bluuebunny/crossref_metadata_2025 huggingface dataset:
Cancer outcomes and cardiopulmonary toxicities for Black patients with breast cancer treated with proton therapy
Authors: Singh Gurbani , Koduri Sravya , Rao Manaahil , Kidorf Meira , Ruff Sarah , Patel Akshar , Bentzen Søren M , Nichols Elizabeth , McAvoy Sarah , Vyfhuis Melissa A L
Published: December 2024

Background

Black women have a 40% higher breast cancer mortality rate than White women and are at a higher risk of acquiring cardiovascular disease. Proton therapy can be used to mitigate cardiac radiation exposure; however, proton therapy remains a scarce resource in the United States. We report on the cardiovascular profiles of patients undergoing proton therapy to determine the potential benefit of the therapy for Black women compared with patients of other races.

Methods

We retrospectively analyzed 599 patients with breast cancer who received proton therapy from June 2016 to December 2021 at the Maryland Proton Treatment Center. A variety of sociodemographic, disease, and treatment variables were analyzed using descriptive statistics.

Results

With a median follow-up of 26 months (range = 0.47-90 months), Black patients made up 31.6% of the population and presented with higher rates of hypertension (P < .001), cardiopulmonary conditions (P < .001), and a higher median body mass index (P = .015) compared with the other cohort, a trend that persisted at the time of post–proton therapy follow-up. Black women had higher rates of triple-negative disease (P < .001), with subsequent greater receipt of neoadjuvant chemotherapy (P = .039). Pulmonary events were 2.6 times more likely to occur in Black patients than in the non-Black cohort after proton therapy (odds ratio = 2.60, 95% CI = 1.39 to 4.88; P = .003).

Conclusions

Black women presenting for proton therapy had higher baseline risks of cardiovascular co-morbidities combined with more aggressive breast cancer biology and a subsequent 2.6-fold increased risk of pulmonary events after proton therapy. Our findings support the use of advanced radiation techniques as a means of sparing important organs at risk, especially in historically marginalized populations.
Cytidine analogs in plant epigenetic research and beyond
Authors: Dvořák Tomaštíková Eva , Pecinka Ales
Published: December 2024

Cytosine (DNA) methylation plays important roles in silencing transposable elements, plant development, genomic imprinting, stress responses, and maintenance of genome stability. To better understand the functions of this epigenetic modification, several tools have been developed to manipulate DNA methylation levels. These tools include mutants of DNA methylation writers and readers, targeted manipulation of locus-specific methylation, and the use of chemical inhibitors. Here, we summarize the effects of commonly used cytidine analog chemical inhibitors, represented by zebularine, 5-azacytidine, and their related compounds, on plants. These analogs are incorporated into chromosomal DNA, where they block the activity of the replicative CG DNA methyltransferase 1 (MET1). This leads to manifold alterations in the plant epigenome, modified developmental programs, or suppression of hybridization barriers. We also highlight the DNA-damaging effects of cytidine analogs, particularly the formation of stable DNA–protein crosslinks between DNA and MET1. This phenomenon sheds new light on specific phenotypes observed upon treatment with cytidine analogs. In conclusion, cytidine analogs are a vital tool for plant genome research and have the potential to open new promising avenues for applications in plant biotechnology and breeding.
Autophagy modulates glioblastoma cell sensitivity to Selinexor-mediated XPO1 inhibition
Authors: Tang Yongjian , Sprinzen Lisa , Terada Yukinori , Kiang Karrie M , Li Chuntao , Zeng Yu , Liu Fangkun , Zhou Hongshu , Liang Xisong , Zhang Jianzhong , Pieper Russell O , Chen Bo , Zhang Liyang
Published: December 2024

Background

Selinexor is a selective inhibitor of exportin-1 (XPO1), a key mediator of the nucleocytoplasmic transport for molecules critical to tumor cell survival. Selinexor’s lethality is generally associated with the induction of apoptosis, and in some cases, with autophagy-induced apoptosis. We performed this study to determine Selinexor’s action in glioblastoma (GBM) cells, which are notoriously resistant to apoptosis.

Methods

Patient-derived GBM cells were treated with Selinexor, and drug response and autophagy levels were monitored. Homozygous C528S XPO1 mutant GBM43 cells were generated by CRISPR/Cas9 editing. Single Selinexor or combination treatment with autophagy inhibitors was evaluated. In addition, bulk-tissue, single-cell, and spatial transcriptome were analyzed, and molecular docking was performed.

Results

Although all cell lines exhibited a dose- and time-dependent reduction of cell viability, the most profound molecular response to Selinexor was induction of autophagy instead of apoptosis. Selinexor-induced autophagy was an on-target consequence of XPO1 inhibition, and could be mitigated by expression of a mutant, Selinexor-resistant form of XPO1, and Selinexor-induced autophagy was related at least in part to nuclear trapping of the transcription factor TFEB. Furthermore, genetic or pharmacologic suppression of autophagy sensitized the cells to Selinexor-induced toxicity in association with the induction of apoptosis. Finally, in intracranial PDX studies, the combination of Selinexor with the autophagy inhibitor chloroquine significantly impeded tumor growth and extended mouse survival relative to single-agent treatment.

Conclusion

These results suggest that activation of autophagy confers a protective mechanism against Selinexor in GBM cells, and that the combination of Selinexor with autophagy inhibitors may serve as a viable means to enhance Selinexor-induced cell death.
A machine learning–assisted systematic review of preclinical glioma modeling: Is practice changing with the times?
Authors: Hirst Theodore C , Wilson Emma , Browne Declan , Sena Emily S
Published: December 2024

Background

Despite improvements in our understanding of glioblastoma pathophysiology, there have been no major improvements in treatment in recent years. Animal models are a vital tool for investigating cancer biology and its treatment, but have known limitations. There have been advances in glioblastoma modeling techniques in this century although it is unclear to what extent they have been adopted.

Methods

We searched Pubmed and EMBASE using terms designed to identify all publications reporting an animal glioma experiment, using a machine learning algorithm to assist with screening. We reviewed the full text of a sample of 1000 articles and then used the findings to inform a screen of all included abstracts to appraise the modeling applications across the entire dataset.

Results

The search identified 26 201 publications of which 13 783 were included at screening. The automated screening had high sensitivity but limited specificity. We observed a dominance of traditional cell line paradigms and the emergence of advanced tumor model systems eclipsed by a large increase in the volume of cell line experiments. Few studies used more than 1 model in vivo and most publications did not verify critical genetic features.

Conclusions

Advanced models have clear advantages in terms of tumor and disease recapitulation and have largely not replaced traditional cell lines which have a number of critical deficiencies that limit their viability in modern animal research. The judicious use of advanced models or more relevant cell lines might improve the translational relevance of future animal glioblastoma experimentation.
Mapping the Geographic Distribution of Dimorphic Mycoses Using a U.S. Commercial Insurance Database
Authors: Goodman Reid , Rauseo Adriana M , Windham Samuel L , Zuniga-Moya Julio C , Powderly William G , Spec Andrej , Mazi Patrick B
Published: December 2024

Background

The dimorphic mycoses (DM) histoplasmosis, blastomycosis, and coccidioidomycosis are classically thought to be geographically restricted to specific regions of the United States. The current scientific consensus is that these geographic boundaries are expanding, but the extent of this expansion remains uncertain.

Methods

This study is a retrospective analysis of >21 million (annually) commercially insured individuals within the United States during 2007-2016. Diagnosis of histoplasmosis, coccidioidomycosis, and blastomycosis were identified using International Classification of Diseases, 9th/10th Revision within the MerativeTM MarketScan® database.

Results

There were 37,513 histoplasmosis, 14,987 coccidioidomycosis, and 2,207 blastomycosis diagnoses during 2007-2016 within 387 Metropolitan Statistical Areas (MSAs). DM were consistently diagnosed outside their historical hyperendemic regions.

Conclusions

New diagnoses of histoplasmosis, coccidioidomycosis, and blastomycosis were routinely made outside their historically defined regions of endemicity. While exposure to hyperendemic regions remains a risk factor for developing a DM infection, clinicians should consider testing any patient presenting with a compatible clinical syndrome, regardless of their geographic history. Increased suspicion of DM infection will lead to fewer missed or delayed diagnoses thereby improving patient outcomes.
Training and usage of language interpretation services among health care providers in a large Canadian pediatric centre
Authors: Brochez Nicholas , Islam Bonnieca , Mian Qaasim , Forbes Karen L
Published: December 2024

Objectives

Canada has a diverse population and one of the highest immigration rates in the world. Non-English or French language preference populations face barriers accessing health care, which leads to increased rates of adverse events. Adequate training of health care providers (HCPs) with language interpretation services (LIS) and having accessible LIS are crucial to improve the quality of patient care. We sought to identify HCPs’ prior training, and use of and attitudes toward LIS in a Canadian tertiary pediatric centre.

Methods

An electronic survey was developed and distributed to a diverse group of pediatric HCPs at the Stollery Children’s Hospital in Edmonton, Alberta between October 2022 and February 2023. Survey completion was anonymous and voluntary. Descriptive statistics were used for quantitative data and thematic analysis for free text responses.

Results

Three hundred forty-five HCPs accessed the survey and 281 (81%) completed it. Fifty-three percent of respondents encountered a pediatric non-English or French language preference patient/family once weekly or more and 51.5% reported no previous training in the use of LIS in patient care. In-person interpreters were perceived as the most effective LIS modality. Barriers to using LIS included: inability to access desired modality and/or language; insufficient time; and lack of comfort in effective usage.

Conclusions

HCPs perceive LIS as integral to patient care and convenient to use, yet most report no prior training. This study identifies multiple barriers to using LIS and suggested improvements include enhancing LIS accessibility, reliability, and LIS education. These results will help inform local LIS initiatives and resource allocation.
Evaluating in times of paradigmatic change: some reflections on how to conduct ex-post evaluations amidst the transformative turn in research and innovation policy
Authors: Wieser Harald
Published: December 2024

The transformative turn in research and innovation (R&I) policy calls for new approaches to monitoring and evaluation, yet most evaluands are still rooted in previous policy paradigms. For evaluators tasked with conducting ex-post evaluations, this situation creates multiple challenges that have received little attention to date. In this ‘voice from the field’, I argue that times of paradigmatic change require an increased awareness about discursive politics, heightened expectations, uncertainties, and the differences between the old and the new in evaluations. Based on recent experiences from an ex-post evaluation of the R&I programme City of Tomorrow, I provide some suggestions for coping with these challenges.
The startle response and prepulse inhibition in psychosis and violence: A combined electromyography and electroencephalography study
Authors: Bang Nina , Pettersen Johanne H , Nesset Merete Berg , Rasmussen Kirsten , Dahl Hilde , Tesli Natalia , Bell Christina  , Vaskinn Anja , Fischer-Vieler Thomas  , Friestad Christine , Andreassen Ole A , Jönsson Erik G , Elvsåshagen Torbjørn , Haukvik Unn K , Moberget Torgeir
Published: December 2024

There is a pressing need for biomarkers of violent behavior risk in psychosis. Previous research indicates that electrophysiological measures of automatic defensive reactions may have potential. The purpose of this study was to investigate associations between violent behavior in individuals with and without psychosis and electromyography (EMG) and electroencephalography (EEG) responses to startling auditory stimuli. EMG and EEG was recorded during an auditory startle paradigm from healthy controls (HC, n=211), individuals with psychosis and a history of violent behavior (violent-PSY, n=18), individuals with psychosis without a history of violence (nonviolent-PSY, n=32), and individuals with a history of violence without psychosis (violent non-PSY, n=22). We estimated the auditory startle response (ASR) and prepulse inhibition (PPI) using EMG (i.e., EMGASR and EMGPPI) and the auditory evoked potential (i.e., AEPASR and AEPPPI) of the EEG. There were no significant effects of group on the EMGASR (p = 0.10) or the 30-ms, 60-ms, and 120-ms prepulse + pulse EMGPPI amplitudes (p = 0.11, p = 0.19, and p = 0.50, respectively). The N1 amplitude of the AEPASR was reduced in the violent-PSY group (p = <.001) and the nonviolent-PSY group (p = .015) compared to HC. The P2 amplitude of the AEPASR was reduced in violent-PSY relative to nonviolent-PSY (p = .003), violent non-PSY (p = .016), and HC (p < .001). Together, these results show that EEG-based neural responses to startling auditory stimuli are promising biomarkers of violence risk in psychosis.
Prediction of phenoconversion into alpha-synucleinopathy in patients with isolated REM sleep behavior disorder using event-related potentials during visuospatial attention tasks
Authors: Choi Kang-Min , Cha Kwang Su , Noh Tae-Gon , Lee Seolah , Shin Yong Woo , Byun Jung-Ick , Jun Jin-Sun , Shin Jung Hwan , Kim Han-Joon , Jung Ki-Young
Published: December 2024

Study Objectives

Isolated rapid eye movement sleep behavior disorder (iRBD) is recognized as a prodromal stage of alpha-synucleinopathies. Predicting phenoconversion in iRBD patients remains a key challenge. We aimed to investigate whether event-related potentials (ERPs) recorded during visuospatial attention tasks can serve as predictors of phenoconversion in iRBD patients.

Methods

We conducted a longitudinal study with 126 iRBD patients (aged 67.1 ± 6.4, 77 males) and 41 healthy controls (aged 66.1 ± 6.9, 29 males). Among the patients, those who further developed synucleinopathies during the follow-up period (average 6.3 years) were classified as converters (iRBD-CV), while the others were non-converters (iRBD-NC). Posner’s visuospatial cueing task was performed at baseline. The N2 and P3 components were acquired for both the cue and target (valid and invalid) stimuli. Based on group comparisons, Kaplan–Meier survival analysis was performed.

Results

Twenty-nine patients converted to alpha-synucleinopathies (aged 69.4 ± 7.1, 14 males). iRBD patients exhibited overall reductions in N2 components for cue, valid, and invalid stimuli compared to HC (p = 0.012, 0.047, and 0.001, respectively). iRBD-CV patients displayed a significant increase in cue-elicited P3 (p < 0.001) and a decreasing trend in cue-elicited N2 (p = 0.079) compared to iRBD-NC. These ERP alterations were strongly associated with faster rate of phenoconversion (p < 0.001 for both components).

Conclusion

Our findings suggest that altered cue-elicited ERPs could serve as early biomarkers for predicting phenoconversion in iRBD patients, likely reflecting attention-related neurodegeneration pathways. These biomarkers potentially enable the detection of preclinical phenotypes in alpha-synucleinopathies, facilitating timely intervention.
Risk perception and mpox vaccine acceptability among people living with HIV in northern Nigeria
Authors: Iliyasu Zubairu , Kwaku Aminatu A , Nass Nafisa S , Umar Amina A , Amole Taiwo G , Abdullahi Hadiza M , Tsiga-Ahmed Fatimah I , Jibo Abubakar M , Fontana Brittany R , Salihu Hamisu M , Aliyu Muktar H
Published: December 2024

Background

There is a dearth of information regarding mpox risk perception and vaccine acceptance among people living with human immunodeficiency virus (HIV), especially in countries with a dual burden of HIV and mpox, such as Nigeria.

Methods

We used an explanatory mixed methods design and structured questionnaires administered to a clinic-based sample of people living with HIV (n=430), followed by in-depth interviews with a purposive subsample (n=20). Data were analysed using binary logistic regression and the framework approach.

Results

More than one-third (38.1% [n=164]) of the respondents self-perceived a high risk of mpox and 64.4% (n=277) indicated a willingness to receive the vaccine. Willingness to accept the mpox vaccine was positively associated with male sex, older age, non-Muslim faith, unmarried status, post-secondary education and current civil service employment. The odds of accepting the mpox vaccine was also higher among respondents who perceived mpox as a serious disease (adjusted odds ratio [aOR] 1.41 [95% confidence interval {CI} 1.12 to 2.35]), self-assessed a higher risk (aOR 1.66 [95% CI 1.19 to 3.06]) and were concerned about contracting the disease (aOR 1.78 [95% CI 1.12 to 3.94]). Reasons for hesitancy included anxiety about vaccine–antiretroviral drug interactions, low risk perception, perceived protection from antiretroviral treatment, the newness of the vaccine, mistrust of authorities and pharmaceutical companies and concerns regarding vaccine safety.

Conclusions

Mpox risk perception and vaccine acceptance were suboptimal. Vaccine acceptance was influenced by sociodemographic, perceived susceptibility and health behaviour-related factors. Targeted risk communication will enhance acceptance of mpox vaccination among people living with HIV in Nigeria.
Effectiveness of Mindfulness-Based Interventions for Reducing Anxiety Among Women With Breast Cancer
Authors: Ahmed Abd-el Naby Abd Allah Rama , Mohammed Mourad Ghada , Osman Abd El-Fatah Wafaa
Published: December 2024

After receiving a diagnosis of breast cancer, patients may experience negative physical, mental, and psychological symptoms. When excessive and uncontrollable, anxiety can become a pathological disorder. Mindfulness-based interventions (MBIs) are psychological approaches that incorporate practices individuals can use to promote awareness, nonjudgmental acceptance, and present-moment focus. We conducted this study to evaluate the effect of MBIs for reducing anxiety among women who had undergone surgical interventions for removal of breast cancer. We used a quasi-experimental design and a convenience sample of 30 women. We used three tools for data collection: a structured questionnaire that collected sociodemographic data and assessed the participants’ knowledge about breast cancer, the Freiburg Mindfulness Inventory, which is a self-reported Likert scale designed to assess core characteristics of mindfulness, and the Hamilton Anxiety Rating Scale that measures the severity of an individual’s anxiety. The results of our study showed that the majority (n = 24; 79.6%) of women who participated in our training program developed high levels of awareness about mindfulness. We found a highly statistically significant difference in the participants’ levels of awareness of mindfulness between the pre- and postprogram evaluations (χ²[29, 30] = 56.143, p < .001), and a highly statistically significant difference in the participants’ anxiety levels between the pre- and postprogram evaluations (χ²[29, 30] = 24.178, p < .001). We concluded that implementing a mindfulness training program significantly reduced the participants’ level of anxiety. We recommend including MBIs in the treatment protocol for women with breast cancer as a method for reducing anxiety.
Nonoperative Management of Pretibial Lacerations in a Nurse-Led Clinic: An Observational Study
Authors: Kosasih Sebastian , Ramsay Dana , Corriero Anna , Shahid Shahab , Whitehouse Kevin , Miranda Ben H.
Published: December 2024

In our tertiary plastic surgery center, patients with wounds that will not be treated surgically, including complex pretibial wounds, that would traditionally have been managed operatively are managed on an outpatient basis in a nurse-led pretibial laceration clinic. We conducted a study to investigate dressing usage and assess correlators with healing time or number of appointments. We collected data regarding dressings used, time to discharge, and number of appointments retrospectively over 14 months between 2019 and 2021. We analyzed the data using linear regression and set the significance at p < .05. We accepted 138 patients for review and dressing management including 76 patients who had been discharged from the clinic at the time of data collection. The median age was 80 years (interquartile range [IQR] 14, 73-87). Time to discharge ranged from 0 to 201 days (median 24.5, IQR 68.5). The number of appointments ranged from 1 to 19 (median 3, IQR 7.25). Linear regression indicated that the number of different types of dressings used was statistically correlated with time to discharge (R
2 = 0.230, F(1,74) = 22.1, p < .005). Similarly, the correlation between the number of dressings used and the number of total appointments was also statistically significant (R
2 = 0.246, F(1,74) = 24.1, p < .005). In patients with conservatively managed pretibial lacerations, the total number of different dressings used (as a surrogate marker for wound complexity
) is predictive of the time the patient spends in follow-up and the total number of hospital contacts. These data may be used to help understand when conservatively managed pretibial lacerations may require more intensive intervention.
Breast Implant Surgery: The Importance of Informed Health Care Decisions and Outcome Monitoring
Authors: Prothe Jessica , Kozak Brenda
Published: December 2024

Breast implant surgery is a popular, globally performed, and frequently requested cosmetic and reconstructive surgical procedure. Breast implant surgery can cause implant-associated systemic symptoms and types of implant-associated cancers, so it is vital to monitor patient outcomes. Most patients who undergo breast implant surgery do not experience health problems. However, patients who do experience health problems as a result of breast implant surgery form a unique patient population. When plastic and aesthetic surgeons, nurses, and other healthcare providers are knowledgeable and experienced in recognizing and treating patients with health problems related to breast implant surgery, the health outcomes of this patient population improve. This article aims to promote informed decision-making and increase patient safety by providing information about the health problems associated with breast implant surgery. This article also highlights recent safety announcements and updates from the United States Food and Drug Administration (FDA). Ensuring the safety of patients undergoing breast implant surgery is a responsibility shared by plastic and aesthetic surgeons, nurses, and other healthcare providers; the general medical community; breast implant manufacturers; and the FDA. These entities must collaborate and coordinate as a united group to accomplish this important goal. The nursing profession can contribute to these collaborative efforts by serving as professional liaisons to these entities and advocating for continued collaborative efforts to increase the safety of patients who have undergone breast implant surgery.
A Virtual Music Mindfulness Tool for Individuals of African descent during COVID-19
Authors: Igbinobaro Eghosa , Watts Amanda , Oshodi Oluwatofunmi , Emile Myrline Cleo , Soumare Aldwin , Takyi Percy , Haida Thema , Washington Hanifa , Allsop AZA Stephen
Published: December 2024

Mental health disparities result from complex factors, including differential diagnoses, lack of access to standard mental health treatments, and inconsistent application of treatments when care is accessed. The COVID-19 pandemic exacerbated these disparities as marginalized groups had less access to testing and care while having higher infection rates. Community-based forms of care, such as music and mindfulness, are affordable and accessible options that can potentially address present mental health disparities. Specifically, music and mindfulness tools can be delivered virtually and are effective means for treating stress-related conditions. However, previous studies measuring the impact of music and mindfulness on stress-related conditions lack representation of people of African descent (PADs) and other marginalized communities. Among many reasons, bias and mistrust in recruitment strategies contribute to the lack of representation in these research studies. In this pilot study, we tested the feasibility of PAD recruitment in a virtual community-based music mindfulness research study and measured the impact of participation on perceived stress. Participants (14) with diagnosed anxiety were enrolled in an 8-week virtual music mindfulness program. We found a significant correlation between time engaged in our music mindfulness platform and lower perceived stress. Future work will evaluate the adoption and efficacy of these virtual strategies in communities when combined with and replacing standard interventions.
Food Quality Scores and Nutrient Ratios Correlate with Healthier Weight and Blood Pressure in a Representative US Cohort
Authors: Damman Christopher J. , Frankenfeld Cara L.
Published: December 2024

Background

Obesity is on the rise, driven in part by changing patterns in food consumption. Nutrient profiling systems (NPSs) aim to guide healthier food choices through labeling and consumer facing technologies that highlight food quality.

Objectives

This study compares four leading NPSs—Nutri-Score (NS), Health Star (HS), NOVA Classification (NC), Food Compass 2.0 (FC) – with nutrient ratios and a nutrient-ratio-based NPS, Nutrient Consume Score (NCS), for their associations with obesity and blood pressure in the U.S. population using NHANES data.

Methods

NHANES (2015–2016) was analyzed for adults aged 20 and older. Dietary intake was assessed via 24-hour recalls, and NPS scores were calculated. Multivariable regression models adjusted for lifestyle factors were used to assess associations with obesity and blood pressure measures.

Results

All NPSs and nutrient ratios were significantly correlated with healthier weight and showed variable associations with blood pressure. Incorporating alcohol and adjusting for bioactives in a ratio-based NPS improved its association with weight outcomes. The food categories contributing to high and low scores were largely consistent across NPSs.

Conclusions

The NPSs and nutrient ratios evaluated were significantly associated with obesity and blood pressure measures. Intervention studies offering real-time NPS feedback on individual food choices are needed next to evaluate for causal impact of NPSs on metabolic health.
Exploring RSV transmission patterns in different age groups in the United States
Authors: Li Ke , Pitzer Virginia E. , Weinberger Daniel M.
Published: December 2024

Respiratory syncytial virus (RSV) infections are a significant public health concern for pediatric populations and older adults, with seasonal winter outbreaks in the United States (US). Little is known about the timing of RSV epidemics across age groups and the relative contribution of within-group and between-group transmission of RSV in each age group. The lack of understanding of age-specific RSV transmission patterns limits our ability to inform vaccination policies. In this study, we examine the timing and transmission patterns of RSV epidemics across different age groups in 12 US states from 2018 to 2024. We found that infants under 1 year and young children aged 1–4 years experienced the earliest epidemic timing, while the elderly group had the latest. Using a semi-mechanistic age-structured spatiotemporal model, we further showed that between-group transmission greatly contributes (>50%) to the burden of RSV hospitalizations for children under 1, school-age children aged 5-17, and adults aged 18-64. By contrast, incidence in the elderly group (above 65 years) was primarily driven by transmission within the age group. Our findings indicate that distinct age groups play unique roles in propagating RSV epidemics in the US, with age-specific transmission patterns that can guide more effective RSV vaccination policies.
Negative Impact of Cenobamate on Cognition: Dose-Dependent and Independent Effects
Authors: Witt Juri-Alexander , Badr Mostafa , Surges Rainer , von Wrede Randi , Helmstaedter Christoph
Published: December 2024

Background

Studies on Cenobamate (CNB) have generally reported neutral to positive effects on objective cognitive performance in patients with epilepsy, but are limited to dosages up to 250 mg/day. However, a case report (Witt et al.,Neurocase, 2024) noted severe memory deterioration at 400 mg/day.

Objective

To examine dose-dependent effects of CNB on cognition.

Methods

In this retrospective longitudinal study, executive functions (EpiTrack®) and episodic memory were assessed in patients with epilepsy during CNB therapy and compared to baseline. Subgroups were stratified by daily CNB doses of ≥300 mg versus <300 mg.

Results

The study included 84 patients. With a mean CNB dose 200.6 ± 114.3 mg (range: 12.5-400.0 mg; 28.6% ≥300 mg) seizure freedom was achieved in 10.7%. Repeated measures ANCOVA revealed a significant decline in executive functions at ≥300 mg (n=84; F = 6.35, p = 0.014). Changes were correlated with CNB dose (r = −0.31, p = 0.004). Significant individual declines according to reliable change indices occurred in 50.0% of patients on higher versus 16.7% on lower CNB doses. In a subgroup undergoing extensive memory testing, verbal retention showed a significant negative, dose-independent effect (n=22; F = 7.95, p = 0.011), with intraindividual declines in 28.6% (≥300 mg) versus 13.3% (<300 mg). Other memory parameters were unaffected.

Conclusion

In the largest longitudinal study to date, higher CNB doses were linked to deterioration in executive functions, while a decline in verbal retention appeared dose-independent. These findings need to be confirmed by systematic studies.
Risk assessment of 2024 cattle H5N1 using age-stratified serosurveillance data
Authors: Chen Lin-Lei , Zhang Xiaojuan , Zhang Kang , Chan Brian Pui-Chun , Yuk Yuen Jacqueline Kwan , Yuen Kwok-Yung , Wang Pui , Yang Yuhe R. , Chen Honglin , To Kelvin Kai-Wang
Published: December 2024

The highly pathogenic avian influenza virus A(H5N1) clade 2.3.4.4b has caused a human outbreak in North America since March 2024. Here, we conducted a serosurveillance study to determine the risk of A(H5N1) clade 2.3.4.4b (2024 cattle H5N1) to general population. In the initial screening of 180 serum specimens encompassing all age groups, 2.2% (4/180) had detectable neutralizing antibody (nAb) titers against 2024 cattle H5N1, with all collected from older adults aged ≥60 years old. Further screening showed that 5.0% (15/300) of adults aged ≥70 years old had detectable nAb titers against the 2024 cattle H5N1. All serum specimens with nAb titer of ≥40 had detectable HI titer, and there was a positive correlation between nAb titer and HA binding (r=0.3311, 95% confidence interval 0.2264 to 0.4283; P<0.0001). The nAb titer against seasonal H1N1 virus was 3.9-fold higher for patients with detectable H5N1 nAb than those without (geometric mean titer: 108.5 [95% CI 56.3-209.1] vs 27.9 [95% CI 21.0-37.0], P=0.0039), but there was no statistically significant difference between H5N1 and H3N2 nAb titer. There was no difference in demographics, comorbidities and clinical frailty scores between individuals with detectable H5N1 nAb and those without. Our findings suggest that most individuals lack nAb response against 2024 cattle H5N1 and there is an urgency to develop and evaluate H5N1 vaccine or prophylactic monoclonal antibodies. Immune imprinting may be responsible for the cross neutralization between H5N1 and H1N1 among older adults.
Monitoring COVID-19 Occurrence in a Resource-limited Setting – COVID-19 Sentinel Surveillance in Malawi
Authors: Ulaya Godwin , Kabaghe Alinune , Saussier Christel , MacLachlan Ellen , Smith-Sreen Joshua , Katumbi Chaplain , Bello George , Tafatatha Terence , Chaponda Limbikani , Mvula Bernard , Kagoli Matthews , Chilima Benson , Bitilinyu-Bangoh Joseph , Chisuwo Laphiod , Babaye Yusuf , Chitenje Moses , Bighignoli Barbara , Bangara Fred , Namakhoma Ireen , Chauma-Mwale Annie , O’Malley Gabrielle , Mirkovic Kelsey , Wadonda-Kabondo Nellie
Published: December 2024

The routine COVID-19 surveillance in Malawi that relied on retrospective reporting could not efficiently steer timely measures to the rapidly evolving pandemic. To monitor real-time changes in infections and inform the COVID-19 response, we implemented an active sentinel surveillance system from July to December 2022. SARS-CoV-2 symptomatic and asymptomatic patients in selected health facilities (HFs) and anyone aged ≥5 years entering at Point of Entry (PoEs) sites were eligible to participate. Self-reported epidemiological and clinical data, and nasopharyngeal specimens were collected from 9,305 participants. A higher overall SARS-CoV-2 RT-PCR positivity rate was observed at HFs, 8.9% among symptomatic and 6.5% among asymptomatic patients, versus 3.5% at PoEs. The positivity trends among symptomatic and asymptomatic patient groups showed a similar pattern throughout the period. This active surveillance complemented routine surveillance, especially during a low incidence period and highlighted the need to target both symptomatic and asymptomatic population.
Multiomic Mendelian randomization-based insights into the role of neutrophil extracellular trap-related genes in sepsis
Authors: Liu Yanbo , Li Yuhui , Chen Jinmin , Cai Yongxia , Lv Lukai
Published: December 2024

Objective: This study aims to elucidate the role of neutrophil extracellular trap-related genes (NRGs) in sepsis risk using a multiomic Mendelian randomization (MR) approach, leveraging genetic variants as instrumental variables to investigate the causal relationships between NRGs and sepsis. Methods: We systematically identified 69 NRGs through literature and database reviews. Genetic data for sepsis cases and controls were extracted from the IEU OpenGWAS Project database. Expression quantitative trait loci (eQTLs), methylation quantitative trait loci (mQTLs), and protein quantitative trait loci (pQTLs) associated with NRGs were obtained from the eQTLGen Consortium, mQTL meta-analysis, and deCODE Genetics datasets, respectively. We employed inverse variance-weighted method, supplemented by MR-Egger regression, weighted median, and Bayesian colocalization analysis, to identify genes significantly associated with sepsis risk. Results: Four genes (CXCR1, CXCR2, ENTPD4, and MAPK3) were significantly associated with sepsis risk. Three CpG sites associated with these genes were identified through mQTL-based MR analysis, and ten proteins showed significant associations with sepsis risk in pQTL-based MR analysis. Summary-data-based MR and colocalization analyses confirmed a causal relationship between CXCR2 and sepsis, unaffected by pleiotropy. The DNA methylation level at cg06547715, located in the CXCR2 enhancer region, was inversely correlated with CXCR2 expression and sepsis risk, suggesting that the DNA methylation status of CXCR2 may modulate gene expression, influencing sepsis risk. Conclusion: Our findings indicate that NRGs, particularly CXCR2, play a crucial role in sepsis susceptibility and highlight the potential of NRGs as therapeutic targets. Targeting CXCR2 and its regulatory mechanisms may offer a new avenue for sepsis management, contributing to the theoretical understanding of sepsis pathogenesis and paving the way for future research into precision medicine for sepsis.
Investigation of an ongoing outbreak of ceftriaxone-resistantSalmonella entericaserovar Typhi in Bangladesh
Authors: Hooda Yogesh , Tanmoy Arif Mohammad , Nath Sudipta Deb , Jui Anannya Barman , Amin Al , Rahman Hafizur , Shorkar Neoyman Nasir , Kanon Naito , Rahman Md Asadur , Garrett Denise O , Islam Mohammad Shahidul , Ahmed ASM Nawshad Uddin , Saha Samir K , Saha Senjuti
Published: December 2024

We report an outbreak of ceftriaxone-resistantSalmonellaTyphi in Bangladesh, with 47 cases identified from April-September 2024. Isolates belong to genotype 4.3.1.2 and harbor theblaCTX- M-15gene on the pCROB1 plasmid. This unique genotype-plasmid lineage represents a recent introduction, necessitating enhanced surveillance, antimicrobial stewardship, and consideration of vaccination strategies.
The association between suicidal ideation with future suicide attempts and service utilization: a population cohort study in Ontario, Canada
Authors: Chan C. , Wodchis W. , Kurdyak P. , Donnelly P.
Published: December 2024

Background

Few studies examine suicidal ideation and its relationship with suicide attempts and health service use using a community sample.

Objective

To examine the association between suicidal ideation with (i) future mental health service use, and (ii) future suicide attempts, in a general population sample.

Methods

Using the 2002 and 2012 Canadian Community Health Surveys – Mental Health cycles linked with health administrative data, this study followed 14,708 Ontarians 15 years and older in a retrospective cohort study to examine patterns of mental health service use within 1 year, and suicide attempts within 5 years of self-reported suicidal ideation.

Results

A total of 2.1% (n=302) of all survey respondents reported suicidal ideation alone in the past year and another 0.5% (n=76) reported having ideation-with-action (i.e. ideation with planning or previous suicide attempt). Ideation-with-action was associated with a higher likelihood of future suicide attempts and future mental health service use, when compared to suicidal ideation alone. However, the majority of survey respondents who attempted suicide within the five-year follow-up period did not report a previous attempt or ideation at baseline.

Conclusion

While suicidal ideation is statistically significantly associated with greater likelihood of suicide attempt within five years, most attempters did not self-report ideation at baseline. Further study is needed to measure suicidal outcomes longitudinally to allow for dynamic expression of suicidal ideation as outcomes such as suicide attempts are measured.

Those with ideation-with-action are more intense users of mental health services than those with ideation alone, indicating that care is reaching the more severe ideators.
Assessing Diagnostic Performance of Plasma Biomarkers in Alzheimer’s Disease: P-tau217 Emerges as the Optimal Marker in Chinese Cohorts
Authors: Wang Shinan , Liu Dequan , Li Haiyan , Jia Xiaodong , Zhou Hailan , Yu Wenying , Li Tong , Pan Liping , Chen Baorong , Wang Yujia , Zhan Nan , Song Yijun , Yan Keqiang
Published: December 2024

The Simoa platform is recognized as a highly sensitive tool for detecting blood-based biomarkers of Alzheimer’s disease (AD). It is extensively utilized in the diagnosis and identification of AD, with accuracy emerging as a pivotal metric for assessing assay performance, gradually gaining acceptance and application. The primary objective of this study was to assess the diagnostic efficacy of multiple biomarkers in AD using the Simoa platform. The ultimate goal was to identify the optimal diagnostic biomarkers and further investigate their practical application value in the Chinese population. The study comprised two cohorts: cohort I consisted of 151 healthy controls and 90 AD patients, while cohort II was sourced from a Chinese population cohort, encompassing 123 healthy controls and 126 AD patients, utilizing publicly available data. All patients underwent plasma biomarker concentration measurements using the Simoa platform. The specificity, sensitivity, and accuracy of these biomarkers for AD diagnosis were compared to evaluate their diagnostic efficacy. The findings revealed that plasma P-tau217 exhibited excellent performance in differentiating AD from healthy controls, with a sensitivity of 95.0%, specificity of 96.0%, and accuracy of 95.7% for AD diagnosis. Conversely, other indicators, including Aβ42, Aβ42/40, T-tau/Aβ42, and P-tau181, demonstrated some diagnostic efficacy but fell short of meeting the diagnostic criteria. P-tau217 stands out as a highly effective biomarker for the diagnosis of AD, exhibiting extensive clinical application potential in the Chinese population. It presents a promising array of clinical prospects for the Chinese population.
Stakeholder perspectives on the barriers and facilitators to integrating cardiovascular disease and diabetes management at primary care in Kenya
Authors: Wambiya Elvis O. A. , Oguta James Odhiambo , Akparibo Robert , Gillespie Duncan , Otieno Peter , Akoth Catherine , Kamano Jemima , Kibe Peter , Kisaka Yvette , Onyango Elizabeth , Gathecha Gladwell , Dodd Peter J.
Published: December 2024

Integrated care is increasingly recognised as a key strategy for the management of multimorbidity. However, evidence on the factors associated with the implementation of integrated care models in low- and middle-income countries remains limited. We explored how stakeholders perceived integrated care, existing challenges, and recommendations for integrating cardiovascular disease and diabetes management at primary health care (PHC) level in Kenya. We conducted a qualitative study using key informant interviews with 16 key stakeholders involved in healthcare delivery, research, and policy on non-communicable diseases (NCDs) in Kenya between February and March 2024. All interviews were audio recorded and transcribed; and the data analysed both inductively and deductively within NVivo software. The deductive analysis was guided by the Rainbow Model of Integrated Care (RMIC) framework, which combines key dimensions necessary for successful integrated care with key elements of primary care. The RMIC framework dimensions include systems, clinical, organisational, professional, functional, and normative integration. Out of the six RMIC dimensions, stakeholders’ description of integrated care included elements of clinical, systems, and professional integration. Key systems level challenges included disparity between policy and practice, inadequate resource allocation, donor-driven priorities, and limited stakeholder collaboration. Fragmented care delivery was a key organisational challenge. Limited resources for integrated care delivery and inadequate staff numbers and capacity were considered key challenges in the functional and professional dimensions of the RMIC framework. Additional challenges included ‘siloed’ mindset (normative) and limited evidence on effective or cost-effective integrated care models. To address the identified barriers, policy-makers should develop clear and adaptable how-to county-specific guidelines for implementation and evaluation of integrated care at PHC level. There is a need for advocacy and research on models of integrated care at PHC level to guide prioritization and resource allocation in Kenya.
Cross-regulation of amino acid synthesis and catabolic electron transfer in bacteria
Authors: Mogi Hisae , Tomita Keisuke , Hirose Atsumi , Yoshino Erika , Kasai Takuya , Kouzuma Atsushi , Watanabe Kazuya
Published: December 2024

Amino acids are essential for life, serving primarily as the building blocks of proteins. Although the intracellular metabolic fate of amino acids is known, their roles in the global regulation of metabolic pathways are poorly characterized. Here, we investigated the function of amino acids as signaling molecules that modulate the catabolic activity of bacterial cells. Using the model bacteriumShewanella oneidensisMR-1, we showed that methionine activates catabolic processes, including extracellular electron transfer, at submillimolar concentrations. This regulation is mediated by MetR, a transcription factor that regulates methionine biosynthesis. In addition, the MetR-mediated regulation of catabolic electron transfer was observed inAeromonas hydrophila. These findings reveal methionine-induced signaling cascades that cross-regulate amino acid biosynthesis and catabolism in bacteria. Our study highlights a novel physiological role for amino acids, suggesting their involvement in the coordinated regulation of anabolism and catabolism, particularly in bacteria that thrive in nutrient-limited habitats.
TMEM63A, associated with hypomyelinating leukodystrophies, is an evolutionarily conserved regulator of myelination
Authors: Halford Julia , Senatore Amanda J. , Berryman Sage , Muñoz Antonio , Semidey Destinee , Doan Ryan A. , Coombs Adam M. , Noimany Brandon , Emberley Katie , Emery Ben , Monk Kelly R. , Murthy Swetha E.
Published: December 2024

Infantile hypomyelinating leukodystrophy 19 (HLD19) is a rare genetic disorder where patients exhibit reduced myelin in central nervous system (CNS) white matter tracts and present with varied neurological symptoms. The causative geneTMEM63Aencodes a mechanosensitive ion channel whose role in myelination has not been explored. Our study shows that TMEM63A is a major regulator of OL-driven myelination in the CNS. In mouse and zebrafish,Tmem63ainactivation led to early deficits in myelination, recapitulating the HLD19 phenotype. OL-specific conditional mouse knockouts ofTmem63aexhibited transient reductions in myelin, indicating that TMEM63A regulates myelination cell-autonomously. We show that TMEM63A is present at plasma membrane and on lysosomes and modulates myelin/myelin-associated protein production. Intriguingly, HLD19-associatedTMEM63Avariants from patients blocked trafficking to cell membrane. Together, our results reveal an ancient role for TMEM63A in fundamental aspects of myelinationin vivoand highlight two exciting new models for the development of treatments for devastating hypomyelinating leukodystrophies.
Biochemical state in tissue can be detected through ultrasound signal
Authors: Ito Kazuyo , Iijima Yuta , Misumi Tomoki , Hayase Gen , Tamura Kazuki , Ikushima Kenji , Yoshino Daisuke
Published: December 2024

Three-dimensional (3D) cell cultures, such as spheroids, are indispensable models for investigating cellular behaviors and responses under conditions that closely resemble in vivo environments. Conventional imaging techniques, including optical microscopy, are often limited by penetration depth and phototoxicity, complicating the analysis of structural and biochemical changes within dense 3D systems. This study demonstrates the application of ultrasound imaging for the non-invasive evaluation of internal dynamics in cancer spheroids over a 15-day period. Scattering-based acoustic parameters revealed spatial variations in brightness and density, correlating with cellular proliferation, apoptosis, and necrosis. Brightness values in central regions progressively decreased after Day 3, approaching near-zero by Day 15, reflecting necrotic core formation. Artificial inhibition of myosin contractility significantly influenced these patterns, providing insights into biomechanical contributions to spheroid organization. The findings establish ultrasound imaging as a label-free, high-penetration technique capable of addressing critical challenges in 3D culture analysis, offering new opportunities for studying cellular dynamics and therapeutic responses in spheroids and organoid models.