bluuebunny/crossref_metadata_2025 huggingface dataset:
Women’s experiences of mistreatment during childbirth and their satisfaction with care: findings from a multicountry community-based study in four countries
Authors: Maung Thae Maung , Mon Nwe Oo , Mehrtash Hedieh , Bonsaffoh Kwame Adu , Vogel Joshua P , Aderoba Adeniyi Kolade , Irinyenikan Theresa Azonima , Balde Mamadou Dioulde , Pattanittum Porjai , Tuncalp Özge , Bohren Meghan A
Published: January 2021

Introduction

Experiences of care and satisfaction are intrinsically linked, as user’s experiences of care may directly impact satisfaction, or indirectly impact user’s expectations and values. Both experiences of care and satisfaction are important to measure so that quality can be monitored and improved. Globally, women experience mistreatment during childbirth at facilities; however, there is limited evidence exploring the mistreatment and women’s satisfaction with care during childbirth.

Methods

This is a secondary analysis of a cross-sectional survey within the WHO study ‘How women are treated during facility-based childbirth’ exploring the mistreatment of women during childbirth in Ghana, Guinea, Myanmar and Nigeria. Women’s experiences of mistreatment and satisfaction with care during childbirth was explored. Multivariable logistic regression modelling was conducted to evaluate the association between mistreatment, women’s overall satisfaction with the care they received, and whether they would recommend the facility to others.

Results

2672 women were included in this analysis. Despite over one-third of women reporting experience of mistreatment (35.4%), overall satisfaction for services received and recommendation of the facility to others was high, 88.4% and 90%, respectively. Women who reported experiences of mistreatment were more likely to report lower satisfaction with care: women were more likely to be satisfied if they did not experience verbal abuse (adjusted OR (AOR) 4.52, 95% CI 3.50 to 5.85), or had short waiting times (AOR 5.12, 95% CI 3.94 to 6.65). Women who did not experience any physical or verbal abuse or discrimination were more likely to recommend the facility to others (AOR 3.89, 95% CI 2.98 to 5.06).

Conclusion

Measuring both women’s experiences and their satisfaction with care are critical to assess quality and provide actionable evidence for quality improvement. These measures can enable health systems to identify and respond to root causes contributing to measures of satisfaction.
Gender-specific association between carbohydrate consumption and blood pressure in Chinese adults
Authors: Liu Ruru , Mi Baibing , Zhao Yaling , Li Qiang , Dang Shaonong , Yan Hong
Published: January 2021

Background

The association between dietary carbohydrate consumption and blood pressure (BP) is controversial. The present study aimed to evaluate the possible gender-specific association of carbohydrate across the whole BP distribution.

Method

Cross-sectional survey including 2241 rural adults was conducted in northwestern China in 2010. BP was measured by trained medical personnel. Dietary information was collected by semiquantitative Food-Frequency Questionnaire. Multivariate quantile regression model was used to estimate the association between total carbohydrates consumption and systolic BP (SBP) and diastolic BP (DBP) at different quantiles. Gender-specific β coefficient and its 95% CI was calculated.

Results

The average carbohydrate intake was 267.4 (SD 112.0) g/day in males and 204.9 (SD 90.7) g/day in females, with only 10.6% of males and 6.5% females consumed at least 65% of total energy from carbohydrates. And more than 80% carbohydrates were derived from refined grains. In females, increased total carbohydrates intake was associated with adverse SBP and DBP. An additional 50 g carbohydrates per day was positively associated with SBP at low and high quantiles (10th–20th and 60th–80th) and with DBP almost across whole distribution (30th–90th), after adjusting for age, fortune index, family history of hypertension, body mass index, physical activity level, alcohol intake and smoke, energy, two nutrient principal components, protein and sodium intake. Both relatively low and high carbohydrate intake were associated with increased SBP, with minimum level observed at 130–150 g carbohydrate intake per day from restricted cubic splines. However, no significant associations were observed in males.

Conclusions

Higher total carbohydrates consumption might have an adverse impact on both SBP and DBP in Chinese females but not males. Additionally, the positive association varies across distribution of BP quantiles. Further research is warranted to validate these findings and clarify the causality.
Estimating the potential impact of Australia’s reformulation programme on households’ sodium purchases
Authors: Coyle Daisy , Shahid Maria , Dunford Elizabeth , Ni Mhurchu Cliona , Mckee Sarah , Santos Myla , Popkin Barry , Trieu Kathy , Marklund Matti , Neal Bruce , Wu Jason
Published: January 2021

Background

On average, Australian adults consume 3500 mg sodium per day, almost twice the recommended maximum level of intake. The Australian government through the Healthy Food Partnership initiative has developed a voluntary reformulation programme with sodium targets for 27 food categories. We estimated the potential impact of this programme on household sodium purchases (mg/day per capita) and examined potential differences by income level. We also modelled and compared the effects of applying the existing UK reformulation programme targets in Australia.

Methods

This study used 1 year of grocery purchase data (2018) from a nationally representative consumer panel of Australian households (Nielsen Homescan) that was linked with a packaged food and beverage database (FoodSwitch) that contains product-specific sodium information. Potential reductions in per capita sodium purchases were calculated and differences across income level were assessed by analysis of variance. All analyses were modelled to the Australian population in 2018.

Results

A total of 7188 households were included in the analyses. The Healthy Food Partnership targets covered 4307/26 728 (16.1%) unique products, which represented 22.3% of all packaged foods purchased by Australian households in 2018. Under the scenario that food manufacturers complied completely with the targets, sodium purchases will be reduced by 50 mg/day per capita, equivalent to 3.5% of sodium currently purchased from packaged foods. Reductions will be greater in low-income households compared with high-income households (mean difference −7 mg/day, 95% CI −4 to −11 mg/day, p<0.001). If Australia had adopted the UK sodium targets, this would have covered 9927 unique products, resulting in a reduction in per capita sodium purchases by 110 mg/day.

Conclusion

The Healthy Food Partnership reformulation programme is estimated to result in a very small reduction to sodium purchases. There are opportunities to improve the programme considerably through greater coverage and more stringent targets.
Improving the quality of blood pressure measurements in an outpatient diabetes clinic
Authors: Iyengar Jennifer J , Johnson Matthew , Khairi Shafaq , Fennelly Jessica E , Wyckoff Jennifer
Published: January 2021

Hypertension is an important modifiable risk factor for cardiovascular disease in patients with diabetes. Despite established guidelines, the percentage of patients meeting the target blood pressure (BP) of <140/90 mm Hg in clinic remains suboptimal. In this project, we sought to improve BP measurement in an outpatient diabetes clinic.

Two interventions were performed: (1) Changes were made to the timing of BP measurement during patient intake and (2) An electronic medical record (EMR) alert reminded staff to repeat BP if the initial reading was above target. Baseline data were collected on 4764 patients, with 72.5% meeting their BP target. After implementation of changes to the timing of BP measurement during patient intake, 73.3% of patients met the target (no significant change). However, after implementation of the EMR alert, there was a statistically significant improvement in patients meeting the target BP at 76.8% (p<0.01). This reduction was driven by the high percentage of patients with an initially elevated BP measurement that came down into goal range on repeat measurement. Those who remained above target despite multiple readings could be referred to a new pharmacist-led hypertension clinic to ensure adequate follow-up and medication adjustment.

It is important to ensure that in clinic BP measurements are taken correctly and adhere to best practices. Use of a single in-clinic BP measurement may result in overtreatment of hypertension. While timing of BP measurement during patient intake was not important, repeating high BP measurements did improve the number of patients in an outpatient diabetes clinic meeting their BP target.
Using a comprehensive audit to identify local context prior to care bundle design and implementation for inadvertent perioperative hypothermia in colorectal surgery
Authors: Tanner Judith , Timmons Stephen , Bayston Roger , Adams Kimberley , Baxendale Bryn
Published: January 2021

Background

The first step in bundle design or implementation is to identify the problem being addressed. Several validated approaches are recommended to facilitate this. These include using systematic reviews, adverse event triggers and risk assessment tools. However, these methods do not fully take the local context into account, which will limit the effectiveness of the bundle.

Aim

This study explores the potential benefit of using a comprehensive audit to identify an organisation’s local context prior to designing and implementing a care bundle.

Method

A comprehensive audit comprising observations of four patient journeys, interviews with 21 staff and clinical data was carried out at one large National Health Service trust in England. A patient warming care bundle was used as the exemplar.

Findings

Each of the three data collection methods identified specific local practices which would be addressed within the planning and implementation stages of a care bundle. These practices would not have been identified through other recommended methods.

Conclusion

A comprehensive audit, comprising observations, interviews and clinical data is a successful method to identify local contextual issues prior to care bundle implementation.
Risk factors of non-typhoidal Salmonella gastroenteritis in hospitalised young children: a case–control study
Authors: Woh Pei Yee , Yeung May Pui Shan , Nelson E Anthony S , Goggins William Bernard III
Published: January 2021

Objective

To explore risk factors associated with non-typhoidal Salmonella gastroenteritis in young children in Hong Kong.

Design

A case–control study.

Setting

Paediatrics wards at three public hospitals in Hong Kong.

Participants

Cases were children aged above 30 days to below 5 years hospitalised for gastroenteritis at three public hospitals in Hong Kong with culture confirmed non-typhoidal Salmonella infection. Controls were age-matched (±2 months) children admitted for a reason other than gastroenteritis.

Main outcomes measures

A face-to-face interview by using standardised questionnaire on exposures 3 days prior to illness. Adjusted OR (aORs) and 95% CIs were calculated using multivariable logistic regression.

Results

A total of 102 cases and 204 age-matched controls were included in the analysis. Multivariable logistic regression revealed that having food purchased from places other than a supermarket, that is, from wet market/restaurant/farm (aOR, 2.64; 95% CI, 1.03 to 6.77; p=0.044) was a significant risk factor for non-typhoidal Salmonella infection. Having a household member with gastroenteritis symptoms (aOR, 2.03; 95% CI, 0.94 to 4.39; p=0.072) was of borderline significance and playing at a children’s indoor playroom was a protective factor (aOR, 0.28; 95% CI, 0.09 to 0.85; p=0.024).

Conclusions

Consumption of food purchased from places other than a supermarket was the identified determinant factor for non-typhoidal Salmonella gastroenteritis in Hong Kong. Parents/caregivers should be alerted to this risk when choosing foods for their young children. The protective effect of playing in an indoor playroom could be confounded by socioeconomic factors and further investigation is required to better understand its potential implication. There was some support for person-to-person transmission and good family hygiene needs to be emphasised.
Research Evaluating Sports ConcUssion Events—Rapid Assessment of Concussion and Evidence for Return (RESCUE-RACER): a two-year longitudinal observational study of concussion in motorsport
Authors: Deakin Naomi D , Suckling John , Hutchinson Peter J
Published: January 2021

Introduction

Concussion is a clinical diagnosis, based on self-reported patient symptoms supported by clinical assessments across many domains including postural control, ocular/vestibular dysfunction, and neurocognition. Concussion incidence may be rising in motorsport which, combined with unresolved challenges to accurate diagnosis and lack of guidance on the optimal return-to-race timeframe, creates a difficult environment for healthcare practitioners.

Methods and analysis

Research Evaluating Sports ConcUssion Events—Rapid Assessment of Concussion and Evidence for Return (RESCUE-RACER) evaluates motorsports competitors at baseline (Competitor Assessment at Baseline; Ocular, Neuroscientific (CArBON) study) and post-injury (Concussion Assessment and Return to motorSport (CARS) study), including longitudinal data. CArBON collects pre-injury neuroscientific data; CARS repeats the CArBON battery sequentially during recovery for competitors involved in a potentially concussive event. As its primary outcome, RESCUE-RACER will develop the evidence base for an accurate trackside diagnostic tool. Baseline objective clinical scoring (Sport Concussion Assessment Tool—5th edition (SCAT5)) and neurocognitive data (Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT)) will be assessed for specificity to motorsport and relationship to existing examinations. Changes to SCAT5 and ocular, vestibular, and reaction time function (Dx 100) will be estimated by the reliability change index as a practical tool for trackside diagnosis. Neuropsychological (Cambridge Neuropsychological Test Automated Battery (CANTAB)) assessments, brain MRI (7 Tesla) and salivary biomarkers will be compared with the new tool to establish utility in diagnosing and monitoring concussive injuries.

Ethics and dissemination

Ethical approval was received from East of England-Cambridge Central Research Ethics Committee (18/EE/0141). Participants will be notified of study outcomes via publications (to administrators) and summary reports (funder communications). Ideally, all publications will be open access.

Trial registration number

February 2019 nationally (Central Portfolio Management System 38259) and internationally (ClinicalTrials.govNCT03844282).
Suicide in Nigeria: observations from the content analysis of newspapers
Authors: Oyetunji Tosin Philip , Arafat S M Yasir , Famori Stephen Oluwaseyi , Akinboyewa Timilehin Blessing , Afolami Michael , Ajayi Moyo Faith , Kar Sujita Kumar
Published: January 2021

Background

Suicide is a global public health problem and Nigeria is one of the epicentres of suicide in the world. However, there is a dearth of research exploring the epidemiological aspects of suicide in Nigeria.

Aim

To examine the demographic information and precipitating events for suicides in Nigeria by analysing the contents of newspaper reports of suicide.

Methods

We searched, collected, and analysed published news reports about suicide from 10 English newspapers in Nigeria. A total of 350 suicide reports were assessed between January 2010 and December 2019 after screening and sorting.

Results

The mean (SD) age of the reported cases was 36.33 (15.48) years. Majority of the reported cases were male (80.6%), married (51.8%), students (33.6%), living in a semi-urban area (40.3%) and among the age group of 25–34 (25.3%). Hanging (48.6%) and poisoning (32.2%) were the most commonly reported methods of suicide. Financial constraints and marital conflicts were most commonly assumed precipitating factors.

Conclusion

This study suggests that being male, married, or living in semi-urban areas are associated with suicide in Nigeria. Further community-based studies are warranted to generalise the findings and adopt appropriate preventive strategies.
Synbindin restrains proinflammatory macrophage activation against microbiota and mucosal inflammation during colitis
Authors: Ai Luoyan , Ren Yimeng , Zhu Mingming , Lu Shiyuan , Qian Yun , Chen Zhaofei , Xu Antao
Published: January 2021

Objective

As a canonical membrane tethering factor, the function of synbindin has been expanding and indicated in immune response. Here, we investigated the role of synbindin in the regulation of toll-like receptor 4 (TLR4) signalling and macrophage response to microbiota during colitis.

Design

Three distinct mouse models allowing global, myeloid-specific or intestinal epithelial cell-specific synbindin heterozygous deletion were constructed and applied to reveal the function of synbindin during dextran sodium sulfate (DSS) colitis. Effects of synbindin on TLR4 signalling and macrophage activation in response to bacterial lipopolysaccharide (LPS) or Fusobacterium nucleatum were evaluated. The colocalisation and interaction between synbindin and Rab7b were determined by immunofluorescence and coimmunoprecipitation. Synbindin expression in circulating monocytes and intestinal mucosal macrophages of patients with active IBD was detected.

Results

Global synbindin haploinsufficiency greatly exacerbated DSS-induced intestinal inflammation. The increased susceptibility to DSS was abolished by gut microbiota depletion, while phenocopied by specific synbindin heterozygous deletion in myeloid cells rather than intestinal epithelial cells. Profoundly aberrant proinflammatory gene signatures and excessive TLR4 signalling were observed in macrophages with synbindin interference in response to bacterial LPS or Fusobacterium nucleatum. Synbindin was significantly increased in intestinal mucosal macrophages and circulating monocytes from both mice with DSS colitis and patients with active IBD. Interleukin 23 and granulocyte-macrophage colony-stimulating factor were identified to induce synbindin expression. Mechanistic characterisation indicated that synbindin colocalised and directly interacted with Rab7b, which coordinated the endosomal degradation pathway of TLR4 for signalling termination.

Conclusion

Synbindin was a key regulator of TLR4 signalling and restrained the proinflammatory macrophage activation against microbiota during colitis.
Possible tumour cell reimplantation during curative endoscopic therapy of superficial Barrett’s carcinoma
Authors: Ehlken Hanno , Schmitz Rüdiger , Riethdorf Sabine , Riethdorf Lutz , Krause Jenny , Karstens Karl-Frederick , Schrader Jörg , Viol Fabrice , Giannou Anastasios , Sterlacci William , Vieth Michael , Clauditz Till , Kähler Christian , Mann Oliver , Izbicki Jakob R , Huber Samuel , Pantel Klaus , Rösch Thomas
Published: January 2021

Background and aims

Endoscopic resection has been established as curative therapy for superficial cancer arising from Barrett’s oesophagus (BE); recurrences are very rare. Based on a case series with unusual and massive early recurrences, we analyse the issue of tumour cell reimplantation.

Methods

This hypothesis was developed on the basis of two out of seven patients treated by circumferential (n=6) or nearly circumferential (n=1) en bloc and R0 endoscopic resection of T1 neoplastic BE. Subsequently, a prospective histocytological analysis of endoscope channels and accessories was performed in 2 phases (cytohistological analysis; test for cell viability) in 22 different oesophageal carcinoma patients undergoing endoscopy. Finally, cultures from two oesophageal adenocarcinoma cell lines were incubated with different triamcinolone concentrations (0.625–10 mg/mL); cell growth was determined on a Multiwell plate reader.

Results

Cancer regrowth in the two suspicious cases (male, 78/71 years) occurred 7 and 1 months, respectively, after curative tumour resection. Subsequent surgery showed advanced tumours (T2) with lymph node metastases; one patient died. On cytohistological examinations of channels and accessories, suspicious/neoplastic cells were found in 4/10 superficial and in all 5 advanced cancers. Further analyses in seven further advanced adenocarcinoma cases showed viable cells in two channel washing specimens. Finally, cell culture experiments demonstrated enhanced tumour cell growth by triamcinolone after 24 hours compared with controls.

Conclusions

Tumour cell reimplanation from contaminated endoscopes and accessories is a possible cause of local recurrence after curative endoscopic therapy for superficial Barrett carcinoma; also, corticosteroid injection could have promoted tumour regrowth in these cases.
Firearm injuries in children: a missed opportunity for firearm safety education
Authors: Stokes Sarah C , McFadden Nikia R , Salcedo Edgardo S , Beres Alana L
Published: January 2021

Background

Surgeons frequently care for children who have sustained gunshot wounds (GSWs). However, firearm safety education is not a focus in general surgery training. We hypothesised that firearm safety discussions do not routinely take place when children present to a trauma centre with a GSW.

Method

A retrospective review of patients <18 years presenting with GSWs to a level 1 paediatric trauma centre from 2009 to 2019 was performed. The primary outcome was discussion of firearm safety with the patient or family. The secondary outcome was notification of child protective services (CPS).

Results

A total of 226 patients with GSWs were identified, 22% were unintentional and 63% were assault. Firearm safety discussions took place in 10 cases (4.4%). Firearm safety discussions were more likely to occur after unintentional injuries compared with other mechanisms (16.0% vs 1.3%, p<0.001). CPS was contacted in 29 cases (13%). CPS notification was more likely for unintentional injuries compared with other mechanisms (40% vs 3.9%, p<0.001) and for younger patients (7 years vs 15 years, p<0.001).

Conclusion

At a paediatric trauma centre, firearm safety discussions occurred in 4.4% of cases of children presenting with a GSW. There is a significant room for improvement in providing safety education interventions.
Mapping of colorectal carcinoma diseases with activation of Wnt/beta-catenin signalling pathway using hierarchical clustering approach
Authors: Mosnier Jean-François , Airaud Fabrice , Métairie Sylvie , Volteau Christelle , Bezieau Stéphane , Denis Marc
Published: January 2021

Aims

To map the colorectal carcinoma (CRC) diseases with significant Wnt signalling pathway activation for delineating their clinicopathological and molecular profiles.

Methods

Mapping is based on hierarchical clustering analyses of a series of 283 CRCs. Data tabulated were histopathological patterns, immunophenotypic differentiation,RAS,RAF,CTNNB1mutations and microsatellite instability status, tumour-infiltrating lymphocytes (TILs) and genetic setting. Beta-catenin expression in more than 10% of cell nuclei in the centre of tumour serves as a surrogate marker of significant activation of Wnt signalling pathway.

Results

Nuclei beta-catenin expression was present in 95% of CRCs; 56% of them met the criteria of high level of nuclei beta-catenin expression (≥10%). Proportion of beta-catenin positive nuclei was significantly higher in younger patients, rectal and left-sided colonic carcinomas. CRCs with high level of nuclei beta-catenin expression were regrouped into three clusters: (1) microsatellite stability (MSS) CRCs with no constitutive MAPK pathway activation including 90% of low-grade adenocarcinoma, NOS, with intestinal differentiation without TILs; (2)RAS-mutated MSS CRCs including low-grade adenocarcinoma, NOS, with intestinal differentiation and mucinous adenocarcinoma without TILs; (3) MSI-H CRCs including bothBRAF-mutated CRCs evolving from serrated pathway andCTNNB1-mutated CRCs associated with Lynch syndrome.

Conclusions

MSS low-grade adenocarcinoma, NOS, with intestinal differentiation without TILs (‘crypt-like adenocarcinoma’) might be the morphological pending of canonical molecular subtype of CRC defined as displayed molecular epithelial differentiation and upregulation of WNT in consensus molecular classification of CRC.
Gene of the month:TLE 1
Authors: Pinto Karen , Chetty Runjan
Published: January 2021

TLE 1is the human homologue belonging to a family of four genes and is located on chromosome 9q21. It consists of 19 exons. Although it does not bind directly to DNA, it acts as a repressor of several signalling pathways via transcription factors. TLE1 protein has several physiological roles in embryogenesis, haematopoiesis, general differentiation, and both neuronal and eye development. Much attention was focused on its expression in the tumour cell nuclei of synovial sarcoma (SS). However, several other soft tissue tumours that do and do not share morphological similarity with SS also display nuclear immunoreactivity for TLE1; hence, caution in interpretation is advocated.
Effects of Vasoactive Drugs on Hepatic and Intestinal Circulation and Intestinal Barrier in Patients with Septic Shock
Authors: Liu Jie , Zheng Min , Zhao Xu , Zha Yong-Jiu , Li Hu-Nian , Huang Guang-Qing
Published: January 2021

In this study, 60 patients with septic shock were selected over the course of 1 year, and the effects of dopamine and norepinephrine combined with dobutamine on hepatic and intestinal circulation and intestinal barrier in patients with septic shock were studied by comparison between the control group and the experimental group. All patients received mechanical ventilation to maintain breathing at 14 to 20 times/min. The experimental group was treated with vascular active drugs after adequate rehydration, and the control group only received adequate rehydration. There were extremely significant differences (p<0.01) in the total effective rate of each group. There were significant differences in the hemodynamic indexes in each group (p<0.05). There was a significant difference in total 24-hour bile output (p<0.01). There were significant differences in liver function and blood lipid values in patients (p<0.01). There were significant differences in the repair of epithelial injury at 0 hour, 48 hours and 96 hours (p<0.01). There were significant differences in the transmembrane resistance of monolayer cells (p<0.01). The expression differences of three proteins ZO-1, occludin and β-actin were also significant, among which the three proteins in the control group were weak, while those in groups A and B were strong. The expression of tight junction protein in monolayer cells was weakly positive in expression and strong in other proteins. In conclusion, vasoactive drugs had significant effects on hepatic and intestinal circulation and intestinal barrier in patients with septic shock.
Transcriptional analysis of multiple ovarian cancer cohorts reveals prognostic and immunomodulatory consequences of ERV expression
Authors: Natoli Marina , Gallon John , Lu Haonan , Amgheib Ala , Pinato David J , Mauri Francesco A , Marafioti Teresa , Akarca Ayse U , Ullmo Ines , Ip Jacey , Aboagye Eric O , Brown Robert , Karadimitris Anastasios , Ghaem-Maghami Sadaf
Published: January 2021

Background

Endogenous retroviruses (ERVs) play a role in a variety of biological processes, including embryogenesis and cancer. DNA methyltransferase inhibitors (DNMTi)-induced ERV expression triggers interferon responses in ovarian cancer cells via the viral sensing machinery. Baseline expression of ERVs also occurs in cancer cells, though this process is poorly understood and previously unexplored in epithelial ovarian cancer (EOC). Here, the prognostic and immunomodulatory consequences of baseline ERV expression was assessed in EOC.

Methods

ERV expression was assessed using EOC transcriptional data from The Cancer Genome Atlas (TCGA) and from an independent cohort (Hammersmith Hospital, HH), as well as from untreated or DNMTi-treated EOC cell lines. Least absolute shrinkage and selection operator (LASSO) logistic regression defined an ERV expression score to predict patient prognosis. Immunohistochemistry (IHC) was conducted on the HH cohort. Combination of DNMTi treatment with γδ T cells was tested in vitro, using EOC cell lines and patient-derived tumor cells.

Results

ERV expression was found to define clinically relevant subsets of EOC patients. An ERV prognostic score was successfully generated in TCGA and validated in the independent cohort. In EOC patients from this cohort, a high ERV score was associated with better survival (log-rank p=0.0009) and correlated with infiltration of CD8+PD1+T cells (r=0.46, p=0.0001). In the TCGA dataset, a higher ERV score was found in BRCA1/2 mutant tumors, compared to wild type (p=0.015), while a lower ERV score was found in CCNE1 amplified tumors, compared to wild type (p=0.019). In vitro, baseline ERV expression dictates the level of ERV induction in response to DNMTi. Manipulation of an ERV expression threshold by DNMTi resulted in improved EOC cell killing by cytotoxic immune cells.

Conclusions

These findings uncover the potential for baseline ERV expression to robustly inform EOC patient prognosis, influence tumor immune infiltration and affect antitumor immunity.
Unexpected role ofSIX1variants in craniosynostosis: expanding the phenotype ofSIX1-related disorders
Authors: Calpena Eduardo , Wurmser Maud , McGowan Simon J , Atique Rodrigo , Bertola Débora R , Cunningham Michael L , Gustafson Jonas A , Johnson David , Morton Jenny E V , Passos-Bueno Maria Rita , Timberlake Andrew T , Lifton Richard P , Wall Steven A , Twigg Stephen R F , Maire Pascal , Wilkie Andrew O M
Published: January 2021

Background

Pathogenic heterozygousSIX1variants (predominantly missense) occur in branchio-otic syndrome (BOS), but an association with craniosynostosis has not been reported.

Methods

We investigated probands with craniosynostosis of unknown cause using whole exome/genome (n=628) or RNA (n=386) sequencing, and performed targeted resequencing ofSIX1in 615 additional patients. Expression of SIX1 protein in embryonic cranial sutures was examined in theSix1nLacZ/+reporter mouse.

Results

From 1629 unrelated cases with craniosynostosis we identified seven differentSIX1variants (three missense, including two de novo mutations, and four nonsense, one of which was also present in an affected twin). Compared with population data, enrichment ofSIX1loss-of-function variants was highly significant (p=0.00003). All individuals with craniosynostosis had sagittal suture fusion; additionally four had bilambdoid synostosis. Associated BOS features were often attenuated; some carrier relatives appeared non-penetrant. SIX1 is expressed in a layer basal to the calvaria, likely corresponding to the dura mater, and in the mid-sagittal mesenchyme.

Conclusion

Craniosynostosis is associated with heterozygousSIX1variants, with possible enrichment of loss-of-function variants compared with classical BOS. We recommend screening ofSIX1in craniosynostosis, particularly when sagittal±lambdoid synostosis and/or any BOS phenotypes are present. These findings highlight the role ofSIX1in cranial suture homeostasis.
Effect of lateral therapy switches to oral moderate-efficacy drugs in multiple sclerosis: a nationwide cohort study
Authors: Buron Mathias Due , Kalincik Tomas , Sellebjerg Finn , Sørensen Per Soelberg , Magyari Melinda
Published: January 2021

Background

Switching between first-line disease-modifying therapies in patients with clinically stable relapsing–remitting multiple sclerosis (RRMS) due to reasons other than disease activity is frequent, but evidence on the effect of this practice is limited. We investigated the effect of switching patients with stable RRMS on occurrences of disability accumulation, relapses and future treatment discontinuation.

Methods

Using the Danish Multiple Sclerosis Registry, we identified patients with RRMS without disease activity who either (1) stayed on injectable platform therapy (interferon-β or glatiramer acetate) or (2) switched to dimethyl fumarate (DMF) or teriflunomide (TFL) and compared treatment outcomes using propensity-score-based methods and marginal structural models (MSM).

Results

We included 3206 patients in the study. We found no change in risk of 6-month confirmed Expanded Disability Status Scale score worsening in patients switching to DMF (HR: 1.15, 95% CI 0.88 to 1.50) or TFL (HR: 1.16, 95% CI 0.92 to 1.46). The risk of suffering any relapse tended to decrease when switching to DMF (HR: 0.73, 95% CI 0.51 to 1.04) and tended to increase when switching to TFL (HR: 1.25, 95% CI 0.96 to 1.63). Absolute risk differences were small. MSM analyses showed similar results but did not find an increased relapse risk in TFL switchers.

Conclusion

Switching from injectable platform therapies to oral first-line therapies in patients with clinically stable RRMS does not increase the risk of disability accumulation. While the postswitch risk of relapses trended towards marginally higher on TFL, this trend was eliminated by adjustment for time-variant confounders.
Efficacy of dietary supplements on improving sleep quality: a systematic review and meta-analysis
Authors: Chan Vicky , Lo Kenneth
Published: January 2021

Purpose

Different dietary supplements aimed at improving sleep quality are available on the market, but there has not been a comprehensive review to evaluate the efficacy of these dietary supplements on subjective sleep quality. We aimed to summarise up-to-date research evidence and to identify the types of dietary supplement that improve subjective sleep quality.

Methods

Multiple databases (Ovid Emcare, Ovid MEDLINE (R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and APA PsycInfo) were used for searching papers published until August 2020. The changes in sleep quality indices, intervention duration and sample size were extracted from every paper. To analyse the effect of dietary supplements on sleep quality, a random effects model with mean difference (MD) and 95% CI was adopted. The heterogeneity across studies was measured by I2 statistics. The quality of included studies was evaluated by Cochrane's risk of bias tool.

Results

Thirty-one randomised controlled trials of dietary supplements were included. Subjective sleep quality was significantly improved by supplementation of amino acids (MD −1.27, 95% CI −2.35 to –0.20; I2=0%), melatonin (MD −1.21, 95% CI −2.17 to –0.24; I2=79%) and vitamin D (MD −1.63, 95% CI −3.15 to –0.10; I2=85%). Although not all studies provided adequate data for meta-analysis, we also discussed how magnesium, zinc, resveratrol and nitrate supplementation may improve sleep quality.

Conclusions

Amino acids, vitamin D and melatonin supplements were significantly beneficial to improve sleep quality. However, high heterogeneity and wide confidence levels were observed in vitamin D and melatonin. Further research on the effect of magnesium, zinc, resveratrol and nitrate supplementation on improving sleep quality is required.
Engaging in advocacy during medical training: assessing the impact of a virtual COVID-19-focused state advocacy day
Authors: Yu Zizi , Moustafa Danna , Kwak Ruby , O'Connor Daniel M , Cavanaugh-Hussey Margaret W , Huang Jennifer T , LaChance Avery H
Published: January 2021

Purpose

The physician voice is crucial to shaping health policy and public health guidelines, particularly during COVID-19. However, there are gaps in health policy and advocacy education within graduate medical education. This study sought to characterise the impact of a virtual COVID-19 focused advocacy day among medical trainees in Massachusetts.

Study design

The half-day event featured speakers drawn from government relations experts, physician advocates, and state and federal legislators as well as breakout discussions among attendees. A 25-question Redcap survey and list of resources/opportunities for continued advocacy was administered to all participants at event's conclusion on 19 May 2020.

Results

There were 60 responses from 141 participants (43% response rate). One-third reported no prior formal health policy instruction, and over half reported getting information from news publications, social media and peers. 58% believed physician involvement in advocacy to be ‘extremely important’ prior to COVID-19; 83% believed the same after onset of COVID-19 (p<0.0001). The most common barriers to advocacy engagement were lack of time and knowledge. Most attendees felt participation increased their knowledge and likelihood to engage in the COVID-19 response, imparted useful skills/knowledge for continued advocacy, increased their interest in future similar events, and that such events should be available to all trainees.

Conclusions

Trainees recognise the importance of health policy and advocacy and value opportunities to gain the necessary skills/knowledge to effect tangible change. Virtual advocacy days can be replicated nationwide to help trainees learn about advocacy efforts and find their legislative voices during COVID-19 and beyond.
Prevalence of frailty and reliability of established frailty instruments in adult elective colorectal surgical patients: a prospective cohort study
Authors: Dale MacLaine Thomas , Baker Oliver , Burke Dermot , Howell Simon J
Published: January 2021

Purpose

Large population studies now demonstrate that frailty is prevalent in all adult age groups. Limited data exist on the association between frailty and surgical outcome in younger patients. The aim of the study was to explore the agreement between frailty identification tools and collect pilot data on their predictive value for frailty-associated outcomes in an adult surgical population.

Study design

Prospective cohort study.

Results

Frailty scores were recorded in 200 patients (91 men), mean (range) age 57 (18–92) years. The prevalence of prefrailty was 52%–67% and that of frailty 2%–32% depending on the instrument used. Agreement between the instruments was poor, kappa 0.08–0.17 in pairwise comparisons. Outcome data were available on 160 patients. Only the frailty phenotype was significantly associated with adverse outcomes, RR 6.1 (1.5–24.5) for postoperative complications. The three frailty scoring instruments studies had good sensitivity (Clinical Frailty Scale (CFS)—90%, Accumulation Deficit (AD)—96%, Frailty Phenotype (FP)—97%) but poor specificity (CFS—12%, AD—13%, FP—18%) for the prediction of postoperative complications. All three instruments were poorly predictive of adverse outcomes with likelihood ratios of CFS—1.02, AD—1.09 and FP—1.17.

Conclusions

This study showed a significant prevalence of prefrailty and frailty in adult colorectal surgical patients of all ages. There was poor agreement between three established frailty scoring instruments. Our data do not support the use of current frailty scoring instruments in all adult colorectal surgical patients. However, the significant prevalence of prefrailty and frailty across all age groups of adult surgical patient justifies further research to refine frailty scoring in surgical patients.
HSV-infection-related herpetic anogenital ulcer disease among PLWH in southeastern US: electronic medical record based analysis
Authors: Ye Yuanfan , Burkholder Greer A , Wiener Howard , Aslibekyan Stella , Khan Ashraf E , Shrestha Sadeep
Published: January 2021

Objectives

The southeastern US is a domestic epicentre for incident HIV with high prevalence of herpes simplex virus (HSV) coinfection. We estimated the incidence rates (IR) of symptomatic herpetic anogenital ulcer disease (HAUD) and assessed its associations with demographic and clinical characteristics, specifically with immunological markers using median, nadir and trajectory CD4 counts.

Methods

Electronic medical records (EMR) of over 7000 people living with HIV (PLWH) attending one of the leading HIV clinics in the southeastern US between 2006 and 2018 were reviewed and analysed. IR of HSV-related HAUD were estimated per 10 000 person years. Joinpoint regressions were performed to examine temporal changes in the trends of IR. All IR and trends were stratified by gender and race. Six CD4 trajectory groups were constructed using the group-based trajectory modelling. Multivariable logistic models were conducted to assess the associations of CD4 counts (nadir, median CD4 and newly defined CD4 trajectory), separately with HAUD.

Results

Of the 4484 PLWH eligible individuals (3429 men, 1031 women and 24 transgender), we observed 425 patients with HSV-related HAUD. The mean log10viral load was higher in HAUD than HAUD-free groups, whereas the median nadir CD4 count (cells/uL) was higher in the non-cases than the case groups (p<0.05). HAUD were more frequent in women than men. Median CD4 (<200 cell/uL) was associated with HAUD (OR=2.1), but there were no significant associations with nadir CD4. Significant associations with declining and sustained low CD4 counts trajectory patterns were observed with HAUD.

Conclusions

There were significant differences between men and women with incident HAUD among PLWH. EMR-based studies can provide innovative trajectory models that can potentially be helpful in guiding screening and clinical care of HAUD among high-risk PLWH.
Comparison of the patterns of chlamydia and gonorrhoea at the oropharynx, anorectum and urethra among men who have sex with men
Authors: Tabesh Marjan , Fairley Christopher K , Hocking Jane S , Williamson Deborah A , Zhang Lei , Xu Xianglong , Bradshaw Catriona S , Chen Marcus Y , Chow Eric PF
Published: January 2021

Objective

Chlamydia and gonorrhoea are common sexually transmitted infections that infect the oropharynx, anorectum and urethra in men who have sex with men (MSM). This study aimed to examine the pattern of infection at more than one site (multisite) for chlamydia and gonorrhoea among MSM.

Methods

This was a retrospective study of MSM attending the Melbourne Sexual Health Centre for the first time between 2018 and 2019. We included MSM aged ≥16 years who had tested forNeisseria gonorrhoeaeandChlamydia trachomatisat all three sites (oropharynx, anorectum and urethra). We compared infections that occurred at a single site (termed single-site infection) and those that occurred at more than one site (termed multisite infections).

Results

Of the 3938 men who were tested for chlamydia and gonorrhoea, 498/3938 men (12.6%, 95% CI 11.5% to 13.6%) had chlamydia at any site, of whom 400/498 (80.3%, 95% CI 78.9% to 81.2%) had single-site chlamydia infection, and 98/498 (19.7%, 95% CI 16.2% to 23.1%) had multisite infections. A similar proportion of men had gonorrhoea at any site (447/3938, 11.4%, 95% CI 10.3% to 12.2%), but among these 447 men, single-site infection was less common (256/447, 57.3%, 95% CI 52.6% to 61.7%, p<0.001) and multisite infection (191/447, 42.7%, 95% CI 38.2% to 47.3%, p<0.001) was more common than chlamydia. There were also marked differences by anatomical site. Urethral infection commonly occurred as single sites (75/122, 61.5%, 95% CI 52.8% to 70.1%) for chlamydia but uncommonly occurred for gonorrhoea (12/100, 12.0%, 95% CI 5.6% to 18.3%, p<0.001). In contrast, anorectal infection uncommonly occurred as multisite infection for chlamydia (98/394, 24.9%, 95% CI 20.6% to 29.1%) but was common (184/309, 59.5%, 95% CI 54.0% to 64.9%, p<0.001) for gonorrhoea.

Conclusions

The markedly different pattern of site-specific infection for chlamydia and gonorrhoea infections among the same MSM suggests significant differences in the transmissibility between anatomical sites and the duration of each infection at each site.
SOLUTION OF THE LOCAL FRACTIONAL GENERALIZED KDV EQUATION USING HOMOTOPY ANALYSIS METHOD
Authors: JAFARI HOSSEIN , PRASAD JYOTI GEETESH , GOSWAMI PRANAY , DUBEY RAVI SHANKER
Published: January 2021

In this paper, we solve the [Formula: see text]-Generalized KdV equation by local fractional homotopy analysis method (LFHAM). Further, we analyze the approximate solution in the form of non-differentiable generalized functions defined on Cantor sets. Some examples and special cases of the main results are also discussed.
Magnitude, timing, and rate of slip along the Atacama fault system, northern Chile: implications for Early Cretaceous slip partitioning and plate convergence
Authors: Seymour N.M. , Singleton J.S. , Gomila R. , Mavor S.P. , Heuser G. , Arancibia G. , Williams S. , Stockli D.F.
Published: January 2021

Displacement estimates along the Atacama fault system (AFS), a crustal-scale sinistral structure that accommodated oblique convergence in the Mesozoic Coastal Cordillera arc, vary widely due to a lack of piercing points. We map the distribution of plutons and mylonitic deformation along the northern
c.
70 km of the El Salado segment and use U–Pb geochronology to establish the slip history of the AFS. Along the eastern branch, mylonitic fabrics associated with the synkinematic
c.
134–132 Ma Cerro del Pingo Complex are separated by 34–38 km, and mylonites associated with a synkinematic
c.
120–119 Ma tonalite are separated by 20.5–26 km. We interpret leucocratic intrusions to be separated across the western branch by
c.
16–20 km, giving a total slip magnitude of
c.
54  ±  6 km across the El Salado segment. Kinematic indicators consistently record sinistral shear, and zircon (U–Th)/He data suggest dip-slip motion was insignificant. Displacement occurred between
c.
133–110 Ma at a slip rate of
c.
2.1–2.6 km Myr
–1
. This slip rate is low compared to modern intra-arc strike-slip faults, suggesting (1) the majority of lateral slip was accommodated along the slab interface or distributed through the forearc or (2) plate convergence rates/obliquity were significantly lower than previously modeled.

Supplementary material:
Full U-Pb, (U-Th)/He, petrographic, and structural data with locations is available at
https://doi.org/10.6084/m9.figshare.c.5262177

Thematic collection:
This article is part of the Isotopic dating of deformation collection available at:
https://www.lyellcollection.org/cc/isotopic-dating-of-deformation
Joint Encryption and Compression-Based Watermarking Technique for Security of Digital Documents
Authors: Singh A. K. , Thakur S. , Jolfaei Alireza , Srivastava Gautam , Elhoseny MD. , Mohan A.
Published: January 2021

Recently, due to the increase in popularity of the Internet, the problem of digital data security over the Internet is increasing at a phenomenal rate. Watermarking is used for various notable applications to secure digital data from unauthorized individuals. To achieve this, in this article, we propose a joint encryption then-compression based watermarking technique for digital document security. This technique offers a tool for confidentiality, copyright protection, and strong compression performance of the system. The proposed method involves three major steps as follows: (1) embedding of multiple watermarks through non-sub-sampled contourlet transform, redundant discrete wavelet transform, and singular value decomposition; (2) encryption and compression via SHA-256 and Lempel Ziv Welch (LZW), respectively; and (3) extraction/recovery of multiple watermarks from the possibly distorted cover image. The performance estimations are carried out on various images at different attacks, and the efficiency of the system is determined in terms of peak signal-to-noise ratio (PSNR) and normalized correlation (NC), structural similarity index measure (SSIM), number of changing pixel rate (NPCR), unified averaged changed intensity (UACI), and compression ratio (CR). Furthermore, the comparative analysis of the proposed system with similar schemes indicates its superiority to them.