bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting Depressive and Anxiety Symptoms Among Lebanese and Syrian adults in a Suburb of Beirut during the Concurrent Crises: A Population-Based Study
Authors: Shamas Hazar , Ragi Marie-Elizabeth , Abi Zeid Berthe , DeJong Jocelyn , McCall Stephen J. ,   with the CAEP Study Group
Published: October 2024

AbstractBackgroundPeople living in low socioeconomic conditions are more prone to depression and anxiety. This study aimed to develop and internally validate prediction models for depressive and anxiety symptoms in Lebanese adults and Syrian refugees residing in a suburb of Beirut, Lebanon.MethodsThis was a population-based study among COVID-19 vulnerable adults in low socioeconomic neighborhoods in Sin-El-Fil, Lebanon. Data were collected through a telephone survey between June and October 2022. The outcomes depressive and anxiety symptoms were investigated for Lebanese and Syrian populations. Depressive and anxiety symptoms were defined as having a PHQ-9 and GAD-7 score of 10 or more respectively. Outcomes’ predictors were identified through LASSO regression, discrimination and model calibrations were assessed using area under curve (AUC) and C-Slope.ResultsOf 2,045 participants, 1,322 were Lebanese, 664 were Syrian, and 59 were from other nationalities. Among Lebanese and Syrian populations, 25.3% and 43.9% had depressive symptoms, respectively. Additional predictors for depressive symptoms were not attending school, not feeling safe at all at home, and not having someone to count on in times of difficulty. Not having legal residency documentation for Syrian adults was a context-specific predictor for depressive symptoms. These predictors were similar to that of anxiety symptoms. Both Lebanese and Syrian models had good discriminations and excellent calibrations.ConclusionThis study highlights the main predictors of poor mental health were financial, health, and social indicators for both Lebanese and Syrian adults during the concurrent crisis in Lebanon. Findings emphasise social protection and financial support are required in populations with low socioeconomic status.Research in contextWhat is already known on this topicThe prevalence of depression and anxiety has increased globally. Vulnerable populations, such as refugees and populations of low socioeconomic status, are more prone to depression and anxiety.What this study addsThis study included Lebanese and Syrian adults residing in low socioeconomic status areas of Sin-El-Fil, Lebanon. This is a population-based comparison of the predictors to poor mental health in Lebanon between refugees and Lebanese. The study highlights the need to meet financial, physical, and social needs of individuals to address mental health.How this study might affect research, practice, or policyThe findings of this study highlight the need to reduce financial stress, address physical pain and social isolation, and advocate for Syrian residency documentation to reduce the occurrence of anxiety and depressive symptoms in people living in low socioeconomic conditions.
“People here live in denial”: A qualitative study of the pervasive impact of stigma on asthma diagnosis and care in Kenya and Sudan
Authors: Ahmed Rana , Mulupi Stephen , Taegtmeyer Miriam , Ardrey Jane , Devereux Graham , Chinouya Martha , Osman Rashid , Hussein ElHafiz , Modawey Sundos , Eltahir Hoyam , Kinyua Caroline , Meme Helen , Shayo Elizabeth H , El Sony Asma , Tolhurst Rachel 
Published: October 2024

AbstractEpidemiological studies show a global increase in asthma, straining healthcare systems in low- and middle-income countries. There are multiple barriers to accessing diagnosis and treatment in Sub-Saharan African countries like Kenya and Sudan such as healthcare infrastructure, diagnostic tools, healthcare workers’ capacities, and cost. Asthma can be well controlled using safe and cost-effective treatments such as inhalers. Stigma related to asthma negatively impacts treatment-seeking and adherence in higher-income settings, with limited information about such impacts in Sub-Saharan Africa.We conducted qualitative interviews and Focus Group Discussions in Kenya and Sudan to explore health systems aspects of diagnosis and management of chronic respiratory diseases. Participants included patients, primary care healthcare workers, hospitals, and community actors. Data were analysed through a framework approach; our initial analysis showed that asthma stigma was prevalent in both countries. Further analysis was done through Health, Stigma, and Discrimination Framework by Stangl.Negative perceptions about the aetiology and prognosis of asthma contribute to stigma. Anticipated, internalized stigma, and enacted stigma affects individuals with asthma, encouraging them to hide their symptoms and resist diagnosis. This contribute to delayed healthcare seeking and treatment uptake, impacting both individuals with asthma and health professionals. Overall, stigma exacerbates challenges in communicating diagnosis, managing the illness, and maintaining psychosocial health and well-being for those with asthma.Poor asthma control can exacerbate fear and stigma. Improving asthma control has the potential to reduce fear and positively influence community norms. The rollout of inhalers and spacers for asthma treatment should be accompanied by deliberate stigma reduction strategies and awareness raising at all levels of the system.
Managing uncertainty and complexity during a public health emergency: Understanding the immediate and ongoing effects of the COVID-19 epidemic on a global Neglected Tropical Disease program
Authors: Sutherland E. , Stelmach R. , Warren N. , Jackson J. , Allen B. , Mwingira U. , Brady M. , Ngondi J. , Hernandez L. , Dahal G. , Kabona G. , Telfort M. , Oydediran F. , Seife F. , Sitoe H. , Baker M. 
Published: October 2024

AbstractWhen COVID-19 emerged as a global pandemic, the World Health Organization (WHO) recommended a pause in the delivery of neglected tropical disease preventative chemotherapy and surveillance. The Act to End NTDs | East program (Act | East) worked with country neglected tropical disease (NTD) programs to develop, support, and implement guidelines that allowed NTD service delivery and surveillance to resume. This paper examines those adaptations that Act | East made as a program to support numerous countries, over a discrete time period, to resume NTD program operations. This paper also examined how the pause and the resumption of service delivery with new guidelines and standard operating procedures in place affected program operations. Specifically, we examine delays in scheduled mass drug administration and disease surveys, coverage achieved by resumed mass drug administration campaigns, and the impact that COVID-19 had on planning and budgeting. We review which adaptations have been retained in a post-COVID-19 landscape, and which may inform NTD and other global health programs, to better respond in future public health emergencies.
An optimal network that promotes the spread of an advantageous variant in an SIR epidemic
Authors: Lopez Samuel , Komarova Natalia L. 
Published: October 2024

AbstractIn the course of epidemics, the pathogen may mutate to acquire a higher fitness. At the same time, such a mutant is automatically at a disadvantage because the resident virus has a head start in accessing the pool of susceptible individuals. We considered a class of tunable small-world networks, where a parameter,p(the rewiring probability), characterizes the prevalence of non-local connections, and we asked, whether the underlying network can influence the fate of a mutant virus. Under an SIR model, we considered two measures of mutant success: the expected height of the peak of mutant infected individuals, and the total number of recovered from mutant individuals at the end of the epidemic. Using these measures, we have found the existence of an optimal (for an advantageous mutant virus) rewiring probability that promotes a larger infected maximum and a larger total recovered population corresponding to the advantageous pathogen strain. This optimal rewiring probability decreases as mean degree and the infectivity of the wild type are increased, and it increases with the mutant advantage. The non-monotonic behavior of the advantageous mutant as a function of rewiring probability may shed light into some of the complex patterns in the size of mutant peaks experienced by different countries during the COVID19 pandemic.
Double haploid development in drug-typeCannabis sativaL. through microspore indirectde-novoplant regeneration
Authors: Tonolo Francesco 
Published: October 2024

AbstractDouble haploid technology (DH) is an essential tool in plant breeding, enabling the rapid production of homozygous lines. However,Cannabis sativaL. has been categorized as recalcitrant to DH induction. In this study, we evaluated the potential to generate DHC. sativaplants via anther culture and indirectde-novoorganogenesis. We examined a THCA-dominant cultivar with a callus induction success of 29.48%. Mixoploidy in the callus indicated spontaneous genome doubling. This is the first report documenting the successful induction of DHC. sativaplants throughde-novoindirect organogenesis. These findings have profound implications for theC. sativabreeding sector by potentially improving efficiency of genome editing and hybrid development in this economically significant species.
Resolving the “Ontogeny Problem” in Vertebrate Paleontology
Authors: Napoli James G. 
Published: October 2024

AbstractOntogenetic change is a major source of phenotypic variation among members of a species and is often of greater magnitude than the anatomical differences that distinguish closely related species. Ontogeny has therefore become a problematic confounding variable in vertebrate paleontology, especially in study systems distant from extant crown clades, rendering taxonomic hypothesis testing (a fundamental process in evolutionary biology) rife with difficulty. Paleontologists have adopted quantitative methods to compensate for the perception that juvenile specimens lack diagnostic apomorphies seen in their adult conspecifics. Here, I critically evaluate these methods and the assumptions that guide their interpretation using a µCT dataset comprising growth series of American and Chinese alligator. I find that several widespread assumptions are scientifically unjustifiable, and that two popular methods – geometric morphometrics and cladistic analysis of ontogeny – have unacceptably high rates of type II error and present numerous procedural difficulties. However, I also identify a suite of ontogenetically invariant characters that differentiate the living species ofAlligatorthroughout ontogeny. These characters overwhelmingly correspond to anatomical systems that develop prior to (and play a signaling role in) the development of the cranial skeleton itself, suggesting that their ontogenetic invariance is a consequence of the widely conserved vertebrate developmental program. These observations suggest that the architecture of the cranium is fixed early in embryonic development, and that ontogenetic remodeling does not alter the topological relationships of the cranial bones or the soft tissue structures they house. I propose a general model for future taxonomic hypothesis tests in the fossil record, in which the hypothesis that two specimens different ontogenetic stages of a single species can be falsified by the discovery of character differences that cannot be attributed plausibly to ontogenetic variation.
Epigenetic responses inBorrelia-infected Ixodesscapularisticks: Over-expression of euchromatic histone lysine methyltransferase 2 and no change in DNA methylation
Authors: MacIntosh Grace Hadley , Nuyens Alexandra C. , Vickery Jessica L. , Berthold Anne , Lloyd Vett K. 
Published: October 2024

AbstractBorrelia burgdorferi, a tick-vectored spirochete bacteria best known for causing Lyme disease, has been found to induce physiological and behavioural changes in its tick vector that can increase tick fitness and its ability to transmit the bacteria. The mechanism by which this bacterium modulates these changes remains unknown. Epigenetics plays a central role in transducing external and internal microbiome environmental influences to the organism, so we investigated DNA methylation and the expression of a key histone modification enzyme inBorrelia-infected and uninfectedIxodes scapularisticks. DNA methylation of the pericentromeric tandem repeats family,Ixodes scapularisRepeats (ISR) were assessed by methylated-DNA immunoprecipitation (MeDIP) followed by qPCR of the ISR regions. DNA methylation of the ISR sequences was found. The different repeats had different levels of DNA methylation, however, these levels were not significantly affected by the presence or absence ofB. burgdorferi. The epigenetic regulatoreuchromatic histone lysine methyltransferase 2(EHMT2) is recognized as having a key role in modulating the organismal stress response to infections. To assessEHMT2transcription inBorrelia-infected and uninfected ticks, real-time reverse transcriptase PCR was performed. Uninfected ticks had over 800X lowerEHMT2expression than infected ticks. This study is among the first to identify a gene that may be involved in producing epigenetic differences in ticks depending on infection status and lays the groundwork for future epigenetic studies ofI. scapularisin response toB. burgdorferias well as other pathogens that these ticks transmit.
Dissecting the Contribution of Transposable Elements to Interphase Chromosome Structure
Authors: Shi Liyang , Xiao Zhen , Babarinde Isaac A. , Xiuling Fu , Ma Gang , Huang Zhouqi , Sun Li , Zhou Xuemeng , He Jiangping , Strunnikov Alexander , Hutchins Andrew P. 
Published: October 2024

AbstractTransposable elements (TEs) occupy nearly half of the human genome and play diverse biological roles. Despite their abundance, the extent to which TEs contribute to three-dimensional (3D) genome structure remains unclear.To investigate this, we developed te_hic, a computational pipeline that integrates genomic data with chromatin interactions. Our analysis reveals that TE sequences are responsible for 3D genome structure in interphase nuclei. This phenomenon is mediated by the recruitment of specific transcription factors to TEs, which enables both the formation and disruption of chromatin contacts. We computationally identified known contact-forming proteins (CTCF, RAD21, SMC3) and breaking proteins (RNF2), as well as novel candidate contact-formers (SMARCA4, MAFK). Knockdown of the predicted contact-formersSMARCA4andMAFKdecreased contacts and loops at and between TEs. Notably,SMARCA4knockdown selectively reduced short-range contacts, highlighting its role in maintaining 3D genome structure mediated by TE binding.Overall, our findings demonstrate that TEs are crucial determinants of 3D genome organization in mammalian cells.Key findingsTEs determine 48% of the 3D genome structure alone, and 70% of heterotypic contacts.A/B compartments, TADs, and loop signatures can be retrieved using TE-mapped reads only.TFs can be divided into contact formers and breakers at TEs.SMARCA4 and MAFK build chromatin contacts between TE sequences.
Study Protocol: LIAM Mc Trial (Linking In with Advice and supports for Men impacted by Metastatic cancer)
Authors: Noonan Brendan , Bredin Philip , Cahill Anita M. , Corkery Stephanie , Johnston Katie E. , Medved Katarina , Cusack Anne Marie , Hegarty Josephine , Saab Mohamad M , Cushen Samantha J. , Connolly Roisin , Palmer Brendan , Dahly Darren , Murphy Mike , Bambury Richard M. , Gleeson Jack P. 
Published: October 2024

AbstractBackgroundThe improved survival rate for many cancers in high-income countries demands a coordinated multidisciplinary approach to survivorship care and service provision to ensure optimal patient outcomes and quality of life. This study assesses the feasibility of introducing a Men’s Health Initiative supportive care intervention programme in Ireland.MethodsThis is a single-arm feasibility study involving a 12-week men’s cancer survivorship programme alongside routine follow-up care in patients with advanced genitourinary malignancies. Men with advanced/metastatic genitourinary cancer (including prostate, kidney, urothelial tract, testicular or penile cancer), are eligible to enrol, with a target of 72 participants over a 2-year period.The intervention programme entails a twice-weekly physiotherapy-led exercise programme, along with dietetics, nursing, and psychosocial components, and regular signposting to additional available services. A Pilot Phase involving analysis of data from the first group of 6 participants to complete the programme is planned, before an Expansion Phase. Assessments will occur at baseline, on completion of the 12-week intervention, and 6 months post-intervention, and will include analyses of exercise/activity levels, body composition, muscle strength, psychological wellbeing, quality of life and resources utilised.The primary endpoints are to determine the feasibility and acceptability of introducing a men’s cancer survivorship intervention programme into routine follow-up care in patients with advanced genitourinary malignancies. Secondary endpoints include impact of the intervention programme on quality of life, cancer-related fatigue, maintenance of weight, changes in body composition and changes in dietary intake and diet quality over the study period, as well as self-care agency and its relationship to quality of life and symptoms experienced. A process evaluation will capture the experiences of participation in the study, and the healthcare costs will be examined as part of the economic analysis.Ethical approval was granted in November 2022, with recruitment commencing in May 2023.DiscussionThe programme described in this protocol provides a supportive and safe environment for the introduction of self-care interventions using a small group-based format supported by individualised counselling according to the participant’s identified needs. Findings will provide direction for the implementation of future supportive care programmes for men’s cancer survivorship care.ClinicalTrials.govIdentifier:NCT05946993; Cancer Trials Ireland #: CTRIAL-IE 23-18; Irish Cancer Society (ICS) Study reference: MHI22BAM, UCC Sponsor Study Code: 22052.
Assessment of the impact of the new blister packaging of Biktarvy®(B/F/TAF) on treatment satisfaction of people living with HIV
Authors: Cruz JP , Santos O , Rodrigues M , Morais R , Borralho T , Ferreira F , Ferreira A , Albuquerque J , Nogueira P , Silva MP , Antunes F 
Published: October 2024

AbstractBackgroundAntiretroviral therapy (ART) is highly effective in people living with HIV (PLHIV), but its success depends on treatment satisfaction and adherence. A determinant of satisfaction regards how the medication is delivered to the patient, namely how it is contained (e.g., bottles, blisters, etc). A new packaging of Biktarvy®has been introduced as a monthly blister, aiming to improve satisfaction, facilitate traceability of daily medication, portability, and discretion (reducing stigma associated with ART), and, ultimately, enhance adherence.GoalsThe study’s objective was to assess the impact of changing the packaging of Biktarvy® (B/F/TAF) from a standard pill bottle to a monthly blister with a weekly calendar on therapy satisfaction. Additionally, the association between treatment satisfaction and selected patients’ characteristics (e.g., ART duration) was evaluated. A secondary goal was to characterize the association between the change of packaging on patient’s adherence.MethodsThis is an observational longitudinal (retrospective and prospective) study with patients following ART for at least six months (ambulatory clinical management) recruited according to a non-probabilistic sequential sampling. Satisfaction was measured at two different moments: at baseline, HIVTSQs were used to assess satisfaction within the previous six months’ use of medication containers (bottles). Six months later, patients filled in the HIVTSQc to assess their perception of satisfaction change with the new packaging (blister). Adherence was assessed by pharmacy medication dispensing at the hospital.ResultsThe study enrolled 105 patients in two selected centers (102 patients completed the study). Patients were significantly more satisfied (HIVTSQc scores) with ART when using the new Biktarvy® blister pack package. Importantly, gains of ART satisfaction were higher among those less satisfied with the bottle packaging. No significant associations were found between HIVTSQc scores and sociodemographic or ART-related variables.
Post-translational modifications orchestrate the intrinsic signaling bias of orphan receptor GPR52
Authors: Zhang Bingjie , Ma Mengna , Ge Wei , Li Shanshan , Yang Guang , Wang Huilan , Lu Boxun , Shui Wenqing 
Published: October 2024

AbstractDespite recent advances in GPCR structure and pharmacology, the regulation of GPCR activation, signaling, and functioning by diverse post-translational modifications (PTMs) has been largely unexplored. Furthermore, for a special category of self-activating orphan GPCRs, it is completely unknown whether and how specific PTMs control their unique signaling profiles and cellular functions. In this study of GPR52, an orphan GPCR with exceedingly high constitutive G protein signaling activity and emerging as a neurotherapeutic target, we discovered its disproportionately low arrestin recruitment activity. Through profiling the N-glycosylation and phosphorylation patterns of the receptor and clarifying their roles in G proteinversusarrestin coupling, we found these two types of PTMs in specific motifs differentially shape the intrinsic signaling bias of GPR52. While N-terminal N-glycosylation promotes constitutive Gs signaling possibly through favoring the self-activating conformation, phosphorylation in helix 8, to our great surprise, suppresses arrestin recruitment and thus attenuates receptor internalization. In addition, we uncovered the counteracting roles of N-glycosylation and phosphorylation in modulating GPR52-dependent accumulation of the huntingtin protein (HTT) in brain striatal cells. Thus, our study provides novel insights into the regulation of intrinsic signaling bias and cellular function of an orphan GPCRviadistinct PTMs in different motifs.
Mitophagy modulation rescues single large-scale mitochondrial DNA deletion (SLSMD) disease symptoms in theC. elegans uaDf5animal model
Authors: Mendel Ryan M. , Matsuno Sofie , Lu Alex , Falk Marni J. , Haroon Suraiya 
Published: October 2024

ABSTRACTSingle largescalemitochondrial DNA (mtDNA)deletions (SLSMD) underlie a range of sporadic or maternally inherited primary mitochondrial diseases having significant morbidity and mortality, including Pearson syndrome, Kearns-Sayre Syndrome, or Chronic Progressive External Ophthalmoplegia. Therapeutic development has been hindered by limited existing knowledge on mtDNA quality control and a lack of SLSMD animal models. To address this challenge, we utilized theC. elegansheteroplasmic SLSMD strain,uaDf5,to objectively screen for potential therapies. As mitophagy modulation has been implicated in mtDNA homeostasis, we screened a library of mitophagy modulating compounds to determine their comparative effects to rescue mitochondrial unfolded protein (UPRmt) stress induction in inuaDf5SLSMD worms. Interestingly, Thiamine was discovered to be an effective positive control, significantly reducing mitochondrial stress in this model. Two lead therapeutic candidates from the mitophagy library screen were Hemin and Celastrol (Tripterin). Celastrol is a mitophagy activating anti-inflammatory and metabolic modifying natural product derived compound, that rescued multiple fitness outcomes (thrashing, development, survival) and reduced the mitochondrial stress inuaDf5animals in a mitophagy-dependent fashion. This study highlights the utility of theuaDf5worm model to enable preclinical identification of therapeutic candidate leads for SLSMD-based heteroplasmic mtDNA diseases and identifies possible therapeutic candidates that serve as mitophagy modulators to improve health and specifically reduce heteroplasmy levels in SLSMD diseases.