bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between malnutrition and adverse renal outcomes in patients with type 2 diabetes
Authors: Fujiwara Momoko , Kimura Hiroshi , Tanaka Kenichi , Saito Hirotaka , Shimabukuro Michio , Asahi Koichi , Watanabe Tsuyoshi , Kazama Junichiro James
Published: October 2024

Introduction

Nutritional management is crucial in patients with chronic kidney disease. Therefore, it is important to assess nutritional status and detect malnutrition, especially in patients with diabetes. However, there is currently a lack of evidence regarding the relationship between nutritional indices and renal function in patients with type 2 diabetes. This study investigated whether the geriatric nutritional risk index (GNRI) is related to renal prognosis in type 2 diabetes patients.

Materials and Methods

The study included 946 type 2 diabetes patients enrolled in the Fukushima Cohort Study. The primary endpoint of this study was a renal event, defined as a combination of a 50% decline in eGFR from baseline and end‐stage kidney disease. All‐cause death and new cardiovascular events were also measured as secondary outcomes. The association between GNRI and these endpoints was assessed using Cox regression analysis.

Results

The median patient age was 66 years, 57% were men, the median eGFR was 67.9 mL/min/1.73 m2, and the median GNRI was 100.0. Compared to patients in the highest GNRI tertile, patients in the lowest tertile had a significantly increased risk of the renal event (HR 5.15, 95% CI 2.51–10.6) and all‐cause death (HR 2.30, 95% CI 1.20–4.42). A significant association was not observed between GNRI levels and cardiovascular events.

Conclusions

We observed an association between poor nutritional status, assessed by GNRI, and adverse outcomes in patients with type 2 diabetes. Nutritional status assessment has potential utility as a prognostic tool for individuals with type 2 diabetes.
Mandarin Fish Ranavirus (MRV) Infection Induced Inflammation and Histologic Lesions in the Gut of Mandarin Fish
Authors: Gao Xinru , Zhang Ziye , Ma Yanping , Hao Le , Huang Wen , Liu Zhenxing , Li Yugu
Published: October 2024

Mandarin fish ranavirus (MRV) is widely spread in China and causes huge economic losses to the mandarin fish (Siniperca chuatsi) aquaculture. However, the pathogenesis of MRV is still unclear. In the present study, mandarin fish were artificially infected with MRV, and then different gut compartments from diseased fish were subjected to histologic analysis by H&E staining, quantification of proinflammatory genes and MRV copies by qPCR. MRV‐MCP protein expression was assessed using indirect fluorescence assay (IFA) and immunohistochemistry. Proliferation of IgM+ B cells was evaluated by indirect fluorescence assay (IFA). Then, we found that MRV infection caused serious histologic lesions along with inflammatory cell infiltration, especially in the foregut. A significant accumulation of IgM+ B cells was detected in the foregut (~6.5‐fold) and hindgut (~3.3‐fold), respectively. The expression of inflammation‐related genes such as IL‐1β, IL‐6, IL‐8, TNF‐α, CSF1r and NCF1 was significantly upregulated in the foregut, varying from ~2.8‐fold to ~11.9‐fold. In addition, MRV exhibited foregut tropism, according to the investigation of viral loads and MCP protein expression. Overall, our findings indicated that MRV‐induced hyperinflammation in the gut eventually led to enteritis. This study provided new insights into uncovering the pathogenesis of MRV infection.
Bone labeling experiments and intraskeletal growth patterns in captive leopard geckos (Eublepharis macularius)
Authors: Schlief Sierra C. , Richman Joy M. , Brink Kirstin S.
Published: October 2024

An understanding of the dynamics of bone growth is key to interpreting life‐history parameters of vertebrates. In this study, we used fluorochrome labels in captive leopard geckos (Eublepharis macularius) to track bone growth and intraskeletal variability from embryonic to adult growth stages. Thirteen individuals were administered fluorochromes from pre‐hatching to 4 years of age. The left tibia, fibula, femur, humerus, radius, and ulna were examined histologically and compared for differences in the number of labels within and between individuals at each sampled growth stage, and the amount of bone growth between labels was calculated. Results suggest that limb elements had differing growth rates; the fibula grew the fastest per day on average and the femur grew the slowest per day on average. All labels administered in ovo were still present in all limb elements in adults except for the tibia, suggesting growth marks are not lost in most elements and accurate calculations of growth rates could be performed in individuals up to 3 years old. All ex ovo labels were accounted for; however, when two fluorochromes were administered 3 weeks apart, the labels could not be differentiated from each other due to the new bone not being deposited at a quantifiable level. Overall, the tibia in leopard geckos is the least reliable limb bone to use for skeletochronology and the humerus, radius, and fibula preserve the longest growth record. This research highlights that, as in other extinct and extant animals, patterns of bone growth are not consistent across reptiles. This study adds to the growing body of knowledge on growth variability in reptiles.
Relationship Between Social Isolation, Loneliness and Psychological Well‐Being in Inflammatory Bowel Disease Patients: The Mediating Role of Disease Activity Social Isolation in Inflammatory Bowel Disease
Authors: Yildirim Yasemin , Artan Yağmur , Unal Nalan Gülşen
Published: October 2024

Aim

To evaluate the relationship between social isolation, loneliness and psychological well‐being in patients with inflammatory bowel disease (IBD). Additionally, we examined the mediating effect of disease activity on the relationships between social isolation, loneliness and psychological well‐being.

Design

Cross‐sectional descriptive study.

Methods

A total of 218 participants were recruited from outpatient clinic at a university hospital in Turkey and from the community membership of the patient support group. Participants provided their socio‐demographic and disease‐related information and completed (online and paper based) the Turkish Lubben Social Network Scale‐6, the Turkish UCLA Loneliness Scale Short Form and the Turkish Psychological Well‐being Scale. The data were analysed using univariate linear regression analysis. This study adhered to the STROBE checklist for reporting.

Results

The majority of the participants (72%) were socially isolated, and over half (54.1%) reported moderate to high levels of loneliness. Participants also had low psychological well‐being. Linear regression analysis revealed that high loneliness level and social isolation were negative predictors of psychological well‐being. The results revealed that the effect of social isolation and loneliness on psychological well‐being was mediated by disease activity.

Conclusion

In line with the findings, it can be recommended to enhance social support and networks, along with regular psychological evaluation, should be integrated into the holistic care approach for IBD patients.

Relevance to Clinical Practice

The findings of this study hold significant implications for the management and support of patients with IBD, particularly within clinical settings in Turkey.

Patient or Public Contribution

Patients were invited to complete questionnaires. The investigators explained the study's content and purpose, and addressed any concerns during the data collection process.
(p)ppGpp Buffers Cell Division When Membrane Fluidity Decreases in Escherichia coli
Authors: Singh Vani , Harinarayanan Rajendran
Published: October 2024

Fluidity is an inherent property of biological membranes and its maintenance (homeoviscous adaptation) is important for optimal functioning of membrane‐associated processes. The fluidity of bacterial cytoplasmic membrane increases with temperature or an increase in the proportion of unsaturated fatty acids and vice versa. We found that strains deficient in the synthesis of guanine nucleotide analogs (p)ppGpp and lacking FadR, a transcription factor involved in fatty acid metabolism exhibited a growth defect that was rescued by an increase in growth temperature or unsaturated fatty acid content. The strain lacking (p)ppGpp was sensitive to genetic or chemical perturbations that decrease the proportion of unsaturated fatty acids over saturated fatty acids. Microscopy showed that the growth defect was associated with cell filamentation and lysis and rescued by combined expression of cell division genes ftsQ, ftsA, and ftsZ from plasmid or the gain‐of‐function ftsA* allele but not over‐expression of ftsN. The results implicate (p)ppGpp in positive regulation of cell division during membrane fluidity loss through enhancement of FtsZ proto‐ring stability. To our knowledge, this is the first report of a (p)ppGpp‐mediated regulation needed for adaptation to membrane fluidity loss in bacteria.
Explanations for language choice in the social context of the L2 classroom
Authors: Rindal Ulrikke
Published: October 2024

The use of students’ first language (L1) in additional language (L2) instruction has been a recurring theme in language education research. While research has documented the amount of L1 use and its purposes in L2 instruction, little research has investigated the multifaceted motives that influence language choices at the micro level of social activity where language learning takes place. This study contributes new perspectives by exploring the beliefs of teachers and students from two cases of Norwegian use during English lessons, applying video‐stimulated recall in semistructured interviews to elicit reflections about observed language choices in concrete classroom interactions. The findings revealed the complexity of factors influencing language choice in the L2 classroom. First, although teachers agreed on a mainly English ideal, competing beliefs led to varying instructional practices. Second, monolingual ideals were stronger among the students in comparison with their teachers, but these ideals operated alongside an affective dimension of language choice in interactions with the teacher and group work with peers. The study demonstrates how teacher and student beliefs are influenced by macro‐level sociopolitical discourses about multilingualism and indicates that language choice is influenced by such beliefs in combination with more temporary stances and roles.
Intra‐Abdominal Candidiasis in Cancer Patients: A 10‐Year Experience in a Middle‐Income Country
Authors: de Almeida Bianca Leal , Arcieri Vitor Ciampone , Razente Danilo Mardegam , Freire Maristela Pinheiro , Guimarães Thais , Araújo Evangelina da Motta Pacheco Alves de , Abdala Edson , Magri Marcello Mihailenko Chaves
Published: October 2024

Background

Invasive candidiasis (IC) represents a significant threat to both mortality and morbidity, especially among vulnerable populations. Intra‐abdominal candidiasis (IAC) frequently occurs in critically ill and cancer patients, with these specific groups carrying a heightened risk for such invasive fungal infections. Despite this, there is a noticeable lack of attention to IAC in cancer patients within the literature, highlighting a critical gap that requires urgent consideration.

Objectives

This study aimed to explore the clinical and epidemiological characteristics of IAC and identify prognostic factors in a cancer centre in a middle‐income country over 10 years.

Patients/Methods

A retrospective cohort observational study of adults diagnosed with IAC was conducted at the Instituto do Cancer do Estado de São Paulo (ICESP), a tertiary hospital specialising in oncological diseases with 499 beds, including 85 intensive care unit (ICU) beds, from December 2009 through May 2021.

Results

A total of 128 episodes were included: 67.2% admitted to the ICU; 54.7% males; and median age 62 years. The predominant diagnosis was peritonitis (75.8%). Blood culture samples were collected from 128 patients upon admission, revealing candidemia in 17.2% (22). The most frequently isolated were C. albicans (n = 65, 50.8%) and C. glabrata (n = 42, 32.8%). Antifungal treatment was administered to 91 (71%) patients, with fluconazole (64.8%) and echinocandins (23.4%) being the most common choices. A significant proportion of these patients had a history of abdominal surgery or antibiotic use. Independent factors associated with 30‐day mortality included the median Sequential Organ Failure Assessment (SOFA) score of 6 (OR = 1.30, 95% CI 1.094–1.562, p = 0.003), days of treatment (median 10.5) (OR = 0.93, 95% CI 0.870–0.993, p = 0.031) and abdominal source control (78.1%) (OR = 0.148, 95% CI 0.030–0.719, p = 0.018). The 30‐day mortality rate was 41.1%.

Conclusions

Our study underscores the critical importance of implementing effective source control as a key strategy for reducing mortality in IAC.
Higher cost of gluten‐free products compared to gluten‐containing equivalents is mainly attributed to staple foods
Authors: Bathrellou Eirini , Bountziouka Vasiliki , Lamprou Despoina , Fragedaki Evanthia , Papachristou Eleftheria , Vriesekoop Frank , Kontogianni Meropi D.
Published: October 2024

The high cost of gluten‐free products (GFPs) is being discussed as a potential barrier to adherence to a gluten‐free diet, rendering monitoring of their pricing an ongoing demand in a market subject to continuous fluctuations. The current study aimed to assess the current pricing status of GFPs in the Greek retail market, with a focus on differences between staple and non‐staple foods. The retail price and packaging weight of all available GFPs and their gluten‐containing (GCPs) counterparts of a GFP‐shopping basket (formulated based on the results of a preceding online survey) were recorded by visiting one store of the five most popular reported supermarket chains. The food categories were grouped into staple (e.g. breads, pasta and flours) and non‐staple (e.g. chips, sweets and sauces) foods. Adjusting for supermarket chain and product type, a quantile mixed regression model was applied to assess the extent to which median product price (per 100 g) differed between GFPs and GCPs. The unique products recorded were 1058 (of which 408 GFPs), with a total of 2165 retail price recordings. While the overall median price/100 g of GFPs was not found to be significantly different from that of GCPs, the median price of staple GFPs was estimated to be higher than staple GCPs (+€1.03 [95% CI: €0.93; €1.13] per 100 g), whilst that of non‐staple GFPs was slightly lower (−€0.20 [95% CI: −€0.37; −€0.02] per 100 g). In conclusion, the persisting higher cost of staple GFPs suggests the need for ongoing financial support for people with coeliac disease.
Exploring the experience of cardiothoracic ICU clinicians during the COVID‐19 pandemic: A grounded theory study
Authors: Hughes Leah , Shelley Benjamin , McPeake Joanne
Published: October 2024

Background

Prior to the COVID‐19 pandemic a flexible approach to visiting was adopted by many Intensive Care Units in the United Kingdom. Due to the rapid spread globally of COVID‐19, significant policy changes were put in place, including the restriction on visitors to patients in hospital. Evidence has emerged demonstrating the negative impact of these restrictions on patients with COVID‐19, their families and the staff caring for them. However, there is limited data about the impact of these restrictions in the non‐COVID ICU environment.

Aim

This study aimed to explore the experiences of staff caring for non‐COVID‐19 patients in a cardiothoracic critical care unit during the COVID‐19 pandemic.

Study Design

This qualitative research study adopted a grounded theory methodological approach. This methodology was used due to the unique situation, with no prior research available. We recruited healthcare staff that worked in a cardiothoracic critical care unit during the COVID‐19 pandemic. Semi structured interviews were carried out, transcribed, and analysed. Using the data collected, a theory was constructed.

Results

Interviews were carried out with 20 healthcare staff from a range of professions including nurses, doctors, and allied health professionals. Following data analysis four main categories emerged from the data: impact and implementation of visiting restrictions; the dehumanisation of patients; end‐of‐life care and witnessing distress. From these four categories, a theory has emerged suggesting that healthcare staff in a non‐covid ICU were regularly exposed to potentially moral injurious events, despite being shielded from caring for patients with COVID‐19.

Conclusions

This study provides a theory that healthcare staff caring for non‐COVID‐19 critical care patients during the period of visiting restrictions were exposed to potentially morally injurious events.

Relevance to clinical practice

Repeated exposure to potentially morally injurious events can lead to the development of moral injury and its adverse consequences. This study highlights the need to support all staff in the post COVID era, including those who worked in a non‐COVID environment.
Cell‐type‐aware regulatory landscapes governing monoterpene indole alkaloid biosynthesis in the medicinal plant Catharanthus roseus
Authors: Li Chenxin , Colinas Maite , Wood Joshua C. , Vaillancourt Brieanne , Hamilton John P. , Jones Sophia L. , Caputi Lorenzo , O'Connor Sarah E. , Buell C. Robin
Published: October 2024

In plants, the biosynthetic pathways of some specialized metabolites are partitioned into specialized or rare cell types, as exemplified by the monoterpenoid indole alkaloid (MIA) pathway of Catharanthus roseus (Madagascar Periwinkle), the source of the anticancer compounds vinblastine and vincristine. In the leaf, the C. roseus MIA biosynthetic pathway is partitioned into three cell types with the final known steps of the pathway expressed in the rare cell type termed idioblast. How cell‐type specificity of MIA biosynthesis is achieved is poorly understood.

We generated single‐cell multi‐omics data from C. roseus leaves. Integrating gene expression and chromatin accessibility profiles across single cells, as well as transcription factor (TF)‐binding site profiles, we constructed a cell‐type‐aware gene regulatory network for MIA biosynthesis.

We showcased cell‐type‐specific TFs as well as cell‐type‐specific cis‐regulatory elements. Using motif enrichment analysis, co‐expression across cell types, and functional validation approaches, we discovered a novel idioblast‐specific TF (Idioblast MYB1, CrIDM1) that activates expression of late‐stage MIA biosynthetic genes in the idioblast.

These analyses not only led to the discovery of the first documented cell‐type‐specific TF that regulates the expression of two idioblast‐specific biosynthetic genes within an idioblast metabolic regulon but also provides insights into cell‐type‐specific metabolic regulation.
Trends in Phototherapy Utilization, Payments, and Geographic Distribution: An Analysis of United States Medicare Part B From 2000 to 2021
Authors: Xia Eric , Kam Lisa , Mostaghimi Arash
Published: October 2024

Background

Trends in phototherapy utilization in the context of new therapeutics have not been evaluated.

Objective

This study aimed to evaluate phototherapy utilization, payments, and geographic distribution for Medicare beneficiaries from 2000 to 2021.

Patients/Methods

A longitudinal analysis of the Medicare Part B National Summary Data Files was conducted to obtain phototherapy utilization and payment amounts. Medicare Physician & Other Practitioners by Provider and Service datasets were used to determine provider type and geographic distribution.

Results

Between 2000 and 2021, total Medicare phototherapy volume increased from 335,152 to 621,850, correlating with a 3.0% annual growth rate (5.0% between 2000 and 2015, −3.1% between 2016 and 2021). Ultraviolet B phototherapy represented the majority of use, rising from 68.1% in 2000 to 78.0% in 2021. Psoralens plus ultraviolet A decreased by 11.3% annually, while laser treatments increased by 17.3%. Between 2013 and 2021, the number of clinics offering phototherapy declined; facilities were available in only 9.9% of counties, mainly clustered along both coasts and east of the Mississippi.

Conclusions

Overall, phototherapy continues to be an important therapeutic option. Limited access in non‐urban areas remains a significant challenge, and further work is necessary to both evaluate this impact and reduce disparities.
Different physical exercise in the treatment of Alzheimer's disease
Authors: Deng Tianqing , Yu Weihua , Lü Yang
Published: October 2024

Alzheimer's disease (AD) is rapidly becoming one of the most expensive, burdening, and deadly diseases of this century. Up to now, there is still a lack of pharmacotherapy with substantial efficacy, and physical exercise is a promising and low‐cost way to aid in delaying the process of AD. The aim of this review is to summarise the efficacy of different physical exercise approaches and doses in the management of AD, including aerobic exercise, resistance exercise and multicomponent exercise. A literature search using MeSH terms for each topic is undertaken using PubMed and the Web of Science Core Collection database, supplemented by hand searching for additional references. Retrieved articles were reviewed, synthesised, and summarised. This review shows that aerobic exercise has been almost unanimously recognised for the improvement of cognition, neuropsychiatric symptoms and activities of daily living. Resistance exercise also shows a good prospect in the above aspects and has a unique advantage in enhancing muscle strength, while multicomponent physical activity does not seen to significantly improve cognitive function. Each type of exercise has a dose effect, but for individuals with AD, the most appropriate exercise dose is still controversial.
Beyond the Win–Win Discourse: Designing Seaweed Farming for Long‐Term Success
Authors: Chaigneau Tomas , Nicolini Giulia , Orchel Katharine , Daniels Carly , Ashton Ian
Published: October 2024

Communication about seaweed aquaculture has so far been dominated by its many socio‐economic and ecological advantages. A key risk of this ‘hype’ is the potential loss of support from communities affected by seaweed cultivation if reality fails to live up to expectations. This could have justice and equity implications for impacted communities, and undermine potential benefits for those communities, as well as affecting the long‐term success of emerging industries. This paper highlights experiences from other marine sectors in which a similar emphasis on benefits has drowned out discussion of potential costs, often leading to initial success but long‐term failure. We highlight the importance of clearly communicating possible negative impacts, and meaningfully engaging stakeholders to shape marine interventions. Finally, we recommend further research into the social dimensions of seaweed farming in geographies where this practice is nascent, and increased attention to the potential trade‐offs of scaling up seaweed cultivation.
A Novel Intravaginal Contraceptive Plug for Cats: A Preliminary Biocompatibility Assessment on Haematology and Vaginal Swab
Authors: Ainun Sella Sofia , Santoso Muhammad Irham Bagus , Yessa Elma Yuliani , Gunanti  , Nasution Ahmad Kafrawi , Saidin Syafiqah , Ulum Mokhamad Fakhrul
Published: October 2024

This preliminary study evaluated the biocompatibility of a novel degradable intravaginal plug contraceptive composed of PEG 4000 and chitosan in cats using haematological profiling and vaginal cytology. Five healthy, non‐pregnant female cats were fully anaesthetised and fitted with an intravaginal plug (10 × 0.3 mm) using an applicator, following oestrogen administration 3 h prior. Blood samples were collected from the cephalic vein on days 0 (pre‐insertion) and 3 and 7 (post‐insertion). Vaginal cytology examinations were conducted on day 0 (pre‐ and post‐oestrogen injection) and days 1, 3 and 7 post‐insertion. Haematological parameters, including red blood cell count, haemoglobin levels, haematocrit values, total white blood cell count and differentiation, showed no significant changes after contraceptive insertion (p > 0.05). Vaginal cytology indicated an acute inflammatory response in one out of five subjects on day three post‐insertion. The distribution of vaginal epithelial cells (parabasal, intermediate and superficial) remained unaffected by contraception. Oestrogen injection resulted in the dominance of superficial cells up to day 7 of observation (p < 0.05). Overall, PEG 4000 and chitosan‐based intravaginal plug contraceptives demonstrated sufficient biocompatibility, indicating their potential as viable contraceptive options for feline use.
Shared Class, Shared Opinion? Policy Preference Congruence Between Citizens and Legislators
Authors: Wüest Reto , Helfer Luzia , Varone Frédéric
Published: October 2024

Recent studies have shown that policymakers and policy outcomes in advanced democracies are biased against the preferences of less affluent and working‐class citizens. One reason for this inequality in substantive representation might be that most policymakers are well‐off themselves. In this paper, we explore the effect of shared class background on the congruence between legislators' and citizens' policy preferences. To do so, we rely on original data from surveys conducted among citizens and active legislators in Switzerland. We focus on six economic and welfare policy proposals where we find differences in opinion between social classes. When we match legislators' and citizens' opinion in a one‐to‐many relationship, we find that social class matters more for lower social classes than for the more affluent, at least for some policy proposals.
Identification of the Novel HLA‐A*03:01:01:122 Allele in a Chinese Individual Using PacBio HiFi Sequencing
Authors: Han Yue , Li Yankun , Wang Yuqi , Ren Juan , Wang Xiaoning
Published: October 2024

HLA‐A*03:01:01:122 differs from HLA‐A*03:01:01:01 by one nucleotide change in intron 3.
Monazite Beats Zircon Regarding Dating of Young Metamorphic Events—An Example From Polycyclic Granitic Gneiss of the Pohorje Mountains, Slovenia
Authors: Li Botao , Massonne Hans‐Joachim , Zhang Junfeng , Yuan Xiaoping , Luo Tao
Published: October 2024

The result of dating U–(Th)–Pb bearing minerals in metamorphic rocks frequently suffers from the interpretative relation of their growth to a specific metamorphic event. This problem occurs in the southern Pohorje Mountains. Therefore, granitic gneiss from this area was studied. Rims of zircon in these rocks gave U–Pb ages around 90 Ma interpreted as an indicator of Late Cretaceous metamorphism. However, in situ dating of monazite with LA–ICP–MS yielded Early Miocene U–Th–Pb ages consistent with contact metamorphism by magmas forming the Pohorje pluton. This is supported by geothermobarometry using compositions of garnet and muscovite in granitic gneiss. This method led to pressure–temperature conditions of 6.5 kbar and 625°C, in line with intrusion depths estimated for the southeastern part of the Pohorje pluton. Consequently, zircon was not suitable for dating the latest metamorphic event but monazite was. Furthermore, monazite dating suggests two main intrusion pulses of magmas differing by 2–3 Ma.
Selection Criteria for Rotor Number and Rotational Direction in Arrays of Closely Spaced Darrieus Turbines
Authors: Mohamed Omar Sherif , Melani Pier Francesco , Soraperra Giuseppe , Brighenti Alessandra , Balduzzi Francesco , Bianchini Alessandro
Published: October 2024

The efficiency gains observed in a pair of closely spaced Darrieus turbines suggest the deployment of multiple turbines as an appealing solution for wind and, particularly, hydrokinetic applications, where the inflow direction is constant. The present study develops some design guidelines for closely spaced hydrokinetic Darrieus turbines by analyzing the trends of both power augmentation and wake development within arrays of multiple rotors, including not only an even number of rotors, which is the usual case in literature, but also an odd one. The analysis is carried out by means of two-dimensional computational fluid dynamics simulations and includes not only the assessment of instantaneous blade forces but also locally sampled flow fields past each blade that allowed the reconstruction of dynamic polar data, contributing to a more comprehensive understanding of the physical mechanisms at play in such compact setups. The study demonstrates a consistent power augmentation mechanism across different layouts, even in the case of an odd number of rotors. This enhancement originates from flow blockage in the mutual interaction areas, favorably altering the inflow angle and subsequently increasing the angle of attack and lift generation. While this mechanism aligns with previous observations on arrays of counter-rotating pairs, its application to multiple turbines introduces complexities due to potential asymmetries in inflow, leading to an uneven power enhancement across turbines within the array. The identified efficiency improvement pattern suggests that maximizing leeward mutual interactions within an array of multiple Darrieus turbines would enhance the overall efficiency of the setup.
A Comparison Between Four Chaotic Indicators in Systems With Hidden Attractors
Authors: Maaita Jamal-Odysseas , Prousalis Dimitrios
Published: October 2024

A nonregular oscillation is not enough to define a system as chaotic. A more in-depth investigation is required to prove the existence of chaotic behavior, which is challenging. Although many scientists use the Lyapunov Characteristic Exponents to detect chaos, it is not the only method. Several scientists have introduced different methods that utilize various properties of dynamical systems. Hidden Attractors may be chaotic or regular. The fact that they have small basins of attraction introduces difficulties in locating and characterizing them. The paper presents four different chaotic indicators based on the evolution of the deviation vectors: the maximal Lyapunov Exponent, the Lyapunov Characteristic Exponents, the Fast Lyapunov Index (FLI), and the Small Alignment Index. It includes their properties and the advantages and disadvantages of each method. Also, it includes the algorithms to calculate them and their implementation in Python. The paper closes with a comparison between the four indices applied to a system with hidden attractors.
Investigation of Nonlinear Dynamic Behaviors of Vertical Rotor System Supported by Aerostatic Bearings
Authors: Qiu Shun , Ke Changlei , Li Kongrong , Zhang Xiaohua , Peng Nan , Liu Liqiang
Published: October 2024

A common issue associated with gas bearing–rotor systems is the tendency to generate self-excited vibrations, leading to instability. To address this problem, the fluid–structure coupling model of an aerostatic bearing–rotor system is established in this paper. Then, a hybrid method combining the finite difference method (FDM) and direct integration method is employed to solve the bearing lubrication equation and rotor motion equation simultaneously. Furthermore, based on the orbits of rotor center, frequency spectrum diagrams, Poincaré maps, waterfall diagrams, and bifurcation diagrams, the effects of rotational speed, rotor mass, orifice diameter, and nominal clearance on the nonlinear dynamic behaviors of the bearing–rotor system are investigated. The results indicate that the system exhibits rich nonlinear behaviors with increasing rotational speed and rotor mass, including the occurrence of typical half-speed whirl. However, the nonlinear vibrations of the system can be restricted by selecting appropriate bearing structural parameters, providing theoretical guidance for the design of aerostatic bearing–rotor systems.
Visual disturbance and Purtscher’s retinopathy heralding an occult femoral fracture
Authors: Corbett James , Small Keith , Gale Jesse
Published: October 2024

An 80-year-old fit and active gentleman presented with left hip pain and a new central scotoma in his right eye after falling from an electric bicycle. He was able to mobilise independently and presented to ophthalmic services where cotton wool spots were found in both eyes and a presumptive diagnosis of Purtscher’s retinopathy (PuR) was made. The patient was referred to the emergency department for assessment of a potential fracture. The subcapital femoral neck fracture was subtle on X-ray and only detected the following day with radiological and orthopaedic review. Two screws were placed to stabilise the fracture with a good outcome for his hip and for his vision. PuR can be seen following trauma to the head, neck or chest, following long bone fracture and in renal failure or pancreatitis. Our case highlights how the non-specific finding of cotton wool spots becomes a highly specific diagnosis in the context of trauma and should lead to careful evaluation for fractures.
Protocol for a phase 2 study of bosutinib for amyotrophic lateral sclerosis using real-world data: induced pluripotent stem cell-based drug repurposing for amyotrophic lateral sclerosis medicine (iDReAM) study
Authors: Imamura Keiko , Izumi Yuishin , Egawa Naohiro , Ayaki Takashi , Nagai Makiko , Nishiyama Kazutoshi , Watanabe Yasuhiro , Murakami Takenobu , Hanajima Ritsuko , Kataoka Hiroshi , Kiriyama Takao , Nanaura Hitoki , Sugie Kazuma , Hirayama Takehisa , Kano Osamu , Nakamori Masahiro , Maruyama Hirofumi , Haji Shotaro , Fujita Koji , Atsuta Naoki , Tatebe Harutsugu , Tokuda Takahiko , Takahashi Naoto , Morinaga Akiko , Tabuchi Riko , Oe Motoki , Kobayashi Mihoko , Lobello Kasia , Morita Satoshi , Sobue Gen , Takahashi Ryosuke , Inoue Haruhisa
Published: October 2024

Introduction

Amyotrophic lateral sclerosis (ALS) is a progressive, severe neurodegenerative disease caused by motor neuron death. Development of a medicine for ALS is urgently needed, and induced pluripotent cell-based drug repurposing identified a Src/c-Abl inhibitor, bosutinib, as a candidate for molecular targeted therapy of ALS. A phase 1 study confirmed the safety and tolerability of bosutinib in a 12-week treatment of ALS patients. The objectives of this study are to evaluate the efficacy and longer-term safety of bosutinib in ALS patients.

Methods and analysis

An open-label, multicentre phase 2 study was designed. The study consisted of a 12-week observation period, a 1-week transitional period, a 24-week study treatment period and a 4-week follow-up period. Following the transitional period, patients whose total Revised ALS Functional Rating Scale (ALSFRS-R) score declined by 1 to 4 points during the 12-week observation period were to receive bosutinib for 24 weeks. In this study, 25 ALS patients will be enrolled; patients will be randomly assigned to the following groups: 12 patients in the 200 mg quaque die (QD) group and 13 patients in the 300 mg QD group of bosutinib. The safety and exploratory efficacy of bosutinib in ALS patients for 24 weeks will be assessed. Efficacy using the ALSFRS-R score will be compared with the external published data from an edaravone study (MCI186-19) and registry data from a multicentre ALS cohort study, the Japanese Consortium for Amyotrophic Lateral Sclerosis Research.

Ethics and dissemination

This study was approved by the ethics committees of Kyoto University, Tokushima University, Kitasato University, Tottori University, Nara Medical University School of Medicine, Toho University and Hiroshima University. The findings will be disseminated in peer-reviewed journals and at scientific conferences.

Trial Registration number

jRCT2051220002; Pre-results,NCT04744532; Pre-results
Patient delay, diagnosis delay, and treatment outcomes among migrant patients with tuberculosis in Shanghai, China, 2018-2020: a mixed-methods study
Authors: Jia Yufei , Jiang Weixi , Xiao Xiao , Lou Zhexun , Tang Shenglan , Chen Jing , Long Qian
Published: October 2024

Objectives

This study aimed to examine patient delay, diagnosis delay and treatment performance among patients with tuberculosis (TB) in Shanghai, China in 2018–2020 focusing on disparities between migrant and local patients with TB.

Design

Mixed-method study.

Setting and participants

Quantitative data were collected from the TB information management system in Shanghai; 17 533 bacteriologically confirmed and clinically diagnosed patients with pulmonary TB registered in 2018–2020 were included. Qualitative interviews were conducted with TB administrators (n=3) and community healthcare providers (two groups, n=10 in total) from Shanghai.

Main outcome measures

Patient delay, diagnosis delay and treatment completion were examined by resident type using descriptive analysis and logistic regressions. Qualitative interviews were conducted to understand factors associated with the disparities.

Results

From 2018 to 2020, migrant patients with TB accounted for 44.40% of total cases. There was no significant difference in patient delay between migrant and local patients (18.47 days on average). 22.12% of migrants and 16.52% of locals experienced diagnosis delays exceeding 14 days, respectively. After adjusting for all variables, migrant patients (OR 1.30, 95% CI 1.18 to 1.44) and initial care seeking at general hospitals (OR 3.76, 95% CI 3.45 to 4.09) were associated with a higher probability of diagnosis delay. 93.9% of migrant patients and 89.4% of the local patients had a successful TB treatment without statistically significant difference after adjusting for all variables. Qualitative interviews revealed a standard approach to managing patients with TB in Shanghai no matter their resident type. Young migrant patients who were able to maintain their jobs in Shanghai often had better treatment adherence. Despite patients’ COVID-19 fear and limited care access in 2020, TB treatment minimally affected for both due to community-based case management.

Conclusions

Migrant patients were more likely to experience diagnosis delay. It should improve awareness and knowledge of TB among healthcare professionals at general hospitals to mitigate the risk of diagnosis delay.
Multiarm, non-randomised, single-centre feasibility study—investigation of the differential biology between benign and malignant renal masses using advanced magnetic resonance imaging techniques (IBM-Renal): protocol
Authors: Horvat-Menih Ines , McLean Mary A , Zamora-Morales Maria Jesus , Wylot Marta , Kaggie Joshua , Khan Alixander S , Gill Andrew B , Duarte Joao , Locke Matthew J , Mendichovszky Iosif , Li Hao , Priest Andrew N , Warren Anne Y , Welsh Sarah J , Jones James O , Armitage James N , Mitchell Thomas J , Stewart Grant D , Gallagher Ferdia A
Published: October 2024

Introduction

Localised renal masses are an increasing burden on healthcare due to the rising number of cases. However, conventional imaging cannot reliably distinguish between benign and malignant renal masses, and renal mass biopsies are unable to characterise the entirety of the tumour due to sampling error, which may lead to delayed treatment or overtreatment. There is an unmet clinical need to develop novel imaging techniques to characterise renal masses more accurately. Renal tumours demonstrate characteristic metabolic reprogramming, and novel MRI methods have the potential to detect these metabolic perturbations, which may therefore aid accurate characterisation. Here, we present our study protocol for the investigation of the differential biology of benign and malignant renal masses using advanced MRI techniques (IBM-Renal).

Methods and analysis

IBM-Renal is a multiarm, single-centre, non-randomised, feasibility study with the aim to provide preliminary evidence for the potential role of the novel MRI techniques to phenotype localised renal lesions. 30 patients with localised renal masses will be recruited to three imaging arms, with 10 patients in each: (1) hyperpolarised [1-13C]-pyruvate MRI, (2) deuterium metabolic imaging (DMI) and (3) sodium MRI. The diagnosis will be made on samples acquired at biopsy or at surgery. The primary objective is the technical development of the novel MRI techniques, with the ultimate aim to understand whether these can identify differences between benign and malignant tumours, while the secondary objectives aim to assess how complementary the techniques are, and if they provide additional information. The exploratory objective is to link imaging findings with clinical data and molecular analyses for the biological validation of the novel MRI techniques.

Ethics and dissemination

This study was ethically approved (UK REC HRA: 22/EE/0136; current protocol version 2.1 dated 11 August 2022). The plans for dissemination include presentations at conferences, publications in scientific journals, a doctoral thesis and patient and public involvement.

Trial registration number

NCT06016075.
Development and validation of a clinical diagnostic model for myocardial ischaemia in borderline coronary lesions based on optical pumped magnetometer magnetocardiography: a prospective observational cohort study
Authors: Yang Shuwen , Feng Lanxin , Zhang Mingduo , Zhang Min , Ma Zhao , Zhang Huan , Zhang YaZhe , Liu Linqi , Zhou Shu , Zhao Xin , Yang Xue Yao , He Jiqiang , Ren Yanlong , Luo Yawei , Xu Feng , Tu Chenchen , Song Xiantao , Zhang Hong-Jia
Published: October 2024

Objectives

To develop and validate a clinical diagnostic model based on optical pumped magnetometer magnetocardiography (OPM-MCG) for the detection of myocardial ischaemia in patients with borderline coronary lesions prior to invasive coronary angiography (ICA).

Design

Prospective observational cohort study.

Setting

Single centre of the China National Clinical Research Centre for Cardiovascular Disease (NCCMRC).

Participants

Adults with borderline coronary lesions on ICA (n=141).

Interventions

Underwent OPM-MCG before ICA and fractional flow reserve measurement.

Results

Five parameters were included in the final diagnostic model: MAgmax-TT, δDtsum-PN, δAgsum-C, δArsum-N and δArmin-N. 1000 bootstrap replications showed that the area under the receiver operating characteristic curve and 95% CI of the diagnostic model were 0.864 (0.803–0.925), with a sensitivity of 79.4%, specificity of 80.8%, positive predictive value of 79.4% and negative predictive value of 80.8%. Decision curve analysis showed a net benefit from the predictive model when the threshold probability of an ischaemic patient was >12%, suggesting the potential utility of the model in the real world.

Conclusions

A nomogram based on five OPM-MCG parameters was developed to assess myocardial ischaemia in patients with borderline coronary lesions and has the potential to reduce the need for unnecessary ICA.

Trial registration number

China Clinical Trial Registry (ChiCTR2300072382).
Food insecurity and other barriers to adherence to a gluten-free diet in individuals with coeliac disease and non-coeliac gluten sensitivity in the Netherlands: a mixed-methods study
Authors: Smeets Sharine M , Kiefte-de Jong Jessica C , van der Velde Laura A
Published: October 2024

Objectives

To determine the prevalence of food insecurity among individuals with coeliac disease (CeD) and non-coeliac gluten sensitivity (NCGS) in the Netherlands and explore its association with diet quality and other barriers to adherence to a gluten-free diet.

Design

Mixed-method design comprising a survey and semistructured interviews.

Setting

An online survey was distributed through social media accounts and the newsletter of the Dutch Association for Celiac Disease. Community-dwelling patients were surveyed and interviewed between June and November 2023.

Participants and outcome measures

In total 548 adults with CeD and NCGS in the Netherlands who adhered to a gluten-free diet completed the survey including questions related to demographics, household food insecurity, financial stress and diet quality. Regression analyses were conducted to assess associations between food insecurity and diet quality, and between food insecurity and perceived difficulty of gluten-free eating and cooking. Additionally, semistructured interviews with eight food insecure adults with CeD were conducted.

Results

The prevalence of food insecurity was 23.2%, with 10.4% reporting very low food security. Very low food insecurity was associated with poorer diet quality (β=−5.5; 95% CI=−9.2 to –1.9; p=0.003). Food insecurity was associated with heightened perceived barriers across multiple themes. In age, income and education adjusted models, compared with food secure participants, low food secure participants were more likely to experience difficulty regarding skills (OR=2.5; 95% CI=1.5 to 4.3; p≤0.001), social circumstances (OR=2.6; 95% CI=1.1 to 6.4; p=0.038), resources (OR=2.5; 95% CI=1.5 to 4.4; p=0.001) and naturally gluten-free products (OR=1.8; 95% CI=1.0 to 3.1; p=0.045) in gluten-free eating and cooking. Participants with very low food security were more likely to experience difficulty regarding skills (OR=4.4; 95% CI=2.4 to 8.1; p≤0.001) and resources (OR=4.2; 95% CI=2.3 to 7.8; p<0.001) in gluten-free eating and cooking. The qualitative analysis provided a deeper understanding of these challenges, including employed strategies to manage costs and insights into the mental burden associated with adhering to a gluten-free diet.

Conclusion

These findings indicate that food insecurity is prevalent among Dutch people with CeD and NCGS, with potential impact on diet quality and adherence to a gluten-free diet. It further provided insight into perceived barriers to adhering to a gluten-free diet among this target population. These challenges should be taken into account by clinicians and policy makers.
Direct oral anticoagulant approvals by four major regulatory agencies: a cross-sectional analysis of premarket and postmarket evidence
Authors: Mooghali Maryam , Zhou Tianna , Ross Joseph S
Published: October 2024

Objectives

To compare the premarket and postmarket evidence of safety and efficacy of direct oral anticoagulants approved for stroke prevention in atrial fibrillation patients across four major regulatory agencies.

Design

Cross-sectional.

Setting

European Medicines Association (EMA), US Food and Drug Administration (FDA), Health Canada and Australian Therapeutic Goods Administration (TGA).

Participants

Apixaban, dabigatran, edoxaban and rivaroxaban marketing authorisations.

Outcome measures

Concordance among regulatory agencies with respect to (1) premarket evidence used to establish efficacy and safety and (2) postmarket safety boxed warnings and postmarketing study requirements.

Results

Apixaban, dabigatran and rivaroxaban were approved by each of the four regulatory agencies; edoxaban was only not approved by TGA. For premarket efficacy evidence, there was concordance across all agencies in terms of phase 3 trials for three (75%) drugs, sample size for three (75%) drugs, primary endpoints for four (100%) drugs, numerical results for three (75%) drugs, agency interpretation of results for four (100%) drugs and number of phase 2 trials for three (75%) drugs. For the premarket safety evidence, there was concordance across all agencies in terms of phase 3 trials for three (75%) drugs, sample size for two (50%) drugs, primary endpoints for four (100%) drugs, numerical results for three (75%) drugs, agency interpretation of results for three (75%) drugs and number of phase 2 trials for zero (0%) drugs. For postmarket safety information, FDA was the only agency that issued boxed warnings (for three (75%) drugs). Additionally, EMA and TGA required postmarketing studies (for four (100%) and two (50%) drugs, respectively), while FDA and Health Canada did not have any postmarketing requirements.

Conclusions

There was a high degree of concordance in the phase 3 trial premarket evidence used to establish efficacy and safety of direct oral anticoagulant approvals across four major regulatory agencies, but discordance in the phase 2 trial premarket evidence used, as well as in postmarket safety boxed warnings and postmarketing study requirements. These discrepancies highlight opportunities for further harmonisation in the evaluation and regulation of medical products globally.