bluuebunny/crossref_metadata_2025 huggingface dataset:
Is metabolic‐dysfunction‐associated fatty liver disease or advanced liver fibrosis associated with erythropoietin stimulating agent hypo‐responsiveness among patients with end‐stage kidney disease on haemodialysis?
Authors: Wong Wei‐Kei , Chan Wah‐Kheong , Ganapathy Shubash , Lim Soo‐Kun
Published: June 2023

Aim

This study aims to determine if metabolic‐dysfunction‐associated fatty liver disease (MAFLD) or advanced liver fibrosis is associated with erythropoietin stimulating agent (ESA) hypo‐responsiveness in hemodialysis patients.

Methods

In a cross‐sectional study of 379 hemodialysis patients, FibroTouch transient elastography was performed on all patients. Erythropoeitin resistance index (ERI) was used to measure the responsiveness to ESA. Patients in the highest tertile of ERI were considered as having ESA hypo‐responsiveness.

Results

The percentage of patients with ESA hypo‐responsiveness who had MAFLD was lower than patients without ESA hypo‐responsiveness. FIB‐4 index was significantly higher in ESA hypo‐responsive patients. In multivariate analysis, female gender (aOR = 3.4, 95% CI = 1.9–6.2, p < 0.001), dialysis duration ≥50 months (aOR = 1.8, 95% CI = 1.1–2.9, p < 0.05), elevated waist circumference (aOR = 0.4, 95% CI = 0.2–0.8, p = 0.005), low platelet (aOR = 2.6, 95% CI 1.3–5.1, p < 0.01), elevated total cholesterol (aOR = 0.5, 95% CI 0.3–0.9, p < 0.05) and low serum iron (aOR = 3.8, 95% CI = 2.3–6.5, p < 0.001) were found to be independent factors associated with ESA hypo–responsiveness. Neither MAFLD nor advanced liver fibrosis was independently associated with ESA hypo–responsiveness. However, every 1 kPA increase in LSM increased the chance of ESA–hyporesponsiveness by 13% (aOR = 1.1, 95% CI =  1.0–1.2, p = 0.002) when UAP and LSM were used instead of presence of MAFLD and advanced liver fibrosis, respectively.

Conclusion

MAFLD and advanced liver fibrosis were not independently associated with ESA hypo‐responsiveness. Nevertheless, higher FIB‐4 score in ESA hypo‐responsive group and significant association between LSM and ESA hypo‐responsiveness suggest that liver fibrosis may be a potential clinical marker of ESA hypo‐responsiveness.
On two arguments for fanaticism
Authors: Russell Jeffrey Sanford
Published: June 2023

Should we make significant sacrifices to ever‐so‐slightly lower the chance of extremely bad outcomes, or to ever‐so‐slightly raise the chance of extremely good outcomes? Fanaticism says yes: for every bad outcome, there is a tiny chance of extreme disaster that is even worse, and for every good outcome, there is a tiny chance of an enormous good that is even better. I evaluate the prospects for Fanaticism, in connection with two other kinds of general ethical principles. First, separability principles, which say that which option is best does not depend in strange ways on what might be going on in distant space and time—jumping off from a recent argument for Fanaticism from Beckstead and Thomas (2023). Second, reflection principles, about how gaining new information makes a difference to which options are best—jumping off from a recent argument for Fanaticism from Wilkinson (2022). It turns out that the situation is unstable: plausible general separability and reflection principles actually tell against Fanaticism, but restrictions of those same principles (with strengthened auxiliary assumptions) support Fanaticism. All of the consistent views that emerge are very strange.
Evaluation of a paraffin‐based moisturizer compared to a ceramide‐based moisturizer in children with atopic dermatitis: A double‐blind, randomized controlled trial
Authors: Gupta Sachin , Ramam M. , Sharma V. K. , Sethuraman G. , Pandey R. M. , Bhari Neetu
Published: June 2023

Background

Moisturizers are first‐line therapy for treatment of atopic dermatitis (AD). Although there are multiple types of moisturizers available, head‐to‐head trials between different moisturizers are limited.

Objective

To evaluate if a paraffin‐based moisturizer is as effective as ceramide‐based moisturizer in children with AD.

Materials and Methods

In this double‐blind, randomized comparative trial of pediatric patients with mild to moderate AD, subjects applied either a paraffin‐based or ceramide‐based moisturizer twice daily. Clinical disease activity using SCOring Atopic Dermatitis (SCORAD), quality of life using Children/Infants Dermatology Life Quality Index (CDLQI/IDLQI), and transepidermal water loss (TEWL) were measured at baseline and at follow‐up at 1, 3, and 6 months.

Results

Fifty‐three patients were recruited (27 ceramide group and 26 paraffin group) with a mean age of 8.2 years and mean disease duration of 60 months. The mean change in SCORAD at 3 months in the ceramide‐based and paraffin‐based moisturizer groups was 22.1 and 21.4, respectively (p = .37). The change in CDLQI/IDLQI, TEWL over forearm and back, amount and days of topical corticosteroid required, median time to remission and disease‐free days at 3 months were similar in both groups. As the 95% confidence interval (CI) of mean change in SCORAD at 3 months in both groups (0.78, 95% CI: −7.21 to 7.52) was not within the predefined margin of equivalence (−4 to +4), the conclusion of equivalence could not be proven.

Conclusion

Both the paraffin‐based and ceramide‐based moisturizers were comparable in improving the disease activity in children with mild to moderate AD.
Overview of muscle fatigue differences between maximal eccentric and concentric resistance exercise
Authors: Nuzzo James L. , Pinto Matheus D. , Nosaka Kazunori
Published: June 2023

Since the 1970s, researchers have studied a potential difference in muscle fatigue (acute strength loss) between maximal eccentric (ECCmax) and concentric (CONmax) resistance exercise. However, a clear answer to whether such a difference exists has not been established. Therefore, the aim of our paper was to overview methods and results of studies that compared acute changes in muscle strength after bouts of ECCmaxand CONmaxresistance exercise. We identified 30 relevant studies. Participants were typically healthy men aged 20–40 years. Exercise usually consisted of 40–100 isokinetic ECCmaxand CONmaxrepetitions of the knee extensors or elbow flexors.Both ECCmaxand CONmaxexercise caused significant strength loss, which plateaued and rarely exceeded 60% of baseline, suggesting strength preservation. In upper‐body muscles, strength loss at the end of ECCmax(31.4 ± 20.4%) and CONmax(33.6 ± 17.5%) exercise was similar, whereas in lower‐body muscles, strength loss was less after ECCmax(13.3 ± 12.2%) than CONmax(39.7 ± 13.3%) exercise. Muscle architecture and daily use of lower‐body muscles likely protects lower‐body muscles from strength loss during ECCmaxexercise. We also reviewed seven studies on muscle fatigue duringcoupledECCmax‐CONmaxexercise and found similar strength loss in the ECC and CON phases. We also found evidence from three studies that more ECC than CON repetitions can be completed at equalrelativeloads. These results indicate that muscle fatigue may manifest differently between ECCmaxand CONmaxresistance exercise. An implication of the results is that prescriptions of ECC resistance exercise for lower‐body muscles should account for greater fatigue resilience of these muscles compared to upper‐body muscles.
Who do we trust? Differences in types of trust and beliefs in conspiracy theories between vaccinated and unvaccinated Europeans across 17 European countries
Authors: Syropoulos Stylianos , Gkinopoulos Theofilos
Published: June 2023

A plethora of research has highlighted that trust in science, political trust, and conspiracy theories are all important contributors to vaccine uptake behavior. In the current investigation, relying on data from 17 countries (N = 30,096) from the European Social Survey we examined how those who received (and wanted to receive the COVID‐19 vaccine) compared to those who did not differ in their trust in: science, politicians and political parties, international organizations and towards people in general. We also examined whether they differed in how much they believed in conspiracy theories. Those who received (or wanted to receive) the COVID vaccine scored significantly higher in all forms of trust, and lower in conspiracy theory beliefs. A logistic regression suggested that trust in science, politicians, international organizations, as well as belief in conspiracy theories were significant predictors, even after accounting for key demographic characteristics.
Characterization of the first HLA‐DQA1 allele with Aspartic Acid in the transmembrane domain, HLA‐DQA1*05:71
Authors: Gil‐Etayo Francisco Javier , Niño Ramírez Jairo Eduardo , Jiménez Hernaz Isabel , García Sanz Ramón , Tejeda Velarde Amalia
Published: June 2023

HLA‐DQA1*05:71, the first HLA‐DQA1 allele with Aspartic Acid at residue 208 in the transmembrane domain.
Zika virus infection in European travellers returning from Thailand in 2022: A GeoSentinel case series
Authors: Seers Timothy , Rothe Camilla , Hamer Davidson H. , Denny Sarah , Spindler Rahel , Schwartz Eli , Johnston Victoria
Published: June 2023

Zika virus is a mosquito‐borne flavivirus which caused major epidemics in the Pacific and the Americas between 2013 and 2015. International travellers have previously acted as a sentinel population for Zika virus transmission in endemic areas, where local transmission may be incompletely captured by local surveillance systems. We report five recent European travellers returning from Thailand with Zika virus infection, highlighting the risk of ongoing endemic transmission in this popular tourist destination.
Chloroplast SRP43 and SRP54 independently promote thermostability and membrane binding of light‐dependent protochlorophyllide oxidoreductases
Authors: Ji Shuiling , Grimm Bernhard , Wang Peng
Published: June 2023

Protochlorophyllide oxidoreductase (POR), which converts protochlorophyllide into chlorophyllide, is the only light‐dependent enzyme in chlorophyll biosynthesis. While its catalytic reaction and importance for chloroplast development are well understood, little is known about the post‐translational control of PORs. Here, we show that cpSRP43 and cpSRP54, two components of the chloroplast signal recognition particle pathway, play distinct roles in optimizing the function of PORB, the predominant POR isoform in Arabidopsis. The chaperone cpSRP43 stabilizes the enzyme and provides appropriate amounts of PORB during leaf greening and heat shock, whereas cpSRP54 enhances its binding to the thylakoid membrane, thereby ensuring adequate levels of metabolic flux in late chlorophyll biosynthesis. Furthermore, cpSRP43 and the DnaJ‐like protein CHAPERONE‐LIKE PROTEIN of POR1 concurrently act to stabilize PORB. Overall, these findings enhance our understanding of the coordinating role of cpSPR43 and cpSRP54 in the post‐translational control of chlorophyll synthesis and assembly of photosynthetic chlorophyll‐binding proteins.
Microbes, metabolites and muscle: Is the gut–muscle axis a plausible therapeutic target in Duchenne muscular dystrophy?
Authors: Marullo Anthony L. , O'Halloran Ken D.
Published: June 2023

Skeletal muscle is the largest metabolic organ making up ∼50% of body mass. Because skeletal muscle has both metabolic and endocrine properties, it can manipulate the microbial populations within the gut. In return, microbes exert considerable influence on skeletal muscle via numerous signalling pathways. Gut bacteria produce metabolites (i.e., short chain fatty acids, secondary bile acids and neurotransmitter substrates) that act as fuel sources and modulators of inflammation, influencing host muscle development, growth and maintenance. The reciprocal interactions between microbes, metabolites and muscle establish a bidirectional gut–muscle axis. The muscular dystrophies constitute a broad range of disorders with varying disabilities. In the profoundly debilitating monogenic disorder Duchenne muscular dystrophy (DMD), skeletal muscle undergoes a reduction in muscle regenerative capacity leading to progressive muscle wasting, resulting in fibrotic remodelling and adipose infiltration. The loss of respiratory muscle in DMD culminates in respiratory insufficiency and eventually premature death. The pathways contributing to aberrant muscle remodelling are potentially modulated by gut microbial metabolites, thus making them plausible targets for pre‐ and probiotic supplementation. Prednisone, the gold standard therapy for DMD, drives gut dysbiosis, inducing a pro‐inflammatory phenotype and leaky gut barrier contributing to several of the well‐known side effects associated with chronic glucocorticoid treatment. Several studies have observed that gut microbial supplementation or transplantation exerts positive effects on muscle, including mitigating the side effects of prednisone. There is growing evidence in support of the potential for an adjunctive microbiota‐directed regimen designed to optimise gut–muscle axis signalling, which could alleviate muscle wasting in DMD.
The metabolic interplay between dietary carbohydrate and exercise and its role in acute appetite regulation in males: a randomized controlled study
Authors: Frampton James , Serrano‐Contreras Jose Ivan , Garcia‐Perez Isabel , Franco‐Becker Georgia , Penhaligan Jack , Tan Abbigail S. Y. , de Oliveira Ana Claudia Cepas , Milner Annabelle J. , Murphy Kevin G. , Frost Gary , Chambers Edward S.
Published: June 2023

An understanding of the metabolic determinants of postexercise appetite regulation would facilitate development of adjunctive therapeutics to suppress compensatory eating behaviours and improve the efficacy of exercise as a weight‐loss treatment. Metabolic responses to acute exercise are, however, dependent on pre‐exercise nutritional practices, including carbohydrate intake. We therefore aimed to determine the interactive effects of dietary carbohydrate and exercise on plasma hormonal and metabolite responses and explore mediators of exercise‐induced changes in appetite regulation across nutritional states. In this randomized crossover study, participants completed four 120 min visits: (i) control (water) followed by rest; (ii) control followed by exercise (30 min at ∼75% of maximal oxygen uptake); (iii) carbohydrate (75 g maltodextrin) followed by rest; and (iv) carbohydrate followed by exercise. An ad libitum meal was provided at the end of each 120 min visit, with blood sample collection and appetite assessment performed at predefined intervals. We found that dietary carbohydrate and exercise exerted independent effects on the hormones glucagon‐like peptide 1 (carbohydrate, 16.8 pmol/L; exercise, 7.4 pmol/L), ghrelin (carbohydrate, −48.8 pmol/L; exercise: −22.7 pmol/L) and glucagon (carbohydrate, 9.8 ng/L; exercise, 8.2 ng/L) that were linked to the generation of distinct plasma 1H nuclear magnetic resonance metabolic phenotypes. These metabolic responses were associated with changes in appetite and energy intake, and plasma acetate and succinate were subsequently identified as potential novel mediators of exercise‐induced appetite and energy intake responses. In summary, dietary carbohydrate and exercise independently influence gastrointestinal hormones associated with appetite regulation. Future work is warranted to probe the mechanistic importance of plasma acetate and succinate in postexercise appetite regulation.

image

Key points

Carbohydrate and exercise independently influence key appetite‐regulating hormones.

Temporal changes in postexercise appetite are linked to acetate, lactate and peptide YY.

Postexercise energy intake is associated with glucagon‐like peptide 1 and succinate levels.
Supplemental Material: Decoupled Oligocene mylonitic shearing and Miocene detachment faulting in the East Humboldt Range metamorphic core complex, northeast Nevada, USA
Authors: Zuza Andrew V. , Dee Seth
Published: June 2023

Details of U-Pb zircon dating, complete datatables of U-Pb zircon dating, and a compilation of muscovite and biotite Argon dates.
Lyme radiculopathy in a septuagenarian
Authors: McKenzie Iona , Tsarfati Elan Micha
Published: June 2023

A man in his 70s presented to hospital in early summer with a 5-week history of progressive lower back and right thigh pain, sensory deficit and right leg weakness. There had been limited response to analgesics in the community. Primary investigations on admission revealed no cause for his symptoms. Five days into admission, history emerged of a possible tick bite with subsequent rash sustained 3 months earlier, raising the possibility of neuroborreliosis leading to radiculopathy. Cerebrospinal fluid demonstrated a lymphocytic pleocytosis. An elevatedBorrelia burgdorferiantibody index confirmed a diagnosis of Lyme neuroborreliosis. The patient was treated successfully with 28 days of intravenous ceftriaxone, analgesia and physiotherapy. Within the literature, Lyme radiculopathy is a common presentation of neuroborreliosis and should be considered and investigated in patients without radiological evidence of a mechanical cause of worsening lower back pain in settings with endemic Lyme disease.
Sixth cranial nerve palsy and dense cerebral venous sinus thrombosis in a child with nephrotic syndrome
Authors: Parija Sucheta , Dash Nikita , Jeyaraj Genickson
Published: June 2023

Nephrotic syndrome (NS) is a common glomerular disease characterised by massive proteinuria, hypoalbuminaemia, oedema and hyperlipidaemia. Cerebral venous sinus thrombosis (CVST) is a rare complication in children with NS. Here, we report a case of relapsing NS on steroid therapy, in a male in early childhood who presented with symptoms of headache, vomiting and double vision. On prism cover test there was 25 PD esotropia with abduction restriction in the left eye. Fundus examination showed bilateral papilloedema. He was diagnosed as sixth cranial nerve palsy of left eye. Neuroimaging reported dense CVST. He was managed with subcutaneous low molecular weight heparin and steroids. After 2 months of treatment, there was a complete resolution of esotropia and optic disc oedema. This case highlights the importance of early diagnosis of acute onset esotropia and sagittal sinus thrombosis in a case of NS.
Developing best practice principles for the provision of programs and services to people transitioning from custody to the community: study protocol for a modified Delphi consensus exercise
Authors: Majeed Tazeen , Breuer Erica , Edwards Layla , Remond Marc , Taylor Jo , Zeki Reem , Hampton Stephen , Grant Luke , Sherwood Juanita , Baldry Eileen , Sullivan Elizabeth
Published: June 2023

Introduction

There is a lack of standard nomenclature and a limited understanding of programmes and services delivered to people in prisons as they transition into the community to support their integration and reduce reoffending related risk factors. The aim of this paper is to outline the protocol for a modified Delphi study designed to develop expert consensus on the nomenclature and best-practice principles of programmes and services for people transitioning from prison into the community.

Methods and analysis

An online, two-phase modified Delphi process will be conducted to develop an expert consensus on nomenclature and the best-practice principles for these programmes. In thepreparatory phase, a questionnaire was developed comprising a list of potential best-practice statements identified from a systematic literature search. Subsequently, a heterogeneous sample of experts including service providers, Community and Justice Services, Not for Profits, First Nations stakeholders, those with lived experience, researchers and healthcare providers will participate in theconsensus building phase(online survey rounds and online meeting) to achieve consensus on nomenclature and best-practice principles. Participants will indicate, via Likert scale, to what extent they agree with nomenclature and best-practice statements. If at least 80% of the experts agree to a term or statement (indicated via Likert scale), it will be included in a final list of nomenclature and best-practice statements. Statements will be excluded if 80% experts disagree. Nomenclature and statements not meeting positive or negative consensus will be explored in a facilitated online meeting. Approval from experts will be sought on the final list of nomenclature and best-practice statements.

Ethics and dissemination

Ethical approval has been received from the Justice Health and Forensic Mental Health Network Human Research Ethics Committee, the Aboriginal Health and Medical Research Council Human Research Ethics Committee, the Corrective Services New South Wales Ethics Committee and the University of Newcastle Human Research Ethics Committee. The results will be disseminated via peer-reviewed publication.
CT perfusion for Assessment of poor Neurological outcome in Comatose Cardiac Arrest Patients (CANCCAP): protocol for a prospective study
Authors: Alcock Susan , Singh Sarbjeet , Wiens Evan J , Singh Navjit , Ande Sudharsana Rao , Lampron Kristen , Huang Beili , Kirkpatrick Iain , Trivedi Anurag , Schaffer Stephen Allan , Shankar Jai Shiva
Published: June 2023

Introduction

Cardiac arrest remains one of the most common causes of death with the majority occurring outside of hospitals (out of hospital cardiac arrest). Despite advancements in resuscitation management, approximately 50% of comatose cardiac arrest patients (CCAP) will suffer a severe unsurvivable brain injury. To assess brain injury, a neurological examination is conducted, however, its reliability in predicting outcomes in the first days following cardiac arrest is limited. Non-contrast CT is the most employed scan to assess hypoxic changes, even though it is not sensitive to early hypoxic-ischaemic changes in the brain. CT perfusion (CTP) has shown high sensitivity and specificity in brain death patients, although its use in predicting poor neurological outcome in CCAP has not yet been explored. The purpose of this study is to validate CTP for predicting poor neurological outcome (modified Rankin scale, mRS≥4) at hospital discharge in CCAP.

Methods and analysis

The CT Perfusion for Assessment of poor Neurological outcome in Comatose Cardiac Arrest Patients study is a prospective cohort study funded by the Manitoba Medical Research Foundation. Newly admitted CCAP receiving standard Targeted Temperature Management are eligible. Patients undergo a CTP at the same time as the admission standard of care head CT. Admission CTP findings will be compared with the reference standard of an accepted bedside clinical assessment at the time of admission. Deferred consent will be used. The primary outcome is a binary outcome of good neurological status, defined as mRs<4 or poor neurological status (mRs≥4) at hospital discharge. A total of 90 patients will be enrolled.

Ethics and dissemination

This study has been approved by the University of Manitoba Health Research Ethics Board. The findings from our study will be disseminated through peer-reviewed journals and presentations at local rounds, national and international conferences. The public will be informed at the end of the study.

Trial registration number

NCT04323020.
Prevalence and factors associated with the utilisation of modern contraceptive methods among married women of childbearing age in Yemen: a secondary analysis of national survey data
Authors: Boah Michael , Adokiya Martin Nyaaba , Hyzam Dalia
Published: June 2023

Objective

Improving reproductive health requires access to effective contraception and reducing the unmet need for family planning in high-fertility countries, such as Yemen. This study investigated the utilisation of modern contraception and its associated factors among married Yemeni women aged 15–49 years.

Design and setting

A cross-sectional study was conducted. Data from the most recent Yemen National Demographic and Health Survey were used in this study.

Participants

A sample of 12 363 married, non-pregnant women aged 15–49 was studied. The use of a modern contraceptive method was the dependent variable.

Data analysis

A multilevel regression model was used to investigate the factors associated with the use of modern contraception in the study setting.

Results

Of the 12 363 married women of childbearing age, 38.0% (95% CI: 36.4 to 39.5) reported using any form of contraception. However, only 32.8% (95% CI: 31.4 to 34.2) of them used a modern contraceptive method. According to the multilevel analysis, maternal age, maternal educational level, partner’s educational level, number of living children, women’s fertility preferences, wealth group, governorate and type of place of residence were statistically significant predictors of modern contraception use. Women who were uneducated, had fewer than five living children, desired more children, lived in the poorest households and lived in rural areas were significantly less likely to use modern contraception.

Conclusions

Modern contraception use is low among married women in Yemen. Some individual-level, household-level and community-level predictors of modern contraception use were identified. Implementing targeted interventions, such as health education on sexual and reproductive health, specifically focusing on older, uneducated, rural women, as well as women from the lowest socioeconomic strata, in conjunction with expanding availability and access to modern contraceptive methods, may yield positive outcomes in terms of promoting the utilisation of modern contraception.
Common factors, Responsiveness and Outcome in Psychotherapy (CROP): study protocol for a naturalistic prospective cohort study of psychotherapy in Denmark
Authors: Lauritzen Line Rettig , Faye Jacobsen Celia , Nielsen Jan , Lunn Susanne , Mathiesen Birgit Bork , Falkenström Fredrik , Poulsen Stig
Published: June 2023

Introduction

The aim of the Common factors, Responsiveness and Outcome in Psychotherapy (CROP) study is to identify client and psychologist characteristics and therapeutic processes associated with the outcome of psychotherapy delivered by psychologists employed in the Danish primary sector or fully self-employed. The study addresses two main questions. First, how are specific characteristics of clients and psychologists related to the outcome of therapy and do these characteristics moderate the outcome of different psychotherapeutic approaches? Second, to what extent do therapists adapt their approach to client characteristics and preferences and how does such responsiveness impact the process and outcome of therapy?

Methods and analysis

The study is a naturalistic prospective cohort study carried out in collaboration with psychologists in private practice in Denmark. Self-reported data are collected from the participating psychologists and their participating clients before, during (weekly and postsession) and after psychotherapy (at end of treatment and 3 months follow-up). The estimated target sample size is 573 clients. The data are analysed using multilevel modelling and structural equation modelling approaches to capture predictors and moderators of the effect and rate of change in psychotherapy as well as session-to-session changes during the therapy process.

Ethics and dissemination

The study has been approved by the IRB at the Department of Psychology, University of Copenhagen (IRB number: IP-IRB/01082018) and the Danish Data Protection Agency. All study data are fully anonymised and all clients have given informed consent to participation in the study. The study findings will be presented in articles in international, peer-reviewed journals as well as to psychotherapy practitioners and other professionals across Denmark.

Trial registration number

NCT05630560.
Assessment of patients’ preferences for new anticancer drugs in China: a best–worst discrete choice experiment on three common cancer types
Authors: Feng Zhe , Meng Jingyi , Sun Yanjun , Xie Tongling , Lu Wenzhang , Wang Guohua , Geng Jinsong
Published: June 2023

Objectives

Despite the advancement in anticancer drug therapies, cancer treatment decisions are often complex and preference-sensitive, making them well suited for studying shared decision-making (SDM). Our study aimed to assess preferences for new anticancer drugs among three common types of patients with cancer to inform SDM.

Design

We identified five attributes of new anticancer drugs and used a Bayesian-efficient design to generate choice sets for a best–worst discrete choice experiment (BWDCE). The mixed logit regression model was applied to estimate patient-reported preferences for each attribute. The interaction model was used to investigate preference heterogeneity.

Setting

The BWDCE was conducted in Jiangsu province and Hebei province in China.

Participants

Patients aged 18 years or older, who had a definite diagnosis of lung cancer, breast cancer or colorectal cancer were recruited.

Results

Data from 468 patients were available for analysis. On average, the most valued attribute was the improvement in health-related quality of life (HRQoL) (p<0.001). The low incidence of severe to life-threatening side effects, prolonged progression-free survival and the low incidence of mild to moderate side effects were also positive predictors of patients’ preferences (p<0.001). Out-of-pocket cost was a negative predictor of their preferences (p<0.001). According to subgroup analysis by type of cancer, the improvement in HRQoL remained the most valuable attribute. However, the relative importance of other attributes varied by type of cancer. Whether patients were newly diagnosed or previously diagnosed cancer cases played a dominant role in the preference heterogeneity within each subgroup.

Conclusions

Our study can assist in the implementation of SDM by providing evidence on patients’ preferences for new anticancer drugs. Patients should be informed of the multiattribute values of new drugs and encouraged to make decisions reflecting their values.
MODIFI: protocol for randomised feasibility study of eye-movement desensitisation and reprocessing therapy (EMDR) for functional neurological disorder (FND)
Authors: Cope Sarah R , Smith Jared G , El-Leithy Sharif , Vanzan Serena , Pentland Caitlin , Pick Susannah , Golder Dawn , Hogwood Patricia , Turner Kati , Billings Jo , Edwards Mark J
Published: June 2023

Introduction

Functional neurological disorder (FND) refers to an involuntary loss of control over and/or aberrant perception of the body. Common presenting symptoms are functional (non-epileptic) seizures, and functional motor disorder, for example, walking difficulties, weakness or tremor. Greater access to effective treatments would lead to reduced distress and disability; and reduce unnecessary healthcare costs.

This study will examine eye-movement desensitisation and reprocessing therapy (EMDR) as a treatment for FND. EMDR is an evidence-based treatment for post-traumatic stress disorder (PTSD), but its use for other conditions is growing. An FND-specific EMDR protocol will be tested, and if the intervention proves feasible with promising clinical outcomes, progression to a substantive study could take place.

Methods and analysis

Fifty adult patients diagnosed with FND will be recruited. It will be a single-blind randomised controlled trial with two arms: EMDR (plus standard neuropsychiatric care; NPC) and standard NPC. The two groups will be compared at baseline (T0), 3 months (T1), 6 months (T2) and 9 months (T3). Measures of feasibility include safety, recruitment, retention, treatment adherence and acceptability. Clinical outcome measures will assess health-related functioning/quality of life, ratings of FND symptoms and severity, depression, anxiety, PTSD, dissociation, service utilisation and other costs. Improvement and satisfaction ratings will also be assessed. Feasibility outcomes will be summarised using descriptive statistics. Exploratory analyses using (linear/logistic) mixed-effect models will examine the rate of change in the groups’ clinical outcome measures across the four time-points.

After the intervention period, a sample of participants, and clinicians, will be invited to attend semistructured interviews. The interviews will be analysed using reflexive thematic analysis.

Ethics and dissemination

This study has been approved by the NHS West Midlands—Edgbaston Research Ethics Committee. Study findings will be published in open access peer-reviewed journals, presented at conferences, and communicated to participants and other relevant stakeholders.

Trial registration

NCT05455450(www.clinicaltrials.gov).
Exercise-related abdominal complaints in a large cohort of runners: a survey with a particular focus on nutrition
Authors: Baart A Mireille , Terink Rieneke , Zwerver Johannes , Witteman Ben J M , Mensink Marco
Published: June 2023

Objectives

Abdominal complaints (AC) during exercise are a common problem in runners. Nutrition is known to play a role in exercise-related AC, but information on the role of habitual dietary intake is limited. We assessed the prevalence of AC in a large cohort of runners, and investigated its association with potential risk factors, with a particular focus on nutritional factors in the habitual diet.

Methods

A total of 1993 runners completed two online questionnaires: a general questionnaire on, among others, running habits and exercise-related AC and a Food Frequency Questionnaire. Runners with and without either upper AC (UAC) or lower AC (LAC) were compared regarding personal characteristics, running characteristics and habitual dietary intake.

Results

1139 runners (57%) reported AC during and/or up to 3 hours after running: 302 runners (15%) reported UAC, 1115 (56%) LAC and 278 (14%) both. In about one-third of runners with AC, these complaints negatively affected their running. Exercise-related AC were positively associated with female gender, younger age and more intense running. Most associations with nutritional factors were observed only for LAC in men, with a higher intake of energy, all macronutrients and grain products in men with LAC. In both men and women, a higher intake of tea and unhealthy choices were associated with AC.

Conclusion

Exercise-related AC were quite prevalent, and in about one-third of the cases, AC impacted their running. Being female, having a younger age and running at higher intensity were positively associated with AC. Some aspects of the habitual diet were associated with AC. Most notable were positive associations for intake of fat, tea and unhealthy choices.
Reliability of major bleeding events in UK routine data versus clinical trial adjudicated follow-up data
Authors: Harper Charlie , Mafham Marion , Herrington William , Staplin Natalie , Stevens William , Wallendszus Karl , Haynes Richard , Landray Martin J , Parish Sarah , Bowman Louise , Armitage Jane
Published: June 2023

Objective

To assess how reliable UK routine data are for ascertaining major bleeding events compared with adjudicated follow-up.

Methods

The ASCEND (A Study of Cardiovascular Events iN Diabetes) primary prevention trial randomised 15 480 UK people with diabetes to aspirin versus matching placebo. The primary safety outcome was major bleeding (including intracranial haemorrhage, sight-threatening eye bleeding, serious gastrointestinal bleeding and other major bleeding (epistaxis, haemoptysis, haematuria, vaginal and other bleeding)) ascertained by direct-participant mail-based follow-up, with >90% of outcomes undergoing adjudication. Nearly all participants were linked to routinely collected hospitalisation and death data (ie, routine data). An algorithm categorised bleeding events from routine data as major/minor. Kappa statistics were used to assess agreement between data sources, and randomised comparisons were re-run using routine data.

Results

When adjudicated follow-up and routine data were compared, there was agreement for 318 major bleeding events, with routine data identifying 281 additional-potential events, and not identifying 241 participant-reported events (kappa 0.53, 95% CI 0.49 to 0.57). Repeating ASCEND’s randomised comparisons using routine data only found estimated relative and absolute effects of allocation to aspirin versus placebo on major bleeding similar to adjudicated follow-up (adjudicated follow-up: aspirin 314 (4.1%) vs placebo 245 (3.2%); rate ratio (RR) 1.29, 95% CI 1.09 to 1.52; absolute excess +6.3/5000 person-years (mean SE±2.1); vs routine data: 327 (4.2%) vs 272 (3.5%); RR 1.21, 95% CI 1.03 to 1.41; absolute excess +5.0/5000 (±2.2)).

Conclusions

Analyses of the ASCEND randomised trial found that major bleeding events ascertained via UK routine data sources provided relative and absolute treatment effects similar to adjudicated follow-up.

Trial registration number

ISRCTN60635500;NCT00135226.
Optimal dosing regimen of CD73 blockade improves tumor response to radiotherapy through iCOS downregulation
Authors: Meziani Lydia , Gerbé de Thoré Marine , Clémenson Céline , Liu Winchygn , Laurent Pierre-Antoine , Mondini Michele , Vozenin Marie-Catherine , Deutsch Eric
Published: June 2023

Background

Irradiation (IR) and immune checkpoint inhibitor (ICI) combination is a promising treatment modality. However, local and distance treatment failure and resistance can occur. To counteract this resistance, several studies propose CD73, an ectoenzyme, as a potential target to improve the antitumor efficiency of IR and ICI. Although CD73 targeting in combination with IR and ICI has shown attractive antitumor effects in preclinical models, the rationale for CD73 targeting based on CD73 tumor expression level deserves further investigations.

Methods

Here we evaluated for the first time the efficacy of two administration regimens of CD73 neutralizing antibody (one dose vs four doses) in combination with IR according to the expression level of CD73 in two subcutaneous tumor models expressing different levels of CD73.

Results

We showed that CD73 is weakly expressed by MC38 tumors even after IR, when compared with the TS/A model that highly expressed CD73. Treatment with four doses of anti-CD73 improved the TS/A tumor response to IR, while it was ineffective against the CD73 low-expressing MC38 tumors. Surprisingly, a single dose of anti-CD73 exerted a significant antitumor activity against MC38 tumors. On CD73 overexpression in MC38 cells, four doses of anti-CD73 were required to improve the efficacy of IR. Mechanistically, a correlation between a downregulation of iCOS expression in CD4+T cells and an improved response to IR after anti-CD73 treatment was observed and iCOS targeting could restore an impaired benefit from anti-CD73 treatment.

Conclusions

These data emphasize the importance of the dosing regimen for anti-CD73 treatment to improve tumor response to IR and identify iCOS as part of the underlying molecular mechanisms. Our data suggest that the selection of appropriate dosing regimen is required to optimize the therapeutic efficacy of immunotherapy–radiotherapy combinations.
Management of immune-related cutaneous adverse events with dupilumab
Authors: Kuo Alyce Mei-Shiuan , Gu Stephanie , Stoll Joseph , Moy Andrea P , Dusza Stephen W , Gordon Allison , Haliasos Elena C , Janjigian Yelena , Kraehenbuehl Lukas , Quigley Elizabeth A , Chapman Paul , Lacouture Mario E , Markova Alina
Published: June 2023

Immune checkpoint inhibitors (ICI) target the PD-1/PD-L1 and CTLA-4 pathways and allows the immune system to deliver antitumor effects. However, it is also associated with well-documented immune-related cutaneous adverse events (ircAEs), affecting up to 70–90% of patients on ICI. In this study, we describe the characteristics of and patient outcomes with ICI-associated steroid-refractory or steroid-dependent ircAEs treated with dupilumab. Patients with ircAEs treated with dupilumab between March 28, 2017, and October 1, 2021, at Memorial Sloan Kettering Cancer Center were included in this retrospective study, which assessed the rate of clinical response of the ircAE to dupilumab and any associated adverse events (AEs). Laboratory values were compared before and after dupilumab. All available biopsies of the ircAEs were reviewed by a dermatopathologist. Thirty-four of 39 patients (87%, 95% CI: 73% to 96%) responded to dupilumab. Among these 34 responders, 15 (44.1%) were complete responders with total ircAE resolution and 19 (55.9%) were partial responders with significant clinical improvement or reduction in severity. Only 1 patient (2.6%) discontinued therapy due to AEs, specifically, injection site reaction. Average eosinophil counts decreased by 0.2 K/mcL (p=0.0086). Relative eosinophils decreased by a mean of 2.6% (p=0.0152). Total serum immunoglobulin E levels decreased by an average of 372.1 kU/L (p=0.0728). The most common primary inflammatory patterns identified on histopathological examination were spongiotic dermatitis (n=13, 33.3%) and interface dermatitis (n=5, 12.8%). Dupilumab is a promising option for steroid-refractory or steroid-dependent immune-related cutaneous adverse events, particularly those that are eczematous, maculopapular, or pruritic. Among this cohort, dupilumab was well-tolerated with a high overall response rate. Nonetheless, prospective, randomized, controlled trials are warranted to confirm these observations and confirm its long-term safety.
Increased risk of congenital malformations in offspring born to women with systemic lupus erythematosus in South Korea: a nationwide population-based study
Authors: Jung Young Mi , Park Jin Kyun , Oh Min-Jeong , Park Chan-Wook , Park Joong Shin , Jun Jong Kwan , Lee Seung Mi , Cho Geum Joon
Published: June 2023

Objectives

The aim of this study was to determine the risk of congenital malformations in offspring born to women with systemic lupus erythematosus (SLE).

Methods

This nationwide population-based study included Korean women who had a singleton pregnancy. The risk of congenital malformations in women with SLE was compared with those without SLE. Multivariable analyses were performed to estimate the OR of congenital malformations. In a sensitivity analysis, the risk of malformation was compared between the offspring of women with SLE and those of propensity-matched women without SLE.

Results

Of a total of 3 279 204 pregnant women, 0.1% had SLE and their offspring had a higher frequency of congenital malformations (17.13% vs 11.99%, p<0.0001). After adjustment for age, parity, hypertension, diabetes, and fetal sex, the SLE group was found to be associated with an increased risk of congenital malformations in the nervous system (adjusted OR (aOR, 1.90; 95% CI, 1.20 to 3.03), eye, ear, face, and neck (aOR, 1.37; 95% CI, 1.09 to 1.71), circulatory system (aOR, 1.91; 95% CI, 1.67 to 2.20), and musculoskeletal system (aOR, 1.26; 95% CI, 1.05 to 1.52). Even after propensity matching, some of the tendencies were maintained.

Conclusions

This nationwide population-based study in South Korea indicates that compared with the general population, neonates born to SLE mothers have a slightly increased risk of congenital malformations affecting the nervous system, head and neck, cardiovascular system, and musculoskeletal system. When a woman with lupus becomes pregnant, careful fetal ultrasound and newborn screening can be helpful in identifying the risk of potential malformations.
Targeted Training for Multi-organization Recommendation
Authors: Tomlinson Kiran , Wan Mengting , Lu Cao , Hecht Brent , Teevan Jaime , Yang Longqi
Published: June 2023

Making recommendations for users in diverse organizations (orgs) is a challenging task for workplace social platforms such as Microsoft Teams and Slack. The current industry-standard model training approaches either use data from all organizations to maximize information or train organization-specific models to minimize noise. Our real-world experiments show that both approaches are poorly suited for the multi-org recommendation setting where different organizations’ interaction patterns vary in their generalizability. We introducetargeted training, which improves on standard practices by automatically selecting a subset of orgs for model development whose data are cleanest and best represent global trends. We demonstrate how and when targeted training improves over global training through theoretical analysis and simulation. Our experiments on large-scale datasets from Microsoft Teams, SharePoint, Stack Exchange, DBLP, and Reddit show that in many cases targeted training can improve mean average precision (MAP) across orgs by 10–15% over global training, is more robust to orgs with lower data quality, and generalizes better to unseen orgs. Our training framework is applicable to a wide range of inductive recommendation models, from simple regression models to graph neural networks (GNNs).
Clinical Effect of Uterosacral and Cardinal Ligament Fixation versus Sacrospinous Ligament Fixation of Vaginal Vault Prolapse: A Retrospective Analysis
Authors: Huang Ling-xiao , Guo Min , Sha Li-xiao , Chen Cong , Lin Xiao-hua , Dong Xiao-xia
Published: June 2023

Objective. This study aimed at comparing sacrospinous ligament fixation (SSLF) with uterosacral and cardinal ligament fixation (USCLF) concerning complications and outcomes in patients with pelvic organ prolapse (POP). Methods. A retrospective analysis was performed on the clinical data of patients with POP stage III or above uterine prolapse treated at Wenzhou People’s Hospital from January 2013 to December 2019. Patients were divided into two groups: USCLF group and SSLF group. The perioperative indicators, postoperative complications, pelvic organ prolapse quantification (POP-Q), Pelvic Floor Distress Inventory-20 (PFDI-20), and POP/Urinary Incontinence Sexual Questionnaire-12 (PISQ-12) scores of the groups were analyzed and compared. Results. (1) The operative time and intraoperative blood loss in the USCLF group were lower than those in the SSLF group, with statistical significance (

p
<
0.05

). (2) The incidence of postoperative buttock pain in the SSLF group was 10.7% (6/56), higher than that in the USCLF group (0/56) (Fisher’s exact test,

p
=
0.027

). (3) At one year of follow-up, significant improvement in Aa, Ba, C, Ap, and Bp values was observed in both groups (

p
<
0.05

). The values of the Aa and Ba sites in the USCLF group were lower than those in the SSLF group one year after surgery (

p
<
0.05

). (4) The PFDI-20 and PISQ-12 scores of the groups one year after surgery were lower than those before surgery (

p
<
0.05

). Conclusion. Uterosacral and cardinal ligament suture fixation leads to less bleeding and better postoperative quality of life than preoperative and may be better than SSLF at preventing the recurrence of anterior wall prolapse after surgery.
Design of Optimal Passive Tuned Mass Damper with Static Output Feedback and Updating Iterative Procedure
Authors: Lai Yong-An , Chang Chi-Hung , Yang Cho-Yen , Chang Chia-Ming
Published: June 2023

In this study, the optimal design issue of a passive tuned mass damper (TMD) was transformed into the nonsparse control gain matrix optimization problem, and a general passive TMD optimization design method to minimize structural mean square responses or impulse response is therefore proposed. The proposed optimization procedure combines the static output feedback (also known as direct output feedback) algorithm and the updating iterative procedure. The proposed method can be applied to variant design scenario, whether the main structure is single-degree-of-freedom (SDOF) or multidegree-of-freedom (MDOF) structures, undamped or damped structures, subjected to wind disturbances or earthquake excitations. In addition, the proposed method is capable to consider the excitation shaping filter, so the design results are more suitable for practical application. The design procedure of the proposed method is presented, and all the required weighting matrices are introduced and derived in detail. Firstly, the SDOF structures are used as the main structure to demonstrate the correctness of the proposed method. The numerical simulation results verify that the obtained optimal design parameters of TMD were found identical to some cases which contain the analytic solution. The accuracy and feasibility of the proposed design method are confirmed. Finally, a passive TMD is optimally designed for a 5-story MDOF structure subjected to Kanai–Tajimi spectrum comparable earthquakes and a 60-story high-rise MDOF structure subjected to Davenport spectrum comparable wind loads for demonstration.