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Georg Nilius,1 Ulrike Domanski,1 Maik Schroeder,1 Karl-Josef Franke,1 Anke Hogrebe,1 Laurent Margarit,2 Maria Stoica,2 Marie-Pia d’Ortho2,3 1HELIOS-Klinik Ambrock, Universität Witten-Herdecke, Hagen, Germany; 2Service de Physiologie – Explorations Fonctionnelles DHU FIRE, Groupe Hospitalier Bichat-Claude Bernard, Assistance Publique-Hopitaux de Paris, 3Université Denis Diderot Paris 7, Paris, France Background: Obstructive sleep apnea (OSA) is a highly prevalent condition; however, the majority of patients remain undiagnosed. There is a potential to expand the diagnostic capacity of sleep laboratories. The study objective was to validate a portable respiratory monitoring device (Alice PDX) against polysomnography (PSG) in the laboratory and to assess its reliability at home.Methods: A total of 85 patients with suspected OSA (80% male, mean age 49.1±13.5 years, body mass index 29.7±6.9 kg/m2, Epworth Sleepiness Scale 10.0±5.1) were randomized to 3 diagnostic nights: 1 night simultaneous in-laboratory PSG and PDX recording; 1 night self-applied PDX at home, and 1 night in-laboratory PSG. Study data were manually scored according to American Academy of Sleep Medicine criteria.Results: The Alice PDX was in diagnostic agreement with simultaneously recorded reference PSG in 96.4% of studies. In 2.4% of studies the in-laboratory PDX underestimated and in 1.2% of studies it overestimated the apnea hypopnea index (AHI). The difference between the AHI from the reference PSG and the home study was similar to the difference between the PSGs (2.79 vs 0.79, p=0.08).Conclusion: In a population with a high suspicion of OSA, the Alice PDX showed a high level of diagnostic agreement with a simultaneous PSG and performed valid home diagnostic studies for OSA. If manually scored, the portable device can be used by sleep specialists for diagnosing moderate-to-severe obstructive sleep apnea in cases with a high pretest probability for the disease over a wide range of disease severity. The technology can be deployed reliably outside of the sleep laboratory setting. Keywords: sleep apnea, diagnostic, portable device, ambulant monitoring, polysomnography

In second language (L2) reading strategy research, two concerns need addressing: (1) the discrepancy in assessing strategy use between written surveys and verbal reports, and (2) the effect of using strategies on readers' comprehension outcomes when different types of comprehension tasks are utilized. The present study addressed these concerns by asking five more-proficient and five less-proficient Chinese English as a foreign language (EFL) university learners to read two domain-specific texts while assessing their strategy use. The results from both quantitative and qualitative analyses revealed a "gap" between the survey and verbal reports for assessing L2 reading strategy use. Additionally, the contribution of strategies to the readers' comprehension was found to vary by comprehension task type. Similarly, the variety of strategy use had a strong association with the readers' performance on only one of three types of comprehension tasks, free recall. The findings hold important implications on L2 reading strategy instruction.

Genetic engineering of allogeneic cell therapeutics that fully prevents rejection by a recipient's immune system would abolish the requirement for immunosuppressive drugs or encapsulation and support large-scale manufacturing of off-the-shelf cell products. Previously, we generated mouse and human hypoimmune pluripotent (HIP) stem cells by depleting HLA class I and II molecules and overexpressing CD47 (B2M-/-CIITA-/-CD47+). To determine whether this strategy is successful in non-human primates, we engineered rhesus macaque HIP cells and transplanted them intramuscularly into four allogeneic rhesus macaques. The HIP cells survived unrestricted for 16 weeks in fully immunocompetent allogeneic recipients and differentiated into several lineages, whereas allogeneic wild-type cells were vigorously rejected. We also differentiated human HIP cells into endocrinologically active pancreatic islet cells and showed that they survived in immunocompetent, allogeneic diabetic humanized mice for 4 weeks and ameliorated diabetes. HIP-edited primary rhesus macaque islets survived for 40 weeks in an allogeneic rhesus macaque recipient without immunosuppression, whereas unedited islets were quickly rejected.

The endocannabinoid system is a highly conserved and ubiquitous signalling pathway with broad-ranging effects. Despite critical pathway functions, gene variants have not previously been conclusively linked to human disease. We identified nine children from eight families with heterozygous, de novo truncating variants in the last exon of DAGLA with a neuro-ocular phenotype characterized by developmental delay, ataxia and complex oculomotor abnormality. All children displayed paroxysms of nystagmus or eye deviation accompanied by compensatory head posture and worsened incoordination most frequently after waking. RNA sequencing showed clear expression of the truncated transcript and no differences were found between mutant and wild-type DAGLA activity. Immunofluorescence staining of patient-derived fibroblasts and HEK cells expressing the mutant protein showed distinct perinuclear aggregation not detected in control samples. This report establishes truncating variants in the last DAGLA exon as the cause of a unique paediatric syndrome. Because enzymatic activity was preserved, the observed mislocalization of the truncated protein may account for the observed phenotype. Potential mechanisms include DAGLA haploinsufficiency at the plasma membrane or dominant negative effect. To our knowledge, this is the first report directly linking an endocannabinoid system component with human genetic disease and sets the stage for potential future therapeutic avenues.

The genetic causes of global developmental delay (GDD) and intellectual disability (ID) are diverse and include variants in numerous ion channels and transporters. Loss-of-function variants in all five endosomal/lysosomal members of the CLC family of Cl- channels and Cl-/H+ exchangers lead to pathology in mice, humans, or both. We have identified nine variants in CLCN3, the gene encoding CIC-3, in 11 individuals with GDD/ID and neurodevelopmental disorders of varying severity. In addition to a homozygous frameshift variant in two siblings, we identified eight different heterozygous de novo missense variants. All have GDD/ID, mood or behavioral disorders, and dysmorphic features; 9/11 have structural brain abnormalities; and 6/11 have seizures. The homozygous variants are predicted to cause loss of ClC-3 function, resulting in severe neurological disease similar to the phenotype observed in Clcn3-/- mice. Their MRIs show possible neurodegeneration with thin corpora callosa and decreased white matter volumes. Individuals with heterozygous variants had a range of neurodevelopmental anomalies including agenesis of the corpus callosum, pons hypoplasia, and increased gyral folding. To characterize the altered function of the exchanger, electrophysiological analyses were performed in Xenopus oocytes and mammalian cells. Two variants, p.Ile607Thr and p.Thr570Ile, had increased currents at negative cytoplasmic voltages and loss of inhibition by luminal acidic pH. In contrast, two other variants showed no significant difference in the current properties. Overall, our work establishes a role for CLCN3 in human neurodevelopment and shows that both homozygous loss of ClC-3 and heterozygous variants can lead to GDD/ID and neuroanatomical abnormalities.

The present study employs a geospatial analytical approach to studying the evenness-clustering and isolation-exposure dimensions of segregation in the context of the St. Louis, Missouri, metropolitan region. In contrast to global indicators of segregation, this approach focuses on the evenness and isolation dimensions at the local level to visualize how they interact across neighborhoods. While not traditionally thought of as a method for theory testing, geographic information systems (GIS) can contribute to the validation process by displaying how constructs interact when applied in an actual geographic context. We examined separately the segregation dimension of racial evenness-exposure and its intersection with Black isolation and poverty isolation. The study used data from 446 census tracts that represent 65 St. Louis area school districts. When visualizing segregation dimensions through spatial mapping, it becomes apparent that communities that appear diverse may have neighborhoods where individuals or groups remain isolated.

South Africa has long grappled with one of the highest HIV and tuberculosis (TB) burdens in the world. The COVID-19 pandemic poses challenges to the country’s already strained health system. Measures to contain COVID-19 virus may have further hampered the containment of HIV and TB in the country and further widened the socioeconomic gap. South Africa’s handling of the pandemic has led to disruptions to HIV/TB testing and treatment. It has, furthermore, influenced social risk factors associated with increased transmission of these diseases. Individuals living with HIV and/or TB also face higher risk of developing severe COVID-19 disease. In this case study, we contextualize the HIV/TB landscape in South Africa and analyze the direct and indirect impact of the COVID-19 pandemic on the country’s efforts to combat these ongoing epidemics.

This article examines the evolving investment behavior of private equity funds in acquiring venture-capital-backed companies in the United States from 2005 to 2022. Historically, strategic acquisitions by corporate buyers have dominated venture capital exits, with financial acquisitions by private equity funds being less emphasized. Using a dataset of 5,530 acquisitions, we conducted multivariate logistic regression analyses to explore the impact of venture capital fund maturity and industry alignment on the likelihood of a private equity acquisition. Our findings reveal a significant relationship between mature venture capital funds and private equity acquisitions, particularly in earlier periods (2005–2010), with industry alignment becoming a stronger predictor in recent years (2017–2022). This shift underscores the increasing importance of industry expertise in private equity funds' acquisition strategies. The research contributes to the literature by highlighting the changing dynamics of venture capital exits and offering insights into the strategic adaptations of private equity funds over time. The findings highlight that the behavioral shift offers opportunities for both venture capital funds, by opening profitable exit avenues, and private equity funds, by leveraging their industry expertise to access valuable deal flow. [ABSTRACT FROM AUTHOR]