bluuebunny/crossref_metadata_2025 huggingface dataset:
Connecting the dots: key insights on ParB for chromosome segregation from single-molecule studies
Authors: Tišma Miloš , Kaljević Jovana , Gruber Stephan , Le Tung B K , Dekker Cees
Published: December 2023

Bacterial cells require DNA segregation machinery to properly distribute a genome to both daughter cells upon division. The most common system involved in chromosome and plasmid segregation in bacteria is the ParABS system. A core protein of this system - partition protein B (ParB) - regulates chromosome organization and chromosome segregation during the bacterial cell cycle. Over the past decades, research has greatly advanced our knowledge of the ParABS system. However, many intricate details of the mechanism of ParB proteins were only recently uncovered using in vitro single-molecule techniques. These approaches allowed the exploration of ParB proteins in precisely controlled environments, free from the complexities of the cellular milieu. This review covers the early developments of this field but emphasizes recent advances in our knowledge of the mechanistic understanding of ParB proteins as revealed by in vitro single-molecule methods. Furthermore, we provide an outlook on future endeavors in investigating ParB, ParB-like proteins, and their interaction partners.
The Parallel Lives of Liddy Bacroff: Transgender (Pre)History and the Tyranny of the Archive in Twentieth-Century Germany
Authors: Ashton Bodie A
Published: December 2023

Pursued by authorities throughout the 1930s, Heinrich Habitz left behind a significant paper trail of official documentation, arrest warrants and imprisonment records. As Germany slipped further under National Socialist oppression, Habitz’s status as a homosexual man who sold sex marked him as a target of police repression. Even after the end of the war, the Hamburg Prosecutor’s Office attempted to locate and again prosecute him under the infamous §175 ‘sodomy law’. By rights, the study of Habitz should provide insights into the continuities of anti-queer repression between authoritarianism and democracy, but for one key point: ‘Heinrich Habitz’ existed only as a paper identity in official bureaucracy, and the ‘man’ authorities repeatedly persecuted was, in fact, a self-identified woman named ‘Liddy Bacroff’. Through a series of semi-autobiographical writings, alongside official paperwork, Liddy Bacroff presents the value of but also the difficulties facing the (re)construction of queer and, in particular, transgender (pre)histories. In this instance, the historian is not just faced with the problem of how this life, and others like it, should be represented in historiographical terms. We are left also with the question of how this victim of National Socialist barbarity should (or rather, can) be remembered: as the paper identity that provided a succession of carceral authorities with the justification to persecute and ultimately murder a cisgender gay man, or as the lived experience of a woman whose unique self-understanding allowed her to carve out her place in a society that otherwise relegated her to its margins.
Diminished Returns of Higher Parental Education on Cognition for Black Adults in Middle and Later Life
Authors: Reynolds Addam , Greenfield Emily A
Published: December 2023

Objectives

Mounting evidence suggests that the protective effects of one’s own higher socioeconomic status (SES) on health are diminished among minoritized racial/ethnic groups in the United States. This study extends this area of research to childhood SES and cognition in middle and later life, focusing on the protective effects of higher parental education among non-Hispanic Black and White adults.

Methods

Harmonizing data from individuals ages 50 and older across the Health and Retirement Study, the Study of Midlife in the United States, and the National Social Life, Health, and Aging Project, we examine whether associations between parental education and two measures of cognition (episodic memory and global cognition) are moderated by racialized identity (non-Hispanic White or Black) using a random-effects individual participant data meta-analysis approach.

Results

Findings indicated a small, but robust, protective effect of higher parental education on both episodic memory and global cognition among adults identified as White. Among adults identified as Black, there was no association between parental education and either cognitive outcome.

Discussion

This study provides evidence that the protective effect of higher parental education on cognition is not the same across racialized populations, consistent with the theory of Minority Diminished Returns. As scholars continue calls for life-course-oriented efforts to reduce racialized cognitive disparities, it is important to consider early-life risk and protective factors in the context of racism.
CIVIC ENGAGEMENT AMONG OLDER MIGRANTS IN EUROPE: EXAMPLES FROM FOUR EUROPEAN COUNTRIES
Authors: Torres Sandra , Ågård Pernilla , Häkkinen Emilia , Dikmans Bas , Peiro-Milian Inma , Serrat Rodrigo
Published: December 2023

Scholarship on old age social exclusion has identified civic engagement as a research area that deserves empirical attention. Research on older people’s civic engagement has in turn pointed out that experiencing life-course deficits in social capital, and/ or having had a life-course that does not resemble the continuity that social gerontology takes for granted, could put people at risk of becoming civically excluded in old age. These are two of the starting points for the European project known as CIVEX, which aims to study the life-course trajectories of civic engagement in groups of older people that have not yet received enough empirical attention. One of these groups is constituted by those who have migrated to the countries in which they are now based as adults, and whose life-course may therefore be more characterized by discontinuity rather than continuity. Departing from 60 life-course qualitative interviews with older migrants that are based in Sweden, Belgium, Spain and Finland, this presentation will draw attention to the ways in which these older people define civic engagement and the manner in which they describe how their migratory life-courses have impacted their civic engagement. The presentation will argue that there is theorizing potential embedded on the migratory life course, and that this could expand the scholarly imagination on old age social exclusion in general, and civic engagement in particular.
LEVERAGING VIDEO TECHNOLOGY TO DELIVER SOCIAL ENGAGEMENT OPPORTUNITIES FOR CARE PARTNERS OF PERSONS WITH DEMENTIA
Authors: Mois George , Lydon Elizabeth , Jones Sarah , Rao Ruchira , Rogers Wendy , Mudar Raksha , Raj Minakshi
Published: December 2023

Care partners of persons with dementia provide critical support towards meeting the needs of their care recipients. Despite the increasing number of family care partners and their growing responsibilities related to caregiving activities, resources available to support their personal needs are limited (e.g., respite from caring, social engagement). Limited opportunities for social engagement can impact care partners’ sense of social connectivity, and ability to maintain their social network. Video technologies present an opportunity to help facilitate social engagement among care partners from the comfort of their homes, however, this area of research is understudied. The goal of our study was to understand the needs and preferences of care partners related to a video technology-based social engagement program. We conducted two focus groups (N=6) with care partners aged 60 or older with experience supporting an family member with dementia for at least six months. Participants watched a demonstration of a social engagement event and engaged in semi structured focus group interviews. We solicited their insights about their needs and preferences, perspectives on utilizing a video technology platform and their attitudes toward the proposed program. Our findings indicate that they see value in participating and are interested in using video technology as long as the program covers diverse topics of interest, there is flexibility in scheduling, and sufficient technology support is offered. The feedback provided by the focus group participants informed the optimization of the program for implementation in a pragmatic clinical trial.
ASSESSING THE QUALITY OF CHATGPT RESPONSES TO DEMENTIA CAREGIVERS’ QUESTIONS POSTED ON SOCIAL MEDIA
Authors: Aguirre Alyssa , Hilsabeck Robin , Smith Tawny , Wang Zhendong , Zou Ning , Xie Bo , He Daqing
Published: December 2023

ChatGPT, an innovative, dialogue-based large-scale artificial intelligent model that responds to complex natural language inquiries, holds great promise to improve dementia caregivers’ quality of life by providing high-quality responses to meet their information needs. However, limited evidence exists on the quality of ChatGPT responses. This exploratory study aimed to address this gap. We first selected 25 social media posts, verified in our NIH-funded project (R56AG075770) as being representative of dementia caregivers’ needs for information about daily care for memory loss and confusion. We then collected ChatGPT responses in March 2023 and assessed their quality using a 4-item rating scale (1 point for each item; scoring range: 0-4; higher score indicates higher quality). This scale includes (1) Factual: Response contained no inaccurate or false information; (2) Interpretation: Response adequately interpreted the poster’s main need and correctly disregarded non-priority details; (3) Application: Response included both educational information and tangible actions; and (4) Synthesis: Response included follow-up actions (e.g., referrals). Three clinicians, each with 15+ years of experience with dementia caregivers, independently rated the responses. All raters agreed on the ratings for 22 (88%) responses initially; disagreements centered on responses’ comprehensiveness and specificity. After reconciliation, all raters agreed on the ratings: 3 (12%) responses received 3 points and 22 (88%) received 4 points, suggesting high quality. Study limitations included small sample, posts representing only one type of information wanted by caregivers, and potential ceiling effect of the rating scale. In our larger project, we will address these limitations and systematically assess ChatGPT responses.
CROSS-SECTIONAL AND LONGITUDINAL ASSOCIATIONS BETWEEN SLEEP DISTURBANCES, DEPRESSIVE AND ANXIETY SYMPTOMS
Authors: Dong Fanghong , Hodgson Nancy
Published: December 2023

Introduction

Older adults often experience elevated sleep disturbances, depressive and anxiety symptoms. However, the role of sleep disturbances in explaining individual variability in depressive and anxiety symptoms among older adults is poorly understood.

Methods

The sample was derived from the National Social Life, Health, and Aging Project, a nationally representative longitudinal study among American older adults. MCI was defined as Montreal Cognitive Assessment scored less than 23. Subjective insomnia symptoms and objective sleep measures (total sleep time, wake after sleep onset, percentage sleep) obtained from actigraphy were used. Validated measures on depressive and anxiety symptoms were collected both at round 2(N=645) and round 3(N=456). Multiple regressions were conducted to establish cross-sectional and longitudinal associations between sleep disturbances, depressive and anxiety symptoms. Results Cross-sectionally, compared to cognitively intact older adults, severe insomnia symptoms were associated with poorer depressive symptoms(B=0.40, p< 0.01) in older adults with MCI. Severe insomnia symptoms were associated with poorer anxiety symptoms(B=0.13, p< 0.01) in older adults, and no interaction effects were found by MCI groups. Longitudinally, insomnia symptoms at round 2 were associated with poorer depressive symptoms and poorer anxiety symptoms in older adults at round 3, but no interaction effects were found by MCI groups. No significant relationships were found between objective sleep disturbances and depressive/anxiety symptoms both cross-sectionally and longitudinally.

Conclusions

The findings provide further insight into insomnia symptoms that may be associated with increased risks for developmental depressive and anxiety symptoms. These data suggest that targeting insomnia treatment may confer long-term mental health benefits.
ATTITUDES TOWARD AGING: EDUCATIONAL INTERVENTIONS FOR MEDICAL STUDENTS
Authors: Keefe Bronwyn
Published: December 2023

Ageism is stereotyping, prejudice, and discrimination based on a person’s age, and in healthcare includes the implicit biases of providers. Like many other forms of prejudice, ageism contributes to health disparities and differences in health outcomes. The implicit and explicit biases of clinicians can impact clinical practice, leading to medical decisions based on stereotypes and prejudices. There is inconclusive evidence on undergraduate and graduate medical learners’ attitudes towards aging. Some studies have found that learners hold negative associations with aging, while others have found a mix of positive and negative views toward caring for older adults. Educational interventions and intergenerational contact are two important strategies for increasing awareness and reducing ageism. Hence, it is important to discuss ageism with students and create programs and curricula to combat ageism to ensure the best care is provided to all of our patients. This session will present results from an interactive online module designed for 4th-year medical students that explores ageism and bias. Students completed the Expectations Regarding Aging Survey pre-post. Preliminary results at pre-test show that 70% believe that as they get older, they will be more forgetful and 75% believe the human body is like a car: when it’s old, it gets worn out. Healthcare professionals need to understand the existing gaps in health equity that our older adult patients experience that contribute to ageist attitudes. By drawing attention to professionals’ implicit and explicit biases towards aging throughout medical training, we are able to help older adults receive better care.
HIGH-INTENSITY INTERVAL TRAINING, SLEEP, AND COGNITION IN OLDER ADULTS: A SYSTEMATIC REVIEW
Authors: Weiss Carleara , Lorenz Rebecca
Published: December 2023

Sleep disturbances have been linked to cognitive and physical decline in older adults. High intensity interval training (HIIT) may resynchronize disrupted sleep-wake cycles, improve sleep quality, and potentially delay detrimental impacts of aging on cognition and physical performance. Comprehensive reviews about the impact of HIIT on cognitive and physical decline in older adults are lacking. A systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) approach to evaluate the impact of HIIT upon sleep and cognition. PubMed, Scopus, and Web of Science were searched for articles. Six publications representing four randomized controlled trials met the inclusion criteria. Data from intervention and control groups included 158 participants, predominately female (70.4%) with median age of 69.5 years. Exercise modalities varied across studies; however, duration of 12-weeks was consistent. HIIT reduced objectively measured sleep onset latency and lowered wake after sleep onset compared to no activity and regular physical activity. However, changes in sleep quality with HIIT did not differ from those achieved with stretching exercise and moderate-intensity physical activity. In addition, only one study investigated the impact of HIIT on both sleep and cognition, indicating improvement in cognitive performance and memory but no significant changes in sleep efficiency. Despite the potential for HIIT to improve sleep outcomes, memory, and cognition, more studies are warranted, particularly those that include diverse populations and larger sample sizes, prior to forming recommendations for use in clinical settings and communities.
Caregiver Accounts of Lucid Episodes in Persons With Advanced Dementia
Authors: Karlawish Jason , Peterson Andrew , Kleid Melanie , Harkins Kristin , Largent Emily A , Stites Shana D , Coykendall Cameron , Clapp Justin T
Published: December 2023

Background and Objectives

Paradoxical lucidity is defined as an instance of unexpected lucid behavior in a person who is assumed to be noncommunicative due to a progressive and pathophysiologic dementing process. To inform studies of the prevalence, characteristics, and impact of these behaviors, this interview study examined caregivers’ experiences of witnessing paradoxical lucidity.

Research Design and Methods

Participants were family caregivers of persons living with advanced dementia caused by a neurodegenerative disease producing significant impairments in communication. Semistructured interviews elicited the caregivers’ experiences of plausible lucid episodes. Data analysis used a thematic analysis approach.

Results

Most caregivers reported at least 1 episode of lucidity. Episodes were typically brief. Most involved utterances, but nonverbal behaviors were also common. The mental capacities associated with these behaviors included recognition, awareness of surroundings, recognizing others’ emotions, and goal-directed behavior. Most caregivers’ reactions were positive. Episodes did not lead to changes in major medical decisions but instead to efforts to either modify or reinforce daily caregiving efforts.

Discussion and Implications

Episodes of lucidity were common, a finding seen in other studies. If prevalence studies confirm this, the qualifier “paradoxical” should be eliminated. The caregivers’ familiarity with the person living with dementia allowed them to attribute meaning to subtle behaviors that might not otherwise be detected or considered lucid. Clinicians who care for persons with advanced-stage dementia should routinely ask caregivers about episodes of lucid communication and their emotional reactions.
Seismotectonic aspects of the Ms 7.3 1948 October 5 Aşgabat (Ashgabat) earthquake, Türkmenistan: right-lateral rupture across multiple fault segments, and continuing urban hazard
Authors: Marshall N , Ou Q , Begenjev G , Bergman E , Bezmenov Y , Dodds N , Gruetzner C , Hudson T , Pierce I , Mirzin R , Rhodes E , Walker R T , Wordsworth P
Published: December 2023

The Ms 7.3 1948 Aşgabat earthquake was one of the most devastating earthquakes of the 20th century, yet little is known about its location, style and causative fault. In this study, we bring together new seismic and geomorphic observations with previously published descriptions of surface rupture and damage distributions to determine the likely source of the earthquake. We determine the epicentre and focal mechanism of this earthquake from digitized historical seismograms and the relocation of regional seismicity to show that the earthquake most likely nucleated close to the city of Aşgabat. The earthquake ruptured a right-lateral strike-slip fault to the southeast of the city, which has a clear long-term expression in the landscape, and also likely reactivated a subparallel concealed thrust along the Gyaursdag anticline east of the city. The earthquake potentially also ruptured a right-lateral segment northwest of Aşgabat, which does not have an identifiable expression in the landscape. Using high-resolution satellite imagery and digital elevation models we investigate the geomorphology of active faulting around Aşgabat and adjacent parts of the Köpetdag (Kopeh Dagh) mountain range front, showing that there are significant strike-slip and oblique strike-slip segments adjacent to the city that apparently did not rupture in 1948, and yet show clear geomorphic expression and potential right-lateral displacement of Parthian-era (∼2000 yr) and post-Sassanian era (∼1500 yr) archaeological remains. Luminescence dating of displaced fluvial terraces west of Aşgabat yields a vertical displacement rate of 0.6 mm yr−1, though the strike-slip rate remains undetermined.
The impact of COVID-19 on health literacy among Chinese rural residents
Authors: Du Yawen , Wang Xiaokang , Cheng Luyue , Wang Yao , Bu Xiaoou , Wang Yanjiao , Wang Pei
Published: December 2023

The outbreak of the Coronavirus disease 2019 (COVID-19) pandemic is an opportunity to improve the health literacy of rural residents. This study aims to explore the levels of health literacy among rural residents during the COVID-19 pandemic and investigate the effects of COVID-19-related variables on the health literacy of rural residents. A total of 882 rural residents aged 15–69 years in Shaanxi province participated in this study and completed the questionnaires about health literacy and COVID-19-related variables. These results showed that although overall health literacy and three aspects of health literacy among rural residents were low and lower than those of Chinese national residents, there was no significant difference in health literacy about safety and emergency between rural residents and Chinese national residents. Additionally, COVID-19-related variables significantly predicted health literacy (i.e. scientific health, safety and emergency and infectious disease prevention). Importantly, unlike other types of health literacy, the effect of a COVID-19-related variable (i.e. the frequency of exposure to news about the COVID-19 pandemic) on infectious disease prevention was only slightly smaller than the effect of high education on infectious disease prevention, and low education was no longer a significant predictor of infectious disease prevention. To conclude, rural residents in Shaanxi province have low health literacy. Education is a major factor affecting the health literacy of rural residents, and the frequency of exposure to news about the pandemic may compensate for the negative impact of low education on health literacy.
SUMMIT-FA: a new resource for improved transcriptome imputation using functional annotations
Authors: Melton Hunter J , Zhang Zichen , Wu Chong
Published: December 2023

Transcriptome-wide association studies (TWAS) integrate gene expression prediction models and genome-wide association studies (GWAS) to identify gene-trait associations. The power of TWAS is determined by the sample size of GWAS and the accuracy of the expression prediction model. Here, we present a new method, the Summary-level Unified Method for Modeling Integrated Transcriptome using Functional Annotations (SUMMIT-FA), which improves gene expression prediction accuracy by leveraging functional annotation resources and a large expression quantitative trait loci (eQTL) summary-level dataset. We build gene expression prediction models in whole blood using SUMMIT-FA with the comprehensive functional database MACIE and eQTL summary-level data from the eQTLGen consortium. We apply these models to GWAS for 24 complex traits and show that SUMMIT-FA identifies significantly more gene-trait associations and improves predictive power for identifying “silver standard” genes compared to several benchmark methods. We further conduct a simulation study to demonstrate the effectiveness of SUMMIT-FA.
Overadjustment bias in systematic reviews and meta-analyses of socio-economic inequalities in health: a meta-research scoping review
Authors: van Zwieten Anita , Dai Jiahui , Blyth Fiona M , Wong Germaine , Khalatbari-Soltani Saman
Published: December 2023

Background

Overadjustment bias occurs when researchers adjust for an explanatory variable on the causal pathway from exposure to outcome, which leads to biased estimates of the causal effect of the exposure. This meta-research review aimed to examine how previous systematic reviews and meta-analyses of socio-economic inequalities in health have managed overadjustment bias.

Methods

We searched Medline and Embase until 16 April 2021 for systematic reviews and meta-analyses of observational studies on associations between individual-level socio-economic position and health outcomes in any population. A set of criteria were developed to examine methodological approaches to overadjustment bias adopted by included reviews (rated Yes/No/Somewhat/Unclear).

Results

Eighty-four reviews were eligible (47 systematic reviews, 37 meta-analyses). Regarding approaches to overadjustment, whereas 73% of the 84 reviews were rated as Yes for clearly defining exposures and outcomes, all other approaches were rated as Yes for <55% of reviews; for instance, 5% clearly defined confounders and mediators, 2% constructed causal diagrams and 35% reported adjusted variables for included studies. Whereas only 2% included overadjustment in risk of bias assessment, 54% included confounding. Of the 37 meta-analyses, 16% conducted sensitivity analyses related to overadjustment.

Conclusions

Our findings suggest that overadjustment bias has received insufficient consideration in systematic reviews and meta-analyses of socio-economic inequalities in health. This is a critical issue given that overadjustment bias is likely to result in biased estimates of health inequalities and accurate estimates are needed to inform public health interventions. There is a need to highlight overadjustment bias in review guidelines.
Immunologic and Virologic Parameters Associated With Human Immunodeficiency Virus (HIV) DNA Reservoir Size in People With HIV Receiving Antiretroviral Therapy
Authors: Blazkova Jana , Whitehead Emily J , Schneck Rachel , Shi Victoria , Justement J Shawn , Rai M Ali , Kennedy Brooke D , Manning Maegan R , Praiss Lauren , Gittens Kathleen , Wender Paul A , Oguz Cihan , Lack Justin , Moir Susan , Chun Tae-Wook
Published: December 2023

Background

A better understanding of the dynamics of human immunodeficiency virus (HIV) reservoirs in CD4+ T cells of people with HIV (PWH) receiving antiretroviral therapy (ART) is crucial for developing therapies to eradicate the virus.

Methods

We conducted a study involving 28 aviremic PWH receiving ART with high and low levels of HIV DNA. We analyzed immunologic and virologic parameters and their association with the HIV reservoir size.

Results

The frequency of CD4+ T cells carrying HIV DNA was associated with higher pre-ART plasma viremia, lower pre-ART CD4+ T-cell counts, and lower pre-ART CD4/CD8 ratios. During ART, the High group maintained elevated levels of intact HIV proviral DNA, cell-associated HIV RNA, and inducible virion-associated HIV RNA. HIV sequence analysis showed no evidence for preferential accumulation of defective proviruses nor higher frequencies of clonal expansion in the High versus Low group. Phenotypic and functional T-cell analyses did not show enhanced immune-mediated virologic control in the Low versus High group. Of considerable interest, pre-ART innate immunity was significantly higher in the Low versus High group.

Conclusions

Our data suggest that innate immunity at the time of ART initiation may play an important role in modulating the dynamics and persistence of viral reservoirs in PWH.
Epidemiology of the 2022 Mpox Outbreak in the US Veterans Health Administration
Authors: Lucero-Obusan Cynthia , Oda Gina , Schirmer Patricia , Edson Connor , Trevino Christina , Elbeik Tarek , Holodniy Mark
Published: December 2023

Background

In May 2022, mpox cases were reported in nonendemic countries, including the United States. We examined mpox infections in the Veterans Health Administration (VHA).

Methods

Mpox diagnostic and whole genome sequencing (WGS) results, demographics, risk factors, hospitalizations, exposures, deaths, and pharmacy and immunization data were obtained from VHA data sources (23 May 2022–31 May 2023).

Results

Of 1144 Veterans tested, 251 (21.9%) were presumptive positive for nonvariola orthopoxvirus (NVO) or confirmed positive for NVO and Monkeypox virus (MPXV). Incidence rate was 7.5 per 100 000 Veterans in care, with the highest rate observed in Veterans aged 25–34 years (13.83 cases per 100 000). Higher odds of NVO or NVO/MPXV positivity was associated with male sex; non-Hispanic Black race/ethnicity; syphilis or human immunodeficiency virus (HIV) positivity; or genital/rectal sample site, whereas older age and vaccination with JYNNEOS or vaccinia (smallpox) had lower odds. Among 209 with confirmatory testing, 90.4% reported intimate contact and/or an epidemiological link, 84.5% were men who have sex with men (MSM), 24.2% received tecovirimat, and 8.1% were hospitalized with 1 death. Eighty-six sequenced samples had evaluable WGS results. All were clade IIb, representing 10 different lineages from 20 states and the District of Columbia.

Conclusions

Mpox affected younger, MSM, non-Hispanic Black, and HIV/syphilis-positive men among US Veterans. Viral diversity was noted across geographic regions. At-risk Veterans would benefit from vaccination and risk reduction strategies for mpox and other sexually transmitted infections.
Bedaquiline for treatment of non-tuberculous mycobacteria (NTM): a systematic review and meta-analysis
Authors: Omar Shatha , Whitfield Michael G , Nolan Margaret B , Ngom Justice T , Ismail Nabila , Warren Rob M , Klopper Marisa
Published: December 2023

Background

Non-tuberculous mycobacteria (NTM) infections are increasing in incidence and associated mortality. NTM are naturally resistant to a variety of antibiotics, complicating treatment. We conducted a literature assessment on the efficacy of bedaquiline in treating NTM species in vitro and in vivo (animal models and humans); meta-analyses were performed where possible.

Method

Four databases were searched using specific terms. Publications were included according to predefined criteria. Bedaquiline’s impact on NTM in vitro, MICs and epidemiological cut-off (ECOFF) values were evaluated. A meta-analysis of bedaquiline efficacy against NTM infections in animal models was performed. Culture conversion, cure and/or relapse-free cure were used to evaluate the efficacy of bedaquiline in treating NTM infection in humans.

Results

Fifty studies met the inclusion criteria: 33 assessed bedaquiline’s impact on NTM in vitro, 9 in animal models and 8 in humans. Three studies assessed bedaquiline’s efficacy both in vitro and in vivo. Due to data paucity, an ECOFF value of 0.5 mg/mL was estimated for Mycobacterium abscessus only. Meta-analysis of animal studies showed a 1.86× reduction in bacterial load in bedaquiline-treated versus no treatment within 30 days. In humans, bedaquiline-including regimens were effective in treating NTM extrapulmonary infection but not pulmonary infection.

Conclusions

Bedaquiline demonstrated strong antibacterial activity against various NTM species and is a promising drug to treat NTM infections. However, data on the genomic mutations associated with bedaquiline resistance were scarce, preventing statistical analyses for most mutations and NTM species. Further studies are urgently needed to better inform treatment strategies.
A network suspected infectious disease model for the development of syphilis transmission from 2015 to 2021 in Hubei province, China
Authors: Zhang Yue , Wang Kai , Zhu Junjie , Wu Jinyi
Published: December 2023

Aims

Understanding the transmission mode of syphilis is essential to prevent and predict its future prevalence and to develop effective control measures. This study aimed to develop a network suspected infectious disease model to simulate the syphilis transmission.

Methods and results

The number of syphilis cases in Wuhan’s Fourth Hospital, Hubei province, China, from October 2015 to July 2021 was collected. The simulation was carried out by interpersonal network-SI (suspected infectious) model based on temporal exponential family random graph models. Late latent syphilis and tertiary syphilis are predicted by December 2025. The validity of simulated value and real data was tested, including determination coefficient (R2), root means square error (RMSE), and means relative error (MRE). Moreover, we developed an online app that can more easily predict the number of syphilis infections in different scenarios by setting different parameters. Results showed that R2, RMSE, and MRE were 0.995, 36.19, and 6.31, respectively. Speed from latent infection to primary syphilis, primary syphilis to secondary syphilis, and susceptible group to latent infection decreased rapidly. The speed of transformation from secondary syphilis to early incubation period and early latent to late latent experienced a process from increase to decreased. Late latent to tertiary syphilis patients increased steadily. The number of late latent patients, early latent, invisible infection, primary syphilis, and secondary syphilis all increased at first and turn to decreased. However, tertiary syphilis continuously kept rising in the whole process. To better make use of the transmission model, an online application was developed (https://alanwu.shinyapps.io/MD-shiny/).

Conclusions

Based on the simulation that late latent and tertiary syphilis were steadily increasing, the prevention and treatment for syphilis were imperative.
Nudges Increase Choosing but Decrease Consuming: Longitudinal Studies of the Decoy, Default, and Compromise Effects
Authors: Polman Evan , Maglio Sam J
Published: December 2023

Research in marketing, psychology, economics, and decision making has long examined what people choose, when people choose, and why people choose. But almost no research has examined how long people consume their choices. Here, we examined an asymmetry between choosing an option and consuming it. Under the aegis of nudges, we conducted two randomized longitudinal experiments on how long people consumed a choice that was incentivized vis-à-vis a decoy effect, default effect, and compromise effect. We found that these nudges influenced choosing and consuming in opposite directions: Participants were more likely to choose the nudged option; however, they consumed it less compared to participants who chose an identical non-nudged option. Our research thus demonstrates that nudges could lead people to consume a nudged option less after choosing it, illuminating the potential for future research to examine the unexplored area of longitudinal, post-acquisition, post-nudge effects.
Is perioperative chemotherapy effective in patients with localized myxoid liposarcoma?
Authors: Masunaga Tomoya , Tsukamoto Shinji , Nitta Yuji , Honoki Kanya , Fujii Hiromasa , Akahane Manabu , Takeda Masayuki , Tanaka Yasuhito , Mavrogenis Andreas F , Errani Costantino , Kawai Akira
Published: December 2023

Background

This study aimed to compare the local recurrence, distant metastasis and disease-specific survival rates of patients with localized myxoid liposarcoma in the surgery and adjuvant chemotherapy group versus the surgery alone group.

Methods

A total of 456 patients in the Japanese National Bone and Soft Tissue Tumour Registry database who had localized myxoid liposarcoma and underwent surgery and adjuvant chemotherapy or surgery alone between 2001 and 2019 were included in this retrospective study. The study adjusted for background differences between patients who underwent surgery and adjuvant chemotherapy (n = 228) or surgery alone (n = 228) using propensity score matching.

Results

Univariate analysis showed no significant difference in local recurrence rate between the two groups (5-year local recurrence-free survival: 98.6% [95% confidence interval: 95.9–99.6] vs. 94.0% [95% confidence interval: 89.7–96.6], P = 0.052). Univariate analysis showed no difference in the incidence of distant metastases between the two groups (5-year distant metastasis-free survival: 80.5% [95% confidence interval: 73.9–85.8] vs. 75.1% [95% confidence interval: 67.7–81.2], P = 0.508). Univariate analysis showed no difference in disease-specific survival between the two groups (5-year disease-specific survival: 92.6% [95% confidence interval: 86.1–96.2] vs. 93.2% [95% confidence interval: 87.6–96.4], P = 0.804). In the high-risk group (n = 203) with high-grade tumours and tumour size ≥10 cm, there were no significant differences in the local recurrence, distant metastasis and disease-specific survival rates between the surgery and adjuvant chemotherapy group and the surgery alone group.

Conclusion

The effect of adjuvant chemotherapy on localized myxoid liposarcoma appears to be limited.
Measuring cosmic bulk flow with Pantheon catalogue in perturbed f(R) gravity
Authors: Yarahmadi M , Salehi A , Farajollahi H
Published: December 2023

This study investigates the cosmic bulk flow through an analysis of luminosity distance variations in a perturbed Friedmann universe governed by f(R) gravity. The Hubble parameter, derived from perturbed Friedmann equations capturing intrinsic temporal fluctuations, is crucial. Redshift tomography is used to analyse observational data from the Pantheon catalogue from 0.015 to z < 2.3. Our objective is to constrain the cosmic bulk flow’s direction and magnitude within this redshift range. At low redshifts (z < 0.06), the predominant bulk flow aligns with the dominating supercluster in the corresponding range, maintaining a relatively constant magnitude, consistent with Lambda cold dark matter (ΛCDM) model predictions. A shift towards (l, b) = (290 ± 21, 15 ± 20) with $v_{\mathrm{bulk}} = 774 \pm 83 \, \mathrm{km\, s}^{-1}$ occurs between 0.06 < z < 0.1, coinciding with the cosmic microwave background dipole. For 0.1 < z < 0.2, the bulk flow shifts to (l, b) = (270 ± 21, 25 ± 20) with $v_{\mathrm{bulk}} = 903 \pm 102 \, \mathrm{km\, s}^{-1}$, supporting Kashlinsky et al.’s result. Beyond z > 0.2, the bulk flow’s magnitude exceeds $1000 \, \mathrm{km\, s}^{-1}$, deviating from ΛCDM model expectations. Our findings suggest that matter density oscillations under f(R) gravity exhibit ΛCDM model properties at low redshifts. However, the microwave background anisotropy shows noticeable fluctuations at higher redshifts, validating prior findings of strong cosmic bulk flows at these scales.
Inferring Viral Transmission Time from Phylogenies for Known Transmission Pairs
Authors: Goldberg Emma E , Lundgren Erik J , Romero-Severson Ethan O , Leitner Thomas
Published: December 2023

When the time of an HIV transmission event is unknown, methods to identify it from virus genetic data can reveal the circumstances that enable transmission. We developed a single-parameter Markov model to infer transmission time from an HIV phylogeny constructed of multiple virus sequences from people in a transmission pair. Our method finds the statistical support for transmission occurring in different possible time slices. We compared our time-slice model results to previously described methods: a tree-based logical transmission interval, a simple parsimony-like rules-based method, and a more complex coalescent model. Across simulations with multiple transmitted lineages, different transmission times relative to the source’s infection, and different sampling times relative to transmission, we found that overall our time-slice model provided accurate and narrower estimates of the time of transmission. We also identified situations when transmission time or direction was difficult to estimate by any method, particularly when transmission occurred long after the source was infected and when sampling occurred long after transmission. Applying our model to real HIV transmission pairs showed some agreement with facts known from the case investigations. We also found, however, that uncertainty on the inferred transmission time was driven more by uncertainty from time calibration of the phylogeny than from the model inference itself. Encouragingly, comparable performance of the Markov time-slice model and the coalescent model—which make use of different information within a tree—suggests that a new method remains to be described that will make full use of the topology and node times for improved transmission time inference.
Global, regional and national burden of CKD in children and adolescents from 1990 to 2019
Authors: Zhao Wen-Man , Li Xun-Liang , Shi Rui , Zhu Yuyu , Wang Zhi-Juan , Wang Xue-Rong , Pan Hai-Feng , Wang De-Guang
Published: December 2023

Background

Chronic kidney disease(CKD) is one of the most prevalent non-communicable health concerns in children and adolescents worldwide; however, data on its incidence, prevalence, disability-adjusted life years (DALYs) and trends in the population are limited. We aimed to assess the global, regional and national trends in CKD burden in children and adolescents.

Methods

In this trend analysis based on the 2019 Global Diseases, Injuries, and Risk Factors Study, CKD incidence, prevalence and DALYs rates per 100 000 population for children and adolescents were reported at the global, regional and national levels, as well as the average annual percentage change (AAPC). These global trends were analyzed by age, sex, region and socio-demographic index (SDI).

Results

Globally, the overall incidence of CKD (all stages including kidney replacement therapy) in children and adolescents showed an increasing trend [AAPC 0.44 (95% confidence interval 0.36–0.52)] between 1990 and 2019. Similarly, the overall prevalence of CKD also showed an upward trend [AAPC 0.46 (0.42–0.51)]. However, the DALYs of CKD showed a continuous decreasing trend [AAPC –1.18 (–1.37 to –0.99)]. The population aged 15–19 years had the largest CKD incidence increase during this period. The largest increase in age-standardized incidence rate (ASIR) was in middle SDI countries [AAPC 0.56 (0.45–0.67)]. The relationship between the ASIR and SDI showed an inverse U-shaped correlation while the relationship between the age-standardized DALYs rate (ASDR) and SDI showed an inverse trend with SDI. Among adolescents (15–19 years), the ASIR continued to increase for five causes of CKD, owing to type 2 diabetes mellitus and hypertension. Most of the disease burden was concentrated in countries with a lower SDI. Andean Latin America and Central Latin America showed the largest increases in CKD ASIR between 1990 and 2019.

Conclusion

The burden of CKD in children and adolescents has increased worldwide, especially in regions and countries with a lower SDI.
Characterization of chloroplast ribulose-5-phosphate-3-epimerase from the microalga Chlamydomonas reinhardtii
Authors: Meloni Maria , Fanti Silvia , Tedesco Daniele , Gurrieri Libero , Trost Paolo , Fermani Simona , Lemaire Stéphane D , Zaffagnini Mirko , Henri Julien
Published: December 2023

Carbon fixation relies on Rubisco and 10 additional enzymes in the Calvin–Benson–Bassham cycle. Epimerization of xylulose-5-phosphate (Xu5P) into ribulose-5-phosphate (Ru5P) contributes to the regeneration of ribulose-1,5-bisphosphate, the substrate of Rubisco. Ribulose-5-phosphate-3-epimerase (RPE, EC 5.1.3.1) catalyzes the formation of Ru5P, but it can also operate in the pentose-phosphate pathway by catalyzing the reverse reaction. Here, we describe the structural and biochemical properties of the recombinant RPE isoform 1 from Chlamydomonas (Chlamydomonas reinhardtii) (CrRPE1). The enzyme is a homo-hexamer that contains a zinc ion in the active site and exposes a catalytic pocket on the top of an α8β8 triose isomerase-type barrel as observed in structurally solved RPE isoforms from both plant and non-plant sources. By optimizing and developing enzyme assays to monitor the reversible epimerization of Ru5P to Xu5P and vice versa, we determined the catalytic parameters that differ from those of other plant paralogs. Despite being identified as a putative target of multiple thiol-based redox modifications, CrRPE1 activity is not affected by both reductive and oxidative treatments, indicating that enzyme catalysis is insensitive to possible redox alterations of cysteine residues. We mapped phosphorylation sites on the crystal structure, and the specific location at the entrance of the catalytic cleft supports a phosphorylation-based regulatory mechanism. This work provides an accurate description of the structural features of CrRPE1 and an in-depth examination of its catalytic and regulatory properties highlighting the physiological relevance of this enzyme in the context of photosynthetic carbon fixation.
Electroacupuncture with intermittent wave stimulation as rehabilitation approach for chronic Bell’s palsy: a randomized controlled trial
Authors: Li Tian , Wang Siyao , Yin Xuan , Zhang Shen , Yang Zhen , Wu Junyi , Huang Zouqin
Published: December 2023

Purpose

To evaluate the effectiveness and safety of electroacupuncture (EA) using intermittent wave stimulation in enhancing facial symmetry and nerve function in chronic Bell’s palsy patients.

Methods

A 6-week assessor-blinded, randomized trial followed by an 18-week observational period was conducted. Sixty individuals with chronic Bell's palsy, showing no signs of recovery after 12 months, were equally divided to receive either 18 sessions of EA using intermittent wave stimulation or Transcutaneous Electrical Stimulation (TES), administered thrice weekly over 6 weeks. The primary outcome measure was the change in the total facial nerve index (TFNI) score from baseline to Week 6, with secondary outcomes including TFNI scores at Weeks 12 and 24, as well as the change in Sunnybrook Facial Grading System (SFG) score from baseline to Week 6, and SFG scores at Weeks 12 and 24.

Results

The EA group showed a significant improvement, with a mean total facial nerve index score increase of 24.35 (4.77) by Week 6 compared with 14.21 (5.12) in the Transcutaneous Electrical Stimulation group (P<.001). This superiority persisted during the 24-week follow-up. While no significant difference was observed in the Sunnybrook Facial Grading System score change from baseline to Week 6, variations were noted at Weeks 12 and 24. No major adverse effects were reported.

Conclusion

EA with intermittent wave stimulation notably enhanced facial symmetry in chronic Bell’s palsy patients over Transcutaneous Electrical Stimulation by Week 6, maintaining this edge throughout the follow-up.
Treatment experiences with focus on IL-6R inhibition in patients with VEXAS syndrome and a case of remission with azacytidine treatment
Authors: Johansen Morten M , El Fassi Daniel , Nielsen Christoffer T H , Krintel Sophine B , Graudal Niels , Hansen Jakob Werner
Published: December 2023

Objectives

The aim of the study was to evaluate the treatment response to interleukin-6-receptor inhibition (IL-6Ri), primarily tocilizumab, in patients with VEXAS syndrome.

Methods

Data were obtained from review of hospital-based clinical records and included symptoms, laboratory data, transfusion history, pathology reports, imaging and treatment.

Results

Fifteen patients were treated with tocilizumab intravenously. Two patients changed treatment to subcutaneous sarilumab. Three discontinued treatment due to treatment failure. Of the 10 patients with treatment-response and prednisone use prior to IL-6Ri, one was tapered off prednisone, one used it intermittently, and seven patients could be reduced to 10 mg or less daily. Three patients exhibited a marked decrease in UBA1-levels during IL-6Ri which corresponded with symptom control and normalization of haemoglobin levels. However, in most a progressive marrow failure occurred as indicated by decreasing platelet levels, increasing MCV, and for some, declining haemoglobin levels and transfusion dependence in spite of control of the inflammatory symptoms and low C-reactive protein levels. One patient became refractory to both tocilizumab and sarilumab, and had previously failed conventional DMARDs, JAK-inhibition, TNFa-inhibition, and interleukin-1R-inhibiton. Treatment with nine cycles of azacytidine resulted in complete symptom remission, discontinuation of prednisone, normalization of biochemical parameters and undetectable UBA1 mutation levels, which has now lasted for 10 months since cessation of azacytidine.

Conclusion

IL-6Ri induces control of inflammatory symptoms and allows decreased prednisone usage in a large subset of VEXAS patients. However, most experience progressive bone marrow failure during IL-6Ri. Azacytidine could be a promising treatment strategy and warrants further investigation.