bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuroimmune Characteristics of Animals with Prenatal Alcohol Intoxication
Authors: Shamakina Inna Yu. , Anokhin Petr K. , Ageldinov Ruslan A. , Kokhan Viktor S.
Published: December 2024

Neuroinflammation can be an important factor of many disorders in central nervous system (CNS) including cognitive dysfunction, affective disorders, and addictive behavior associated with prenatal alcohol exposure and presented in early adulthood. In this study we used an experimental rodent model of prenatal alcohol (PA) exposure (consumption of a 10% ethanol solution by female Wistar rats throughout pregnancy), multiplex immunofluorescence analysis of interleukins (IL-1α, IL-1β, IL-3, IL-6, IL-9, and IL-12), tumor necrosis factor (TNF-α), and chemokine CCL5, as well as quantitative real-time PCR to assess the level of cytokine mRNAs in the prefrontal cortex of the sexually mature (PND60) offspring – male and female rats with prenatal alcohol intoxication and control animals. Significant decrease in the content of TNF-α and interleukins IL-1β, IL-3, IL-6, IL-9 was detected in the prefrontal cortex of male, but not in the female PA offspring. Importantly, PA males also showed decrease in the level of TNF-α mRNA in the prefrontal cortex by 45% compared to the control males, which may underlie the detected decrease in its content. Taken together, our study demonstrates that a number of neuroimmune factors are regulated in a sex-specific manner in the prefrontal cortex and are differentially affected in males and females by the prenatal exposure to alcohol. Sex factor must be taken into account when conducting further translational studies of the fetal alcohol spectrum disorders and developing new methods for prevention and therapy.
Vimentin and Desmin Intermediate Filaments Maintain Mitochondrial Membrane Potential
Authors: Dayal Alexander A. , Parfenteva Olga I. , Huiying Wang , Shakhov Anton S. , Alieva Irina B. , Minin Alexander A.
Published: December 2024

Intermediate filaments (IFs) represented by a diverse range of proteins, are one of the three main cytoskeleton components in different types of animal cells. IFs provide mechanical strength to cells and help position the nucleus and organelles in the cell. Desmin is an IF protein typical of muscle cells, while vimentin, which has a similar structure, is expressed in many mesenchymal cells. Both proteins are synthesized during myogenesis and regeneration of damaged muscle tissue and form a mixed IF network. Both desmin and vimentin regulate mitochondrial activity, including mitochondrial localization and maintenance of mitochondrial membrane potential, in the corresponding cells, but the role of mixed IFs in the control of mitochondrial functions remains unclear. To investigate how a simultaneous presence of these proteins affects mitochondrial membrane potential, we used BHK21 cells expressing both vimentin and desmin IFs. Expression of vimentin or desmin individually or both proteins simultaneously was suppressed using gene knockout and/or RNA interference. It was found that disruption of biosynthesis of either vimentin or desmin did not affect the mitochondrial membrane potential, which remained unchanged compared to cells expressing both proteins. Simultaneous abolishment of both proteins resulted in a 20% reduction in the mitochondrial membrane potential, indicating that both vimentin and desmin play an equally important role in its maintenance.
Contribution of malnutrition to infant and child deaths in Sub-Saharan Africa and South Asia
Authors: Madewell Zachary J , Keita Adama Mamby , Das Priya Mehta-Gupta , Mehta Ashka , Akelo Victor , Oluoch Ogony Benard , Omore Richard , Onyango Dickens , Sagam Caleb K , Cain Carrie Jo , Chukwuegbo Cornell , Kaluma Erick , Luke Ronita , Ogbuanu Ikechukwu Udo , Bassat Quique , Kincardett Milton , Mandomando Inacio , Rakislova Natalia , Varo Rosauro , Xerinda Elisio G , Dangor Ziyaad , du Toit Jeanie , Lala Sanjay G , Madhi Shabir A , Mahtab Sana , Breines Markus Roos , Degefa Ketema , Heluf Helina , Madrid Lola , Scott J. Anthony G , Sow Samba O , Tapia Milagritos D , El Arifeen Shams , Gurley Emily S , Hossain Mohammad Zahid , Islam Kazi Munisul , Rahman Afruna , Mutevedzi Portia C , Whitney Cynthia G , Blau Dianna M , Suchdev Parminder S , Kotloff Karen L
Published: December 2024

Introduction

Malnutrition contributes to 45% of all childhood deaths globally, but these modelled estimates lack direct measurements in countries with high malnutrition and under-5 mortality rates. We investigated malnutrition’s role in infant and child deaths in the Child Health and Mortality Prevention Surveillance (CHAMPS) network.

Methods

We analysed CHAMPS data from seven sites (Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone and South Africa) collected between 2016 and 2023. An expert panel assessed each death to determine whether malnutrition was an underlying, antecedent or immediate cause or other significant condition. Malnutrition was further classified based on postmortem anthropometry using WHO growth standards for underweight (z-scores for weight-for-age <−2), stunting (length-for-age <−2), and wasting (weight-for-length or MUAC Z-scores <−2).

Results

Of 1601 infant and child deaths, malnutrition was considered a causal or significant condition in 632 (39.5%) cases, including 85 (13.4%) with HIV infection. Postmortem measurements indicated 90.1%, 61.2% and 94.1% of these cases were underweight, stunted and wasted, respectively. Most malnutrition-related deaths (n=632) had an infectious cause (89.1%). The adjusted odds of having malnutrition as causal or significant condition were 2.4 (95% CI 1.7 to 3.2) times higher for deaths involving infectious diseases compared with other causes. Common pathogens in the causal pathway for malnutrition-related deaths includedKlebsiella pneumoniae(30.4%),Streptococcus pneumoniae(21.5%),Plasmodium falciparum(18.7%) andEscherichia coli/Shigella(17.2%).

Conclusion

Malnutrition was identified as a causal or significant factor in 39.5% of under-5 deaths in the CHAMPS network, often in combination with infectious diseases. These findings highlight the need for integrated interventions addressing both malnutrition and infectious diseases to effectively reduce under-5 mortality.
Accuracy of radiologists and radiology residents in detection of paediatric appendicular fractures with and without artificial intelligence
Authors: M Yogendra Praveen , Goh Adriel Guang Wei , Yee Sze Ying , Jawan Freda , Koh Kelvin Kay Nguan , Tan Timothy Shao Ern , Woon Tian Kai , Yeap Phey Ming , Tan Min On
Published: December 2024

Objectives

We aim to evaluate the accuracy of radiologists and radiology residents in the detection of paediatric appendicular fractures with and without the help of a commercially available fracture detection artificial intelligence (AI) solution in the hopes of showing potential clinical benefits in a general hospital setting.

Methods

This was a retrospective study involving three associate consultants (AC) and three senior residents (SR) in radiology, who acted as readers. One reader from each human group interpreted the radiographs with the aid of AI. Cases were categorised into concordant and discordant cases between each interpreting group. Discordant cases were further evaluated by three independent subspecialty radiology consultants to determine the final diagnosis. A total of 500 anonymised paediatric patient cases (aged 2–15 years) who presented to a tertiary general hospital with a Children’s emergency were retrospectively collected. Main outcome measures include the presence of fracture, accuracy of readers with and without AI, and total time taken to interpret the radiographs.

Results

The AI solution alone showed the highest accuracy (area under the receiver operating characteristic curve 0.97; AC: 95% CI −0.055 to 0.320, p=0; SR: 95% CI 0.244 to 0.598, p=0). The two readers aided with AI had higher area under curves compared with readers without AI support (AC: 95% CI −0.303 to 0.465, p=0; SR: 95% CI −0.154 to 0.331, p=0). These differences were statistically significant.

Conclusion

Our study demonstrates excellent results in the detection of paediatric appendicular fractures using a commercially available AI solution. There is potential for the AI solution to function autonomously.
Effects of the dyadic FirstStep2Health intervention on parents’ behaviour and anthropometric outcomes: a secondary analysis of a cluster randomised trial
Authors: Ling Jiying , Kao Tsui-Sui Annie , Robbins Lorraine B , Kerver Jean M , Zhang Nanhua , Shi Yan
Published: December 2024

Objectives

This study aimed to examine the preliminary efficacy of theFirstStep2Healthversus usual care control on improving parents’ lifestyle behaviours (moderate to vigorous physical activity, screen time, fruit/vegetable and fibre intake, skin carotenoids), nutrition and physical activity knowledge, self-efficacy, support, parenting style, feeding practices, home environment, anthropometric outcomes (body mass index, % body fat) and blood pressure from baseline to postintervention after adjusting for random cluster effects.

Design

A cluster randomised controlled trial with 10 Head Start daycare centres (five intervention, five control) was conducted using computer-generated randomisation after baseline data collection.

Setting

US Head Start daycare centres.

Participants

95 parent-child dyads (53 intervention, 42 control).

Interventions

The 16-week, dyadic,FirstStep2Healthintervention included: (1) a daycare-based child programme on healthy mindful eating and physical activity, (2) child letters to parents to connect school learning with home practice, (3) social media-based parent programme to assist parents to promote healthy eating and physical activity at home, (4) virtual group parent meetings via Zoom on topics related to healthy eating and physical activity and (5) weekly motivational messages to increase parental motivation to build a healthy home environment.

Results

Mixed-effect models were used to examine intervention effects, adjusting for baseline outcome and cluster effects at the daycare and classroom levels. Intervention parents engaged in more moderate to vigorous physical activity (B=0.49, p=0.874) postintervention than controls, although not significantly. However, intervention parents showed significantly higher nutrition knowledge (B=0.87, p=0.009), physical activity knowledge (B=0.95, p=0.049), nutrition self-efficacy (B=0.74, p=0.025) and physical activity self-efficacy (B=0.86, p=0.013) compared with controls at postintervention. Fibre intake was also significantly higher (B=2.99, p=0.049), and intervention parents had lower % body fat (B=−2.56, p=0.005) and systolic blood pressure (B=−10.98, p=0.005) postintervention. No significant effects were found for fruits/vegetables intake, parental support for healthy behaviours, home physical activity environment or authoritative parenting style.

Conclusions

Future endeavours to proactively engage parents in a dyadic childhood obesity prevention approach such as theFirstStep2Healthintervention are warranted to improve outcomes among both children and parents.

Trial registration number

NCT04164277.
Aortic stiffness after living kidney donation: a systematic review and meta-analysis
Authors: Rodriguez Rosendo A , McNeill Kylie , Agharazii Mohsen , Bugeja Ann , Clark Edward G , Burns Kevin D
Published: December 2024

Objectives

Increased aortic stiffness measured with carotid-femoral pulse wave velocity (cf-PWV) has been associated with adverse cardiovascular outcomes. Some studies have reported increased cf-PWV in living kidney donors after nephrectomy. This review aimed to determine the effects of living kidney donation on cf-PWV, glomerular filtration rate (GFR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and their differences versus non-nephrectomised healthy individuals.

Design

Systematic review and meta-analysis.

Data sources

Electronic databases (MEDLINE, EMBASE, Cochrane Central databases, Cochrane Register of Controlled Trials, Cochrane Methodology Register, Health Technology Database, Technologies in Health, EBM Reviews, ProQuest and ‘Grey Matters Light’). Databases were searched from inception to December 2022.

Eligibility criteria

We searched for studies that measured cf-PWV in living kidney donors before and/or after nephrectomy. Non-nephrectomised healthy individuals included as controls were the comparators. Studies that provided age-adjusted cf-PWV reference values in normotensive healthy individuals were also included.

Outcome measures

We evaluated the mean differences in cf-PWV, GFR and BP before-and-after nephrectomy and their mean differences versus non-nephrectomised healthy comparators. We also explored differences in yearly adjusted cf-PWV changes between donors and normotensive healthy individuals.

Data extraction/synthesis

Two independent reviewers extracted data and assessed risk of bias (Risk of Bias tool for non-Randomised studies: ROBINS-I) and quality of evidence (GRADE). Pooled effect estimates were calculated using the inverse variance method and analysed with random effect models.

Results

Nine interventional (652 donors; 602 controls) and 6 reference studies (6278 individuals) were included. cf-PWV increased at 1-year postdonation (p=0.03) and was on average 0.4 m/s (95% CI 0.07; 0.60) higher than in healthy controls (p=0.01). These differences were non-significant 5 years postnephrectomy (p=0.54). GFR decreased after nephrectomy (p<0.001) and remained reduced compared with healthy controls (p<0.001), but SBP and DBP were not significantly different (p≥0.14). Yearly changes in cf-PWV postnephrectomy were similar to age-adjusted reference values in healthy normotensive individuals (p=0.76).

Conclusions

Aortic stiffness increases independent of BP 1 year after kidney donation, but the long-term effects seem minimal. These findings may impact future consent of prospective living kidney donors.

PROSPERO registration number

CRD42020185551.
Menstrual hygiene practice needs, and depression among refugee women in Jordan: a cross-sectional study
Authors: Muhaidat Nadia , Al Karmi Joud , Ibrahim Omar Bassam , Raiq Neven Amer , Alhanbali Abdulrahman E , Ghanem Hadeel H , Khamis Tala , Haddad Tala A , Karam Abdulrahman M , Alshrouf Mohammad Ali
Published: December 2024

Objectives

To investigate menstrual hygiene practices among women residing in Jordanian refugee camps, and explore their potential relationships with mental health and other sociodemographic characteristics.

Design

Descriptive cross-sectional study.

Setting and participants

A total of 387 women were included between January and March 2023, using a convenience sampling method, from five main refugee camps in Jordan.

Main outcome measures

Menstrual hygiene practices assessed by the Menstrual Practice Needs Scale (MPNS-36) and mental health assessed by the Patient Health Questionnaire-9 (PHQ-9).

Results

The study included 387 women with an average age of 33.16±9.52 years. The mean±SD MPNS-36 score for the sample was 1.92±0.52. The mean (SD) PHQ-9 score was 10.77±5.94. Moreover, the MPNS-36 overall score had a significant negative correlation with PHQ-9 scores (r=−0.368, p<0.001). Multivariable linear regression found that PHQ-9 score (B=−0.0279, p<0.001), and number of children (B = −0.0423, p=0.004) were negative predictors of the MPNS-36 score, while income was a positive predictor of the MPNS-36 score (B=0.0004, p=0.013).

Conclusion

The study highlights potential associations between menstrual hygiene habits and mental health among refugee women, alongside other sociodemographic traits. This highlights the importance of improving the accessibility of menstrual products and promoting menstrual health management among underserved populations, particularly those in refugee camps.
Cost-effectiveness of human papillomavirus (HPV) vaccination in Tunisia: a modelling study
Authors: Khiari Hyem , Makni Karima , Meddeb Khedija , Jaidane Olfa , Hsairi Mohamed
Published: December 2024

Objectives

The objective of this study is to assess the cost utility of the implementation of the human papillomavirus (HPV) vaccination programme in Tunisia in addition to the current cytology screening strategy. This study is very important to guide health policy decision-makers and to help them allocate their scarce healthcare resources.

Design

We used a previously described Markov model on the Online Cost Effectiveness Analysis tool programmed with R Software. The Markov cohort model was used to simulate the natural history of HPV infection and cervical cancer for a cohort of 100 000 females aged from 10 to 84 years. The model was calibrated with Tunisian parameters to calculate the long-term health benefits and costs of different cervical cancer preventive strategies in Tunisia.

Outcome measures

The primary outcome was the incremental cost-effectiveness ratio (ICER) of the implementation of HPV vaccination to the current cytology screening strategy to fight against cervical cancer. The ICER was calculated per life-years saved and per quality-adjusted life-year (QALY) gained, expressed in 2020 US$. Thresholds were fixed at one to three times the gross domestic product (GDP). One-way sensitivity analyses were carried out concerning the coverage rate of the cytology screening and vaccination as well as for the vaccination cost and doses.

Results

Compared with screening alone, the combined strategy predicted an ICER of US$1920.8 year of life saved and US$2239.3/QALY which is still lower than the GDP per capita of Tunisia in 2020 (US$3319). Sensitivity analysis showed that the cost-effectiveness of adding vaccination to the existing screening programme did not exceed the GDP per capita by varying the cost per dose upwards to US$45 (ICER would be US$2910/QALY) and vaccination coverage up to 100% (ICER of US$3245/QALY). However, the combined strategy exceeds the GDP per capita threshold when the cytological screening coverage rises to 70%, causing the ICER to rise to US$4787/QALY.

Conclusion

This study showed that compared with screening alone, the implementation of HPV vaccination in addition to the current cytology screening programme in Tunisia would be considered cost-effective on the basis of the threshold GDP per capita. Improvement of the current screening programme itself also remains important and provides further potential to achieve optimal cervical cancer prevention strategies.
Long-term trends in English general practice consultation rates from 1995 to 2021: a retrospective analysis of two electronic health records databases
Authors: Wyatt Steven , Mohammed Mohammed A , de Dumast Lyvia , Marshall Tom
Published: December 2024

Objectives

Although primary care is central to healthcare provision, inconsistent methods and data sources mean that relatively little is known about long-term trends in general practice consultation rates. We aimed to explore long-term trends in English general practice consultation rates using two electronic health records databases, Clinical Practice Research Datalink Gold and Aurum, from 1995 to 2021.

Methods

Consultations were identified and classified using a set of rules and code lists. Consultation rates were calculated as the ratio of the count of consultations and the registration duration. We used negative binomial regression to model the relationship between the number of consultations and the patient’s age, sex and year from each database. These models are then used to estimate annual crude consultation rates for England.

Results

The number of general practices in the Gold database decreased from 346 (1995) to 41 (2021), while in Aurum, it increased from 555 (1995) to 1347 (2021). In Gold, the average number of consultations per person-year increased from 2.91 in 1995 to 5.12 in 2012, then fell to 4.59 in 2019 and to 4.12 in 2021. In Aurum, average consultations per person-year rose from 2.17 (1995) to 4.89 (2012), then fell to 4.76 (2019) and rose again to 5.40 (2021). Half of the total increase in consultations from Aurum was due to a new consultation code, for ‘AccurX consultations’, an electronic messaging system for communication with patients.

Conclusion

Trends in general practice consultation showed three distinct epochs: rising from 1995 to 2012, falling from 2012 to 2019 and rising in Aurum but falling in Gold from 2019 to 2021. Consultation rates in Gold were higher than Aurum until the inclusion of a new consultation code in Aurum in 2019, which underscores the need for operational definitions of a consultation.
Prevalence of cataract and its associated factors among adults aged 40 years and above living in Durame town, Southern Ethiopia, 2023: a community-based cross-sectional study
Authors: Latebo Ashenafi Abebe , Assefa Natnael Lakachew , Ferede Tarekegn Wuletaw , Bekele Matiyas Mamo , Demilew Ketemaw Zewdu
Published: December 2024

Objective

This study aimed to assess the prevalence of cataract and associated factors among adults aged 40 years and above in Durame town, Southern Ethiopia.

Design

A community-based cross-sectional study was conducted using a systematic random sampling method.

Setting

The study was conducted in Durame town, Southern Ethiopia.

Participants

The study included 734 adults aged ≥40 years who lived in Durame town for more than 6 months.

Main outcome measures

Data were collected using face-to-face interviews completed by an interviewer and ophthalmic examinations.

Results

A total of 734 study participants aged 40 years and above were involved. The prevalence of cataract was 29.16% (95% CI: 25.89% to 32.59%). Factors associated with the prevalence of cataract were older age of 70–95 years (adjusted odds ratio (AOR)=8.60, 95% CI: 3.09 to 23.90), being diabetic (AOR=2.27, 95% CI: 1.37 to 3.74), exposure to sunlight (AOR=2.83, 95% CI: 1.45 to 5.53), trauma to eye (AOR=2.39, 95% CI: 1.19 to 4.81), hypertension (AOR=1.86, 95% CI:1.16 to 2.99) and glaucoma (AOR=5.36,95% CI: 3.13 to 9.18).

Conclusion

The prevalence of cataract was lower than previous national survey results. Old age, known history of trauma to eye, hypertension, diabetes, exposure to sunlight and glaucoma had statistically significant association with cataract.
Characteristics of people who report firearm suicidal ideation in the USA
Authors: Mueller-Williams Amelia Cromwell , Ilgen Mark A , Hicks Brain M
Published: December 2024

Objectives

Firearms are the most common method of suicide, yet little is known about the attributes of people who contemplate firearm suicide. The objective of this study was to describe people who endorse firearm suicidal ideation (FASI) in terms of associations with gun ownership and experiences, mental health problems, substance use, antisocial behaviour and personality characteristics.

Methods

Data were collected as part of a national online survey of adults living in the USA, the cross-sectional sample from wave 8 was analysed (N=1579). Logistic regression and analysis of variance models were fit to examine the associations between lifetime FASI and gun ownership and experience, and several mental health, substance use, antisocial behaviour and personality variables.

Results

The rate of lifetime FASI was 10.2% (n=161). FASI was associated with gun ownership and more experience with firearms, as well as higher levels of depressed mood, anxiety, suicidal ideation, self-harm behaviours, past suicide attempts, alcohol and drug use, antisocial behaviour and intimate partner violence. In terms of personality traits, FASI was associated with greater negative emotions, desire for power but also feeling powerless, and lower agreeableness and conscientiousness.

Conclusions

While not common, FASI is not rare and has a profile characterised by higher-intensity mental health problems, substance use, antisocial behaviour and personality traits associated with severe externalising problems and suicide. Research on FASI as a distinct construct should continue given the high lethality of firearms as a method of suicide.
KIF21A-associated peripheral neuropathy defined by impaired binding with TUBB3
Authors: Borja Nicholas A , Zafeer Mohammad Faraz , Bivona Stephanie , Peart LéShon , Gultekin Sakir Humayun ,   Undiagnosed Diseases Network, Bademci Guney , Tekin Mustafa
Published: December 2024

KIF21Aencodes a kinesin motor protein associated with isolated congenital fibrosis of the extraocular muscles (CFEOM), which occurs when the autoinhibitory interaction between its motor and third coiled-coil domains is disrupted. In this study, we describe a female child who is heterozygous for a novel de novo missense variant inKIF21Ap.Leu664Pro, located in the second coiled-coil domain that was absent in her unaffected parents and in healthy population cohorts. She presented with progressive peripheral neuropathy, hypoplasia of the corpus callosum and strabismus in the absence of CFEOM. Protein modelling predicts that the KIF21A variant leads to significant alterations in its structure as well as binding with TUBB3. Co-immunoprecipitation data was consistent with decreased binding of KIF21A p.Leu664Pro to TUBB3 in vitro compared with reference. Taken together, we delineate aKIF21A-related phenotype defined by progressive peripheral neuropathy, brain anomalies, developmental delay and comitant strabismus potentially stemming from the disruption of the interaction between KIF21A and TUBB3.
Portraying the full picture of Neurofibromatosis–Noonan syndrome: a systematic review of literature
Authors: Trimeche Omeyma , Sakka Rania , Hajji Ekram , Missaoui Abdelmouhaymen , Ben Amor Bilel , Bayar Ines , Abid Sana , Marmouch Hela , Sayedi Hanen , Khochtali Ines
Published: December 2024

Background and aims

Neurofibromatosis–Noonan syndrome (NFNS) is an extremely rare genetic entity combining the clinical phenotype of two conditions: neurofibromatosis type 1 syndrome (NF1) and Noonan syndrome (NS). Nevertheless, many inconsistencies reside in our understanding of this condition, mainly its clinical features and genetic background. Through this systematic review, we aim to shed light on the epidemiological features, the broad clinical spectrum, the underlying genetic defects and the associated comorbidities of NFNS.

Methods

Medline, Scopus and Google Scholar were searched for publications on the clinical and genetic features of patients with NFNS. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed and the study protocol was registered in PROSPERO.

Results

Of 951 records screened, 42 were eligible. The mean age at diagnosis was 14.7 years ranging from 0 to 69 years. As for the circumstance of discovery of NFNS, it was dominated by family investigation followed by neurofibromas, facial dysmorphia and short stature (SS). Prematurity was noted in 40.9% of cases. The hallmark features of NFNS at diagnosis were ‘café au lait’ macules, typical facial dysmorphia of NS, postnatal SS, pectus abnormalities, broad neck and lentigines. Macrocephaly, scoliosis and cardiopathies occurred in 26%, 42.4% and 36.9% of cases, respectively. Tumours were found in 18.4% of cases. As for the genetic foundation of NFNS,NF1gene mutations were depicted in 87.5% of individuals.

Conclusions

Based on our findings, we emphasise on the importance of searching for NS features in patients with NF1 since the prognosis, comorbidities and consequently management could be altered.

PROSPERO registration number

42024522238.
Disease-modifying treatment and disability progression in subclasses of patients with primary progressive MS: results from the Big MS Data Network
Authors: Lorscheider Johannes , Signori Alessio , Subramaniam Suvitha , Benkert Pascal , Vukusic Sandra , Trojano Maria , Hillert Jan , Glaser Anna , Hyde Robert , Spelman Tim , Magyari Melinda , Elberling Frederik , Pontieri Luigi , Koch-Henriksen Nils , Sørensen Per Soelberg , Gerlach Oliver , Prat Alexandre , Girard Marc , Eichau Sara , Grammond Pierre , Horakova Dana , Ramo-Tello Cristina , Roos Izanne , Buzzard Katherine , Lechner Scott Jeanette , Sánchez-Menoyo José Luis , Alroughani Raed , Prévost Julie , Kuhle Jens , Gray Orla , Mathey Guillaume , Michel Laure , Ciron Jonathan , De Sèze Jérôme , Maillart Elisabeth , Ruet Aurelie , Labauge Pierre , Zephir Helene , Kwiatkowski Arnaud , van der Walt Anneke , Kalincik Tomas , Butzkueven Helmut ,   On behalf of Italian MS Register,   On behalf of Observatoire Français de la Sclérose en Plaques (OFSEP),   On behalf of MSBase Study Group,   On behalf of Swedish MS Registry
Published: December 2024

Background

Effectiveness of disease-modifying treatment (DMT) in people affected by primary progressive multiple sclerosis (PPMS) is limited. Whether specific subgroups may benefit more from DMT in a real-world setting remains unclear. Our aim was to investigate the potential effect of DMT on disability worsening among patients with PPMS stratified by different disability trajectories.

Methods

Within the framework of the Big MS Data network, we merged data from the Observatoire Français de la Sclérose en Plaques, the Swedish and Italian MS registries, and MSBase. We identified patients with PPMS that started DMT or were never treated during the observed period. Subpopulations with comparable baseline characteristics were selected by propensity score matching. Disability outcomes were analysed in time-to-recurrent event analyses, which were repeated in subclasses with different disability trajectories determined by latent class mixed models.

Results

Of the 3243 included patients, we matched 739 treated and 1330 untreated patients with a median follow-up of 3 years after pairwise censoring. No difference in the risk of confirmed disability worsening (CDW) was observed between the groups in the fully matched dataset (HR 1.11, 95% CI 0.97 to 1.23, p=0.127). However, we found a lower risk for CDW among the class of treated patients with an aggressive disability trajectory (n=360, HR 0.68, 95% CI 0.50 to 0.92, p=0.014).

Conclusions

In line with previous studies, our data suggest that DMT does not ameliorate disability worsening in PPMS, in general. However, we observed a beneficial effect of DMT on disability worsening in patients with aggressive predicted disability trajectories.
Analysis of GFAP variants in UK Biobank suggests underdiagnosis or incomplete penetrance of adult-onset Alexander disease
Authors: Gagliardi Delia , Wade Charles , Tucci Arianna , Houlden Henry , Chataway Jeremy , Barkhof Frederik , Lynch David S
Published: December 2024

Background

Alexander disease is an autosomal dominant leukodystrophy caused by heterozygous pathogenic variants in the glial fibrillar acidic protein (GFAP) gene. Although increasingly recognised, there is evidence that Alexander disease, particularly later-onset disease, is significantly underdiagnosed and its true prevalence is unknown (the only population-based prevalence was estimated at one in 2.7 million). Using the extensive UK Biobank dataset, we analysed the frequency of pathogenic and likely pathogenic variants,GFAPvariants, within the UK population and identified clinical and radiological phenotypes linked to these variants.

Methods

Pathogenic, likely pathogenic andGFAPvariants of uncertain significance were identified in the UK Biobank whole-exome sequencing data (n=4 70 000). Demographic information, previous medical history—including symptoms associated with Alexander disease—collected from self-reported data and hospital records, family history and various MRI metrics were compared between variant carriers and controls.

Results

We identified 36 unique pathogenic and likely pathogenicGFAPvariants in 106 carriers, yielding a carrier frequency of approximately 1 in 4435. Modelling based on the UK population estimated a prevalence of 6.8 per 100 000. Carriers of pathogenic and likely pathogenicGFAPvariants had higher odds of bladder dysfunction (OR 3.17, p<0.0001), upper airway dysfunction (OR 7.82, p=0.004) and psychiatric conditions (OR 1.51, p=0.04). Additionally, carriers were more likely to report a paternal history of dementia (OR 2.79, p<0.0001). MRI data revealed significant atrophy in brainstem regions among variant carriers.

Conclusion

Pathogenic and likely pathogenicGFAPvariants are more prevalent in the general population than previously expected and are associated with clinical and radiological characteristics of Alexander disease. This study indicates that Alexander disease may be under-reported, misdiagnosed, or exhibit reduced penetrance.
Increase inNeisseria gonorrhoeaeinfections after ending COVID-19 lockdown measures in Amsterdam, the Netherlands
Authors: Teker Buhari , Schim van der Loeff Maarten F , Boyd Anders , Hoornenborg Elske , Stam Arjen J , de Vries Henry J C , Jongen Vita Willemijn
Published: December 2024

Objective

Various European countries noted increasingNeisseria gonorrhoeae(Ng) positivity among cis-gender women and heterosexual men. We assessed changes over time in Ng among men who exclusively have sex with men (MSM), men who exclusively have sex with women (MSW), men who have sex with men and women (MSMW), women and transgender and gender diverse people (TGP).

Methods

We analysed data collected between 2018 and 2023 at the Centre for Sexual Health, Amsterdam. We modelled temporal changes in Ng positivity rates (ie, number of positive results per 100 tests) using relative risk regression with a covariate representing three time periods: pre-COVID-19 (1 January 2018–12 March 2020), during COVID-19 (13 March 2020–1 March 2022), and post-COVID-19 (2 March 2022–31 December 2023).

Results

We included 110 878 consultations pre-COVID-19, 84 917 during COVID-19 and 108 282 post-COVID-19. Positivity rates of Ng went from 12.4% to 13.0% in MSM, 1.7% to 2.3% in MSW, 6.7% to 9.9% in MSMW, 1.3% to 2.9% in women and 8.1% to 10.4% in TGP pre-COVID-19 and post-COVID-19, respectively. Significant increases were observed among MSW (relative risk (RR)=1.31,95% CI 1.12 to 1.53), MSMW (RR=1.47, 95% CI 1.26 to 1.72) and women (RR=2.25, 95% CI 2.03 to 2.49). An increased number of sexual partners and inconsistent condom use were associated with an increased Ng risk.

Conclusion

A substantial relative increase in Ng risk among MSW, MSMW and women, but not MSM or TGP, was observed post-COVID-19. Changes in sexual behaviour were associated with these changes. Continuous surveillance of Ng in heterosexual individuals is needed to monitor changes, alongside implementing prevention strategies for sexually transmitted infections.
Cyclic and monotonic undrained response of unsaturated filtered copper tailings
Authors: Gallardo Ricardo , Sáez Esteban , Lopez-Caballero Fernando
Published: December 2024

This article studies the undrained behavior of filtered copper tailings in unsaturated conditions under monotonic and cyclic loading at controlled matric suction. Two dry densities with the same water content were used. The material behavior was studied in terms of the increase of saturation, the evolution of suction, and volumetric strain during the transition from unsaturated to saturated conditions. The results show that, during the shearing, suction decreases and the degree of saturation increases, regardless of the type of load applied (cyclic or monotonic). This effect is related to the volume reduction of the air phase during the transition to a fully saturated condition. In terms of undrained shear strength, the evolution of the material is studied in terms of the phase transformation line, comparing its location in saturated and unsaturated cases. Regarding the cyclic strength ratio, the unsaturated condition shows a higher value than the saturated case by about 26% and 58% for the high and low densities, respectively. However, when the volumetric strain is higher than 3% or the double amplitude axial strain exceeds 2%, a cyclic strain localization takes place, leading to an extension failure over the sample.
Evaluation of floodplain restoration projects in the interior Columbia River basin using a combination of remote sensing and field data
Authors: Roni Philip , Burgess Shelby , Ross Kai , Clark Chris , Kvistad Jake , Krall Michelle , Camp Reid , Arams Alex , Camp Meghan J.
Published: December 2024

Floodplain habitat restoration has become a common component of river restoration throughout the Pacific Northwest and is critical to the recovery of Pacific salmon ( Oncorhynchus spp.) and steelhead ( Oncorhynchus mykiss), yet little information exists on the physical or biological response to these habitat restoration efforts. Using an extensive post-treatment design and a combination of remote sensing and field surveys, we sampled 17 floodplain projects designed to benefit anadromous fish in the Columbia River Basin. We detected significant increases in side channel metrics (area, length, and the ratio of bankfull side-channel to main channel length), sinuosity, pool frequency, large wood, and the morphological quality index. On average, juvenile Chinook ( Oncorhynchus tshawytsch), coho ( Oncorhynchus kisutch), steelhead, and salmonid combined abundance was 1.17, 4.62, 1.62, and 1.65 times higher, respectively, in treatment reaches compared to control reaches, though these increases were only significant for steelhead and all salmonids combined. Our study demonstrated that a combination of remote sensing and field data can be used to monitor floodplain and instream habitat and detect fish response to floodplain restoration projects.
Calibration of accelerometer transmitters to enable estimation of field metabolic rates in walleye
Authors: Ritchie Erin B. , Raby Graham D. , Smith Kurtis A. , Bzonek Paul A. , Brownscombe Jacob W.
Published: December 2024

Bioenergetic modelling is valuable for addressing many questions in animal ecology. However, applying these models to wild animals is limited by challenges with collecting in situ energetics data. To enable field applications, we conducted laboratory experiments using a swim tunnel respirometer on wild ( n = 28) and hatchery-origin ( n = 19) walleye ( Sander vitreus) to calibrate acoustic accelerometer transmitters (InnovaSea V13A and V16AT) for estimating metabolic rate ( ṀO2). Walleye (0.36–3.06 kg) underwent ramp- Uc rit swim trials ( n = 70) across four temperatures (5–21°C). Using mixed effects models, we analyzed critical swimming speed ( Ucrit), swimming speed, tailbeat frequency, and ṀO2 as functions of body mass, acceleration, sex, and water temperature. ṀO2 decreased with body mass and increased with higher swimming speeds, acceleration values, and water temperatures. Notably, ṀO2 increased more rapidly with acceleration at higher temperatures. No mass-specific sex differences were observed across measured parameters, and there were no differences in Ucrit or ṀO2 between control and tagged fish. These findings support the use of accelerometers to generate field estimates of energy expenditure in wild walleye.
Measurement of the electric potential and the magnetic field in the shifted analysing plane of the KATRIN experiment
Authors:   KATRIN Collaboration, Aker M. , Batzler D. , Beglarian A. , Behrens J. , Beisenkötter J. , Biassoni M. , Bieringer B. , Biondi Y. , Block F. , Bobien S. , Böttcher M. , Bornschein B. , Bornschein L. , Caldwell T. S. , Carminati M. , Chatrabhuti A. , Chilingaryan S. , Daniel B. A. , Debowski K. , Descher M. , Barrero D. Díaz , Doe P. J. , Dragoun O. , Drexlin G. , Edzards F. , Eitel K. , Ellinger E. , Engel R. , Enomoto S. , Felden A. , Fengler C. , Fiorini C. , Formaggio J. A. , Forstner C. , Fränkle F. M. , Gauda K. , Gavin A. S. , Gil W. , Glück F. , Grössle R. , Gumbsheimer R. , Hannen V. , Hasselmann L. , Haußmann N. , Helbing K. , Heyns S. , Hickford S. , Hiller R. , Hillesheimer D. , Hinz D. , Höhn T. , Huber A. , Jansen A. , Karl C. , Kellerer J. , Khosonthongkee K. , Köhler C. , Köllenberger L. , Kopmann A. , Kovač N. , Krause H. , La Cascio L. , Lasserre T. , Lauer J. , Le T. L. , Lebeda O. , Lehnert B. , Li G. , Lokhov A. , Machatschek M. , Mark M. , Marsteller A. , Martin E. L. , McMichael K. , Melzer C. , Mertens S. , Mohanty S. , Mostafa J. , Müller K. , Nava A. , Neumann H. , Niemes S. , Parno D. S. , Pavan M. , Pinsook U. , Poon A. W. P. , Poyato J. M. L. , Pozzi S. , Priester F. , Ráliš J. , Ramachandran S. , Robertson R. G. H. , Rodenbeck C. , Röllig M. , Sack R. , Saenz A. , Salomon R. , Schäfer P. , Schlösser M. , Schlösser K. , Schlüter L. , Schneidewind S. , Schrank M. , Schürmann J. , Schütz A. K. , Schwemmer A. , Schwenck A. , Šefčík M. , Siegmann D. , Simon F. , Spanier F. , Spreng D. , Sreethawong W. , Steidl M. , Štorek J. , Stribl X. , Sturm M. , Suwonjandee N. , Jerome N. Tan , Telle H. H. , Thorne L. A. , Thümmler T. , Titov N. , Tkachev I. , Urban K. , Valerius K. , Vénos D. , Weinheimer C. , Welte S. , Wendel J. , Wiesinger C. , Wilkerson J. F. , Wolf J. , Wüstling S. , Wydra J. , Xu W. , Zadorozhny S. , Zeller G.
Published: December 2024

The projected sensitivity of the effective electron neutrino-mass measurement with the KATRIN experiment is below 0.3 eV (90 % CL) after 5 years of data acquisition. The sensitivity is affected by the increased rate of the background electrons from KATRIN’s main spectrometer. A special shifted-analysing-plane (SAP) configuration was developed to reduce this background by a factor of two. The complex layout of electromagnetic fields in the SAP configuration requires a robust method of estimating these fields. We present in this paper a dedicated calibration measurement of the fields using conversion electrons of gaseous

$$^\textrm{83m}$$

83m

Kr, which enables the neutrino-mass measurements in the SAP configuration.
$$(g-2)_{e,\mu }$$ and lepton flavor violating decays in a left-right model
Authors: Hue L. T. , Phan Khiem Hong , Hong T. T. , Nguyen T. Phong , Nha N. H. T.
Published: December 2024

General expressions for one-loop contributions associated with lepton-flavor violating decays of the standard model-like Higgs boson

$$h\rightarrow e_b^\pm e_a^\mp $$

h
→

e
b
±

e
a
∓

and gauge boson

$$Z\rightarrow e^\pm _b e_a^\mp $$

Z
→

e
b
±

e
a
∓

are introduced in the unitary gauge. The results are used to discuss these decays as new physics signals in a minimal left-right symmetric model containing only one bidoublet Higgs and a

$$SU(2)_R$$

S
U

(
2
)

R

Higgs doublet accommodating data of neutrino oscillations and

$$(g-2)_{\mu }$$

(
g
-
2
)

μ

. The numerical investigation indicates that some of these decay rates can reach near future experimental sensitivities.
Detecting gravitational waves via coherence degradation induced by the Unruh effect
Authors: Barros Pedro H. M. , Costa Helder A. S.
Published: December 2024

We investigate the effects of a gravitational wave background on the coherence degradation induced by the Unruh effect of a uniformly accelerated single-qubit and quantum interferometric circuit. In both systems, we use the formalism of the evolution of the density matrix of the detector-field system, where after the interaction the field degrees of freedom are traced out to obtain the reduced density matrix of the detector. In this background, we calculate the quantum coherence and interferometric visibility in the long-wavelength regime and large interaction time. Our results indicate that the gravitational wave transfers energy to the internal states of the detector, causing, together with the Unruh effect, changes in them, amplifying the coherence degradation of the system. This amplification occurs when the polarization modes of the gravitational wave are in resonance and have modulated amplitudes. For the case of a short-wavelength, the detector does not respond to the gravitational wave because its oscillation is so fast that the detector does not have time to respond within the system timescale. Therefore, it is possible to detect the signature of gravitational waves in the coherence degradation induced by the Unruh effect within the regimes studied here.
Holographic drag force with translational symmetry breaking
Authors: Tahery Sara , Bitaghsir Fadafan Kazem , Mojarrad Lamanjouei Sahar
Published: December 2024

In order to investigate how the drag force is affected by translational symmetry breaking (TSB), we utilize a holographic model in which the background metric remains translational symmetric while a graviton mass or other fields in the theory break this symmetry. We calculate analytically the drag force, considering an asymptotic

$$\hbox {AdS}_5$$

AdS
5

in which parameter

$$\alpha $$

α

arises from TSB. This parameter can be intuitively understood as a measure of TSB strength and we anticipate that non-zero values of it will affect the drag force. In this asymptotic

$$\hbox {AdS}_5$$

AdS
5

background, we will demonstrate that a decrease in

$$\alpha $$

α

results in a reduction of the drag force. Moreover, we study the diffusion constant, which falls with increasing

$$\alpha $$

α

. It will eventually be shown that at lower values of

$$\alpha $$

α

or

$$\mu $$

μ

(chemical potential), the transverse diffusion coefficient is larger than the longitudinal one, and the speed of the heavy quark has minimal impact on the ratio.
Inflation models with Peccei–Quinn symmetry and axion kinetic misalignment
Authors: Lee Hyun Min , Menkara Adriana G. , Seong Myeong-Jung , Song Jun-Ho
Published: December 2024

We propose a consistent framework with the U(1) Peccei–Quinn (PQ) symmetry for obtaining the initial condition for axion kinetic misalignment from inflation. We introduce a PQ complex scalar field and an extra Higgs doublet, which are conformally coupled to gravity, and three right-handed neutrinos for the seesaw mechanism. In the DFSZ type scenarios for the axion, we obtain the PQ anomalies from the Standard Model quarks carrying nonzero PQ charges in some of two Higgs doublet models, solving the strong CP problem by the QCD potential for the axion. Assuming that the PQ symmetry is explicitly violated in the scalar potential by quantum gravity effects, we show that a sufficiently large initial axion velocity can be obtained before the QCD phase transition while avoiding the axion quality problem. As inflation is driven by the radial distance from the origin in the space of scalar fields close to the pole of the kinetic terms in the Einstein frame, we obtain successful inflationary predictions and set the initial axion velocity at the end of inflation. Focusing on the pure PQ inflation with a small running quartic coupling for the PQ field, we discuss the post-inflationary dynamics for the inflaton and the axion. As a result, we show that a sufficiently high reheating temperature can be obtained dominantly from the Higgs-portal couplings to the PQ field, while being consistent with axion kinetic misalignment, the stability for the Higgs fields during inflation and the non-restoration of the PQ symmetry after reheating.
Porous CuF2 derived from MOFs as cathode materials for Li-ion batteries
Authors: Xu Hanchen , Yu Zhiyong , Tian Lujia , Du Suni , Zhao Yichun , Cheng Jingsai , Liu Hanxing , Yuan Zhongzhi
Published: December 2024

Copper fluoride (CuF2) has demonstrated great potential as a cathode material for LIBs owing to its high energy density. In this study, a two-step synthesis method was proposed to prepare porous CuF2 by using Cu-based metal-organic frameworks (MOFs). N2 adsorption-desorption isotherms, along with SEM and TEM analyses, proved that the intermediates CuO exerted a certain influence on the pore structure of the final CuF2 products. The porous CuF2 achieved a first discharge capacity of 554 mAh ⋅ g[Formula: see text] at 0.1C. At a high current density of 5C, it delivered a rate capacity of 413 mAh ⋅ g[Formula: see text] within 1.5–4.2 V. The results of electrochemical impedance spectroscopy show that varying degrees of porosity influence the lithium-ion diffusion coefficient, leading to differences in electrochemical performances.
GPTs and Hallucination
Authors: Waldo Jim , Boussard Soline
Published: December 2024

Why do large language models hallucinate?