assess YAP expression in LUAD cell lines. CCK-8 assay, xenograft tumor model, immunochemistry and GFP-mRFP-LC3 fusion proteins were utilized to evaluate the effect of YAP on autophagy of LUAD cells in vitro and in vivo. Autophagy inhibitor treatment and rescue experiments were carried out to elucidate the mechanism by which YAP manipulates autophagy in LUAD cells.

Results

YAP was significantly overexpressed in samples of LUAD patients and its expression level is related to 5-year survival. YAP manipulated the proliferation and autophagy in A549 and H1299 LUAD cells. YAP could induce activation of Akt/mTOR signaling pathway via suppressing PTEN in a Hippo-pathway-dependent manner. 3-Methyladenine impeded autophagy flux and promoted the proliferation in vitro and in vivo.

Conclusions

Hippo pathway critical transcriptional coactivators YAP manipulates the proliferation of lung adenocarcinoma, which is regulated by PTEN/AKT/mTOR autophagic signaling.
MicroRNA regulation of cancer stem cells in the pathogenesis of breast cancer
Authors: Niu Tong , Zhang Weiwei , Xiao Wei
Published: January 2021

Breast cancer is the most common cancer among women and accounts for 30% of all female malignancies worldwide. Breast cancer stem cells (BCSCs) are a small population of breast cancer cells that exhibit multiple characteristics including differentiation capacity, self-renewal and therapeutic resistance. Recently, BCSCs have attracted attention due to their modulation of breast tumor behaviors and drug resistance. miRNAs are small noncoding mRNAs involved in virtually all biological processes, including stem cell development, maintenance and differentiation. In breast cancer, miRNAs appear to be multi-faceted since they can act as either suppressors or oncogenes to regulate breast cancer progression. This review summarizes the critical roles of miRNAs in regulating multiple signaling pathways such as Wnt/β-catenin, Notch, PI3K/AKT/mTOR, BMI-1 and STAT3 that are important for the BCSC maintenance.
ADAM10 is involved in the oncogenic process and chemo-resistance of triple-negative breast cancer via regulating Notch1 signaling pathway, CD44 and PrPc
Authors: Cheng Yuanyuan , Lin Lishuang , Li Xiaoyan , Lu Aiqi , Hou Chenjian , Wu Qian , Hu Xiaomu , Zhou Zhongwen , Chen Zhongqing , Tang Feng
Published: January 2021

Background

Triple-negative breast cancer (TNBC) is the most challenging breast cancer subtype to treat, because it is so aggressive with shorter survival. Chemotherapy remains the standard treatment due to the lack of specific and effective molecular targets. The aim of the present study is to investigate the potential roles of A Disintegrin and Metalloproteinase 10 (ADAM10) on TNBC cells and the effects of combining ADAM10 expression and neoadjuvant chemotherapy treatment (NACT) to improve the overall survival in breast cancer patients.

Methods

Using a series of breast cancer cell lines, we measured the expression of ADAM10 and its substrates by quantitative real-time PCR assay (qRT-PCR) and western blot analysis. Cell migration and invasion, cell proliferation, drug sensitivity assay, cell cycle and apoptosis were conducted in MDA-MB-231 cells cultured with ADAM10 siRNA. The effect of ADAM10 down-regulation by siRNA on its substrates was assessed by western blot analysis. We performed immunohistochemical staining for ADAM10 in clinical breast cancer tissues in 94 patients receiving NACT.

Results

The active form of ADAM10 was highly expressed in TNBC cell lines. Knockdown of ADAM10 in MDA-MB-231 cells led to a significant decrease in cell proliferation, migration, invasion and the IC50value of paclitaxel and adriamycin, while induced cell cycle arrest and apoptosis. And these changes were correlated with down-regulation of Notch signaling, CD44 and cellular prion protein (PrPc). In clinical breast cancer cases, a high ADAM10 expression in pre-NACT samples was strongly associated with poorer response to NACT and shorter overall survival.

Conclusions

These data suggest the previously unrecognized roles of ADAM10 in contributing to the progression and chemo-resistance of TNBC.
Variation of physical durability between LLIN products and net use environments: summary of findings from four African countries
Authors: Kilian Albert , Obi Emmanuel , Mansiangi Paul , Abílio Ana Paula , Haji Khamis Ameir , Blaufuss Sean , Olapeju Bolanle , Babalola Stella , Koenker Hannah
Published: January 2021

Background

Physical durability of long-lasting-insecticidal nets (LLIN) is an important aspect of the effectiveness of LLIN as a malaria prevention tool, but there is limited data on performance across locations and products. This secondary analysis of data from the VectorWorks project from 10 sites in four African countries involving six LLIN brands provides such data.

Methods

A total of 4672 campaign nets from 1976 households were recruited into prospective cohort studies 2–6 months after distribution through campaigns and followed for 3 years in Mozambique, Nigeria, DRC and Zanzibar, Tanzania. LLIN products included two 100 denier polyester LLIN (DawaPlus® 2.0, PermaNet® 2.0) distributed in five sites and four 150 denier polyethylene LLIN (Royal Sentry®, MAGNet®, DuraNet©, Olyset™ Net) distributed in five sites. Primary outcome was LLIN survival in serviceable condition and median survival in years. Net use environment and net care variables were collected during four household surveys. Determinants of physical durability were explored by survival analysis and Cox regression models with risk of failure starting with the first hanging of the net.

Results

Definite outcomes for physical durability were obtained for 75% of study nets. After 31 to 37 months survival in serviceable condition varied between sites by 63 percentage-points, from 17 to 80%. Median survival varied by 3.7 years, from 1.6 to 5.3 years. Similar magnitude of variation was seen for polyethylene and polyester LLIN and for the same brand. Cox regression showed increasing net care attitude in combination with exposure to net related messages to be the strongest explanatory variable of survival. However, differences between countries also remained significant. In contrast, no difference was seen for LLIN material types.

Conclusions

Variation in net use environment and net care is the main reason for differences in the physical durability of LLIN products in different locations. While some of these factors have been identified to work across countries, other factors remain poorly defined and further investigation is needed in this area. Grouping LLIN brands by similar textile characteristics, such as material or yarn strength, is insufficient to distinguish LLIN product performance suggesting a more differentiated, composite metric is needed.
Molecular characterization of G6PD mutations reveals the high frequency of G6PD Aures in the Lao Theung population
Authors: Sanephonasa Amkha , Cheepsunthorn Chalisa Louicharoen , Khaminsou Naly , Savongsy Onekham , Nuchprayoon Issarang , Leecharoenkiat Kamonlak
Published: January 2021

Background

The prevalence and genotypes of G6PD deficiency vary worldwide, with higher prevalence in malaria endemic areas. The first-time assessment of G6PD deficiency prevalence and molecular characterization ofG6PDmutations in the Lao Theung population were performed in this study.

Methods

A total of 252 unrelated Lao Theung participants residing in the Lao People’s Democratic Republic (PDR) were recruited. All participant samples were tested for G6PD enzyme activity andG6PDgene mutations. The amplification refractory mutation system (ARMS)-PCR for detecting G6PD Aures was developed.

Results

TheG6PDmutations were detected in 11.51% (29/252) of the participants. Eight G6PD mutations were detected. The G6PD Aures was the most common mutation identified in this cohort, which represented 58.62% (17/29) of all mutation. The mutation pattern was homogenous, predominantly involving the G6PD Aures mutation (6.75%), followed by 1.19% G6PD Union and 0.79% each G6PD Jammu, G6PD Mahidol and G6PD Kaiping. One subject (0.4%) each carried G6PD Viangchan and G6PD Canton. Interestingly, one case of coinheritance of G6PD Aures and Quing Yan was detected in this cohort. Based on levels of G6PD enzyme activity, the prevalence of G6PD deficiency in the Lao Theung population was 9.13% (23/252). The prevalence of G6PD deficient males and females (activity < 30%) in the Lao Theung population was 6.41% (5/78) and 1.72% (3/174), respectively, and the prevalence of G6PD intermediate (activity 30–70%) was 5.95% (15/252).

Conclusions

The G6PD Aures mutation is highly prevalent in the Lao Theung ethnic group. The common G6PD variants in continental Southeast Asian populations, G6PD Viangchan, Canton, Kaiping, Union and Mahidol, were not prevalent in this ethnic group. The technical simplicity of the developed ARMS-PCR will facilitate the final diagnosis of the G6PD Aures.
Spatio-temporal and -spectral feature maps in photoplethysmography imaging and infrared thermography
Authors: Paul Michael , Behr Sabrina Caprice , Weiss Christoph , Heimann Konrad , Orlikowsky Thorsten , Leonhardt Steffen
Published: January 2021

Background

Only a small fraction of the information available is generally used in the majority of camera-based sensing approaches for vital sign monitoring. Dedicated skin pixels, for example, fall into this category while other regions are often disregarded early in the processing chain.

Methods

We look at a simple processing chain for imaging where a video stream is converted to several other streams to investigate whether other image regions should also be considered. These streams are generated by mapping spatio-temporal and -spectral features of video segments and, thus, compressing the information contained in several seconds of video and encoding these in a new image. Two typical scenarios are provided as examples to study the applicability of these maps: face videos in a laboratory setting and measurements of a baby in the neonatal intensive care unit. Each measurement consists of the synchronous recording of photoplethysmography imaging (PPGI) and infrared thermography (IRT). We report the results of a visual inspection of those maps, evaluate the root mean square (RMS) contrast of foreground and background regions, and use histogram intersections as a tool for similarity measurements.

Results

The maps allow us to distinguish visually between pulsatile foreground objects and an image background, which is found to be a noisy pattern. Distortions in the maps could be localized and the origin could be discovered. The IRT highlights subject contours for the heart frequency band, while silhouettes show strong signals in PPGI. Reflections and shadows were found to be sources of signals and distortions. We can testify advantages for the use of near-infrared light for PPGI. Furthermore, a difference in RMS contrast for pulsatile and non-pulsatile regions could be demonstrated. Histogram intersections allowed us to differentiate between the background and foreground.

Conclusions

We introduced new maps for the two sensing modalities and presented an overview for three different wavelength ranges. The maps can be used as a tool for visualizing aspects of the dynamic information hidden in video streams without automation. We propose focusing on an indirect method to detect pulsatile regions by using the noisy background pattern characteristic, for example, based on the histogram approach introduced.
Trimester effects of source-specific PM10 on birth weight outcomes in the Avon Longitudinal Study of Parents and Children (ALSPAC)
Authors: Chen Yingxin , Hodgson Susan , Gulliver John , Granell Raquel , Henderson A. John , Cai Yutong , Hansell Anna L.
Published: January 2021

Background

Evidence suggests that exposure to particulate matter with aerodynamic diameter less than 10 μm (PM10) is associated with reduced birth weight, but information is limited on the sources of PM10 and exposure misclassification from assigning exposures to place of residence at birth.

Methods

Trimester and source-specific PM10 exposures (PM10 from road source, local non-road source, and total source) in pregnancy were estimated using dispersion models and a full maternal residential history for 12,020 births from the Avon longitudinal study of parents and children (ALSPAC) cohort in 1990–1992 in the Bristol area. Information on birth outcomes were obtained from birth records. Maternal sociodemographic and lifestyle factors were obtained from questionnaires. We used linear regression models for continuous outcomes (birth weight, head circumference (HC), and birth length (BL) and logistic regression models for binary outcomes (preterm birth (PTB), term low birth weight (TLBW) and small for gestational age (SGA)). Sensitivity analysis was performed using multiple imputation for missing covariate data.

Results

After adjustment, interquartile range increases in source specific PM10 from traffic were associated with 17 to 18% increased odds of TLBW in all pregnancy periods. We also found odds of TLBW increased by 40% (OR: 1.40, 95%CI: 1.12, 1.75) and odds of SGA increased by 18% (OR: 1.18, 95%CI: 1.05, 1.32) per IQR (6.54 μg/m3) increase of total PM10 exposure in the third trimester.

Conclusion

This study adds to evidence that maternal PM10 exposures affect birth weight, with particular concern in relation to exposures to PM10 from road transport sources; results for total PM10 suggest greatest effect in the third trimester. Effect size estimates relate to exposures in the 1990s and are higher than those for recent studies – this may relate to reduced exposure misclassification through use of full residential history information, changes in air pollution toxicity over time and/or residual confounding.
Clinico-microbiological profile of Burkholderia cepacia keratitis: a case series
Authors: Ho Ming-Chih , Kang Eugene Yu-Chuan , Yeh Lung-Kun , Ma David H. K. , Lin Hsin-Chiung , Tan Hsin-Yuan , Chen Hung-Chi , Hsiao Ching-Hsi
Published: January 2021

Background

Burkholderia cepacia, an opportunistic pathogen mainly affecting patients with cystic fibrosis or immunocompromised, has rarely been documented as a cause of corneal infection. The clinical and microbiological profiles of B. cepacia keratitis are reported herein.

Methods

We retrospectively reviewed the medical record of 17 patients with culture-proven B. cepacia keratitis, treated between 2000 and 2019 at Chang Gung Memorial Hospital, Taiwan. Our data included predisposing factors, clinical presentations, treatments, and visual outcomes of B. cepacia keratitis as well as the drug susceptibility of the causative agent.

Results

The most common predisposing factor for B. cepacia keratitis was preexisting ocular disease (seven, 41.2%), particularly herpetic keratitis (five). Polymicrobial infection was detected in seven (41.2%) eyes. All B. cepacia isolates were susceptible to ceftazidime. Main medical treatments included levofloxacin or ceftazidime. Surgical treatment was required in five (29.4%) patients. Only four (23.5%) patients exhibited final visual acuity better than 20/200.

Conclusions

B. cepacia keratitis primarily affects patients with preexisting ocular disease, particularly herpetic keratitis, and responds well to ceftazidime or fluoroquinolones. However, the visual outcomes are generally poor.
Children’s outdoor active mobility behaviour and neighbourhood safety: a systematic review in measurement methods and future research directions
Authors: Zougheibe Roula , Xia Jianhong (Cecilia) , Dewan Ashraf , Gudes Ori , Norman Richard
Published: January 2021

Background

Numerous studies have examined the association between safety and primary school-aged children’s forms of active mobility. However, variations in studies’ measurement methods and the elements addressed have contributed to inconsistencies in research outcomes, which may be forming a barrier to advancing researchers’ knowledge about this field. To assess where current research stands, we have synthesised the methodological measures in studies that examined the effects of neighbourhood safety exposure (perceived and measured) on children’s outdoor active mobility behaviour and used this analysis to propose future research directions.

Method

A systematic search of the literature in six electronic databases was conducted using pre-defined eligibility criteria and was concluded in July 2020. Two reviewers screened the literature abstracts to determine the studies’ inclusion, and two reviewers independently conducted a methodological quality assessment to rate the included studies.

Results

Twenty-five peer-reviewed studies met the inclusion criteria. Active mobility behaviour and health characteristics were measured objectively in 12 out of the 25 studies and were reported in another 13 studies. Twenty-one studies overlooked spatiotemporal dimensions in their analyses and outputs. Delineations of children’s neighbourhoods varied within 10 studies’ objective measures, and the 15 studies that opted for subjective measures. Safety perceptions obtained in 22 studies were mostly static and primarily collected via parents, and dissimilarities in actual safety measurement methods were present in 6 studies. The identified schematic constraints in studies’ measurement methods assisted in outlining a three-dimensional relationship between ‘what’ (determinants), ‘where’ (spatial) and ‘when’ (time) within a methodological conceptual framework.

Conclusions

The absence of standardised measurement methods among relevant studies may have led to the current diversity in findings regarding active mobility, spatial (locality) and temporal (time) characteristics, the neighbourhood, and the representation of safety. Ignorance of the existing gaps and heterogeneity in measures may impact the reliability of evidence and poses a limitation when synthesising findings, which could result in serious biases for policymakers. Given the increasing interest in children’s health studies, we suggested alternatives in the design and method of measures that may guide future evidence-based research for policymakers who aim to improve children’s active mobility and safety.
Measuring the impact of spatial perturbations on the relationship between data privacy and validity of descriptive statistics
Authors: Broen Kelly , Trangucci Rob , Zelner Jon
Published: January 2021

Background

Like many scientific fields, epidemiology is addressing issues of research reproducibility. Spatial epidemiology, which often uses the inherently identifiable variable of participant address, must balance reproducibility with participant privacy. In this study, we assess the impact of several different data perturbation methods on key spatial statistics and patient privacy.

Methods

We analyzed the impact of perturbation on spatial patterns in the full set of address-level mortality data from Lawrence, MA during the period from 1911 to 1913. The original death locations were perturbed using seven different published approaches to stochastic and deterministic spatial data anonymization. Key spatial descriptive statistics were calculated for each perturbation, including changes in spatial pattern center, Global Moran’s I, Local Moran’s I, distance to the k-th nearest neighbors, and the L-function (a normalized form of Ripley’s K). A spatially adapted form of k-anonymity was used to measure the privacy protection conferred by each method, and its compliance with HIPAA and GDPR privacy standards.

Results

Random perturbation at 50 m, donut masking between 5 and 50 m, and Voronoi masking maintain the validity of descriptive spatial statistics better than other perturbations. Grid center masking with both 100 × 100 and 250 × 250 m cells led to large changes in descriptive spatial statistics. None of the perturbation methods adhered to the HIPAA standard that all points have a k-anonymity > 10. All other perturbation methods employed had at least 265 points, or over 6%, not adhering to the HIPAA standard.

Conclusions

Using the set of published perturbation methods applied in this analysis, HIPAA and GDPR compliant de-identification was not compatible with maintaining key spatial patterns as measured by our chosen summary statistics. Further research should investigate alternate methods to balancing tradeoffs between spatial data privacy and preservation of key patterns in public health data that are of scientific and medical importance.