Remote sensing-based mangrove blue carbon assessment in the Asia-Pacific: A systematic review.

Accurate measuring, mapping, and monitoring of mangrove forests support the sustainable management of mangrove blue carbon in the Asia-Pacific. Remote sensing coupled with modeling can efficiently and accurately estimate mangrove blue carbon stocks at larger spatiotemporal extents. This study aimed to identify trends in remote sensing/modeling employed in estimating mangrove blue carbon, attributes/variations in mangrove carbon sequestration estimated using remote sensing, and to compile research gaps and opportunities, followed by providing recommendations for future research. Using a systematic literature review approach, we reviewed 105 remote sensing-based peer-reviewed articles (1990 - June 2023). Despite their high mangrove extent, there was a paucity of studies from Myanmar, Bangladesh, and Papua New Guinea. The most frequently used sensor was Sentinel-2 MSI, accounting for 14.5 % of overall usage, followed by Landsat 8 OLI (11.5 %), ALOS-2 PALSAR-2 (7.3 %), ALOS PALSAR (7.2 %), Landsat 7 ETM+ (6.1 %), Sentinel-1 (6.7 %), Landsat 5 TM (5.5 %), SRTM DEM (5.5 %), and UAV-LiDAR (4.8 %). Although parametric methods like linear regression remain the most widely used, machine learning regression models such as Random Forest (RF) and eXtreme Gradient Boost (XGB) have become popular in recent years and have shown good accuracy. Among a variety of attributes estimated, below-ground mangrove blue carbon and the valuation of carbon stock were less studied. The variation in carbon sequestration potential as a result of location, species, and forest type was widely studied. To improve the accuracy of blue carbon measurements, standardized/coordinated and innovative methodologies accompanied by credible information and actionable data should be carried out. Technical monitoring (every 2-5 years) enhanced by remote sensing can provide accurate and precise data for sustainable mangrove management while opening ventures for voluntary carbon markets to benefit the environment and local livelihood in developing countries in the Asia-Pacific region.

Low handgrip strength is related to elevated echogenicity in patients with chronic kidney disease: A pilot, cross-sectional and exploratory study.

OBJECTIVES: Evaluate associations between triceps braqui muscle ultrasound measures (TB US) and handgrip strength (HGS), and the sensibility of TB US for low HGS in non-dialysis-dependent chronic kidney disease (nd-CKD) patients. PARTICIPANTS AND METHODS: This pilot, cross-sectional, and exploratory study evaluated TB cross-sectional images from A-mode US and processed by FIJI-Image J to obtain muscle thickness (MT), echogenicity (EI), cross-sectional area (CSA), pennation angle (PA), and fascicle length (Lf) associating them with absolute HGS by simple and, multiple linear regression. The HGS was normalized to body mass index (BMI) and separated into low HGS (HGS/BMI≤10p according to sex and age) and adequate HGS (HGS/BMI>10p) groups. The body composition was from multifrequency bioimpedance. ROC analysis verified the TB US diagnostic accuracy to low HGS. RESULTS: Were included 42 (21M/21F) adults with 65.5 (60-70) y median age, 47.22% in 3b CKD stage. The low HGS group (45.23%) showed a higher fat mass (FM), TB muscle medium head's PA, and EI than adequate HGS (p<0.05). In crude model, a pixels increase in EI was associated with a 0.452kgf HGS reduction (p=0.019); adjusted for sex, age, and FM, a one-unit increase in EI was associated with a 0.510kgf HGS reduction (p=0.011). The EI also showed moderate diagnostic accuracy (AUC=0.730; CI 95%=0.589; 0.919) to low HGS and a sensitivity of 86.9% (cutoff≥13.52 pixels). CONCLUSION: In nd-CKD patients, of all measurements from US, the EI was the most associated with HGS, and the only one sensitive to low HGS diagnosis.

Heterozygous loss-of-function SMC3 variants are associated with variable growth and developmental features.

Heterozygous missense variants and in-frame indels in SMC3 are a cause of Cornelia de Lange syndrome (CdLS), marked by intellectual disability, growth deficiency, and dysmorphism, via an apparent dominant-negative mechanism. However, the spectrum of manifestations associated with SMC3 loss-of-function variants has not been reported, leading to hypotheses of alternative phenotypes or even developmental lethality. We used matchmaking servers, patient registries, and other resources to identify individuals with heterozygous, predicted loss-of-function (pLoF) variants in SMC3, and analyzed population databases to characterize mutational intolerance in this gene. Here, we show that SMC3 behaves as an archetypal haploinsufficient gene: it is highly constrained against pLoF variants, strongly depleted for missense variants, and pLoF variants are associated with a range of developmental phenotypes. Among 14 individuals with SMC3 pLoF variants, phenotypes were variable but coalesced on low growth parameters, developmental delay/intellectual disability, and dysmorphism, reminiscent of atypical CdLS. Comparisons to individuals with SMC3 missense/in-frame indel variants demonstrated an overall milder presentation in pLoF carriers. Furthermore, several individuals harboring pLoF variants in SMC3 were nonpenetrant for growth, developmental, and/or dysmorphic features, and some had alternative symptomatologies with rational biological links to SMC3. Analyses of tumor and model system transcriptomic data and epigenetic data in a subset of cases suggest that SMC3 pLoF variants reduce SMC3 expression but do not strongly support clustering with functional genomic signatures of typical CdLS. Our finding of substantial population-scale LoF intolerance in concert with variable growth and developmental features in subjects with SMC3 pLoF variants expands the scope of cohesinopathies, informs on their allelic architecture, and suggests the existence of additional clearly LoF-constrained genes whose disease links will be confirmed only by multilayered genomic data paired with careful phenotyping.

Diagnostic genome sequencing improves diagnostic yield: a prospective single-centre study in 1000 patients with inherited eye diseases.

PURPOSE: Genome sequencing (GS) is expected to reduce the diagnostic gap in rare disease genetics. We aimed to evaluate a scalable framework for genome-based analyses 'beyond the exome' in regular care of patients with inherited retinal degeneration (IRD) or inherited optic neuropathy (ION). METHODS: PCR-free short-read GS was performed on 1000 consecutive probands with IRD/ION in routine diagnostics. Complementary whole-blood RNA-sequencing (RNA-seq) was done in a subset of 74 patients. An open-source bioinformatics analysis pipeline was optimised for structural variant (SV) calling and combined RNA/DNA variation interpretation. RESULTS: A definite genetic diagnosis was established in 57.4% of cases. For another 16.7%, variants of uncertain significance were identified in known IRD/ION genes, while the underlying genetic cause remained unresolved in 25.9%. SVs or alterations in non-coding genomic regions made up for 12.7% of the observed variants. The RNA-seq studies supported the classification of two unclear variants. CONCLUSION: GS is feasible in clinical practice and reliably identifies causal variants in a substantial proportion of individuals. GS extends the diagnostic yield to rare non-coding variants and enables precise determination of SVs. The added diagnostic value of RNA-seq is limited by low expression levels of the major IRD disease genes in blood.

Intrinsic deletion at 10q23.31, including the PTEN gene locus, is aggravated upon CRISPR-Cas9-mediated genome engineering in HAP1 cells mimicking cancer profiles.

The CRISPR-Cas9 system is a powerful tool for studying gene functions and holds potential for disease treatment. However, precise genome editing requires thorough assessments to minimize unintended on- and off-target effects. Here, we report an unexpected 283-kb deletion on Chromosome 10 (10q23.31) in chronic myelogenous leukemia-derived HAP1 cells, which are frequently used in CRISPR screens. The deleted region encodes regulatory genes, including PAPSS2, ATAD1, KLLN, and PTEN We found that this deletion was not a direct consequence of CRISPR-Cas9 off-targeting but rather occurred frequently during the generation of CRISPR-Cas9-modified cells. The deletion was associated with global changes in histone acetylation and gene expression, affecting fundamental cellular processes such as cell cycle and DNA replication. We detected this deletion in cancer patient genomes. As in HAP1 cells, the deletion contributed to similar gene expression patterns among cancer patients despite interindividual differences. Our findings suggest that the unintended deletion of 10q23.31 can confound CRISPR-Cas9 studies and underscore the importance to assess unintended genomic changes in CRISPR-Cas9-modified cells, which could impact cancer research.

Soils under seal carcasses with varying degrees of decomposition: oasis of nutrients and vegetation in Antarctica.

Areas of high concentration of seal carcasses have been observed in localized areas of James Ross Island, Antarctica. Such carcasses show an unusual vegetation development, in a semi-arid area with bare soils under intense winds, high salinity and sandy texture. We investigated carcasses of seals around a lake in James Ross Island, with four different stages of decomposition, with three replicates: Seal (S01), with recently mummified carcasses; S02, with partially degraded carcasses; S03, with broken carcasses with partially degraded exposed bones, and S04, with completely broken, scattered skeletons. The vegetation showed a maximum degree of development in carcasses at stages S02 and S03, with the environment between the skin and the skeleton as the preferred place for vegetation establishment. The chemical alteration was greater with increasing carcass decomposition but reduced with the spreading and final decomposition of the bones, with anomalous values observed only in the vicinity of the carcasses. It is concluded that the presence of carcasses of seals, concentrated in wet places, even in a semi-desert climate, represent important oases of nutrients, with a combination of physical and chemical effects throughout the decomposition process that favor plant establishment and succession.

The Fundamental Role of Oxime and Oxime Ether Moieties in Improving the Physicochemical and Anticancer Properties of Structurally Diverse Scaffolds.

The present review explores the critical role of oxime and oxime ether moieties in enhancing the physicochemical and anticancer properties of structurally diverse molecular frameworks. Specific examples are carefully selected to illustrate the distinct contributions of these functional groups to general strategies for molecular design, modulation of biological activities, computational modeling, and structure-activity relationship studies. An extensive literature search was conducted across three databases, including PubMed, Google Scholar, and Scifinder, enabling us to create one of the most comprehensive overviews of how oximes and oxime ethers impact antitumor activities within a wide range of structural frameworks. This search focused on various combinations of keywords or their synonyms, related to the anticancer activity of oximes and oxime ethers, structure-activity relationships, mechanism of action, as well as molecular dynamics and docking studies. Each article was evaluated based on its scientific merit and the depth of the study, resulting in 268 cited references and more than 336 illustrative chemical structures carefully selected to support this analysis. As many previous reviews focus on one subclass of this extensive family of compounds, this report represents one of the rare and fully comprehensive assessments of the anticancer potential of this group of molecules across diverse molecular scaffolds.

Brominated flame retardants and natural organobrominated compounds in a vulnerable delphinid species along the Brazilian coast.

Guiana dolphins, Sotalia guianensis, are vulnerable to extinction along their distribution on the Brazilian coast and assessing chemical pollution is of utmost importance for their conservation. For this study, 51 carcasses of Guiana dolphins were sampled across the Brazilian coast to investigate legacy and emerging brominated flame retardants (BFRs) as well as the naturally-produced MeO-BDEs. PBDEs and MeO-BDEs were detected in all samples analyzed, whereas emerging BFRs were detected in 16 % of the samples, all in Rio de Janeiro state. PBDE concentrations varied between 2.24 and 799 ng.g-1 lipid weight (lw), emerging BFRs between 0.12 and 1.51 ng.g-1 lw and MeO-BDEs between 3.82 and 10,247 ng.g-1 lw. Concentrations of legacy and emerging BFRs and natural compounds varied considerably according to the sampling site and reflected both the local anthropogenic impact of the region and the diversity/mass of biosynthesizers. The PBDE concentrations are lower than what was found for delphinids in the Northern Hemisphere around the same sampling period and most sampling sites presented mean concentrations lower than the limits for endocrine disruption known to date for marine mammals of 460 ng.g-1 lw, except for sampled from Santa Catarina state, in Southern Brazil. Conversely, MeO-BDE concentrations are higher than those of the Northern Hemisphere, particularly close to the Abrolhos Bans and Royal Charlotte formation, that are hotspots for biodiversity. Despite the elevated concentrations reported for this group, there is not much information regarding the effects of such elevated concentrations for these marine mammals. The distinct patterns observed along the Brazilian coast show that organobrominated compounds can be used to identify the ecological segregation of delphinids and that conservation actions should be planned considering the local threats.

Heterozygous loss-of-function SMC3 variants are associated with variable and incompletely penetrant growth and developmental features.

Heterozygous missense variants and in-frame indels in SMC3 are a cause of Cornelia de Lange syndrome (CdLS), marked by intellectual disability, growth deficiency, and dysmorphism, via an apparent dominant-negative mechanism. However, the spectrum of manifestations associated with SMC3 loss-of-function variants has not been reported, leading to hypotheses of alternative phenotypes or even developmental lethality. We used matchmaking servers, patient registries, and other resources to identify individuals with heterozygous, predicted loss-of-function (pLoF) variants in SMC3, and analyzed population databases to characterize mutational intolerance in this gene. Here, we show that SMC3 behaves as an archetypal haploinsufficient gene: it is highly constrained against pLoF variants, strongly depleted for missense variants, and pLoF variants are associated with a range of developmental phenotypes. Among 13 individuals with SMC3 pLoF variants, phenotypes were variable but coalesced on low growth parameters, developmental delay/intellectual disability, and dysmorphism reminiscent of atypical CdLS. Comparisons to individuals with SMC3 missense/in-frame indel variants demonstrated a milder presentation in pLoF carriers. Furthermore, several individuals harboring pLoF variants in SMC3 were nonpenetrant for growth, developmental, and/or dysmorphic features, some instead having intriguing symptomatologies with rational biological links to SMC3 including bone marrow failure, acute myeloid leukemia, and Coats retinal vasculopathy. Analyses of transcriptomic and epigenetic data suggest that SMC3 pLoF variants reduce SMC3 expression but do not result in a blood DNA methylation signature clustering with that of CdLS, and that the global transcriptional signature of SMC3 loss is model-dependent. Our finding of substantial population-scale LoF intolerance in concert with variable penetrance in subjects with SMC3 pLoF variants expands the scope of cohesinopathies, informs on their allelic architecture, and suggests the existence of additional clearly LoF-constrained genes whose disease links will be confirmed only by multi-layered genomic data paired with careful phenotyping.

Hemizygous variants in protein phosphatase 1 regulatory subunit 3F (PPP1R3F) are associated with a neurodevelopmental disorder characterized by developmental delay, intellectual disability and autistic features.

Protein phosphatase 1 regulatory subunit 3F (PPP1R3F) is a member of the glycogen targeting subunits (GTSs), which belong to the large group of regulatory subunits of protein phosphatase 1 (PP1), a major eukaryotic serine/threonine protein phosphatase that regulates diverse cellular processes. Here, we describe the identification of hemizygous variants in PPP1R3F associated with a novel X-linked recessive neurodevelopmental disorder in 13 unrelated individuals. This disorder is characterized by developmental delay, mild intellectual disability, neurobehavioral issues such as autism spectrum disorder, seizures and other neurological findings including tone, gait and cerebellar abnormalities. PPP1R3F variants segregated with disease in affected hemizygous males that inherited the variants from their heterozygous carrier mothers. We show that PPP1R3F is predominantly expressed in brain astrocytes and localizes to the endoplasmic reticulum in cells. Glycogen content in PPP1R3F knockout astrocytoma cells appears to be more sensitive to fluxes in extracellular glucose levels than in wild-type cells, suggesting that PPP1R3F functions in maintaining steady brain glycogen levels under changing glucose conditions. We performed functional studies on nine of the identified variants and observed defects in PP1 binding, protein stability, subcellular localization and regulation of glycogen metabolism in most of them. Collectively, the genetic and molecular data indicate that deleterious variants in PPP1R3F are associated with a new X-linked disorder of glycogen metabolism, highlighting the critical role of GTSs in neurological development. This research expands our understanding of neurodevelopmental disorders and the role of PP1 in brain development and proper function.

Quantifying quality: The impact of measures of school quality on children's academic achievement across diverse societies.

Recent decades have seen a rapid acceleration in global participation in formal education, due to worldwide initiatives aimed to provide school access to all children. Research in high income countries has shown that school quality indicators have a significant, positive impact on numeracy and literacy-skills required to participate in the increasingly globalized economy. Schools vary enormously in kind, resources, and teacher training around the world, however, and the validity of using diverse school quality measures in populations with diverse educational profiles remains unclear. First, we assessed whether children's numeracy and literacy performance across populations improves with age, as evidence of general school-related learning effects. Next, we examined whether several school quality measures related to classroom experience and composition, and to educational resources, were correlated with one another. Finally, we examined whether they were associated with children's (4-12-year-olds, N = 889) numeracy and literacy performance in 10 culturally and geographically diverse populations which vary in historical engagement with formal schooling. Across populations, age was a strong positive predictor of academic achievement. Measures related to classroom experience and composition were correlated with one another, as were measures of access to educational resources and classroom experience and composition. The number of teachers per class and access to writing materials were key predictors of numeracy and literacy, while the number of students per classroom, often linked to academic achievement, was not. We discuss these results in the context of maximising children's learning environments and highlight study limitations to motivate future research. RESEARCH HIGHLIGHTS: We examined the extent to which four measures of school quality were associated with one another, and whether they predicted children's academic achievement in 10 culturally and geographically diverse societies. Across populations, measures related to classroom experience and composition were correlated with one another as were measures of access to educational resources to classroom experience and composition. Age, the number of teachers per class, and access to writing materials were key predictors of academic achievement across populations. Our data have implications for designing efficacious educational initiatives to improve school quality globally.

Programming protein phase-separation employing a modular library of intrinsically disordered precision block copolymer-like proteins creating dynamic cytoplasmatic compartmentalization.

The control of supramolecular complexes in living systems at the molecular level is an important goal in life-sciences. Spatiotemporal organization of molecular distribution & flow of such complexes are essential physicochemical processes in living cells and important for pharmaceutical processes. Membraneless organelles (MO) found in eukaryotic cells, formed by liquid-liquid phase-separation (LLPS) of intrinsically disordered proteins (IDPs) control and adjust intracellular organization. Artificially designed compartments based on LLPS open up a novel pathway to control chemical flux and partition in vitro and in vivo. We designed a library of chemically precisely defined block copolymer-like proteins based on elastin-like proteins (ELPs) with defined charge distribution and type, as well as polar and hydrophobic block domains. This enables the programmability of physicochemical properties and to control adjustable LLPS in vivo attaining control over intracellular partitioning and flux as role model for in vitro and in vivo applications. Tailor-made ELP-like block copolymer proteins exhibiting IDP-behavior enable LLPS formation in vitro and in vivo allowing the assembly of membrane-based and membraneless superstructures via protein phase-separation in E. coli. Subsequently, we demonstrate the responsiveness of protein phase-separated spaces (PPSSs) to environmental physicochemical triggers and their selective, charge-dependent and switchable interaction with DNA or extrinsic and intrinsic molecules enabling their selective shuttling across semipermeable phase boundaries including (cell)membranes. This paves the road for adjustable artificial PPSS-based storage and reaction spaces and the specific transport across phase boundaries for applications in pharmacy and synthetic biology.

Episignature analysis of moderate effects and mosaics.

DNA methylation classifiers ("episignatures") help to determine the pathogenicity of variants of uncertain significance (VUS). However, their sensitivity is limited due to their training on unambiguous cases with strong-effect variants so that the classification of variants with reduced effect size or in mosaic state may fail. Moreover, episignature evaluation of mosaics as a function of their degree of mosaicism has not been developed so far. We improved episignatures with respect to three categories. Applying (i) minimum-redundancy-maximum-relevance feature selection we reduced their length by up to one order of magnitude without loss of accuracy. Performing (ii) repeated re-training of a support vector machine classifier by step-wise inclusion of cases in the training set that reached probability scores larger than 0.5, we increased the sensitivity of the episignature-classifiers by 30%. In the newly diagnosed patients we confirmed the association between DNA methylation aberration and age at onset of KMT2B-deficient dystonia. Moreover, we found evidence for allelic series, including KMT2B-variants with moderate effects and comparatively mild phenotypes such as late-onset focal dystonia. Retrained classifiers also can detect mosaics that previously remained below the 0.5-threshold, as we showed for KMT2D-associated Kabuki syndrome. Conversely, episignature-classifiers are able to revoke erroneous exome calls of mosaicism, as we demonstrated by (iii) comparing presumed mosaic cases with a distribution of artificial in silico-mosaics that represented all the possible variation in degree of mosaicism, variant read sampling and methylation analysis.

Depression in older adults during the COVID-19 pandemic: A systematic review.

BACKGROUND: Depression affected 5.7% of people aged 60 years and over prior to the pandemic and has increased by approximately 28%. The aim of this study is to identify and describe factors associated with depressive symptoms, the diagnostic assessment instruments and interventions used to evaluate and treat depression in adults aged 60 years and older since the onset of the COVID-19 pandemic. METHODS: Four electronic databases were systematically searched to identify eligible studies published since the beginning of the COVID-19 pandemic. A total of 832 articles were screened, of which 53 met the inclusion criteria. RESULTS: Factors contributing to depressive symptoms in older adults prior to the pandemic were grouped into the following categories: sociodemographic characteristics (i.e., being female); loneliness and weak social support; limitations in daily functioning, physical activity and neurocognitive impairment; and clinical factors. The following groups of factors directly related to the pandemic were found: stress-related factors and feelings or worries related to the pandemic; information access (e.g., receiving news about COVID-19 through the media); factors directly related to COVID-19 (e.g., having infected acquaintances); and factors related to the measures that were taken to reduce the spread of COVID-19 (e.g., confinement measures). The most frequently used instrument to assess depressive symptoms was the Geriatric Depression Scale Short Form (GDS-SF). Four studies implemented interventions during the pandemic that led to significant reductions in depressive symptoms and feelings of loneliness. CONCLUSIONS: Improved understanding of pandemic-associated risk factors for depression can inform person-cantered care. It is important continued mental healthcare for depression for older adults throughout crises, such as the COVID-19 pandemic. Remote delivery of mental healthcare represents an important alternative during such times. It is crucial to address depression in older adults (which often causes disability), since the pandemic situation has increased depressive symptoms in this population.

Sex and pubertal influences on the neurodevelopmental underpinnings of schizophrenia: A case for longitudinal research on adolescents.

Sex is a significant source of heterogeneity in schizophrenia, with more negative symptoms in males and more affective symptoms and internalizing comorbidity in females. In this narrative review, we argue that there are likely sex differences in the pathophysiological mechanisms of schizophrenia-spectrum disorders (SZ) that originate during puberty and relate to the sex-specific impacts of pubertal maturation on brain development. Pubertal maturation might also trigger underlying (genetic or other) vulnerabilities in at-risk individuals, influencing brain development trajectories that contribute to the emergence of SZ. This review is the first to integrate links between pubertal development and neural development with cognitive neuroscience research in SZ to form and evaluate these hypotheses, with a focus on the frontal-striatal and frontal-limbic networks and their hypothesized contribution to negative and mood symptoms respectively. To test these hypotheses, longitudinal research with human adolescents is needed that examines the role of sex and pubertal development using large cohorts or high risk samples. We provide recommendations for such studies, which will integrate the fields of psychiatry, developmental cognitive neuroscience, and developmental endocrinology towards a more nuanced understanding of the role of pubertal factors in the hypothesized sex-specific pathophysiological mechanisms of schizophrenia.

Safety and Family-Centered Care during Restriction of Hospital Visits due to COVID-19: The Experience of Family Members.

BACKGROUND: Person and Family Centered Care (PFCC) has demonstrated important contributions to health care outcomes. However, in response to the need for safety due to the pandemic COVID-19, measures were taken to restrict hospital visits. So, the aim of this study was to understand the healthcare experience of family members of patients hospitalized during the pandemic period regarding safety and person- and family-centered care. METHODS: Qualitative interpretative study, conducted through semi-structured interviews with six family members of people hospitalized during the pandemic period. Content analysis was performed using Atlas.ti software version 22 (Berlin, Germany) and Bardin's methodology. RESULTS AND CONCLUSIONS: Restrictions on hospital visits due to the pandemic of COVID-19 have led to a distancing of families from the hospital setting and influenced healthcare practice, making it difficult to involve families in the care process. In some cases, healthcare professionals made efforts to provide PFCC, attempting to minimize the impact of the visitation restriction. However, there were reported experiences of care delivery that did not consider social and psychological factors and did not place the person and family at the center of the care process, relying instead on the biomedical model. These practices left out important factors for the provision of safe care. It is crucial, even in pandemic settings, that healthcare professionals provide person- and family-centered care to the extent possible, promoting the safety of care. The family should be involved in the care of the person in the inpatient setting.

Target-enriched nanopore sequencing and de novo assembly reveals co-occurrences of complex on-target genomic rearrangements induced by CRISPR-Cas9 in human cells.

The CRISPR-Cas9 system is widely used to permanently delete genomic regions via dual guide RNAs. Genomic rearrangements induced by CRISPR-Cas9 can occur, but continuous technical developments make it possible to characterize complex on-target effects. We combined an innovative droplet-based target enrichment approach with long-read sequencing and coupled it to a customized de novo sequence assembly. This approach enabled us to dissect the sequence content at kilobase scale within an on-target genomic locus. We here describe extensive genomic disruptions by Cas9, involving the allelic co-occurrence of a genomic duplication and inversion of the target region, as well as integrations of exogenous DNA and clustered interchromosomal DNA fragment rearrangements. Furthermore, we found that these genomic alterations led to functional aberrant DNA fragments and can alter cell proliferation. Our findings broaden the consequential spectrum of the Cas9 deletion system, reinforce the necessity of meticulous genomic validations, and introduce a data-driven workflow enabling detailed dissection of the on-target sequence content with superior resolution.

Organochlorine contaminants in Rio skate (Rioraja agassizii), an endangered batoid species, from southeastern coast of Brazil.

A global movement towards decreases in elasmobranch overfishing has been noted in the last decades. However, discussion concerning the effects of POP contamination on the health and survival of these organisms is still recent. These compounds can affect the immune and endocrine systems of both sharks and batoids, impairing reproduction and impacting species recruitment, acting synergistically alongside overfishing effects. In this context, this study investigated the concentration of organochlorine compounds in liver of 29 individuals of Rioraja agassizii, a commercially exploited skate classified as Vulnerable by IUCN and as Endangered in Brazil. Contaminant concentrations were higher in adults compared to juveniles. Distinct contamination profiles were observed, suggesting different groups within the investigated population and revealing contaminants as a potential tool to assess population ecology. PCB levels were considered a concern as they resemble concentrations in ecosystems from the northern hemisphere, where deleterious effects on elasmobranchs have been observed.

The Implications of Family Members' Absence from Hospital Visits during the COVID-19 Pandemic: Nurses' Perceptions.

BACKGROUND: In response to the COVID-19 pandemic, several measures were taken to prevent the transmission of infection in the hospital environment, including the restriction of visits. Little is known about the consequences of these directives, but it is expected that they will have various implications. Thus, this study aimed to understand the consequences of measures to restrict visits to hospitalized individuals. METHODS: A qualitative interpretive study was conducted through semistructured interviews with 10 nurses chosen by convenience. Content analysis was performed using Atlas.ti software, version 22 (Berlin, Germany). RESULTS: Twenty-two categories and eight subcategories were identified and grouped according to their scope: implications for the patient, implications for the family, and implications for care practice. CONCLUSIONS: The identified categories of implications of restricting hospital visits (implications for patients, relatives, and care practices) are incomparably more negative than positive and have a strong potential to cause safety events in the short to long term, also jeopardizing the quality of care. There is the risk of stagnation and even setback due to this removal of families from the hospital environment, not only in terms of safety and quality of care but also with regard to person- and family-centered care.

SGLT2 Inhibition with Empagliflozin as a Possible Therapeutic Option for Postprandial Hypoglycemia After Bariatric Surgery.

PURPOSE: Since SGLT2 inhibitors may reduce postprandial hyperglycemia, this study aimed to evaluated whether empagliflozin might be useful in the treatment of postprandial hypoglycemia (PPH) postbariatric surgery (BS). PATIENTS AND METHODS: Fourteen patients who underwent BS, nine without type 2 diabetes and five with diabetes before surgery and in remission after surgery, were included. Seven of them presented symptoms of PPH (hypoglycemic group; HG) and seven were asymptomatic (nonhypoglycemic group (NHG)). A meal tolerance test was performed before and after administration of a daily dose of empagliflozin (EMPA) 25 mg for 3 days. Plasma glucose and serum insulin levels were measured. RESULTS: In HG, compared with NHG, in the basal test, the area under the curve (AUC) of plasma glucose levels (AUCgly) was smaller (158.3 ± 25.3 vs 276.6 ± 79.2 mg h dL-1; p = 0.001) while the AUC of insulin levels (AUCins) did not differ, leading to a higher AUCins/AUCgly ratio (0.79 ± 0.46 vs 0.38 ± 0.20; p = 0.055) and a lower HOMA-IR (0.92 ± 0.22 vs 1.75 ± 0.77; p = 0.030). The HG after EMPA, but not the NHG, showed significant increases in glycemia leading to greater AUCgly (158.0 ± 25.3 to 197.2 ± 51.6 mg h dL-1; p = 0.043) without significant changes in AUCins. HOMA-IR increased only in the HG (0.92 ± 0.20 vs 1.61 ± 0.30; p = 0.025) and, when both groups were analyzed together, both before and post EMPA, a significant correlation was found between HOMA-IR and AUCgly values (r = 0.594; p = 0.002). CONCLUSION: Our results suggest that empagliflozin increased glycemic levels in patients with PPH possibly through increases in hepatic glucose production.