bluuebunny/crossref_metadata_2025 huggingface dataset:
Necrotising enterocolitis, late-onset sepsis and mortality after routine probiotic introduction in the UK
Authors: Granger Claire , Dermyshi Elda , Roberts Eve , Beck Lauren C , Embleton Nicholas , Berrington Janet
Published: August 2021

Objective

To compare necrotising enterocolitis (NEC), late-onset sepsis (LOS), focal intestinal perforation (FIP) and mortality in infants from a single neonatal unit before and after probiotic introduction.

Design

Retrospective review of infants <32 weeks admitted January 2009–December 2012 (no probiotic) and January 2013–December 2017 (routine probiotics). Infants included were admitted before day 3, and not transferred out before day 3. NEC, LOS and FIP were defined with standard definitions.

Patients

1061 infants were included, 509 preprobiotic and 552 postprobiotic. Median gestation, birth weight and antenatal steroid use did not differ, and proportions of extremely low birthweight infants were similar (37% and 41%).

Results

Overall unadjusted risk of NEC (9.2% (95% CI 7.1 to 12.1) vs 10.6% (95% CI 8.2 to 13.4), p=0.48), LOS (16.3% (95% CI 13.2 to 19.6) vs 14.1% (95% CI 11.5 to 17.4), p=0.37) and mortality (9.2% (95% CI 7.1 to 12.1) vs 9.7% (95% CI 7.6 to 12.6), p=0.76) did not differ, nor proportion of surgical NEC. In multiple logistic regression, accounting for gestation, birth weight, antenatal steroid, maternal milk, chorioamnionitis and sex, probiotic receipt was not significantly associated with NEC (adjusted OR (aOR) 1.08 (95% CI 0.71 to 1.68), p=0.73), LOS or mortality. In subgroup (645 infants) >28 weeks, aOR for NEC in the probiotic cohort was 0.42 (95% CI 0.2 to 0.99, p=0.047). FIP was more common in the probiotic cohort (OR 2.3 (95% CI 1.0 to 5.4), p=0.04), not significant in regression analysis (2.11 (95% CI 0.97 to 4.95), p=0.05).

Conclusions

Probiotic use in this centre did not reduce overall mortality or rates of NEC, LOS or FIP but subgroup analysis identified NEC risk reduction in infants >28 weeks, and LOS reduction <28 weeks.
Serious health threats of novel adulterants of the street heroin: a report from India during the COVID-19 pandemic
Authors: Mahintamani Tathagata , Ghosh Abhishek , Jain Rajeev
Published: August 2021

The COVID-19 pandemic and a consequent nationwide lockdown in India for several weeks had restricted the access to street heroin and treatment for substance abuse. Use of cutting agents to increase the volume or psychoactive effect has been widely practised under such circumstances. Our patient with opioid use disorder chased heroin with an unknown cutting agent to enhance psychoactive effect from the limited quantities of heroin. He suffered from an abrupt onset sedation, weakness, postural imbalance, slurred speech, cognitive dysfunctions and disinhibited behaviour. Symptoms rapidly reversed following abstinence and initiation of buprenorphine–naloxone. Gas chromatography-mass spectrometric analysis of the adulterant revealed high concentrations of benzodiazepines and barbiturates, alongside the usual cutting agents—caffeine and acetaminophen. Abrupt reduction in availability of ‘street drugs’ in conjunction with poor healthcare access can lead to the use of novel adulterants with potentially serious clinical and public health implications.
Benefit of cochlear implantation in a patient with Myhre syndrome
Authors: Di Cesare Tiziana , Rossi Giorgia , Girotto Giorgia , Di Nardo Walter
Published: August 2021

Myhre syndrome is a rare disorder characterised by short stature, skeletal anomalies, facial dysmorphism and hearing loss (HL), resulting from heterozygous mutations of theSMAD4gene. We describe the benefits of cochlear implant (CI) in a patient with sensorineural HL carrying a mutation (NM_005359.6: c.1498A>G; p.lle500Val) within theSMAD4gene, detected by whole-exome sequencing. The CI was inserted through the round window despite otospongiotic abnormalities. Pure-tone audiometry improved up to 20 dBHL. Speech perception in noise (Simplified Noise Reduction - SNR +10) increased from 0% pre implantation with hearing aids to 50% post implantation. The postoperative setting of the electrical stimulation limits yielded an asymmetric map, with lower levels for central electrodes and higher levels for lateral ones. Action potential could not be evoked via medial electrodes, suggesting a cochlear nerve dysfunction. Outcomes related to quality of life and cognitive impairment improved. CI was shown to be an effective auditory rehabilitation strategy.
Coronary artery thrombus resulting in ST-elevation myocardial infarction in a patient with COVID-19
Authors: Green Clara , Nadir Adnan , Lester Will , Dosanjh Davinder
Published: August 2021

COVID-19 is a prothrombotic condition that is also associated with raised troponin levels and myocardial damage. We present a case of a 54-year-old man who was admitted with respiratory failure due to COVID-19 and developed a ST-elevation myocardial infarction (STEMI) during his admission. His coronary angiogram did not show any significant coronary artery disease other than a heavily thrombosed right coronary artery. In view of heavy thrombus burden, the right coronary artery was treated with thrombus retrieval using a distal embolic protection device in addition to manual thrombectomy and direct (intracoronary) thrombolysis without the need for implantation of a coronary stent. After successful revascularisation, triple antithrombotic therapy was instituted with an oral anticoagulant in addition to dual antiplatelets. This case illustrates the association of COVID-19 with coronary artery thrombosis, which may require disparate management of a STEMI than that resulting from atherosclerotic coronary artery disease.
Galactosaemia occurring in association with primary ovarian insufficiency, Addison’s disease and chronic myeloid leukaemia
Authors: Khoury Brandon , Shakir Mohamed KM , Hoang Thanh Duc
Published: August 2021

Classic galactosaemia is the most severe type, inherited in an autosomal recessive fashion and normally detected on newborn screening. It is caused by an inability to digest galactose due to a deficiency of galactose-1-phosphate uridyltransferase (GALT), resulting in an intolerance of feeds in the neonatal period, failure to thrive, hypoglycaemia, jaundice, cataracts, hepatomegaly, vomiting, diarrhoea, developmental delay and an increased risk ofEscherichia colisepsis. The long-term sequelae of this disorder include cognitive impairment, neurological symptoms, such as ataxia, nutritional deficiencies, such as calcium and vitamin D, and gonadal dysfunction. We report here a case of a 34-year-old woman with classic galactosaemia diagnosed in adulthood, developing primary ovarian insufficiency and osteoporosis as well as primary adrenal insufficiency and chronic myeloid leukaemia, which are two associations not seen in current literature. Further studies are needed to determine if an association exists between these diseases.
Direct selective laser trabeculoplasty in open angle glaucoma study design: a multicentre, randomised, controlled, investigator-masked trial (GLAUrious)
Authors: Congdon Nathan , Azuara-Blanco Augusto , Solberg Yoram , Traverso Carlo E , Iester Michele , Cutolo Carlo Alberto , Bagnis Alessandro , Aung Tin , Fudemberg Scott J , Lindstrom Richard , Samuelson Thomas , Singh Kuldev , Blumenthal Eytan Z , Gazzard Gus
Published: August 2021

Introduction

Laser trabeculoplasty is an effective and widely used treatment for glaucoma. A new laser technology, the Eagle direct selective laser trabeculoplasty (DSLT) device, may provide automated, fast, simple, safe and effective laser treatment for glaucoma in a broader range of clinical settings. This trial aims to test the hypothesis that translimbal DSLT is effective and not inferior to selective laser trabeculoplasty (SLT) in reducing intraocular pressure (IOP) in open angle glaucoma (OAG).

Methods and analysis

This is a multicentre, randomised, controlled, investigator-masked study. The primary efficacy outcome is intergroup difference in mean change from baseline IOP measured at 6 months. Secondary outcomes include mean percentage reduction in IOP at 3, 6 and 12 months; proportion of participants with at least 20% reduction in IOP from baseline at 6 months; change in ocular hypotensive medications at 12 months and evaluation of safety. Participants were aged >= 40 years with OAG, including exfoliative or pigmentary glaucoma, or ocular hypertension with untreated or washed out IOP 22–35 mm Hg. Treatments: DSLT: 120 shots, 3 ns, 400 µm spot size, energy 1.4–1.8 mJ delivered at the limbus over 2 s. SLT: approximately 100 shots, 3 ns, 400 µm spot size administered 360 degrees at the limbus using any gonioscopy lens, energy 0.3–2.6 mJ. A sample size of 164 is sufficient to detect a non-inferiority margin of 1.95 mm Hg for change from baseline IOP.

Clinical trial registration number

NCT03750201,ISRCTN14033075.
Topical carbonic anhydrase inhibitors and glaucoma in 2021: where do we stand?
Authors: Stoner Ari , Harris Alon , Oddone Francesco , Belamkar Aditya , Verticchio Vercellin Alice Chandra , Shin Joshua , Januleviciene Ingrida , Siesky Brent
Published: August 2021

Carbonic anhydrase inhibitors (CAIs) have been used for many decades in the treatment of glaucoma. Systemic CAIs were an early treatment option to lower intraocular pressure by reducing aqueous humour production; however, frequent side effects including polyuria and paresthesia contributed to the eventual development of topical CAIs. As topical drug development evolved over time, prostaglandin analogues and beta-blockers have become the gold standard of glaucoma therapies. Although prescribed less often than other classes of topical glaucoma therapies, topical CAIs continue to be used in combination therapies with beta-blockers and alpha agonists. Topical CAIs have also been demonstrated to alter biomarkers of ocular haemodynamics, which have relevance in glaucoma. The purpose of this review is to review and summarise the current state of topical CAI prescribing trends, known efficacy and suggested mechanisms and potential influence on ocular haemodynamics for the future of glaucoma management.
Joint associations of metabolically healthy abdominal obesity and non-alcoholic fatty liver disease with prediabetes and diabetes in Chinese adults
Authors: Zhang Junfeng , Xu Qiaoyan , Lai Fangfang , Chen Ning , Lin Mingzhu , Liu Yongwen , Zhang Wei , Liu Changqin , Wang Shunqin , Li Zhibin
Published: August 2021

Introduction

We aimed to evaluate the joint associations of metabolically healthy abdominal obesity (MHAO) with non-alcoholic fatty liver disease (NAFLD) on risks of diabetes and prediabetes.

Research design and methods

Baseline information of 1318 adults with abdominal obesity (waist circumference ≥90 cm for men and 80 cm for women) from an ongoing cohort study in Xiamen, China were analyzed. Metabolic health was identified as none of the criteria of metabolism syndrome, except for obesity, was met.

Results

MHAO and metabolically unhealthy abdominal obesity (MUAO) were identified on 173 (13.1%) and 1145 (86.9%) subjects. NAFLD was further diagnosed on 60 (34.7%) in MHAO and 721 (63.0%) in MUAO groups (p<0.001). Both MUAO (vs MHAO) and NAFLD (vs non-NAFLD) were independently associated with increased risks of diabetes as well as prediabetes plus diabetes, with the adjusted ORs (95% CIs) of 9.40 (3.38 to 26.14) and 2.02 (1.47 to 2.77), respectively. Compared with MHAO and non-NAFLD, MHAO and NAFLD showed significantly increased risks of prediabetes plus diabetes with the adjusted ORs (95% CIs) of 2.87 (1.32 to 6.27, p=0.008). And there were significantly positive trends between increasing categories jointly by MHAO and NAFLD (from MHAO and non-NAFLD, MHAO and NAFLD, MUAO and non-NAFLD to MUAO and NAFLD) with risks of diabetes and prediabetes plus diabetes (both trend tests: p<0.001).

Conclusions

About 35% of subjects with MHAO accompanied by NAFLD showed excessive risk of prediabetes plus diabetes compared with MHAO and non-NAFLD. Thus, NAFLD should be screened and intervened even for those subjects with metabolically healthy obesity (MHO) and should be considered as one additional criterion when defining and diagnosing MHO.
CPD in the remote environment: a role for practice-based small group learning?
Authors: Eager Michael Mathew , Capella S C , Willman A , Taylor N
Published: August 2021

Background

Continuous professional development (CPD) is recognised as essential and mandated by the Royal College of General Practitioners and other medical professional colleges. However, it can be difficult to maintain when deployed and remote from normal training and support structures. There is no literature directly discussing how military doctors in the deployed and remote environment maintain CPD and if practice-based small group learning (PBSGL) could be an appropriate tool to facilitate this in future.

Aim

To describe the CPD experience of medical officers (MOs) working for the Defence Medical Services (DMS) and assess if offering PBSGL would be welcomed and likely beneficial.

Design and setting

This is a quantitative survey of doctors working in primary care within the DMS.

Method

A questionnaire was designed to elicit opinions, current practice and previous experience of CPD within the deployed and firm base environments. It also aimed to elicit prior experience of and appetite for PBSGL as a solution. This was then distributed via email to MOs working for the DMS.

Results

130 responses (25%) were received. 122 (96%) had heard of PBSGL, 56% had participated in PBSGL in the firm base. 60% agreed or strongly agreed PBSGL was an effective way to maintain CPD. 73% reported eLearning as a mode of maintaining CPD while deployed or working in a remote environment.

Conclusion

This study demonstrated that many general practitioners deployed to remote locations feel that CPD provision could be improved and that PBSGL is a potential solution.
Impact of the gate-keeping policies of China’s primary healthcare model on the future burden of tuberculosis in China: a protocol for a mathematical modelling study
Authors: You Xinyi , Gu Jing , Xu Dong Roman , Huang Shanshan , Xue Hao , Hao Chun , Ruan Yunzhou , Sylvia Sean , Liao Jing , Cai Yiyuan , Peng Liping , Wang Xiaohui , Li Renzhong , Li Jinghua , Hao Yuantao
Published: August 2021

Introduction

In the past three decades, China has made great strides in the prevention and treatment of tuberculosis (TB). However, the TB burden remains high. In 2019, China accounted for 8.4% of global incident cases of TB, the third highest in the world, with a higher prevalence in rural areas. The Healthy China 2030 highlights the gate-keeping role of primary healthcare (PHC). However, the impact of PHC reforms on the future TB burden is unclear. We propose to use mathematical models to project and evaluate the impacts of different gate-keeping policies.

Methods and analysis

We will develop a deterministic, population-level, compartmental model to capture the dynamics of TB transmission within adult rural population. The model will incorporate seven main TB statuses, and each compartment will be subdivided by service providers. The parameters involving preference for healthcare seeking will be collected using discrete choice experiment (DCE) method. We will solve the deterministic model numerically over a 20-year (2021–2040) timeframe and predict the TB prevalence, incidence and cumulative new infections under the status quo or various policy scenarios. We will also conduct an analysis following standard protocols to calculate the average cost-effectiveness for each policy scenario relative to the status quo. A numerical calibration analysis against the available published TB prevalence data will be performed using a Bayesian approach.

Ethics and dissemination

Most of the data or parameters in the model will be obtained based on secondary data (eg, published literature and an open-access data set). The DCE survey has been reviewed and approved by the Ethics Committee of the School of Public Health, Sun Yat-sen University. The approval number is SYSU [2019]140. Results of the study will be disseminated through peer-reviewed journals, media and conference presentations.
Co-designing a dashboard of predictive analytics and decision support to drive care quality and client outcomes in aged care: a mixed-method study protocol
Authors: Ludlow Kristiana , Westbrook Johanna , Jorgensen Mikaela , Lind Kimberly E , Baysari Melissa T , Gray Leonard C , Day Richard O , Ratcliffe Julie , Lord Stephen R , Georgiou Andrew , Braithwaite Jeffrey , Raban Magdalena Z , Close Jacqueline , Beattie Elizabeth , Zheng Wu Yi , Debono Deborah , Nguyen Amy , Siette Joyce , Seaman Karla , Miao Melissa , Root Jo , Roffe David , O’Toole Libby , Carrasco Marcela , Thompson Alex , Shaikh Javed , Wong Jeffrey , Stanton Cynthia , Haddock Rebecca
Published: August 2021

Introduction

There is a clear need for improved care quality and quality monitoring in aged care. Aged care providers collect an abundance of data, yet rarely are these data integrated and transformed in real-time into actionable information to support evidence-based care, nor are they shared with older people and informal caregivers. This protocol describes the co-design and testing of a dashboard in residential aged care facilities (nursing or care homes) and community-based aged care settings (formal care provided at home or in the community). The dashboard will comprise integrated data to provide an ‘at-a-glance’ overview of aged care clients, indicators to identify clients at risk of fall-related hospitalisations and poor quality of life, and evidence-based decision support to minimise these risks. Longer term plans for dashboard implementation and evaluation are also outlined.

Methods

This mixed-method study will involve (1) co-designing dashboard features with aged care staff, clients, informal caregivers and general practitioners (GPs), (2) integrating aged care data silos and developing risk models, and (3) testing dashboard prototypes with users. The dashboard features will be informed by direct observations of routine work, interviews, focus groups and co-design groups with users, and a community forum. Multivariable discrete time survival models will be used to develop risk indicators, using predictors from linked historical aged care and hospital data. Dashboard prototype testing will comprise interviews, focus groups and walk-through scenarios using a think-aloud approach with staff members, clients and informal caregivers, and a GP workshop.

Ethics and dissemination

This study has received ethical approval from the New South Wales (NSW) Population & Health Services Research Ethics Committee and Macquarie University’s Human Research Ethics Committee. The research findings will be presented to the aged care provider who will share results with staff members, clients, residents and informal caregivers. Findings will be disseminated as peer-reviewed journal articles, policy briefs and conference presentations.
What work-related exposures are associated with post-traumatic stress disorder? A systematic review with meta-analysis
Authors: Coenen Pieter , van der Molen Henk F
Published: August 2021

Objectives

Although there is evidence that work-related exposures cause post-traumatic stress disorder (PTSD), there are few quantitative studies assessing the degree to which these factors contribute to PTSD. This systematic review with meta-analysis identified work-related exposures associated with PTSD, and quantified their contribution to this disorder.

Methods

We searched Medline, PsycINFO, Embase, PILOTS and Web of Science (2005–10 September 2019) for longitudinal studies on work-related exposures and PTSD. We described included articles, and conducted meta-analyses for exposures with sufficient homogeneous information. We performed subgroup analyses for risk of bias, study design and PTSD ascertainment. We assessed evidence quality using Grades of Recommendations, Assessment, Development and Evaluation, and estimated population attributable fractions.

Results

After screening 8590 records, we selected 33 studies (n=5 719 236). From what was moderate quality evidence at best, we identified various work-related exposures that were associated with PTSD, mainly involving individuals in the military and first responder (eg, police or fire brigade) occupations. These exposures included the number of army deployments (OR: 1.15 (95% CI 1.14 to 1.16)), combat exposure (OR 1.89 (95% CI 1.46 to 2.45)), army deployment (OR 1.79 (95% CI 1.45 to 2.21)) and confrontation with death (OR 1.63 (95% CI 1.41 to 1.90)). Effects were robust across subgroups and exposures attributed modestly (7%–34%) to PTSD. We identified additional exposures in other occupations, including life threats, being present during an attack, and hearing about a colleague’s trauma.

Conclusions

We identified various work-related exposures associated with PTSD and quantified their contribution. While exposure assessment, PTSD ascertainment and inconsistency may have biased our findings, our data are of importance for development of preventive interventions and occupational health guidelines.
Impact of social restrictions during the COVID-19 pandemic on the physical activity levels of adults aged 50–92 years: a baseline survey of the CHARIOT COVID-19 Rapid Response prospective cohort study
Authors: Salman David , Beaney Thomas , E Robb Catherine , de Jager Loots Celeste A , Giannakopoulou Parthenia , Udeh-Momoh Chinedu T , Ahmadi-Abhari Sara , Majeed Azeem , Middleton Lefkos T , McGregor Alison H
Published: August 2021

Objectives

Physical inactivity is more common in older adults, is associated with social isolation and loneliness and contributes to increased morbidity and mortality. We examined the effect of social restrictions to reduce COVID-19 transmission in the UK (lockdown), on physical activity (PA) levels of older adults and the social predictors of any change.

Design

Baseline analysis of a survey-based prospective cohort study.

Setting

Adults enrolled in the Cognitive Health in Ageing Register for Investigational and Observational Trials cohort from general practitioner practices in North West London were invited to participate from April to July 2020.

Participants

6219 cognitively healthy adults aged 50–92 years completed the survey.

Main outcome measures

Self-reported PA before and after the introduction of lockdown, as measured by metabolic equivalent of task (MET) minutes. Associations of PA with demographic, lifestyle and social factors, mood and frailty.

Results

Mean PA was significantly lower following the introduction of lockdown from 3519 to 3185 MET min/week (p<0.001). After adjustment for confounders and prelockdown PA, lower levels of PA after the introduction of lockdown were found in those who were over 85 years old (640 (95% CI 246 to 1034) MET min/week less); were divorced or single (240 (95% CI 120 to 360) MET min/week less); living alone (277 (95% CI 152 to 402) MET min/week less); reported feeling lonely often (306 (95% CI 60 to 552) MET min/week less); and showed symptoms of depression (1007 (95% CI 612 to 1401) MET min/week less) compared with those aged 50–64 years, married, cohabiting and not reporting loneliness or depression, respectively.

Conclusions and implications

Markers of social isolation, loneliness and depression were associated with lower PA following the introduction of lockdown in the UK. Targeted interventions to increase PA in these groups should be considered.
Home spirometry utilisation in telemedicine clinic for cystic fibrosis care during COVID-19 pandemic: a quality improvement process
Authors: Compton Martina , List Rhonda , Starheim Elissa , Somerville Lindsay , Williamson Lauren , Murray Rachel , Jennings Deirdre , Bruschwein Heather , Albon Dana
Published: August 2021

Introduction

The Cystic Fibrosis (CF) Foundation chronic care guidelines recommend monitoring spirometry during quarterly multidisciplinary visits to identify early lung function decline. During the COVID-19 pandemic, the CF adult clinic at University of Virginia (UVA) transitioned from the classic CF care model to a model that included quarterly multidisciplinary telemedicine visits. While using telemedicine, CF care needed to include spirometry monitoring. Only a fraction of adult CF patients at UVA owned and used home spirometers (HS) in March 2020.

Aim

The specific aims of this quality improvement (QI) project were to increase the percentage of eligible adult CF patients who owned an HSs from 37% to 85% and to increase the percentage of adult CF patients seen at UVA with available spirometry in telemedicine from 50% to 95% by 31 December 2020.

Methods

Following the Model for Improvement QI methodology, a standardised process was developed for monitoring forced expiratory volume in 1 s with HS during multidisciplinary telemedicine visits during the COVID-19 pandemic.

Intervention

(1) HSs were distributed to eligible patients and (2) Home spirometry was monitored in eligible patients with each telemedicine visit and results were used for clinical care decisions.

Results

Both specific aims were achieved ahead of expected date. In March 2020, the beginning of the pandemic, 37% (49/131) of patients owned an HS and 50% (9/18) of patients seen via telemedicine performed spirometry at home. By September 2020, 97% (127/131) of adult patients at UVA owned an HS and by October 2020, 96% (24/25) of patients provided spirometry results during their telemedicine encounters.

Conclusion

Employing QI tools to standardise the process of monitoring spirometry data with home devices via telemedicine is reliable and sustainable and can be replicated across centres that provide care for patients with CF.
Increasing the low-risk threshold for patients with upper gastrointestinal bleeding during the COVID-19 pandemic: a prospective, multicentre feasibility study
Authors: Dunne Philip , Livie Victoria , McGowan Aaron , Siu Wilson , Chaudhary Sardar , Groome Maximillian , Phull Perminder , Fraser Andrew , Morris Allan John , Penman Ian D , Stanley Adrian J
Published: August 2021

Objective

During the COVID-19 pandemic, we extended the low-risk threshold for patients not requiring inpatient endoscopy for upper gastrointestinal bleeding (UGIB) from Glasgow Blatchford Score (GBS) 0–1 to GBS 0–3. We studied the safety and efficacy of this change.

Methods

Between 1 April 2020 and 30 June 2020 we prospectively collected data on consecutive unselected patients with UGIB at five large Scottish hospitals. Primary outcomes were length of stay, 30-day mortality and rebleeding. We compared the results with prospective prepandemic descriptive data.

Results

397 patients were included, and 284 index endoscopies were performed. 26.4% of patients had endoscopic intervention at index endoscopy. 30-day all-cause mortality was 13.1% (53/397), and 33.3% (23/69) for pre-existing inpatients. Bleeding-related mortality was 5% (20/397). 30-day rebleeding rate was 6.3% (25/397). 84 patients had GBS 0–3, of whom 19 underwent inpatient endoscopy, 0 had rebleeding and 2 died. Compared with prepandemic data in three centres, there was a fall in mean number of UGIB presentations per week (19 vs 27.8; p=0.004), higher mean GBS (8.3 vs 6.5; p<0.001) with fewer GBS 0–3 presentations (21.5% vs 33.3%; p=0.003) and higher all-cause mortality (12.2% vs 6.8%; p=0.02). Predictors of mortality were cirrhosis, pre-existing inpatient status, age >70 and confirmed COVID-19. 14 patients were COVID-19 positive, 5 died but none from UGIB.

Conclusion

During the pandemic when services were under severe pressure, extending the low-risk threshold for UGIB inpatient endoscopy to GBS 0–3 appears safe. The higher mortality of patients with UGIB during the pandemic is likely due to presentation of a fewer low-risk patients.
Epigenetic promoter alterations in GI tumour immune-editing and resistance to immune checkpoint inhibition
Authors: Sundar Raghav , Huang Kie-Kyon , Kumar Vikrant , Ramnarayanan Kalpana , Demircioglu Deniz , Her Zhisheng , Ong Xuewen , Bin Adam Isa Zul Fazreen , Xing Manjie , Tan Angie Lay-Keng , Tai David Wai Meng , Choo Su Pin , Zhai Weiwei , Lim Jia Qi , Das Thakur Meghna , Molinero Luciana , Cha Edward , Fasso Marcella , Niger Monica , Pietrantonio Filippo , Lee Jeeyun , Jeyasekharan Anand D , Qamra Aditi , Patnala Radhika , Fabritius Arne , De Simone Mark , Yeong Joe , Ng Cedric Chuan Young , Rha Sun Young , Narita Yukiya , Muro Kei , Guo Yu Amanda , Skanderup Anders Jacobsen , So Jimmy Bok Yan , Yong Wei Peng , Chen Qingfeng , Göke Jonathan , Tan Patrick
Published: August 2021

Objectives

Epigenomic alterations in cancer interact with the immune microenvironment to dictate tumour evolution and therapeutic response. We aimed to study the regulation of the tumour immune microenvironment through epigenetic alternate promoter use in gastric cancer and to expand our findings to other gastrointestinal tumours.

Design

Alternate promoter burden (APB) was quantified using a novel bioinformatic algorithm (proActiv) to infer promoter activity from short-read RNA sequencing and samples categorised into APBhigh, APBintand APBlow.Single-cell RNA sequencing was performed to analyse the intratumour immune microenvironment. A humanised mouse cancer in vivo model was used to explore dynamic temporal interactions between tumour kinetics, alternate promoter usage and the human immune system. Multiple cohorts of gastrointestinal tumours treated with immunotherapy were assessed for correlation between APB and treatment outcomes.

Results

APBhighgastric cancer tumours expressed decreased levels of T-cell cytolytic activity and exhibited signatures of immune depletion. Single-cell RNAsequencing analysis confirmed distinct immunological populations and lower T-cell proportions in APBhightumours. Functional in vivo studies using ‘humanised mice’ harbouring an active human immune system revealed distinct temporal relationships between APB and tumour growth, with APBhightumours having almost no human T-cell infiltration. Analysis of immunotherapy-treated patients with GI cancer confirmed resistance of APBhightumours to immune checkpoint inhibition. APBhighgastric cancer exhibited significantly poorer progression-free survival compared with APBlow(median 55 days vs 121 days, HR 0.40, 95% CI 0.18 to 0.93, p=0.032).

Conclusion

These findings demonstrate an association between alternate promoter use and the tumour microenvironment, leading to immune evasion and immunotherapy resistance.
Incident aortic stenosis in 49 449 men and 42 229 women investigated with routine echocardiography
Authors: Stewart Simon , Chan Yih-Kai , Playford David , Strange Geoffrey A
Published: August 2021

Objective

We addressed the paucity of data describing the characteristics and consequences of incident aortic stenosis (AS).

Methods

Adults undergoing echocardiography with a native aortic valve (AV) and no AS were studied. Subsequent age-specific and sex-specific incidence of AS were derived from echocardiograms conducted a median of 2.8 years apart. Progressive AV dysfunction and individually linked mortality were examined per AS category.

Results

49 449 men (53.9%, 60.9±15.8 years) and 42 229 women (61.6±16.9 years) with no initial evidence of AS were identified. Subsequently, 6293 (6.9%) developed AS—comprising 5170 (5.6%), 636 (0.7%), 339 (0.4%) and 148 (0.2%) cases of mild, moderate, severe low-gradient and severe high-gradient AS, respectively. Age-adjusted incidence rates of all grades of AS were 17.5 cases per 1000 men/annum and 18.7 cases per 1000 women/annum: rising from ~5 to ~40 cases per 1000/annum in those aged <30 years vs >80 years. Median peak AV velocity increased by +0.57 (+0.36 to +0.80) m/s in mild AS compared with +2.75 (+2.40 to +3.19) m/s in severe high-gradient AS cases between first and last echocardiograms. During subsequent median 7.7 years follow-up, 24 577 of 91 678 cases (26.8%) died. Compared with no AS, the adjusted risk of all-cause mortality was 1.42-fold higher in mild AS, 1.92-fold higher in moderate AS, 1.95-fold higher in severe low-gradient AS and 2.27-fold higher in severe, high-gradient AS cases (all p<0.001).

Conclusions

New onset AS is a common finding among older patients followed up with echocardiography. Any grade of AS is associated with higher mortality, reinforcing the need for proactive vigilance.
The impact of software-based metal artifact reduction on the liquid embolic agent Onyx in cone-beam CT: a systematic in vitro and in vivo study
Authors: Schmitt Niclas , Weyland Charlotte S , Wucherpfennig Lena , Sommer Christof M , Bendszus Martin , Möhlenbruch Markus A , Vollherbst Dominik F
Published: August 2021

Background

Onyx is frequently used for endovascular embolization of intracranial arteriovenous malformations (AVMs) and dural arteriovenous fistulas (dAVFs). One drawback of using Onyx is the generation of artifacts in cone-beam CT (CBCT). These artifacts can represent an obstacle for the detection of periprocedural hemorrhage or planning of subsequent radiosurgery. This study investigates the effect of artifact reduction by the syngo DynaCT SMART Metal Artifact Reduction (MAR) software.

Methods

A standardized in vitro tube model (n=10) was filled with Onyx 18 and CBCT image acquisition was conducted in a brain imaging phantom. Furthermore, post-interventional CBCT images of 20 patients with AVM (n=13) or dAVF (n=7), each treated with Onyx, were investigated. The MAR software was applied for artifact reduction. Artifacts of the original and the post-processed images were analyzed quantitatively (standard deviation in a region of interest on the layer providing the most artifacts) and qualitatively. For the patient images, the effect of the MAR software on brain parenchyma on artifact-free images was further investigated.

Results

Quantitative and qualitative analyses of both datasets demonstrated a lower degree of artifacts in the post-processed images (eg, patient images: 38.30±22.03 density units (no MAR; mean SD±SD) vs 19.83±12.31 density units (with MAR; p<0.001). The MAR software had no influence on the brain parenchyma in artifact-free images.

Conclusion

The MAR software significantly reduced the artifacts evoked by Onyx in CBCT without affecting the visualization of brain parenchyma on artifact-free images. Applying this software could thus improve the quality of periprocedural CBCT images after embolization with Onyx.
Patterns of negative seroconversion in ongoing surveys of SARS-CoV-2 antibodies among workers in New York’s largest healthcare system
Authors: Sembajwe Grace , Rasul Rehana , Jacobs Yehuda , Edwards Keisha , Chambers Lewis Lorraine , Chang Tylis , Lowe William , Moline Jacqueline
Published: August 2021

Objectives

Given the importance of continued COVID-19 surveillance, our objective was to present findings from a short follow-up survey of workforce SARS-CoV-2 antibody testing in previously seropositive participants and describe associations between work locations and negative seroconversion.

Methods

We conducted a follow-up cross-sectional survey on previously seropositive healthcare workers, using questionnaires and serology testing. Eligible employees previously consented to be contacted were invited by email to participate in a survey and laboratory blood draws. SAS V.9.4 was used to describe employee characteristics and seroconversion status. Binomial regression models were used to calculate unadjusted and adjusted prevalence ratios (PRs) of seronegativity. The multivariable analyses included age, gender, race/ethnicity, region of residence, work location, prior diagnosis/PCR results and days between antibody tests. Unadjusted and adjusted PRs 95% CIs and p values were reported.

Results

Of the 3990 employees emailed in the follow-up, 1631 completed an exposure survey and generated a blood-draw requisition form. Average time between serology testing was 4 months. Of the 955 employees with complete serology results, 79.1% were female, 53.4% were white and 46.4% resided in Long Island; 176 participants seroconverted to negative. In multivariable regression analyses adjusted for gender, race/ethnicity and region of residence, younger employees (<20–30 years), intensive care unit workers and those with no/negative prior PCR results were more likely to have negative seroconversion.

Conclusions and relevance

Patterns of negative seroconversion showed significant differences by sociodemographic and workplace characteristics. These results contribute information to workplace serosurveillance.
Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL)
Authors: Tan Rhea YY , Drazyk Anna M , Urankar Kathryn , Bailey Clare , Gräf Stefan , Markus Hugh , Giffin Nicola J
Published: August 2021

A 44-year-old Caucasian man presented with seizures and cognitive impairment. He had marked retinal drusen, and MR brain scan showed features of cerebral small vessel disease; he was diagnosed with a leukoencephalopathy of uncertain cause. He died at the age of 46 years and postmortem brain examination showed widespread small vessel changes described as a vasculopathy of unknown cause. Seven years postmortem, whole-genome sequencing identified a homozygous nonsenseHTRA1mutation (p.Arg302Ter), giving a retrospective diagnosis of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy.
Child involvement in meal preparation and grocery shopping is associated with lower levels of food fussiness among young children
Authors: Broad Julia , Forbes Laura , Darlington Gerarda , Ma David W.L. , Haines Jess
Published: August 2021

This study examined associations between child food involvement and food fussiness. Analyses used survey data from 62 children ages 1.5 to 5.9 years who participated in the Guelph Family Health Study Pilot. Overall involvement (β = –0.51, p = 0.02), involvement in meal preparation (β = –0.42, p = 0.009), and involvement in grocery shopping (β = –0.29, p = 0.04) were inversely associated with food fussiness. Experimental research including larger, more diverse samples is needed to test whether food involvement reduces food fussiness among young children.

Novelty:

Our study identified significant, inverse associations between child food involvement and food fussiness
Fine-scale altitudinal gradients influence the relationships between structural attributes and aboveground biomass in Central Africa
Authors: Menanzala Miambam Eymard , Loubota Panzou Grace Jopaul , Bocko Yannick Enock , Loumeto Jean Joël
Published: August 2021

There is increasing interest in altitude effects on structural attributes and aboveground biomass (AGB) in tropical forests. However, we continue to lack a clear understanding of relationships between structural attributes and AGB along altitudinal gradients in Central Africa. Using a new network of 76 permanent plots of 0.5 ha, the relationships between structural attributes and AGB were explored along fine-scale altitudinal gradients in the Republic of Congo. We chose four fine-scale altitudinal gradients (71–350 m, 350–550 m, 550–650 m, and 650–853 m) and measured the diameter and heights of 4192 trees with a ≥10 cm diameter and calculated the structural attributes and the AGB for each 0.5 ha plot. For a given diameter, trees were shorter and had narrower crowns in the altitudinal gradient of 71–350 m than in the other altitudinal gradients. The relationships between structural attributes and AGB differ along fine-scale altitudinal gradients, with higher stem density, wood density, crown depth, and AGB for the altitudinal gradient of 71–350 m. These results provide important advances in our understanding of the relationships between structural attributes and AGB along fine-scale altitudinal gradients in Central Africa. They should improve AGB estimates for the low altitudinal gradient when combined with other field and remotely sensed data sets in Central Africa.
Exact solution of two-potential system under same range approximation and its implication
Authors: Sarkar P. , Khirali B. , Laha U. , Sahoo P.
Published: August 2021

In this paper, exact analytical expressions for the Jost solution and Jost function are derived for motion in the nuclear Manning–Rosen plus the Hulthén potential to study both the bound and scattering state observables. The proton-deuteron and alpha-carbon systems are studied to judge the merit of our approach. Our results are found in reasonable agreement with experimental data.
On the positivity of the first Chern class of an Ulrich vector bundle
Authors: Lopez Angelo Felice
Published: August 2021

We study the positivity of the first Chern class of a rank [Formula: see text] Ulrich vector bundle [Formula: see text] on a smooth [Formula: see text]-dimensional variety [Formula: see text]. We prove that [Formula: see text] is very positive on every subvariety not contained in the union of lines in [Formula: see text]. In particular, if [Formula: see text] is not covered by lines we have that [Formula: see text] is big and [Formula: see text]. Moreover we classify rank [Formula: see text] Ulrich vector bundles [Formula: see text] with [Formula: see text] on surfaces and with [Formula: see text] or [Formula: see text] on threefolds (with some exceptions).
Estimates of the topological degree of a class of piecewise linear maps with applications
Authors: Poggiolini Laura , Spadini Marco
Published: August 2021

We provide some new estimates for the topological degree of a class of continuous and piecewise linear maps based on a classical integral computation formula. We provide applications to some nonlinear problems that exhibit a local [Formula: see text] structure.
On generalized zero-divisor graphs of a non-commutative ring with respect to an ideal
Authors: Baruah Priyanka Pratim , Patra Kuntala
Published: August 2021

Let R be a non-commutative ring, and I be an ideal of R. In this paper, we generalize the definition of the zero-divisor graph of R with respect to I, and define several generalized zero-divisor graphs of R with respect to I. In this paper, we investigate the ring-theoretic properties of R and the graph-theoretic properties of all the generalized zero-divisor graphs. We study some basic properties of these generalized zero-divisor graphs related to the connectedness, the diameter and the girth. We also investigate some properties of these generalized zero-divisor graphs with respect to primal ideals.
Two-phase intracontinental deformation mode in the context of India–Eurasia collision: insights from a structural analysis of the West Kunlun–Southern Junggar transect along the NW margin of the Tibetan Plateau
Authors: Chen Hanlin , Lin Xiubin , Cheng Xiaogan , Gong Junfeng , Bian Shuang , Wu Lei , Jia Chengzao , Yang Shufeng , Guo Zhaojie , Jia Dong
Published: August 2021

The convergence of India and Eurasia, which began in the early Cenozoic, established the Tibetan Plateau and the Circum-Tibetan Plateau Basin and Orogen System. When and how the convergence-driving strain propagated into this system is important in deciphering the growth processes of the Tibetan Plateau. We conducted a structural analysis of the West Kunlun–southern Junggar transect along the NW margin of the Tibetan Plateau to establish the propagation of deformation and, through this, to determine the plateau growth processes. Our results suggest a two-phase deformation mode. The first-stage features deformation confined to pre-existing weak zones (e.g. the West Kunlun orogen, the Buchu Uplift and the Tian Shan orogen) during the Paleogene, when the intracontinental strain is speculated to be mainly consumed by shortening of these weak zones. The second stage is characterized by deformation propagating into the foreland regions since the early Miocene, where shortening along the foreland fold–thrust belts on a scale of tens of kilometres and decreasing basinwards had a key role in absorbing intracontinental strain. We suggest that this two-phase deformation mode may reflect a shift in the governing mechanism of the expansion of the Tibetan Plateau from a rigid block to a critical wedge taper style.

Thematic collection:
This article is part of the Fold-and-thrust belts collection available at:
https://www.lyellcollection.org/cc/fold-and-thrust-belts
Self-Ordering of Porous Anodic Alumina Fabricated by Anodizing in Chromic Acid at High Temperature
Authors: Kikuchi Tatsuya , Yamashita Motoki , Iwai Mana , Suzuki Ryosuke O.
Published: August 2021

Anodizing Al in chromic acid is a very useful surface finishing process for corrosion protection and nanoscale porous structure fabrication, whereas the self-ordering of porous anodic alumina (PAA) in chromic acid has never been found to date. Herein, we provide a self-ordered PAA film possessing numerous sub100-nm-scale characteristic bumps through anodizing in chromic acid at high temperature. Anodizing of high purity Al plates in a 0.3 M chromic acid solution at conventional low temperatures, such as 293 K, leads to the formation of a disordered PAA film, whereas anodizing at a high temperature of 348 K causes the self-ordering behavior of the pore structure. The PAA film grown in the initial stage possessed the highest regularity, and it decreased with anodizing time due to pore branching during anodizing. A highly ordered PAA film measuring approximately 340 nm in interpore distance can be fabricated by short-term, two-step anodizing in chromic acid at 348 K and 120 V. The ordered PAA film possesses a characteristic nanostructure consisting of hexagonally arranged 100-nm-scale pores and sub100-nm-scale disordered bumps on their pore walls without any electrolyte chromate anion.
Characterization of the A-type potassium current in murine gastric fundus smooth muscles
Authors: Amberg Gregory C. , Lee Ji Yeon , Koh Sang Don , Sanders Kenton M.
Published: August 2021

Transient outward, or “A-type,” currents are rapidly inactivating voltage-gated potassium currents that operate at negative membrane potentials. A-type currents have not been reported in the gastric fundus, a tonic smooth muscle. We used whole cell voltage clamp to identify and characterize A-type currents in smooth muscle cells (SMCs) isolated from murine fundus. A-type currents were robust in these cells with peak amplitudes averaging 1.5 nA at 0 mV. Inactivation was rapid with a time constant of 71 ms at 0 mV; recovery from inactivation at −80 mV was similarly rapid with a time constant of 75 ms. A-type currents in fundus were blocked by 4-aminopyridine (4-AP), flecainide, and phrixotoxin-1 (PaTX1). Remaining currents after 4-AP and PaTX1 displayed half-activation potentials that were shifted to more positive potentials and showed incomplete inactivation. Currents after tetraethylammonium (TEA) displayed half inactivation at −48.1 ± 1.0 mV. Conventional microelectrode and contractile experiments on intact fundus muscles showed that 4-AP depolarized membrane potential and increased tone under conditions in which enteric neurotransmission was blocked. These data suggest that A-type K+ channels in fundus SMCs are likely active at physiological membrane potentials, and sustained activation of A-type channels contributes to the negative membrane potentials of this tonic smooth muscle. Quantitative analysis of Kv4 expression showed that Kcnd3 was dominantly expressed in fundus SMCs. These data were confirmed by immunohistochemistry, which revealed Kv4.3-like immunoreactivity within the tunica muscularis. These observations indicate that Kv4 channels likely form the A-type current in murine fundus SMCs.
Investigating Helicobacter pylori-related pyloric hypomotility: functional, histological, and molecular alterations
Authors: Ashraf Aya Aly , Gamal Sarah Mahmoud , Ashour Hend , Aboulhoda Basma Emad , Rashed Laila Ahmed , Harb Inas Anas , Abdelfattah Gaber Hassan , El-Seidi Eman Ahmed , Shawky Heba Mohamed
Published: August 2021

This work is investigating functional, histopathological, and molecular changes underlying Helicobacter pylori hypomotility and is correlating these with miR-1, whose disturbance is supposed to be involved in smooth muscle dysfunction and cell proliferation according to literature. Epithelial to mesenchymal transition and reduced ghrelin hormone may contribute to H. pylori infection-associated hypomotility. H. pylori infection was associated with reduced pyloric miR-1 expression. Targeting miR-1 could be valuable in the clinical management of pyloric hypofunction.