bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIV-1 N-myristoylation-dependent hijacking of late endosomes/lysosomes to drive Gag assembly in macrophages
Authors: Guajardo-Contreras Gabriel I. , Abdalla Ana L. , Chen Alex , Niu Meijuan , Beauchamp Erwan , Berthiaume Luc G. , Cochrane Alan W. , Mouland Andrew J. 
Published: October 2024

ABSTRACT
Macrophages represent an important viral reservoir in HIV-1-infected individuals. Different from T cells, HIV-1 assembly in macrophages occurs at intracellular compartments termed virus-containing compartments (VCCs). Our previous research in HeLa cells – in which assembly resembles that found in infected T cells – suggested that late endosomes/lysosomes (LELs) play a role in HIV-1 trafficking towards its assembly sites. However, the role of LELs during assembly at VCCs is not fully understood. Herein, we used the HIV-1-inducible cell line THP-1 GagZip as a model to study HIV-1 Gag intracellular trafficking and assembly in macrophages. We demonstrated LEL involvement at VCCs using various microscopy techniques and biochemical approaches. Live-cell imaging revealed that HIV-1 repositions LELs towards the plasma membrane and modulates their motility. We showed that Arl8b-mediated LEL repositioning is not responsible for Gag trafficking to VCCs. Additionally, the inhibition of myristoylation by PCLX-001 decreased the presence of Gag on endosomes and inhibited VCC formation in both the THP-1 cell line and primary macrophages. In conclusion, we present evidence supporting the idea that HIV-1 manipulates the LEL trajectory to guide Gag to VCCs in an N-myristoylation-dependent manner.
Histidine-rich calcium-binding protein: a molecular integrator of cardiac excitation–contraction coupling
Authors: Mackrill John James 
Published: October 2024

ABSTRACT
During mammalian cardiomyocyte excitation–contraction coupling, Ca2+ influx through voltage-gated Ca2+ channels triggers Ca2+ release from the sarcoplasmic reticulum (SR) through ryanodine receptor channels. This Ca2+-induced Ca2+ release mechanism controls cardiomyocyte contraction and is exquisitely regulated by SR Ca2+ levels. The histidine-rich calcium-binding protein (HRC) and its aspartic acid-rich paralogue aspolin are high-capacity, low-affinity Ca2+-binding proteins. Aspolin also acts as a trimethylamine N-oxide demethylase. At low intraluminal Ca2+ concentrations, HRC binds to the SR Ca2+-ATPase 2, inhibiting its Ca2+-pumping activity. At high intraluminal Ca2+ levels, HRC interacts with triadin to reduce Ca2+ release through ryanodine receptor channels. This Review analyses the evolution of these Ca2+-regulatory proteins, to gain insights into their roles. It reveals that HRC homologues are present in chordates, annelid worms, molluscs, corals and sea anemones. In contrast, triadin appears to be a chordate innovation. Furthermore, HRC is evolving more rapidly than other cardiac excitation–contraction coupling proteins. This positive selection (or relaxed negative selection) occurs along most of the mammalian HRC protein sequence, with the exception being the C-terminal cysteine-rich region, which is undergoing negative selection. The histidine-rich region of HRC might be involved in pH sensing, as an adaptation to air-breathing, endothermic and terrestrial life. In addition, a cysteine-rich pattern within HRC and aspolin is also found in a wide range of iron–sulfur cluster proteins, suggesting roles in redox reactions and metal binding. The polyaspartic regions of aspolins are likely to underlie their trimethylamine N-oxide demethylase activity, which might be mimicked by the acidic regions of HRCs. These potential roles of HRCs and aspolins await experimental verification.
Nas diásporas e encruzilhadas do cotidiano escolar: as travessias dos currículos praticados de uma escola municipal de Manaus
Authors: Simões Ceane Andrade 
Published: October 2024

O presente ensaio emerge de um processo de estudo iniciado a partir da busca de compreensão das experiências educativas de uma comunidade escolar situada na fissura entre a idealização da cidade modernizada e a cidade praticada por aqueles e aquelas que são jogados para as suas margens, oriundos e oriundas de diferentes movimentos diaspóricos, e que, a despeito de não serem convidados e convidadas a compor o clube da humanidade, nas palavras do líder indígena e pensador Ailton Krenak, ainda teimam em inventar e criar os seus saber[es]xistências. Diante da presença de filhos da comunidade haitiana, chegada à cidade de Manaus no fluxo migratório ocorrido nos anos de 2010 e, mais recentemente, da comunidade venezuelana, cuja presença se intensificou a partir do ano de 2018, minha aposta é que o cerne das experiências curriculares produzidas na EMEF Prof. Waldir Garcia se adere a uma perspectiva fronteiriça, de encruzilhada, enredadas em diálogo com/nas diásporas vividas pelos seus sujeitos e que rasuram e desorganizam os limites e controles impostos à escola. Conhecer tais travessias, como recurso metafórico que permite entender os seus currículos praticados, exige considerar muito seriamente as gingas e as vozes dos sujeitos que a integram e o modo como atribuem significados, performatizam e narrativizam as práticas de educação, vida e arte no solo da escola, transcriando e (re)territorializando as suas múltiplas experiências existenciais e processos identitários.
Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and Prognostic Nutritional Index as Prognostic Markers for Lung Carcinoma
Authors: Mi Hai-li , Wei Wen-lu , Zhang Dong-hui , Liang Hua-ying , Yue Cai-feng , Xu Jing-ning 
Published: October 2024

Aims/Background Lung cancer (LC) remains one of the most common malignant tumours worldwide, and assessment of its progression is important for ensuring better prognostic outcomes for patients. This study was designed to explore the prognostic role of certain indices, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and prognostic nutritional index (PNI) in patients with LC, to help clinics to better determine the prognosis of patients with LC, and to allow them to intervene in a timely manner. Methods A retrospective analysis of 116 initially diagnosed patients with LC in China from 2018 to 2020 was conducted. The counts of neutrophils (NEU), lymphocytes (LYM), and monocytes (MON), as well as albumin levels, were obtained from laboratory databases. The PNI was calculated using a specific formula. The progression-free survival (PFS) curves were plotted using the Kaplan–Meier method, and the Log-rank test was used to compare survival among different groups. The potential prognostic role of these indicators was assessed with univariate and multivariate regression analysis. Results Multivariate Cox regression demonstrated that the PNI (hazard ratio (HR): 0.513, 95% confidence interval (CI): 0.288–0.917, p = 0.024), NLR (HR: 2.038, 95% CI: 1.128–3.682, p = 0.018), and tumour type (small cell lung cancer vs. non-small cell lung cancer) (HR: 2.145, 95% CI: 1.308–3.520, p = 0.003) were significantly associated with PFS. The median PFS for patients with low and high PNI was 10 and 11.5 months, respectively. Conclusion The NLR, PLR, and PNI are all significantly associated with the prognostic survival of LC patients.
Sputtered aluminum nitride waveguides for the telecommunication spectrum with less than 0.16 dB/cm propagation loss
Authors: Singh Radhakant , Raghuwanshi Mohit , Sundarapandian Balasubramanian , Thomas Rijil , Kirste Lutz , Suckow Stephan , Lemme Max C. 
Published: October 2024

We report the fabrication and characterization of photonic waveguides from sputtered aluminum nitride (AlN). The AlN films were deposited on 6” silicon substrates with a 3 µm buried silicon oxide layer using reactive DC magnetron sputtering at a temperature of 700°C. The resulting uncladded polycrystalline waveguides exhibit propagation losses of 0.137 ± 0.005 dB/cm at wavelengths of 1310 nm and 0.154 ± 0.008 dB/cm at a wavelength of 1550 nm in the TE polarization. These results are the best reported for sputtered AlN waveguides in the C-band and the first report in the O-band. These performances are comparable to those of the best-reported AlN waveguides, which are epitaxially grown by metal-organic chemical vapor deposition (MOCVD) on sapphire substrates. Our findings highlight the potential of sputtered AlN for photonic platforms working in the telecom spectrum.
Adverse health outcomes in offspring of parents with alcohol-related liver disease: Nationwide Danish cohort study
Authors: Jepsen Peter , West Joe , Larsen Anna Kirstine Kjær , Kann Anna Emilie , Kraglund Frederik , Morling Joanne R. , Crooks Colin , Askgaard Gro 
Published: October 2024

Background
Parental drinking can cause harm to the offspring. A parent’s diagnosis of alcohol-related liver disease (ALD) might be an opportunity to reach offspring with preventive interventions. We investigated offspring risk of adverse health outcomes throughout life, their association with their parent’s educational level and diagnosis of ALD.

Methods and findings
We used nationwide health registries to identify offspring of parents diagnosed with ALD in Denmark 1996 to 2018 and age- and sex-matched comparators (20:1). We estimated the incidence rate ratios (IRRs) of hospital contacts with adverse health outcomes, overall and in socioeconomic strata. We used a self-controlled design to examine whether health outcomes were more likely to occur during the first year after the parent’s ALD diagnosis.
The 60,804 offspring of parents with ALD had a higher incidence rate of hospital contacts from age 15 to 60 years for psychiatric disease, poisoning, fracture or injury, alcohol-specific diagnoses, other substance abuse, and of death than comparators. Associations were stronger for offspring with low compared to high socioeconomic position: The IRR for admission due to poisoning was 2.2 versus 1.0 for offspring of an ALD parent with a primary level versus a highly educated ALD parent. Offspring had an increased risk for admission with psychiatric disease and poisoning in the year after their parent’s ALD diagnosis. For example, among offspring whose first hospital contact with psychiatric disease was at age 13 to 25 years, the IRR in the first year after their parent’s ALD diagnosis versus at another time was 1.29 (95% CI 1.13, 1.47). Main limitation was inability to include adverse health outcomes not involving hospital contact.

Conclusions
Offspring of parents with ALD had a long-lasting higher rate of health outcomes associated with poor mental health and self-harm that increased shortly after their parent’s diagnosis of ALD. Offspring of parents of low educational level were particularly vulnerable. This study highlights an opportunity to reach out to offspring in connection with their parent’s hospitalization with ALD.
HIV-related perceived stigma and internalized stigma among people living with HIV/AIDS in Africa: A systematic review and meta-analysis
Authors: Tadesse Gebresilassie , Rtbey Gidey , Andualem Fantahun , Takelle Girmaw Medfu , Melkam Mamaru , Tadesse Abate Asnake , Wassie Yilkal Abebaw , Tekleslassie Alemayehu Tekletsadik , Geremew Gebremariam Wulie , Dires Eshetie Andargie , Tinsae Techilo , Fentahun Setegn , Nakie Girum 
Published: October 2024

Background
HIV-related stigma has significant adverse impacts on people living with HIV/AIDS, such as psychological distress, decreased quality of life, a reluctance to get screened and treated, and a reluctance to disclose their status due to fear of stereotypes or rejection.

Objectives
To determine the pooled prevalence and factors associated with HIV-related perceived stigma and internalized stigma among people living with HIV/AIDS in Africa.

Methods
Articles that assessed the prevalence and associated factors of HIV-related perceived stigma and internalized stigma were reviewed. PubMed, EMBASE, Google Scholar, African Journal Online, CINAHL, and Science Direct were the databases used to search the primary studies. The data was extracted through a Microsoft Excel spreadsheet and exported to STATA version 14 for further analysis. The I2 test was applied to test heterogeneity, whereas Egger’s test and funnel plot were used to check publication bias.

Results
In this study, the total sample size was 28,355 (for perceived stigma) and 22,732 (for internalized stigma). The overall pooled prevalence of HIV-related perceived stigma and internalized stigma was determined to be 41.23% and 35.68%, respectively. Based on the subgroup analysis results, the highest pooled prevalence of perceived stigma was observed in Nigeria (50.04%), followed by Ethiopia (41.72%), while the highest prevalence of internalized stigma was observed in Ethiopia (56.13%), followed by Cameroon (44.66%). Females (OR = 1.63: 1.31, 2.02) and rural dwellers (OR = 1.93: 1.36, 2.74) had more odds of experiencing HIV-related perceived stigma.

Conclusion and recommendation
This study concluded that four in ten and more than one-third of people living with HIV/AIDS suffered from perceived and internalized stigma. Thus, special considerations must be given to women and rural dwellers. It is recommended to implement multi-level interventions and foster empowerment and support for individuals living with HIV.
Investigating the effects of a daily multidisciplinary intensive outpatient rehabilitation program on innovative biomarkers in people with Parkinson’s disease: Study protocol for a phase III randomized controlled clinical trial
Authors: Saibene Francesca Lea , Agliardi Cristina , Salvatore Anna , Arcuri Pietro , Castagna Anna , Gobbo Silvia , Merlo Federico , Bowman Thomas , Anastasi Denise , Pagliari Chiara , Farina Elisabetta , Alberoni Margherita , Calabrese Elena , La Rosa Francesca , Arienti Chiara , Saresella Marina , Guerini Franca Rosa , Cattaneo Davide , Baglio Francesca , Clerici Mario , Navarro Jorge , Meloni Mario 
Published: October 2024

Background
To date, there has been no medication that has prevented the progression of Parkinson’s disease (PD). Many benefits of intensive and multidisciplinary rehabilitation program for PD are supported by clinical, epidemiological, and experimental data. The main question is whether high-intensity motor and cognitive exercises have an effect on the disease’s biological mechanisms.

Objective
This study protocol is a Randomized Controlled Trial (RCT) designed to determine the efficacy of an experimental, intensive, and multidisciplinary treatment in comparison to a home-based self-treatment in improving biomolecular and functional parameters in PD.

Methods
A total of 72 participants will be randomly allocated to two different groups, experimental (n = 36) and control group (n = 36). The rehabilitation program will last 6 consecutive weeks and will involve the execution of a total of 30 sessions, one for each day of the week from Monday to Friday. Participants allocated to the control group will carry out a home-based self-treatment program that includes muscle-stretching and active mobilization exercises for 40’/day for 6 consecutive weeks. The primary outcome measure is the effects of both treatments on a new set of molecular biomarkers such as oligomeric alpha-synuclein and neurotrophic factors measured in peripheral neural derived extracellular vesicles (NDEVs). Secondary outcomes will include changes of motor and non-motor symptoms, balance and gait performance and cognitive functioning. This RCT has been registered as “Intensive Multidisciplinary Rehabilitation and Biomarkers in Parkinson’s Disease” on 30 May, 2022 to ClinicalTrials.gov with the Study ID number: NCT05452655.

Discussion
This rehabilitation program is believed to be crucial in modifying biomolecular and functional parameters in people with PD. We expect that this study will provide additional evidence to understand the impact of an aerobic and intensive rehabilitation program on brain plasticity in patients with PD.
Intra-articular corticosteroid injections for osteoarthritis: A qualitative study of patients’ and clinicians’ experiences
Authors: Moore Andrew J. , Palmer Cecily K. , Barker Karen L. , Gooberman-Hill Rachael , Judge Andy , Wylde Vikki , Whitehouse Michael R. 
Published: October 2024

Background
Osteoarthritis is a leading cause of joint pain and disability. Intra-articular corticosteroid injections (IACs) are often used in primary care once other recommended treatments have failed. Evidence shows that IACs provide short-term relief of osteoarthritis symptoms, yet little is known about patients’ and primary care clinicians’ experiences and beliefs about their use. We explored patients’ and primary care clinicians’ views about IACs, including the benefits, disadvantages, perceived risks of treatment, when they are used, and factors that affect decision-making.

Methods
We conducted individual interviews with patients and primary care clinicians and used inductive thematic analysis to investigate their views and experiences of intra-articular corticosteroid injections for osteoarthritis (IACs).

Findings
We interviewed 38 patients and 19 primary care clinicians. We identified 6 patient themes: variation in access; awareness of IACs; views of risk and trust; effectiveness of IACs; variation in onset and effect duration; and an alternative to undesirable treatments. In the interviews with clinicians, we identified an overarching theme of caution and competence, which included eight subthemes: confidence and (dis)comfort with practical procedures; risk of adverse outcomes; training; uncertainty about evidence and guidelines; technical uncertainties; IACs use on the osteoarthritis pathway; perceived benefits and impacts of IACs; and the possibility of placebo.

Conclusion
Patients and clinicians valued IACs’ potential to relieve symptoms and improve quality of life. Variability in patients’ access to treatment appears related to clinicians’ confidence in delivering injections and their concerns about the evidence base. Variation in dose frequency and timing reflect clinicians’ uncertainty about current guidance. Despite variation in effectiveness patients preferred IACs to other forms of pain medication and to delay or avoid surgery. IACs were mostly used as an adjunct treatment before surgery was offered. These findings can inform further research into the effectiveness of IACs and improvements in information and guidance.
High-risk human papillomavirus testing for cervical cancer screening in Uganda: Considering potential harms and benefits in a low-resource setting
Authors: Sultanov Marat , Koot Jaap A. R. , de Bock Geertruida H. , Greuter Marcel J. W. , Beltman Jogchum J. , de Fouw Marlieke , de Zeeuw Janine , Kabukye Johnblack , Stekelenburg Jelle , van der Schans Jurjen 
Published: October 2024

Objectives
The World Health Organization supports both the screen-and-treat (ST) approach and the screen, triage and treat (STT) approach to cervical cancer screening using high-risk human papillomavirus (hrHPV) testing. For Uganda, the sequence of hrHPV-ST and hrHPV-STT could be similar, with visual inspection with acetic acid (VIA) after positive hrHPV tests in both. To consider potential tradeoffs (overtreatment in ST versus missed cancer cases in STT), we compared hrHPV-STT with VIA triage (STT-VIA), and STT with HPV 16/18 genotyping risk stratification, to hrHPV-ST for Uganda, in terms of overtreatment, cervical cancer incidence, and life years, for the general female population of Uganda.

Methods
A microsimulation model of cervical cancer was adapted. Incremental benefit-harm ratios of STT were calculated as ratios of prevented overtreatment to reduced life years, and to increased cancer cases. Additional scenarios with 20% difference in intra- and inter-screening follow-up between ST and STT were modeled.

Results
Both STT strategies resulted in life year losses on average compared to ST. STT-VIA prevented more overtreatment but led to increased cervical cancer incidence and life year losses. STT-G-VIA resulted in better harm-benefit ratios and additional costs. With better follow-up, STT prevented overtreatment and improved outcomes.

Discussion
For Uganda, the STT approach appears preferrable, if the screening sequences of hrHPV-based ST and STT are similar in practice. While VIA triage alone would reduce overtreatment the most, it could also result in more cancer cases. Risk stratification via genotyping could improve STT. Potential follow-up differences and resource availability should be considered by decision-makers when planning Uganda’s hrHPV-based screening strategy.
Factors influencing physical activity and sedentary behaviour in contact centres during the COVID-19 pandemic and their relevance for the future of hybrid working
Authors: Manner Jillian , Sivaramakrishnan Divya , Baker Graham , Lloyd Scott , Jepson Ruth 
Published: October 2024

Background
The COVID-19 pandemic changed the way many industries work, including contact centres, with some employees working from home and new on-site restrictions/measures in place representing even greater challenges for employers around staff engagement and wellbeing. This study aimed to understand the interplay of individual, social, environmental and organisational factors influencing physical activity and sedentary behaviour in UK contact centre employees, how the pandemic impacted these factors, and their relevance for the future of hybrid working.

Methods
Individual interviews (n = 33) were conducted with participants (staff working full and part time, on site and from home) from four UK contact centres. A topic guide based on the ecological model was developed to understand current barriers and facilitators to physical activity and (reducing) sedentary behaviour during and outside of working hours. Thematic analysis was carried out using a codebook and a deductive coding approach to identify themes.

Results
Three key insights are provided. First, participants felt they were generally sitting more and moving less since the first UK-wide lockdown. Second, factors which negatively impacted on these behaviours were evident across all levels of the ecological model. These included individual and social barriers (e.g., lack of motivation and preferable physical activity options) as well as environmental and organisational barriers (e.g., poor home office setup, back-to-back virtual meetings). There were a mix of new and existing barriers (exacerbated by the pandemic) and several of these were linked to homeworking. Third, organisational support requirements (e.g., homeworking ergonomic support) and existing facilitators (such as the provision of informational support and flexible working arrangements) were identified.

Conclusion
Solutions to reduce sedentary behaviours and increase physical activity in contact centres need to address barriers from the individual to the organisational level. Whilst the study was undertaken in the UK, the results are like to be applicable globally.

Trial registration
Clinical trial registration: The trial for the wider project has been registered on the ISRCTN database: http://www.isrctn.com/ISRCTN11580369.