bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of the long non‐coding RNA ZFAS1 attenuates ferroptosis by sponging miR‐150‐5p and activates CCND2 against diabetic cardiomyopathy
Authors: Ni Tingjuan , Huang Xingxiao , Pan Sunlei , Lu Zhongqiu
Published: October 2021

Diabetic cardiomyopathy (DbCM) is responsible for increased morbidity and mortality in patients with diabetes and heart failure. However, the pathogenesis of DbCM has not yet been identified. Here, we investigated the important role of lncRNA‐ZFAS1 in the pathological process of DbCM, which is associated with ferroptosis. Microarray data analysis of DbCM in patients or mouse models from GEO revealed the significance of ZFAS1 and the significant downregulation of miR‐150‐5p and CCND2. Briefly, DbCM was established in high glucose (HG)–treated cardiomyocytes and db/db mice to form in vitro and in vivo models. Ad‐ZFAS1, Ad‐sh‐ZFAS1, mimic miR‐150‐5p, Ad‐CCND2 and Ad‐sh‐CCND2 were intracoronarily administered to the mouse model or transfected into HG‐treated cardiomyocytes to determine whether ZFAS1 regulates miR‐150‐5p and CCND2 in ferroptosis. The effect of ZFAS1 on the left ventricular myocardial tissues of db/db mice and HG‐treated cardiomyocytes, ferroptosis and apoptosis was determined by Masson staining, immunohistochemical staining, Western blotting, monobromobimane staining, immunofluorescence staining and JC‐1 staining. The relationships among ZFAS1, miR‐150‐5p and CCND2 were evaluated using dual‐luciferase reporter assays and RNA pull‐down assays. Inhibition of ZFAS1 led to reduced collagen deposition, decreased cardiomyocyte apoptosis and ferroptosis, and attenuated DbCM progression. ZFAS1 sponges miR‐150‐5p to downregulate CCND2 expression. Ad‐sh‐ZFAS1, miR‐150‐5p mimic, and Ad‐CCND2 transfection attenuated ferroptosis and DbCM development both in vitro and in vivo. However, transfection with Ad‐ZFAS1 could reverse the positive effects of miR‐150‐5p mimic and Ad‐CCND2 in vitro and in vivo. lncRNA‐ZFAS1 acted as a ceRNA to sponge miR‐150‐5p and downregulate CCND2 to promote cardiomyocyte ferroptosis and DbCM development. Thus, ZFAS1 inhibition could be a promising therapeutic target for the treatment and prevention of DbCM.
Moderate temperature and UV‐C light processing of Uruset apple juice: Optimization of bioactive components and evaluation of the impact on volatile profile, HMF and color
Authors: Yıkmış Seydi , Barut Gök Sıla , Levent Okan , Kombak Esengül
Published: October 2021

In this study, the aim was primarily to optimize the process conditions for the enrichment of bioactive components in Uruset apple juice with UV‐C light and moderate heat treatment. UV‐C light was applied to Uruset apple juice at five different UV‐C doses between 84.6 and 169.1 mJ/cm2 using a batch benchtop UV‐C reactor and five different temperatures (40, 45, 50, 55, and 60°C). Total phenolic content (TPC), total flavonoid content (TFC), total antioxidant capacity (1,1‐diphenyl‐2‐picrylhydrazyl [DPPH]), cupric reducing antioxidant capacity (CUPRAC), ascorbic acid and total anthocyanin content (TAC) were evaluated for optimization (response surface methodology) of process conditions. The effect of moderate temperature‐UV‐C light (40°C and 97.33 mJ/cm2) on the HMF (hydroxymethylfurfural) content, optical microstructure and color value of the Uruset apple juice (UUA), fresh Uruset apple juice (FUA) and pasteurized Uruset apple juice (PUA) were then evaluated. At the end of the optimization, TPC (852.83 mg GAE/L), TFC (539.91 mg CE/L), DPPH (71.97%), CUPRAC (79.17%), ascorbic acid (5.96 mg/100 mL), and TAC (211.71 mg/L) were determined. The PUA sample obtained a higher score than the UAA sample in terms of total color change (ΔE). As a result, UV‐C light and moderate heat treatment of Uruset apple juice was found to be successful.

Practical Applications

Fresh apple juices are important sources of bioactive components such as phenolics, carotenoids, vitamin C, and organic acids. The results provided in the study by the combination of moderate heat and UV‐C light could be suggested as an alternative pasteurization process in order to prevent and/or reduce the negative effect on nutritional and sensorial properties of juice of using the heat pasteurization process alone. The number of studies related to preservation of fresh apple juice in terms of Uruset apple variety is fairly limited. Furthermore, the reactor used in the study could be transferred to the fruit juice industry after a scaling‐up feasibility study.
Analysis of vibration acceleration levels and quality deterioration of Chinese bayberry fruit in semi‐vacuum package by express delivery
Authors: Jiang Qiao‐Jun , Jin Wei‐Wei , Zhang Wei‐Yi , Zhang Zhicheng , You Li‐Fan , Bi Yuqing , Yuan Lei‐Ming
Published: October 2021

Recent years have witnessed rapid advances in the transportation of Chinese bayberry fruit in China by express delivery (ED). The mainstream express packaging is a fruit basket filled with Chinese bayberry fruit. In order to analyze the vibration, impact and quality changes of bayberry fruit in the actual ED process, BiQi (BQ) and Dongkui (DK) bayberry fruit were selected as experimental objects. Real‐time acceleration and temperature of Chinese bayberry fruit in the package were recorded during ED transportation. Headspace CO2 gas concentration and squeezed juice percentage were measured when unpacking. The firmness and electronic nose (E‐nose) linear discriminant analysis (LDA) statistical results were measured during the 2‐day shelf life. The results show that semivacuum packaging can reduce the vibration intensity of Chinese bayberry fruit in the package. Whether it was BQ or DK bayberry fruit, the fruit quality of Chinese bayberry fruit sent by ED was considerably worse than that of road vehicle (RV) transportation when unpacking. The LDA statistics of E‐nose data showed that ED‐treated bayberry fruit barely constituted the fresh part. However, differences were noticed between the varieties. Compared with DK bayberry fruit, BQ bayberry fruit had more of its juice squeezed; further, its firmness had decreased more. In conclusion, multiple impacts and high‐intensity vibrations are the main reason for Chinese bayberry fruit damage during ED transportation. Compared to BQ bayberry fruit, DK bayberry fruit is more resistant to mechanical damage and is more suitable for ED.

Practical Applications

Cultivar Dongkui bayberry is more resistant to mechanical damage than BiQi bayberry after many aspects of comparison, and is suitable for express delivery (ED) transportation. To reduce the mechanical damage of bayberry fruit, it is suggested to improve the impact‐resistant design of existing packaging styles, with simply adding a layer of absorbent pad to the bottom of the fruit basket. The form of foam box semivacuum packaging is not only suitable to bayberry, but also to others such as strawberries during ED transportation.
Prenatal predictors of postpartum depression trajectories from birth to 24 months amongst smoking women
Authors: Frndak Seth , Syed Samie , Saleh Julian , Kocher Megan , Wen Xiaozhong
Published: October 2021

Aims and Objectives

We aimed to identify postpartum depression (PPD) trajectories and examine relevant predictors amongst smoking women.

Background

PPD can adversely affect families. Predictors of PPD trajectories amongst smoking women are understudied.

Design

Longitudinal cohort study.

Methods

A cohort of 49 U.S. women (current or ex‐smoking) completed the Edinburgh Postnatal Depression Scale from birth to 24 months postpartum. Latent class growth modelling was used to identify PPD trajectories. Predictors of PPD trajectories were identified, adjusting for confounders. Effect modification by prenatal Patient Health Questionnaire (PHQ) depression score was also assessed. STROBE guidelines were followed in reporting results.

Results

Three PPD trajectories were identified: non‐PPD, transient PPD and chronic PPD. In multinomial logistic regression, social support was associated with lower odds of membership in the chronic PPD trajectory compared to non‐PPD trajectory: being married or having a partner sharing resources (odds ratio OR = .14 [.02, .85], p‐value = .03), greater partner support (OR = .87 [.77, .98], p‐value = .02) and greater family/friends support (OR = .53 [.34, .82], p‐value = .004). Transient PPD showed no differences with non‐PPD on any predictors. In ordinal logistic regression models, social support was associated with lower odds of membership in a more severe PPD depression trajectory when prenatal PHQ depression score was in the low range (being married or having a partner sharing resources: p for effect modification = .06; partner support: p for effect modification = .05; and family/friends support: p for effect modification = .005).

Relevance to Clinical Practice

Compared to the general population, chronic PPD trajectories were more common amongst smoking women. Social support was an important predictor of more severe PPD trajectories, especially when prenatal depression is low.

Conclusion

Our findings indicated that social support might decrease likelihood of severe PPD trajectories, especially when prenatal depression was low. Relevant predictors of transient PPD remained elusive.
The role of adverse childhood experience and social support type in postpartum depression in Turkey
Authors: Ilter Bahadur Evin , Asena Muhammed , Yavuz Yılmaz , Karabulut Erdem , Ozmert Elif Nursel
Published: October 2021

Background

Improved knowledge of causal and protective factors is crucial for Postpartum depression (PPD) prevention and management.

Aims

To investigate the relationship between adverse childhood experience (ACE), perceived social support and PPD in a middle‐income non‐Western country, and to investigate which type of ACE and which sources of social support were associated with PPD.

Methods

The study was cross‐sectional study and conducted in a one center from Turkey during March–June 2019. Women up to 1‐week postpartum were included in the study. The Edinburgh Postpartum Depression Scale (EPDS), a validated ACE questionnaire, and the Multidimensional Scale of Perceived Social Support were completed.

Results

Nine hundred women took part in the study. The proportion identified with PPD and ACE were 10% and 8.8%, respectively. In bivariate analysis, having previous PPD, unwanted pregnancy, insufficient antenatal care, low family income, history of ACE, and perception of low social support were associated with PPD (p < 0.05). Family support was perceived as beneficial, in both women with no history or ≥2 instances of ACE. However, perceived support from friends and/or a special person was lowest in the ≥2 ACE group (p < 0.05). In logistic regression, unwanted pregnancy, emotional abuse, and neglect, incarceration of a household member, and poor special person support were factors significantly associated with developing PPD (p = 0.005).

Conclusions

Emotional abuse, neglect, household dysfunction, and perceived poor support from a special person were risk factors for PPD. A history of maternal childhood trauma and poor social support might indicate the need for early PPD interventions.
Hepatitis B screening practices and viral control among persons living with HIV in urban Senegal
Authors: Ramírez Mena Adrià , Tine Judicaël M. , Fortes Louise , Ndiaye Ousseynou , Ka Daye , Ngom Ndeye Fatou , Ramette Alban , Bittel Pascal , Seydi Moussa , Wandeler Gilles ,   for SEN‐B
Published: October 2021

Chronic hepatitis B virus (HBV) infection affects >10% of the general population and is the leading cause of liver cirrhosis and cancer in West Africa. Despite current recommendations, HBV is often not tested for in clinical routine in the region. We included all people living with HIV (PLWH) in care between March and July 2019 at Fann University Hospital in Dakar (Senegal) and proposed hepatitis B surface antigen (HBsAg) test to those never tested. All HBsAg‐positive underwent HIV and HBV viral load (VL) and liver stiffness measurement. We evaluated, using logistic regression, potential associations between patient characteristics and (a) HBV testing uptake; (b) HIV/HBV co‐infection among individual HBsAg tested. We determined the proportion of co‐infected who had HBV DNA >20 IU/ml on ART and sequenced HBV polymerase in those with HBV replication.of 1076 PLWH in care, 689 (64.0%) had never had an HBsAg test prior to our HBV testing intervention. Women and individuals >40 years old were less likely to have been previously tested. After HBV testing intervention,107/884 (12.1%) PLWH were HBsAg‐positive. Seven of 58 (12.1%) individuals newly diagnosed with HIV/HBV co‐infection had a detectable HBV VL, of whom five were HIV‐suppressed. Two patients on ART including 3TC and AZT as backbone showed the presence of the triple resistance mutation 180M/204I/80V. In this Senegalese urban HIV clinic, the majority of patients on ART had never been tested for HBV infection. One in ten co‐infected individuals had a detectable HBV VL despite HIV suppression, and 8% were not receiving a TDF‐containing regimen.
Resilience of haplodiploids to being exploited by sexually deceptive plants
Authors: Brunton‐Martin Amy L. , Gaskett Anne. C. , Kokko Hanna
Published: October 2021

In species with obligate sexual reproduction, scarcity of males can occasionally limit female reproductive success. It is unclear, however, whether this impacts population‐level persistence. Sexually deceptive orchids attract mate‐searching male insects who lose time, mating opportunities and may even become sperm depleted by mating with flowers. These insects are almost exclusively haplodiploid, and able to reproduce regardless of sperm availability – which might mitigate costs of deception. We model the population dynamics of deceived diploid or haplodiploid pollinators. The model reveals that haplodiploidy can enhance prospects for coexistence. If ‘sperm theft' by orchids is severe enough to generate unmated females in the local pollinator pool, this enhances the production of sons, which are subsequently available to act as pollinators. The mechanism relies on female haplodiploids being able to reproduce with or without sperm; this is absent in many diploid insects – where unmated females do not reproduce. We show that this gives haplodiploids an ability to maintain higher population densities, and to persist up to higher orchid densities, than diploids. Our model identifies the enhanced resilience of haplodiploid pollinators against deceptive exploitation as a possible reason why these systems have persisted.
Teaching Peace After George Floyd: Notes from St. Paul
Authors: Aguilar‐San Juan Karín
Published: October 2021

In the weeks and months after George Floyd’s killing at the hands of the police, gun violence and premature death continued to spur Minnesotans and the rest of the nation to massive street protests for police and prison abolition. Undergraduate students in St. Paul, Minnesota, found themselves at the global epicenter of grassroots political action, sometimes with little formal grounding in social movement theories or the history of peace and justice struggles. To make the study of peace, justice, and social movements relevant and compelling for an increasingly multiracial generation of young activists, this article links concepts from disparate scholarly frameworks, including Asian American activist studies and the history of the Vietnam antiwar movement.
The relationship between the severity of insomnia and falls in the elderly
Authors: İleri İbrahim , Borazan Funda Yıldırım , Cavusoglu Cagatay , Göker Berna
Published: October 2021

Background

Insomnia is associated with depression, cognitive impairment, hypertension, myocardial infarction, stroke, metabolic syndrome and prostate cancer in the elderly. The aim of this study is to investigate the relationship between severity of insomnia and falls.

Methods

This cross‐sectional study was conducted in a single geriatric outpatient clinic at a university teaching hospital. Patients with active infection, who could not complete insomnia severity index (ISI) test because of cognitive impairment and who could not perform handgrip strength and timed up and go (TUG) tests were excluded from the study.

Results

A total of 215 patients were included in this study. Logistic regression analysis showed that there is significant relationship between poorer TUG performance, mild insomnia, moderate insomnia, severe insomnia and falls in the elderly (odds ratio (OR) = 1.04, CI: 1.00–1.09, P = 0.041, OR = 2.43, CI: 1.22–4.85, P = 0.011, OR = 3.84, CI:1.35–10.94, P = 0.012, OR = 5.81, CI:1.00–33.72, P = 0.050).

Conclusions

In this study we showed that there is a relationship between the severity of insomnia and falls.
Anchoring Measurement of the Middle‐Income Class to Subjective Evaluation
Authors: Pittau M. Grazia , Zelli Roberto
Published: October 2021

What constitutes the middle class is hotly debated. Following an income‐based approach, a main issue concerns how to fix the income boundaries that define the middle‐income tier. This paper offers a novel model‐based approach to the use of self‐reported class evaluation for identifying those boundaries. The self‐declared status responses are modeled using a non‐conventional parametrization of an ordered logistic model. In this parametrization, the cut‐points of the model are directly interpretable as income boundaries, and the variance of the errors captures the idiosyncratic heterogeneity of the outcome variable. The use of subjective data is exemplified in the estimation of the middle class in Kazakhstan over the period 2003–2015.
Detection of an HLA‐DRB1*07 variant, HLA‐DRB1*07:130, in a Russian Kalmyk individual
Authors: Loginova Maria , Smirnova Daria , Kutyavina Svetlana , Kashin Konstantin , Paramonov Igor
Published: October 2021

One nucleotide replacement in codon 177 of HLA‐DRB1*07:01:01:01 results in a novel allele, HLA‐DRB1*07:130.
Development of a veterinary emergency open standard competency framework using a competency‐based model of medical education
Authors: Noyes Julie A. , Stewart Samuel D. , Gabarro Jana P. , Welch Patrick M.
Published: October 2021

Objective

To address the shortage of emergency veterinarians, the profession is exploring accelerated training pathways. We sought to contribute to the solution by developing the foundation for an open standard, competency‐based veterinary emergency training curriculum for use by any program. We also developed a curricular delivery, tracking, and assessment system to demonstrate how the framework can be integrated into training programs. 

Design

Hybrid Delphi method. 

Setting

Academia and referral practice. 

Animals

None.

Interventions

None.

Measurements and Main Results

An emergency veterinary competency framework was developed by adapting the human Model of the Clinical Practice of Emergency Medicine, which aligns with the Competency‐Based Veterinary Education framework, to produce 4 areas of core competency: Patient Care, Interpersonal/Communication, Professionalism, and Practice‐based Learning/Improvement. A comprehensive list of veterinary emergency skills was generated and organized within the framework utilizing the hybrid Delphi method. An initial survey completed by 133 emergency and critical care specialists and emergency room clinicians produced data regarding the value of specific skills. An 11‐member focus group consisting of survey participants iterated upon the survey results to produce a master library of skills and cases, including 56 Patient Care, 43 Interpersonal/Communication, 11 Practice‐based Learning/Improvement, and 20 Professionalism skills, as well as 155 case types. The curricular delivery system tracks and assesses case management proficiency and development of knowledge and professional skills using a patient care eLearning program and simulation training environment. 

Conclusions

The increasing need for emergency veterinarians is a shared industry‐wide challenge. To contribute toward a collective solution, we have undergone an evidence‐based process to create the foundation for an open standard competency framework composed of a library of skills and cases. We offer this open standard framework to the veterinary profession and hope it continues to grow and evolve as we drive toward developing competency‐based training programs that address the shortage of emergency veterinarians.
A Lockpick's Guide to dataARC: Designing Infrastructures and Building Communities to Enable Transdisciplinary Research
Authors:   University of Glasgow, Opitz Rachel , Strawhacker Colleen ,   National Science Foundation, Buckland Philip ,   Umea University, Cothren Jackson ,   University of Arkansas, Dawson Tom ,   University of St Andrews, Dugmore Andrew ,   University of Edinburgh, Hambrecht George , Koster Willem ,   University of St Andrews, Lethbridge Emily ,   Stofnun Árna Magnússonar Í Íslenskum Fræðum, Mainland Ingrid ,   University of Highlands and Islands, McGovern Tom ,   City University of New York, Newton Anthony ,   University of Edinburgh, Palsson Gisli ,   Umea University, Ryan Tom ,   City University of New York, Streeter Richard ,   University of St Andrews, Stade Elisabeth ,   University of Colorado Boulder, Szabo Vicki ,   Western Carolina University, Thompson Polly ,   University of Edinburgh
Published: October 2021

The North Atlantic Biocultural Organization (NABO) community initiated dataARC to develop digital research infrastructures to support their work on long-term human-ecodynamics in the North Atlantic. These infrastructures were designed to address the challenges of sharing research data, the connections between those data and high-level interpretations, and the interpretations themselves. In parallel, they were also designed to support the reuse of diverse data that underpin transdisciplinary synthesis research and to contextualise materials disseminated widely to the public more firmly in their evidence base. This article outlines the research infrastructure produced by the project and reflects on its design and development. We outline the core motivations for dataARC's work and introduce the tools, platforms and (meta)data products developed. We then undertake a critical review of the project's workflow. This review focuses on our understanding of the needs of stakeholder groups, the principles that guided the design of the infrastructure, and the extent to which these principles are successfully promoted in the current implementation. Drawing on this assessment, we consider how the infrastructure, in whole or in part, might be reused by other transdisciplinary research communities. Finally, we highlight key socio-technical gaps that may emerge as structural barriers to transdisciplinary, engaged, and open research if left unaddressed.
A Novel Concept for Energy-Optimal, Independent-Phase Control of Brushless Motor Drivers
Authors: Ghorbanpour Amin , Richter Hanz
Published: October 2021

In this work, a new drive concept for brushless direct current (BLDC) motors is introduced. Energy regeneration is optimally managed with the aim of improving the energy efficiency of robot motion controls. The proposed scheme has three independent regenerative drives interconnected in a wye configuration. An augmented model of the robot, joint mechanisms, and BLDC motors is formed, and then a voltage-based control scheme is developed. The control law is obtained by specifying an outer-loop torque controller followed by minimization of power consumption via online constrained quadratic optimization. An experiment is conducted to assess the performance of the proposed concept against an off-the-shelf driver. It is shown that, in terms of energy regeneration and consumption, the developed driver has better performance. Furthermore, the proposed concept showed a reduction of 15% energy consumption for the conditions of the study.
Speed- and Range-Based Filter Design for Dual-Stage Actuator Control
Authors: Peyton Jones J. C. , Mitrovic A. , Clayton G. M.
Published: October 2021

Dual-stage actuators, which combine two actuators with different characteristics, have gained interest due to their large-range, high-resolution positioning capabilities. Control of such systems is challenging because it requires balancing the relative contributions of the individual actuators in terms of speed, range, and precision. The most common approach is to allocate effort to the actuators based on frequency but this can lead to misallocation in the case of low-frequency short-range trajectories. In this paper, the problem of trajectory allocation in dual-stage actuator systems is addressed using a recently developed range-based filter. The theoretical basis of the range-based filter is rigorously derived for the first time and insights regarding its use, specifically its reinterpretation as a speed-based filter, and its range-frequency response characteristics are presented. The new analysis not only explains the behavior of the filter clearly, but it provides a more robust strategy for incorporating range constraints in filter design for different desired trajectories.
Complete Genome Sequences of Four Halophilic Thermus thermophilus Strains Isolated from Arima Hot Spring in Japan
Authors: Miyazaki Kentaro , Tomariguchi Natsuki , Ueno Yuko
Published: October 2021

We isolated four
Thermus thermophilus
strains from Arima Hot Spring in Japan. Complete genome sequencing revealed that they showed average nucleotide identities of ≥99.21% to each other and to strains previously isolated from the same spot, but of ≤97.86% to strains from geographically different spots in Japan, reflecting habitat-specific genomic conservation.
Courtship Ritual of Male and Female Nuclei during Fertilization in Neurospora crassa
Authors: Brun Sylvain , Kuo Hsiao-Che , Jeffree Chris E. , Thomson Darren D. , Read Nick
Published: October 2021

Using live-cell fluorescence imaging, for the first time we have observed live male and female nuclei during sexual reproduction in the model fungus
Neurospora crassa
. This study reveals the specific behavior of resident female nuclei within the trichogyne (the female organ) after fertilization and the extraordinary manner in which male nuclei migrate across the trichogyne toward their final destination, the protoperithecium, where karyogamy takes place.
Aneuploidy Underlies Tolerance and Cross-Tolerance to Drugs in Candida parapsilosis
Authors: Yang Feng , Lu Hui , Wu Hao , Fang Ting , Berman Judith , Jiang Yuan-ying
Published: October 2021

Candida parapsilosis
is an emerging major human fungal pathogen, especially in neonates. Aneuploidy, having uneven numbers of chromosomes, is a well-known mechanism for adapting to stress in
Candida albicans
, the most common human fungal pathogen.
Akkermansia muciniphila Alleviates Dextran Sulfate Sodium (DSS)-Induced Acute Colitis by NLRP3 Activation
Authors: Qu Siwen , Fan Lina , Qi Yadong , Xu Chaochao , Hu Yingying , Chen Shujie , Liu Wei , Liu Weili , Si Jianmin
Published: October 2021

The gut microbiota and host immune response interaction influences the progression of intestinal inflammatory disease. As a well-recognized next-generation probiotic,
Akkermansia muciniphila
has been proved to play a crucial role in the progression of colitis, but its underlying mechanism remains inconclusive.
Identification and Functional Characterization of Two Homologous SpoVS Proteins Involved in Sporulation of Bacillus thuringiensis
Authors: Liu Xinlu , Zhang Ruibin , Hou Shuo , Liu Huanhuan , Wang Jiaojiao , Yu Qingyue , Peng Qi , Song Fuping
Published: October 2021

There is only one
spoVS
gene in
B. subtilis
, and its effects on sporulation have been reported. In this study, two homologous
spoVS
genes were found and identified in
B. thuringiensis
.
BReATHE interventions (Beating Regional Asthma Through Health Education)—an innovative approach to children’s asthma care in the North East and North Cumbria, UK: an interventional study
Authors: Townshend Jennifer Katherine , Hails Sally , Levey Ruth , DeZwart Patty , McKean Michael , Moss Samantha
Published: October 2021

To objective of this project was to reduce unplanned hospital admission rates in children related to asthma to the Newcastle upon Tyne Hospitals National Health Service Trust (NUTH).

Multiple educational interventions were introduced both locally and regionally including: a collection of educational materials aimed at young people and families, schools, primary care and secondary care on the website www.beatasthma.co.uk; regional training days; a nurse-led one-stop clinic; a new pathway following an acute attendance to hospital with an asthma attack; a local asthma service and cascade training for schools.

The primary outcome measure was reduction in unplanned hospital admission rates in children due to asthma to the NUTH.

Results showed that admission rates had been increasing at a sustained rate of approximately 30% each year in the 3 years prior to our intervention. After the Beating Regional Asthma Through Health Education interventions, unplanned admissions to NUTH reduced by 29% and this reduction has been sustained for the last 3 years. This compares with a regional increase of 10% over the same time period.

In conclusion, simple but effective educational interventions resulted in a significant and sustained reduction in unplanned asthma admissions to NUTH. Further work is underway to extend the reach of these interventions into primary care and schools.
Rare case of Sjögren’s syndrome antibody (SSA-Ro52kDA)-associated interstitial lung disease and myositis with pipe stem capillaries
Authors: Ramu Anitha , Kaur Navneet , Jain Ruchi
Published: October 2021

Necrotising myopathy with pipestem capillaries is a distinct form of inflammatory myopathy exhibiting only sparse inflammation on biopsy, with clinical presentation and histopathological profile entirely different from dermatomyositis, polymyositis or inclusion body myositis. A 51-year-old non-diabetic man presents with progressively worsening shortness of breath and myalgias with only mild proximal muscle weakness and elevated serum creatine kinase. Autoimmune workup, ordered after ruling out infectious and cardiac aetiologies, returned positive for Sjögren’s syndrome antibody (SSA/Ro-52). Lung imaging and biopsy were suggestive of cryptogenic organising pneumonia and muscle biopsy showed myositis with pipestem capillaries and abnormal deposition of membrane attack complex with only sparse inflammation. The patient received high-dose steroids, mycophenolate mofetil, intravenous immunoglobulin and rituximab with improvement in muscle symptoms. However, his pulmonary findings progressed, requiring evaluation for a lung transplant. This case emphasises the need for further research to better understand this disease entity and improve mortality and morbidity in these patients.
Cervical avulsion during induced labour: diagnosis, intraoperative management and postoperative course
Authors: Hill Meghan G , Sung Wei Lin T , Connolly Leanne R , Dawson Timothy E
Published: October 2021

We report the presentation, operative management and follow-up of a 31-year-old nulliparous woman who experienced a cervical avulsion injury (CAI) during labour. The woman was induced with dinoprostone gel, followed by oxytocin infusion and had a prolonged active phase. During the second stage, fetal decelerations were noted and the consultant asked to make a plan for delivery. When assessing to perform a midpelvic instrumental delivery, a cord of tissue was felt below the fetal head. A caesarean delivery was recommended based on this finding. After delivery, injuries to the broad ligament, posterior lower uterine segment vagina and cervix were repaired. The cervix was retained with the intent that some tissue be salvaged. At 6-week follow-up, transvaginal ultrasound confirmed blood flow in the cervical tissue, though cervical insufficiency was suspected on clinical examination. Our findings reinforce the seriousness of CAI and support conservative surgical management as opposed to trachelectomy or hysterectomy.
Intraosseous solitary myofibroma of the orbit in an adolescent woman
Authors: Goel Ruchi , Agarwal Ayushi , Raghav Shweta , Saran Ravindra Kumar
Published: October 2021

A 16-year-old woman presented with a painless, progressive, hard swelling in the left inferolateral orbital wall for the past 1 year. There was no diminution of vision or limitation of ocular motility. Imaging revealed an intraosseous, well-defined, expansile, soft tissue lesion in the inferolateral wall of the left orbit. A left anterior orbitotomy with complete surgical excision was performed. Histopathological evaluation of the specimen revealed fascicular pattern of spindle cells with a rich network of slit-like, branching blood vessels. Tumour cells exhibited smooth muscle actin and vimentin positivity but were negative for CD-34 and STAT-6. In absence of any systemic manifestation, a diagnosis of intraosseous solitary orbital myofibroma was made. The case highlights the importance of integrating clinical, radiological and histopathological features in overcoming the diagnostic challenge of differentiating myofibroma from other mesenchymal neoplasms. It also brings forth the importance of complete resection and curettage to prevent recurrence.
Enoxaparin-induced Wunderlich syndrome in a young patient with anti-GAD 65-associated opsoclonus and limbic encephalitis: a rare complication in a rare disease
Authors: Gomathy Saranya B , Das Animesh , Pandit Awadh Kishor , Srivastava Achal Kumar
Published: October 2021

Wunderlich syndrome is a rare condition characterised by acute spontaneous non-traumatic renal haemorrhage into the subcapsular and perirenal spaces. Our case of anti-GAD65-associated autoimmune encephalitis (AE), aged 30 years, developed this complication following use of enoxaparin and was managed by selective glue embolisation of subsegmental branches of right renal cortical arteries. Our case had opsoclonus as one of the clinical manifestations, which has till now been described in only two patients of this AE. This patient received all forms of induction therapies (steroids, plasmapheresis, intravenous immunoglobulin and rituximab) following which she had good improvement in her clinical condition. The good response to immunotherapy is also a point of discussion as this has been rarely associated with anti-GAD65 AE.
Haematuria, a widespread petechial rash, and headaches following the Oxford AstraZeneca ChAdOx1 nCoV-19 Vaccination
Authors: Waraich Ammar , Williams George
Published: October 2021

With increasing presentations of headaches following COVID-19 vaccination, we present one of the UK’s earliest proven cases of vaccine-induced thrombotic thrombocytopaenia (VITT), with the aim of giving colleagues a case to compare other patients against. Our patient was a 48-year-old man who presented with frank haematuria, a widespread petechial rash, and headaches, 2 weeks after receiving the first dose of the Oxford AstraZeneca ChAdOx1 nCoV-19 vaccine. He had a platelet count of 14×109/L and an extensive cerebral venous sinus thrombosis (CVST) with subarachnoid haemorrhage on imaging. He developed localising neurological signs and experienced a cardiopulmonary arrest. He was successfully resuscitated and transferred to a tertiary care centre for urgent thrombectomy. This case illustrates how the diagnosis of VITT should be based on the platelet count and imaging—and how patients with VITT should be cared for in centres with urgent neurosurgical and interventional radiology services.
The Individual Water Insecurity Experiences (IWISE) Scale: reliability, equivalence and validity of an individual-level measure of water security
Authors: Young Sera L , Bethancourt Hilary J , Ritter Zacchary R , Frongillo Edward A
Published: October 2021

Objective

The lack of a validated and cross-culturally equivalent scale for measuring individual-level water insecurity has prevented identification of those most vulnerable to it. Therefore, we developed the 12-item Individual Water InSecurity Experiences (IWISE) Scale to comparably measure individual experiences with access, use, and stability (reliability) of water. Here, we examine the reliability, cross-country equivalence, and cross-country and within-country validity of the scale in a cross-sectional sample.

Methods

IWISE items were implemented by the Gallup World Poll among nationally representative samples of 43 970 adults (>15 y) in 31 low-income and middle-income countries (LMICs). Internal consistency was assessed with Cronbach’s alpha. Equivalence was tested using multigroup confirmatory factor analysis (MGCFA), the alignment method, and item response theory. Cross-country validity was assessed by regressing mean national IWISE scores on measures of economic, social, and water infrastructure development. Within-country validity was tested with logistic regression models of dissatisfaction with local water quality by IWISE score and regressing individual IWISE scores on per capita household income and difficulty getting by on current income.

Findings

Internal consistency was high; Cronbach’s alpha was ≥0.89 in all countries. Goodness-of-fit statistics from MGCFA, the proportion of equivalent item thresholds and loadings in the alignment models, and Rasch output indicated equivalence across countries. Validity across countries was also established; country mean IWISE scores were negatively associated with gross domestic product and percentage of the population with access to basic water services, but positively associated with fertility rate. Validity within countries was also demonstrated; individuals’ IWISE scores were positively associated with greater odds of dissatisfaction with water quality and negatively associated with lower financial standing.

Conclusions

The IWISE Scale provides an equivalent measure of individual experiences with water access and use across LMICs. It will be useful for establishing and tracking changes in the prevalence of water insecurity and identifying groups who have been ‘left behind’.
Reflex syncope in the UK Armed Forces
Authors: Parsons Iain , Ellwood J , Stacey M J , Gall N , Grundy-Bowers M , Chowienczyk P , Woods D
Published: October 2021

Introduction

Reflex syncope is the most common subtype of syncope and, despite not being associated with increased mortality, often results in significant morbidity and costly diagnostics. Reflex syncope can be of concern for certain occupational groups and may be exacerbated by some occupations. Reflex syncope in the military is anecdotally common but the extent in the UK Armed Forces (UKAF) is unknown. The aim of this study was to assess the incidence and prevalence of reflex syncope in the UKAF.

Methods

A retrospective search of the Defence Medical Information Capability Programme using prespecified read-codes was performed at defence primary healthcare centres over the period of 1 January 2019 to 1 January 2020. Data were obtained on 76 103 service personnel (SP) (53% of the UKAF).

Results

The overall syncope case rate for the UKAF was 10.5 per 1000 person-years (p-yrs). In comparing services there was a significantly increased risk of syncope in the British Army (10.7 per 1000 p-yrs) compared with the Royal Air Force (8.6 per 1000 p-yrs) (p=0.0365), SP who served overseas (16.7 per 1000 p-yrs) in comparison with UK medical centres (10.3 per 1000 p-yrs) (p<0.0001), and British Army units that regularly took part in State Ceremonial and Public Duties (15.8 per 1000 p-yrs vs 10.2 per 1000 p-yrs) (p=0.0035). Army training units conferred a significantly reduced risk of syncope (p<0.0001).

Conclusions

These data are the first to define the incidence and prevalence of syncope in the UKAF. Orthostasis and heat are probable triggers, although recruits are potentially protected. These data offer opportunities to improve the health and well-being of SP, with economic, logistical and reputational benefits for the UKAF. Further research to identify personnel at risk of future syncopal events may allow for targeted use of countermeasures.
Measurement of C1-Inhibitor function alone is sufficient for diagnosis of hereditary angioedema
Authors: Kiani-Alikhan Sorena , Walker Elizabeth , Hickey Alaco , Grigoriadou Sofia , Buckland Matt , Scott Chris
Published: October 2021

The World Allergy Organisiation/European Academy of Allergy and Clinical Immunology (WAO/EAACI) 2017/2018 guidelines recommend measuring complement4 levels, followed by C1-inhibitor level and function for diagnosis of hereditary angioedema (HAE). We analysed 6 months’ worth of data generated in our laboratory which is a specialist regional immunology service and also provides laboratory service for the Barts Health immunology department, which is a GA2LEN/HAEi-Angioedema Centre of Excellence and Reference (ACARE) and hence, investigates a large number of patients for HAE. We found that an efficient and sensitive approach for laboratory diagnosis of HAE is to only test the C1-inhibitor function. This approach had a sensitivity of 100% and reduced the cost of laboratory investigations for HAE diagnosis by 45%.
Prospective Predictive Performance Comparison between Clinical Gestalt and Validated COVID-19 Mortality Scores
Authors: Soto-Mota Adrian , Marfil-Garza Braulio Alejandro , Castiello-de Obeso Santiago , Martinez Rodriguez Erick Jose , Carrillo Vazquez Daniel Alberto , Tadeo-Espinoza Hiram , Guerrero Cabrera Jessica Paola , Dardon-Fierro Francisco Eduardo , Escobar-Valderrama Juan Manuel , Alanis-Mendizabal Jorge , Gutierrez-Mejia Juan
Published: October 2021

Most COVID-19 mortality scores were developed at the beginning of the pandemic and clinicians now have more experience and evidence-based interventions. Therefore, we hypothesized that the predictive performance of COVID-19 mortality scores is now lower than originally reported. We aimed to prospectively evaluate the current predictive accuracy of six COVID-19 scores and compared it with the accuracy of clinical gestalt predictions. 200 patients with COVID-19 were enrolled in a tertiary hospital in Mexico City between September and December 2020. The area under the curve (AUC) of the LOW-HARM, qSOFA, MSL-COVID-19, NUTRI-CoV, and NEWS2 scores and the AUC of clinical gestalt predictions of death (as a percentage) were determined. In total, 166 patients (106 men and 60 women aged 56±9 years) with confirmed COVID-19 were included in the analysis. The AUC of all scores was significantly lower than originally reported: LOW-HARM 0.76 (95% CI 0.69 to 0.84) vs 0.96 (95% CI 0.94 to 0.98), qSOFA 0.61 (95% CI 0.53 to 0.69) vs 0.74 (95% CI 0.65 to 0.81), MSL-COVID-19 0.64 (95% CI 0.55 to 0.73) vs 0.72 (95% CI 0.69 to 0.75), NUTRI-CoV 0.60 (95% CI 0.51 to 0.69) vs 0.79 (95% CI 0.76 to 0.82), NEWS2 0.65 (95% CI 0.56 to 0.75) vs 0.84 (95% CI 0.79 to 0.90), and neutrophil to lymphocyte ratio 0.65 (95% CI 0.57 to 0.73) vs 0.74 (95% CI 0.62 to 0.85). Clinical gestalt predictions were non-inferior to mortality scores, with an AUC of 0.68 (95% CI 0.59 to 0.77). Adjusting scores with locally derived likelihood ratios did not improve their performance; however, some scores outperformed clinical gestalt predictions when clinicians’ confidence of prediction was <80%. Despite its subjective nature, clinical gestalt has relevant advantages in predicting COVID-19 clinical outcomes. The need and performance of most COVID-19 mortality scores need to be evaluated regularly.
Trough levels of ipilimumab in serum as a potential biomarker of clinical outcomes for patients with advanced melanoma after treatment with ipilimumab
Authors: Koguchi Yoshinobu , Iwamoto Noriko , Shimada Takashi , Chang Shu-Ching , Cha John , Curti Brendan D , Urba Walter J , Piening Brian D , Redmond William L
Published: October 2021

Background

Immune checkpoint blockade (ICB) using anti-CTLA-4 and anti-PD-1/PD-L1 has revolutionized the treatment of advanced cancer. However, ICB is effective for only a small fraction of patients, and biomarkers such as expression of PD-L1 in tumor or serum levels of CXCL11 have suboptimal sensitivity and specificity. Exposure–response (E-R) relationships have been observed with other therapeutic monoclonal antibodies. There are many factors influencing E-R relationships, yet several studies have shown that trough levels of anti-PD-1/PD-L1 correlated with clinical outcomes. However, the potential utility of anti-CTLA-4 levels as a biomarker remains unknown.

Methods

Serum was obtained at trough levels at weeks 7 and 12 (after doses 2 and 4) from patients with advanced melanoma who received ipilimumab alone (3 mg/kg every 3 weeks for four treatments) via an expanded access program (NCT00495066). We have successfully established a proteomics assay to measure the concentration of ipilimumab in serum using an liquid chromatography with tandem mass spectrometry-based nanosurface and molecular-orientation limited proteolysis (nSMOL) approach. Serum samples from 38 patients were assessed for trough levels of ipilimumab by the nSMOL assay.

Results

We found that trough levels of ipilimumab were higher in patients who developed immune-related adverse events but did not differ based on the presence or absence of disease progression. We found that patients with higher trough levels of ipilimumab had better overall survival when grouped based on ipilimumab trough levels. Trough levels of ipilimumab were inversely associated with pretreatment serum levels of CXCL11, a predictive biomarker we previously identified, and soluble CD25 (sCD25), a prognostic biomarker for advanced melanoma, as well as C reactive protein (CRP) and interleukin (IL)-6 levels at week 7.

Conclusions

Our results suggest that trough levels of ipilimumab may be a useful biomarker for the long-term survival of patients with advanced melanoma treated with ipilimumab. The association of ipilimumab trough levels with pretreatment serum levels of CXCL11 and sCD25 is suggestive of a baseline-driven E-R relationship, and the association of ipilimumab trough levels with on-treatment levels of CRP and IL-6 is suggestive of response-driven E-R relationship. Our findings highlight the potential utility of trough levels of ipilimumab as a biomarker.

Trial registration number

NCT00495066.
Monitoring social–ecological networks for biodiversity and ecosystem services in human-dominated landscapes
Authors: Firkowski Carina Rauen , Schwantes Amanda M. , Fortin Marie-Josée , Gonzalez Andrew
Published: October 2021

The demand the human population is placing on the environment has triggered accelerated rates of biodiversity change and created trade-offs among the ecosystem services we depend upon. Decisions designed to reverse these trends require the best possible information obtained by monitoring ecological and social dimensions of change. Here, we conceptualize a network framework to monitor change in social–ecological systems. We contextualize our framework within Ostrom’s social–ecological system framework and use it to discuss the challenges of monitoring biodiversity and ecosystem services across spatial and temporal scales. We propose that spatially explicit multilayer and multiscale monitoring can help estimate the range of variability seen in social–ecological systems with varying levels of human modification across the landscape. We illustrate our framework using a conceptual case study on the ecosystem service of maple syrup production. We argue for the use of analytical tools capable of integrating qualitative and quantitative knowledge of social–ecological systems to provide a causal understanding of change across a network. Altogether, our conceptual framework provides a foundation for establishing monitoring systems. Operationalizing our framework will allow for the detection of ecosystem service change and assessment of its drivers across several scales, informing the long-term sustainability of biodiversity and ecosystem services.