bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the effects of extended interval dosing of natalizumab and drug concentrations on brain atrophy in multiple sclerosis
Authors: Toorop Alyssa A , Noteboom Samantha , Steenwijk Martijn D , Gravendeel Job W , Jasperse Bas , Barkhof Frederik , Strijbis Eva MM , Rispens Theo , Schoonheim Menno M , van Kempen Zoé LE , Killestein Joep
Published: January 2024

Background:

Extended interval dosing (EID) of natalizumab treatment is increasingly used in multiple sclerosis. Besides the clear anti-inflammatory effect, natalizumab is considered to have neuroprotective properties as well.

Objectives:

This study aimed to study the longitudinal effects of EID compared to standard interval dosing (SID) and natalizumab drug concentrations on brain atrophy.

Methods:

Patients receiving EID or SID of natalizumab with a minimum radiological follow-up of 2 years were included. Changes in brain atrophy measures over time were derived from clinical routine 3D-Fluid Attenuated Inversion Recovery (FLAIR)-weighted magnetic resonance imaging (MRI) scans using SynthSeg.

Results:

We found no differences between EID ( n = 32) and SID ( n = 50) for whole brain (−0.21% vs −0.16%, p = 0.42), ventricular (1.84% vs 1.13%, p = 0.24), and thalamic (−0.32% vs −0.32%, p = 0.97) annualized volume change over a median follow-up of 3.2 years. No associations between natalizumab drug concentration and brain atrophy rate were found.

Conclusion:

We found no clear evidence that EID compared to SID or lower natalizumab drug concentrations have a negative impact on the development of brain atrophy over time.
White and gendered aesthetics and attitudes of #pandemicbaking and #quarantinebaking
Authors: Sobande Francesca
Published: January 2024

Foodwork is a political matter, and baking is no exception. Many messages are associated with the symbolic significance of baking, such as idealised notions of white, middle-class domesticity, femininity and visibility. The rise in home-baking during the COVID-19 pandemic resulted in a surge in social media content, which conveys much about the different meanings ascribed to baking. Relatedly, scholarship on ‘COVID-19 foodwork, race, gender, class and food justice’ highlights that intersecting oppressions are implicated in such matters. Drawing on different lines of research that specify and address structural power relations (e.g. gendered whiteness), I analyse the aesthetics and accompanying attitudes conveyed via Instagram posts about #pandemicbaking and #quarantinebaking. In doing so, I draw and build on critical studies of whiteness and digital food media, and connections between consumerism and COVID-19. This work considers what such online content suggests about the relationship between a ‘feminised, white, aestheticised ethos’ and digital discourse and depictions regarding food, family, domesticity, work and rest. Consequently, this research ponders over whether the labour and framing involved in documenting #pandemicbaking and #quarantinebaking on Instagram reflects a neoliberal form of entrepreneurial ‘freelance feminism’, which is animated by the tension between the ‘frequently polarized figures of “the feminist” and “the housewife”’. I examine the significance of three key themes related to #pandemicbaking and #quarantinebaking: (1) Gendered domestic labour and digital depictions and discourses of motherhood; (2) productivity, pausing and so-called ‘soulfulness’; and (3) domestic minimalism and aesthetics of whiteness. In turn, this article critically reflects on the relationship between mediated constructions of gendered whiteness and baking, while echoing calls for more research that explicitly addresses dynamics between digital whiteness, class, aesthetics, gendered racial capitalism, foodwork, feminism and online content creation.
Effect of sarcopenia on mortality in acute stroke patients receiving endovascular treatment
Authors: Beşler Muhammed Said , Çay Nurdan , Sayın Bige
Published: January 2024

Background

To investigate the effect of sarcopenia on mortality in patients with acute ischemic stroke caused by anterior circulation large artery occlusion who underwent endovascular treatment.

Methods

Acute ischemic stroke patients (n = 194) treated with mechanical thrombectomy who underwent chest computed tomography between 2019 and 2022 (median age, 69 [interquartile range: 61–77], 95 females, 99 males) were evaluated retrospectively. The cross-sectional area and density of the pectoralis muscle [pectoralis muscle area (PMA) and pectoralis muscle density (PMD)] at the level of the aortic arch and the erector spinae muscle at the T12 level [erector spinae muscle area (ESMA) and erector spinae muscle density (ESMD)] were measured. The association between skeletal muscle parameters and mortality outcomes was investigated using the receiver operating characteristic (ROC) curve and multivariable logistic regression analyses.

Results

The 90-day mortality rate was 32% in the study population (n = 62). The ROC analysis revealed that ESMD [area under the curve (AUC): 0.765] and PMD (AUC: 0.759) performed best in the prediction of 90-day mortality. In the multivariable logistic regression analysis, PMD [odds ratio (OR): 0.896; 95% confidence interval (CI): 0.846–0.948; p < 0.001], ESMA (OR: 0.929; 95% CI: 0.878–0.983; p = 0.011), and ESMD (OR: 0.947; 95% CI: 0.913–0.983; p = 0.004), but not PMA, were independent risk factors for 90-day mortality.

Conclusion

PMD, ESMA, and ESMD may be risk factors for 90-day mortality after mechanical thrombectomy for acute ischemic stroke.
Effects of omalizumab on lung function in patients with moderate-to-severe allergic asthma: a systematic review and meta-analysis
Authors: Liao Junyi , Tang Jia , Jiang Yuanping , Wang Youwen , Ding Jiali , He Yong
Published: January 2024

Background:

With the rise of targeted treatments for asthma, treatment with omalizumab is a new option.

Objectives:

To assess the improvement of pulmonary function with additional omalizumab treatment in patients (⩾6 years old) with moderate-to-severe allergic asthma.

Data sources and methods:

Observational studies of randomized controlled trials of add-on omalizumab for the treatment of patients with moderate-to-severe allergic asthma, published from the establishment till August 2022, were retrieved from WAN FANG DATA, PubMed, CNKI, Embase, Cochrane, and Web of Science databases. Data extraction and quality evaluation were performed on the literature that met the inclusion criteria, using RevMan 5.3 to analyze the data.

Results:

A total of 11 randomized controlled clinical trials were included, involving a total of 3578 patients with asthma, 1856 patients in the omalizumab group, and 1722 patients in the control group. The improvement in Forced expiratory volume in 1 s as a percentage of predicted normal and Forced expiratory volume in 1 s was more pronounced in the omalizumab-treated group [MD = 3.91, 95% confidence interval (CI): 1.89–5.94, p = 0.0002; MD = 0.09, 95% CI: 0.05–0.13, p < 0.0001], while the improvement in Morning Peak expiratory flow rate was not statistically different between the two groups (MD = 3.64, 95% CI: −22.17–29.45, p = 0.78).

Conclusion:

Additional omalizumab treatment showed some improvement in lung function in patients with moderate-to-severe asthma.

Trial registration:

PROSPERO ID:CRD42022378498.
Management and Amelioration of Knee Joint Osteoarthritis in Adults Using a Novel High-Functional Bovine Collagen Peptide as a Nutritional Therapy: A Double-Blind, Prospective, Multicentric, Randomized, Active and Placebo Controlled, Five-Arm, Clinical Study to Evaluate the Efficacy, Safety, and Tolerability
Authors: Devasia Sheena , Joseph Jinu T. , P.S. Stephena , Koizumi Seiko , Clarke Liz , V.T. Sriraam , Kailas Abhilash Parameswaran , Madhavan Shajil
Published: January 2024

Objective

The various functionalities of collagen peptides have generated a large interest in utilizing the bioactive peptides as a nutritional therapy to ameliorate various physiological degenerative conditions. Collagen peptides are observed to reduce the pain and aligned difficulties with respect to osteoarthritis. Here we report the enhanced ameliorating property of novel high-functional “Wellnex” Type J collagen peptides following a double-blind randomized active and placebo-controlled 5-arm clinical trial ( n = 100) by using it as a nutritional supplement in subjects with knee joint osteoarthritis in comparison with conventional bovine collagen peptides. The efficacy, safety, and tolerability were also studied.

Design

Dosages of 2.5, 5.0, and 10.0 g of high-functional Type J bovine collagen peptides, 10.0 g of conventional collagen peptides, and 10.0 g of placebo were given to the 5 groups for a period of 90 days. The Western Ontario McMaster Universities Arthritis Index (WOMAC) score, Pain Scale, Quality of Life (QoL), Physician’s Impression of change Score (PICS), serum C-terminal cross-linked telopeptide of type II collagen (CTX-II) levels and Magnetic Resonance Imaging Osteoarthritis Knee Score (MOAKS) parameters were monitored.

Results

Type J 2.5 g showed significant improvement in WOMAC, QoL, CTX, and MOAKS and observed to be equivalent to conventional collagen peptide 10-g supplementation in terms of efficacy.

Conclusion

The two significant outcomes of the study were that Type J 10.0 g, Type J 5.0 g, Type J 2.5 g and conventional collagen peptides 10.0 g supplementation were observed to be beneficial nutraceutical therapies for knee joint osteoarthritis, and Type J 2.5 g supplementation was equivalent to conventional collagen peptides 10.0-g supplementation in terms of efficacy.
Characteristics of primary Sjogren’s syndrome with articular manifestations at initial treatment
Authors: Zhao Lin , Wang Zheng , Xu Mingxi , Xing Yida , Kong Xiaodan
Published: January 2024

Objectives:

Articular manifestations have been reported in 19.3%–53.5% of patients with primary Sjogren’s syndrome. Our aim was to profile the clinical characteristics of Chinese patients with primary Sjogren’s syndrome who presented with articular manifestations at the time of initial treatment.

Methods:

We conducted a retrospective study of 129 primary Sjogren’s syndrome patients admitted to the second Affiliated Hospital of Dalian Medical University between April 2016 and December 2021 for initial treatment. Clinical and serological features, extra-articular involvement, and initial treatment were compared between primary Sjogren’s syndrome patients with and without articular manifestations.

Results:

Fifty-seven (44.2%) primary Sjogren’s syndrome patients had articular manifestations (mean age at diagnosis: 53.4 years), of which 42 (73.7%) presented with symmetrical distribution, 21 (36.8%) patients had rheumatoid factor positivity, and 11 (20.0%) patients had anti-cyclic citrullinated peptide antibodies positivity (mean 6.8 RU/mL); imaging examinations showed no signs of structural damage in these patients. The presence of articular manifestations showed positive correlation with anti-cyclic citrullinated peptide antibody level (odds ratio (OR) 1.01, 95% confidence interval (CI): 1.00–1.02; p = 0.049), C-reactive protein level (OR 1.15, 95% CI: 1.10–1.20; p = 0.000), and European League Against Rheumatism Sjogren syndrome disease activity index scores (OR 1.18, 95% CI: 1.11–1.25; p = 0.000). Ninety (69.8%) primary Sjogren’s syndrome patients received hydroxychloroquine therapy. Hydroxychloroquine treatment was significantly less frequently used in articular manifestation patients (35 (70.0%) vs 55 (85.9%); p = 0.038).

Conclusions:

Symmetrical polyarthritis was the most common clinical manifestation of primary Sjogren’s syndrome patients with articular manifestations in this cohort. Articular manifestations were associated with higher prevalence of C-reactive protein level, and European League Against Rheumatism Sjogren syndrome disease activity index score.
The role of the ideal of coherence between school and family in valuing cooperative practices of religious education
Authors: Broer Nico , de Muynck Bram , Boele-de Bruin Laura , Vries Albert de , de With Fianne N.
Published: January 2024

Children’s religious education is vital for the formation of pupils in Dutch Orthodox Protestant schools. Therefore, it seems self-evident that parents and teachers cooperate. This article presents research on parents’ and teachers’ opinions about the helpfulness of cooperative practices in religious education. A total of 1346 parents and teachers completed questionnaires developed from a previous study. This article finds that parents and teachers cherish the ideal of ‘coherence between school and family’ although differences between the respondent groups and school types occurred. Moreover, the research shows that this ideal influences the valuing of cooperative practices of religious education.
Can spatial patterns mitigate the urban heat island effect? Evidence from German metropolitan regions
Authors: Li Wenzheng , Schmidt Stephan
Published: January 2024

This study examines the efficacy of urban spatial patterns at alleviating the urban heat island (UHI) effect in Germany’s city regions ( Großstadtregionen) using multivariate and non-parametric regression methods. Urban spatial patterns are quantified using five landscape metrics that capture the spatial arrangement of urban footprints and greenspaces, along with a polycentricity index that measures the distribution of human activities. The results indicate that certain features of urban fabric, including fragmentation, mixed land use, and regular-shaped urban patches, have the potential to mitigate the UHI effect. Moreover, dispersing multiple smaller greenspaces throughout the urban area demonstrates a greater cooling effect compared to having a single large and more aggregated park. In addition, our analysis reveals that a doubling (100%) of the polycentricity degree corresponds to a significant decrease in both day- and night-time UHI effects, with reductions of 10.4% and 24.6%, respectively. This study confirms that polycentric development yields greater benefits in reducing urban heat for large-sized city regions compared to medium- and small-sized ones; and its effectiveness is mostly pronounced near urban center(s). These findings suggest that polycentric development represents an efficient and feasible strategy for urban thermal planning of large-sized city regions, surpassing other commonly discussed urban configurations, such as compact or dispersed urban development.
Semantic classifiers in Guodian bamboo manuscripts: Reconstructing categories in the ancient Chinese mind
Authors: Xu Yanru
Published: January 2024

Ancient Chinese scripts are one of the most complex writing systems in the world. Many graphs contain components referred to as unpronounced semantic classifiers. These components bear a semantic relationship to the meaning of the word written by the graph. It is proposed that the set of semantic components, as well as the specific semantic concepts that they encode, reflect a cognitive map of knowledge organization of the community of script users at a particular place and time. By analyzing the semantic classifiers within a constrained manuscript corpus, it is possible to build a network that models aspects of the ancient Chinese knowledge organization as reflected in this corpus. With the help of the digital tool iClassifier, a corpus-based study is conducted based on the sample texts, Guodian bamboo manuscripts. Additionally, a list of semantic classifiers is presented, two prominent categories 心 [heart/senses & emotion] and 辵 [road + foot/movement] are analyzed, and a visualization network of the sample corpus is drawn.
Unveiling the climate–conflict nexus: Examining the influence of weather extremes on conflict emergence in the Philippine Bangsamoro
Authors: Delina Laurence L , Gaviola Jon , Pagkalinawan Homer
Published: January 2024

Extreme weather events have been closely associated with the escalation of violent conflicts. This article introduces empirical evidence that underscores the vulnerability of conflict emergence to extended deficit rainfall values within Maguindanao, a province situated in the Bangsamoro region of the southern Philippines. Using a combination of satellite data, hydrological analysis and an examination of conflict databases, our study unveils the pivotal role played by protracted droughts and intensified precipitation in fostering human insecurity, consequently elevating the likelihood of violent conflicts. Our research spotlights the climate–conflict nexus within this relatively less-explored geographical area. Our findings underscore a robust association between instances of violent conflicts, protracted deficits or episodes of intense rainfall, and the subsequent surge in food prices. Notably, disruptions in food prices align temporally with heightened participation in violent conflicts by individuals. In essence, the emergence of violent conflicts exacerbates fragility, thereby engendering a vicious cycle that intertwines climate change, conflict dynamics and the pursuit of peace.
Review of Regulatory Mechanism on Crypto Income
Authors: Sekhar G. V. Satya
Published: January 2024

Some countries are actively considering taxing income from cryptocurrency exchanges. In addition to this, in many national and international policy decisions related to Cryptocurrency, regulators also focus on issues such as customer data, money laundering schemes and supporting terrorism. This article intends to examine the regulatory regime of cryptocurrency regulators—from a country-specific perspective.
Plumbogaidonnayite, PbZrSi3O9⋅2H2O, a new Pb-member of the gaidonnayite group from the Saima alkaline complex, Liaoning Province, China
Authors: Wu Bin , Gu Xiangping , Gui Xin , Bonnetti Christophe , Rao Can , Wang Rucheng , Wan Jianjun , Song Wenlei
Published: January 2024

Plumbogaidonnayite, ideally PbZrSi3O9⋅2H2O, is a new gaidonnayite-group mineral discovered as a secondary product derived from the alteration of eudialyte from the Saima alkaline complex, China. It occurs as aggregates (up to 1 mm) composed of subhedral to anhedral or platy crystals (individually 5–50 μm), associated closely with microcline, natrolite, aegirine, gaidonnayite, georgechaoite, zircon, bobtraillite and britholite-(Ce) in eudialyte pseudomorphs. The crystals are transparent, colourless or light brown with a vitreous lustre. Plumbogaidonnayite is brittle with conchoidal fracture, and it has a Mohs hardness of ~5 and a calculated density of 3.264 g/cm3. It is optically biaxial (+) with α = 1.61(3), β = 1.63(3) and γ = 1.66(4). The calculated 2V is 80°, with the optical orientations X, Y and Z parallel to the crystallographic a, b and c axes, respectively. The empirical formula is (Pb0.70Ca0.17Ba0.01K0.11Na0.01Y0.01)Σ1.01(Zr1.00Hf0.01Ti0.01)Σ1.02Si3.01O9⋅2H2O calculated on the basis of nine oxygen atoms per formula unit and assuming the occurrence of two H2O groups. Plumbogaidonnayite is orthorhombic, P21nb, a = 11.7690(4) Å, b = 12.9867(3) Å, c = 6.66165(16) Å, V = 1018.17(5) Å3 and Z = 4. The nine strongest lines of its powder XRD pattern [d in Å (I, %) (hkl)] are: 6.489 (36) (020), 5.803 (100) (101), 4.661 (27) (021), 4.336 (29) (121), 3.640 (30) (221), 3.114 (79) (112), 2.947 (27) (400), 2.622 (27) (241) and 2.493 (27) (312). Plumbogaidonnayite has a similar spiral chain framework structure with gaidonnayite and georgechaoite, which is composed of SiO4 tetrahedra and ZrO6 octahedra, but with disordered extra-framework sites (cations and H2O groups) characterised by the substitution of 2Na+ (K+)→Pb2+ (Ca2+) + □ (vacancy). The discovery of plumbogaidonnayite adds a new perspective on the cation ordering and heterovalent substitution mechanism in gaidonnayite-group minerals.
Feasibility and preliminary efficacy of different intensities of functional training in elderly type 2 diabetes patients with cognitive impairment: a pilot randomised controlled trial
Authors: Ghahfarrokhi Majid Mardaniyan , Shirvani Hossein , Rahimi Mostafa , Bazgir Behzad , Shamsadini Alireza , Sobhani Vahid
Published: January 2024

Background

Aging and type-2 diabetes (T2D) are the most important risk factors for cognitive impairment and Alzheimer’s disease. Exercise training is an effective, safe, and practical intervention in improving glucose metabolism, physical function, and cognitive disorders. This pilot study investigated the feasibility and preliminary efficacy of high-intensity low-volume (HIFT) vs. low-intensity high-volume (LIFT) functional training in elderly T2D patients with cognitive impairment.

Methods

Forty-eight elderly T2D patients (31 female, 17 male, age 67.5 ± 5.8 years, MMSE score 18.8 ± 2.6, FBG 209.5 ± 37.9) were randomly assigned to HIFT, LIFT and control groups. Cognitive impairment was diagnosed with MMSE ≤ 23 based Iranian society. The SDMT, CVLT-II, BVMT-R, and Stroop tests were used to evaluated processing speed, learning, memory and attention respectively. Physical fitness tests include: tandem stance and walk test; TUG; 6MWT, 10MWT; SSST; 5TSTS; and hand grip was used to evaluated static and dynamic balance, agility, walking endurance, gait speed, lower limb function and lower and upper body strength respectively. As well as, Biochemical (FBG, insulin, HOMA-IR, HbA1c) and physiological outcomes (SBP, and DBP) were assessed. The HIFT group performed six weeks of functional training (three sessions per week) with 120–125% of the lactate threshold. The LIFT group performed six weeks of functional training (five sessions per week) with a 70–75% lactate threshold. Feasibility, safety, and acceptability of exercise programs were assessed at the end of the study.

Result

HIFT showed a higher adherence rate (91% vs. 87.5%), safety, and acceptability compared to LIFT. MMSE and Stroop scores, 6MWT, FBG, insulin, HOMA-IR, HbA1c, SBP, and DBP significantly improved in HIFT (all,P ≤ 0.004) and LIFT (all,P ≤ 0.023). Changes in 6MWT, FBG, insulin, HOMA-IR, and HbA1c in HIFT (all,P ≤ 0.001) and LIFT (all,P ≤ 0.008) were significant compared to the control group. Changes in Stroop scores were significant only in the HIFT group compared to the control group (P = 0.013). SDMT, CVLT-II, BVMT-R, balance test, 10MWT, SSST, TUG and hang grip significantly improved only in HIFT (all,P ≤ 0.038).

Conclusion

HIFT vs. LIFT is a safe, feasible, and effective approach for improving some aspects of physical, biochemical, and cognitive function in elderly T2D patients with cognitive impairment. This pilot study provides initial proof-of-concept data for the design and implementation of an appropriately powered randomised controlled trial (RCT) of HIFT vs. LIFT in a larger sample of elderly T2D patients with cognitive impairment.

Trial registration

Randomized controlled trial (RCT) (Iranian Registry of Clinical Trials, trial registration number: IRCT20230502058055N1. Date of registration: 11/06/2023.
Association between prevalence and severity of chronic kidney disease and employment status: a nationwide study in Korea
Authors: Choi Seoyeong , Jang Suk-Yong , Choi Eunjeong , Park Yu shin
Published: January 2024

Background

The prevalence of chronic kidney disease (CKD) is increasing globally, and understanding the association between CKD and employment status is crucial. This cross-sectional study aimed to investigate the association of CKD with employment and occupation type among patients with CKD.

Methods

We analyzed data from 36,732 Korean adults aged ≥ 30 years, who participated in the Korean National Health and Nutrition Examination Survey between 2014 and 2021. CKD was detected based on the estimated glomerular filtration rate, and the employment status of the participants was classified into distinct categories: full-time permanent employment, unemployment, self-employment, and precarious employment. We analyzed the data using multiple logistic regression.

Results

We observed a significant association between CKD and a higher likelihood of unemployment compared to that in individuals without CKD (odds ratio, 1.70; 95% confidence interval, 1.47–1.96). This association was more prominent in patients with severe CKD. In the multivariable logistic analysis, patients with CKD had a higher likelihood for precarious employment (odds ratio, 1.29; 95% confidence interval, 0.92–1.88), self-employment (odds ratio, 1.3; 95% confidence interval, 0.90–1.88), and unemployment (odds ratio, 2.10; 95% confidence interval, 1.51–2.92) compared to individuals without CKD.

Conclusions

Our study demonstrated that CKD is associated with a higher likelihood of unemployment and engagement in precarious employment. These findings highlight the challenges faced by patients with CKD in obtaining stable employment and emphasize the need for interventions to improve the employment outcomes of individuals with CKD.
Pattern and determinants of contraceptive use among the muslim women in Wajir and Lamu counties in Kenya: a cross-sectional study
Authors: Abdi Batula , Okal Jerry , Serour Gamal , Were Vincent , Temmerman Marleen , Gichangi Peter
Published: January 2024

Background

Improving access to family planning (FP) is associated with positive health benefits that includes averting nearly a third of all maternal deaths and 10% of childhood deaths. Kenya has made great strides in improving access to family planning services. However, amid this considerable progress, regional variation has been noted which begs the need for a clearer understanding of the the patterns and determinants that drive these inconsistencies.

Methods

We conducted a cross-sectional study that involved 663 Muslim women of reproductive age (15–49 years) from Wajir and Lamu counties in Kenya between March and October 2018.The objective of this study was to understand patterns and determinants of contraceptive use in two predominantly Muslim settings of Lamu and Wajir counties that have varying contraceptive uptake. Eligible women were interviewed using a semi-structured questionnaire containing socio-demographic information and history of family planning use. Simple and multiple logistic regression were used to identify determinants of family planning use. The results were presented as Crude Odds Ratio (COR) and Adjusted Odds Ratio (AOR) ratios at 95% confidence interval. A p-value of 0.05 was considered statistically significant.

Results

Of the 663 Muslim women of reproductive age consenting to participate in the study, 51.5%, n = 342 and 48.5%, n = 321 were from Lamu and Wajir County, respectively. The prevalence of women currently using contraceptive was 18.6% (n = 123). In Lamu, the prevalence was 32.8%, while in Wajir, it was 3.4%. The determinants of current contraceptive use in Lamu include; marital status, age at marriage, employment status, discussion with a partner on FP, acceptability of FP in culture, and willingness to obtain information on FP. While in Wajir, determinants of current contraceptive use were education, and the belief that family planning is allowed in Islam.

Conclusions

Our study found moderately high use of contraceptives among Muslim women of reproductive age in Lamu county and very low contraceptive use among women in Wajir. Given the role of men in decision making, it is critical to design male involvement strategy particularly in Wajir where the male influence is very prominent. It is critical for the government to invest in women and girls’ education to enhance their ability to make informed decisions; particularly in Wajir where FP uptake is low with low education attainment. Further, our findings highlight the need for culturally appropriate messages and involvement of religious leaders to demystify the myths and misconception around family planning and Islam particularly in Wajir.
Health care management adequacy among French persons with severe profound intellectual and multiple disabilities: a longitudinal study
Authors: Baumstarck Karine , Hamouda Ilyes , Aim Marie-Anastasie , Anzola Any Beltran , Khaldi-Cherif Sherezad , Felce Agnès , Maincent Kim , Lind Katia , Auquier Pascal , Billette de Villemeur Thierry , Rousseau Marie-Christine ,   and the EVAL-P. L. H. Group, Boutalbi Narjess , Dany Lionel , Heng Ponha , Julien Patrick , Kemlin Isabelle , Lenormand Stéphane , Pietra Stéphane , Roger Julie , Valkov Maria , Willocq Daniel
Published: January 2024

Background

The care organization of persons with profound intellectual and multiple disabilities (PIMD) varies by country according to the health care system. This study used a large sample of French individuals with severe PIMD/polyhandicap to assess: 1) the adequacy of care setting over a 5-year period and 2) health care consumption.

Methods

The longitudinal study used data from the French EVALuation PoLyHandicap (EVAL-PLH) cohort of persons with severe PIMD/polyhandicap who were receiving managed in specialized care centres and residential facilities. Two assessments were performed: wave 1 (T1) in 2015–2016 and wave 2 (T2) in 2020–2021. The inclusion criteria were as follows: age > 3 years at the time of inclusion; age at onset of cerebral lesion younger than 3 years old; and severe PIMD. The adequacy of the care setting was based on the following: i) objective indicators, i.e., adequacy for age and adequacy for health status severity; ii) subjective indicators, i.e., self-perception of the referring physician about medical care adequacy and educational care adequacy. Health care consumption was assessed based on medical and paramedical care.

Results

Among the 492 persons assessed at the 2 times, 50% of individuals at T1 and 46% of individuals at T2 were in an inadequate care setting based on age and severity. Regarding global subjective inadequacy, the combination of medical adequacy and educational adequacy, 7% of individuals at T1 and 13% of individuals at T2 were in an inadequate care setting. At T2, a majority of individuals were undermonitored by medical care providers (general practitioners, physical medicine rehabilitation physicians, neurologists, orthopaedists, etc.). Important gaps were found between performed and prescribed sessions of various paramedical care (physiotherapy, occupational therapy, psychomotor therapy, etc.).

Conclusions

This study revealed key elements of inadequate care management for persons with severe PIMD/polyhandicap in France. Based on these important findings, healthcare workers, familial caregivers, patients experts, and health decision-makers should develop appropriate care organizations to optimize the global care management of these individuals.

Trial registration

NCT02400528, registered 27/03/2015.
Unmet needs in EGFR exon 20 insertion mutations in Central and Eastern Europe: reimbursement, diagnostic procedures, and treatment availability
Authors: Hochmair Maximilian J. , Unk Mojca , Spasic Jelena , Cerić Timur , Konsoulova Assia , Dediu Mircea , Bogos Krisztina , Hegmane Alinta , Oselin Kersti , Stojiljkovic Marko , Roblek Tina , Jakopovic Marko
Published: January 2024

Lung cancer remains the leading cause of cancer-related deaths in Europe, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of cases. NSCLC is a heterogeneous disease encompassing various oncogenic alterations. Among them, EGFR exon 20 insertion mutations, constituting 0.3–2.2% of NSCLC cases, rank as the third most common EGFR alteration after exon 19 deletions and the L858R point mutation in exon 21, also known as “typical” EGFR alterations. Recent advancements in understanding the molecular pathogenesis of NSCLC have led to significant breakthroughs in targeted therapies, revolutionizing treatment options for patients with specific genetic alterations.

This article presents the outcomes of a Virtual Meeting conducted on the online platform (provided Within3©) from September 19 to October 30, 2022. The meeting focused on addressing the challenges in the diagnosis and treatment of NSCLC patients with EGFR exon 20 insertion mutations. The participants consisted of healthcare professionals from ten Central and Eastern European countries who shared their experiences and opinions on various aspects, including epidemiology, treatment options, and diagnostic approaches employed in their respective healthcare institutions. The discussions were facilitated through open-ended and multiple-choice questions.

The primary objective of this article is to provide an overview of the identified challenges associated with the diagnosis and treatment of this heterogeneous disease, based on the assessments of the meeting participants. Among the major emerging challenges discussed, the reimbursement issues concerning next-generation sequencing (NGS), a recommended method in NSCLC molecular diagnosis, and the availability of approved targeted treatments to enhance patient outcomes were of paramount importance. Furthermore, fostering community awareness of lung cancer and promoting harmonized lung cancer care were identified as areas deserving greater attention. Notably, the rapidly evolving treatment landscape, particularly with NGS for NSCLC patients with genomic alterations like EGFR, ALK, RET, MET, NTRK, and ROS1, necessitates prioritizing the development of new drugs, even for the relatively smaller subgroup with exon 20 insertion mutations.
Identification of a novel intronic mutation of MAGED2 gene in a Chinese family with antenatal Bartter syndrome
Authors: Yan Xu , Hu Yueyue , Zhang Xin , Gao Xia , Zhao Yang , Peng Haiying , Ouyang Liu , Zhang Changjun
Published: January 2024

Background

Antenatal Bartter syndrome is a life-threatening disease caused by a mutation in the MAGED2 gene located on chromosome Xp11. It is characterized by severe polyhydramnios and extreme prematurity. While most reported mutations are located in the exon region, variations in the intron region are rarely reported.

Methods

In our study, we employed whole exome sequencing and Sanger sequencing to genotype members of this family. Additionally, a minigene assay was conducted to evaluate the impact of genetic variants on splicing.

Results

Our findings reveal a novel intronic variant (NM_177433.3:c.1271 + 4_1271 + 7delAGTA) in intron 10 of the MAGED2 gene. Further analysis using the minigene assay demonstrated that this variant activated an intronic cryptic splice site, resulting in a 96 bp insertion in mature mRNA.

Conclusions

Our results indicate that the novel intronic variant (c.1271 + 4_1271 + 7delAGTA) in intron 10 of the MAGED2 gene is pathogenic. This expands the mutation spectrum of MAGED2 and highlights the significance of intronic sequence analysis.
Remotely supervised spirometry versus laboratory-based spirometry during the COVID-19 pandemic: a retrospective analysis
Authors: Kołtowski Łukasz , Basza Mikołaj , Bojanowicz Wojciech , Dąbrowiecki Piotr , Soliński Mateusz , Górska Katarzyna , Korczyński Piotr , Eggert Lauren E.
Published: January 2024

Background

The COVID-19 pandemic has constrained access to spirometry, and the inherent risk of infectious transmission during aerosol-generating procedures has necessitated the rapid development of Remotely Supervised Spirometry (RSS). This innovative approach enables patients to perform spirometry tests at home, using a mobile connected spirometer, all under the real-time supervision of a technician through an online audio or video call.

Methods

In this retrospective study, we examined the quality of RSS in comparison to conventional Laboratory-based Spirometry (LS), using the same device and technician. Our sample included 242 patients, with 129 undergoing RSS and 113 participating in LS. The RSS group comprised 51 females (39.5%) with a median age of 37 years (range: 13–76 years). The LS group included 63 females (55.8%) with a median age of 36 years (range: 12–80 years).

Results

When comparing the RSS group to the LS group, the percentage of accurate Forced Expiratory Volume in one second (FEV1) measurements was 78% (n = 101) vs. 86% (n = 97), p = 0.177; for Forced Vital Capacity (FVC) it was 77% (n = 99) vs. 82% (n = 93), p = 0.365; and for both FEV1 and FVC, it was 75% (n = 97) vs. 81% (n = 92), p = 0.312, respectively.

Conclusions

Our findings demonstrate no significant difference in the quality of spirometry testing between RSS and LS, a result that held true across all age groups, including patients aged over 65 years. The principal advantages of remote spirometry include improved access to pulmonary function tests, reduced infectious risk to curtail disease spread, and enhanced convenience for patients.
Alpha-1-antitrypsin-deficiency is associated with lower cardiovascular risk: an approach based on federated learning
Authors: Zöller Daniela , Haverkamp Christian , Makoudjou Adeline , Sofack Ghislain , Kiefer Saskia , Gebele Denis , Pfaffenlehner Michelle , Boeker Martin , Binder Harald , Karki Kapil , Seidemann Christian , Schmeck Bernd , Greulich Timm , Renz Harald , Schild Stefanie , Seuchter Susanne A. , Tibyampansha Dativa , Buhl Roland , Rohde Gernot , Trudzinski Franziska C. , Bals Robert , Janciauskiene Sabina , Stolz Daiana , Fähndrich Sebastian
Published: January 2024

Background

Chronic obstructive pulmonary disease (COPD) is an inflammatory multisystemic disease caused by environmental exposures and/or genetic factors. Inherited alpha-1-antitrypsin deficiency (AATD) is one of the best recognized genetic factors increasing the risk for an early onset COPD with emphysema. The aim of this study was to gain a better understanding of the associations between comorbidities and specific biomarkers in COPD patients with and without AATD to enable future investigations aimed, for example, at identifying risk factors or improving care.

Methods

We focused on cardiovascular comorbidities, blood high sensitivity troponin (hs-troponin) and lipid profiles in COPD patients with and without AATD. We used clinical data from six German University Medical Centres of the MIRACUM (Medical Informatics Initiative in Research and Medicine) consortium. The codes for the international classification of diseases (ICD) were used for COPD as a main diagnosis and for comorbidities and blood laboratory data were obtained. Data analyses were based on the DataSHIELD framework.

Results

Out of 112,852 visits complete information was available for 43,057 COPD patients. According to our findings, 746 patients with AATD (1.73%) showed significantly lower total blood cholesterol levels and less cardiovascular comorbidities than non-AATD COPD patients. Moreover, after adjusting for the confounder factors, such as age, gender, and nicotine abuse, we confirmed that hs-troponin is a suitable predictor of overall mortality in COPD patients. The comorbidities associated with AATD in the current study differ from other studies, which may reflect geographic and population-based differences as well as the heterogeneous characteristics of AATD.

Conclusion

The concept of MIRACUM is suitable for the analysis of a large healthcare database. This study provided evidence that COPD patients with AATD have a lower cardiovascular risk and revealed that hs-troponin is a predictor for hospital mortality in individuals with COPD.
Eligibility of patients with chronic obstructive pulmonary disease for inclusion in randomised control trials investigating triple therapy: a study using routinely collected data
Authors: Whittaker Hannah R. , Torkpour Aria , Quint Jennifer
Published: January 2024

Background

Randomised control trials (RCTs) with strict eligibility criteria can lead to trial populations not commonly seen in clinical practice. We described the proportion of people with chronic obstructive pulmonary disease (COPD) in England eligible for RCTs investigating treatment with triple therapy.

Methods

MEDLINE and Clinicaltrials.gov were searched for RCTs investigating triple therapy and eligibility criteria for each trial were extracted. Using routinely collected primary care data from Clinical Practice Research Datalink Aurum linked with Hospital Episode Statistics, we defined a population of COPD patients registered at a general practice in England, who were ≥ 40 years old, and had a history of smoking. Inclusion date was January 1, 2020. Patients who died earlier or left the general practice were excluded. Eligibility criteria for each RCT was applied to the population of COPD patients and the proportion of patients meeting each trial eligibility criteria were described.

Results

26 RCTs investigating triple therapy were identified from the literature. The most common eligibility criteria were post-bronchodilator FEV1% predicted 30–80%, ≥ 2 moderate/≥ 1 severe exacerbations 12-months prior, no moderate exacerbations one-month prior and no severe exacerbations three-months prior, and the use of maintenance therapy or ICS use prior to inclusion. After applying each RCT eligibility criteria to our population of 79,810 COPD patients, a median of 11.2% [interquartile range (IQR) 1.8–17.4] of patients met eligibility criteria. The most discriminatory criteria included the presence exacerbations of COPD and previous COPD related medication use with a median of 67.6% (IQR 8.5–73.4) and 63% (IQR 69.3–38.4) of COPD patients not meeting these criteria, respectively.

Conclusion

Data from these RCTs may not be generalisable to the wider population of people with COPD seen in everyday clinical practice and real-world evidence studies are needed to supplement trials to understand effectiveness in all people with COPD.
Stress granules affect the dual PI3K/mTOR inhibitor response by regulating the mitochondrial unfolded protein response
Authors: Lin Nan , Sun Liankun , Chai Jiannan , Qi Hang , Zhao Yuanxin , Ma Jiaoyan , Xia Meihui , Hu Xiaoqing
Published: January 2024

Drug resistance remains a challenge in ovarian cancer. In addition to aberrant activation of relevant signaling pathways, the adaptive stress response is emerging as a new spotlight of drug resistance in cancer cells. Stress granules (SGs) are one of the most important features of the adaptive stress response, and there is increasing evidence that SGs promote drug resistance in cancer cells. In the present study, we compared two types of ovarian cancer cells, A2780 and SKOV3, using the dual PI3K/mTOR inhibitor, PKI-402. We found that SGs were formed and SGs could intercept the signaling factor ATF5 and regulate the mitochondrial unfolded protein response (UPRmt) in A2780 cells. Therefore, exploring the network formed between SGs and membrane-bound organelles, such as mitochondria, which may provide a new insight into the mechanisms of antitumor drug functions.
Unraveling the underlying pathogenic factors driving nonalcoholic steatohepatitis and hepatocellular carcinoma: an in-depth analysis of prognostically relevant gene signatures in hepatocellular carcinoma
Authors: Ni Yuan , Lu Maoqing , Li Ming , Hu Xixi , Li Feng , Wang Yan , Xue Dong
Published: January 2024

Background

Nonalcoholic steatohepatitis (NASH) is a progressive manifestation of nonalcoholic fatty liver disease (NAFLD) that can lead to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Despite the growing knowledge of NASH and HCC, the association between the two conditions remains to be fully explored. Bioinformatics has emerged as a valuable approach for identifying disease-specific feature genes, enabling advancements in disease prediction, prevention, and personalized treatment strategies.

Materials and methods

In this study, we utilized CellChat, copy number karyotyping of aneuploid tumors (CopyKAT), consensus Non-negative Matrix factorization (cNMF), Gene set enrichment analysis (GSEA), Gene set variation analysis (GSVA), Monocle, spatial co-localization, single sample gene set enrichment analysis (ssGSEA), Slingshot, and the Scissor algorithm to analyze the cellular and immune landscape of NASH and HCC. Through the Scissor algorithm, we identified three cell types correlating with disease phenotypic features and subsequently developed a novel clinical prediction model using univariate, LASSO, and multifactor Cox regression.

Results

Our results revealed that macrophages are a significant pathological factor in the development of NASH and HCC and that the macrophage migration inhibitory factor (MIF) signaling pathway plays a crucial role in cellular crosstalk at the molecular level. We deduced three prognostic genes (YBX1, MED8, and KPNA2), demonstrating a strong diagnostic capability in both NASH and HCC.

Conclusion

These findings shed light on the pathological mechanisms shared between NASH and HCC, providing valuable insights for the development of novel clinical strategies.
The challenge of controlling an auditory BCI in the case of severe motor disability
Authors: Séguin Perrine , Maby Emmanuel , Fouillen Mélodie , Otman Anatole , Luauté Jacques , Giraux Pascal , Morlet Dominique , Mattout Jérémie
Published: January 2024

Background

The locked-in syndrome (LIS), due to a lesion in the pons, impedes communication. This situation can also be met after some severe brain injury or in advanced Amyotrophic Lateral Sclerosis (ALS). In the most severe condition, the persons cannot communicate at all because of a complete oculomotor paralysis (Complete LIS or CLIS). This even prevents the detection of consciousness. Some studies suggest that auditory brain–computer interface (BCI) could restore a communication through a « yes–no» code.

Methods

We developed an auditory EEG-based interface which makes use of voluntary modulations of attention, to restore a yes–no communication code in non-responding persons. This binary BCI uses repeated speech sounds (alternating “yes” on the right ear and “no” on the left ear) corresponding to either frequent (short) or rare (long) stimuli. Users are instructed to pay attention to the relevant stimuli only. We tested this BCI with 18 healthy subjects, and 7 people with severe motor disability (3 “classical” persons with locked-in syndrome and 4 persons with ALS).

Results

We report online BCI performance and offline event-related potential analysis. On average in healthy subjects, online BCI accuracy reached 86% based on 50 questions. Only one out of 18 subjects could not perform above chance level. Ten subjects had an accuracy above 90%. However, most patients could not produce online performance above chance level, except for two people with ALS who obtained 100% accuracy. We report individual event-related potentials and their modulation by attention. In addition to the classical P3b, we observed a signature of sustained attention on responses to frequent sounds, but in healthy subjects and patients with good BCI control only.

Conclusions

Auditory BCI can be very well controlled by healthy subjects, but it is not a guarantee that it can be readily used by the target population of persons in LIS or CLIS. A conclusion that is supported by a few previous findings in BCI and should now trigger research to assess the reasons of such a gap in order to propose new and efficient solutions.

Clinical trial registrations: No. NCT02567201 (2015) and NCT03233282 (2013).