bluuebunny/crossref_metadata_2025 huggingface dataset:
The Adoption of Artificial Intelligence Technologies in Arab Newsrooms: Potentials and Challenges
Authors: Harb Zahera , Arafat Rana
Published: October 2024

Arab newsrooms and journalists are still attempting to process how to benefit from using artificial intelligence (AI) in their daily news production. Many have started experimenting with generative AI. However, in countries with strong economies, or in newsrooms funded by strong economies like in the UAE, Saudi Arabia, and Qatar, news organizations have endorsed AI technologies beyond ChatGPT and similar tools. The majority of Arab journalists, however, are yet to understand what is meant by AI. Very few news organizations in the region have strategically approached the question of AI. Arab newsrooms need to examine when and why they need to use AI technologies, whether they have the infrastructure or can afford the resources. Implementing AI in Arab newsrooms presents an additional set of challenges, including language complexities, cultural sensitivities, potential biases in algorithms, and the need for tailored solutions that resonate with local audiences. The ethical implications present its own set of challenges. ChatGPT has proven to generate inaccurate data in Arabic. Resources are to be put in place to ensure the model is trained on a diverse and comprehensive dataset of Arabic text. Implementing bias detection and mitigation techniques to ensure the models are free from biases and offensive content is crucial. Newsrooms operating in authoritarian regimes have to be aware of governments' attempts to use generative AI to whitewash and promote state-centered actions and policies. Maintaining editorial integrity remains an important consideration.
Antibiotic-induced loss of gut microbiome metabolic output correlates with clinical responses to CAR T-cell therapy
Authors: Prasad Rishika , Rehman Abdur , Rehman Lubna , Darbaniyan Faezeh , Blumenberg Viktoria , Schubert Maria-Luisa , Mor Uria , Zamir Eli , Schmidt Sabine , Hayase Tomo , Chang Chia-Chi , McDaniel Lauren , Flores Ivonne , Strati Paolo , Nair Ranjit , Chihara Dai , Fayad Luis E. , Ahmed Sairah , Iyer Swaminathan P. , Wang Michael , Jain Preetesh , Nastoupil Loretta J. , Westin Jason , Arora Reetakshi , Turner Joel , Khawaja Fareed , Wu Ranran , Dennison Jennifer B. , Menges Meghan , Hidalgo-Vargas Melanie , Reid Kayla , Davila Marco L. , Dreger Peter , Korell Felix , Schmitt Anita , Tanner Mark R. , Champlin Richard E. , Flowers Christopher R. , Shpall Elizabeth J. , Hanash Samir , Neelapu Sattva S. , Schmitt Michael , Subklewe Marion , Francois-Fahrmann Johannes , Stein-Thoeringer C. K. , Elinav Eran , Jain Michael D. , Hayase Eiko , Jenq Robert R. , Saini Neeraj Y.
Published: October 2024

Antibiotic (ABX)–induced microbiome dysbiosis is widespread in oncology, adversely affecting outcomes and side effects of various cancer treatments, including immune checkpoint inhibitors and chimeric antigen receptor T-cell (CAR-T) therapies. In this study, we observed that prior exposure to broad-spectrum ABXs with extended anaerobic coverage such as piperacillin-tazobactam and meropenem was associated with worse anti-CD19 CAR-T therapy survival outcomes in patients with large B-cell lymphoma (N = 422) than other ABX classes. In a discovery subset of these patients (n = 67), we found that the use of these ABXs was in turn associated with substantial dysbiosis of gut microbiome function, resulting in significant alterations of the gut and blood metabolome, including microbial effectors such as short-chain fatty acids (SCFAs) and other anionic metabolites, findings that were largely reproduced in an external validation cohort (n = 58). Broader evaluation of circulating microbial metabolites revealed reductions in indole and cresol derivatives, as well as trimethylamine N-oxide, in patients who received ABX treatment (discovery, n = 40; validation, n = 28). These findings were recapitulated in an immune-competent CAR-T mouse model, in which meropenem-induced dysbiosis led to a systemic dysmetabolome and decreased murine anti-CD19 CAR-T efficacy. Furthermore, we demonstrate that SCFAs can enhance the metabolic fitness of CAR-Ts, leading to improved tumor killing capacity. Together, these results suggest that broad-spectrum ABX deplete metabolically active commensals whose metabolites are essential for enhancing CAR-T efficacy, shedding light on the intricate relationship between ABX exposure, microbiome function and their impact on CAR-T efficacy. This highlights the potential for modulating the microbiome to augment CAR-T immunotherapy. This trial was registered at www.clinicaltrials.gov as #NCT06218602.
Soluble B-cell maturation antigen levels for disease monitoring in oligosecretory and nonsecretory relapsed multiple myeloma
Authors: Ikeda Daisuke , Aikawa Shuichi , Misono Chiho , Oura Mitsuaki , Fujii Fuminari , Sakuma Hajime , Toho Masanori , Uehara Atsushi , Tabata Rikako , Narita Kentaro , Takeuchi Masami , Watari Tomohisa , Otsuka Yoshihito , Matsue Kosei
Published: October 2024

Soluble B-cell maturation antigen (sBCMA) is elevated on multiple myeloma (MM) cells. We investigated whether sBCMA levels correlated with other myeloma tumor volume indicators and its utility in monitoring oligosecretory/nonsecretory (O-S/Non-S) MM. In 115 patients with newly diagnosed MM, sBCMA was compared with M-protein levels, bone marrow plasma cells (BMPCs), circulating tumor cells (CTCs), and total diffusion volume (tDV; estimated by whole-body diffusion-weighted magnetic resonance imaging) at diagnosis. sBCMA levels increased significantly with International Staging System stage, chromosome 1q21 gain/amplification, and CTC levels. sBCMA also correlated strongly with %BMPC (r = 0.65) and moderately with tDV (r = 0.55) and paraprotein levels (involved immunoglobulin in IgG and IgA subtypes, r = 0.44 and 0.4; involved free light-chain levels in light-chain-only MM, r = 0.61, all P < .05). Longitudinal changes in sBCMA were consistent with disease status in both 17 O-S/Non-S and other secretory MM cases. Furthermore, sBCMA levels increased as early as 6 months prerelapse in almost all O-S/Non-S relapsed patients. Thus, sBCMA correlates strongly with total tumor volume in MM, as assessed using different modalities. We suggest that sBCMA is useful, not only for monitoring responses in patients with O-S/Non-S MM but also for early relapse detection and prediction.
Foscarnet eyedrops for the treatment of refractory herpetic keratitis
Authors: Awh Caroline C. , Knapp Austen N. , Goshe Jeffrey M. , See Craig W. , Lowder Careen Y.
Published: October 2024

Purpose

The purpose of this case series is to describe the clinical course of patients receiving foscarnet eyedrops for the treatment of refractory herpetic keratitis.

Observations

Six patients diagnosed with herpetic keratitis were treated with foscarnet 24 mg/mL (2.4%) eyedrops with resulting improvement in keratitis.

Conclusion

Topical foscarnet may be a safe and effective treatment for herpetic keratitis in conjunction with, or as an alternative to, conventional antiviral therapy. This is an off-label use of foscarnet.
Understanding rhizospheric microbial dynamics in gladiolus corms through quorum sensing and quorum quenching for disease control and growth promotion
Authors: Hameed Akhtar , Riaz Kashif , Jameel Sahar , Aslam Hafiz Muhammad Usman , Alam Muhammad Waqar , Zaheer Muhammad Saqlain , Riaz Muhammad Waheed , Rizwan Muhammad , Aljowaie Reem M. , Elshikh Mohamed S.
Published: October 2024

Gladiolus, a widely cultivated cut flower known for its aesthetically pleasing multicoloured spikes, has earned significant commercial popularity. A comprehensive understanding of the rhizosphere bacterial community associated with gladiolus is imperative for revealing its potential benefits. Molecular characterization is considered an effective method to gain insights into the structural and functional aspects of microbial populations. The soil characteristics and bacterial communities in the rhizosphere are typically influenced by quorum sensing (QS) and quorum quenching (QQ) mechanisms. This study aims to explore the niceties and diversity of rhizospheric bacterial populations linked with gladiolus corms, with a specific focus on understanding the dynamics of QS and QQ mechanisms in their complex interactions. The isolation of bacterial strains was achieved through the serial dilution method on nutrient agar (NA) media. The identification of the isolates was accomplished by amplifying 16 S rRNA gene sequences via polymerase chain reaction (PCR) via the use of universal primers. Sequence analysis was conducted via BLAST on the National Center for Biotechnology Information (NCBI) database. The characteristics of the isolated bacteria were elucidated via biosensors. This study identified three QS strains and five QQ strains. A consortium of quenchers was formulated utilizing five strains that demonstrated efficacy in mitigating the impact of disease on gladiolus and fostering growth. Among the three treatments—Scale, Descale, and Descale and Cut Half (DSC)—the DSC treatment emerged as the most effective. This treatment exhibited a broader range of variation in biological parameters over time, aligning with prevailing trends in the local market.
Interventions delivered by primary or community healthcare professionals to support people living at home with dementia with activities of daily living: a systematic review and narrative synthesis
Authors: Chester Helen , Bradbury Barbara , Santer Miriam , Morrison Leanne , Fader Mandy , Ward Jane , Manthorpe Jill , Murphy Catherine
Published: October 2024

Background

Most people living with dementia live in their own home supported by family carers. One of the most challenging problems they face is managing toilet-use and continence. Carers have repeatedly asked for better advice from healthcare professionals. The purpose of this systematic review was to inform the development of an intervention to support healthcare professionals to provide existing continence management advice to the carers of people living at home with dementia. It aimed to identify and synthesise lessons from the development and evaluation of interventions, involving primary or community healthcare professionals, to support the provision of management advice aimed at supporting people living at home with dementia and their carers with activities of daily living. Due to a lack of relevant continence or toilet-use interventions, this included, but was not limited to, toileting or continence care.

Methods

Literature (February 2009-November 2022) was searched using five databases: MEDLINE (Ovid); PsycINFO (Ovid); EMBASE (Ovid); Cumulative Index to Nursing and Allied Health Literature (CINAHL) (EBSCO); and Cochrane Central Register of Controlled Trials (CENTRAL). Empirical studies using a variety of methodologies were included and thus the quality of papers appraised using the Mixed-Methods Appraisal Tool. No studies were excluded based on quality. A narrative synthesis was undertaken.

Results

Twelve articles reporting on 10 interventions were included. Most comprised the provision of online resources only, although some combined these with online or face-to-face contact with healthcare professionals. A variety of methodologies was utilised including randomised controlled trials. The quality of included studies was variable. Six main themes were identified: mode of delivery; targeted and tailored resources; content, design and navigation; credibility; user involvement in the development and evaluation of information resources; and role of professionals and organisations.

Conclusions

Despite the urgent need to better support people living at home with dementia and their carers, this review highlights the paucity of studies reporting on interventions delivered within primary and community healthcare contexts to provide management advice aimed at supporting this population with activities of daily living. This review has identified important considerations that will potentially aid the development, delivery and evaluation of such interventions.

Systematic Review Registration

PROSPERO International Prospective Register of Systematic Reviews CRD42022372456.
Pregnancy and delivery after functional hemispherectomy for Rasmussen’s encephalitis: a case report
Authors: Jost Elena , Merz Waltraut M. , Kupczyk Patrick A. , Tascón Padrón Laura , Weber Eva C. , Bien Christian G. , Kosian Philipp
Published: October 2024

Background

Rasmussen’s encephalitis (RE) is a rare neurologic disorder characterized by progressive seizures and unilateral cerebral atrophy with onset during childhood and unknown etiology. When medical therapy appears refractory, surgical disconnection of the affected hemisphere is indicated. Quality of life after functional hemispherectomy is largely good, affected females may therefore pursue pregnancy. However, data on pregnancy and delivery in RE post hemispherectomy is extremely rare.

Case presentation

We present the case of a patient with left functional hemispherectomy for RE at the age of seven, who experienced two successful pregnancies. In both pregnancies, her post-surgical symptoms including right-sided spasticity, cephalgia, dizziness, and impairment of vision and speech deteriorated but improved to pre-pregnancy level after delivery. Neurologic sequelae post-hemispherectomy overlapped with clinical signs of preeclampsia and required close diagnostic surveillance during both pregnancies.

Conclusion

There are no data on the interaction between RE, hemispherectomy and pregnancy, making maternal and fetal risk assessment difficult. Due to the complexity of the condition and symptoms, management of RE in pregnancy remains highly challenging and requires an interdisciplinary approach. This is the first case description of two successful pregnancies in a woman with RE and status post-hemispherectomy. Further evidence is urgently required to improve counseling and management of affected women.
Health literacy demand and attitudes toward COVID-19 prevention measures among Korean American older adults and their caregivers
Authors: Han Hae-Ra , Yun Ji-Young , Min Deborah , Razaz Maryam
Published: October 2024

Background

Health literacy has been linked to positive attitudes toward COVID-19 preventive measures among adolescents and young- or middle-aged adult populations. This study examined the relationship between health literacy and attitudes toward COVID-19 preventive measures among non-English speaking Korean American older adults and their caregivers. The study additionally investigated how sociodemographic characteristics were associated with attitudes.

Methods

COVID-19 survey data was collected from potential participants for an ongoing randomized controlled trial involving both Korean American older adults and their caregivers in the Baltimore-Washington and the New York Metropolitan areas (ClinicalTrials.gov Identifier: NCT03909347). Korean American older adults with normal cognition and their caregivers were allowed to participate in the survey. We used latent profile analysis to find unique clusters of participants with a similar pattern of responses to attitudes toward COVID-19 preventive measures. Based on the analysis, we employed multinomial logistic regression to investigate how health literacy and sociodemographic characteristics were associated with the clusters.

Results

We found three clusters based on participant responses to COVID-19 preventive measures—Positive, Negative, or Mixed. Health literacy was not associated with COVID-19 related attitudes in the study sample. Men were 2.37 times more likely to be categorized as Mixed than having Positive Attitudes compared to women. The odds of a person living in the New York metropolitan area being categorized as having Mixed Attitudes compared to Positive Attitudes were also 2.67 times more than for a person living in the Baltimore-Washington area.

Conclusions

Differences in attitudes toward COVID-19 preventive measures were found among sociodemographic variables but not health literacy. Investigating what information channels or methods drive perception of public health information such as COVID-19 may help identify effective dissemination strategies for non-English speaking Korean older adults.
My virtual escape from patient life: a feasibility study on the experiences and benefits of individualized virtual reality for inpatients in palliative cancer care
Authors: Gerlach Christina , Haas Laura , Greinacher Anja , Lantelme Jonah , Guenther Melanie , Thiesbonenkamp-Maag Julia , Alt-Epping Bernd , Wrzus Cornelia
Published: October 2024

Background

Cancer patients benefit from Virtual Reality (VR) in burdensome situations, but evidence is scarce for palliative situations. Based on earlier work in palliative care, individualized VR interventions like seeing the patient’s home may address a patient’s wish to be at home and thus have a greater effect compared to standard VR content. Yet, some patients and relatives may be concerned about their privacy. Also, patient stakeholders raised concerns about triggering depressed mood or homesickness.

Aim

To test the feasibility and safety of individualized vs. standard 360°video VR interventions in palliative cancer inpatients.

Methods

Prospective observational study with patient-reported outcome measurement using validated instruments of well-being (MDBF), symptoms and psychosocial burden (IPOS), cybersickness (SSQ), presence experience (SPES), subjective benefit (2 items), content analysis of interviews, and field notes. Individualized VR content was recorded with action camcorder-technology to protect the patients’ privacy.

Results

Seventeen patients participated, median age 65 years (range 20–82), 9 women (53%), 8 single or widowed (47%), 4 childless (23.5%), 4 academics (23.5%), with a median length of stay of 9 days (1–75) in the hematology (10), palliative care (3), or radiotherapy (2) unit of a German university hospital. Eight patients (53.3%) chose their own home environments or family for individualized VR-content. All participants enjoyed the intervention. Compared to standard VR content the individualized VR tended to have a stronger effect on well-being and emotional touch. It was not inferior in terms of psychosocial burden and cybersickness. No subjective and relevant side effects occurred. The patients well tolerated the assessments. However, most patients demanded a lighter headset and a desire for more interactivity.

Conclusions

Individualization of VR content shows potential for enhancement of immersion, which improves the VR experience and does not harm in terms of depressed mood or worsening of symptoms. The patients’ and family desire for privacy is feasible with the support of family members who recorded the individualized videos, which is easily manageable today. We suggest a pragmatic randomized clinical trial to compare the effects of individualized vs. standard VR-content.

Trial registration

Registered at German Clinical Trials Register (Deutsches Register Klinischer Studien; DRKS); registration number: DRKS00032172; registration date: 11/07/2023.
Undergraduate musculoskeletal ultrasound training based on current national guidelines—a prospective controlled study on transferability
Authors: Weimer Andreas , Recker Florian , Vieth Thomas , Buggenhagen Holger , Schamberger Christian , Berthold Rainer , Berthold Svenja , Stein Stephan , Schmidmaier Gerhard , Kloeckner Roman , Neubauer Ricarda , Müller Lukas , Weinmann-Menke Julia , Weimer Johannes
Published: October 2024

Introduction

Musculoskeletal ultrasound (MSUS) is integral to routine clinical diagnostics for musculoskeletal and joint disorders. This study aims to establish and validate a sonography course tailored to undergraduate medical students acquiring MSUS-specific skills at a German university.

Methods

A blended learning training concept, comprising 24 instruction sessions of 45 min each, was designed based on the current national guidelines of the German Society for Ultrasound in Medicine (DEGUM). This program was integrated into the clinical phase of the undergraduate students’ medical education. The self-perceived improvement in competency and the effectiveness of the course design were evaluated using a a 7-point Likert scale questionnaire. Objective learning success was evaluated via a written test and a “Direct Observation of Practical Skills” practical exam. Control groups included medical students without MSUS training (control group 1) and doctors who had completed DEGUM-certified basic MSUS courses (control group 2). Both control groups completed the written test, while control group 2 also took the practical final exam. The study involved 146 participants: 56 were allocated to the study group, 44 to control group 1, and 46 to control group 2.

Results

The study group rated their skills significantly higher after the course (p < 0.01). Participants expressed high satisfaction with the course design, the teaching materials, and the teachers. The study group's performance on the final written test was comparable to those of control group 2 (p = 0.06) and significantly superior to control group 1 (p < 0.001). Additionally, the study group’s performance on the practical final exam was not significantly different from control group 2 (p = 0.28), with both groups achieving scores exceeding 80%.

Conclusion

Both subjective and objective measures of learning suggest that an MSUS course designed for postgraduates can be effectively adapted for undergraduate medical students. Incorporating MSUS training into the clinical curriculum is recommended to enhance future medical professionals' educational experience and practical skills.
Seasonal stability of the rumen microbiome contributes to the adaptation patterns to extreme environmental conditions in grazing yak and cattle
Authors: Guo Wei , Zhou Mi , Li Fuyong , Neves André Luis Alves , Ma Tao , Bi Sisi , Wang Weiwei , Long Ruijun , Guan Le Luo
Published: October 2024

Background

The rumen microbiome plays an essential role in maintaining ruminants’ growth and performance even under extreme environmental conditions, however, which factors influence rumen microbiome stability when ruminants are reared in such habitats throughout the year is unclear. Hence, the rumen microbiome of yak (less domesticated) and cattle (domesticated) reared on the Qinghai-Tibetan Plateau through the year were assessed to evaluate temporal changes in their composition, function, and stability.

Results

Rumen fermentation characteristics and pH significantly shifted across seasons in both cattle and yak, but the patterns differed between the two ruminant species. Ruminal enzyme activity varied with season, and production of xylanase and cellulase was greater in yak compared to cattle in both fall and winter. The rumen bacterial community varied with season in both yak and cattle, with higher alpha diversity and similarity (beta diversity) in yak than cattle. The diversity indices of eukaryotic community did not change with season in both ruminant species, but higher similarity was observed in yak. In addition, the similarity of rumen microbiome functional community was higher in yak than cattle across seasons. Moreover, yak rumen microbiome encoded more genes (GH2 and GH3) related to cellulose and hemicellulose degradation compared to cattle, and a new enzyme family (GH160) gene involved in oligosaccharides was uniquely detected in yak rumen. The season affected microbiome attenuation and buffering values (stability), with higher buffering value in yak rumen microbiome than cattle. Positive correlations between antimicrobial resistance gene (dfrF) and CAZyme family (GH113) and microbiome stability were identified in yak, but such relationship was negatively correlated in cattle.

Conclusions

The findings of the potential of cellulose degradation, the relationship between rumen microbial stability and the abundance of functional genes varied differently across seasons and between yak and cattle provide insight into the mechanisms that may underpin their divergent adaptation patterns to the harsh climate of the Qinghai-Tibetan Plateau. These results lay a solid foundation for developing strategies to maintain and improve rumen microbiome stability and dig out the potential candidates for manufacturing lignocellulolytic enzymes in the yak rumen to enhance ruminants’ performance under extreme environmental conditions.
Risk stratification in breast screening workshop
Authors: Anderson Andrew , Visintin Cristina , Antoniou Antonis , Pashayan Nora , Gilbert Fiona J. , Hackshaw Allan , Bhatt Rikesh , Hill Harry , Wright Stuart , Payne Katherine , Rogers Gabriel , Shinkins Bethany , Taylor-Phillips Sian , Given-Wilson Rosalind
Published: October 2024

Population screening for breast cancer (BC) is currently offered in the UK for women aged 50 to 71 with the aim of reducing mortality. There is additional screening within the national programme for women identified as having a very high risk of BC. There is growing interest in further risk stratification in breast screening, which would require a whole population risk assessment and the subsequent offer of screening tailored to the individual’s risk. Some women would be offered more intensive screening than others or no screening. This might provide a better balance of screening benefits and harms for each individual than the current population age-based programme alone. The UK National Screening Committee (UK NSC) is considering using decision-analytic and other models to evaluate different risk stratification screening strategies and identify remaining gaps in evidence. This paper reports the proceedings of a UK NSC workshop where experts in the field discussed both risk prediction models, as well as decision-analytic models providing a benefit-harm analysis/economic evaluation of risk-stratified screening programmes (see Table 1). The aim of the meeting was to present and discuss the current work of experts, including some data which had not been published at the time of the meeting, to inform the UK NSC. The workshop was not intended to present a balanced evaluation of how to deliver screening in future. Areas for further work identified included methods for comparing models to assess accuracy, the optimum risk assessment tools, the digital screening infrastructure, acceptability of stratification, choice of screening test and reducing inequalities. A move to risk stratification of the whole programme would require a careful phased introduction with continuing assessment of real-world evidence during deployment.
The deficient CLEC5A ameliorates the behavioral and pathological deficits via the microglial Aβ clearance in Alzheimer’s disease mouse model
Authors: Lin Yu-Yi , Chang Wen-Han , Hsieh Shie-Liang , Cheng Irene Han-Juo
Published: October 2024

Background

Alzheimer’s disease (AD) is a neurodegenerative disease that causes cognitive dysfunction in older adults. One of the AD pathological factors, β-Amyloid (Aβ), triggers inflammatory responses and phagocytosis of microglia. C-type lectin domain family 5 member A (CLEC5A) induces over-reactive inflammatory responses in several virus infections. Yet, the role of CLEC5A in AD progression remains unknown. This study aimed to elucidate the contribution of CLEC5A to Aβ-induced microglial activation and behavioral deficits.

Methods

The AD mouse model was crossed with Clec5a knockout mice for subsequent behavioral and pathological tests. The memory deficit was revealed by the Morris water maze, while the nociception abnormalities were examined by the von Frey filament and hotplate test. The Aβ deposition and microglia recruitment were identified by ELISA and immunohistochemistry. The inflammatory signals were identified by ELISA and western blotting. In the Clec5a knockdown microglial cell model and Clec5a knockout primary microglia, the microglial phagocytosis was revealed using the fluorescent-labeled Aβ.

Results

The AD mice with Clec5a knockout improved Aβ-induced memory deficit and abnormal nociception. These mice have reduced Aβ deposition and increased microglia coverage surrounding the amyloid plaque, suggesting the involvement of CLEC5A in AD progression and Aβ clearance. Moreover, the phagocytosis was also increased in the Aβ-stressed Clec5a knockdown microglial cell lines and Clec5a knockout primary microglia.

Conclusion

The Clec5a knockout ameliorates AD-like deficits by modulating microglial Aβ clearance. This study implies that targeting microglial Clec5a could offer a promising approach to mitigate AD progression.
Development will (try to) find its way: a qualitative study of Chilean adolescent mental health during and after lockdown
Authors: Espinoza Camila , Canessa Florencia , van der Veek Shelley , Alink Lenneke , van der Voort Anja
Published: October 2024

Background

The COVID-19 pandemic has had a well-evidenced impact on adolescents, who are especially sensitive to pandemic disruptions given the critical role of socialization in their development. In Chile too, evidence shows increases in mental health complaints among adolescents over the lockdown period. Our study aimed at exploring the experiences of Chilean adolescents regarding their mental health during the lockdown and school closure (March 2020-December 2021), and during the return to on-site education (2022) as informed by adolescents and school staff, with a focus on family, school, and social sources of risk and support for adolescents’ wellbeing during these periods.

Methods

Using a qualitative approach, we conducted semi-structured interviews with 19 adolescents and 16 staff members from schools in an urban area of Chile.

Results

Through thematic analysis, we generated five themes: [1] Adolescents in a mental health crisis, comprising a range of distressing experiences and mental health problems. This crisis was fueled by alterations in the functioning of adolescents’ systems: [2] Broken support systems (peers and school); [3] The school agenda must go on, reflecting schools’ strict compliance with the educational curriculum; and [4] Blurred boundaries between home and school life and within the family. Finally [5], Development will (try to) find its way describes how most participants experienced a bouncing back to wellbeing in the course of the school year upon return, and how some developmental milestones took place despite the abnormal conditions, providing evidence for resilience amid pandemic adversity.

Conclusions

The findings give insight into how the exchanges between the adolescent and the social systems they are embedded in were interfered. The results help us understand the challenges for mental health during and after the pandemic, and highlight adolescents’ capacity to thrive as normality was restored. The results also underscore the importance of upholding stability across adolescents’ systems and routines, in order to mitigate impacts on wellbeing amid abnormal circumstances. The findings are relevant for development-informed initiatives in policy design in the aftermath of the pandemic and in future crisis management responses.
Predictive value of tumor microenvironment on pathologic response to neoadjuvant chemotherapy in patients with undifferentiated pleomorphic sarcomas
Authors: Guegan Jean Philippe , El Ghazzi Nathan , Vibert Julien , Rey Christophe , Vanhersecke Lucile , Coindre Jean Michel , Toulmonde Maud , Spalato Ceruso Mariella , Peyraud Florent , Bessede Alban , Italiano Antoine
Published: October 2024

Undifferentiated pleomorphic sarcomas (UPS) represent a prevalent and aggressive subtype of soft tissue sarcomas (STS) in adults. Despite advancements in loco regional treatments, many patients with high grade STS, including UPS, develop metastatic disease. Neoadjuvant chemotherapy is a standard approach to mitigate this risk, but response variability necessitates refined patient selection strategies. This study investigated the correlation between UPS microenvironment and neoadjuvant chemotherapy response in resectable UPS. The NEOSARCOMICS study (NCT02789384) enrolled patients with resectable STS from six sarcoma centers in France. Patients received anthracycline based chemotherapy, followed by surgery. Histological response, gene expression profiling, and multiplex immunohistofluorescence were performed on baseline and post treatment tumor samples. Plasma proteomics was analyzed to identify biomarkers. Good responders to neoadjuvant chemotherapy showed enrichment in genes related to stemness and cell cycle regulation, while poor responders exhibited immune related gene enrichment. Proteomic profiling revealed immune pathway activation and downregulation of cell cycle pathways in non responders. Despite being associated with a good prognosis, high immune infiltration, particularly of CD8 + T cells and CD20 + B cells, predicts a poor response to neoadjuvant chemotherapy in UPS, suggesting the need for alternative therapeutic strategies for patients with inflamed UPS.Ongoing clinical trials are exploring the efficacy of combining chemotherapy with immune checkpoint inhibitors to improve outcomes.
Infectious etiology of intussusception in Indian children less than 2 years old: a matched case-control analysis
Authors: Praharaj Ira , Reddy Samarasimha Nusi , Nair Nayana Prabhakaran , Tate Jacqueline Elizabeth , Giri Sidhartha , Thiyagarajan Varunkumar , Mohan Venkata Raghava , Revathi Rajendiran , Maheshwari Kalaivanan , Hemavathy Priya , Kumar Nirmal , Gupte Mohan Digambar , Arora Rashmi , Senthamizh Sowmiya , Mekala Suhasini , Goru Krishna Babu , Pamu Padmalatha , Badur Manohar , Pradhan Subal , Dash Mrutunjay , Mohakud Nirmal Kumar , Ray Rajib Kumar , Gathwala Geetha , Gupta Madhu , Kanojia Ravi , Gupta Rajkumar , Goyal Suresh , Sharma Pramod , Mathew Mannancheril Abraham , Kochukaleekal Jacob Tarun John , Sundaram Balasubramanian , Girish Kumar Chethrapilly Purusothaman , Dorairaj Priyadarshini , Pitchumani Ramasubramaniam , Maniam Raghul , Kumaravel Sambandan , Jain Hemant , Goswami Jayanta Kumar , Wakhlu Ashish , Gupta Vineeta , Liu Jie , Houpt Eric R. , Parashar Umesh D. , Kang Gagandeep
Published: October 2024

Background

Enteric infections are hypothesized to be associated with intussusception in children. A small increase in intussusception following rotavirus vaccination has been seen in some settings. We conducted post-marketing surveillance for intussusception following rotavirus vaccine, Rotavac introduction in India and evaluated association of intussusception with enteric pathogens.

Methods

In a case-control study nested within a large sentinel hospital-based surveillance program in India, stool samples from 272 children aged less than 2 years admitted for intussusception and 272 age-, gender- and location-matched controls were evaluated with Taqman array card based molecular assays to detect enteric viruses, bacterial enteropathogens and parasites. Matched case-control analysis with conditional logistic regression evaluated association of enteropathogens with intussusception. Population attributable fractions (PAF) were calculated for enteropathogens significantly associated with intussusception.

Results

The most prevalent enteropathogens in cases and controls were enteroaggregative Escherichia coli, adenovirus 40/41, adenovirus C serotypes and enteroviruses. Children with intussusception were more likely to harbor adenovirus C serotypes (adjusted odds-ratio (aOR) = 1.74; 95% confidence interval (CI) 1.06–2.87) and enteroviruses (aOR = 1.77; 95% CI 1.05–2.97) than controls. Rotavirus was not associated with increased intussusception risk. Adenovirus C (PAF = 16.9%; 95% CI 4.7% − 27.6%) and enteroviruses (PAF = 14.7%; 95% CI 4.2% − 24.1%) had the highest population attributable fraction for intussusception.

Conclusion

Adenovirus C serotypes and enteroviruses were significantly associated with intussusception in Indian children. Rotavirus was not associated with risk of intussusception.
An adaptive parameter-free seismic data denoising approach by combining general cross-validation thresholding and pixel connectivity in synchrosqueezed domain
Authors: Zeng Zhiyi , Han Peng , Zhang Wei , Zhou Yong , Deng Xubiao , Zhang Da , Shi Yaqian , Chang Ying , Ji Hu , Dai Rui , Zhang Jianzhong
Published: October 2024

High signal-to-noise ratio (SNR) seismic waveform data are conductive to various studies in seismology. Seismic denoising aims to enhance SNR by eliminating additive noise through signal processing while preserving important features of the seismic signal. Conventional parametric seismic denoising methods often require selecting appropriate parameters to achieve optimal results, which may be limiting when dealing with various types and scales of seismic data. Here, we develop an adaptive parameter-free denoising method by combining general cross-validation (GCV) thresholding and pixel connectivity in synchrosqueezed (SS) domain. In this denoising framework, the synchrosqueezed continuous wavelet transform (SS-CWT) is first applied to obtain a high-resolution time–frequency representation. Then, the GCV approach, which allows for choosing the (nearly) optimal threshold without relying on any prior knowledge about the noise level, is employed to attenuate most of the low-energy noise. After that, the relatively isolated high-energy residual noise remaining in the SS-CWT spectrum is removed using pixel connectivity thresholding. Finally, the inverse SS-CWT is applied to the thresholded spectrum to obtain the denoised seismic record. As the thresholds for GCV and pixel connectivity are derived from the spectrum characteristics of the data being analyzed, the proposed denoising approach is highly adaptive and parameter-free. We demonstrate the effectiveness and versatility of the proposed denoising framework using synthetic data and real seismic data from diverse monitoring scenarios, including land, ocean, and emerging distributed acoustic sensing (DAS). The results indicate that the method is a stable and efficient tool for seismic data denoising.

Graphical Abstract
Analytical microscopy techniques using coaxial and oblique illuminations to detect thin glass particulates generated from glass vials for parenteral drug products
Authors: Sanni Adedayo M. , Opalade Adedamola A. , Shamirian Armen , Mattson Spencer , Driscoll Eric , St. Martin Michael , Mohan Shikhar , Trimmer Brooke , Bunch Tarq , Ovadia Robert , Yoon Jungjoo , Ma Sarina , Foti Chris
Published: October 2024

Glass vials are the most widely used primary containers for the packaging of parenteral products due to their optical clarity, general inertness, and hermetic properties, but under certain circumstances, they can pose safety concerns. Most of these issues are related to the potential formation of glass particulates through delamination or precipitation, resulting from the chemical interaction between the drug product and the inner surface of the glass vial. Hence, it is imperative for pharmaceutical companies to conduct product-vial compatibility studies to determine the appropriate packaging/container closure system. To support this development activity, scientists need to develop analytical methods to detect subvisible glass particulates in parenteral products, along with the appropriate positive controls, to facilitate detection and identification. This paper outlines the utilization of coaxial/episcopic and oblique illumination microscopy, combined with spectroscopic techniques, to detect thin glass particulates generated from a modified procedure. It also showcases the importance of angle-dependent lighting in visualizing positive control samples containing thin glass particulates. The analytical microscopy techniques discussed in this paper can assist scientists in selecting suitable container closure systems for developing parenteral products.
Adjuvant Docetaxel and Cyclophosphamide With or Without Epirubicin for Early Breast Cancer: Final Analysis of the Randomized DBCG 07-READ Trial
Authors: Jensen Maj-Britt , Balslev Eva , Knoop Ann Søegaard , Tuxen Malgorzata K. , Højris Inger , Jakobsen Erik H. , Cold Søren , Danø Hella , Glavicic Vesna , Kenholm Julia , Ejlertsen Bent
Published: October 2024

The primary analysis of the DBCG 07-READ trial reported in 2017 provided evidence of no overall benefit from adjuvant anthracyclines in patients with early
TOP2A
normal breast cancer in disease-free survival (DFS), distant disease-free survival (DDFS), or overall survival (OS). We performed a protocol-scheduled analysis of DDFS, DFS, and OS on the basis of 10-year follow-up. Full details on incident heart failure (HF) and second cancers were presented. Patients in the intention-to-treat population assigned to epirubicin and cyclophosphamide followed by docetaxel (EC-D) had longer DDFS (adjusted hazard ratio [HR], 0.79 [95% CI, 0.64 to 0.98];
P
= .03) and DFS (HR
Adjusted
, 0.83 [95% CI, 0.69 to 0.99];
P
= .04) than patients assigned to docetaxel and cyclophosphamide (DC). There was no statistically significant difference in mortality rates. The 10-year cumulative risk of HF was 2.1% (95% CI, 1.4 to 3.3) with EC-D and 1.1% (95% CI, 0.6 to 2.0) with DC (HR
Unadjusted
, 2.12 [95% CI, 1.03 to 4.35];
P
= .04). In conclusion, anthracycline followed by docetaxel improved outcome compared with DC in patients with
TOP2A
normal early breast cancer, and no clinical value of
TOP2A
testing was shown. The risk of HF was doubled in patients receiving anthracycline; however, overall, the risk of HF was low.
Smartphone Magnetometers for Assessing Programmable Shunt Valve Settings: A Proof-of-Concept Study
Authors: McCoy Carlie , Patel Smruti K. , Skoch Jesse
Published: October 2024

BACKGROUND AND OBJECTIVES:

Programmable shunt valves (PSVs) used to treat hydrocephalus require specialized valve-specific devices that determine their setting. However, these devices are typically only accessible in major medical centers. This study explores the feasibility of using smartphone magnetometers to assess PSV settings.

METHODS:

We investigated 2 PSVs, the Codman Certas Plus and Medtronic Strata II, using 3 different smartphones. Free open-source software was used to measure magnetic flux densities of the shunts, and PSV-specific algorithms were developed to interpret these measurements. All measurements were performed ex vivo.

RESULTS:

We demonstrated that this method could accurately determine PSV settings with 100% accuracy in ex vivo blinded trials. The technique was effective even with a scalp analog simulating different skin thicknesses.

CONCLUSION:

This proof-of-concept study suggests that smartphones can be used for PSV assessment. However, further development and validation are needed to refine this method for clinical use. This technology could enhance PSV management accessibility, allowing for remote or at-home evaluations by trained individuals or caregivers, thus improving patient care in underserved areas.
UVB radiation suppresses Dicer expression through β-catenin
Authors: Aktary Zackie , Petit Valérie , Berlin Irina , Raymond Jeremy , Berger Frederique , Charoenchon Nisamanee , Sage Evelyne , Bertrand Juliette , Larue Lionel
Published: October 2024

Ultraviolet (UV) rays prompt a natural response in epidermal cells, particularly within melanocytes. The changes in gene expression and related signaling pathways in melanocytes following exposure to UV radiation are still not entirely understood. Our findings reveal that UVB irradiation suppresses the expression of Dicer (also known as Dicer1). This repression is intricately linked to the activation of the phosphoinositide 3-kinase (PI3K), ribosomal S6 kinase (RSK) and Wnt–β-catenin signaling pathways, and is directly associated with transcriptional repression by β-catenin (also known as CTNNB1). Notably, we have identified specific binding sites for the TCF/LEF–β-catenin complex in the Dicer promoter. Collectively, these results emphasize the significance of the UV-induced pathway involving the TCF/LEF–β-catenin complex, which impacts Dicer expression. UV radiation also reduced the levels of specific microRNAs known to be important in the biology of melanocytes. This pathway holds potential importance in governing melanocyte physiology.
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

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

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.