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Age-Related Macular Degeneration (AMD) is a highly prevalent form of retinal disease amongst Western communities over 50 years of age. A hallmark of AMD pathogenesis is the accumulation of drusen underneath the retinal pigment epithelium (RPE), a biological process also observable in vitro. The accumulation of drusen has been shown to predict the progression to advanced AMD, making accurate characterisation of drusen in vitro models valuable in disease modelling and drug development. More recently, deposits above the RPE in the subretinal space, called reticular pseudodrusen (RPD) have been recognized as a sub-phenotype of AMD. While in vitro imaging techniques allow for the immunostaining of drusen-like deposits, quantification of these deposits often requires slow, low throughput manual counting of images. This further lends itself to issues including sampling biases, while ignoring critical data parameters including volume and precise localization. To overcome these issues, we developed a semi-automated pipeline for quantifying the presence of drusen-like deposits in vitro, using RPE cultures derived from patient-specific induced pluripotent stem cells (iPSCs). Using high-throughput confocal microscopy, together with three-dimensional reconstruction, we developed an imaging and analysis pipeline that quantifies the number of drusen-like deposits, and accurately and reproducibly provides the location and composition of these deposits. Extending its utility, this pipeline can determine whether the drusen-like deposits locate to the apical or basal surface of RPE cells. Here, we validate the utility of this pipeline in the quantification of drusen-like deposits in six iPSCs lines derived from patients with AMD, following their differentiation into RPE cells. This pipeline provides a valuable tool for the in vitro modelling of AMD and other retinal disease, and is amenable to mid and high throughput screenings.

Qdenga® has been approved by the European Medicines Agency (EMA) for individuals > 4 years of age and for use according to national recommendations. The vaccine shows high efficacy against virologically confirmed dengue and severe dengue in clinical studies on 4–16-year old's living in endemic areas. For individuals 16–60 years old only serological data exists and there is no data for individuals > 60 years. Its use as a travel vaccine is still unclear. We present the studies behind the approval and the recommendations for travelers as issued by the Swedish Society for Infectious Diseases Physicians.

Latinos are at an increased risk of hypertension-related disparities. Biological, behavioral, cultural, and structural factors have been identified as underlying mechanisms driving these disparities. However, the influence of Latino settlement patterns on hypertension management practices has been rarely explored, particularly from a qualitative lens. Using data from semi-structured interviews conducted with Latinos with hypertension (n ​= ​26), we sought to develop a comprehensive understanding of the social and contextual factors influencing Latinos' hypertension management practices in new and established Latino destination states (Iowa and California, respectively). Participants described hypertension management as a complex phenomenon being influenced by factors at each level of the ecological model. However, some factors were more salient depending on place of residence. Specifically, while Latinos in Iowa were more likely to discuss how challenges of being an immigrant impacted their hypertension management, those in California had a preference to talk about how culture shapes the way they manage their hypertension. This study extends efforts to identify the underlying mechanisms driving Latinos' hypertension-related disparities. Results highlight the need to consider place of residence as a key contextual factor. Tailoring interventions to place may be necessary to effectively address Latinos’ hypertension-related needs.

Summary: To assess the transcriptomic profile of disease-specific cell populations, fibroblasts from patients with primary open-angle glaucoma (POAG) were reprogrammed into induced pluripotent stem cells (iPSCs) before being differentiated into retinal organoids and compared with those from healthy individuals. We performed single-cell RNA sequencing of a total of 247,520 cells and identified cluster-specific molecular signatures. Comparing the gene expression profile between cases and controls, we identified novel genetic associations for this blinding disease. Expression quantitative trait mapping identified a total of 4,443 significant loci across all cell types, 312 of which are specific to the retinal ganglion cell subpopulations, which ultimately degenerate in POAG. Transcriptome-wide association analysis identified genes at loci previously associated with POAG, and analysis, conditional on disease status, implicated 97 statistically significant retinal ganglion cell-specific expression quantitative trait loci. This work highlights the power of large-scale iPSC studies to uncover context-specific profiles for a genetically complex disease.

Summary: We assessed the pluripotency of human induced pluripotent stem cells (iPSCs) maintained on an automated platform using StemFlex and TeSR-E8 media. Analysis of transcriptome of single cells revealed similar expression of core pluripotency genes, as well as genes associated with naive and primed states of pluripotency. Analysis of individual cells from four samples consisting of two different iPSC lines each grown in the two culture media revealed a shared subpopulation structure with three main subpopulations different in pluripotency states. By implementing a machine learning approach, we estimated that most cells within each subpopulation are very similar between all four samples. The single-cell RNA sequencing analysis of iPSC lines grown in both media reports the molecular signature in StemFlex medium and how it compares to that observed in the TeSR-E8 medium. : Stem Cells Research; Transcriptomics; Automation Subject Areas: Stem Cells Research, Transcriptomics, Automation

We report the generation of the hiPSC line CERAi001-A-6 from primary human dermal fibroblasts. Reprogramming was performed using episomal vector delivery of OCT4, SOX2, KLF4, L-MYC, LIN28 and shRNA for p53.

A terapêutica transfusional é uma das mais importantes intervenções da medicina. Sendo a transfusão de sangue um procedimento complexo, não isento de riscos e frequente no Centro de Terapia Intensiva - CTI, torna-se essencial uma atuação profissional competente. O objetivo deste estudo é descrever a formação dos profissionais médicos e de enfermagem que atuam em CTI, relacionada à prática transfusional. A pesquisa foi realizada em um hospital universitário localizado no Triângulo Mineiro. Foi aplicado um instrumento estruturado e confeccionado para conhecer a participação dos profissionais na prática transfusional e qual a sua abordagem no processo de formação. Referem participar do processo transfusional 64% dos profissionais de saúde, os quais se sentem informados sobre o assunto. No entanto, 54% não participaram de atualização, 73% não participaram de programas de capacitação e 89% receberam informação sobre alguns aspectos da transfusão através de aulas teóricas. Considerando os resultados, torna-se necessário rever o processo de formação destes profissionais, bem como dos programas de capacitação sobre medicina transfusional oferecidos pelas instituições.Transfusion therapy is one of the most important interventions in medicine. However, blood transfusion is a complex proceeding, which is not devoid of risk but as it is common in the Intensive Care Unit (ICU), professional experience is essential. The objective of this study is to describe the level of instruction of medical and nursing professionals who work with transfusions in the Intensive Care Unit. This study was carried out in a University Hospital located in the Triângulo Mineiro region. A structured instrument was developed and applied to discover the professionals' participation in the transfusion practice and their approach to the process of instruction. About 64% of healthcare professionals participate in the transfusion process, all of whom felt they were informed about this subject. However, 54% did not participate in recycling training courses, 73% did not participate in training programs and 89% received information on some theoretical aspects of transfusion in classes. In light of the results, it is important to review the education of these professionals, as well as training programs on transfusion medicine offered by institutions.

Low-flow vascular malformations (LFVMs) account for over 90% of all vascular malformations, with the highest prevalence in the head and neck region. Intralesional sclerotherapy is the treatment of choice for subcutaneous LFVMs, although there is no consensus on optimal agent selection or dosage. Mild sclerosing agents, such as bleomycin, are commonly used in sensitive anatomical areas, including the head and neck, due to their favorable safety profile, despite slightly lower efficacy. This study presents our experience with fluoroscopy-guided, percutaneous or permucosal sclerotherapy using bleomycin for head and neck LFVMs, evaluating its safety and clinicoradiological outcomes. In total, 18 patients treated from December 2018 to August 2023 were retrospectively identified. All 50 procedures evaluated were technically successful, and over half of the patients who completed treatment showed marked improvement (lesion volume reduction of at least 50% on MRI). Most cases were managed on an outpatient basis, with no major complications during follow-up. Only one case of posttreatment intralesional hematoma required percutaneous drainage, resulting in a 2% complication rate. Our results support intralesional bleomycin sclerotherapy as a safe and effective treatment modality for head and neck LFVMs., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Head and neck squamous cell carcinomas (HNSCCs) represent a heterogeneous group of malignancies with multifactorial aetiologies. High-risk human papillomavirus (hrHPV) infections, particularly HPV16, and the dysregulation of telomerase activity, specifically through its catalytic subunit, telomerase reverse transcriptase (TERT) are among the key contributors to HNSCC development and progression. HPV promotes oncogenesis via the E6 and E7 oncoproteins, which inactivate tumour suppressors TP53 and RB1, leading to unchecked cellular proliferation. Concurrently, telomerase activation plays a critical role in HNSCC by maintaining telomere length, thus enabling cellular immortality, and facilitating tumour development and progression. The interplay between HPV and telomerase is significant; HPV oncoprotein E6 enhances telomerase activity through multiple regulatory mechanisms, including upregulating TERT expression. Beyond telomere maintenance, TERT influences signalling pathways, cellular metabolism, and the tumour microenvironment, contributing to aggressive tumour behaviour and poor prognosis. This review integrates the roles of HPV and telomerase in HNSCC, focusing on their molecular mechanisms and interactions that drive carcinogenesis and influence disease progression. Understanding the synergistic effects of HPV and TERT in HNSCC may be crucial for risk stratification, prognostic assessment, and the development of novel therapeutic strategies targeting these specific molecular pathways., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Electrical cardioversion (ECV) is frequently performed in symptomatic atrial fibrillation., Objective: This study aimed to assess the association of ECV with infarcts on brain magnetic resonance imaging (bMRI) and clinical outcomes., Methods: The Swiss Atrial Fibrillation Cohort Study included 2386 patients; 1731 patients were evaluated by bMRI. ECVs were recorded by questionnaire. Patients were assigned to categories by number of ECVs performed before enrollment (0, 1, ≥2). A bMRI study was conducted at baseline and after 2 years (n = 1227) and analyzed for large noncortical or cortical infarcts and small noncortical infarcts. Clinical outcomes were recorded during follow-up. Associations of ECV and outcome measures were assessed by multivariate analyses., Results: There was no independent association between the number of ECVs and infarct prevalence (large noncortical or cortical infarcts and small noncortical infarcts) on baseline bMRI (ECV 1 vs 0: odds ratio [OR], 0.95 [95% CI, 0.68-1.24]; ECV ≥2 vs 0: OR, 1.04 [0.72-1.44]) or between ECVs performed during follow-up and new infarcts on bMRI at 2 years (OR, 1.46 [0.54-3.31]). ECVs were not associated with overt stroke or transient ischemic attack (ECV 1 vs 0: hazard ratio [HR], 1.36 [0.88-2.10]; ECV ≥2 vs 0: HR, 1.53 [0.94-2.48]), hospitalization for heart failure (ECV 1 vs 0: HR, 1.06 [0.82-1.37]; ECV ≥2 vs 0: HR, 1.03 [0.77-1.38]), or death (ECV 1 vs 0: HR, 0.90 [0.70-1.15]; ECV ≥2 vs 0: HR, 0.91 [0.69-1.20])., Conclusion: There was no association between ECV performed before enrollment and cerebral infarcts on baseline bMRI or between ECV performed during follow-up and new infarcts at 2 years. Moreover, ECV was not associated with clinical events., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Current knowledge of the natural history of patients with porto-sinusoidal vascular disorder (PSVD) is derived from small studies. The aim of the present study was to determine the natural history of PSVD and prognostic factors in a large multicenter cohort of patients., Methods: We performed a retrospective study on patients with PSVD and signs of portal hypertension (PH) prospectively registered in 27 centers., Results: A total of 587 patients were included, median age of 47 years and 38% were women. Four-hundred and one patients had an associated condition, which was graded as severe in 157. Median follow-up was 68 months. At diagnosis, 64% of patients were asymptomatic while 36% had a PH-related complication: PH-related bleeding in 112 patients, ascites in 117, and hepatic encephalopathy in 11. In those not presenting with bleeding, the incidence of first bleeding was 15% at 5 years, with a 5-year rebleeding rate of 18%. The 5-year cumulative incidence of new or worsening ascites was 18% and of developing portal vein thrombosis was 16%. Fifty (8.5%) patients received a liver transplantation and 109 (19%) died, including 55 non-liver-related deaths. Transplant-free survival was 97% and 83% at 1 and 5 years, respectively. Variables independently associated with transplant-free survival were age, ascites, serum bilirubin, albumin and creatinine levels at diagnosis and severe associated conditions. This allowed for the creation of a nomogram that accurately predicted prognosis., Conclusions: The prognosis of PSVD is strongly determined by the severity of the associated underlying conditions and parameters of liver and renal function., Impact and Implications: Porto-sinusoidal vascular liver disorder (PSVD) is a rare entity that usually affects young people, frequently causes severe complications of portal hypertension, and may reduce life expectancy. To date, there is scarce information regarding its clinical manifestations, natural history and prognostic factors. The present study, including the largest number of patients with PSVD reported so far, shows that overall, when managed at centers of expertise, the prognosis of patients with PSVD is good, with LT-free survival rates of 83% and 72% at 5 and 10 years, respectively. Presence and severity of an underlying associated condition, presence of ascites, age and bilirubin, albumin and creatinine levels were associated with poor prognosis. These results are important to know for hepatologists. A final model combining these parameters enabled development of a nomogram that predicts prognosis with good discrimination and calibration capacity and can be easily applied in clinical practice., (Copyright © 2024 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Maternal stress during pregnancy can impact offspring health, increasing the risk of neuropsychiatric disorders. The human placenta plays a crucial role in understanding this effect, influencing fetal programming as it connects maternal and fetal circulation. Our hypothesis centers on maternal stress influencing children's outcomes through placental DNA methylation, targeting three cortisol-regulating genes: NR3C1, FKBP5, and HSD11B2. In this pilot study, chorionic villi and maternal decidua placental layers from 45 mother-infant dyads (divided into two groups based on high/low maternal stress exposure) were analyzed for DNA methylation at the genes of interest via targeted bisulfite sequencing. Pregnant women provided four saliva samples throughout a day for cortisol determinations and were assessed for the presence of depressive symptoms at each of the three trimesters of pregnancy. Newborns underwent neurodevelopmental assessments and salivary cortisol evaluations at 7 weeks. Increased maternal diurnal cortisol levels in the first trimester of pregnancy was significantly associated with elevated DNA methylation at exon 1D of the NR3C1 gene and lower DNA methylation at intron 7 of the FKBP5 gene, both in chorionic villi samples. Elevated DNA methylation at introns 1 and 7 of FKBP5 in the maternal decidua were strongly linked to an anticipated delivery. DNA methylation at the HSD11B2 promoter region was uniformly low across all placental samples. No associations with newborn neurodevelopment were found. These results emphasize the importance of exploring layer-specific methylation differences at distinct pregnancy stages, highlighting the complex interplay between maternal stress, placental epigenetic modifications, and fetal development throughout the prenatal period., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Objective: To evaluate the effectiveness of nonpharmacological conservative therapies for women with CPP., Data Sources: A systematic search of electronic databases (Amed, CINAHL, PsycINFO, SportDiscuss, Medline, PubMed, Embase, and Cochrane Central Register of Controlled Trials) was performed in January 2023, and updated in December 2023., Study Eligibility Criteria: Randomized controlled trials comparing a nonpharmacological conservative therapy to inert (eg, placebo, usual care) or nonconservative (eg, surgical, pharmacological) treatment were included. Conservative therapies of interest to this review were: multimodal physical therapy, predominantly psychological approaches, acupuncture, and other tissue-based monotherapies (eg, electrophysical agents, manual stretching)., Study Appraisal and Synthesis Methods: All study data were aggregated, and analyses of the included studies were performed. Effects on pain; sexual measures; psychological and physical function; health-related quality of life; symptom severity/bother; pelvic floor muscle function and morphometry; perceived improvement; and adverse events were analyzed. Meta-analyses (random effects model) were conducted using postintervention scores for data that included similar interventions and outcomes. Standardized mean differences were calculated. A narrative summary of findings that could not be included in the meta-analysis is provided. The quality of the evidence was assessed with the Physiotherapy Evidence Database scale and the certainty of evidence with Grading of Recommendations, Assessment, Development, and Evaluations criteria., Results: Of 5776 retrieved studies, 38 randomized controlled trials including 2168 women (mean age 35.1±8.6) were included. Meta-analyses revealed that multimodal physical therapy resulted in lower pain intensity compared to inert or nonconservative treatments in both the short (standardized mean difference -1.69, 95% confidence interval -2.54, -0.85; high certainty) and intermediate-terms (standardized mean difference -1.82, 95% confidence interval -3.13, -0.52; moderate certainty), while predominantly psychological approaches resulted in no difference in pain intensity (standardized mean difference -0.18, 95% confidence interval -0.56, 0.20; moderate certainty) and a slight difference in sexual function (standardized mean difference -0.28, 95% confidence interval -0.52, -0.04; moderate certainty). The level of evidence regarding the meta-analysis of the effects of acupuncture on pain intensity (standardized mean difference 1.08, 95% confidence interval -1.38, 3.54, nonstatistically significant results in favor of control treatment) precluded any statement of certainty. A limited number of trials investigated individual tissue-based monotherapies, providing a restricted body of evidence., Conclusion: This systematic review with meta-analysis revealed that multimodal physical therapy is effective in women with chronic pelvic pain with a high certainty of evidence., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Macrobenthic communities play a crucial role in the functioning of estuarine ecosystems and serve as bioindicators of environmental quality. This study assessed the ecological quality of an estuarine system using the AMBI and M-AMBI indices. The following parameters were considered: (i) environmental factors (total organic matter, organic carbon, grain size, calcium carbonate), (ii) sediment trace metals (Pb, Zn, Cu, Cr, Co, Ni, Hg, Li, As), (iii) species composition (morphological and molecular identification), and (iv) anthropogenic activities. The results demonstrated notable differences between study areas, reflecting hydrodynamic processes and human activities. The AMBI index indicated that all areas exhibited conditions classified as "slightly disturbed." However, the composition of the ecological groups and M-AMBI results differed according to the identification method. This approach allowed for a more complete understanding of communities, by integrating the influence of anthropogenic activities on the sediment and macrobenthic communities, highlighting the importance of using both identification methodologies., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Joana Marujo Neves reports financial support was provided by Foundation for Science and Technology. Joana Marujo Neves reports equipment, drugs, or supplies, statistical analysis, and writing assistance were provided by Portuguese Institute for the Sea and Atmosphere. Joana Marujo Neves reports equipment, drugs, or supplies was provided by Marine and Environmental Sciences Centre. Joana Marujo Neves reports a relationship with Foundation for Science and Technology that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To examine racial and ethnic differences in telemedicine mental health (tele-MH) use among nursing home (NH) long-stay residents with Alzheimer's disease and related dementias (ADRD) during the pandemic., Design: Observational study., Setting and Participants: The 2020-2021 Minimum Data Set 3.0, Medicare datasets, and Nursing Home Compare data were linked. A total of 259,467 NH long-stay residents with ADRD and 14,159 NHs were included., Methods: The outcome variable was the percentage of NH ADRD long-stayers who used tele-MH in 2021. The main independent variables were NH racial and ethnic compositions (ie, percentages of Black and Hispanic residents) and individual race and ethnicity. We conducted a set of logistic regression models with NH random effect. We first included only individual characteristics and then added NH characteristics., Results: Approximately 7% and 35% of the study cohort had tele-MH use and MH use in 2021, respectively. In our study cohort, 13.7% were Black, 6.6% were Hispanic, and 79.7% were White residents. The mean age was 83.4. After adjusting for NH characteristics, we found residents in NHs with a high proportion of Hispanic residents were more likely to use tele-MH both compared with those in NHs with a low proportion (odds ratio [OR], 1.867; 95% CI, 1.566-2.226), whereas residents in NHs with a high proportion of Black residents were less likely to use tele-MH both compared with those in NHs with a low proportion (OR, 0.843; 95% CI, 0.928-0.997)., Conclusions and Implications: Telemedicine may offer an opportunity for NHs with a higher proportion of Hispanic residents to better address their needs for MH services. However, NHs with a higher proportion of Black residents may face challenges in telemedicine adoption. Future studies are needed to better understand factors that could impact tele-MH use in NHs and reasons that lead to racial and ethnic differences., Competing Interests: Disclosure The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Retinitis Pigmentosa type 25 (RP25) is a form of inherited retinal dystrophy characterized by a progressive loss of rod photoreceptors, subsequent degeneration of cone photoreceptors, and eventually, the retinal pigment epithelium. Caused by mutations in the EYS gene, it is believed to be critical for the structural and functional integrity of the retina. Using a non-integrative RNA reprogramming method, we have generated human induced pluripotent stem cell (hiPSC) lines from RP25 patient and from carriers but asymptomatic daughters. These three hiPSC lines maintain a normal karyotype, exhibit pluripotency gene expression, and can differentiate into the three germ layers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Cold atmospheric plasma has recently gained much attention due to its antimicrobial effects. Among others, plasma has proven its potential to combat microbial biofilms. Yet, knowledge of complex network interactions between individual microbial species in natural infection environments of the biofilm as well as plasma-biofilm inactivation pathways is limited. This study reports the effects of a cold plasma generated by a pulsed streamer corona discharge in air on single- and mixed-species biofilms of P. aeruginosa and S. aureus. The plasma causes significant biofilm biomass reduction, bacteria inactivation, and alteration in intracellular metabolism. For single-species biofilms S. aureus is found more tolerant to plasma than P. aeruginosa, and mixed-species biofilms display higher tolerance of both bacteria to plasma than in single-species biofilms. A comparison between wet and dehydrated biofilms reveals reduced plasma efficacy in wet environments. Consequently, biofilm dehydration prior to the plasma treatment facilitates penetration of plasma reactive species leading to higher bacteria inactivation. The evaluation of plasma-generated gaseous reactive species reveals O 3 and NO 2 being dominant species contributing to the etching mechanism of the overall plasma anti-biofilm effect. Despite the strong anti-biofilm effect is obtained, the biofilm regrowth on the next day after plasma treatment implies on the inability of pulsed streamer corona discharge to permanently eradicate biofilms on a surface. The search for adequate plasma treatment conditions of biofilms remains crucial to avoid the appearance of more adaptive biofilms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: The advocacy Women Against Lung Cancer in Europe (WALCE) promoted the European Program for the Routine Testing of Patients With Advanced Lung Cancer (EPROPA) and provided a free-of-charge molecular profiling platform for NSCLC sample characterization with the aim of increasing the detection of targetable drivers and improving patients' access to clinical trials in Europe., Methods: From January 2021 to December 2023, 20 centers located at five different European countries (Greece, Slovenia, Romania, Albania, and Italy) joined EPROPA, with 555 patients with advanced NSCLC registered to the program. Anonymized patients' clinical-pathological data were shared through the EPROPA web platform and tissue samples were collected at the Molecular Pathology Unit of the Reference Center (University of Turin) for molecular analyses. A comprehensive genomic profiling by a targeted next-generation sequencing approach has been performed and molecular reports have been discussed within the molecular tumor board to assess patients' eligibility for clinical trials., Results: The average turnaround time was eight days, with only 30 out of 555 tissue samples (6%) not suitable for molecular analysis. In the 525 analyzed samples, a total of 570 molecular alterations have been identified, including 264 pathogenic targetable oncogenic alterations and 113 cases with co-occurring mutations. A total of 18 molecular alterations with potential germline and hereditary cancer syndrome implications have been reported. The identification of a clinical trial was considered for 205 patients. After molecular tumor board discussion, 30 patients were enrolled and treated in clinical studies available in Europe. Survival outcomes were significantly improved in patients with targetable molecular alterations receiving a matched targeted therapy., Conclusion: This data confirmed the feasibility and usefulness of the program in the real-world practice scenario, supporting the implementation of next-generation sequencing-based molecular characterization of NSCLC samples, to reduce the unequal access to tests, drugs, and clinical trials in Europe., Competing Interests: Disclosure Dr. Passiglia received consultants’ and advisory fees from AstraZeneca, BMS, Novartis, Pfizer, Roche, MSD, Amgen, Johnson and Johnson, Sanofi, Beigene, Gilead, Regeneron, Pharmamar, Thermo Fisher Scientific. Dr. Bironzo reports personal fees (as advisor) from Seagen, Regeneron, Pierre Fabre, and Janssen and research grants (Institution) from Pfizer and Roche. Dr. Tabbò reports personal fees (as speaker bureau) from AstraZeneca, Novartis, Roche, and Takeda. Dr. Buffoni reports personal fees (as advisor) from AstraZeneca, BMS, MSD, Novartis. Dr. Mazilu reports personal fees (as speaker bureau, advisor, manuscript writer, or travel expenses) from Accord, Angelini, Astellas, AstraZeneca, Bayer, BMS, Eli Lilly, Ipsen, Johnson & Johnson Romania, Merck, MSD, Novartis, Pfizer, Roche, Sandoz, Sanofi. Dr. Pignataro reports personal fees (as speaker bureau) from AstraZeneca, BMS, Novartis, Roche, and Takeda. Dr. Araujo reports personal fees (as speaker bureau, advisor, manuscript writer, or travel expenses) from Astellas, AstraZeneca, BMS, Eli Lilly Oncology, Janssen, MSD, Novartis, Pfizer, Roche. Dr. Paz-Ares reports personal fees (honoraria or travel expenses) from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Incyte, Ipsen, Lilly, Merck Serono, Mirati, MSD, Novartis, PharmaMar, Pfizer, Roche/Genentech, Sysmex. Other relationships (immediate family member) with Amgen, Ipsen, Merck, Novartis, Pfizer, Roche, Sanofi, and Servier. Cofounder of Altum Sequencing and an external board member for Genomica. Dr. Felip reports personal fees (as speaker bureau, advisor, or travel expenses) from AbbVie, Amgen, AstraZeneca, Bayer, BeiGene, BMS, Boeringher Ingelheim, Daichii Sankyo, Eli Lilly, F. Hoffmann-La Roche, Genentech, Gilead, GlaxoSmithKline, Janssen, Medical Trends, Medscape, Merck Serono, Merck Sharp & Dohme, Novartis, Peervoice, Peptomyc, Pfizer, Regeneron, Roche, Sanofi, Takeda, Touch Oncology, Turning Point. Ms. Comanescu reports personal fees (as advisor) from Novartis A.C.B. reports personal fees (as advisor or support for attending meetings) from BMS, Sanofi, and Takeda. Dr. Scotti reports personal fees (as speaker bureau or advisor) from AstraZeneca, BMS, MSD, Roche, Novatis, and Takeda. Research grant from AstraZeneca. Dr. Linardou reports personal fees (as advisor) from Amgen, AstraZeneca, BMS, GSK, MSD, Novartis, Pfizer, and Roche. Dr. Mohorcic reports personal fees (as advisor or support for attending meetings) from Amgen, BMS, Boehringer Ingelheim, Elli Lilly, Janssen, MSD, Pfizer, Roche, and Takeda. Dr. Malapelle reports personal fees (as speaker bureau or advisor) from Amgen Inc., AstraZeneca, Boehringer Ingelheim, Diatech, Eli Lilly & Company, GlaxoSmithKline, Hedera, Janssen Biotech, Merck Sharpe & Dohme Corporation, Novartis, Qiagen, Roche Health Solutions Inc., Thermo Fisher Scientific. Leadership Role: International Society of Liquid Biopsy and The Journal of Liquid Biopsy - Elsevier Spouse Dependent: Roche. Dr. Righi received consultants’ fees from AstraZeneca, Novartis, Roche, Amgen, BeiGene, Novartis, and Eli Lilly. Dr. Scagliotti reports personal fees (as consultant/advisor) from AstraZeneca, Bayer, BeiGene, Eli Lilly, J&J, MSD, Pfizer, Roche, and Takeda. Dr. Novello reports personal fees (as speaker bureau or advisor) from Eli Lilly, MSD, Roche, Takeda, Pfizer, Astra Zeneca, Amgen, Thermo Fisher, Novartis, Sanofi, Janssen, unrelated to the current work. The remaining authors declare no conflict of interest., (Copyright © 2024 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

The accumulation of nitrogen (N) in moss tissue has proven to be a reliable marker of increasing N deposition. However, this measurement does not offer additional data about the origin of pollution. In this respect, the analysis of the N isotopic ratios might be a helpful tool in providing supplementary information about the nature of the nitrogenous species in biomonitoring surveys. Furthermore, isotopic signatures have been extensively used in the study of N and carbon (C) biogeochemical cycles. The main purpose of this study was to determine N and C elemental contents and their stable isotopes in mosses to investigate atmospheric pollution patterns across Europe. We aimed at identifying the main N polluted areas and evaluating the potential use of isotopic signatures in the attribution of pollution sources at a regional scale. With these objectives in mind, >1300 samples from 15 countries from Europe, all of them participants of the ICP-Vegetation programme 2005-2006, were analyzed for their C and N contents and δ 15 N and δ 13 C. The results were compared to those derived from EMEP model, which provided modeled deposition and emission data, as well as to the predominant land uses at the sampling sites (based on CORINE Land Cover). This evaluation suggests that additional measurements of stable C and N isotopes in mosses could be a valuable tool in European environmental surveys. Such measurements not only provide useful information for identifying probable pollution sources but also enable the quantification of their contributions, serving as biological indicators of significant environmental processes. This study presents the first quantitative assessment of major atmospheric nitrogen (N) sources based on stable isotope analysis on a European scale, establishing a framework for evaluating historical changes in N across the region., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

In the past years, increasing attention has been paid to the role of extracellular vesicles (EVs) as mediators of intercellular communication in cancer. These small size particles mediate the intercellular transfer of important bioactive molecules involved in malignant initiation and progression. Hypoxia, or low partial pressure of oxygen, is recognized as a remarkable feature of solid tumors and has been demonstrated to exert a profound impact on tumor prognosis and therapeutic efficacy. Indeed, the high-pitched growth rate and chaotic neovascular architecture that embodies solid tumors results in a profound reduction in oxygen pressure within the tumor microenvironment (TME). In response to oxygen-deprived conditions, tumor cells and their surrounding milieu develop homeostatic adaptation mechanisms that contribute to the establishment of a pro-tumoral phenotype. Latest evidence suggests that the hypoxic microenvironment that surrounds the tumor bulk may be a clincher for the observed elevated levels of circulating EVs in cancer patients. Thus, it is proposed that EVs may play a role in mediating intercellular communication in response to hypoxic conditions. This review focuses on the EVs-mediated crosstalk that is established between tumor cells and their surrounding immune, endothelial, and stromal cell populations, within the hypoxic TME., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Raised emissions of biologically reactive nitrogen (N) have intensified N deposition, enhancing tree productivity globally. Nonetheless, the drivers of forest sensitivity to N deposition remain unknown. We used stem growth data from 62,000 trees across Europe combined with N deposition data to track the effects of air temperature and precipitation on tree growth's sensitivity to N deposition and how it varied depending on leaf form over the past 30 years. Overall, N deposition enhanced conifer growth (until 30 kg N ha -1  yr -1 ) while decreasing growth for broadleaved angiosperms. Lower temperatures led to higher growth sensitivity to N deposition in conifers potentially exacerbated by N limitation. In contrast, higher temperatures stimulated growth sensitivity to N deposition for broadleaves. Higher precipitation equally increased N deposition sensitivity in all leaf forms. We conclude that air temperature and leaf form are decisive in disentangling the effect of N deposition in European forests, which provides crucial information to better predict the contribution of N deposition to land carbon sink enhancement., Competing Interests: Declaration of competing interest We declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

We developed a mobile laboratory allowing field exposure of lung tissue models to ambient air at localities with various pollution sources (Background, Industrial, Traffic, Urban) in different seasons (summer/fall/winter). In samples originating from healthy and asthmatic individuals, we assessed the parameters of toxicity, lipid peroxidation and immune response; we further performed comprehensive monitoring of air pollutants at sampling sites. We measured lactate dehydrogenase (LDH) and adenylate kinase (AK) production and transepithelial electrical resistance (TEER), analyzed 15-F 2t -isopostane (IsoP) and a panel of 20 cytokines/chemokines/growth factors. In the ambient air, we detected particulate matter (PM), and other relevant chemicals (benzene, benzo[a]pyrene (BaP), NOx). In the Traffic locality, we found very high concentrations of ultrafine particles and NOx and observed low TEER values in the exposed samples, indicating significant traffic-related toxicity of the ambient air. In the Urban locality, sampled in winter, we observed high PM and BaP levels. We found lower AK levels in samples from healthy individuals exposed in this locality than in the asthmatic samples. In the samples from the Industrial locality, sampled in summer, we detected higher concentrations of TNFα, MIP-1α, Eotaxin, GROα, GM-CSF, IL-6 and IL-7 than in the Urban locality samples. We hypothesize that pollen or other plant-related components of the ambient air were responsible for this response. In conclusion, our data proved the feasibility of our mobile laboratory for field measurements of the biological response of lung tissue models exposed to ambient air, reflecting not only the levels of toxic compounds, but also season-specific parameters., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Accumulating evidence suggests that spontaneous preterm labor is a syndrome caused by multiple pathological processes. The breakdown of maternal-fetal tolerance has been proposed as a key mechanism of idiopathic spontaneous preterm labor, often viewed as a chronic inflammatory process resulting from the maternal immune system's impaired tolerance of the fetus from early pregnancy. Regulatory T cells are crucial for maintaining maternal-fetal tolerance. Even a partial reduction in their levels can disrupt this tolerance, leading to adverse pregnancy outcomes such as preterm labor. Given the complexity of the T lymphocyte-mediated immune response, identifying candidate signaling pathways involved in maternal-fetal tolerance is challenging. However, current literature highlights the importance of the functional and developmental markers FoxP3, CD45RA, Helios, and CD39 due to their immunosuppressive abilities essential for maintaining pregnancy., Objective: This study aimed to determine whether changes in numbers of selected regulatory T cell subpopulations in the first trimester are associated with subsequent spontaneous preterm labor., Study Design: This prospective study enrolled 43 women with early singleton pregnancies, excluding those with autoimmune diseases, diabetes mellitus (type 1, type 2), primary hypertension, or who had been treated with vaginal progesterone prior to sample collection. We analyzed regulatory T cell subpopulations in maternal circulation using the DURAClone IM T cell kit, focusing on the following subsets: CD4+CD25+FoxP3+, CD4+CD25+FoxP3+CD45RA, CD4+CD25+FoxP3+Helios+, and CD4+CD25+FoxP3+CD39-., Results: Among the participants, 7 experienced spontaneous preterm labor between the 23rd and 33rd weeks of gestation, while 36 delivered at term. The preterm group showed a significant reduction in numbers of all analyzed regulatory T cell subpopulations: CD4+CD25+FoxP3+ (median 0.0410×10ˆ9/L vs median 0.0550×10ˆ9/L, P=.0217), CD4+CD25+FoxP3+CD45RA- (median 0.0310×10ˆ9/L vs median 0.0420×10ˆ9/L, P=.0216), CD4+CD25+FoxP3+Helios+ (median 0.0270×10ˆ9/L vs median 0.0370×10ˆ9/L, P=.0260), CD4+CD25+FoxP3+CD39- (median 0.0300×10ˆ9/L vs median 0.0420×10ˆ9/L, P=.0427)., Conclusion: Early first trimester alterations in specific regulatory T cell subpopulations, including diminished levels of CD4+CD25+FoxP3+, CD4+CD25+FoxP3+CD45RA-, CD4+CD25+FoxP3+Helios+, and CD4+CD25+FoxP3+CD39-, are associated with idiopathic spontaneous preterm labor. These findings suggest that early changes in these lymphocyte subpopulations may be linked to spontaneous preterm birth. This highlights the need for further research to understand the mechanisms underlying regulatory T-cell dynamics and their impact on pregnancy outcomes., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The aim of this prospective study was to assess the duration of culture-viable SARS-CoV-2 and to monitor the emergence of mutations in a cohort of 23 kidney transplant recipients (KTRs) from June 2022 to June 2023. Combined nares/oropharyngeal swabs were collected weekly starting as soon as possible after symptom onset. The time from symptom onset to a negative culture was 11 days (interquartile range, 8-14), while the time to negative reverse transcriptase quantitative polymerase chain reaction was 18 days (interquartile range, 15-30). Beyond the first swab, 21.7% had a positive culture, and 8.7% replicated viable virus for longer than 30 days. T cell depletion (rate ratio, 2.5; 95% confidence interval [95% CI], 1.9-3.3; P < .001) and time from transplantation (rate ratio, 0.93; 95% CI, 0.90-0.97; P = .006) were associated with the time of viable virus shedding. A cycle threshold value of 24.2 demonstrated a 91.3% negative predictive value of viability (95% credible interval [95% CrI], 76-100). The odds of viability decreased by 69% per week of infection (odds ratio, 0.31; 95% CrI, 0.12-0.76). Overall, ribonucleic acid sequencing did not show accelerated molecular evolution though mutation rate could be increased in molnupiravir-treated KTRs. In conclusion, viable SARS-CoV-2 is eliminated rapidly, the risk of virus evolution is low, and prolonged self-isolation is generally unnecessary for most KTRs., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Melanoma is one of the most aggressive types of skin cancer, and the need for advanced platforms to study this disease and to develop new treatments is rising. 3D bioprinted tumor models are emerging as advanced tools to tackle these needs, with the design of adequate bioinks being a fundamental step to address this challenging process. Thus, this work explores the synergy between two biobased nanofibers, nanofibrillated cellulose (NFC) and lysozyme amyloid nanofibrils (LNFs), to create pectin nanocomposite hydrogel bioinks for the 3D bioprinting of A375 melanoma cell-laden living constructs. The incorporation of LNFs (5, 10 or 15 wt%) on a pectin-NFC suspension originates inks with enhanced rheological properties (shear viscosity and yield point) and proper shear-thinning behavior. The crosslinked hydrogels mimic the stiffness of melanoma tissues, being stable under physiological and cell-culture conditions, and non-cytotoxic towards A375 melanoma cells. P-NFC-LNFs (10 %) reveals good printability (Pr = 0.89) and printing accuracy (51 ± 2 %), and when loaded with A375 cells (3 × 10 6 cells mL -1 ) the bioink originates 3D-constructs with high cell viability (92 ± 1 %) after 14 days. The potential of the constructs as 3D in vitro platforms is corroborated by a drug-screening test with doxorubicin, where cells within the model displayed high sensitivity to the drug., Competing Interests: Declaration of competing interest The authors proclaim that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this manuscript., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Increasing the proportion of low-carbon inhalers prescribed within the NHS forms a central part of net-zero policy. Yet, the patients' perspective on this strategy has not been determined. We aimed to establish if environmental issues are important to respiratory patients and whether this may influence inhaler choice., Methods: We conducted a survey of 61 respiratory patients at the Royal Free NHS Foundation Trust, London to establish their perspective on the environmental impact of inhalers., Results: We identified that 70.5 % (43/61) of patients did not know that inhalers could contribute to climate change. Furthermore, 85.3 % (52/61) of patients felt it was 'quite' or 'very important' to reduce their own contribution to climate change. Importantly, 59 % (36/61) of patients would actively want to change inhalers and 26.2 % (16/61) would consider changing inhalers based on this information. There was no significant difference based on age (< or ≥ 60 years) (Chi 2  = 1.2, p = 0.28) or gender (Chi 2  = 0.88, p = 0.77)., Discussion: These findings demonstrate that environmental issues are important to respiratory patients. Despite this, the environmental impact of inhalers is not routinely discussed with patients. Once provided with this information patients actively want to change to low-carbon inhalers. Hence, the environmental impact of inhalers should be shared with patients to help us to achieve a net-zero NHS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Competing Interests: Conflicts of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Both 10 Hz repetitive transcranial magnetic stimulation (rTMS) as well as 18 Hz deep TMS (dTMS) constitute effective, FDA-approved TMS treatment protocols for depression. However, not all patients experience sufficient symptom relief after either of these protocols. Biomarker-guided treatment stratification could aid in personalizing treatment and thereby enhancing improvement. An individual alpha frequency (iAF)-based EEG-biomarker, Brainmarker-I, can differentially stratify patients to depression treatments. For instance, an iAF close to 10 Hz was associated with better improvement to 10 Hz rTMS, possibly reflecting entrainment of endogenous oscillations to the stimulation frequency. Accordingly, we examined whether 18 Hz dTMS would result in better improvement in individuals whose iAF lies around 9 Hz, a harmonic frequency of 18 Hz. Curve fitting and regression analyses were conducted to assess the relation between iAF and improvement. For treatment stratification purposes, correlations with iAF-distance to 10 Hz compared 18 Hz dTMS (N = 114) to 10 Hz rTMS (N = 72). We found a robust quadratic effect, indicating that patients with an iAF around 9 Hz exhibited least symptom improvement (r 2 =0.126, p<.001). Improvement correlated positively with iAF-distance to 10 Hz (p=.003). A secondary analysis in 20 Hz figure-of-eight data confirmed this direction. A significant interaction of iAF-distance and stimulation frequency between 10 and 18 Hz datasets emerged (p=.026). These results question entrainment of endogenous oscillations by their harmonic frequency for 18 Hz, and suggest that 10 Hz and 18 Hz TMS target different subgroups of depression patients. This study adds to iAF stratification, augmenting Brainmarker-I with alternative TMS protocols (18 Hz/20 Hz) for patients with a slower iAF, thereby broadening clinical applicability and relevance of the biomarker., Competing Interests: Declaration of competing interest Dr. Alyagon is an EEG consultant for BrainsWay Ltd. Dr. Downar has received research support from NIH, CIHR, Brain Canada, Ontario Brain Institute, the Klarman Family Foundation, the Arrell Family Foundation, and the Buchan Family Foundation, in-kind equipment support for investigator-initiated trials from MagVenture, is an advisor for BrainCheck, Arc Health Partners and Salience Neuro Health, and is a co-founder of Ampa Health. Dr. Zangen is an inventor of Deep TMS coils and has financial interest in BrainsWay Ltd. Dr. Sack is chief scientific advisor at PlatoScience Medical, scientific advisor at Alpha Brain Technologies, Founder and CEO of Neurowear Medical, Director of the International Clinical TMS Certification Course (www.tmscourse.eu), and receives equipment support from MagVenture, Magstim, and Deymed. Victoria Middleton and Aimee Halloran are employees of Salience Health. Dr. Donachie is Chief Medical Officer at Salience Health. Dr. Arns holds equity/stock in neurocare and Sama Therapeutics, serves as consultant to Synaeda, Sama Therapeutics and Roche and is named inventor on patents and intellectual property but receives no royalties. Brainclinics Foundation received equipment support from MagVenture and Deymed. All other authors report no biomedical financial interests or potential conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Problem and Background: The assessment of advantages and drawbacks associated with varying birthing positions has predominantly centered around medical or technical considerations and few studies have accounted for a woman's ability to attune to her bodily instincts during labor and birth. The objective of this study was to define the concept of dynamic birth positions and its significance within the birthing process., Methods: This hybrid concept analysis consisted of three phases: theoretical, fieldwork, and analytical. Science Direct, PubMed and Google Scholar were searched with related terms in the theoretical phase. In the fieldwork phase, seven professionals and six mothers with the experience of dynamic birth positions were interviewed. After each interview, qualitative content analysis was conducted. During the final phase, descriptions and themes from the first two phases were combined., Results: In the theoretical phase, the definition of dynamic birth positions included descriptions answering the Who, What, When, Where, and Why questions. In the fieldwork phase, the results present two distinct categories that define dynamic birth positions: "Women's choice, women's power" and "A flow between rest and activity." The final analysis phase of this study indicated that dynamic birth positioning is characterized by the organic progression through a variety of postures that seamlessly merge rest and activity throughout the labor and birthing process, guided by the woman's individual preferences., Conclusions: The definition of dynamic birth positions redefines birth as an evolving, dynamic journey characterized by a fluid interplay of movements and moments of rest, transcending conventional fixation on static positions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

In recent decades, interest in non-traditionally colored eggs has increased. For breeders, this market interest means breeding lines of laying hens that lay eggs of varied colors, such as the blue-green eggshells (Dominant Greenshell) in this study. This study presents the results of genotyping the polymorphism of the O locus responsible for shell coloration and photometric measurement of eggshell color based on the CIELAb system, which was carried out on the unique Czech breeding population Dominant Greenshell. The aim was to use a combination of phenotyping using the CIELab System method and genotyping of the O locus using the end-point PCR approach with the main focus on the accuracy of distinguishing shell color genotypes, streamlining the selection of dominant homozygotes in the O locus, optimizing this technology for the most efficient and cost-effective selection procedure in practical hen breeding. The optometric method was able to reliably distinguish only dominant and recessive phenotypes and eliminate from the population only undesirable recessive homozygotes with a white colored shell. The parameter a* (redness/greenness) from the CIELab color space turned out to be absolutely key for distinguishing dominant and recessive phenotypes. Using the CART methodology, a classification tree built on discriminating optometric characteristics a-blunt was obtained, however, for the group of desirable O/O homozygotes, the selection approach would result in incorrect genotyping of 31% of individuals. Therefore, a combined approach based on rapid and simple elimination of recessive homozygotes using phenotyping (CIELab photometric measurement) and molecular identification of the EAV-HP insertion in the SLCO1B3 gene in dominant phenotypes, regardless of color intensity affected by laying time/order, and allowing reliable elimination, has proven to be the most effective method to distinguish heterozygotes from the breeding population. The combination of optometric and molecular selection methods then leads to more efficient selection, reduction of overall selection costs. This process led to the stabilization of the breeding population within one generation and the achievement of a pure homozygous line with regard to eggshell color., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Body image concerns are prevalent among adolescents globally, including in urban and semi-rural India. These concerns have the potential to hinder adolescents' participation in everyday activities, thereby obstructing both social and academic development. In semi-rural India, where opportunities are constrained by limited resources, the impact of these concerns can be particularly detrimental. Given the scarcity of psychometrically valid measures to evaluate the impact of these concerns specifically within the semi-rural Indian context, this study aimed to culturally adapt and validate the Body Image Life Disengagement Questionnaire (BILD-Q) for use in Hindi among adolescents in semi-rural India. A total of 960 adolescents completed the Hindi version of the BILD-Q, alongside supplementary measures related to body image. Through exploratory factor analysis, a singular dimension of body image life disengagement emerged as the most fitting. The 9-item one-factor model gained further support through confirmatory factor analysis. The scale demonstrated robust internal consistency and test-retest reliability. Analysis confirmed the scale's ability to compare scores between boys and girls without measurement bias. This study introduces a culturally adapted version of the BILD-Q as a valid and reliable measure for assessing the impact of body image concerns on life disengagement among Hindi-speaking adolescents in semi-rural India., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest. PCD and MD have provided independent consultancy and advice to the Dove Self-Esteem Project and Dove brand (Unilever), (Copyright © 2024. Published by Elsevier Ltd.)

Introduction: Maternal SARS-CoV-2 infection can affect pregnancy outcome, but the placental response to and the effect of timing of infection is not well studied. The aim of this study was to investigate the placental levels of inflammatory and cardiovascular markers in pregnancies complicated by SARS-CoV-2 infection compared to non-infected pregnancies, and to investigate whether there was an association between time point of infection during pregnancy and placental inflammatory and cardiovascular protein levels., Methods: Placental samples from a prospectively recruited pregnancy cohort of SARS-CoV-2-infected (n = 53) and non-infected (n = 50) women were analysed for 177 inflammatory and cardiovascular proteins, using an antibody-based proximity extension assay. In the SARS-CoV-2-infected group, half of the women were infected before 20 weeks of gestation, and five women were hospitalised for severe SARS-CoV-2 infection. Single-protein analyses were performed with linear mixed effects models, followed by Benjamini-Hochberg correction for multiple testing. Multi-protein analyses were performed using principal component analysis and machine learning algorithms., Results: The perinatal outcomes and the placental levels of inflammatory or cardiovascular proteins in women with SARS-CoV-2 infection were similar to those in non-infected women. There were no differences in inflammatory or cardiovascular protein levels between early and late pregnancy SARS-CoV-2 infection, nor any linear correlations between protein levels and gestational age at time of infection., Discussion: Women with SARS-CoV-2 infection during pregnancy without clinical signs of placental insufficiency have no changes in inflammatory or cardiovascular protein patterns in placenta at time of birth regardless of the timing of the infection., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The main complication in hemophilia A treatment is the development of inhibitory antibodies against factor (F)VIII. Immune tolerance induction, the gold standard for eradicating anti-FVIII antibodies, is efficient in only 60% to 80% of cases. This underscores the need for more efficient induction of tolerance in patients with hemophilia A with FVIII inhibitors., Objectives: In this study, we explored whether red blood cells (RBCs) can be utilized as antigen delivery system to modulate the immune response against FVIII., Methods: Two promiscuously HLA-DR-presented peptides derived from the A2 and C1 domains of FVIII were fused to the TAT cell-penetrating peptide and incubated with RBCs., Results: Biotinylated TAT-A2 and TAT-C1 peptides were found to interact with RBCs as shown by flow cytometry and imaging flow cytometry. Moreover, macrophages efficiently phagocytosed TAT-FVIII peptide-treated RBCs. Using mass spectrometry-based immunopeptidomics we established that TAT-FVIII peptides were presented on major histocompatibility complex class II of macrophages that phagocytosed TAT peptide-pulsed RBCs. Specifically, the TAT-A2 peptide exhibited efficient processing and presentation on HLA-DR molecules. Importantly, incubation of TAT-C1 peptide-treated RBCs-loaded macrophages with a FVIII-specific T-cell hybridoma led to a significant increase in IL-2 production, suggesting functional presentation of TAT-C1-derived peptides by macrophages., Conclusion: Our findings indicate that RBCs can serve as effective vehicle for the delivery of FVIII-derived peptides to antigen-presenting cells. The successful display of T-cell epitopes on antigen-presenting cell using ex vivo-loaded RBC may be potentially utilized to modulate pathogenic immune responses such as observed in a subset of patients with hemophilia A., Competing Interests: Declaration of competing interests There are no competing interests to disclose., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Tea (Camellia sinensis (L.) O. Kuntze) plants have a strong ability to accumulate selenium (Se). However, the question of how tea plants affect Se availability has received little attention. In this study, five tea cultivars, including Soubei (SB), Aolǜ (AL), Longjing43 (LJ), Zhaori (ZR) and Fenglǜ (FL), were chosen for the study. Quantitative Microbial Ecology Chip and high-throughput sequencing were used to explore the effects of five tea cultivars on soil functions, microbial community structures and Se availability. The results showed that the total soil Se content in the FL garden was lower compared to LJ and SB gardens, whereas available Se was highest in the FL garden. Based on the Bray-Curtis distances, tea cultivar was the main factor affecting bacterial and fungal community structures. The abundance of functional genes concerning carbon, nitrogen, phosphorus and sulfur cycling processes varied among tea gardens. The higher soil NH 4 + and NO 3 - contents, and higher abundance of functional genes like nifH, amoA1 and narG, whereas lower total nitrogen in the FL garden than in the AL and LJ tea gardens demonstrated that the FL tea plants induced microbes to accelerate soil nitrogen cycling processes. Dominant microbes that positively related with functional genes like nifH, narG, and amoA1 were also positively related with the available Se content. In conclusion, tea cultivars could regulate soil functions through affecting microbial community structures and then affecting the soil Se availability. The soil nitrogen cycle processes are suggested to be closely related with Se transformation in tea gardens., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Wastewater monitoring data can be used to estimate disease trends to inform public health responses. One commonly estimated metric is the rate of change in pathogen quantity, which typically correlates with clinical surveillance in retrospective analyses. However, the accuracy of rate of change estimation approaches has not previously been evaluated., Objectives: We assessed the performance of approaches for estimating rates of change in wastewater pathogen loads by generating synthetic wastewater time series data for which rates of change were known. Each approach was also evaluated on real-world data., Methods: Smooth trends and their first derivatives were jointly sampled from Gaussian processes (GP) and independent errors were added to generate synthetic viral load measurements; the range hyperparameter and error variance were varied to produce nine simulation scenarios representing different potential disease patterns. The directions and magnitudes of the rate of change estimates from four estimation approaches (two established and two developed in this work) were compared to the GP first derivative to evaluate classification and quantitative accuracy. Each approach was also implemented for public SARS-CoV-2 wastewater monitoring data collected January 2021-May 2023 at 25 sites in North Carolina, USA., Results: All four approaches inconsistently identified the correct direction of the trend given by the sign of the GP first derivative. Across all nine simulated disease patterns, between a quarter and a half of all estimates indicated the wrong trend direction, regardless of estimation approach. The proportion of trends classified as plateaus (statistically indistinguishable from zero) for the North Carolina SARS-CoV-2 data varied considerably by estimation method but not by site., Discussion: Our results suggest that wastewater measurements alone might not provide sufficient data to reliably track disease trends in real-time. Instead, wastewater viral loads could be combined with additional public health surveillance data to improve predictions of other outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: There are few studies in unselected populations describing reproductive outcomes in women with polycystic ovary syndrome (PCOS) at the end of their reproductive years., Objective: To compare parity and maternal age at deliveries and explore factors associated with advanced maternal age in a large, unselected population-based cohort, followed prospectively for 25 years., Study Design: Women randomly selected from the general population and included in the prospective Australian Longitudinal Study on Women's Health were assessed approximately every third year from 1996 (age 18-23 years) to 2021 (age 43-48 years). Women with and without self-reported PCOS diagnosis (n=981 and n=13,266, respectively) were compared., Results: Overall 9.9% of women reported having PCOS by 43 to 48 years. Compared to women without PCOS, those with PCOS had fewer births (1.7±1.3 vs 1.9±1.2, P<.001), and more were nulliparous (23% vs 18%, P=.003). Women with PCOS were older at their first and second childbirths (29.5±5.5 vs 28.8±5.5 years and 32.1±5.2 vs 31.1±5.0 years, P<.001 for both). PCOS was associated with increased odds of advanced maternal age at first childbirth, adjusted odds ratio (aOR) 1.40 (95% confidence interval 1.10-1.80), and increased odds of gestational diabetes, aOR 3.90 (2.99-5.10). However, type 2 diabetes and hypertension were not associated with advanced maternal age (aOR 0.81 (0.43-1.50) and aOR 0.78 (0.59-1.03)), respectively. Within the PCOS group, a late PCOS diagnosis was associated with increased odds of advanced maternal age, aOR 1.98 (1.22-3.22)., Conclusion: Women with PCOS have lower parity and give birth at a later age than women without PCOS. PCOS is associated with advanced maternal age, with subsequent increased pregnancy complications. Later PCOS diagnosis is associated with double the rate of advanced maternal age at birth, emphasizing the importance of timely diagnosis., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The lack of synthesized information regarding biodiversity is a major problem among researchers, leading to a pervasive cycle where ecologists make field campaigns to collect information that already exists and yet has not been made available for a broader audience. This problem leads to long-lasting effects in public policies such as spending money multiple times to conduct similar studies in the same area. We aim to identify this knowledge gap by synthesizing information available regarding two Brazilian long-term biodiversity programs and the metadata generated by them. Using a unique dataset containing 1904 metadata, we identified patterns of metadata distribution and intensity of research conducted in Brazil, as well as where we should concentrate research efforts in the next decades. We found that the majority of metadata were about vertebrates, followed by plants, invertebrates, and fungi. Caatinga was the biome with least metadata, and that there's still a lack of information regarding all biomes in Brazil, with none of them being sufficiently sampled. We hope that these results will have implications for broader conservation and management guiding, as well as to funding allocation programs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)