bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of replication of hepatitis B virus using transcriptional repressors that target the viral DNA
Authors: Bloom Kristie , Kaldine Haajira , Cathomen Toni , Mussolino Claudio , Ely Abdullah , Arbuthnot Patrick 
Published: September 2019

AbstractBackgroundChronic infection with hepatitis B virus (HBV) is a serious global health problem. Persistence of the virus occurs as a result of stability of the replication intermediate comprising covalently closed circular DNA (cccDNA). Development of drugs that are capable of disabling this cccDNA is vital.MethodsTo investigate an epigenetic approach to inactivating viral DNA, we engineered transcriptional repressors that comprise an HBV DNA-binding domain of transcription activator like effectors (TALEs) and a fused Krüppel Associated Box (KRAB). These repressor TALEs (rTALEs) targeted the viralsurfaceopen reading frame and were placed under transcription control of constitutively active or liver-specific promoters.ResultsEvaluation in cultured cells and following hydrodynamic injection of mice revealed that the rTALEs significantly inhibited production of markers of HBV replication without evidence of hepatotoxicity. Increased methylation of HBV DNA at CpG island II showed that the rTALEs caused intended epigenetic modification.ConclusionsEpigenetic modification of HBV DNA is a new and effective means of inactivating the virus in vivo. The approach has therapeutic potential and avoids potentially problematic unintended mutagenesis of gene editing.
Testing a pyriproxyfen auto-dissemination station attractive to gravid Anopheles gambiae sensu stricto for the development of a novel attract-release -and-kill strategy for malaria vector control
Authors: Mbare Oscar , Lindsay Steven W. , Fillinger Ulrike 
Published: September 2019

Abstract

Background
Larviciding is an effective supplementary tool for malaria vector control, but the identification and accessibility of aquatic habitats impedes application. Dissemination of the insect growth regulator, pyriproxyfen (PPF), by gravid Anopheles might constitute a novel application strategy. This study aimed to explore the feasibility of using an attractive bait-station to contaminate gravid Anopheles gambiae sensu stricto with PPF and subsequently transfer PPF to larval habitats.

Methods
A bait-station was developed comprising of an artificial pond containing water treated with 20 ppm cedrol, an oviposition attractant, and a netting-cover treated with PPF. Three identical semi-field cages were used to assess the potential of gravid Anopheles to transfer PPF from the bait-station to ponds. Gravid females were released in two semi-field cages, one with PPF on its bait-station (test) and one without PPF (control). No mosquitoes were released in the third cage with a PPF-treated station (control). Transfer of PPF to open ponds was assessed by monitoring emergence of late instar insectary-reared larvae introduced into the ponds. The amount of PPF carried by a mosquito and transferred to water was quantified using liquid chromatography-mass spectrometry.

Results
In the controls, 86% (95% CI 81–89%) of larvae introduced into open ponds developed into adults, indicating that wind did not distribute PPF in absence of mosquitoes. Emergence inhibition was observed in the test cage but was dependent on the distance between pond and bait-station. Only 25% (95% CI 22–29%) of larvae emerged as adults from ponds 4 m from the bait-station, but 92% (95% CI 89–94%) emerged from ponds 10 m away. Each mosquito was contaminated on average with 112 μg (95% CI 93–123 μg) PPF resulting in the transfer of 230 ng/L (95% CI 180–290 ng/L) PPF to 100 ml volumes of water.

Conclusions
The bait-stations successfully attracted gravid females which were subsequently dusted with effective levels of PPF. However, in this study design, attraction and dissemination was limited to short distances. To make this approach feasible for malaria vector control, stronger attractants that lure gravid females from longer distances, in landscapes with many water bodies, and better PPF delivery systems are needed.
High-volume workflow and performance comparisons for Chlamydia trachomatis and Neisseria gonorrhoeae testing using automated molecular platforms
Authors: Frontzek André , Aretzweiler Gudrun , Winkens Daniela , Duncan Dana , Marlowe Elizabeth M. 
Published: September 2019

Abstract

Background
The global burden of sexually transmitted infections (STIs) is high and there have been reports of increasing chlamydial and gonorrheal infections. High-volume screening programs for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are an important component of STI control. This study evaluated the high-volume workflow and performance of the cobas® CT/NG assay for use on the automated Roche cobas® 6800 system, with the cobas p 480 instrument for pre-analytics, compared with the Aptima Combo 2 assay on the Hologic Panther system.

Methods
High-volume workflow and performance were evaluated using paired female urine specimens. Workflow analysis (n = 376) included hands-on time (HoT), number of manual interventions, and time to first and last results. For performance assessment, paired results from the cobas CT/NG and Aptima Combo 2 assays, for both CT and NG, were compared and two-sided 95% confidence intervals calculated to provide estimates of positive percent agreement (PPA), negative percent agreement (NPA), and overall percent agreement (OPA) between the tests. McNemar’s test was used for significance testing.

Results
Pre-analytical preparations and system start-up on the cobas 6800 system required 00:27:38 (hr:min:sec) HoT whilst the Panther system required 00:30:43. The cobas 6800 system required eight interactions and 00:43:59 HoT to process 376 samples. The Panther system required six interactions and 00:39:10 HoT. Time to first results was 02:53:00 on the cobas c6800 system for 96 samples and 03:28:29 on the Panther system for five samples. The cobas 6800 system delivered all 376 results 3 h faster than the Panther system (07:45:26 and 10:47:30, respectively). The performance correlation between both assays was high (PPA, NPA and OPA > 99% for both CT and NG). McNemar’s test revealed no statistically significant difference between the assays.

Conclusion
For high-volume automated CT/NG testing, both the cobas 6800 system and Panther system provided accurate results. Although less manual intervention steps were needed for the Panther system, improved turnaround time was obtained with the cobas 6800 system with less risk for contamination. The additional testing capacity on the cobas 6800 system would allow a growing service to deliver more results in a single shift.
Is the place of birth related to the mother’s satisfaction with childbirth? A cross-sectional study in a rural district of the Lao People’s Democratic Republic (Lao PDR)
Authors: Takayama Tomomi , Phongluxa Khampheng , Nonaka Daisuke , Sato Chika , Gregorio Ernesto R. , Inthavong Nouhak , Pongvongsa Tiengkham , Kounnavong Sengchanh , Kobayashi Jun 
Published: September 2019

AbstractBackgroundThe place of birth has been rapidly changing from home to health facility in Lao People’s Democratic Republic (Lao PDR) following the strategy to improve the maternal and neonatal mortality. This change in the place of birth might affect the mother’s satisfaction with childbirth. The objective of this study was to assess whether the place of birth is related to the mother’s satisfaction with childbirth in a rural district of the Lao PDR.MethodsA community-based survey was implemented in 21 randomly selected hamlets in Xepon district, Savannakhet province, between February and March, 2016. Questionnaire-based interviews were conducted with mothers who experienced a normal vaginal birth in the past 2 years. Satisfaction with childbirth was measured by the Satisfaction with Childbirth Experience Questionnaire. Using the median, the outcome variable was dichotomized into “high satisfaction group” and “low satisfaction group”. Logistic regression was performed to assess the association between place of birth and satisfaction with childbirth. Three models were examined: In Model 1, only the predictor of interest (i.e., place of birth) was included. In Model 2, the predictor of interest and the obstetrical predictors were included. In Model 3, in addition to these predictors, socio-demographic and economic predictors were included. A mixed-effects model was used to account for the hierarchical structure.ResultsAmong the 226 mothers who were included in data analysis, 60.2% gave birth at the health facility and the remaining 39.8% gave birth at home. Logistic regression analysis showed that the mothers who gave birth at the health facility were significantly more likely to have a higher level of satisfaction compared to the mothers who gave birth at home (crude odds ratio: 5.44, 95% confidence interval: 3.03 to 9.75). This association remained even after adjusting for other predictors (adjusted odds ratio: 6.05, 95% confidence interval: 2.81 to 13.03).ConclusionFacility-based birth was significantly associated with a higher level of satisfaction with childbirth among the mothers in the study district where maternal and neonatal mortalities are relatively high. The findings of the present study support the promotion of facility-based birth in a rural district of the Lao PDR.
Outcomes of immediate oncoplastic surgery and adjuvant radiotherapy in breast cancer patients
Authors: Borm Kai Joachim , Schönknecht Christine , Nestler Andrea , Oechsner Markus , Waschulzik Birgit , Combs Stephanie Elisabeth , Münch Stefan , Niemeyer Markus , Duma Marciana Nona 
Published: September 2019

Abstract

Background
Oncoplastic surgery techniques lead to a rearrangement of the breast tissue and impede target definition during adjuvant radiotherapy (RT). The aim of this study was to assess local control rates after immediate oncoplastic surgery and adjuvant RT.

Methods
This study comprises 965 patients who underwent breast-conserving therapy and adjuvant RT between 01/2000 and 12/2005. 288 patients received immediate oncoplastic surgery (ONC) and 677 patients breast-conserving surgery only (NONC). All patients were treated with adjuvant external tangential-beam RT (total dose: 50/50.4 Gy; fraction dose 1.8/2.0 Gy). An additional boost dose of 10–16 Gy to the primary tumor bed was given in 900 cases (93.3%). Local control rates (LCR), Progression free survival (PFS) and overall survival (OS) were assessed retrospectively after a median follow-up period of 67 (Q25-Q75: 51–84) months.

Results
No significant difference was found between ONC and NONC in regard to LCR (5-yr: ONC 96.8% vs. NONC 95.3%; p = 0.25). This held also true for PFS (5-yr: ONC 92.1% vs. NONC 89.3%; p = 0.09) and OS (5-yr: ONC 96.0% vs. NONC 94.8%; p = 0.53). On univariate analyses G2–3 (p = 0.04), a younger age (p = 0.01), T-stage (p < 0.01) lymph node involvement (p < 0.01) as well as triple negative tumors (p < 0.01) were identified as risk factors for local recurrence. In a propensity score stratified Cox-regression model no significant impact of oncoplastic surgery on local control rate was found (HR: 2.05, 95% CI [0.93; 4.51], p = 0.08).

Conclusion
Immediate oncoplastic surgery seems not to affect the effectiveness of adjuvant whole breast RT on local control rates in breast cancer patients.
Trastuzumab use in older patients with HER2-positive metastatic breast cancer: outcomes and treatment patterns in a whole-of-population Australian cohort (2003–2015)
Authors: Daniels Benjamin , Kiely Belinda E. , Tang Monica , Tervonen Hanna , Pearson Sallie-Anne 
Published: September 2019

Abstract

Background
Older patients with HER2-positive metastatic breast (HER2 + MBC) cancer are underrepresented in clinical trials. We aim to describe the treatment patterns and overall survival (OS) for older women receiving trastuzumab for HER2 + MBC.

Methods
Retrospective, whole-of-population cohort study using demographic, dispensing, and medical services data for Australian women ≥ 65 years initiating trastuzumab for HER2 + MBC between 2003 and 2015. We describe time-on-trastuzumab; type and timing of other cancer treatments; rates of cardiac monitoring; and OS from trastuzumab initiation for HER2 + MBC.

Results
Of 5404 women initiating trastuzumab for HER2 + MBC, 1583 (29%) were ≥ 65 years old, and the proportion of older patients increased from 20% in 2003 to 38% in 2015. The median age for older women was 73 years and 516 (33%) were ≥ 75 years. Most older patients (92%) received ≥3medicines for comorbidities other than cancer. Median (IQR) time on trastuzumab was 14.1 months (5.9–32.1) and on all chemotherapy was 5.6 months (3.3–10.8). 74% received ≥1 chemotherapy agent and 56% received endocrine therapy. Half (49%) of patients had a cardiac assessment prior to initiating trastuzumab and overall 1228 (76%) had ≥1 cardiac assessment during the study period. At a median follow-up of 6 years, 73% of patients had died and the median OS was 25.6 months (IQR 10.7–58.7).

Conclusions
Older patients comprise a growing proportion of patients treated with HER2-targeted therapies in the real-world but they remain underrepresented in trials of these agents. Few trials report duration or OS estimates for older patients but our estimates are similar to those from trials that have. Although cardiac monitoring was a requirement of accessing trastuzumab during our study period, many patients did not undergo a cardiac assessment.
Different levels of cardiometabolic indicators in multiple vs. singleton children
Authors: Fonseca Maria João , Santos Ana Cristina , Barros Henrique 
Published: September 2019

Abstract

Background
We aimed to compare cardiometabolic indicators in singletons and multiples at age 7 and explore the birthweight mediation effect.

Methods
We studied 5431 singletons and 103 sets of multiples from Generation XXI birth cohort. Anthropometric measurements, body composition, and fasting blood samples were obtained. Age- and sex-specific z-scores were calculated (additionally height-specific for blood pressure). Adjusted regression coefficients and respective 95% confidence intervals [β (95%CI)] were computed using path analysis.

Results
Multiples had lower weight [− 0.419 (− 0.616;-0.223)], height [− 0.404 (− 0.594;-0.213)], BMI [− 0.470 (− 0.705;-0.234)], fat mass index [− 0.359 (− 0.565;-0.152)], waist circumference [− 0.342 (− 0.537;-0.147)], and waist-to-height ratio [− 0.165 (− 0.326;-0.003)] z-scores. These results were explained by the indirect effect via birthweight, which was also negative and significant for all the aforementioned cardiometabolic indicators, while no direct effect was present. There were also significant indirect effects regarding fat-free mass index, glucose, insulin, and blood pressure, though the total effects were not significant, due to the balance between direct and indirect effects. The only significant direct effect was regarding diastolic blood pressure [− 0.165 (− 0.302;-0.028)].

Conclusions
At age 7, multiples presented better cardiometabolic indicators explained by lower weight at birth, except for the lower blood pressure which was independent of an effect via birthweight.
Prepulse inhibition in patients with bipolar disorder: a systematic review and meta-analysis
Authors: Mao Zhen , Bo Qijing , Li Weidi , Wang Zhimin , Ma Xin , Wang Chuanyue 
Published: September 2019

AbstractBackgroundPrepulse inhibition (PPI) is a measurement method for the sensory gating process, which helps the brain adapt to complex environments. PPI may be reduced in patients with bipolar disorder (BD). This study investigated PPI deficits in BD and pooled the effect size of PPI in patients with BD.MethodsWe conducted a literature search on PPI in patients with BD from inception to July 27, 2019 in PubMed, Embase, Cochrane Library databases, and Chinese databases. No age, sex, and language restriction were set. The calculation formula was PPI = 100 - [100*((prepulse - pulse amplitude) / pulse amplitude)]. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of studies.ResultsTen eligible papers were identified, of which five studies including a total of 141 euthymic patients and 132 healthy controls (HC) were included in the meta-analysis. Compared with HC, euthymic patients with BD had significantly lower PPI at the 60 ms interstimulus interval (ISI) between pulse and prepulse (P = 0.476, I2 = 0.0%, SMD = − 0.32, 95% CI = − 0.54 - -0.10). Sensitivity analysis shows no significant change in the combined effect value after removing any single study. There was no publication bias using the Egger’s test at 60 ms (P = 0.606). The meta-analysis of PPI at the 60 ms ISI could have significant clinical heterogeneity in mood episode state, as well as lack of data on BD I or II subtypes.ConclusionsEuthymic patients with BD show PPI deficits at the 60 ms, suggesting a deficit in the early sensory gate underlying PPI. The PPI inhibition rate at a 60 ms interval is a stable index. More research is needed in the future to confirm this outcome, and to delve deeper into the mechanisms behind deficits.
Integrated and simplified approaches to community management of acute malnutrition in rural Kenya: a cluster randomized trial protocol
Authors: Kimani-Murage Elizabeth Wambui , Pythagore Hermann , Mwaniki Elizabeth , Daniel Tewoldeberha , Samburu Betty , Cuellar Pilar Charle , Mbochi Regina , Njiru James , Wangare Lucy , Karimurio Lydia , Agutu Olivia , Maina Lucy Gathigi , Okoth Peter , Raburu Judith , Wanjohi Milka , Macharia Triza , Zerfu Taddese Alemu 
Published: September 2019

Abstract

Background
In many low income countries, the majority of acutely malnourished children are either brought to the health facility late or never at all due to reasons related to distance and associated costs. Integrated community case management (iCCM) is an integrated approach addressing disease and malnutrition through use of community health volunteers (CHVs) in children under-5 years. Evidence on the potential impact and practical experiences on integrating community-based management of acute malnutrition as part of an iCCM package is not well documented. In this study, we aim to investigate the effectiveness and cost effectiveness of integrating management of acute malnutrition into iCCM.

Methods
This is a two arm parallel groups, non-inferiority cluster randomized community trial (CRT) employing mixed methods approach (both qualitative and quantitative approaches). Baseline and end line data will be collected from eligible (malnourished) mother/caregiver-child dyads. Ten community units (CUs) with a cluster size of 24 study subjects will be randomized to either an intervention (5 CUs) and a control arm (5 CUs). CHV in the control arm, will only screening and refer MAM/SAM cases to the nearby health facility for treatment by healthcare professionals. In the intervention arm, however; CHVs will be trained both to screen/diagnose and also treat moderate acute malnutrition (MAM) and severe acute malnutrition (SAM) without complication. A paired-matching design where each control group will be matched with intervention group with similar characteristics will be matched to ensure balance between the two groups with respect to baseline characteristics. Qualitative data will be collected using key informant and in-depth interviews (KIIs) and focused group discussions (FGDs) to capture the views and experiences of stakeholders.

Discussion
Our proposed intervention is based on an innovative approach of integrating and simplifying SAM and MAM management through CHWs bring the services closer to the community. The trial has received ethical approval from the Ethics Committee of AMREF Health Africa - Ethical and Scientific Review Committee (AMREF- ESRC), Nairobi, Kenya. The results will be disseminated through workshops, policy briefs, peer-reviewed publications, and presented to local and international conferences.

Trial registration
PACTR201811870943127; Pre-results. 26 November 2018.
Systematic review of burnout among healthcare providers in sub-Saharan Africa
Authors: Dubale Benyam W. , Friedman Lauren E. , Chemali Zeina , Denninger John W. , Mehta Darshan H. , Alem Atalay , Fricchione Gregory L. , Dossett Michelle L. , Gelaye Bizu 
Published: September 2019

AbstractBackgroundBurnout is characterized by physical and emotional exhaustion from long-term exposure to emotionally demanding work. Burnout affects interpersonal skills, job performance, career satisfaction, and psychological health. However, little is known about the burden of burnout among healthcare providers in sub-Saharan Africa.MethodsRelevant articles were identified through a systematic review of PubMed, Web of Science (Thomson Reuters), and PsycINFO (EBSCO). Studies were selected for inclusion if they examined a quantitative measure of burnout among healthcare providers in sub-Saharan Africa.ResultsA total of 65 articles met our inclusion criteria for this systematic review. Previous studies have examined burnout in sub-Saharan Africa among physicians (N = 12 articles), nurses (N = 26), combined populations of healthcare providers (N = 18), midwives (N = 2), and medical or nursing students (N = 7). The majority of studies assessed burnout using the Maslach Burnout Inventory. The highest levels of burnout were reported among nurses, although all healthcare providers showed high burnout. Burnout among healthcare providers is associated with their work environments, interpersonal and professional conflicts, emotional distress, and low social support.ConclusionsAvailable studies on this topic are limited by several methodological challenges. More rigorously designed epidemiologic studies of burnout among healthcare providers are warranted. Health infrastructure improvements will eventually be essential, though difficult to achieve, in under-resourced settings. Programs aimed at raising awareness and coping with burnout symptoms through stress management and resilience enhancement trainings are also needed.