bluuebunny/crossref_metadata_2025 huggingface dataset:
Interstate Human Trafficking Youth Survivors: Clinical and Forensic Considerations
Authors: Kar Jeena , Rahmani Mariam , Jo Youngshuk , Pumariega Andres
Published: March 2024

Child trafficking continues to be underreported due to multiple factors including differences in state laws, lack of a centralized database, and overall under-recognition. The care of such youth often entails forensic as well as significant clinical considerations given their traumatization. We report on our experience with a 14-year-old female who presented to an Emergency Department (ED), brought in by law enforcement after her parents filed a missing person report in a different state, with concerns about human trafficking; the patient expressed suicidal ideation in our ED. The patient was placed under involuntary hold, after obtaining collateral from the her parents. During the hospitalization, legal challenges presented barriers to safe discharge and a need to collaborate for providing care between disciplines and across state lines. At the same time, through validation and support in the therapeutic milieu of an adolescent psychiatric unit, she was able to understand that she had just survived sexual assault and began to process the impact of it. Although no medication changes were made, the patient began to develop insight at the time of discharge to the Child Protective Team.
Methods for Extended Sleep EEG Recording in Autism: A Sleep Deprivation–Based, Natural Sleep–Recording Protocol and Feasibility Study
Authors: Kaku Sowmyashree Mayur , James Manjula William , Elizabeth VT  , Mysore Ashok , Sarma Gosala RK
Published: March 2024

Background:

Electroencephalography (EEG) has been used to research individuals with autism spectrum disorder (ASD). Such individuals are known to have a higher prevalence of EEG abnormalities and seizures. Extended EEG recordings, particularly those including sleep, are known to significantly improve the yield of these abnormalities. However, obtaining extended sleep recordings without sedation in autistic individuals is challenging. This study explores practical and feasible protocols for recording EEG in awake and sleep states in children and adolescents with ASD.

Methods:

Extended EEG recordings using detailed sleep deprivation and recording protocol were done.

Results:

132 children and adolescents with ASD and sleep deprivation completed extended EEG recording in natural sleep. Only nine autistic children required melatonin along with sleep deprivation.

Conclusions:

Extended EEG recording can be achieved by following a rigorous sleep deprivation protocol that is customized, along with providing an autism-friendly recording room environment. This is important in identifying and increasing the yield of epileptiform discharges. We also propose technical guidelines and considerations for EEG recording in children and adolescents with ASD.
Translation and Psychometric Evaluation of the Perceived Stress Scale–Child
Authors: Tavakkoli Nafise , Masoodi Armon , Khavari Sayd Abdolah , Farnia Samaneh
Published: March 2024

Background:

Precise assessment of chronic stress is a key prerequisite to effective stress management among children. Nonetheless, there are limited valid and reliable instruments for this purpose. This study was conducted to translate the Perceived Stress Scale–Child (PSSC) into Persian and evaluate its psychometric properties.

Methods:

This methodological study was conducted in 2020. The 14-item PSSC was translated into Persian using the forward–backward translation method. Item impact score was calculated for face validity assessment, and content validity ratio (CVR) and content validity index (CVI) were calculated for content validity assessment. Construct validity was also assessed using exploratory and confirmatory factor analyses. For factor analysis, 140 children were purposefully selected from two specialty psychology clinics in Sari, Iran, to complete PSSC. Reliability of PSSC was evaluated through the internal consistency and composite reliability methods. SPSS (v. 26.0) and the SmartPLS software were used for data analysis at a significance level of less than .05.

Results:

Most participants were male (50.7%) and aged 10–12 years (62.2%). The mean of participants’ age was 9.56 ± 1.68 years. The impact score, CVR, and CVI values of all PSSC items were more than 1.5, 0.42, and 0.79, respectively. Exploratory factor analysis indicated that the Persian PSSC had two factors that explained 67.24% of its total variance. Confirmatory factor analysis also confirmed this factor structure. Cronbach’s alpha values of PSSC and its two factors were 0.916, 0.840, and 0.824, respectively.

Conclusion:

The Persian PSSC has acceptable validity and reliability and can be used for stress assessment and screening among children.
X-linked Adrenoleukodystrophy Masquerading as Mood Disorder in an Adolescent Boy
Authors: Chauhan Nidhi , Adarsh Himani , Bhagwat Chandana , Saini Arushi Gahlot
Published: March 2024

X-linked adrenoleukodystrophy (ALD) is a demyelinating neurodegenerative disease of the brain with neurological manifestations in the majority of cases. However, a small proportion of cases also present solely with psychiatric symptoms. Here, we discuss the case of a 13-year-old boy presenting with mood symptoms, behavioral changes, and cognitive impairment. A neurodegenerative disease was suspected based on the atypical findings in history and abnormal neurological examination. Neuroimaging and pathogenic variations in the ABCD1 gene confirmed the diagnosis. Thorough history and detailed examination remain the cornerstone in arriving at the right diagnosis, aided by need-based advanced investigations.
Prevalence of Mental Health Problems and Substance Use Among School-going Adolescents of Tribal Ethnicity: A Preliminary Study from North-East India
Authors: Ali Arif , Gujar Nilesh Maruti , Deuri Sonia P. , Deuri Sailendra K.
Published: March 2024

Background:

Mental health disparities are more pronounced among marginalized and ethnic communities due to a multitude of societal and environmental factors. These include family dynamics, cultural influences, geographic location, ethnicity, and socioeconomic status, all of which contribute to increased vulnerability to mental health issues within these populations.

Aim:

The aim of this study was to examine the occurrence of mental health issues and substance use among adolescents belonging to tribal communities.

Methods and Materials:

The current research adopts a cross-sectional descriptive study design and was conducted across five Indian states, with a particular focus on the north-eastern region, including Assam, Meghalaya, Nagaland, Manipur, and Arunachal Pradesh. The selection of districts and schools was done based on convenience sampling in the initial phase of the study. From each state, two schools were selected where the tribal population was high. In each district, a list of schools (20 schools) was prepared based on census data where the tribal population was high. Following the selection of schools within the district, a randomized sampling approach, employing the lottery method, was utilized to choose 10 schools from the compiled list. Subsequently, a total enumeration method was employed for the selection of school-going adolescents, ensuring the inclusion of all individuals within the chosen schools. A total of 983 adolescents belonging to tribal communities participated in the study after providing both assent and parental consent. A socio-demographic datasheet, strengths and difficulties questionnaire (SDQ), and Brief Screener for Tobacco, Alcohol, and Other Drugs (BSTAD) were administered.

Results:

In the context of school-going adolescents, Arunachal Pradesh exhibited a higher prevalence of mental health issues, including emotional and behavioral problems, at 41.9%, surpassing the rates observed in Assam (32.8%), Meghalaya (31.4%), Nagaland (26%), and Manipur (14.22%). The finding shows that the use of alcohol was higher in Arunachal Pradesh (29.03%) as compared to other states; 29.44% of students from Nagaland sniffed or huffed, which was the highest among the five states; and 28.04% of students from Meghalaya took illegal drugs like marijuana, cocaine, etc., which was the highest among the five states.

Conclusion:

Proactive measures are urgently required to tackle the mental health obstacles confronting tribal adolescents. Implementing targeted mental health programs tailored to their specific needs is crucial for ensuring their well-being and fostering resilience within these communities.
The Halal Way of Clubbing: A Study of Second-Generation Muslim Youth’s Resistance and the Subculture It Has Generated
Authors: Mohammadi Fatemeh
Published: March 2024

This study examined two second-generation Muslim youth clubs in the city of Ottawa. First-generation mosques and community centres have ample space for youth. Still, as a form of defiance against their parents, these youth have created youth clubs outside of Ottawa’s residential areas. The clubs had devised an original form of ‘fun’ for themselves, which, despite being ‘halal’, was not approved by their parents and thus represented a form of resistance against them. These youth clubs have exacerbated tensions within the Muslim community in Canada. This article contends that a Muslim youth subculture is emerging among second-generation immigrants, which is consistent with aspects of the Birmingham School and post-subcultural theories. Steve Redhead argues that today’s youth continue to resist not through style but by ‘lengthy clubbing’. A total of 26 young women and men were interviewed alongside 10 months of fieldwork.
Associations of prior pulmonary tuberculosis with the incident COPD: a prospective cohort study
Authors: Zeng Zhilin , Chen Huilong , Shao Zhonghe , Guan Yunlong , Zhan Yuan , Cao Xi , Li Si , Hao Xingjie
Published: March 2024

Background:

Prior pulmonary tuberculosis (PTB) might be associated with the development of chronic obstructive pulmonary disease (COPD). However, the impact of prior PTB on the risk of incident COPD has not been studied in a large prospective cohort study of the European population.

Objectives:

This study aimed to investigate the association of prior PTB with the risk of COPD.

Design:

Prospective cohort study.

Methods:

A multivariable Cox proportional model was used to estimate the hazard ratio (HR) and 95% confidence interval (95% CI) for the association of prior PTB with COPD. Subgroup analyses were further conducted among individuals stratified by age, sex, body mass index, smoking status, drinking status, physical activity, and polygenic risk score (PRS).

Results:

The study involved a total of 216,130 participants, with a median follow-up period of 12.6 years and 2788 incident cases of COPD. Individuals with a prior history of PTB at baseline had an 87% higher risk of developing incident COPD compared to those without such history [adjusted hazard ratio (aHR) = 1.87; 95% confidence interval (CI): 1.26–2.77; p = 0.002]. Subgroup analysis revealed that individuals having prior PTB history presented a higher risk of incident COPD among individuals who were aged from 50 to 59 years with aHR of 2.47 (1.02–5.95, p = 0.044), older than 59 years with aHR of 1.81 (1.16–2.81, p = 0.008), male with aHR of 2.37 (1.47–3.83, p < 0.001), obesity with aHR of 3.35 (2.16–5.82, p < 0.001), previous smoking with aHR of 2.27 (1.39–3.72, p < 0.001), current drinking with aHR of 1.98 (1.47–3.83, p < 0.001), low physical activity with aHR of 2.62 (1.30–5.26, p = 0.007), and low PRS with aHR of 3.24 (1.61–6.53, p < 0.001), as well as high PRS with aHR of 2.43 (1.15–5.14, p = 0.019).

Conclusion:

A history of PTB is an important independent risk factor for COPD. Clinical staff should be aware of this risk factor in patients with prior PTB, particularly in countries or regions with high burdens of PTB.
Patient preferences for active ulcerative colitis treatments and fecal microbiota transplantation
Authors: Marshall Deborah A. , MacDonald Karen V. , Kao Dina , Bernstein Charles N. , Kaplan Gilaad G. , Jijon Humberto , Hazlewood Glen , Panaccione Remo , Nasser Yasmin , Raman Maitreyi , Moayyedi Paul
Published: March 2024

Background:

Fecal microbiota transplantation (FMT) is a promising treatment for active ulcerative colitis (UC). Understanding patient preferences can identify treatment features that may impact treatment decisions, improve shared decision-making, and contribute to patient-centered care, which is especially important in the context of novel treatments like FMT.

Objectives:

We aimed to quantify preferences for active UC treatments, specifically FMT and biologics, and identify patient characteristics associated with different preference patterns.

Design:

This is a cross-sectional survey study.

Methods:

We administered a discrete choice experiment (DCE) survey to elicit preferences in a sample of Canadian adults with UC. DCE data were analyzed using a main-effects mixed logit model and used to predict uptake of hypothetical scenarios reflecting alternative combinations of treatment features. Latent class modeling identified heterogeneity in patient preference patterns.

Results:

Participants’ ( n = 201) mean age was 47.1 years (SD: 14.5 years), 58% were female, and most (84%) had at least some post-secondary education. Almost half were willing to undergo FMT. When considering treatments for active UC, the most important attributes were chance of remission and severity of rare unknown side effects. All else equal, participants were most likely to uptake treatment that involves oral capsules/pills. Participants in the class with the highest utility for chance of remission were younger, had more severe disease, and 58% indicated that they would be willing to undergo FMT.

Conclusion:

We identified characteristics of UC patients who are more likely to be interested in FMT using preference elicitation methods. Patient-centered care can be enhanced by knowing which patients are more likely to be interested in FMT, potentially improving satisfaction with and adherence to treatments for active UC to maximize the effectiveness of treatment while considering heterogeneity in patient preferences.
Whole-genome resequencing of Chinese indigenous sheep provides insight into the genetic basis underlying climate adaptation
Authors: Jin Meilin , Wang Huihua , Liu Gang , Lu Jian , Yuan Zehu , Li Taotao , Liu Engming , Lu Zengkui , Du Lixin , Wei Caihong
Published: April 2024

Background

Chinese indigenous sheep are valuable resources with unique features and characteristics. They are distributed across regions with different climates in mainland China; however, few reports have analyzed the environmental adaptability of sheep based on their genome. We examined the variants and signatures of selection involved in adaptation to extreme humidity, altitude, and temperature conditions in 173 sheep genomes from 41 phenotypically and geographically representative Chinese indigenous sheep breeds to characterize the genetic basis underlying environmental adaptation in these populations.

Results

Based on the analysis of population structure, we inferred that Chinese indigenous sheep are divided into four groups: Kazakh (KAZ), Mongolian (MON), Tibetan (TIB), and Yunnan (YUN). We also detected a set of candidate genes that are relevant to adaptation to extreme environmental conditions, such as drought-prone regions (TBXT, TG, and HOXA1), high-altitude regions (DYSF, EPAS1, JAZF1, PDGFD, and NF1) and warm-temperature regions (TSHR, ABCD4, and TEX11). Among all these candidate genes, eight ABCD4, CNTN4, DOCK10, LOC105608545, LOC121816479, SEM3A, SVIL, and TSHR overlap between extreme environmental conditions. The TSHR gene shows a strong signature for positive selection in the warm-temperature group and harbors a single nucleotide polymorphism (SNP) missense mutation located between positions 90,600,001 and 90,650,001 on chromosome 7, which leads to a change in the protein structure of TSHR and influences its stability.

Conclusions

Analysis of the signatures of selection uncovered genes that are likely related to environmental adaptation and a SNP missense mutation in the TSHR gene that affects the protein structure and stability. It also provides information on the evolution of the phylogeographic structure of Chinese indigenous sheep populations. These results provide important genetic resources for future breeding studies and new perspectives on how animals can adapt to climate change.
Real-world advantage and challenge of post-autologous stem cell transplantation MRD negativity in high-risk patients with double-hit multiple myeloma
Authors: Tao Yi , Jin Shiwei , Yang Dan , Pan Mengmeng , Ouyang Wanyan , Liu Yuanfang , Wang Yan , Zhang Weiping , Mi Jianqing
Published: April 2024

Background

Autologous stem-cell transplantation (ASCT) remains a beneficial approach for patients with newly diagnosed multiple myeloma (NDMM) in the age of novel therapeutic agents. Nevertheless, limited real-world data is available to establish criteria for identifying high-risk ASCT patients.

Methods

We analyzed outcomes for 168 NDMM patients who underwent ASCT at our center from December 2015 to December 2022. We investigated the impact of the number of high-risk cytogenetics (HRCA), defined as t(4;14), t(14;16), 1q21 gain/amplification, and del(17p), as well as the post-ASCT minimal residual disease (MRD) status as prognostic indicators. We assessed progression-free survival (PFS) and overall survival (OS), and focused on identifying risk factors.

Results

The cohort included 42% of patients (n = 71) with 0 HRCA, 42% (n = 71) with 1 HRCA, and 16% (n = 26) with ≥ 2 HRCA. After a median follow-up of 31 months, the median PFS was 53 months (95% CI, 37–69), and OS was not reached for the entire cohort. Despite similar rates of MRD-negativity post-ASCT, patients with ≥ 2 HRCA, termed “double hit” (DH), had a significantly higher risk of progression/mortality than those with 0 or 1 HRCA. Multivariate analysis highlighted DH (HR 4.103, 95% CI, 2.046–8.231) and MRD positivity post-ASCT (HR 6.557, 95% CI, 3.217–13.366) as adverse prognostic factors for PFS, with DH also linked to inferior OS. As anticipated, DH patients with post-ASCT MRD positivity displayed the poorest prognosis, with a median PFS of 7 months post-ASCT. Meanwhile, DH patients with MRD negativity post-ASCT showed improved prognosis, akin to MRD-negative non-DH patients. It is noteworthy to exercise caution, as DH patients who initially achieved MRD negativity experienced a 41% cumulative loss of that status within one year.

Conclusions

This study strongly advocates integrating DH genetic assessments for eligible ASCT patients and emphasizes the importance of ongoing MRD monitoring, as well as considering MRD-based treatment adaptation for those patients in real-world settings.
Oncologists’ perceptions of tumor genomic profiling and barriers to communicating secondary hereditary risks to African American cancer patients
Authors: Hall Michael J. , D’Avanzo Paul A. , Chertock Yana , Kelly Patrick J. A. , Brajuha Jesse , Singley Katie , Luck Caseem C. , Bass Sarah B.
Published: April 2024

Background

Tumor genomic profiling (TGP) identifies targets for precision cancer treatments, but also secondary hereditary risks. Oncologists are poorly trained to communicate the results of TGP, especially among patients with lower health literacy, poorer genetics knowledge, and higher mistrust. African American (AA) patients are especially vulnerable to poor understanding due to significant cancer disparities and lower uptake of TGP. The goal of this research is to inform the development of an internet-based brief educational support for oncologists to prepare them to provide better decisional support related to TGP for their AA cancer patients.

Methods

This mixed-methods study used semi-structured interviews of oncologists to inform development of an online survey with a convenience sample of US-based oncologists (n = 50) to assess perceptions of the challenges of TGP and communicating results to AA patients.

Results

Most interviewed oncologists felt it was important to consider racial/cultural differences when communicating about hereditary risks. Cost, family dynamics, discrimination concerns, and medical mistrust were identified as particularly salient. Survey respondents’ views related to AAs and perceptions of TGP were strongly associated with years since completing training, with recent graduates expressing stronger agreement with statements identifying barriers/disadvantages to TGP for AA patients.

Conclusions

Oncologists who had more recently completed training expressed more negative perceptions of TGP and more perceived challenges in communicating about TGP with their AA patients. Focused training for oncologists that addresses barriers specific to AAs may be helpful in supporting improved communication about TGP and improved decisional support for AA patients with cancer considering TGP to evaluate their tumors.
Nature, prevalence, and risk factors for self-neglect among older people: a pilot study from Vellore, South India
Authors: Devaraj Vibisha , Rose Anuradha , Abraham Vinod Joseph
Published: April 2024

Changes in demography in developing countries haves led to new issues among older rural populations, such as self-neglect which is under researched.Self-neglect identified as poor self-care, unsafe living quarters, inadequate medical care and poor utilization of services increase the odds of morbidity and mortality.

Methods Our study was conducted in Kaniyambadi, a rural block in Vellore district in the state of Tamil Nadu, India. Ten villages were randomly selected. The study was conducted among people older than 60 years who were selected by random sampling using a computer-generated list. The following assessments were done: (i) A 19-item questionnaire was used to assess self-neglect, (ii) Katz index of daily living to assess functional activity, (iii) Mini Mental State Examination to evaluate cognition, (iv) Geriatric Depression Scale to identify depression, (v) Duke Social Support Index to measure social supports. Clinical data and anthropometric data were also collected. Data were entered into Epidata v3.1. All analyses were performed using SPSS v23.0.

Results One hundred fourteen people above 60 years of age participated. The prevalence of self-neglect was 21.1% (95% CI 14.9%—29%); about half of the elderly population (47.38%) refused to seek or follow medical advice. Lower levels of education (OR 3.678, 95% CI 1.017 – 13.301), lower social class (OR 4.455, 95% CI 1.236 – 16.050) and functional impairment (3.643, 95% CI 1.373 – 9.668) were found to be significant factors associated with self–neglect. Though prevalence of comorbidities (70%) and depression (27%) were high, there was no statistical evidence of association with self-neglect.
Assessing the implementation fidelity, feasibility, and sustainability of community-based house improvement for malaria control in southern Malawi: a mixed-methods study
Authors: Tizifa Tinashe A. , Kabaghe Alinune N. , McCann Robert S. , Gowelo Steven , Malenga Tumaini , Nkhata Richard M. , Chapeta Yankho , Nkhono William , Kadama Asante , Takken Willem , Phiri Kamija S. , van Vugt Michele , van den Berg Henk , Manda-Taylor Lucinda
Published: April 2024

Background

Despite significant success in the fight against malaria over the past two decades, malaria control programmes rely on only two insecticidal methods: indoor residual spraying and insecticidal-treated nets. House improvement (HI) can complement these interventions by reducing human-mosquito contact, thereby reinforcing the gains in disease reduction. This study assessed the implementation fidelity, which is the assessment of how closely an intervention aligns with its intended design, feasibility, and sustainability of community-led HI in southern Malawi.

Methods

The study, conducted in 22 villages (2730 households), employed a mixed-methods approach. Implementation fidelity was assessed using a modified framework, with longitudinal surveys collecting data on HI coverage indicators. Quantitative analysis, employing descriptive statistics, evaluated the adherence to HI implementation. Qualitative data came from in-depth interviews, key informant interviews, and focus groups involving project beneficiaries and implementers. Qualitative data were analysed using content analysis guided by the implementation fidelity model to explore facilitators, challenges, and factors affecting intervention feasibility.

Results

The results show that HI was implemented as planned. There was good adherence to the intended community-led HI design; however, the adherence could have been higher but gradually declined over time. In terms of intervention implementation, 74% of houses had attempted to have eaves closed in 2016-17 and 2017-18, compared to 70% in 2018–19. In 2016–17, 42% of houses had all four sides of the eaves closed, compared to 33% in 2018–19. Approximately 72% of houses were screened with gauze wire in 2016-17, compared to 57% in 2018-19. High costs, supply shortages, labour demands, volunteers’ poor living conditions and adverse weather were reported to hinder the ideal HI implementation. Overall, the community described community-led HI as feasible and could be sustained by addressing these socioeconomic and contextual challenges.

Conclusion

Our study found that although HI was initially implemented as planned, its fidelity declined over time. Using trained volunteers facilitated the fidelity and feasibility of implementing the intervention. A combination of rigorous community education, consistent training, information, education and communication, and intervention modifications may be necessary to address the challenges and enhance the intervention’s fidelity, feasibility, and sustainability.
A serial mediating effect of perceived family support on psychological well-being
Authors: An Jing , Zhu Xuanyu , Shi Zhan , An Jinlong
Published: April 2024

Family has a significant impact on individual mental health. Based on social support theory, family system theory and the Mental Health Continuum Short Form (MHC-SF), this research constructed a model of the pathway of perceived family support on psychological well-being and the results empirically clarified that perceived family support has a significant positive relationship with emotional well-being, social well-being, and psychological well-being (P < 0.001). Emotional well-being positively influences social well-being and psychological well-being (P < 0.001). Social well-being positively affects psychological well-being (P < 0.001). There were direct mediating effects of emotional well-being (13.45%), direct mediating effects of social well-being (32.82%) and a serial mediating effect (28.07%) between perceived family support and psychological well-being (P < 0.001).
Clinical teaching self-efficacy positively predicts professional fulfillment and negatively predicts burnout amongst Thai physicians: a cross-sectional survey
Authors: Tipwong Arunee , Hall Nathan C. , Snell Linda , Chamnan Parinya , Moreno Matthew , Harley Jason M.
Published: April 2024

Background

Clinician teachers (physicians who teach in clinical settings) experience considerable psychological challenges in providing both educational training and patient care. This study aimed to determine the prevalence of physician burnout and professional fulfillment, and to identify internal and external factors associated with mental health outcomes among Thai clinician teachers working in non-university teaching hospitals.

Method

A one-time online questionnaire was completed by physicians at 37 governmental, non-university teaching hospitals in Thailand, with 227 respondents being assessed in the main analyses. Four outcomes were evaluated including burnout, professional fulfillment, quality of life, and intentions to quit.

Results

The observed prevalence of professional fulfillment was 20%, and burnout was 30.7%. Hierarchical regression analysis showed a significant internal, psychological predictor (clinical teaching self-efficacy) and external, structural predictors (multiple roles at work, teaching support), controlling for the background variables of gender, years of teaching experience, family roles, and active chronic disease, with clinical teaching self-efficacy positively predicting professional fulfillment (b = 0.29, p ≤.001) and negatively predicting burnout (b = − 0.21, p =.003).

Conclusions

Results highlight the importance of faculty development initiatives to enhance clinical teaching self-efficacy and promote mental health among Thai physicians.
Cue-driven microbial cooperation and communication: evolving quorum sensing with honest signaling
Authors: Czárán Tamás , Scheuring István , Zachar István , Számadó Szabolcs
Published: April 2024

Background

Quorum sensing (QS) is the ability of microorganisms to assess local clonal density by measuring the extracellular concentration of signal molecules that they produce and excrete. QS is also the only known way of bacterial communication that supports the coordination of within-clone cooperative actions requiring a certain threshold density of cooperating cells. Cooperation aided by QS communication is sensitive to cheating in two different ways: laggards may benefit from not investing in cooperation but enjoying the benefit provided by their cooperating neighbors, whereas Liars explicitly promise cooperation but fail to do so, thereby convincing potential cooperating neighbors to help them, for almost free. Given this double vulnerability to cheats, it is not trivial why QS-supported cooperation is so widespread among prokaryotes.

Results

We investigated the evolutionary dynamics of QS in populations of cooperators for whom the QS signal is an inevitable side effect of producing the public good itself (cue-based QS). Using spatially explicit agent-based lattice simulations of QS-aided threshold cooperation (whereby cooperation is effective only above a critical cumulative level of contributions) and three different (analytical and numerical) approximations of the lattice model, we explored the dynamics of QS-aided threshold cooperation under a feasible range of parameter values. We demonstrate three major advantages of cue-driven cooperation. First, laggards cannot wipe out cooperation under a wide range of reasonable environmental conditions, in spite of an unconstrained possibility to mutate to cheating; in fact, cooperators may even exclude laggards at high cooperation thresholds. Second, lying almost never pays off, if the signal is an inevitable byproduct (i.e., the cue) of cooperation; even very cheap fake signals are selected against. And thirdly, QS is most useful if local cooperator densities are the least predictable, i.e., if their lattice-wise mean is close to the cooperation threshold with a substantial variance.

Conclusions

Comparing the results of the four different modeling approaches indicates that cue-driven threshold cooperation may be a viable evolutionary strategy for microbes that cannot keep track of past behavior of their potential cooperating partners, in spatially viscous and in well-mixed environments alike. Our model can be seen as a version of the famous greenbeard effect, where greenbeards coexist with defectors in a evolutionarily stable polymorphism. Such polymorphism is maintained by the condition-dependent trade-offs of signal production which are characteristic of cue-based QS.
Childhood urbanicity is associated with emotional episodic memory-related striatal function and common variation in NTRK2
Authors: Zhang Xiao , Zhang Yuyanan , Yan Hao , Yu Hao , Zhang Dai , Mattay Venkata S. , Tan Hao Yang , Yue Weihua
Published: April 2024

Background

Childhoods in urban or rural environments may differentially affect the risk of neuropsychiatric disorders, possibly through memory processing and neural response to emotional stimuli. Genetic factors may not only influence individuals’ choices of residence but also modulate how the living environment affects responses to episodic memory.

Methods

We investigated the effects of childhood urbanicity on episodic memory in 410 adults (discovery sample) and 72 adults (replication sample) with comparable socioeconomic statuses in Beijing, China, distinguishing between those with rural backgrounds (resided in rural areas before age 12 and relocated to urban areas at or after age 12) and urban backgrounds (resided in cities before age 12). We examined the effect of childhood urbanicity on brain function across encoding and retrieval sessions using an fMRI episodic memory paradigm involving the processing of neutral or aversive pictures. Moreover, genetic association analyses were conducted to understand the potential genetic underpinnings that might contribute to memory processing and neural mechanisms influenced by early-life urban or rural environments.

Results

Episodic memory retrieval accuracy for more difficult neutral stimuli was similar between those with urban and rural childhoods, whereas aversive stimuli elicited higher retrieval accuracy in the urban group (P = 0.023). For aversive stimuli, subjects with urban childhood had relatively decreased engagement of the striatum at encoding and decreased engagement of the hippocampus at retrieval. This more efficient striatal encoding of aversive stimuli in those with urban childhoods was associated with common variation in neurotrophic tyrosine kinase receptor type 2 (NTRK2) (right striatum: P = 1.58×10−6). These findings were confirmed in the replication sample.

Conclusions

We suggest that this differential striatal processing of aversive stimuli observed in individuals with urban or rural childhoods may represent mechanisms by which childhood urbanicity may affect brain circuits, heightening behavioral responses to negative stressors associated with urban environments. NTRK2-associated neural processes in the striatum may play a role in these processes.
Sodium-glucose cotransporter 2 inhibitors, inflammation, and heart failure: a two-sample Mendelian randomization study
Authors: Guo Wenqin , Zhao Lingyue , Huang Weichao , Chen Jing , Zhong Tingting , Yan Shaodi , Hu Wei , Zeng Fanfang , Peng Changnong , Yan Hongbing
Published: April 2024

Background

Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are increasingly recognized for their role in reducing the risk and improving the prognosis of heart failure (HF). However, the precise mechanisms involved remain to be fully delineated. Evidence points to their potential anti-inflammatory pathway in mitigating the risk of HF.

Methods

A two-sample, two-step Mendelian Randomization (MR) approach was employed to assess the correlation between SGLT-2 inhibition and HF, along with the mediating effects of inflammatory biomarkers in this relationship. MR is an analytical methodology that leverages single nucleotide polymorphisms as instrumental variables to infer potential causal inferences between exposures and outcomes within observational data frameworks. Genetic variants correlated with the expression of the SLC5A2 gene and glycated hemoglobin levels (HbA1c) were selected using datasets from the Genotype-Tissue Expression project and the eQTLGen consortium. The Genome-wide association study (GWAS) data for 92 inflammatory biomarkers were obtained from two datasets, which included 14,824 and 575,531 individuals of European ancestry, respectively. GWAS data for HF was derived from a meta-analysis that combined 26 cohorts, including 47,309 HF cases and 930,014 controls. Odds ratios (ORs) and 95% confidence interval (CI) for HF were calculated per 1 unit change of HbA1c.

Results

Genetically predicted SGLT-2 inhibition was associated with a reduced risk of HF (OR 0.42 [95% CI 0.30–0.59], P < 0.0001). Of the 92 inflammatory biomarkers studied, two inflammatory biomarkers (C-X-C motif chemokine ligand 10 [CXCL10] and leukemia inhibitory factor) were associated with both SGLT-2 inhibition and HF. Multivariable MR analysis revealed that CXCL10 was the primary inflammatory cytokine related to HF (MIP = 0.861, MACE = 0.224, FDR-adjusted P = 0.0844). The effect of SGLT-2 inhibition on HF was mediated by CXCL10 by 17.85% of the total effect (95% CI [3.03%–32.68%], P = 0.0183).

Conclusions

This study provides genetic evidence supporting the anti-inflammatory effects of SGLT-2 inhibitors and their beneficial impact in reducing the risk of HF. CXCL10 emerged as a potential mediator, offering a novel intervention pathway for HF treatment.

Graphical Abstract
Intranasal delivery of phenytoin loaded layered double hydroxide nanoparticles improves therapeutic effect on epileptic seizures
Authors: Zhang Jingxin , Zuo Huali , Fu Yanlu , Cao Yina , Li Qiwei , Zhang Qi , Zheng Yuyi , Wang Yi , Wu Di , Chen Weiyu , Fang Jiajia
Published: April 2024

Improving the efficiency of antiseizure medication entering the brain is the key to reducing its peripheral toxicity. A combination of intranasal administration and nanomedicine presents a practical approach for treating epileptic seizures via bypassing the blood-brain barrier. In this study, phenytoin (PHT) loaded layered double hydroxide nanoparticles (BSA-LDHs-PHT) were fabricated via a coprecipitation − hydrothermal method for epileptic seizure control. In this study, we expound on the preparation method and characterization of BSA-LDHs-PHT. In-vitro drug release experiment shows both rapid and continuous drug release from BSA-LDHs-PHT, which is crucial for acute seizure control and chronic epilepsy therapy. In-vivo biodistribution assays after intranasal administration indicate excellent brain targeting ability of BSA-LDHs. Compared to BSA-Cyanine5.5, BSA-LDHs-Cyanine5.5 were associated with a higher brain/peripheral ratio across all tested time points. Following intranasal delivery with small doses of BSA-LDHs-PHT, the latency of seizures in the pentylenetetrazole-induced mouse models was effectively improved. Collectively, the present study successfully designed and applied BSA-LDHs-PHT as a promising strategy for treating epileptic seizures with an enhanced therapeutic effect.
Mitochondria-mediated ferroptosis induced by CARD9 ablation prevents MDSCs-dependent antifungal immunity
Authors: Zhang Zhiyong , Li Pengfei , Chen Ying , Chen Yuxi , Wang Xiuzhu , Shen Sunan , Zhao Yue , Zhu Yanan , Wang Tingting
Published: April 2024

Background

Caspase Recruitment Domain-containing protein 9 (CARD9) expressed in myeloid cells has been demonstrated to play an antifungal immunity role in protecting against disseminated candidiasis. Hereditary CARD9 ablation leads to fatal disseminated candidiasis. However, the myeloid cell types and molecular mechanisms implicated in CARD9 protecting against disseminated candidiasis remain wholly elusive.

Methods

The role of CARD9 ablation in exacerbating disseminated candidiasis was determined in vivo and in vitro. The molecular mechanism by which CARD9 ablation promotes acute kidney injury in disseminated candidiasis was identified by RNA-sequencing analysis. The expression of mitochondrial proteins and ferroptosis-associated proteins were measured by Quantitative real-time PCR and western blot.

Results

CARD9 ablation resulted in a reduced proportion of myeloid-derived suppressor cells (MDSCs) and a substantially lower expression of solute carrier family 7 member 11 (SLC7A11) in the kidneys, which increased susceptibility to acute kidney injury and renal ferroptosis during disseminated Candida tropicalis (C. tropicalis) infection. Moreover, CARD9-deficient MDSCs were susceptible to ferroptosis upon stimulation with C. tropicalis, which was attributed to augmented mitochondrial oxidative phosphorylation (OXPHOS) caused by reduced SLC7A11 expression. Mechanistically, C-type lectin receptors (CLRs)-mediated recognition of C. tropicalis promoted the expression of SLC7A11 which was transcriptionally manipulated by the Syk-PKCδ-CARD9-FosB signaling axis in MDSCs. FosB enhanced SLC7A11 transcription by binding to the promoter of SLC7A11 in MDSCs stimulated with C. tropicalis. Mitochondrial OXPHOS, which was negatively regulated by SLC7A11, was responsible for inducing ferroptosis of MDSCs upon C. tropicalis stimulation. Finally, pharmacological inhibition of mitochondrial OXPHOS or ferroptosis significantly increased the number of MDSCs in the kidneys to augment host antifungal immunity, thereby attenuating ferroptosis and acute kidney injury exacerbated by CARD9 ablation during disseminated candidiasis.

Conclusions

Collectively, our findings show that CARD9 ablation enhances mitochondria-mediated ferroptosis in MDSCs, which negatively regulates antifungal immunity. We also identify mitochondria-mediated ferroptosis in MDSCs as a new molecular mechanism of CARD9 ablation-exacerbated acute kidney injury during disseminated candidiasis, thus targeting mitochondria-mediated ferroptosis is a novel therapeutic strategy for acute kidney injury in disseminated candidiasis.
Nesprin proteins: bridging nuclear envelope dynamics to muscular dysfunction
Authors: Zi-yi Zhou , Qin Qin , Fei Zhou , Cun-Yu Cao , Lin Teng
Published: April 2024

This review presents a comprehensive exploration of the pivotal role played by the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex, with a particular focus on Nesprin proteins, in cellular mechanics and the pathogenesis of muscular diseases. Distinguishing itself from prior works, the analysis delves deeply into the intricate interplay of the LINC complex, emphasizing its indispensable contribution to maintaining cellular structural integrity, especially in mechanically sensitive tissues such as cardiac and striated muscles. Additionally, the significant association between mutations in Nesprin proteins and the onset of Dilated Cardiomyopathy (DCM) and Emery-Dreifuss Muscular Dystrophy (EDMD) is highlighted, underscoring their pivotal role in disease pathogenesis. Through a comprehensive examination of DCM and EDMD cases, the review elucidates the disruptions in the LINC complex, nuclear morphology alterations, and muscular developmental disorders, thus emphasizing the essential function of an intact LINC complex in preserving muscle physiological functions. Moreover, the review provides novel insights into the implications of Nesprin mutations for cellular dynamics in the pathogenesis of muscular diseases, particularly in maintaining cardiac structural and functional integrity. Furthermore, advanced therapeutic strategies, including rectifying Nesprin gene mutations, controlling Nesprin protein expression, enhancing LINC complex functionality, and augmenting cardiac muscle cell function are proposed. By shedding light on the intricate molecular mechanisms underlying nuclear-cytoskeletal interactions, the review lays the groundwork for future research and therapeutic interventions aimed at addressing genetic muscle disorders.
Dietary quality and dietary greenhouse gas emissions in the USA: a comparison of the planetary health diet index, healthy eating index-2015, and dietary approaches to stop hypertension
Authors: Frank Sarah M. , Jaacks Lindsay M , Meyer Katie , Rose Donald , Adair Linda S , Avery Christy L , Taillie Lindsey Smith
Published: April 2024

Background

The Planetary Health Diet Index (PHDI) measures adherence to the dietary pattern presented by the EAT-Lancet Commission, which aligns health and sustainability targets. There is a need to understand how PHDI scores correlate with dietary greenhouse gas emissions (GHGE) and how this differs from the carbon footprints of scores on established dietary recommendations. The objectives of this study were to compare how the PHDI, Healthy Eating Index-2015 (HEI-2015) and Dietary Approaches to Stop Hypertension (DASH) relate to (a) dietary GHGE and (b) to examine the influence of PHDI food components on dietary GHGE.

Methods

We used life cycle assessment data from the Database of Food Recall Impacts on the Environment for Nutrition and Dietary Studies to calculate the mean dietary GHGE of 8,128 adult participants in the 2015–2016 and 2017–2018 cycles of the National Health and Nutrition Examination Survey (NHANES). Poisson regression was used to estimate the association of (a) quintiles of diet score and (b) standardized dietary index Z-scores with dietary GHGE for PHDI, HEI-2015, and DASH scores. In secondary analyses, we used Poisson regression to assess the influence of individual PHDI component scores on dietary GHGE.

Results

We found that higher dietary quality on all three indices was correlated with lower dietary GHGE. The magnitude of the dietary quality-dietary GHGE relationship was larger for PHDI [-0.4, 95% CI (-0.5, -0.3) kg CO2 equivalents per one standard deviation change] and for DASH [-0.5, (-0.4, -0.6) kg CO2-equivalents] than for HEI-2015 [-0.2, (-0.2, -0.3) kg CO2-equivalents]. When examining PHDI component scores, we found that diet-related GHGE were driven largely by red and processed meat intake.

Conclusions

Improved dietary quality has the potential to lower the emissions impacts of US diets. Future efforts to promote healthy, sustainable diets could apply the recommendations of the established DASH guidelines as well as the new guidance provided by the PHDI to increase their environmental benefits.
Longitudinal associations of screen time, physical activity, and sleep duration with body mass index in U.S. youth
Authors: Zink Jennifer , Booker Robert , Wolff-Hughes Dana L. , Allen Norrina B. , Carnethon Mercedes R. , Alexandria Shaina J. , Berrigan David
Published: April 2024

Background

Youth use different forms of screen time (e.g., streaming, gaming) that may be related to body mass index (BMI). Screen time is non-independent from other behaviors, including physical activity and sleep duration. Statistical approaches such as isotemporal substitution or compositional data analysis (CoDA) can model associations between these non-independent behaviors and health outcomes. Few studies have examined different types of screen time, physical activity, and sleep duration simultaneously in relation to BMI.

Methods

Data were baseline (2017–2018) and one-year follow-up (2018–2019) from the Adolescent Brain Cognitive Development Study, a multi-site study of a nationally representative sample of U.S. youth (N = 10,544, mean [SE] baseline age = 9.9 [0.03] years, 48.9% female, 45.4% non-White). Participants reported daily minutes of screen time (streaming, gaming, socializing), physical activity, and sleep. Sex-stratified models estimated the association between baseline behaviors and follow-up BMIz-score, controlling for demographic characteristics, internalizing symptoms, and BMIz-score at baseline.

Results

In females, isotemporal substitution models estimated that replacing 30 min of socializing (β [95% CI] = -0.03 [-0.05, -0.002]), streaming (-0.03 [-0.05, -0.01]), or gaming (-0.03 [-0.06, -0.01]) with 30 min of physical activity was associated with a lower follow-up BMIz-score. In males, replacing 30 min of socializing (-0.03 [-0.05, -0.01]), streaming (-0.02 [-0.03, -0.01]), or gaming (-0.02 [-0.03, -0.01]) with 30 min of sleep was associated with a lower follow-up BMIz-score. In males, replacing 30 min of socializing with 30 min of gaming was associated with a lower follow-up BMIz-score (-0.01 [-0.03, -0.0001]). CoDA estimated that in males, a greater proportion of time spent in baseline socializing, relative to the remaining behaviors, was associated with a higher follow-up BMIz-score (0.05 [0.02, 0.08]). In females, no associations between screen time and BMI were observed using CoDA.

Conclusions

One-year longitudinal associations between screen time and BMI may depend on form of screen time, what behavior it replaces (physical activity or sleep), and participant sex. The alternative statistical approaches yielded somewhat different results. Experimental manipulation of screen time and investigation of biopsychosocial mechanisms underlying the observed sex differences will allow for causal inference and can inform interventions.