bluuebunny/crossref_metadata_2025 huggingface dataset:
Cumulative Febrile, Respiratory, and Gastrointestinal Illness Among Infants in Rural Guatemala and Association With Neurodevelopmental and Growth Outcomes
Authors: Olson Daniel , Lamb Molly M. , Connery Amy K. , Colbert Alison M. , Calvimontes Diva M. , Bauer Desiree , Paniagua-Avila M. Alejandra , Martínez María Alejandra , Arroyave Paola , Hernandez Sara , Colborn Kathryn L. , Roell Yannik , Waggoner Jesse J. , Natrajan Muktha S. , Anderson Evan J. , Bolaños Guillermo A. , El Sahly Hana M. , Munoz Flor M. , Asturias Edwin J.
Published: June 2023

Background:

Infectious disease exposures in early life are increasingly recognized as a risk factor for poor subsequent growth and neurodevelopment. We aimed to evaluate the association between cumulative illness with neurodevelopment and growth outcomes in a birth cohort of Guatemalan infants.

Methods:

From June 2017 to July 2018, infants 0–3 months of age living in a resource-limited region of rural southwest Guatemala were enrolled and underwent weekly at-home surveillance for caregiver-reported cough, fever, and vomiting/diarrhea. They also underwent anthropometric assessments and neurodevelopmental testing with the Mullen Scales of Early Learning (MSEL) at enrollment, 6 months, and 1 year.

Results:

Of 499 enrolled infants, 430 (86.2%) completed all study procedures and were included in the analysis. At 12–15 months of age, 140 (32.6%) infants had stunting (length-for-age Z [LAZ] score < –2 SD) and 72 (16.7%) had microcephaly (occipital-frontal circumference [OFC] < –2 SD). In multivariable analysis, greater cumulative instances of reported cough illness (beta = –0.08/illness-week, P = 0.06) and febrile illness (beta = –0.36/illness-week, P < 0.001) were marginally or significantly associated with lower MSEL Early Learning Composite (ELC) Score at 12–15 months, respectively; there was no association with any illness (cough, fever, and/or vomiting/diarrhea; P = 0.27) or with cumulative instances of diarrheal/vomiting illness alone (P = 0.66). No association was shown between cumulative instances of illness and stunting or microcephaly at 12–15 months.

Conclusions:

These findings highlight the negative cumulative consequences of frequent febrile and respiratory illness on neurodevelopment during infancy. Future studies should explore pathogen-specific illnesses, host response associated with these syndromic illnesses, and their association with neurodevelopment.
Laparoscopic Sleeve Gastrectomy With Transit Loop Bipartition and Transit Bipartition in Type 2 Diabetic Patients With Obesity: A Retrospective Analysis
Authors: Demir Canan , Arslan Ergin , Sariyildiz Gülçin , Anil Cüneyd , Banli Oktay
Published: June 2023

Aim:

We aimed to compare 1-year postoperative results of patients with obesity and type 2 diabetes mellitus (T2DM) who underwent laparoscopic sleeve gastrectomy with transit bipartition (LSG-TB) and transit loop bipartition (LSG-TLB) and mini gastric bypass (MGB).

Patients and Methods:

This is a retrospective comparison of 2 novel bariatric surgery techniques with MGB. Primary outcome measure of the study was a rate of T2DM remission. Secondary outcomes included excess body mass index (BMI) loss, improvement in hepatosteatosis, and duration of operation. Revision surgery needs were also assessed.

Results:

Overall, 32 patients underwent the LSG-TLB, 15 underwent LSG-TB, and 50 underwent MGB. Mean age and sex distribution were comparable for all groups. Presurgical BMI was similar in MGB and LSG + TB groups, whereas LSG + TLB group had significantly lower BMI values compared with the MGB group. In both groups, BMI values reduced significantly compared with respective baseline values. Excess BMI loss was significantly higher in patients who underwent LSG-TLB compared with patients treated with LSG-TB and MGB. Bariatric surgery procedures lasted shorter in LSG-TLB than in LSG-TB. However, the shortest of all was MGB. The remission of T2DM rates were 71% and 73.3% in LSG-TLB and LSG-TB groups, respectively (P > 9.999). The rate of revision surgeries was comparable in both groups.

Conclusion:

In conclusion, LSG-TLB took less time and provided significantly higher excess BMI loss compared with LSG-TB. T2DM remission and improvement rates were similar in both groups. LSG-TLB seemed like a promising bariatric surgery technique in patients with obesity and T2DM.
Systematic single-cell analysis reveals dynamic control of transposable element activity orchestrating the endothelial-to-hematopoietic transition
Authors: Feng Cong , Tie Ruxiu , Xin Saige , Chen Yuhao , Li Sida , Hu Xiaotian , Zhou Yincong , Liu Yongjing , Hu Yueming , Hu Yanshi , Pan Hang , Wu Zexu , Chao Haoyu , Zhang Shilong , Ni Qingyang , Huang Jinyan , Luo Wenda , Huang He , Chen Ming
Published: June 2023

Background

The endothelial-to-hematopoietic transition (EHT) process during definitive hematopoiesis in vertebrate is highly conserved. Stage-specific expression of transposable elements (TEs) has been detected during zebrafish EHT and may promote hematopoietic stem cell formation by activating inflammatory signaling. However, little is known about how TEs contribute to the EHT process in human and mouse.

Results

We reconstructed the single-cell EHT trajectories of human and mouse, and resolved the dynamic expression patterns of TEs during EHT. Most TEs presented a transient co-upregulation pattern along the conserved EHT trajectories. Enhanced TE activation was tightly associated with the temporal relaxation of epigenetic silencing systems. TE products can be sensed by multiple pattern recognition receptors, triggering inflammatory signaling to facilitate the emergence of hematopoietic stem cells. Furthermore, we observed that hypoxia-related signals were enriched in cells with higher TE expression. Additionally, we constructed the hematopoietic cis-regulatory network of accessible TEs and identified potential enhancers derived by TEs, which may boost the expression of specific EHT marker genes.

Conclusions

Our study provides a systematic vision on how TEs are dynamically controlled to promote the hematopoietic fate decision through transcriptional and cis-regulatory networks, and pre-train the immunity of nascent hematopoietic stem cells.
Drebrin Regulates Collateral Axon Branching in Cortical Layer II/III Somatosensory Neurons
Authors: Dorskind Joelle M. , Sudarsanam Sriram , Hand Randal A. , Ziak Jakub , Amoah-Dankwah Maame , Guzman-Clavel Luis , Soto-Vargas John Lee , Kolodkin Alex L.
Published: June 2023

Proper cortical lamination is essential for cognition, learning, and memory. Within the somatosensory cortex, pyramidal excitatory neurons elaborate axon collateral branches in a laminar-specific manner that dictates synaptic partners and overall circuit organization. Here, we leverage mouse models, single-cell labeling and imaging approaches to identify intrinsic regulators of laminar-specific collateral, also termed interstitial, axon branching. We developed new approaches for the robust, sparse, labeling of layer II/III pyramidal neurons to obtain single-cell quantitative assessment of axon branch morphologies. We combined these approaches with cell-autonomous loss-of-function (LOF) and over-expression (OE) manipulations in anin vivocandidate screen to identify regulators of cortical neuron axon branch lamination. We identify a role for the cytoskeletal binding protein drebrin (Dbn1) in regulating layer II/III cortical projection neuron (CPN) collateral axon branchingin vitro.LOF experiments show that Dbn1 is necessary to suppress the elongation of layer II/III CPN collateral axon branches within layer IV, where axon branching by layer II/III CPNs is normally absent. Conversely,Dbn1OE produces excess short axonal protrusions reminiscent of nascent axon collaterals that fail to elongate. Structure-function analyses implicate Dbn1S142phosphorylation and Dbn1 protein domains known to mediate F-actin bundling and microtubule (MT) coupling as necessary for collateral branch initiation upon Dbn1 OE. Taken together, these results contribute to our understanding of the molecular mechanisms that regulate collateral axon branching in excitatory CPNs, a key process in the elaboration of neocortical circuit formation.

Significance Statement

Laminar-specific axon targeting is essential for cortical circuit formation. Here, we show that the cytoskeletal protein drebrin (Dbn1) regulates excitatory layer II/III cortical projection neuron (CPN) collateral axon branching, lending insight into the molecular mechanisms that underlie neocortical laminar-specific innervation. To identify branching patterns of single cortical neuronsin vivo, we have developed tools that allow us to obtain detailed images of individual CPN morphologies throughout postnatal development and to manipulate gene expression in these same neurons. Our results showing that Dbn1 regulates CPN interstitial axon branching bothin vivoandin vitroand may aid in our understanding of how aberrant cortical neuron morphology contributes to dysfunctions observed in Autism Spectrum Disorder (ASD) and epilepsy.
Cryogenic tensile performance of 3D printed onyx–continuous carbon fiber composites
Authors: Siddiqui Sanna F. , Archer Andre , Fandetti Dustin , McGee Carl
Published: June 2023

Purpose

The aerospace, energy and automotive industries have seen wide use of composite materials because of their excellent mechanical properties, along with the benefit of weight reduction savings. As such, the purpose of this study is to provide an understanding of the mechanical performance of these materials under extreme operational conditions characteristic of in-service environments.

Design/methodology/approach

This study is novel in that it has evaluated the tensile performance and fracture response of additively manufactured continuous carbon fiber embedded in an onyx matrix (i.e. nylon with chopped carbon fiber) at cryogenic and room temperatures, for specimens manufactured with an angle between the specimen lying plane and the working build plane of 0°, 45° and 90°.

Findings

Research findings reveal enhanced tensile properties (i.e. ultimate tensile strength and modulus of elasticity) by the 0° (X) built specimens, as compared with the 45° (XZ45) and 90° (Z) built specimens at cryogenic temperature. A reduction in ductility is observed at cryogenic temperature for all build orientations. Fractographic analysis reveals the presence of fiber pullout/elongation, pores within the onyx matrix and chopped carbon fiber near fracture zone of the onyx matrix.

Research limitations/implications

Research findings present tensile properties (i.e. ultimate tensile strength, modulus of elasticity and elongation%) for three-dimensional (3D)-printed onyx with and without reinforcing continuous carbon fiber composites at cryogenic and room temperatures. Reinforcement of continuous carbon fibers and reduction to cryogenic temperatures appears to result, in general, in an increase in the tensile strength and modulus of elasticity, with a reduction in elongation% as compared with the onyx matrix tensile performance reported at room temperature. Fracture analysis reveals continuous carbon fiber pull out for onyx–carbon fiber samples tested at room temperature and cryogenic temperatures, suggesting weak onyx matrix–continuous carbon fiber adhesion.

Originality/value

To the best of the authors’ knowledge, this study is the first study to report on the cryogenic tensile properties and fracture response exhibited by 3D-printed onyx–continuous carbon fiber composites. Evaluating the viability of common commercial 3D printing techniques in producing composite parts to withstand cryogenic temperatures is of critical import, for aerospace applications.
Leadership and collective learning: a case study of a social entrepreneurial organisation in Sweden
Authors: Eslahchi Morteza
Published: June 2023

Purpose

This paper aims to enrich the scholarly discourse on learning within small social entrepreneurial organisations by examining how leadership can facilitate conditions conducive to collective learning during crises.

Design/methodology/approach

A longitudinal single-case study was conducted on a social entrepreneurial organisation in Sweden, operating within the integration field. The study involved comprehensive interviews and observations. Using a longitudinal approach facilitated an in-depth analysis of the organisation’s development over time.

Findings

The findings underscore that shifts in leadership can significantly influence collective learning. Specifically, the results suggest that establishing trust between the CEO and team members is a pivotal factor in cultivating conditions for collective learning and fostering the related processes, which persisted even during the pandemic. This trust catalysed inclusive and interactive actions that encouraged team members’ participation in day-to-day decision-making and strategic planning. Consequently, the organisation successfully leveraged its diverse knowledge resources, promoting knowledge sharing and experience exchange, crucial components of successful collective learning.

Research limitations/implications

This paper advocates for a departure from conventional leadership perspectives, proposing that a focus on team–leader relationships – a form of leadership in practice – can offer valuable insights into cultivating collective learning. This approach underscores the significance of collaboration and engagement among team members in promoting collective learning and accentuates the role of leadership in creating these conditions.

Practical implications

The examples provided on structuring, organising and leading virtual meetings could offer valuable insights for leaders. With the increasing adoption of hybrid workplaces combining remote and office environments, communication challenges within teams may arise. Therefore, these examples can aid leaders in formulating effective communication strategies that bridge the gap between remote and in-person team members, ensuring that everyone stays informed and engaged.

Originality/value

This study seized a unique opportunity to explore how leadership can create favourable conditions for collective learning during crises by collecting data both before and during the Covid-19 pandemic.
Intravenous anakinra for the treatment of haemophagocytic lymphohistiocytosis/macrophage activation syndrome: A systematic review
Authors: Charlesworth James E. G. , Kavirayani Akhila
Published: June 2023

Background

Haemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS) has a potentially high mortality rate. Anakinra, an interleukin‐1 receptor antagonist, is now recommended early in HLH/MAS, with intravenous (IV) use proposed in critically unwell patients. This systematic review establishes the literature relating to IV anakinra in secondary HLH/MAS (sHLH/MAS).

Methods

We screened Embase, PubMed, and Medline, including all reports of IV anakinra for HLH or MAS. We extracted age, HLH/MAS trigger, continuous infusion or bolus dosing, and survival.

Results

Twenty‐nine case reports/series identified 87 patients (median age 22 years, range 22 months to 84 years), all with sHLH. Amongst identifiable triggers, 43% were systemic infection, 33% rheumatological, 9% oncological. Children had predominantly a rheumatological trigger (48%), whilst adults were more commonly infection‐driven (50%). Overall, rheumatologically triggered disease showed greater survival (83.3%), particularly compared with oncological triggers (42.9%). Children had a greater survival, particularly under 10 years (83%, vs. adults, 63%).

Conclusions

Despite IV anakinra recipients likely to be critically unwell, this cohort had similar disease triggers and survival compared to large historical cohorts, and enhances awareness of age and trigger‐specific survival patterns. IV anakinra had a wide therapeutic dosing range and tolerability, regardless of trigger, demonstrating substantial utility in severe sHLH/MAS.
Performance Measurement and Discharge Data Based Analysis of Ultrasonic Assisted μEDM for Ti6Al4V
Authors: Raza Sohaib , Airao Jay , Nirala Chandrakant Kumar
Published: June 2023

Unconventional machining of difficult-to-cut conductive materials with high accuracy, low heat-affected zone formation, and the ability to cut intricate geometries entitles micro-electrical discharge machining (μEDM) as the most versatile technology in micromachining. Ultrasonic vibration assistance further enhances the material-removing ability of the μEDM process while imparting several other benefits. The present work proposes a comparative study between the unassisted and ultrasonic vibration assisted μEDM to the tool electrode for machining microslots on Ti6Al4V material using an in-house developed tool holder. The characteristics of the discharge waveforms were captured using a data acquisition system at high sampling rates. The pulse discrimination system is used to perform an in-depth study of the discharge pulses. μEDM milling experiments were performed to machine microslots at varying input voltages, capacitances, and feed rates. The ultrasonic vibrations proved beneficial in addressing the primary issue associated with the μEDM process, i.e., the material removal rate (MRR) with a maximum of 35% increment. Applying ultrasonic vibrations reduced the recast layer and tool wear rate (TWR) and increased the surface finish.
Mitigation of the Pressure Pulsations in an Axial Turbine at Speed-No-Load With Independent Guide Vanes Opening
Authors: Kranenbarg Jelle , Jonsson Pontus P. , Mulu Berhanu G. , Cervantes Michel J.
Published: June 2023

Hydraulic turbines are operated more frequently at no-load conditions, also known as speed-no-load (SNL), to provide a spinning reserve that can rapidly connect to the electrical grid. As intermittent energy sources gain popularity, turbines will be required to provide spinning reserves more frequently. Previous studies show vortical flow structures in the vaneless space and the draft tube and rotating stall between the runner blades of certain axial turbines operating at SNL conditions. These flow phenomena are associated with pressure pulsations and torque fluctuations which put high stress on the turbine. The origin of the instabilities is not fully understood and not extensively studied. Moreover, mitigation techniques for SNL must be designed and explored to ensure the safe operation of the turbines at off-design conditions. This study presents a mitigation technique with independent control of each guide vane. The idea is to open some of the guide vanes to the best efficiency point (BEP) angle while keeping the remaining ones closed, aiming to reduce the swirl and thus avoid the instability to develop. The restriction is to have zero net torque on the shaft. Results show that the flow structures in the vaneless space can be broken down, which decreases pressure and velocity fluctuations. Furthermore, the rotating stall between the runner blades is reduced. The time-averaged flow upstream of the runner is changed while the flow below the runner remains mainly unchanged.
Supporting Coaches to Learn Through and From Their Everyday Experiences: A 1:1 Coach Development Workflow for Performance Sport
Authors: Muir Bob , North Julian
Published: June 2023

This paper overviews an intensive 1:1 coach development workflow developed and used in U.K. performance and high-performance sport. The workflow has been field tested with over 60 coaches in mainly Olympic and Paralympic settings in a variety of sports. The workflow proposes six main stages: “beginning new relationships,” “seeking first to understand,” “preparing for reflective conversations,” “engaging in reflective conversations,” “working with difference,” and “supporting change.” The stages are tailored pragmatically to context, and the workflow does not suggest a fixed sequence. The application of the workflow requires adaptive expertise based on considerable coach development experience and a breadth and depth of coaching and coach development knowledge. The workflow suggests the need for coach developers to build and support trusting, collaborative, and supportive relationships with the coach, as a foundation for the coach development task. Coach development practices and the workflow are continually being developed and refined in a U.K. context, and future work will provide case studies, evidence of outcomes, and refinements to the work.
IPAC integrates rewarding and environmental memory during the acquisition of morphine CPP
Authors: Liu Huan-Min , Liao Ming-Lu , Liu Guan-Xi , Wang Lai-Jian , Lian Dian , Ren Jie , Chi Xin-Tian , Lv Zhuo-Ran , Liu Meng , Wu Yan , Xu Ting , Wei Jia-You , Feng Xia , Jiang Bin , Zhang Xue-Qin , Xin Wen-Jun
Published: June 2023

The association between rewarding and drug-related memory is a leading factor for the formation of addiction, yet the neural circuits underlying the association remain unclear. Here, we showed that the interstitial nucleus of the posterior limb of the anterior commissure (IPAC) integrated rewarding and environmental memory information by two different receiving projections from ventral tegmental area (VTA) and nucleus accumbens shell region (NAcSh) to mediate the acquisition of morphine conditioned place preference (CPP). A projection from the VTA GABAergic neurons (VTA
GABA
) to the IPAC lateral region GABAergic neurons (IPACL
GABA
) mediated the effect of morphine rewarding, whereas the pathway from NAcSh dopamine receptor 1–expressing neurons (NAcSh
D1
) to the IPAC medial region GABAergic neurons (IPACM
GABA
) was involved in the acquisition of environmental memory. These findings demonstrated that the distinct IPAC circuits VTA
GABA
→
IPACL
GABA
and NAcSh
D1R
→
IPACM
GABA
were attributable to the rewarding and environmental memory during the acquisition of morphine CPP, respectively, and provided the circuit-based potential targets for preventing and treating opioid addiction.
Cooperation between physiological defenses and immune resistance produces asymptomatic carriage of a lethal bacterial pathogen
Authors: Chen Grischa Y. , Thorup Natalia R. , Miller Abigail J. , Li Yao-Cheng , Ayres Janelle S.
Published: June 2023

Animals evolved two defense strategies to survive infections. Antagonistic strategies include immune resistance mechanisms that operate to kill invading pathogens. Cooperative or physiological defenses mediate host adaptation to the infected state, limiting physiological damage and disease, without killing the pathogen, and have been shown to cause asymptomatic carriage and transmission of lethal pathogens. Here, we demonstrate that physiological defenses cooperate with the adaptive immune response to generate long-term asymptomatic carriage of the lethal enteric murine pathogen,
Citrobacter rodentium
. Asymptomatic carriage of genetically virulent
C. rodentium
provided immune resistance against subsequent infections. Immune protection was dependent on systemic antibody responses and pathogen virulence behavior rather than the recognition of specific virulent antigens. Last, we demonstrate that an avirulent strain of
C. rodentium
in the field has background mutations in genes that are important for LPS structure. Our work reveals insight into how asymptomatic infections can arise mechanistically with immune resistance, mediating exclusion of phenotypically virulent enteric pathogen to promote asymptomatic carriage.
Structural disruption of Ntox15 nuclease effector domains by immunity proteins protects against type VI secretion system intoxication in Bacteroidales
Authors: Bosch Dustin E. , Abbasian Romina , Parajuli Bishal , Peterson S. Brook , Mougous Joseph D.
Published: June 2023

Bacteroidales use type VI secretion systems (T6SS) to competitively colonize and persist in the colon. We identify a horizontally transferred T6SS with Ntox15 family nuclease effector (Tde1) that mediates interbacterial antagonism among Bacteroidales, including several derived from a single human donor. Expression of cognate (Tdi1) or orphan immunity proteins in acquired interbacterial defense systems protects against Tde1-dependent attack. We find that immunity protein interaction induces a large effector conformational change in Tde nucleases, disrupting the active site and altering the DNA-binding site. Crystallographic snapshots of isolated Tde1, the Tde1/Tdi1 complex, and homologs from
Phocaeicola vulgatus
(Tde2/Tdi2) illustrate a conserved mechanism of immunity inserting into the central core of Tde, splitting the nuclease fold into two subdomains. The Tde/Tdi interface and immunity mechanism are distinct from all other polymorphic toxin–immunity interactions of known structure. Bacteroidales abundance has been linked to inflammatory bowel disease activity in prior studies, and we demonstrate that Tde and T6SS structural genes are each enriched in fecal metagenomes from ulcerative colitis subjects. Genetically mobile Tde1-encoding T6SS in Bacteroidales mediate competitive growth and may be involved in inflammatory bowel disease. Broad immunity is conferred by Tdi1 homologs through a fold-disrupting mechanism unique among polymorphic effector–immunity pairs of known structure.

IMPORTANCE

Bacteroidales are related to inflammatory bowel disease severity and progression. We identify type VI secretion system (T6SS) nuclease effectors (Tde) which are enriched in ulcerative colitis and horizontally transferred on mobile genetic elements. Tde-encoding T6SSs mediate interbacterial competition. Orphan and cognate immunity proteins (Tdi) prevent intoxication by multiple Tde through a new mechanism among polymorphic toxin systems. Tdi inserts into the effector central core, splitting Ntox15 into two subdomains and disrupting the active site. This mechanism may allow for evolutionary diversification of the Tde/Tdi interface as observed in colicin nuclease–immunity interactions, promoting broad neutralization of Tde by orphan Tdi. Tde-dependent T6SS interbacterial antagonism may contribute to Bacteroidales diversity in the context of ulcerative colitis.
Development and Application of a Nanobody-Based Competitive ELISA for Detecting Antibodies against Hepatitis E Virus from Humans and Domestic Animals
Authors: Chen Yiyang , Zhang Meimei , Chen Tianxiang , Wang Jiaxi , Zhao Qin , Zhou En-Min , Liu Baoyuan
Published: June 2023

HEV is thought to be a zoonotic infection and is widespread worldwide; it is beneficial to establish a more convenient and spectral method for HEV antibody detection. In this study, a convenient, time-saving, reproducible, highly sensitive, specific, and novel nanobody-based cELISA was developed and can be used to detect IgG antibodies against mammalian HEV. It provides a new technique for serological evaluation and ELISA-based diagnosis of HEV infection.
SARS-CoV-2 case detection using community event-based surveillance system—February–September 2020: lessons learned from Senegal
Authors: Seck Oumy , Loko Roka Jerlie , Ndiaye Mamadou , Namageyo-Funa Apophia , Abdoulaye Sam , Mangane Abdoulaye , Dieye Ndeye Licka , Ndoye Babacar , Diop Boly , Ting Jim , Pasi Omer
Published: June 2023

The COVID-19 pandemic necessitated the rapid development and implementation of effective surveillance systems to detect and respond to the outbreak in Senegal. In this documentation, we describe the design and implementation of the Community Event-Based Surveillance (CEBS) system in Senegal to strengthen the existing Integrated Disease Surveillance and Response system. The CEBS system used a hotline and toll-free number to collect and triage COVID-19-related calls from the community. Data from the CEBS system were integrated with the national system for further investigation and laboratory testing. From February to September 2020, a total of 10 760 calls were received by the CEBS system, with 10 751 calls related to COVID-19. The majority of calls came from the Dakar region, which was the epicentre of the outbreak in Senegal. Of the COVID-19 calls, 50.2% were validated and referred to health districts for further investigation, and 25% of validated calls were laboratory-confirmed cases of SARS-CoV-2. The implementation of the CEBS system allowed for timely detection and response to potential COVID-19 cases, contributing to the overall surveillance efforts in the country. Lessons learned from this experience include the importance of decentralised CEBS, population sensitisation on hotlines and toll-free usage, and the potential role of Community Health Workers in triaging alerts that needs further analysis. This experience highlights the contribution of a CEBS system in Senegal and provides insights into the design and operation of such a system. The findings can inform other countries in strengthening their surveillance systems and response strategies.
Stakeholder-identified barriers and enablers to ultrasound implementation in inflammatory bowel disease services in the UK: a qualitative interview study
Authors: Radford Shellie , Leighton Paul , Coad Jane , Moran Gordon
Published: June 2023

Objectives

The study sought to explore and better understand the perceptions and experiences of stakeholders in relation to the use of ultrasound for the assessment of inflammatory bowel disease (IBD) in adults in the UK.

Design

A qualitative semistructured interview study, using template analysis and normalisation process theory, was undertaken.

Setting

Interviews were conducted using virtual meeting software.

Results

Fourteen participants were enrolled between 2nd of June 2021 and 6th of September 2021. Participants were from the following roles: medical gastroenterology and radiology doctors, IBD nurse specialists, patients living with IBD, healthcare service managers. Participants reported that perceived barriers included reliance on established imaging and care pathways, reluctance to change, lack of trust in ultrasound in relation to perceived lack of precision and the initial financial and time outlay in establishing an ultrasound service. Participants were enthusiastic for the uptake of ultrasound and discussed enablers to ultrasound uptake including the benefits to patients in terms of reduction in waiting times and earlier diagnosis and treatment allocation, reduced number of hospital appointments and patients having better understanding of their health.

Conclusion

There are perceived barriers to achieving implementation of ultrasound. There is scant literature to effectively assess these reported barriers. Therefore, there is further research required in the areas of the impact of the use of ultrasound for the assessment of IBD in the UK.
Melatonin effects on sleep quality of COVID-19 patients: a protocol for systematic review and meta-analysis of randomised controlled trials with trial sequential analysis
Authors: Zhang Juan Juan , Sun Ran , Guo Sha , Zhang Hong
Published: June 2023

Introduction

Sleep disturbance is one of the common complaints of patients with COVID-19 infection. Melatonin is a physiological indoleamine involved in circadian rhythm regulation and it is currently used for secondary sleep disorders caused by various diseases. Some clinical randomised controlled trials (RCTs) have obtained a small amount of evidence and controversial results in support of their therapeutic effect on sleep disorders, but no studies have summarised and evaluated RCTs in all current databases to obtain conclusive results. Therefore, the aim of this systematic review and meta-analysis was to determine the efficacy and safety of melatonin in the treatment of sleep disturbances in patients with COVID-19.

Methods and analysis

We will search for RCT-type studies of melatonin in the treatment of sleep disturbances in patients with COVID-19. From inception to October 2022 will be available on PubMed/MEDLINE, Web of Science, Embase, CINAHL, PsycINFO, LILACS, SCOPUS, Cochrane Central Register of Controlled Trials, ICTRP, Wanfang Data, VIP database and CNKI, VIP database, China Biomedical Literature Database to search for eligible studies. There are no language and geographical restrictions. Two authors will independently screen and select eligible studies, assess methodological quality and perform data extraction. Two additional authors will independently extract data from each study. Then, meta-analysis will then be carried out using a fixed-effects or random-effects model, using the mean difference for continuous outcomes and the relative risk for dichotomous outcomes. Risk of bias assessment will be assessed using the Cochrane risk-of-bias tool. Heterogeneity between studies was assessed by Cochrane Q-test and I2. The quality of evidence for each outcome will be assessed using the Grading of Recommendations Assessment, Development and Evaluation methodology. Funnel plots, Begg’s test and Egger’s test will be used to assess the risk of publication bias. Subgroup analysis, data synthesis, meta-analysis and overall incidence of adverse events will be performed using Review Manager V.5.4 software and Stata software. Trial sequential analysis will be performed if appropriate.

Ethics and dissemination

This study is an extraction review of data from existing studies, and thus it is unnecessary to obtain ethical approval. The results of this systematic review will be published in a peer-reviewed journal.

PROSPERO registration number

CRD42022359221.
Psychosocial dysfunction of children and adolescents during the COVID-19 lockdown in Ecuador: a cross-sectional study
Authors: Erazo Carlos V , Cifuentes Amelia C , Navas Adriana M , Carrión Freddy G , Caicedo-Gallardo Jose D , Andrade Mateo , Moncayo Ana L
Published: June 2023

Objective

Although the risk of morbidity and mortality of children and adolescents was lower during the COVID-19 pandemic, it appears that their mental health was strongly impacted. The goal of this study is to document psychological dysfunction among children and adolescents who underwent confinement due to COVID-19 in Ecuador.

Design

A cross-sectional, internet-based questionnaire.

Setting

Ecuador.

Participants

A total of 1077 caregivers of children and adolescents (4–16 years old).

Outcome measures

Caregivers responded to Pediatric Symptom Checklist-35 to assess psychosocial dysfunction.

Results

The prevalence of psychosocial dysfunction was 20.8%, with internalising symptoms being the most common (30.7%). The prevalence of psychosocial dysfunction was higher in children who had a poor family relationship during confinement (prevalence ratio (PR) 2.23; 95% CI 1.22 to 4.07), children who never helped with housework (PR 2.63; 95% CI 1.13 to 6.14) and those whose caregivers were worried about children’s need for emotional therapy (PR 2.86; 95% CI 1.97 to 4.15). Never playing video games (PR 0.34; 95% CI 0.17 to 0.69) or playing video games infrequently (PR 0.39; 95% CI 0.20 to 0.79) was a protective factor for the psychosocial problems of children and adolescents.

Conclusion

Our study demonstrates that children and adolescents have experienced a deterioration of mental health due to the pandemic. Family factors played an important role in the mental health of children during the lockdown. When a public crisis occurs, supportive mental health policies should be developed and implemented to promote children’s psychological welfare.
Changes in weekly working hours, proportion of doctors with hours above the limitations of European Working Time Directive (EWTD) and time spent on direct patient care for doctors in Norway from 2016 to 2019: a study based on repeated surveys
Authors: Rosta Judith , Rø Karin Isaksson
Published: June 2023

Objectives

To compare the total weekly working hours, proportions with work hours above the limitations of European working time directive (EWTD) and time spent on direct patient care in 2016 and 2019 for doctors working in different job positions in Norway.

Design

Repeated postal surveys in 2016 and 2019.

Setting

Norway.

Participants

Representative samples of doctors; the response rates were 73.1% (1604/2195) in 2016 and 72.5% (1511/2084) in 2019.

Main outcome measures

Self-reported weekly working hours, proportions with hours above the limitations of EWTD defined as >48 hours/week and time spent on direct patient care.

Analyses

Linear mixed models with estimated marginal means and proportions.

Results

From 2016 to 2019, the weekly working hours increased significantly for male general practitioners (GPs) (48.7 hours to 50.9 hours) and male hospital doctors in leading positions (48.2 hours to 50.5 hours), and significantly decreased for female specialists in private practice (48.6 hours to 44.9 hours). The proportion of time spent on direct patient care was noted to be similar between genders and over time. In 2019, it was higher for specialists in private practice (66.4%) and GPs (65.5%) than for doctors in other positions, such as senior hospital consultants (43.5%), specialty registrars (39.8%) and hospital doctors in leading positions (34.3%). Working >48 hours/week increased significantly for both male and female GPs (m: 45.2% to 57.7%; f: 27.8% to 47.0%) and hospital doctors in leading positions (m: 34.4% to 57.1%; f: 17.4% to 46.4%), while it significantly decreased for female specialty registrars (13.2% to 6.9%).

Conclusions

Working hours increased significantly for GPs and hospital doctors in leading positions from 2016 to 2019, resulting in increased proportions of doctors with work hours above the EWTD. As work hours above the EWTD can be harmful for health personnel and for safety at work, initiatives to reduce long working weeks are needed.
Impact of practicing internal benchmarking on continuous improvement of cataract surgery outcomes: a retrospective observational study at Aravind Eye Hospitals, India
Authors: Balu Ganesh-Babu Subburaman , Gupta Sachin , Ravilla Ravindran D , Ravilla Thulasiraj D , Mertens Helen , Webers Carroll , Vasudeva Rao Shyam , van Merode Frits
Published: June 2023

Objective

We aim to assess the effectiveness of a cataract surgery outcome monitoring tool used for continuous quality improvement. The objectives are to study: (1) the quality parameters, (2) the monitoring process followed and (3) the impact on outcomes.

Design and procedures

In this retrospective observational study we evaluated a quality improvement (QI) method which has been practiced at the focal institution since 2012: internal benchmarking of cataract surgery outcomes (CATQA). We evaluated quality parameters, procedures followed and clinical outcomes. We created tables and line charts to examine trends in key outcomes.

Setting

Aravind Eye Care System, India.

Participants

Phacoemulsification surgeries performed on 718 120 eyes at 10 centres (five tertiary and five secondary eye centres) from 2012 to 2020 were included.

Interventions

An internal benchmarking of surgery outcome parameters, to assess variations among the hospitals and compare with the best hospital.

Outcome measures

Intraoperative complications, unaided visual acuity (VA) at postoperative follow-up visit and residual postoperative refractive error (within ±0.5D).

Results

Over the study period the intraoperative complication rate decreased from 1.2% to 0.6%, surgeries with uncorrected VA of 6/12 or better increased from 80.8% to 89.8%, and surgeries with postoperative refractive error within ±0.5D increased from 76.3% to 87.3%. Variability in outcome measures across hospitals declined. Additionally, benchmarking was associated with improvements in facilities, protocols and processes.

Conclusion

Internal benchmarking was found to be an effective QI method that enabled the practice of evidence-based management and allowed for harnessing the available information. Continuous improvement in clinical outcomes requires systematic and regular review of results, identifying gaps between hospitals, comparisons with the best hospital and implementing lessons learnt from peers.
Acute paediatric asthma treatment in the prehospital setting: a retrospective observational study
Authors: Craig Simon , Delardes Belinda , Nehme Ziad , Wilson Catherine , Dalziel Stuart , Nixon Gillian M , Powell Colin , Graudins Andis , Babl Franz E
Published: June 2023

Objectives

To describe the incidence of and patterns of ‘escalated care’ (care in addition to standard treatment with systemic corticosteroids and inhaled bronchodilators) for children receiving prehospital treatment for asthma.

Design

Retrospective observational study.

Setting

State-wide ambulance service data (Ambulance Victoria in Victoria, Australia, population 6.5 million)

Participants

Children aged 1–17 years and given a final diagnosis of asthma by the treating paramedics and/or treated with inhaled bronchodilators from 1 July 2019 to 30 June 2020.

Primary and secondary outcome measures

We classified ‘escalation of care’ as parenteral administration of epinephrine, or provision of respiratory support. We compared clinical, demographic and treatments administered between those receiving and not receiving escalation of care.

Results

Paramedics attended 1572 children with acute exacerbations of asthma during the 1 year study period. Of these, 22 (1.4%) had escalated care, all receiving parenteral epinephrine. Patients with escalated care were more likely to be older, had previously required hospital admission for asthma and had severe respiratory distress at initial assessment.

Of 1307 children with respiratory status data available, at arrival to hospital, the respiratory status of children had improved overall (normal/mild respiratory distress at initial assessment 847 (64.8%), normal/mild respiratory distress at hospital arrival 1142 (87.4%), p<0.0001).

Conclusions

Most children with acute exacerbations of asthma did not receive escalated therapy during their pre-hospital treatment from ambulance paramedics. Most patients were treated with inhaled bronchodilators only and clinically improved by the time they arrived in hospital.
circ-0000512 inhibits PD-L1 ubiquitination through sponging miR-622/CMTM6 axis to promote triple-negative breast cancer and immune escape
Authors: Dong Li-Feng , Chen Fang-Fang , Fan Yang-Fan , Zhang Kun , Chen Hui-Hui
Published: June 2023

Background

This study reported the function and mechanism of circ-0000512 in the progression of triple-negative breast cancer (TNBC).

Methods

circ-0000512 expression in TNBC tissues and paired adjacent normal tissues and cells was examined by qRT-PCR. Moreover, circ-0000512 expression in TNBC cells was modulated by transfection. Thereafter, colony formation assay, Transwell assay and flow cytometry were conducted to observe cell proliferation, migration and apoptosis. TNBC cells were treated with cycloheximide and the protease inhibitor MG132. Later, ubiquitination assay was performed to detect programmed cell death ligand 1 (PD-L1) ubiquitination in TNBC cells. The T cell killing ability was assessed by the T cell-mediated tumor cell killing assay. IFNγ and IL-2 levels were detected by ELISA. The percentage of activated T cells was detected with a flow cytometer. In addition, dual luciferase reporter gene assay and RNA immunoprecipitation assay were carried out to evaluate the binding between two genes. In vivo study was conducted on mice. CD8+ T cells in xenograft tumors were detected by immunohistochemistry.

Results

circ-0000512 was upregulated in patients with TNBC. circ-0000512 knockdown attenuated the proliferation and migration of TNBC cells and enhanced their apoptosis. circ-0000512 overexpression had opposite effects. circ-0000512 knockdown enhanced the PD-L1 protein ubiquitination in TNBC cells by inhibiting CMTM6. Meanwhile, circ-0000512 promoted CMTM6 expression by sponging miR-622. circ-0000512 knockdown increased the ratio of CD8+T cells and the lethality of T cells against TNBC cells. Besides, circ-0000512 knockdown inhibited the growth of TNBC cells in immunodeficient nude mice and normal immune mice and increased the ratio of CD8+T cells in xenograft tumors of normal immune mice.

Conclusions

circ-0000512 inhibited PD-L1 ubiquitination by sponging the miR-622/CMTM6 axis, thus promoting TNBC progression and immune escape.
Systematic literature review informing the 2022 update of the EULAR recommendations for the management of ANCA-associated vasculitis (AAV): Part 2 - Treatment of eosinophilic granulomatosis with polyangiitis and diagnosis and general management of AAV
Authors: Sanchez-Alamo Beatriz , Schirmer Jan Henrik , Hellmich Bernhard , Jayne David , Monti Sara , Tomasson Gunnar , Luqmani Raashid Ahmed
Published: June 2023

Objective

To summarise and update evidence to inform the 2022 update of the European Alliance of Associations of Rheumatology (EULAR) recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).

Methods

Three systematic literature reviews (SLR) were performed. PubMed, EMBASE and the Cochrane library were searched from 1 February 2015 to 25 February 2022. The evidence presented herein covers the treatment of eosinophilic granulomatosis with polyangiitis (EGPA) as well as diagnostic testing and general management of all AAV syndromes.

Results

For the treatment of EGPA, diagnostic procedures and general management 3517, 4137 and 4215 articles were screened and 26, 110 and 63 articles were included in the final evidence syntheses, respectively. For EGPA patients with newly diagnosed disease without unfavourable prognostic factors, azathioprine (AZA) combined with glucocorticoids (GC) is not superior to GC monotherapy to induce remission (LoE 2b). In patients with active EGPA and unfavourable prognostic factors, cyclophosphamide or rituximab can be used for remission induction (LoE 2b). Treatment with Mepolizumab added to standard treatment results in higher rates of sustained remission in patients with relapsing or refractory EGPA without active organ-threatening or life-threatening manifestations (LoE 1b) and reduces GC use. Kidney biopsies have prognostic value in AAV patients with renal involvement (LoE 2a). In the context of suspected AAV, immunoassays for proteinase 3 and myeloperoxidase-ANCA have higher diagnostic accuracy compared with indirect immunofluorescent testing (LoE 1a).

Conclusion

This SLR provides current evidence to inform the 2022 update of the EULAR recommendations for the management of AAV.
Characterization of an EPS-producing bifidobacterial strain based on integration of phenotypic and complete genome sequencing data
Authors: Liu Dianbin , Huang Haohan , Han Jinzhi , Wu Qiong , Xiang Yaoyao , Liu Yan , Wei Yanxia
Published: June 2023

Bifidobacterium and Lactobacillus are known to be common members of the human intestinal microbiota, which play important roles in maintaining the homeostasis of host gut microenvironment. Several bifidobacterial and lactobacilli strains have been used as probiotics for health benefits. The exopolysaccharides (EPSs) produced by strains from Bifidobacterium and Lactobacillus are considered as beneficial traits mediating these beneficial effects. In this study, 21 strains belonging to Bifidobacterium and Lactobacillus were isolated from healthy infants’ stool and were screened for EPS-producing ability. Among these strains, Bifidobacterium longum XZM1 showed the highest EPS productivity, which was further confirmed and characterized. The complete genome of strain XZM1 was sequenced, which revealed the presence of a gene cluster for EPS production. Furthermore, comparative genome analysis was performed among XZM1 and other strains from B. longum species. Following purification, the molecular weight (Mw) of EPS from XZM1 was determined as 4023 Da (Mw) through gel permeation chromatography. Analysis of the EPS hydrolysates revealed that the EPS was composed of mannose, glucose, galactose, arabinose, and fucose. Additionally, the EPS exhibited higher scavenging abilities toward hydroxyl than 1,1-diphenyl-2-picrylhydrazyl free radical. Overall, these results suggest that XZM1 from B. longum species may be a promising probiotic candidate.