bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiplexed assay of variant effect reveals residues of functional importance in the BRCA1 coiled-coil and serine cluster domains
Authors: Nagy Gregory , Diabate Mariame , Banerjee Tapahsama , Adamovich Aleksandra I. , Smith Nahum , Jeon Hyeongseon , Dhar Shruti , Liu Wenfang , Burgess Katherine , Chung Dongjun , Starita Lea M. , Parvin Jeffrey D.
Published: November 2023

Delineating functionally normal variants from functionally abnormal variants in tumor suppressor proteins is critical for cancer surveillance, prognosis, and treatment options. BRCA1 is a protein that has many variants of uncertain significance which are not yet classified as functionally normal or abnormal. In vitro functional assays can be used to identify the functional impact of a variant when the variant has not yet been categorized through clinical observation. Here we employ a homology-directed repair (HDR) reporter assay to evaluate over 300 missense and nonsense BRCA1 variants between amino acid residues 1280 and 1576, which encompasses the coiled-coil and serine cluster domains. Functionally abnormal variants tended to cluster in residues known to interact with PALB2, which is critical for homology-directed repair. Multiplexed results were confirmed by singleton assay and by ClinVar database variant interpretations. Comparison of multiplexed results to designated benign or likely benign or pathogenic or likely pathogenic variants in the ClinVar database yielded 100% specificity and 100% sensitivity of the multiplexed assay. Clinicians can reference the results of this functional assay for help in guiding cancer treatment and surveillance options. These results are the first to evaluate this domain of BRCA1 using a multiplexed approach and indicate the importance of this domain in the DNA repair process.
The impact of corporate digital transformation on the export product quality: Evidence from Chinese enterprises
Authors: Qian Jing , She Qunzhi
Published: November 2023

The digital economy has become a driving force in the rapid development of the global economy and the promotion of export trade. Pivotal in its advent, the digital transformation of enterprises utilizes cloud computing, big data, artificial intelligence, and other digital technologies to provide an impetus for evolution and transformation in various industries and fields. in enhancing quality and efficiency. This has been critical for enhancing both quality and efficiency in enterprises based in the People’s Republic of China. Through the available data on its listed enterprises, this paper measures their digital transformation through a textual analysis and examines how this transformation influences their export product quality. We then explore the possible mechanisms at work in this influence from the perspective of enterprise heterogeneity. The results find that: (1) Digital transformation significantly enhances the export product quality in an enterprises, and the empirical findings still hold after a series of robustness tests; (2) Further mechanism analysis reveals that the digital transformation can positively affect export product quality through the two mechanisms of process productivity (φ), the ability to produce output using fewer variable inputs, and product productivity (ξ), the ability to produce quality with fewer fixed outlays; (3) In terms of enterprise heterogeneity, the impact of digital transformation on export product quality is significant for enterprises engaged in general trade or high-tech industries and those with strong corporate governance. In terms of heterogeneity in digital transformation of enterprise and the regional digital infrastructure level, the higher the level of digital transformation and regional digital infrastructure, the greater the impact of digital transformation on export product quality. This paper has practical implications for public policies that offer vital aid to enterprises as they seek digital transformation to remain sync with the digital economy, upgrade their product quality, and drive the sustainable, high-quality, and healthy development of their nation’s economy.
“Exceptionally challenging time for all of us”: Qualitative study of the COVID-19 experiences of partners of diplomatic personnel
Authors: Brooks Samantha K. , Patel Dipti , Greenberg Neil
Published: November 2023

Background

Although the romantic partners of diplomatic personnel frequently accompany their spouses to overseas postings and face the challenges of having to adjust to new cultures and separation from friends and family, they have rarely been the focus of academic research. This study explores the lived experiences of the partners/spouses of diplomatic personnel from the United Kingdom’s Foreign, Commonwealth and Development Office (FCDO) during the COVID-19 pandemic.

Methods

Partners of FCDO staff took part in semi-structured interviews about how COVID-19 had affected their lives and their perceptions of the organisation’s response to the pandemic. Thematic analysis was used to analyse the data.

Results

Eleven partners of FCDO staff took part, who between them had lived in 14 different countries during the pandemic. The analysis identified six key themes: deployment-specific challenges such as travel restrictions, quarantine and evacuation; children; impacts of the pandemic including financial and psychological; perceptions of the organisational response to COVID-19; support and help-seeking; and suggestions for the future. Overall participants reported experiencing a number of challenges, many of which left them feeling powerless and not in control of their own lives. Participants frequently described a lack of clarity around policies and support. Social support appeared to be valuable, but many participants wanted more support from the organisation and from informal networks.

Conclusions

Diplomatic (and similar) organisations could enhance the wellbeing of the partners of their staff through improved communication and support. Keeping families informed about restrictions, requirements, policies and available help during a crisis, and reaching out to them to offer advice and support, would likely be beneficial. It is important that lessons are learned from the COVID-19 crisis in order for organisations to be able to support their employees and families if another prolonged crisis were to occur.
Exercise performance is not improved in mice with skeletal muscle deletion of natriuretic peptide clearance receptor
Authors: Jia Brigitte , Hasse Alexander , Shi Fubiao , Collins Sheila
Published: November 2023

Natriuretic peptides (NP), including atrial, brain, and C-type natriuretic peptides (ANP, BNP, and CNP), play essential roles in regulating blood pressure, cardiovascular homeostasis, and systemic metabolism. One of the major metabolic effects of NP is manifested by their capacity to stimulate lipolysis and the thermogenesis gene program in adipocytes, however, in skeletal muscle their effects on metabolism and muscle function are not as well understood. There are three NP receptors (NPR): NPRA, NPRB, and NPRC, and all three NPR genes are expressed in skeletal muscle and C2C12 myocytes. In C2C12 myocytes treatment with either ANP, BNP, or CNP evokes the cGMP signaling pathway. Since NPRC functions as a clearance receptor and the amount of NPRC in a cell type determines the signaling strength of NPs, we generated a genetic model with Nprc gene deletion in skeletal muscle and tested whether enhancing NP signaling by preventing its clearance in skeletal muscle would improve exercise performance in mice. Under sedentary conditions, Nprc skeletal muscle knockout (MKO) mice showed comparable exercise performance to their floxed littermates in terms of maximal running velocity and total endurance running time. Eight weeks of voluntary running-wheel training in a young cohort significantly increased exercise performance, but no significant differences were observed in MKO compared with floxed control mice. Furthermore, 6-weeks of treadmill training in a relatively aged cohort also increased exercise performance compared with their baseline values, but again there were no differences between genotypes. In summary, our study suggests that NP signaling is potentially important in skeletal myocytes but its function in skeletal muscle in vivo needs to be further studied in additional physiological conditions or with new genetic mouse models.
Confidence interval comparison: Precision of maximum likelihood estimates in LLOQ affected data
Authors: Bülow Tanja , Hilgers Ralf-Dieter , Heussen Nicole
Published: November 2023

When data is derived under a single or multiple lower limits of quantification (LLOQ), estimation of distribution parameters as well as precision of these estimates appear to be challenging, as the way to account for unquantifiable observations due to LLOQs needs particular attention. The aim of this investigation is to characterize the precision of censored sample maximum likelihood estimates of the mean for normal, exponential and Poisson distribution affected by one or two LLOQs using confidence intervals (CI).

In a simulation study, asymptotic and bias-corrected accelerated bootstrap CIs for the location parameter mean are compared with respect to coverage proportion and interval width. To enable this examination, we derived analytical expressions of the maximum likelihood location parameter estimate for the assumption of exponentially and Poisson distributed data, where the censored sample method and simple imputation method are used to account for LLOQs. Additionally, we vary the proportion of observations below the LLOQs.

When based on the censored sample estimate, the bootstrap CI led to higher coverage proportions and narrower interval width than the asymptotic CI. The results differed by underlying distribution. Under the assumption of normality, the CI’s coverage proportion and width suffered most from high proportions of unquantifiable observations. For exponentially and Poisson distributed data, both CI approaches delivered similar results. To derive the CIs, the point estimates from the censored sample method are preferable, because the point estimate of the simple imputation method leads to higher bias for all investigated distributions. This biased simple imputation estimate impairs the coverage proportion of the respective CI.

The bootstrap CI surpassed the asymptotic CIs with respect to coverage proportion for the investigated choice of distributional assumptions. The variety of distributions for which the methods are suitable gives the applicant a widely usable tool to handle LLOQ affected data with appropriate approaches.
Development of a hospital frailty risk score for community-dwelling older adults using data from electronic hospital records in South Korea
Authors: Kim Hee-Sun , Kim Jinhee , Bae Gihwan
Published: November 2023

Purpose

We aimed to develop the Korean Hospital Frailty Risk Score (K-HFRS) by applying the International Classification of Diseases-10 codes to community-dwelling older adults’ medical data.

Methods

We selected data from 2,761 people with no missing main variable values from the Korean Frailty and Aging Cohort Data (KFACD) and National Health Insurance Database (NHID) for analysis. Frailty was determined based on modified Fried’s phenotype [MFP] and Korean Frailty Index for Primary Care [KFI-PC] in the KFACD. A previously established method calculated the K-HFRS, verified by the area under the receiver operating characteristic (ROC) curve. The calculated cutoff value predicted the medical use.

Results

The respective K-HFRSs of the frailty group using the MFP and KFI-PC criteria ranged from 3.64 (±3.03) to 8.15 (±5.72) and 4.07 (±3.42) to 9.10 (±6.28), with 7.67 (±5.40) and 8.59 (±6.03) when four diagnoses were included. The K-HFRS of the frailty group using the KFI-PC criteria was higher than that using the MFP criteria. With four diagnoses included using the MFP criteria, the adjusted odds ratio (OR) for medical expenditures in the frailty group compared to the non-frailty group was 3.01 (95% confidence interval [CI] 2.52–3.60, p < .001); for the number of emergency room (ER) visits was 2.19 (95% CI 1.77–2.70, p < .001); for inpatient days was 2.48 (95% CI 2.08–2.96, p < .001). With four diagnoses included using the KFI-PC criteria, the adjusted OR value for medical expenditures was 2.77 (95% CI 2.35–3.27, p < .001); for the number of ER visits was 1.87 (95% CI 1.51–2.32, p < .001); for inpatient days was 2.07 (95% CI 1.75–2.45, p < .001).

Conclusion

This study substantiated that the K-HFRS can measure frailty efficiently at a lower cost. Follow-up studies are needed for additional validity.
An indirect comparison of efficacy including histologic assessment and safety in biologic therapy in ulcerative colitis: Systemic review and network meta-analysis
Authors: Chae Kyungsun , Seo Yeon Sook , Yu Yun Mi , Chang Min Jung , Choi Junjeong
Published: November 2023

Backgrounds and aims

There are currently no studies comparing histologic remission of FDA-approved biologics for moderate to severe ulcerative colitis (UC), except for one head-to-head VARSITY trial. The current study employs a network meta-analysis to compare the efficacy, including histologic remission and safety of biologic agents for UC.

Methods

Using four electronic databases, including Pubmed, EMBASE, The Cochrane Library, and ClinicalTrials.gov, a search was conducted of all literature published until September 2022. Included were studies of randomized controlled trials with adult patients with moderate to severe UC using biologics approved by the FDA. An odd ratio with a 95 percent credible interval and ranking information was calculated for each endpoint.

Results

The results of the network meta-analysis did not reveal statistically significant differences among biological agents. However, the ranking information for each biological agent exhibited the following patterns. Vedolizumab was ranked first for overall efficacy endpoints in the maintenance phase, including histologic remission. Except for histologic remission, Ustekinumab was identified as the top-ranked drug for induction phase efficacy endpoints other than histologic remission. Adalimumab was identified as the top-ranked drug for maintenance phase corticosteroid-free remission. Vedolizumab was identified as the top-ranked drug in the induction phase for Treatment Emergent Adverse Events (TEAE). Adalimumab was identified as the top-ranked drug in the induction phase for infection. For TEAE and infection in the maintenance phase and Treatment Emergent Severe Adverse Events (TESAE) in both the induction and maintenance phases, Ustekinumab was determined to be the top-ranked medication.

Conclusions

Including histologic remission, for the overall efficacy endpoints in the maintenance phase, VDZ was identified as the first rank drug, but there was no statistically significant difference between biologics. Therefore, the generalization of the results of this study is bounded due to the intrinsic limitations of the study provided.
Subcortical life, evolution of flattened body, and constrained mating posture in the earwig Platylabia major (Insecta: Dermaptera: “Anisolabididae”)
Authors: Kamimura Yoshitaka , Lee Chow-Yang
Published: November 2023

Many animals take advantage of the shaded, humid, and protected environments in subcortical spaces, i.e., thin spaces under the loosened bark of dead trees. Permanent inhabitants of subcortical spaces often show specialized morphologies, such as a miniaturized or dorsoventrally flattened body. However, the evolutionary consequences of these specialized morphologies on behavioral, ecological, and life-history traits have been little studied. We studied the mating biology and anatomy of Platylabia major (usually placed in the family Anisolabididae), which is an obligate inhabitant of subcortical spaces with a paper-like flattened body, and compared them with those of two thicker, spongiphorid earwigs, Nesogaster amoenus and Paralabellula curvicauda. Mating trials in various settings showed that Pl. major requires thin spaces sandwiched by two planes to accomplish genital coupling and insemination. In contrast, the thicker species, although also frequently found in subcortical spaces, could mate on a single horizontal plane due to the ability of the male to twist its abdomen through approximately 180°. Examination by micro-computed tomography and a reagent-based clearing technique revealed no substantive differences in the configuration of mid-abdominal musculature between the species. The dorsal and lateral muscles of Pl. major, which are almost parallel to the antero-posterior body axis for accommodation within the thin abdomen, seemed incapable of producing the power to twist the abdomen. The abdominal musculature conforms to a simple pattern in both male and female earwigs, which is repeated in each of the pregenital segments. We conclude that small differences in the range of motion of each abdominal segment can result in large differences in possible mating postures and positions. Surgical experiments also demonstrated that both right and left penises of Pl. major are competent and used for insemination with no lateral bias, as in most other earwigs with twin penises studied to date.
Iron, folic acid, and vitamin D supplementation during pregnancy: Did pregnant Chilean women meet the recommendations during the COVID pandemic?
Authors: Mujica-Coopman María F. , Garmendia María Luisa , Corvalán Camila
Published: November 2023

Background

Antenatal micronutrient supplementation has been defined as a priority for Low-and Middle-income Countries (LMICs). However, it is also relevant to assess its performance in middle-high income countries, such as Chile, particularly given the post-pandemic food insecurity context.

Aim

To assess the use (frequency and doses) of daily recommended supplementation (iron (15–30 mg), folic acid (FA) (400–800 μg/day), and vitamin (VD) (400 IU)) in a sample of Chilean pregnant women.

Methods

In 1, 507 pregnant women selected from public health care registries of the Southeast area of Santiago-Chile, we collected maternal, supplement use, sociodemographic, and nutritional information at the first (<15 weeks), second (24–28 weeks), and third trimesters (32–36 weeks) of gestation by using a researcher administer online questionnaire.

Results

The median (IQR) age of women was 29 (25–33) years. Pre-conceptional supplementation was rare (24%), but it reached >93% in the first trimester; thereafter supplement use decreased to 79% in the second and 84% in the third trimesters, particularly in women with lower income (p<0.05), lower education (p<0.05), and with excess weight (p<0.05). Use of iron supplements in the first trimester was rare (<21%) as well as the use of VD supplements across pregnancy (<31%). Most FA (70%) and iron (80%) supplement users, exceeded the recommended daily dose while ~40% of VD users took less than the recommended dose.

Conclusions

In this sample of Chilean women, timely initiation of FA, iron, and VD supplementation was low and doses were not aligned with the recommendations. Strengthening adherence and quality of micronutrient supplementation programs delivered through public primary care could benefit particularly the most vulnerable women.
Improving accuracy in state of health estimation for lithium batteries using gradient-based optimization: Case study in electric vehicle applications
Authors: El Marghichi Mouncef , Dangoury Soufiane , zahrou Younes , Loulijat Azeddine , Chojaa Hamid , Banakhr Fahd A. , Mosaad Mohamed I.
Published: November 2023

Significant improvements in battery performance, cost reduction, and energy density have been made since the advancements of lithium-ion batteries. These advancements have accelerated the development of electric vehicles (EVs). The safety and effectiveness of EVs depend on accurate measurement and prediction of the state of health (SOH) of lithium-ion batteries; however, this process is uncertain. In this study, our primary goal is to enhance the accuracy of SOH estimation by reducing uncertainties in state of charge (SOC) estimation and measurements. To achieve this, we propose a novel method that utilizes the gradient-based optimizer (GBO) to evaluate the SOH of lithium batteries. The GBO minimizes a cost with the aim of selecting the optimal candidate for updating the SOH through a memory-fading forgetting factor. We evaluated our method against four robust algorithms, namely particle swarm optimization-least square support vector regression (PSO-LSSV), BCRLS-multiple weighted dual extended Kalman filtering (BCRLS-MWDEKF), Total least square (TLS), and approximate weighted total least squares (AWTLS) in hybrid electric vehicle (HEV) and electric vehicle (EV) applications. Our method consistently outperformed the alternatives, with the GBO achieving the lowest maximum error. In EV scenarios, GBO exhibited maximum errors ranging from 0.65% to 1.57% and mean errors ranging from 0.21% to 0.57%. Similarly, in HEV scenarios, GBO demonstrated maximum errors ranging from 0.81% to 3.21% and mean errors ranging from 0.39% to 1.03%. Furthermore, our method showcased superior predictive performance, with low values for mean squared error (MSE) (<1.8130e-04), root mean squared error (RMSE) (<1.35%), and mean absolute percentage error (MAPE) (<1.4).
Uric acid levels and risk of cognitive impairment: Dose-response meta-analysis of prospective cohort studies
Authors: Liu Qianqian , Peng Min , Yang Tiantian , Si Guomin
Published: November 2023

Purpose

Studying the effects of uric acid levels on cognitive function and quantifying the dose-response relationship.

Methods

Based on PubMed and Embase search terms, we identified prospective cohort studies that included blood uric acid as a risk factor and cognitive impairment as a result up to September 2022. We extracted pooled relative risks (RRs) and corresponding 95% confidence intervals (CIs).

Results

Nine reports (including 488,915 participants and 5516 cognitive impairment cases) with median follow-up of 8.8–22 years were eligible for analyses. Compared with lowest category of blood uric acid concentration, the combined RR of cognitive impairment events in the highest classification was 0.81 (95% CI: 0.70–0.92, P < 0.001). Dose-response analysis of eight reports (including 484,297 participants and 5059 cognitive impairment cases) showed that there was no evidence of a curvilinear relationship between blood uric acid levels and cognitive impairment (P = 0.51 for nonlinear relationship). The summary RR of cognitive impairment for an increase of 1 mg/dL blood uric acid level was 0.98 (95% CI: 0.95–1.00; linear trend P = 0.07, I2 = 67.1%, heterogeneity P < 0.05). There was also a linear negative association between blood uric acid levels and cognitive impairment risk in the male subgroup analysis (RR = 0.97, 95% CI: 0.95–0.99, P < 0.05).

Conclusion

Levels of blood uric acid are not related to risk of cognitive impairment. A subgroup analysis shows that the rise in blood uric acid levels in the male population is related to a decreased risk of cognitive impairment. These results need to be confirmed by further studies.
Development of a sensitive real-time quaking-induced conversion (RT-QuIC) assay for application in prion-infected blood
Authors: Thomas Charlotte M. , Salamat M. Khalid F. , de Wolf Christopher , McCutcheon Sandra , Blanco A. Richard Alejo , Manson Jean C. , Hunter Nora , Houston E. Fiona
Published: November 2023

Efforts to prevent human-to-human transmission of variant Creutzfeldt-Jakob disease (vCJD) by contaminated blood would be aided by the development of a sensitive diagnostic test that could be routinely used to screen blood donations. As blood samples from vCJD patients are extremely rare, here we describe the optimisation of real-time quaking-induced conversion (RT-QuIC) for detection of PrPSc (misfolded prion protein, a marker of prion infection) in blood samples from an established large animal model of vCJD, sheep experimentally infected with bovine spongiform encephalopathy (BSE). Comparative endpoint titration experiments with RT-QuIC, miniaturized bead protein misfolding cyclic amplification (mb-PMCA) and intracerebral inoculation of a transgenic mouse line expressing sheep PrP (tgOvARQ), demonstrated highly sensitive detection of PrPSc by RT-QuIC in a reference sheep brain homogenate. Upon addition of a capture step with iron oxide beads, the RT-QuIC assay was able to detect PrPSc in whole blood samples from BSE-infected sheep up to two years before disease onset. Both RT-QuIC and mb-PMCA also demonstrated sensitive detection of PrPSc in a reference vCJD-infected human brain homogenate, suggesting that either assay may be suitable for application to human blood samples. Our results support the further development and evaluation of RT-QuIC as a diagnostic or screening test for vCJD.
Development and initial validation of the Orthotic Patient-Reported Outcomes—Mobility (OPRO-M): An item bank for evaluating mobility of people who use lower-limb orthoses
Authors: Balkman Geoffrey S. , Bamer Alyssa M. , Stevens Phillip M. , Weber Eric L. , Morgan Sara J. , Salem Rana , Amtmann Dagmar , Hafner Brian J.
Published: November 2023

Lower limb orthoses (LLOs) are externally-applied leg braces that are designed to improve or maintain mobility in people with a variety of health conditions that affect lower limb function. Clinicians and researchers are therefore often motivated to measure LLO users’ mobility to select or assess the effectiveness of these devices. Patient-reported outcome measures (PROMs) can provide insights into important aspects of a LLO user’s mobility for these purposes. However, few PROMs are available to measure mobility of LLO users. Those few that exist have issues that may limit their clinical or scientific utility. The objective of this study was to create a population-specific item bank for measuring mobility of LLO users. Previously-developed candidate items were administered in a cross-sectional study to a large national sample of LLO users. Responses from study participants (n = 1036) were calibrated to a graded response statistical model using Item Response Theory methods. A set of 39 items was found to be unidimensional, locally independent, and function without bias due to characteristics unrelated to mobility. The set of final calibrated items, termed the Orthotic Patient-Reported Outcomes—Mobility (OPRO-M) item bank, was evaluated for initial evidence of convergent, divergent, and known groups construct validity. OPRO-M was strongly correlated with existing PROMs designed to measure aspects of physical function. Conversely, OPRO-M was weakly correlated with PROMs that measured unrelated constructs, like sleep disturbance and depression. OPRO-M also showed an ability to differentiate groups with expected mobility differences. Two fixed-length short forms were created from the OPRO-M item bank. Items on the short forms were selected based on statistical and clinical criteria. Collectively, results from this study indicate that OPRO-M can effectively measure mobility of LLO users, and OPRO-M short forms can now be recommended for use in routine clinical practice and research studies.
Validation of the Austin Assessment: A screening tool for cerebral visual impairment related visual issues
Authors: McDowell Nicola , Butler Philippa
Published: November 2023

Cerebral visual impairment is the most common cause of vision impairment affecting children in the economically developed world with a prevalence rate of approximately 3.4%. Currently there are limited options for screening for cerebral visual impairment, resulting in many children going undiagnosed, especially those that have normal visual acuity. The aim of this research was to validate an iPad App called the Austin Assessment, which was developed as a potential screening tool for cerebral visual impairment related visual issues. The research involved three separate phases: (1) creating a database of normative ranges for children aged 5–18 across the different variables of the Austin Assessment, (2) using the Austin Assessment to screen children aged 5–13 to assess the effectiveness of the Austin Assessment as a screening tool for CVI related visual issues, and (3) conducting specific validation research assessing children using the Austin Assessment and an already validated visual search tool. Each phase used different quantitative research methodologies to help show the effectiveness of the Austin Assessment as a screening tool for cerebral visual impairment related visual issues. From phase one of the research, thresholds were established for three variables of the Austin Assessment for the age groupings of 5–8, 9–12 and 13–18. If a child meets one of these thresholds this indicates further assessment is required to determine if they do in fact have cerebral visual impairment related visual issues. Phase two identified 17 children out of 270 who had clinical findings indicating visual issues; potentially indicative of CVI; investigation into the nature of these visual issues is ongoing. Phase three found that the Austin Assessment has moderate diagnostic value for each age group, with good sensitivity and specificity, making it effective at distinguishing those children who have visual issues from those who have typical vision. Further investigation is needed to confirm this initial validation.
BREATHLEssness in INDIA (BREATHE-INDIA)–Study protocol for the co-design of a community breathlessness intervention in India using realist methods and intervention mapping
Authors: Clark Joseph , Salins Naveen , Pearson Mark , Spathis Anna , Currow David C. , Williams Siân , Johnson Miriam
Published: November 2023

Background

Breathlessness that persists despite treatment of causal disease(s) is disabling, associated with high therapy-related costs and poor socioeconomic outcomes. Low resource countries bear a disproportionate burden of respiratory problems, often characterised by disabling breathlessness. Low-cost self-management breathlessness-targeted interventions are effective and deliverable in community settings but have been developed in high-income countries. We aim to understand how breathlessness self-management works in ‘real life’ populations and cultural contexts, to develop programme theory and co-design a prototype intervention to improve persistent breathlessness management in India.

Methods and analysis

Using a Realist approach, Intervention Mapping and the Medical Research Council Complex Intervention Framework we will undertake two phases of work supported by our Expert Group (of respiratory, primary, palliative care physicians) and key stakeholder groups (opinion leader clinicians, community health workers and people with lived experiences of breathlessness). 1) Realist review and evaluation to identify and refine evidence and theory for breathlessness self-management, producing intervention and implementation programme theory. We will identify literature through our Expert Group, scoping searches and systematic searches (Medline, Ebscohost, CINAHL, Scopus, Psychinfo). We will map intervention components to ‘what works, for whom, and where.’ 2) Intervention development using Intervention Mapping to map intervention and implementation programme theory to intervention components, develop materials to support intervention delivery, and co-design a prototype educational intervention ready for early acceptability and delivery-feasibility testing and evaluation planning in India. Use of stakeholder groups is to allow people with experience of breathlessness and/or its management to contribute their views on content developed by our team based upon review of secondary data sources. Experts and Stakeholders are therefore not research subjects but are included as extended members of the study team and will not follow informed consent procedures. Experts and stakeholders will be acknowledge in outputs arising from our project if they wish to be. Our review conduct will be consistent with RAMESES quality standards.

Discussion

At the conclusion of our study, we will have co-designed a breathlessness intervention for use in the community setting in India ready for further evaluation of: effectiveness, socioeconomic outcomes, acceptability and transferability to other low resource settings.
Continuing Medical Education Questions: November 2023
Authors: Yaghoobi Mohammad
Published: November 2023

Article Title: Effectiveness of Fenofibrate in Treatment-Naïve Patients With Primary Biliary Cholangitis: A Randomized Clinical Trial
The loss of opportunity in the health field: the causal link and the protection of the right to compensable physical and moral integrity in Spain
Authors: Martínez Cristóbal Daniel
Published: November 2023

Loss of opportunity is a term used by Spanish jurisprudence in the health field, and despite the fact that it is a widely used doctrine, it presents doubtful aspects in the requirements to grant compensation and the configuration of damage. The present study analyzes the origin and the perspectives that treat the loss of opportunity with the purpose of solving the problem that constitutes the causal relationship between the activity of a subject and the damage produced. It emphasizes the difficult treatment for the application of the loss of opportunity technique, requiring for its application the causal uncertainty together with the pre-existence of an ideal situation to obtain a benefit or advantage that has not occurred. The connection between the two will enable the application of the loss of opportunity or expectations, determining the calculation of the compensation in a motivated manner by the Courts based on the probability of the lost opportunity.
Bordeaux mixture accelerates ripening, delays senescence, and promotes metabolite accumulation in jujube fruit
Authors: Wang Qianjin , Tian Shan , Duan Xuehui , Zhang Mengqian , Zhao Xusheng , Li Yueyue
Published: November 2023

The old, but eco-friendly pesticide, Bordeaux mixture (Bm), is widely used in agriculture. Here, the effects of Bm on preharvest fruit ripening, and postharvest senescence of fruit and the accumulation of antioxidants were studied in Ziziphus jujuba. A 200× dilution of Bm enhanced preharvest ripening and retarded jujube fruit postharvest senescence. Treatment with Bm increased the reddening index and promoted the accumulation of total phenolics (TP) and the total antioxidant capacity (TAC) in preharvest fruit. However, this Bm-accelerated ripening could be partly reversed using dimethylthiourea (DMTU), a specific scavenger of reactive oxygen species. Compared with preharvest fruit, Bm treatment decreased weight loss and decay and increased firmness in postharvest fruit. Similarly, Bm-delayed senescence was partly reversed using dimethylthiourea. Moreover, the decrease in TP and TAC during storage was partly impeded by Bm. A higher H2O2 content was detected in preharvest fruit than in postharvest fruit. Moreover, this Bm-induced H2O2 accumulation was significantly mitigated using dimethylthiourea. Interestingly, both preharvest and postharvest spraying with Bm significantly enhance copper and calcium accumulation in fruit. Thus, Bm can be widely used before or after harvest to improve fruit quality.
Does it occur or not? – A structured approach to support students in determining the spontaneity of chemical reactions
Authors: Hofer Elisabeth , Steininger Rosina
Published: November 2023

Thermodynamics is a central topic of chemistry as it holds a crucial role in understanding chemical processes. Due to its complexity, level of abstraction and amount of “mathematics”, chemical thermodynamics is one of the most challenging subjects resulting in a huge number of inappropriate conceptions. To determine whether a chemical reaction is spontaneous in a particular direction, students need to apply a huge amount of chemical knowledge when completing a complex, multi-step thinking process. In a Design-Based Research project, we developed “unmathematical” instructional material that aims at supporting students in accomplishing this demanding task. By providing a step-by-step instruction and incorporating scaffolding measures, students are guided through four successive tasks. The material was implemented in more than ten upper secondary chemistry classes and four teacher education courses and was proved to be proper for independent work, supporting students in connecting thermodynamics to basic chemical knowledge. Working on the material enables students to overcome barriers in the field of chemical thermodynamics and to successfully complete tasks in the area of thermodynamics and physical chemistry. Teachers can easily adapt the material to specific contents, levels, and teaching requirements. Further, the supportive material can be applied to offer differentiated and individualised learning paths.
Defining competencies for training non-native Korean speaking teachers: a Q methodology approach
Authors: Kim Su Eun , Fraschini Nicola , Park Hyunjin
Published: November 2023

Learners of Korean are increasing globally, but this growth can only be sustained by training local non-native teachers. To address this issue, this paper identifies the subjective perspectives of Korean language teaching professionals about the main competencies needed by non-native Korean teachers. Following a Q methodology protocol, 35 teachers sorted 42 statements about non-native Korean teacher competencies. The analysis identified four perspectives. Factor 1 stresses the ability to adapt teaching to the learning context and Korean language proficiency. Factor 2 stresses the importance of pursuing continuous professional development without deeming a near-native language proficiency essential. Factor 3 stresses the need to love the language and the ability to maintain advanced language skills. Factor 4 again stresses the need to love the Korean language, the profession, and the importance of a strong sense of responsibility as an educator. Results are discussed with reference to teacher training program design.
Complex turbulent exchange coefficient in Akerblom–Ekman model
Authors: Bykov Philipp L. , Gordin Vladimir A.
Published: November 2023

The turbulent exchange in boundary layer models is usually
characterized by a scalar eddy viscosity coefficient
assumed to be a positive function of the vertical variable.
We introduce a more general form for the turbulence exchange description, which includes two functions that describe the turbulence without any assumption about their positivity. We construct a model of the Akerblom–Ekman type, but with a complex coefficient of turbulent exchange.
The basic quality criterion for these models and algorithms is the maximal agreement with meteorological observations. We optimize the agreement between the global meteorological archive of high-resolution wind observations that are provided by World Meteorological Organization (WMO) in Binary Universal Form for the Representation (BUFR). The main result of our work is that agreement between model solutions and observations will be much better if the turbulent exchange coefficient is optimized in the space of all complex-valued functions, and not limited to the cone of real positive functions.
Current state of stem cell research in non-human primates: an overview
Authors: Wu Junmo , Shi Yuxi , Yang Shanshan , Tang Zengli , Li Zifan , Li Zhuoyao , Zuo Jiawei , Ji Weizhi , Niu Yuyu
Published: November 2023

The remarkable similarity between non-human primates (NHPs) and humans establishes them as essential models for understanding human biology and diseases, as well as for developing novel therapeutic strategies, thereby providing more comprehensive reference data for clinical treatment. Pluripotent stem cells such as embryonic stem cells and induced pluripotent stem cells provide unprecedented opportunities for cell therapies against intractable diseases and injuries. As continue to harness the potential of these biotechnological therapies, NHPs are increasingly being employed in preclinical trials, serving as a pivotal tool to evaluate the safety and efficacy of these interventions. Here, we review the recent advancements in the fundamental research of stem cells and the progress made in studies involving NHPs.
Development and Validation of Secularity Scale for Muslims
Authors: Ertit Volkan
Published: November 2023

There is currently no secularity scale with strong psychometric properties that would allow for the examination of the secularization process experienced by Muslims. Thus, the purpose of this article is to develop a psychometrically sound and quick-to-apply scale that can be used to measure the degree of secularity among Muslims. For exploratory factor analysis (EFA), an inventory with 65 items was applied to 1,573 university students, and it yielded a two-factor structure with an internal reliability of 0.975 for Daily Life factor and 0.952 for Faith and Prayer factor. After EFA, the confirmatory factor analysis (CFA) was performed with 4,391 individuals, and a structure that can be deemed very solid was found. The measurement invariance was also examined, and it was discovered that the scale can be used for various populations. In addition, the scale has convergent validity, a high test-retest result, and discriminant validity. The 25-item Secularity Scale has a new theoretical approach – which is not only based on faith and prayer but also daily life activities – and sound psychometric properties. Examining how secularity manifests itself in Muslim societies might be useful in describing, predicting, and explaining how individuals act in a variety of contexts. The scale might also help to avoid the use of approach utilized in Christian-centred secularity debates in the case of Muslim-majority societies.
Braucht es eine Gesellschaft mit gebundenem Vermögen?
Authors: Schlömer-Laufen Nadine , Reiff Annika , Kay Rosemarie
Published: November 2023

Über den Vorschlag zur Einführung der GmbH-Sonderform „Gesellschaft mit gebundenem Vermögen“ wird derzeit in Deutschland kontrovers diskutiert. In diesem Beitrag überprüfen Nadine Schlömer-Laufen, Annika Reiff und Rosemarie Kay die positiven Effekte, welche die Initiatoren der geplanten Rechtsform zusprechen, unter ökonomischen Aspekten. Es zeigt sich, dass diese Rechtsform für die Mehrheit der Unternehmen aus ökonomisch rationaler Sicht nicht vorteilhaft ist – weder im Zusammenhang mit der Nachfolge im Unternehmen noch mit der Neugründung. Auch als Signal für nachhaltiges zweckorientiertes Wirtschaften kann diese Rechtsform nicht dienen. Da das Interesse der Unternehmen in Deutschland überschaubar sein dürfte und die Kernelemente (Asset lock und Zugehörigkeit zur „Wertefamilie“) des Vorschlags nahezu vollumfänglich in jeder Rechtsform zu verwirklichen sind, bezweifeln die Autorinnen die Notwendigkeit einer solchen neuen Rechtsform.
Development of TiO2/Al2O3 based Mg composite materials: properties and applications
Authors: Sohail Mohammad , BiBi Huma , Omer Muhammad , Ullah Ikram , Ullah Ihsan , Adnan Rauf , Zakir Ullah
Published: November 2023

Mg alloys/Mg-based composites are utilized significantly in the construction of missiles, aerospace and automobiles due to their lightweight, specific strength, and hardness. In the recent work, Mg-based two-components (Mg–TiO2/Mg–Al2O3) and three-components (Mg–TiO2–Al2O3) composites were fabricated through solid-phase synthesis (powder metallurgy method). Temperature (30 °C), pressure (760 mm Hg) and concentration factors were optimized prior to experiments. The characterization of obtained composites were performed through different physicochemical methods like Surface analyzer, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). FTIR analysis verified the composite fabrication. SEM determined microstructures and particle size of the materials in µm dimensions. XRD confirmed the homogeneity and crystalline nature of the obtained composites. The surface area of the produced samples was observed to vary from 40 to 70 m2/g. These properties allow the prepared composites to play the main role in different adsorption applications and catalytic analysis. The prepared materials were considered to be used as catalyst for the formation of CNTs. The catalytic efficiency was observed to be 80 % for the growth of CNTs.
VIRUSES AND THEIR PENETRATION THROUGH FIBROUS STRUCTURES: A REVIEW
Authors: MILITKÝ Jiří , WIENER JAKUB , KŘEMENÁKOVÁ DANA
Published: November 2023

In the first part of this review the necessary information about structure and chemical composition of viruses are briefly discussed on the basic level. Main types of interaction of viruses with human cells are briefly described. The basic method of suppressing the spread of viruses from the surroundings of a healthy person and into the surroundings of an infected person is the use of protective equipment, especially face masks and respirators, where the active element is a fibrous structure. The protective functions of these structures depend on their composition (usually hydrophobic materials), construction (fabrics, knitted fabrics, nonwoven fabrics, nano-meshes), morphology (porosity, thickness, pore distribution), the form of virus propagation (usually in water droplets as a type of aerosol), interaction conditions with the surface of the protective layer (speed of impact, conditions of capture on the surface of the fibrous phase, speed of penetration) and the method of virus inactivation (usually contact or very short-range interaction). It is therefore a very complicated problem that is often solved using a combination of mathematical modeling and simulation. The purpose is to present some methods of solving problems related to the protective function of fiber structures, which allow the specification of the suitability of these structures for real use.
ONLINE WEAR ANALYSIS OF CARD CLOTHINGS
Authors: FISCHER HOLGER , HEILOS KATHARINA , THAL DANIEL , FAASEN ANDRÉ , HOFMANN MARCEL
Published: November 2023

The processing of abrasive fibres in the carding process, in particular high-performance fibres such as glass, carbon or aramid fibres, can cause increased wear of the card clothing. In the FutureTex project ‘HPFGarnitur’, the wear of card clothing was investigated and an online wear measurement system has been developed. The aim of the project was both, to optimize the clothings to enable gentler processing of the fibres, and to develop a digital monitoring system to observe the degree of wear of the clothings, which offers a new possibility for maintenance prediction and production planning in the sense of Industry 4.0.
MARCH5 promotes STING pathway activation by suppressing polymer formation of oxidized STING
Authors: Son Kyungpyo , Jeong Seokhwan , Eom Eunchong , Kwon Dohyeong , Kang Suk‐Jo
Published: November 2023

Stimulator of interferon genes (STING) is a core DNA sensing adaptor in innate immune signaling. STING activity is regulated by a variety of post‐translational modifications (PTMs), including phosphorylation, ubiquitination, sumoylation, palmitoylation, and oxidation, as well as the balance between active and inactive polymer formation. It remains unclear, though, how different PTMs and higher order structures cooperate to regulate STING activity. Here, we report that the mitochondrial ubiquitin ligase MARCH5 (Membrane Associated Ring‐CH‐type Finger 5, also known as MITOL) ubiquitinates STING and enhances its activation. A long‐term MARCH5 deficiency, in contrast, leads to the production of reactive oxygen species, which then facilitate the formation of inactive STING polymers by oxidizing mouse STING cysteine 205. We show that MARCH5‐mediated ubiquitination of STING prevents the oxidation‐induced STING polymer formation. Our findings highlight that MARCH5 balances STING ubiquitination and polymer formation and its control of STING activation is contingent on oxidative conditions.
Trends and limitations of lignin as a starting material
Authors: Covinich Laura G. , Area María C.
Published: November 2023

This editorial envisions a future in which greater value is obtained from technical lignins. The currently available amounts of such lignins are immense, and the costs are often in line with lignin’s fuel value. Key challenges are associated with lignin’s complexity. When envisioning future prospects for lignin, it is important to consider any differences between different types of technical lignin as a starting material.