bluuebunny/crossref_metadata_2025 huggingface dataset:
Lapatinib sensitivity in nasopharyngeal carcinoma is modulated by SIRT2-mediated FOXO3 deacetylation
Authors: Aimjongjun Sathid , Mahmud Zimam , Jiramongkol Yannasittha , Alasiri Glowi , Yao Shang , Yagüe Ernesto , Janvilisri Tavan , Lam Eric W.-F.
Published: November 2019

Background

Chemoresistance is an obstacle to the successful treatment of nasopharyngeal carcinoma (NPC). Lapatinib is a targeted tyrosine kinase inhibitor therapeutic drug also used to treat NPC, but high doses are often required to achieve a result. To investigate the mechanism for the development of Lapatinib resistance, we characterised a number of NPC cell lines to determine the role of FOXO3 and sirtuins in regulating NPC resistance.

Methods

Sulforhodamine B (SRB) assays, Clonogenic assays, Protein extraction, quantification and western blotting, RT qPCR, Co-immunoprecipitation assay.

Results

To explore novel treatment strategies, we first characterized the Lapatinib-sensitivity of a panel of NPC cell lines by SRB and clonogenic cytotoxic assays and found that the metastatic NPC (C666–1 and 5-8F) cells are highly resistant whereas the poorly metastatic lines (6-10B, TW01 and HK-1) are sensitive to Lapatinib. Western blot analysis of the Lapatinib-sensitive 6-10B and resistant 5-8F NPC cells showed that the expression of phosphorylated/inactive FOXO3 (P-FOXO3;T32), its target FOXM1 and its regulator SIRT2 correlate negatively with Lapatinib response and sensitivity, suggesting that SIRT2 mediates FOXO3 deacetylation to promote Lapatinib resistance. In agreement, clonogenic cytotoxic assays using wild-type and foxo1/3/4−/− mouse embryonic fibroblasts (MEFs) showed that FOXO1/3/4-deletion significantly attenuates Lapatinib-induced cytotoxicity, confirming that FOXO proteins are essential for mediating Lapatinib response. SRB cell viability assays using chemical SIRT inhibitors (i.e. sirtinol, Ex527, AGK2 and AK1) revealed that all SIRT inhibitors can reduce NPC cell viability, but only the SIRT2-specific inhibitors AK1 and AGK2 further enhance the Lapatinib cytotoxicity. Consistently, clonogenic assays demonstrated that the SIRT2 inhibitors AK1 and AGK2 as well as SIRT2-knockdown increase Lapatinib cytotoxicity further in both the sensitive and resistant NPC cells. Co-immunoprecipitation studies showed that besides Lapatinib treatment, SIRT2-pharmaceutical inhibition and silencing also led to an increase in FOXO3 acetylation. Importantly, SIRT2 inhibition and depletion further enhanced Lapatinib-mediated FOXO3-acetylation in NPC cells.

Conclusion

Collectively, our results suggest the involvement of SIRT2-mediated FOXO3 deacetylation in Lapatinib response and sensitivity, and that SIRT2 can specifically antagonise the cytotoxicity of Lapatinib through mediating FOXO3 deacetylation in both sensitive and resistant NPC cells. The present findings also propose that SIRT2 can be an important biomarker for metastatic and Lapatinib resistant NPC and that targeting the SIRT2-FOXO3 axis may provide novel strategies for treating NPC and for overcoming chemoresistance.
Circulating tumour DNA (ctDNA) as a biomarker in metachronous melanoma and colorectal cancer- a case report
Authors: Calapre Leslie , Warburton Lydia , Millward Michael , Gray Elin S.
Published: November 2019

Background

Circulating tumour DNA (ctDNA) has emerged as a promising blood-based biomarker for monitoring disease status of patients with advanced cancers. The presence of ctDNA in the blood is a result of biological processes, namely tumour cell apoptosis and/or necrosis, and can be used to monitor different cancers by targeting cancer-specific mutation.

Case presentation

We present the case of a 67 year old Caucasian male that was initially treated with BRAF inhibitors followed by anti-CTLA4 and then anti-PD1 immunotherapy for metastatic melanoma but later developed colorectal cancer. The kinetics of ctDNA derived from each cancer type were monitored targeting BRAF V600R (melanoma) and KRAS G13D (colon cancer), specifically reflected the status of the patient’s tumours. In fact, the discordant pattern of BRAF and KRAS ctDNA was significantly correlated with the clinical response of melanoma to pembrolizumab treatment and progression of colorectal cancer noted by PET and/or CT scan. Based on these results, ctDNA can be used to specifically clarify disease status of patients with metachronous cancers.

Conclusions

Using cancer-specific mutational targets, we report here for the first time the efficacy of ctDNA to accurately provide a comprehensive outlook of the tumour status of two different cancers within one patient. Thus, ctDNA analysis has a potential clinical utility to delineate clinical information in patients with multiple cancer types.
Comparability of three intraocular pressure measurement: iCare pro rebound, non-contact and Goldmann applanation tonometry in different IOP group
Authors: Chen Min , Zhang Lina , Xu Jia , Chen Xinyi , Gu Yuxiang , Ren Yuping , Wang Kaijun
Published: November 2019

Background

Measurement of intraocular pressure (IOP) is essential for glaucoma patients. Many factors such as central corneal thickness (CCT) can affect the accuracy of IOP measurement. The purpose of this study was to evaluate the agreement of IOP measured by non-contact tonometer (NCT), iCare pro rebound tonometer (iCare), and Goldmann applanation tonometer (GAT) in different IOP group.

Methods

This was a Hospital-based cross-sectional study. Two hundred subjects were enrolled in this study. All subjects underwent IOP measurement using an NCT–iCare–GAT sequence. Bland-Altman, Pearson correlation and intraclass correlation analysis were performed using SPSS 17.0 software. The influence of CCT on each IOP measurement methods was evaluated by linear regression analysis.

Results

The mean difference (Δ) of NCT–GAT did not differ from (Δ) iCare–GAT in IOP < 10 and 10–21 mmHg group. However, (Δ) NCT–GAT was significantly higher than (Δ) iCare–GAT in IOP 22–30 and > 30 mmHg group (P < 0.05). Bland–Altman analysis showed significant agreement between the three devices (P < 0.01). IOP measurements of the three methods were significantly correlated with CCT (P < 0.01).

Conclusions

ICare pro shows a higher agreement with GAT over a wide range of IOP compared with NCT. The consistency between the three tonometers was similar in a low and normal IOP range. However, NCT shows a greater overestimate of IOP in moderate and higher IOP group. The variability of IOP measurement affected by CCT is NCT > iCare pro > GAT.
Study protocol: a clinical trial for improving mental health screening for Aboriginal and Torres Strait Islander pregnant women and mothers of young children using the Kimberley Mum's Mood Scale
Authors: Carlin Emma , Blondell Sarah J. , Cadet-James Yvonne , Campbell Sandra , Williams Melissa , Engelke Catherine , Taverner Des , Marriott Rhonda , Edmonds Karen , Atkinson David , Marley Julia V.
Published: November 2019

Background

Improving the rates of, and instruments used in, screening for perinatal depression and anxiety among Aboriginal and Torres Strait Islander women are important public health priorities. The Kimberley Mum’s Mood Scale (KMMS) was developed and later validated as an effective and acceptable perinatal depression and anxiety screening tool for the Kimberley region under research conditions. Other regions have expressed interest in using the KMMS with perinatal Aboriginal and Torres Strait Islander women. It is, however, important to re-evaluate the KMMS in a larger Kimberley sample via a real world implementation study, and to test for applicability in other remote and regional environments before recommendations for wider use can be made. This paper outlines the protocol for evaluating the process of implementation and establishing the ‘real world’ validity and acceptability of the KMMS in the Kimberley, Pilbara and Far North Queensland in northern Australia.

Methods

The study will use a range of quantitative and qualitative methods across all sites. KMMS validation/revalidation internal consistency of Part 1 will be determined using Cronbach’s alpha. Equivalence for identifying risk of depression and anxiety compared to a standard reference assessment will be determined from receiver operating characteristic curves. Sensitivity and specificity will be determined based on these cut-points. Qualitative methods of phenomenology will be used to explore concepts of KMMS user acceptability (women and health professionals). Additional process evaluation methods will collate, assess and report on KMMS quality review data, consultations with health service administrators and management, field notes, and other documentation from the research team. This information will be reported on using the Dynamic Sustainability Framework.

Discussion

This project is contributing to the important public health priority of screening Aboriginal and Torres Strait Islander women for perinatal depression and anxiety with tools that are meaningful and responsive to cultural and clinical needs. Identifying and addressing barriers to implementation contributes to our understanding of the complexity of improving routine clinical practie.

Trial registration

The study was registered retrospectively on 15/05/2019 with the Australian and New Zealand Clinical Trial registry (ACTRN12619000580178).
Delay in treatment seeking and associated factors among suspected pulmonary tuberculosis patients in public health facilities of Adama town, eastern Ethiopia
Authors: Wondawek Tirusew Maru , Ali Musa Mohammed
Published: November 2019

Background

In low-income countries, delays in treatment seeking among tuberculosis patients contribute to easy transmission and high prevalence of tuberculosis.

Objective

The aim of this study was to determine the magnitude of delays in treatment-seeking and risk factors among pulmonary tuberculosis suspected patients in health facilities located in Adama, Ethiopia.

Method

A health-facility based cross-sectional study was conducted at Adama from December 20, 2015, to March 1, 2016, among 598 tuberculosis suspected patients. Data was collected from all study participants on the same day of tuberculosis diagnosis using a structured questionnaire. Epi-Info 3.5.3 and Statistical package for the social sciences (SPSS) version 16.0 were used for data entry and analysis respectively. A bivariate and multivariable regression model was used to investigate the association between delay in seeking-treatment and various factors. Odds ratio with 95% CI and P-value < 0.05 were considered as cut off point to measure the strength and significance of the association.

Results

Among 598 pulmonary tuberculosis suspected patients, 79 (13.2%) were smear-positive. Among smear-positive participants, 61(77.2%) delayed seeking treatment and 275 (46%) patients delayed seeking treatment for > 30 days. The following factors were significantly associated with a delay in seeking treatment: female sex OR = 1.57, 95% CI (1.14, 2.18), low monthly income OR = 1.45, 95% CI (1.05, 2.01), lack of knowledge regarding tuberculosis OR = 1.67, 95% CI (1.13, 2.48), and cure rate of tuberculosis OR = 1.836, 95% CI (1.25, 2.69).

Conclusion

Nearly half of pulmonary tuberculosis suspected patients delayed seeking treatment in our study area. Female sex, low income, family size of five and greater, no knowledge about tuberculosis and cure rate were factors contributing to delay in treatment-seeking among suspected tuberculosis patients.
Autotransplantation of mature impacted tooth to a fresh molar socket using a 3D replica and guided bone regeneration: two years retrospective case series
Authors: Wu Ye , Chen Jiaming , Xie Fuping , Liu Huanhuan , Niu Gang , Zhou Lin
Published: November 2019

Background

The aim of this study was to evaluate the clinical outcome of autotransplantation of mature third molars to fresh molar extraction sockets using 3D replicas.

Methods

Ten patients underwent teeth autotransplantation with or without GBR. We observed the mobility, percussion, radiography examination, the probing depth and the masticatory function of the transplanted teeth during 2 years following up, which were transplanted into fresh molar sockets by using 3D replicas, and GBR when it is necessary.

Results

The average extra-oral time of donor tooth had been shortened to 1.65 min when used the 3D replica. Some probing depth of the transplanted tooth were deeper than 3 mm at 4 or 5 weeks temporarily. And one patient felt slight sensitive when chewing with soft food at 4 weeks, then disappeared. The clinical examination of the autotransplantation teeth during 1 year follow-up showed no sign of failure.

Conclusions

The tooth autotransplantation using 3D replica with or without GBR is an effective method which can reduce the extra-oral time of the donor teeth and may result in less failure.
Specialty choice determinants among Mexican medical students: a cross-sectional study
Authors: Gutiérrez-Cirlos Carlos , Naveja J. Jesús , García-Minjares Manuel , Martínez-González Adrián , Sánchez-Mendiola Melchor
Published: November 2019

Background

The choice of medical specialty is related to multiple factors, students’ values, and specialty perceptions. Research in this area is needed in low- and middle-income countries, where the alignment of specialty training with national healthcare needs has a complex local interdependency. The study aimed to identify factors that influence specialty choice among medical students.

Methods

Senior students at the National Autonomous University of Mexico (UNAM) Faculty of Medicine answered a questionnaire covering demographics, personal experiences, vocational features, and other factors related to specialty choice. Chi-square tests and factor analyses were performed.

Results

The questionnaire was applied to 714 fifth-year students, and 697 provided complete responses (response rate 81%). The instrument Cronbach’s alpha was 0.8. The mean age was 24 ± 1 years; 65% were women. Eighty percent of the students wanted to specialize, and 60% had participated in congresses related to the specialty of interest. Only 5% wanted to remain as general practitioners. The majority (80%) wanted to enter a core specialty: internal medicine (29%), general surgery (24%), pediatrics (11%), gynecology and obstetrics (11%) and family medicine (4%). The relevant variables for specialty choice were grouped in three dimensions: personal values that develop and change during undergraduate training, career needs to be satisfied, and perception of specialty characteristics.

Conclusions

Specialty choice of medical students in a middle-income country public university is influenced by the undergraduate experience, the desire to study a subspecialty and other factors (including having skills related to the specialty and type of patients).
Intern preparedness for the CanMEDS roles and the Dunning-Kruger effect: a survey
Authors: Prozesky Detlef Richard , Molwantwa Mmoloki Cornelius , Nkomazana Oathokwa , Kebaetse Masego Baitseng
Published: November 2019

Background

The purpose of this study was to determine whether the first cohort of graduates from a new undergraduate medical programme in Botswana were adequately prepared for internship.

Methods

The authors surveyed 27 interns and 13 intern supervisors on site, who rated intern preparedness for 44 tasks using a previously validated instrument. Tasks were grouped according to the seven roles of the physician in the CanMEDS framework and Cronbach α values confirmed internal consistency. To determine the direction of differences between intern and supervisor ratings for tasks Likert scale ratings were treated as interval data and mean scores calculated. Rating frequencies for each role were compared using the χ2 statistic. Reasons for differences between intern and supervisor ratings were explored by determining correlations between scores using the Spearman ρ statistic, and analysing qualitative data generated by the questionnaire.

Results

Preparedness for all seven roles and the majority of tasks was found to be between ‘Fairly well prepared’ and ‘Well prepared’. The ratings for four roles (Medical expert, Communicator, Collaborator, Professional) differed statistically, but not for the three others (Leader, Health advocate, Scholar). Interns rated their proficiency higher than their supervisors for the tasks in six roles; for the ‘Professional’ role intern ratings were mostly lower. Correlations between intern and supervisors scores were only significant for three roles (Medical expert, Communicator, Collaborator). Qualitative data provided further insights into the reasons for these associations.

Conclusions

Intern preparedness for tasks and roles varied but was generally satisfactory. Based on the analysis of the data seeming discrepancies in between interns and supervisor ratings were investigated and explanations are offered. For three roles the data indicate that their component tasks are understood in the same way by interns and supervisors, but not for the other roles. The Dunning-Kruger effect offers a plausible explanation for higher intern scores for tasks in six of the roles. For the ‘Professional’ role differences between interns’ internal, individual understanding and supervisors’ external, group understanding may explain lower intern scores. The fact that respondents may understand the tasks they rate differently has implications for all research of this nature.
Economic evaluation studies in the field of HIV/AIDS: bibliometric analysis on research development and scopes (GAPRESEARCH)
Authors: Tran Bach Xuan , Nguyen Long Hoang , Turner Hugo C. , Nghiem Son , Vu Giang Thu , Nguyen Cuong Tat , Latkin Carl A. , Ho Cyrus S. H. , Ho Roger C. M.
Published: November 2019

Background

The rapid decrease in international funding for HIV/AIDS has been challenging for many nations to effectively mobilize and allocate their limited resources for HIV/AIDS programs. Economic evaluations can help inform decisions and strategic planning. This study aims to examine the trends and patterns in economic evaluation studies in the field of HIV/AIDS and determine their research landscapes.

Methods

Using the Web of Science databases, we synthesized the number of papers and citations on HIV/AIDS and economic evaluation from 1990 to 2017. Collaborations between authors and countries, networks of keywords and research topics were visualized using frequency of co-occurrence and Jaccards’ similarity index. A Latent Dirichlet Allocation (LDA) analysis to categorize papers into different topics/themes.

Results

A total of 372 economic evaluation papers were selected, including 351 cost-effectiveness analyses (CEA), 11 cost-utility analyses (CUA), 12 cost-benefit analyses (CBA). The growth of publications, their citations and usages have increased remarkably over the years. Major research topics in economic evaluation studies consisted of antiretroviral therapy (ART) initiation and treatment; drug use prevention interventions and prevention of mother-to-child transmission interventions. Moreover, lack of contextualized evidence was found in specific settings with high burden HIV epidemics, as well as emerging most-at-risk populations such as trans-genders or migrants.

Conclusion

This study highlights the knowledge and geographical discrepancies in HIV/AIDS economic evaluation literature. Future research directions are also informed for advancing economic evaluation in HIV/AIDS research.
Evaluation of the impact of a brief educational message on clinicians’ awareness of risks of ionising-radiation exposure in imaging investigations: a pilot pre-post intervention study
Authors: Young Ben , Cranwell Jo , Fogarty Andrew W. , Skelly Rob , Sturrock Nigel , Norwood Mark , Shaw Dominick , Lewis Sarah , Langley Tessa , Thurley Peter
Published: November 2019

Background

In the context of increasing availability of computed tomography (CT) scans, judicious use of ionising radiation is a priority to minimise the risk of future health problems. Hence, education of clinicians on the risks and benefits of CT scans in the management of patients is important.

Methods

An educational message about the associated lifetime cancer risk of a CT scan was added to all CT scan reports at a busy acute teaching hospital in the UK. An online multiple choice survey was completed by doctors before and after the intervention, assessing education and knowledge of the risks involved with exposure to ionising radiation.

Results

Of 546 doctors contacted at baseline, 170 (31%) responded. Over a third (35%) of respondents had received no formal education on the risks of exposure to ionising radiation. Over a quarter (27%) underestimated (selected 1 in 30,000 or negligible lifetime cancer risk) the risk associated with a chest, abdomen and pelvis CT scan for a 20 year old female. Following exposure to the intervention for 1 year there was a statistically significant improvement in plausible estimates of risk from 68.3 to 82.2% of respondents (p < 0.001). There was no change in the proportion of doctors correctly identifying imaging modalities that do or do not involve ionising radiation.

Conclusions

Training on the longterm risks associated with diagnostic radiation exposure is inadequate among hospital doctors. Exposure to a simple non-directional educational message for 1 year improved doctors’ awareness of risks associated with CT scans. This demonstrates the potential of the approach to improve knowledge that could improve clinical practice. This approach is easily deliverable and may have applications in other areas of clinical medicine. The wider and longer term impact on radiation awareness is unknown, however, and there may be a need for regular mandatory training in the risks of radiation exposure.
The oral glucose tolerance test-derived incremental glucose peak is associated with greater arterial stiffness and maladaptive arterial remodeling: The Maastricht Study
Authors: Foreman Yuri D. , Brouwers Martijn C. G. J. , Berendschot Tos T. J. M. , van Dongen Martien C. J. M. , Eussen Simone J. P. M. , van Greevenbroek Marleen M. J. , Henry Ronald M. A. , Houben Alfons J. H. M. , van der Kallen Carla J. H. , Kroon Abraham A. , Reesink Koen D. , Schram Miranda T. , Schaper Nicolaas C. , Stehouwer Coen D. A.
Published: November 2019

Background

Daily glucose variability may contribute to vascular complication development irrespective of mean glucose values. The incremental glucose peak (IGP) during an oral glucose tolerance test (OGTT) can be used as a proxy of glucose variability. We investigated the association of IGP with arterial stiffness, arterial remodeling, and microvascular function, independent of HbA1c and other confounders.

Methods

IGP was calculated as the peak minus baseline plasma glucose value during a seven-point OGTT in 2758 participants (age: 60 ± 8 years; 48% women) of The Maastricht Study, an observational population-based cohort. We assessed the cross-sectional associations between IGP and arterial stiffness (carotid-femoral pulse wave velocity [cf-PWV], carotid distensibility coefficient [carDC]), arterial remodeling (carotid intima-media thickness [cIMT]; mean [CWSmean] and pulsatile [CWSpuls] circumferential wall stress), and microvascular function (retinal arteriolar average dilatation; heat-induced skin hyperemia) via multiple linear regression with adjustment for age, sex, HbA1c, cardiovascular risk factors, lifestyle factors, and medication use.

Results

Higher IGP was independently associated with higher cf-PWV (regression coefficient [B]: 0.054 m/s [0.020; 0.089]) and with higher CWSmean (B: 0.227 kPa [0.008; 0.446]). IGP was not independently associated with carDC (B: − 0.026 10−3/kPa [− 0.112; 0.060]), cIMT (B: − 2.745 µm [− 5.736; 0.245]), CWSpuls (B: 0.108 kPa [− 0.054; 0.270]), retinal arteriolar average dilatation (B: − 0.022% [− 0.087; 0.043]), or heat-induced skin hyperemia (B: − 1.380% [− 22.273; 19.513]).

Conclusions

IGP was independently associated with aortic stiffness and maladaptive carotid remodeling, but not with carotid stiffness, cIMT, and microvascular function measures. Future studies should investigate whether glucose variability is associated with cardiovascular disease.
Prospective study of hemoglobin A1c and incident carotid artery plaque in Chinese adults without diabetes
Authors: Xu Renying , Zhang Ting , Wan Yanping , Fan Zhuping , Gao Xiang
Published: November 2019

Background

Diabetes has been reported to be associated with carotid artery plaque (CAP). However, it remains unclear whether hemoglobin A1c (HbA1c) level, a marker for long-term glycemic status, is associated with altered CAP risk in individuals with fasting blood glucose (FBG) concentrations below the current cutoff for diabetes.

Methods

Included were 16,863 Chinese adults (aged 18 years or more; 9855 men and 7008 women) with fasting blood glucose < 7.0 mmol/L at baseline (2013). Both HbA1c level and CAP (assessed via ultrasound B-mode imaging) were annually assessed during 2014–2018. All the participants were further classified into three groups based on baseline HbA1c level: ≤ 5.6%, 5.7–6.4%, and ≥ 6.5%. We used Cox proportional-hazards model to evaluate the association between HbA1c level and incident CAP, adjusting for a series of potential confounders.

Results

During 5 years of follow up, 3942 incident CAP cases were identified. Individuals with higher baseline HbA1c had higher future risk of CAP (p-trend < 0.001). In the full-adjusted model, each percent increase of HbA1c was associated with a 56% (HR = 1.56, 95% CI 1.37, 1.78) higher risk of CAP. Excluding participants with chronic inflammation, as assessed by high-sensitivity C-reactive protein and white blood cell, and those with FBG ≥ 5.6 mmol/L at baseline generated similar results.

Conclusions

Elevated HbA1c level was associated with high risk of developing CAP in Chinese adults without FBG defined diabetes.
Laccases: structure, function, and potential application in water bioremediation
Authors: Arregui Leticia , Ayala Marcela , Gómez-Gil Ximena , Gutiérrez-Soto Guadalupe , Hernández-Luna Carlos Eduardo , Herrera de los Santos Mayra , Levin Laura , Rojo-Domínguez Arturo , Romero-Martínez Daniel , Saparrat Mario C. N. , Trujillo-Roldán Mauricio A. , Valdez-Cruz Norma A.
Published: November 2019

The global rise in urbanization and industrial activity has led to the production and incorporation of foreign contaminant molecules into ecosystems, distorting them and impacting human and animal health. Physical, chemical, and biological strategies have been adopted to eliminate these contaminants from water bodies under anthropogenic stress. Biotechnological processes involving microorganisms and enzymes have been used for this purpose; specifically, laccases, which are broad spectrum biocatalysts, have been used to degrade several compounds, such as those that can be found in the effluents from industries and hospitals. Laccases have shown high potential in the biotransformation of diverse pollutants using crude enzyme extracts or free enzymes. However, their application in bioremediation and water treatment at a large scale is limited by the complex composition and high salt concentration and pH values of contaminated media that affect protein stability, recovery and recycling. These issues are also associated with operational problems and the necessity of large-scale production of laccase. Hence, more knowledge on the molecular characteristics of water bodies is required to identify and develop new laccases that can be used under complex conditions and to develop novel strategies and processes to achieve their efficient application in treating contaminated water. Recently, stability, efficiency, separation and reuse issues have been overcome by the immobilization of enzymes and development of novel biocatalytic materials. This review provides recent information on laccases from different sources, their structures and biochemical properties, mechanisms of action, and application in the bioremediation and biotransformation of contaminant molecules in water. Moreover, we discuss a series of improvements that have been attempted for better organic solvent tolerance, thermo-tolerance, and operational stability of laccases, as per process requirements.
A qualitative study into female sex workers’ experience of stigma in the health care setting in Hong Kong
Authors: Ma Haixia , Loke Alice Yuen
Published: November 2019

Background

Hong Kong has gained a good reputation for its quality public health care services. However, there is a growing recognition that social stigma is a potential obstacle when female sex workers (FSWs) access health care services. There are a lack of studies focusing on how FSWs experience and cope with stigma when accessing health care services in Hong Kong.

Objective

This study aims to explore how FSWs experience stigma and develop coping strategies when accessing health care services in Hong Kong.

Methods

This is a qualitative interview study. Staff of non-governmental organizations (NGOs) that serve sex workers in Hong Kong facilitated the process of recruiting the participants. In-depth individual interviews were conducted with 22 FSWs, focusing on their experiences of stigma and coping strategies when accessing health care services. A directed content analysis approach was adopted to analyze the data.

Results

The interview data can be grouped into three themes: experience of stigma in the health care setting; coping with the stigma of sex work; and the call for non-judgmental holistic health care.

Conclusion

This study contributes to an understanding of the experience of stigma and stigma coping strategies of FSWs when accessing health care services in Hong Kong. stigmaremains an important issue for a large proportion of FSWs when they seek timely professional help, openly disclose their sex work identity, and receive comprehensive health care services. The study also highlights the need to address multiple healthcare needs of FSWs beyond STDs. Moreover, the study contributes to increasing awareness of, and respect for, the human right of FSWs to receive non-discriminatory health services.
Maternal exposure to ambient fine particulate matter and risk of premature rupture of membranes in Wuhan, Central China: a cohort study
Authors: Wang Kun , Tian Yu , Zheng Huabo , Shan Shengshuai , Zhao Xiaofang , Liu Chengyun
Published: November 2019

Background

The associations between maternal exposure to ambient PM2.5 during pregnancy and the risk of premature rupture of membranes (PROM) and preterm premature rupture of membranes (PPROM) are controversial. And no relevant study has been conducted in Asia. This study aimed to determine the association between maternal exposure to ambient PM2.5 during pregnancy and the risk of (P)PROM.

Methods

A cohort study including all singleton births in a hospital located in Central China from January 2015 through December 2017 was conducted. Multivariable logistic regression models, stratified analysis, generalized additive model, and two-piece-wise linear regression were conducted to evaluate how exposure to ambient PM2.5 during pregnancy is associated with the risks of PROM and PPROM.

Results

A total of 4364 participants were included in the final analysis, where 11.71 and 2.34% of births were complicated by PROM and PPROM, respectively. The level of PM2.5 exhibited a degree of seasonal variation, and its median concentrations were 63.7, 59.3, 55.8, and 61.8 μg/m3 for the first trimester, second trimester, third trimester, and the whole duration of pregnancy, respectively. After adjustment for potential confounders, PROM was positively associated with PM2.5 exposure (per 10 μg/m3) [Odds Ratio (OR) = 1.14, 95% Confidence Interval (CI), 1.02–1.26 for the first trimester; OR = 1.09, 95% CI, 1.00–1.18 for the second trimester; OR = 1.13, 95% CI, 1.03–1.24 for the third trimester; OR = 1.35, 95% CI, 1.12–1.63 for the whole pregnancy]. PPROM had positive relationship with PM2.5 exposure (per 10 μg/m3) (OR = 1.17, 95% CI, 0.94–1.45 for first trimester; OR = 1.11, 95% CI, 0.92–1.33 for second trimester; OR = 1.19, 95% CI, 0.99–1.44 for third trimester; OR = 1.53, 95% CI, 1.03–2.27 for the whole pregnancy) Positive trends between the acute exposure window (mean concentration of PM2.5 in the last week and day of pregnancy) and risks of PROM and PPROM were also observed.

Conclusions

Exposure to ambient PM2.5 during pregnancy was associated with the risk of PROM and PPROM.
Systematic review of carbapenem-resistant Enterobacteriaceae causing neonatal sepsis in China
Authors: Ding Yijun , Wang Yajuan , Hsia Yingfen , Sharland Mike , Heath Paul T.
Published: November 2019

Background

Carbapenems are β-lactam antibiotics which are used to treat severe infections caused by multidrug resistant Enterobacteriacea. The recent emergence and rapid spread of Enterobacteriaceae resistant to carbapenems is a global concern. We undertook a systematic review of the antibiotic susceptibility and genotypic characteristics of carbapenem-resistant Enterobacteriaceae in Chinese neonates.

Methods

Systematic literature reviews were conducted (PubMed/Medline, Embase, Wanfang medical online databases, China National Knowledge Infrastructure (CNKI) database) regarding sepsis caused by carbapenem-resistant Enterobacteriaceae in Chinese neonates aged 0-30 days.

Results

17 studies were identified. Eleven patients in the six studies reported the source of infection. Ten patients (10/11, 90.9%) were hospital-acquired infections. Genotypic data were available for 21 isolates in 11 studies (20 K. pneumoniae, 1 E. coli). NDM-1 was the most frequently reported carbapenem-resistant genotype (81.0%, 17/21). Carbapenem-resistant Klebsiella pneumoniae and Escherichia coli were resistant to many antibiotic classes with the exception of colistin and fosfomycin. Sequence type 105 (ST105) was the most commonly reported K. pneumoniae ST type (30.8%; 4/13), which was from the same hospital in Western China. ST17 and ST20 were the second and third most common K. pneumoniae ST type, 23.1% (3/13) and 15.4% (2/13) respectively. The three strains of ST17 are all from the same hospital in central China. The two strains of ST20, although not from the same hospital, belong to the eastern part of China.

Conclusions

Klebsiella pneumoniae with the NDM-1 genotype was the leading cause of neonatal carbapenem resistant sepsis in China. Hospital acquired infection is the main source of carbapenem resistant sepsis. There is currently no licenced antibiotic regimen available to treat such an infection in China. Improved surveillance, controlling nosocomial infection and the rational use of antibiotics are the key factors to prevent and reduce its spread.
Early features of autism spectrum disorder: a cross-sectional study
Authors: Parmeggiani Antonia , Corinaldesi Arianna , Posar Annio
Published: November 2019

Background

Autism spectrum disorder is characterized by impairment in social interaction and communication along with repetitive, restricted, and stereotyped behaviors, interests and activities. It is important to detect this condition as soon as possible and promptly begin targeted treatments. This study aimed to report on age at onset, early signs, and mode at onset in 105 Italian patients with autism spectrum disorder, searching for correlations with a series of clinical and instrumental variables.

Methods

This retrospective cross-sectional study considered the following five categories of symptoms at onset: language, social interaction and relationships, stereotyped behavior and activities, motor skills, and regulation. Three modes of presentation were considered: a delay, a stagnation, or a regression of development, which were defined modes of onset of autism spectrum disorder. The age at onset, the category of clinical features, and the mode at onset were considered in the entire sample and statistically analyzed for several clinical variables. Statistical analysis was performed utilizing Fisher Exact test and Chi Square test.

Results

The first symptoms between 7 and 12 months were evident in 41.9% of cases, and between 13 and 24 months in 27.6%; no significant differences for the age at onset related to diagnosis, etiopathogenesis, early onset epilepsy, and intelligence quotient level emerged. Social interaction and relationships (93.3%) and language (92.4%) were the categories of early signs more represented in our sample. Delay in spoken language (to be understood as both verbal production and verbal comprehension) was one of the most common (even though not specific) symptoms prompting initial medical consultation for a possible diagnosis of autism spectrum disorder. At onset, patients without intellectual disability manifested stagnation more often than delay or regression of development; patients with a severe/profound intellectual disability more frequently showed delay or regression of development. Language signs at onset were less frequent in cases with regression, whereas motor skill disorders prevailed in cases with delay at onset. Feeding problems were more numerous in cases with delay and stagnation of development.

Conclusions

These data contribute to identifying an early trend of autism spectrum disorder, useful also for pediatricians.
Left ventricular wall findings in non-electrocardiography-gated contrast-enhanced computed tomography after extracorporeal cardiopulmonary resuscitation
Authors: Sugiyama Kazuhiro , Takahashi Masamichi , Miyazaki Kazuki , Ishida Takuto , Kobayashi Mioko , Hamabe Yuichi
Published: November 2019

Background

Few studies have reported left ventricular wall findings in contrast-enhanced computed tomography (CE-CT) after extracorporeal cardiopulmonary resuscitation (ECPR). This study examined left ventricular wall CE-CT findings after ECPR and evaluated the association between these findings and the results of coronary angiography and prognosis.

Methods

We evaluated out-of-hospital cardiac arrest patients who were treated with ECPR and subsequently underwent both non-electrocardiography-gated CE-CT and coronary angiography at our center between January 2011 and April 2018. Left ventricular wall CE-CT findings were classified as follows: (1) homogeneously enhanced (HE; the left ventricular wall was homogeneously enhanced), (2) segmental defect (SD; the left ventricular wall was not segmentally enhanced according to the coronary artery territory), (3) total defect (TD; the entire left ventricular wall was not enhanced), and (4) others. Successful weaning from extracorporeal membrane oxygenation, survival to hospital discharge, and predictive ability of significant stenosis on coronary angiography were compared among patients with HE, SD, and TD patterns.

Results

A total of 74 patients (median age, 59 years) were eligible, 50 (68%) of whom had initial shockable rhythm. Twenty-three (31%) patients survived to hospital discharge. HE, SD, TD, and other patterns were observed in 19, 33, 11, and 11 patients, respectively. The rates of successful weaning from extracorporeal membrane oxygenation (84% vs. 39% vs. 9%, p < 0.01) and survival to hospital discharge (47% vs. 27% vs. 0%, p = 0.02) were significantly different among patients with HE, SD, and TD patterns. In post hoc analysis, patients with HE patterns had a significantly higher success rate of weaning from extracorporeal membrane oxygenation than those with SD and TD patterns. SD predicted significant stenosis with a sensitivity of 74% and specificity of 94%.

Conclusions

Homogenously enhanced left ventricular wall might be a predictor of good left ventricular function recovery. In contrast, total enhancement defect in the entire left ventricular wall was associated with poor outcomes. Contrast defect matching the coronary artery territory could predict significant coronary artery stenosis with good specificity. The left ventricular wall findings in non-electrocardiography-gated CE-CT after ECPR might be useful for diagnosis and prognostic prediction.
Correlation of homologous recombination deficiency induced mutational signatures with sensitivity to PARP inhibitors and cytotoxic agents
Authors: Póti Ádám , Gyergyák Hella , Németh Eszter , Rusz Orsolya , Tóth Szilárd , Kovácsházi Csenger , Chen Dan , Szikriszt Bernadett , Spisák Sándor , Takeda Shunichi , Szakács Gergely , Szallasi Zoltan , Richardson Andrea L. , Szüts Dávid
Published: November 2019

Background

Homologous recombination (HR) repair deficiency arising from defects in BRCA1 or BRCA2 is associated with characteristic patterns of somatic mutations. In this genetic study, we ask whether inactivating mutations in further genes of the HR pathway or the DNA damage checkpoint also give rise to somatic mutation patterns that can be used for treatment prediction.

Results

Using whole genome sequencing of an isogenic knockout cell line panel, we find a universal HR deficiency-specific base substitution signature that is similar to COSMIC signature 3. In contrast, we detect different deletion phenotypes corresponding to specific HR mutants. The inactivation of BRCA2 or PALB2 leads to larger deletions, typically with microhomology, when compared to the disruption of BRCA1, RAD51 paralogs, or RAD54. Comparison with the deletion spectrum of Cas9 cut sites suggests that most spontaneously arising genomic deletions are not the consequence of double-strand breaks. Surprisingly, the inactivation of checkpoint kinases ATM and CHK2 has no mutagenic consequences. Analysis of tumor exomes with biallelic inactivating mutations in the investigated genes confirms the validity of the cell line models. We present a comprehensive analysis of sensitivity of the investigated mutants to 13 therapeutic agents for the purpose of correlating genomic mutagenic phenotypes with drug sensitivity.

Conclusion

Our results suggest that no single genomic mutational class shows perfect correlation with sensitivity to common treatments, but the contribution of COSMIC signature 3 to base substitutions, or a combined measure of different features, may be reasonably good at predicting platinum and PARP inhibitor sensitivity.
Diuron exposure and Akt overexpression promote glioma formation through DNA hypomethylation
Authors: Briand Joséphine , Nadaradjane Arulraj , Bougras-Cartron Gwenola , Olivier Christophe , Vallette François M. , Cartron Pierre-François
Published: November 2019

Background

Diuron is an environmental component listed as a likely human carcinogen. Several other studies report that diuron can be oncogenic for bladder, urothelial, skin, and mammary cells. No study mentions the putative effect of diuron on the glioma occurrence.

Objectives

We here wanted to investigate the effects of diuron exposure on the glioma occurrence while wishing to incriminate a putative implication of DNA methylation modulation in this process.

Methods

In in vivo model of glioma, diuron exposure was firstly compared or combined with oncogenic overexpressions already known to promote gliomagenesis. ELISA quantifying the 5-methylcytosine level on DNA was performed to examine the global DNA methylation level. Quantitative real-time polymerase chain reaction and proximity ligation in situ assay were performed to identify the molecular causes of the diuron-induced changes of DNA methylation. The signatures diuron-induced changes of DNA methylation were analyzed in a cohort of 23 GBM patients.

Results

Diuron exposure is not sufficient to promote glioma, such as the oncogenic overexpression of Akt or Ras. However, the combination of diuron exposure and Akt overexpression promotes glioma. We observed that the diuron/Akt-induced glioma is characterized by three phenotypic signatures characterizing cancer cells: a global DNA hypomethylation, a loss of sensitivity to cell death induction, and a gain of signals of immune escape. Our data associated these phenotypes with three aberrant DNA methylation signatures: theLLT1,PD-L1, andBcl-whypomethylations. Strikingly, we observed that these three concomitant hypomethylations were only observed in GBM patients having a potential exposure to diuron via their professional activity.

Conclusions

As single player, diuron is not an oncogenic of glioma, but it can participate to the glioma formation in association with other events (also devoid of oncogenic property as single player) such as Akt overexpression.
Existence and multiplicity of solutions for fractional Schödinger equation involving a critical nonlinearity
Authors: Yun Yongzhen , An Tianqing , Ye Guoju
Published: November 2019

In this paper, we investigate the fractional Schödinger equation involving a critical growth. By using the principle of concentration compactness and the variational method, we obtain some new existence results for the above equation, which improve the related results on this topic.
Hepatic sclerosing hemangioma mimics hepatic malignancies: a case report and multidisciplinary approach
Authors: Sweed Dina M. , Fayed Zeinab A. , Sweed Enas M. , El-Sherif Ahmed , Mohamady Mohamed
Published: November 2019

Background

Hepatic sclerosing hemangiomas (HSH) are rare benign vascular tumors that mimic radiologically hepatic malignancies. HSH is characterized by extensive fibrosis and hyalinosis as a result of degeneration and thrombosis. Pre-operative diagnosis is very difficult and most of the cases undergo surgical resections.

Case presentation

A 65 years old, hepatitis C virus-infected female presented by an accidentally discovered hepatic focal lesion. Magnetic resonance imaging (MRI) showed a T2 hyperintense mass displaying peripheral enhancement in porto-venous phase. The patient had a simultaneous typical hepatic hemangioma and multiple vertebral bodies’ hemangiomata. Tissue-guided biopsy revealed a densely sclerotic stroma containing vascular spaces with occasional obliteration of the lumen. Immunohistochemical staining was performed for Pan CK, CD34, SMA, VEGF, and c-Kit which confirmed the vascular nature of neoplasm and the involuting phase of hemangioma development. The patient was reassured and recommended for a regular radiological follow-up to reassess the lesion size.

Conclusion

The definitive preoperative diagnosis of HSH is still problematic. However, the awareness of surgeons by this entity, peripheral enhancement in porto-venous phase on dynamic MRI, the presence of simultaneous typical hepatic hemangioma in the absence of cancer history could raise suspicion for HSH. Liver biopsy is still the gold standard in approaching the accurate diagnosis.
Highlights from the previous volumes
Authors: Ramlow Lokas , Malki M. , Uhrig G. S. , Drossinos Y. , Türkan A.
Published: November 2019

Partial synchronization as a model for unihemispheric sleep Delocalization of edge states in topological phases Fractal agglomerates fragment into dissimilar fragments Light D-wave axial-tensor K2(1820) meson at finite temperature