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Human herpesvirus 6 viremia and encephalitis in CAR T-cell recipients

Abstract Human herpesvirus 6 reactivation in chimeric antigen receptor T-cell recipients is reported to be rare. Our patient cohort (n = 119) experienced a sevenfold higher incidence of viremia than a previous study and 2 cases of encephalitis. Further studies are needed to determine risk factors for infection.

Author Correction: A guidance to intelligent metamaterials and metamaterials intelligence

Clinical outcomes of living kidney transplantation from donors aged 70 years and older: a Japanese multicenter study

Attitudes of blood and plasma donors towards biobanking for longitudinal health research

Background Blood and plasma donations provide a unique opportunity for setting up a biobank. Remainders of donations can be stored together with questionnaire data to allow for longitudinal health research. Insight in the attitude and understanding of potential concerns of donors towards biobanking allows incorporating their perspective in the set-up of biobanks as such. Methods In an online survey in July/August 2021 among 409 Dutch donors, we asked about their attitudes towards the collection and storage of remainders of donations, questionnaires, and DNA, and towards the storage period, data sharing and linkage, and feeding back results and outcomes. Results The overall attitude of participating donors towards biobanking remainders of donations is very positive with 99% indicating willingness to provide their consent and 94% to fill out questionnaires. Most respondents (74%, n = 292/395) would agree to a long-term storage of 30 years. When asked about potential concerns, respondents mostly mentioned personal data security (30%), commercial use of data (11%) and misuse of data (5%). Also, 40% (n = 155/390) showed some hesitance towards the storage of DNA, including 28% (n = 111/390) who would give conditional consent if being informed on for instance DNA utilisation. Finally, the majority would like to receive feedback of research results, and indicated this to contribute to a greater likelihood of biobank participation. Conclusion Our findings show high support among surveyed donors for the storage of donation remainders in a biobank, provided high data security standards and clear communication about data protection measures and usage of biobank data and materials.

Breaking the silence: restoring <i>CEBPA</i> to fight leukemia

New finds shed light on diet and locomotion in Australopithecus deyiremeda

High power density gallium nitride radio frequency transistors via enhanced nucleation in heteroepitaxy

Mapping defect distribution in transparent single-walled carbon nanotube film with electrical resistance tomography

Abstract We extend the application of electrical resistance tomography (ERT) to visualize I G / I D distribution in transparent single-walled carbon nanotube (SWCNT) thin films. By establishing the correlation between disorder and resistance through experimental measurements, we successfully converted ERT-reconstructed conductivity distributions into I G / I D maps. This approach enabled the detection of a defect region with an I G / I D ratio of approximately 15 embedded in a pristine SWCNT film ( I G / I D = 18.1), corresponding to a minimum detectable resistance ratio ( R / R 0 ) of 1.59. Moreover, in a sample containing two defect regions introduced by plasma irradiation at 20 and 40 W, ERT successfully distinguished them despite the small difference in I G / I D ratio (1.1). Simulation studies revealed that positional deviations in reconstructed images can be attributed to electrode misalignment, contact resistance variation, and plasma-induced defect expansion. These results demonstrate the feasibility of ERT as a non-destructive, high-resolution technique for evaluating disorder variations in conductive thin films. Furthermore, due to its conductivity-based imaging principle, the method is applicable to other materials such as graphene, indium tin oxide (ITO), and metal nanowire networks, offering promise for real-time monitoring and quality assurance in large-area optoelectronic device manufacturing.

Overexpression of PTPRCAP inhibits biological function of lung adenocarcinoma through apoptosis pathway

Background PTPRCAP (protein tyrosine phosphatase receptor C-associated protein) has been implicated in tumor suppression in several malignancies; however, its role in lung adenocarcinoma (LUAD) remains unclear. This study aimed to investigate the expression profile and functional significance of PTPRCAP in LUAD. Methods Forty-five pairs of LUAD and adjacent non-tumor tissues were collected from patients undergoing surgery at Chengde Medical University Affiliated Hospital. PTPRCAP mRNA and protein levels were quantified by RT-qPCR and immunohistochemistry (IHC), respectively, and correlated with clinicopathological features. A549 and H1299 LUAD cell lines and BEAS-2B normal bronchial epithelial cells were used for in vitro assays. PTPRCAP was overexpressed via plasmid transfection (OE group) and compared with vector-transfected controls (Vector group). Functional assays included CCK-8 proliferation, scratch wound healing, Transwell migration/invasion, and Annexin V-PE apoptosis assays. Apoptosis-related proteins (Bax, Bcl-2, and cleaved caspase-3) were evaluated by Western blot. The effect of overexpression PTPRCAP on tumor growth was observed through nude mouse xenografts. Results PTPRCAP mRNA and protein levels were significantly lower in LUAD tissues than in adjacent non-tumor tissues (P &lt; 0.05). Low PTPRCAP expression correlated with advanced TNM stage and poor differentiation (P &lt; 0.05). In vitro, PTPRCAP expression was markedly reduced in A549 and H1299 cells compared with BEAS-2B. Overexpression of PTPRCAP significantly suppressed proliferation, migration, and invasion (P &lt; 0.001), and increased apoptosis rates in both cell lines (P &lt; 0.01). Mechanistically, PTPRCAP upregulation elevated pro-apoptotic Bax and cleaved caspase-3 while downregulating anti-apoptotic Bcl-2 (P &lt; 0.05). In vivo xenograft experiments demonstrated that overexpression PTPRCAP inhibited tumor growth in nude mice (P &lt; 0.001). Conclusions PTPRCAP is downregulated in LUAD and acts as a tumor suppressor by promoting apoptosis and inhibiting proliferation, migration, and invasion. These findings suggest PTPRCAP as a potential therapeutic target for LUAD.

More than an emotional support PET

Genetic architecture and mechanisms of host-microbiome interactions from a multi-cohort analysis of outbred laboratory rats

Abstract The intestinal microbiome influences health and disease. Its composition is affected by host genetics and environmental exposures. Understanding host genetic effects is critical but challenging in humans, due to the difficulty of detecting, mapping and interpreting them. To address this, we analyse host genetic effects in four cohorts of outbred laboratory rats exposed to distinct but controlled environments. We show that polygenic host genetic effects are consistent across cohort environments. We identify three replicated microbiome-associated loci, one of which involves the sialyltransferase gene  St6galnac1 and Paraprevotella . We find a similar association in a human cohort, between ST6GAL1 and Paraprevotella , both of which have been linked with immune and infectious diseases. Moreover, we find indirect (i.e. social) genetic effects on microbiome phenotypes, which substantially increase the total genetic variance. Finally, we identify a novel mechanism whereby indirect genetic effects can contribute to “missing heritability”.

Genetic variation of cutaneous leishmaniasis causative species in Ethiopia

Retraction: Preterm birth is not associated with asymptomatic/mild SARS-CoV-2 infection per se: Pre-pregnancy state is what matters

Rbm38 deficiency impairs erythroid heme biosynthesis and induces porphyria via reduced ferrochelatase expression

Abstract RNA splicing and processing are critical for erythropoiesis, because dysregulation of RNA splicing ultimately disrupts protein synthesis. The RNA-binding protein Rbm38 is highly expressed during terminal erythropoiesis. Although in vitro studies have implicated Rbm38 as a key regulator of erythroid differentiation, the landscape of RNA splicing regulated by Rbm38 and its role in terminal erythropoiesis in vivo have not been fully elucidated. Here, we generated whole-body and conditional knockout mouse models for Rbm38 and found that mature red blood cell (RBC) production was impaired in the bone marrow of Rbm38-deficient mice. Rbm38–/– RBCs exhibited reduced hemoglobin content and increased susceptibility to oxidative stress–induced hemolysis. These mutant mice also developed microcytic hypochromic anemia, along with dysregulated iron homeostasis. Additionally, they exhibited decreased mitochondrial heme biosynthesis and accumulation of free protoporphyrin IX (PPIX) in erythrocytes and feces, resembling human erythropoietic protoporphyria (EPP). Mechanistically, Rbm38 regulates the incorporation of ferrous iron (Fe2+) into PPIX to form heme by modulating alternative splicing, messenger RNA decay, and translation of the porphyrin metabolic enzyme gene Ferrochelatase (Fech). Importantly, enforced expression of Fech largely restored erythroid differentiation defects and ameliorated anemia in Rbm38–/– transplants. We further demonstrated that genetic variants in the human RBM38 gene locus influence PPIX levels in erythrocytes from healthy cohorts. Our findings demonstrate that Rbm38 governs terminal erythropoiesis by orchestrating RNA splicing, stability, and translation during heme biosynthesis.

The global hydrogen budget

Facet-dependent adsorbate-mediated strong metal-support interaction in Ni/TiO2

Research on the detection of foreign materials in tobacco shreds based on hyperspectral reflection imaging technology combined with machine learning

A qualitative exploration of the experience of individual-level stigma among adolescents with a chronic illness

Background Much of the research measuring stigma experience related to illness in children and adolescents has been conducted using measures developed from adult perspectives. However, children and adolescents are different from adults developmentally, and stigma is a subjective concept. As the first step in a multi-phase process to develop generic measures of individual-level stigma for use with adolescents with an illness, a qualitative study was conducted to explore the lived experiences of the different forms of individual-level stigma among adolescents with various illnesses. Methods Semi-structured interviews, utilizing multiperspectival interpretive phenomenological analysis, were conducted to identify commonalities in the experiences of perceived, enacted, and internalized stigma among adolescents with different chronic conditions recruited from illness-specific clinics at 2 general hospitals and a public clinic. Results The adolescents’ experience of perceived stigma was centered on negative treatments they anticipated receiving due to their illnesses, rather than a focus that also included awareness of illness-specific stereotypes, as suggested by the Modified Labelling Theory. Their awareness of illness-specific stereotypes was limited and mainly internalized, manifesting itself as negative self-beliefs. Their fear of negative treatments, also internalized, led them to conceal their illnesses and have negative feelings about themselves. They experienced enacted stigma mainly in interpersonal relationships in overt and subtle ways. Their interpretations of some of the treatments they received from others influenced their experience of enacted stigma. Furthermore, the adolescents’ experience of individual-level stigma was influenced by their level of development, cognitive maturity, and changes in their peer groups. Also, their experience of stigma bore some similarities with adults. Conclusions The study found that the adolescents’ experience of the different forms of individual-level stigma bore some similarities with adults as well as there were differences. The differences were due to the influence of social and cognitive development. The findings should inform quantitative assessments of individual-level stigma in adolescents with an illness.

<i>LEF1</i> intragenic deletion induces a dominant-negative isoform and unveils a Wnt/β-catenin vulnerability in T-ALL

Abstract T-cell acute lymphoblastic leukemia (T-ALL) represents a group of aggressive hematological malignancies characterized by unfavorable prognosis, urging the need for innovative therapeutic strategies. LEF1 is a member of the lymphoid enhancer factor (LEF)/T-cell factor family of DNA-binding transcription factors, known for their interaction with nuclear β-catenin in the context of the Wnt signaling pathway. Although the implication of LEF1 in colon cancer is well documented, its clinical relevance and functional consequences remain elusive in T-ALL. In this study, we provide valuable insights into the prevalence and significance of LEF1 alterations in a comprehensive cohort of 474 pediatric and adult patients with T-ALL enrolled in the FRALLE-2000 (French group for childhood ALL) and GRAALL 2003-2005 (Group for Research on Adult Acute Lymphoblastic Leukemia) trials, respectively. LEF1 alterations were detected in 63 cases (13%), including 9 point mutations (14.3%), 18 large deletions (28.6%), and, strikingly, 36 focal deletions (57.1%), which emerge as the most recurrent subtype. LEF1-altered cases were associated with increased central nervous system involvement and improved initial treatment response. Importantly, we unveil the existence of a previously undescribed dominant-negative LEF1 isoform resulting from focal deletions of the exons 2-3. This novel truncated protein, previously unreported in the literature, is associated with the disruption of the Wnt pathway and T-cell receptor signaling, which can be exploited as a therapeutic strategy to enhance chemosensitivity in LEF1-deleted T-ALL cases. The trials were registered at www.clinicaltrials.gov as #NCT00222027 (GRAALL 2003) and #NCT00327678 (GRAALL 2005); FRALLE2000T protocol (FRALLE-2000).

Measuring and mitigating debugging effectiveness decay in code language models