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Background Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cancer. Large-scale metabolomic data have associated metabolic alterations with the pathogenesis and progression of renal carcinoma and have correlated mitochondrial activity with poor survival in a subset of patients. The aim of this study was to determine whether targeting mitochondria-lysosome interaction could be a novel therapeutic approach using patient-derived organoids as avatar for drug response. Methods RNAseq data analysis and immunohistochemistry were used to show overexpression of Purinergic receptor 4 (P2XR4) in clear cell carcinomas. Seahorse experiments, immunofluorescence and fluorescence cell sorting were used to demonstrate that P2XR4 regulates mitochondrial activity and the balance of radical oxygen species. Pharmacological inhibitors and genetic silencing promoted lysosomal damage, calcium overload in mitochondria and cell death via both necrosis and apoptosis. Finally, we established patient-derived organoids and murine xenograft models to investigate the antitumor effect of P2XR4 inhibition using imaging drug screening, viability assay and immunohistochemistry. Results Our data suggest that oxo-phosphorylation is the main source of tumor-derived ATP in a subset of ccRCC cells expressing P2XR4, which exerts a critical impact on tumor energy metabolism and mitochondrial activity. Prolonged mitochondrial failure induced by pharmacological inhibition or P2XR4 silencing was associated with increased oxygen radical species, changes in mitochondrial permeability (i.e., opening of the transition pore complex, dissipation of membrane potential, and calcium overload). Interestingly, higher mitochondrial activity in patient derived organoids was associated with greater sensitivity to P2XR4 inhibition and tumor reduction in a xenograft model. Conclusion Overall, our results suggest that the perturbed balance between lysosomal integrity and mitochondrial activity induced by P2XR4 inhibition may represent a new therapeutic strategy for a subset of patients with renal carcinoma and that individualized organoids may be help to predict drug efficacy.

Carnitine, a powerful antioxidant, has an essential role in sperm energy metabolism. Among carnitines, only L-carnitine’s effect on stallion semen has been tested and not acetyl-L-Carnitine. Therefore, we aimed to determine the ideal concentrations of L-carnitine (LC) and acetyl-L-carnitine (AC) and their effects on stallion semen cooled at 5℃ for up to 48 hours. Semen was extended to 50 x 106 sperm/ml in commercial extender (Control), and concentrations of 5, 10, and 15 mmol/l of LC and AC were evaluated in Experiment 1. Sperm motility and plasma membrane integrity were assessed by CASA and epifluorescence microscopy, respectively. In Experiment 2, the combination of the intermediate doses of LC (10 mmol/l) and AC (10 mmol/l) was tested. Sperm parameters were evaluated as in Experiment 1 and in addition, DNA fragmentation index (DFI), production of reactive oxygen species (ROS), and lipid peroxidation (PEROX) were evaluated by flow cytometry. All analyses were performed at 0, 24, and 48 hours after semen collection, processing, and cooled-stored at 5°C. In Experiments 1 and 2, the groups supplemented with LC and AC or LC+AC had higher plasma membrane integrity and motility parameters compared to Control group (p < 0.05). The LC and AC combination did not change sperm parameters compared to LC or AC alone (p > 0.05). No differences (p > 0.05) were observed for DFI, ROS, and PEROX. In conclusion, LC and AC’s addition, alone or in combination, enhanced sperm motility and plasma membrane integrity of stallion sperm after cooled-storage at 5℃ for up to 48 hours.

Given two eigenforms, it is a natural question to ask if the product of the eigenforms is again an eigenform. In the case of elliptic modular forms, this was answered in the full level case by Duke and Ghate and in the general level case by Johnson. In this paper, we consider the case of genus two Siegel modular forms with general congruence level.

Home health aides are paid professionals who provide long-term care to an expanding population of adults who need it. However, aides' work is often unrecognized by the broader caregiving team despite being in demand and crucial to care---an invisibility reinforced by ill-suited technological tools. In order to understand the invisible work aides perform and its relationship to technology design, we interviewed 13 aides employed by home care agencies in New York City. These aides shared examples that demonstrated the intertwined nature of both types of invisible work (i.e., emotions- and systems-based) and expanded the sociological mechanisms of invisibility (i.e., sociocultural, sociolegal, sociospatial) to include the sociotechnical. Through these findings, we investigate the opportunities, tensions, and challenges that could inform the design of tools created for these important, but often overlooked, frontline caregivers.

Home care workers (HCWs) provide essential care in patients' homes but are often underappreciated and work in stressful and isolated environments with diverse and intersecting support needs. This paper describes a computer-mediated peer support program that centers around sharing circles: spaces for personal, narrative storytelling to encourage HCWs to collaboratively reflect on their home care experiences and build rapport and shared identity with their peers. We describe the design of this program and a 12-week deployment that we conducted to evaluate the program with 42 HCWs in New York City. Our findings show that participants engaged in multiple types of peer support including emotional validation, learning how to navigate the workplace and patient care, defining and enabling good home care praxis, and building understanding around purpose and identity as HCWs. We discuss how these findings inform the design of technology and use of holistic pedagogies, such as storytelling, to enable this support in computer-mediated peer support programs. Such programs can help researchers and practitioners interested in addressing diverse needs that occur in intersectional contexts, such as that of HCWs and other marginalized populations.

Primary ciliary dyskinesia (PCD) is characterized by impaired mucociliary clearance, recurrent respiratory infections, and progressive airway damage and obstructive lung disease. While the association of ciliary ultrastructure defect/genotype with severity of airflow obstruction has been well characterized, their association with airway abnormalities on chest computed tomography (CT) has been minimally evaluated.We sought to delineate the association of ciliary defect class/genotype with chest CT scores in children with PCD.Cross-sectional analysis of children with PCD (N=146) enrolled in a prospective multicenter observational study, stratified by defect type: ODA (outer dynein arm), ODA/IDA (outer and inner dynein arm), IDA/MTD (inner dynein arm and microtubular disorganization), and Normal/Near Normal ultrastructure with associated genotypes. CTs were scored utilizing the Melbourne-Rotterdam Annotated Grid Morphometric Analysis for PCD (MERAGMA-PCD), evaluating airway abnormalities in a hierarchical order: atelectasis, bronchiectasis, bronchial wall thickening, mucus plugging/tree in bud opacities. Volume fraction of each component was expressed as % of total lung volume. %Disease was computed as the sum of all components. Regression analyses were utilized to describe the association between clinical predictors and CT scores.Acceptable chest CTs were obtained in 141 children (71 male): 57 ODA, 20 ODA/IDA, 40 IDA/MTD, 24 Normal/Near Normal. Mean (SD) age was 8.5 (4.6) years, forced expiratory volume in 1 second (FEV1) % predicted was 82.4 (19.5), and %Disease was 4.6 (3.5). Children with IDA/MTD defects had higher %Disease compared to children with ODA defects (2.71% higher (95%CI: 1.37-4.06, p0.001)), driven by higher %Mucus plugging (2.35% higher (1.43-3.26, p0.001)). Increasing age, lower BMI, and lower FEV1 were associated with higher %Disease (0.23%, 95%CI: 0.11-0.35, p0.001; 0.03%, 95%CI: 0.01-0.04, p=0.008; and 0.05%, 95%CI: 0.01-0.08, p=0.011, respectively).Children with IDA/MTD defects had significantly greater airway disease on CT, primarily mucus plugging, compared to children with ODA defects.

Warrior psychotherapy (WP) is a therapeutic concept which can be used to restore and improve functioning in all people. The idea behind warrior psychotherapy is to utilize traditional core values from the United States Military Service Branches and translate these traits into useful clinical tools, promoting optimal performance, and improved resilience, along with overall wellness and mental health. [ Psychiatr Ann . 2023;53(4):179–183.]

Apolipoprotein L1 (APOL1)-associated focal segmental glomerulosclerosis (FSGS) is the dominant form of FSGS in Black individuals. There are no targeted therapies for this condition, in part because the molecular mechanisms underlying APOL1's pathogenic contribution to FSGS are incompletely understood. Studying the transcriptomic landscape of APOL1 FSGS in patient kidneys is an important way to discover genes and molecular behaviors that are unique or most relevant to the human disease. With the hypothesis that the pathology driven by the high-risk APOL1 genotype is reflected in alteration of gene expression across the glomerular transcriptome, we compared expression and co-expression profiles of 15,703 genes in 16 Black patients with FSGS at high-risk vs 14 Black patients with a low-risk APOL1 genotype. Expression data from APOL1-inducible HEK293 cells and normal human glomeruli were used to pursue genes and molecular pathways uncovered in these studies. We discovered increased expression of APOL1 and nine other significant differentially expressed genes in high-risk patients. This included stanniocalcin, which has a role in mitochondrial and calcium-related processes along with differential correlations between high- and low-risk APOL1 and metabolism pathway genes. There were similar correlations with extracellular matrix- and immune-related genes, but significant loss of co-expression of mitochondrial genes in high-risk FSGS, and an NF-κB-down regulating gene, NKIRAS1, as the most significant hub gene with strong differential correlations with NDUF family (mitochondrial respiratory genes) and immune-related (JAK-STAT) genes. Thus, differences in mitochondrial gene regulation appear to underlie many differences observed between high- and low-risk Black patients with FSGS.

O Brasil tem enfrentado sérios problemas com o abastecimento de fertilizantes potássicos nos últimos anos. Isso tem causado a elevação dos preços e até mesmo escassez do principal fertilizante potássico utilizado pelos produtores, o cloreto de potássio. Por isso, o objetivo do presente trabalho foi avaliar um silicato de potássio nacional (K6) como fonte alternativa ao uso do cloreto de potássio para a cultura do feijão-vagem. Para tanto, sementes de feijão-vagem cv. Macarrão Rasteiro foram semeadas a campo em espaçamento de 0,50 x 0,20 m. Empregou-se o delineamento em blocos ao acaso com quatro tratamentos e cinco repetições. Os tratamentos foram constituídos da seguinte maneira: (i) testemunha – sem adubação potássica; (ii) cloreto de potássio; (iii) silicato de potássio – K6; (iv) 50% cloreto de potássio + 50% K6. Os fertilizantes foram aplicados no momento da semeadura e as doses determinadas com base na análise de solo e nas recomendações para a cultura. Foi realizada avaliação de altura de plantas, massa fresca e seca da parte aérea, massa fresca e seca de vagens, estimativa de produtividade e ocorrência de oídio, através de notas de severidade. Verificou-se que não houve influência da adubação potássica sobre o crescimento das plantas. De maneira geral, a produtividade de vagens apresentou baixa influência da adubação. Entretanto, a produtividade total de vagens foi maior em plantas adubadas com K6 em comparação a plantas adubadas com cloreto de potássio. A aplicação de K6 também contribuiu para a redução da severidade de oídio. Dessa forma, nós concluímos que o K6 é uma fonte de potássio viável em substituição ao cloreto de potássio para o feijão-vagem.

Protein N-linked glycosylation is a structurally diverse post-translational modification that stores biological information in a larger order of magnitude than other post-translational modifications such as phosphorylation, ubiquitination and acetylation. This gives N-glycosylated proteins a diverse range of properties and allows glyco-codes (glycan-related information) to be deciphered by glycan-binding proteins (GBPs). The intervillous space of the placenta is richly populated with membrane-bound and secreted glycoproteins. Evidence exists to suggest that altering the structural nature of their N-glycans can impact several trophoblast functions, which include those related to interactions with decidual cells. This review summarizes trophoblast-related activities influenced by N-glycan–GBP recognition, exploring how different subtypes of trophoblasts actively adapt to characteristics of the decidualized endometrium through cell-specific expression of N-glycosylated proteins, and how these cells receive decidua-derived signals via N-glycan–GBP interactions. We highlight work on how changes in N-glycosylation relates to the success of trophoblast infiltration, interactions of immunomodulators, and uterine angiogenesis. We also discuss studies that suggest aberrant N-glycosylation of trophoblasts may contribute to the pathogenesis of pregnancy complications (e.g. pre-eclampsia, early spontaneous miscarriages and hydatidiform mole). We propose that a more in-depth understanding of how N-glycosylation shapes trophoblast phenotype during early pregnancy has the potential to improve our approach to predicting, diagnosing and alleviating poor maternal/fetal outcomes associated with placental dysfunction.

Background The utilisation of massed therapy for treating posttraumatic stress disorder (PTSD) is gaining strength, especially prolonged exposure. However, it is unknown whether massed prolonged exposure (MPE) is non-inferior to standard prolonged exposure (SPE) protocols in the long term. The current study aimed to assess whether MPE was non-inferior to SPE at 12 months post-treatment, and to ascertain changes in secondary measure outcomes. Methods A multi-site non-inferiority randomised controlled trial (RCT) compared SPE with MPE in 12 clinics. The primary outcome was PTSD symptom severity (CAPS-5) at 12 months post-treatment commencement. Secondary outcome measures included symptoms of depression, anxiety, anger, disability, and quality of life at 12 weeks and 12 months post-treatment commencement. Outcome assessors were blinded to treatment allocation. The intention-to-treat sample included 138 Australian military members and veterans and data were analysed for 134 participants (SPE = 71, MPE = 63). Results Reductions in PTSD severity were maintained at 12 months and MPE remained non-inferior to SPE. Both treatment groups experienced a reduction in depression, anxiety, anger, and improvements in quality of life at 12 weeks and 12 months post-treatment commencement. Treatment effects for self-reported disability in the SPE group at 12 weeks were not maintained, with neither group registering significant effects at 12 months. Conclusions The emergence of massed protocols for PTSD is an important advancement. The current study provides RCT evidence for the longevity of MPE treatment gains at 12 months post-treatment commencement and demonstrated non-inferiority to SPE. Promisingly, both treatments also significantly reduced the severity of comorbid symptoms commonly occurring alongside PTSD.

Chukrasia tabularis A. Juss produces a valuable timber but plantations are susceptible to attack by the shoot-tip borer Hypsipyla robusta Moore. An integrated pest management (IPM) approach is desirable to limit the extent of damage. Therefore, this study was undertaken to evaluate the deployment of IPM measures in plantations in Vietnam. Data on tree damage and the biology of H. robusta were gathered in 4 provinces over one year and used to build an investigation schedule. Two preliminary IPM trials were then established in which Bacillus thuringiensis and Metarhizium anisopliae were applied to the foliage when the damage incidence (P%) was in the range 5–10%; and insecticides (Carbaryl, Carbosulfan) were applied when the P% exceeded 10%. In addition, larvae and pupae were removed manually over time. In the first trial, the combination of manual and biological control methods reduced the damage index (DI) of trees from 4 tolerant families by 82% compared to the untreated control plots. In the second trial using standard planting stock, application of insecticides was required to reduce the DI by 83%. Six extended IPM trials were undertaken using the same IPM protocols and these reduced the DI to the same extent as in the preliminary trials. Over an 18-month period, the deployment of IPM increased height growth by 19–22% and diameter growth by 38–41% compared to the controls. These findings highlight the value of planting improved seed and the benefit of adopting an IPM approach to manage the shoot-tip borer.

In Brazil, scorpion stings are recorded in high numbers with an increasing epidemiological situation in most municipalities. In the present study, data between 1998 and 2018 in Americana, São Paulo, were analyzed.In total, 4122 records on scorpion stings were georeferenced using a Garmin eTREX 30X global positioning system device, with WGS84 datum projection and Universal Transverse Mercator zone 23S. Multiple Poisson regression was used to explore the relationship between the incidence rates of stings and urban planning areas (UPAs). Eight quantitative variables were used to establish the environmental and anthropic characterization of UPAs associated or not associated with scorpionism. A spatial analysis was performed for geoprocessing maps of Americana using spatial statistics tools (optimized hotspot analysis and kernel density function) from cartographic clusters in the ArcMap software, version 10.5.The optimized hotspot analysis tool identified spatial clusters with high values of the incidence of scorpion stings in the surroundings of all UPAs in the municipality. The estimation of the kernel function of event intensity showed a wide distribution of stings across the area of the entire municipal territory, with UPA-02 and UPA-06 exhibiting the highest occurrence of scorpion stings. Six significant hotspots were established as highest-event-density areas (with occurrences of 160-270) and were contiguous to 4 environmental protection areas, located in more peripheral regions, and to 2 municipal cemeteries, which were located in urban central areas.This analysis showed that the risk of scorpion stings in different Americana's UPAs has increased occurrence and incidence intensity.

The association between organ laterality abnormalities and ciliary ultrastructural defect or genotype in primary ciliary dyskinesia is poorly understood.To determine if there is an association between presence/type of laterality abnormality and ciliary ultrastructural defect and genotype.Participants with primary ciliary dyskinesia in a multicenter, prospective study were grouped based on ciliary ultrastructural defect or genotype. In a retrospective analysis of this data, the association of ciliary ultrastructural defect or genotype and likelihood of a laterality abnormality was evaluated by logistic regression adjusted for presence of two loss-of-function versus one or more not-loss-of-function variants.Of 559 participants, 286 (51.2%), 215 (38.5%), and 58 (10.4%) were identified as having situs solitus, situs inversus totalis, and situs ambiguus, respectively; heterotaxy, defined as situs ambiguus with complex cardiovascular defects, was present in 14 (2.5%). Compared to group with inner dynein arm defects with microtubular disorganization, laterality defects were more likely in the outer dynein arm defects group (OR 2.07, 95% CI 1.21-3.54, P0.01) and less likely in the normal/near normal ultrastructure group (OR 0.04, 95% CI 0.013-0.151, P0.01). Heterotaxy was present in 11 of 242 (4.5%) in the outer dynein arm defects group but zero of 96 in the inner dynein arm defects with microtubular disorganization group (P=0.038).In primary ciliary dyskinesia, risk of a laterality abnormality differs by ciliary ultrastructure defect. Pathophysiologic mechanisms underlying these differences require further exploration.

This paper presents new experimental and numerical evidence that perforations in a pipe wall result in a low-frequency bandgap within which sound waves rapidly attenuate. These perforations are modelled as an acoustically soft boundary condition on the pipe wall and show that a low frequency bandgap is created from 0 Hz. The upper bound of this bandgap is determined by the dimensions and separation of the perforations. An analytical model based on the transfer matrix method is proposed. This model is validated against numerical predictions for the pipe with varying perforation geometries. A numerical study is undertaken to model the effect of perforations with ideal acoustically soft boundary conditions and surrounded with an air gap. Close agreement is found between the numerical and analytical models. Experimental evidence shows that the width of the bandgap is accurately predicted with the numerical and analytical models.

Objectives Collective intelligence, the “wisdom of the crowd,” seeks to improve the quality of judgments by aggregating multiple individual inputs. Here, we evaluate the success of collective intelligence strategies applied to probabilistic diagnostic judgments. Methods We compared the performance of individual and collective intelligence judgments on two series of clinical cases requiring probabilistic diagnostic assessments, or “forecasts”. We assessed the quality of forecasts using Brier scores, which compare forecasts to observed outcomes. Results On both sets of cases, the collective intelligence answers outperformed nearly every individual forecaster or team. The improved performance by collective intelligence was mediated by both improved resolution and calibration of probabilistic assessments. In a secondary analysis looking at the effect of varying number of individual inputs in collective intelligence answers from two different data sources, nearly identical curves were found in the two data sets showing 11–12% improvement when averaging two independent inputs, 15% improvement averaging four independent inputs, and small incremental improvements with further increases in number of individual inputs. Conclusions Our results suggest that the application of collective intelligence strategies to probabilistic diagnostic forecasts is a promising approach to improve diagnostic accuracy and reduce diagnostic error.

The attenuation of acoustic waves by silencers is typically achieved through the employment of rigidly backed cavities, connected to a main waveguide by a perforated panel. This invokes a resonant response at frequencies determined by the dimensions of the perforation and the rigidly backed cavity. A limiting factor in this approach is that to achieve low frequency attenuation, either large cavity depths are required, which is often impractical, or narrow neck regions need to be used, where performance is limited due to the viscothermal losses. Within this paper, a non-rigidly backed perforated pipe is presented where the pressure release condition at each perforation creates an acoustic sound-soft boundary condition. By the introduction of sound-soft boundary conditions, a low frequency band gap is created as the first order mode is shifted to a non-zero value, the frequency of which is determined by the dimensions and separation of the perforations. Experimental results displaying this band gap are presented along with numerical models verifying the phenomenon and an ideal analytical model based upon the transfer matrix method.

During the planning process for an onshore wind farm, the establishment of accurate background noise levels at nearby noise sensitive receptors is vital in determining the allowable noise limits at these locations. This is typically achieved through background noise monitoring at a selection of representative noise sensitive receptors. As onshore windfarms have become more prevalent, areas suitable for wind farm development are increasingly within the vicinity of operational wind farms. The result of this is background noise monitoring at receptors is now often influenced by nearby operational wind farms and is not a true representation of the unaffected noise levels at these locations. Current good UK practice (as set out in the Institute of Acoustics document 'A good practice guide to the application of ETSU-R-97 for the assessment and rating of wind turbine noise') proposes a number of solutions to account for this additional wind farm noise. One solution is to consider directional filtering or the subtraction of the predicted noise levels from the measured baseline data. Whilst both approaches are valid, it can often be unclear which approach is most appropriate for a particular scenario. Within this paper, the limitations of current good practice are discussed, and an alternative methodology is proposed which combines both approaches to establish the unaffected background noise levels. Specific examples of where this alternative approach has been used are presented within the paper as validation.

People who experience human trafficking (HT) visit emergency departments (ED). The International Classification of Diseases, Clinical Modification (ICD-10-CM) introduced codes to document HT in June 2018. The aim of this study is to identify characteristics of ED patients who experienced forced labor or sexual exploitation as a documented external cause of morbidity in US visits.Nationally representative surveillance based on patient visits to 989 hospital-owned EDs in the Nationwide Emergency Department Sample in 2019 became available in 2021. Eight ICD-10-CM codes to classify HT as an external cause of morbidity were combined into one HT variable for analysis in 2021-2022.A weighted count of 517 of 33.1 million ED visits (0.0016%) documented HT as an external cause of morbidity. Of them, sexual exploitation (71.6%) was documented more frequently than labor exploitation (28.4%). Most HT-related codes were visits by females (87.3%) from large metropolitan areas, and identified as white. Approximately 40% of visits were from ZIP codes with a median household income less than $48,000 annually. Relative to all other ED visits, patients with HT as an external cause of morbidity had higher odds of being female (OR = 6.54, 95% CI:3.59, 11.92) and being a minor (OR = 1.76, 95% CI:1.02, 3.04).HT was rarely documented as an external cause of morbidity in 989 hospitals' ED visits from a nationally representative sample in 2019. Documentation of recently added HT ICD-10-CM codes does not appear to have been implemented sufficiently to yield an unbiased representation of those who experienced HT and presented in the ED. Efforts to enhance the utility of ICD-10-CM HT codes for surveillance and documentation must first address ED personnel training on identification and response to HT. In doing so, ED personnel also need to address ethical concerns (e.g. stigma, confidentiality, risk of patient harm) and allow for informed consent among trafficked patients in order to be scaled up responsibly.

In versified texts congruence is one facet of the concordance between the edges of metrical constituents and those of grammatical constituents. Congruence may be characterized roughly as the requirement that no element within a syntactic constituent be in a stronger metrical position than the final element in that constituent. If break strength is defined in terms applicable to any constituent structure tree, syntactic as well as metrical, incongruences are discrepancies between the relative strengths of two breaks in metrical structure and the relative strengths of their counterparts in syntactic structure. Although our primary source of data is classical French verse, the characterization of congruence we present is a rather abstract one that does not make reference to features that are specific to French poetic forms or to the grammatical structure of the French language. This should make this characterization applicable in other poetic traditions.

Glycoengineering of recombinant glycans and glycoconjugates is a rapidly evolving field. However, the production and exploitation of glycans has lagged behind that of proteins and nucleic acids. Biosynthetic glycoconjugate production requires the coordinated cooperation of three key components within a bacterial cell: a substrate protein, a coupling oligosaccharyltransferase, and a glycan biosynthesis locus. While the acceptor protein and oligosaccharyltransferase are the products of single genes, the glycan is a product of a multigene metabolic pathway. Typically, the glycan biosynthesis locus is cloned and transferred en bloc from the native organism to a suitable Escherichia coli strain. However, gene expression within these pathways has been optimized by natural selection in the native host and is unlikely to be optimal for heterologous production in an unrelated organism. In recent years, synthetic biology has addressed the challenges in heterologous expression of multigene systems by deconstructing these pathways and rebuilding them from the bottom up. The use of DNA assembly methods allows the convenient assembly of such pathways by combining defined parts with the requisite coding sequences in a single step. In this study, we apply combinatorial assembly to the heterologous biosynthesis of the Campylobacter jejuni N-glycosylation (pgl) pathway in E. coli. We engineered reconstructed biosynthesis clusters that faithfully reproduced the C. jejuni heptasaccharide glycan. Furthermore, following a single round of combinatorial assembly and screening, we identified pathway clones that outperform glycan and glycoconjugate production of the native unmodified pgl cluster. This platform offers a flexible method for optimal engineering of glycan structures in E. coli.

Cystic Fibrosis (CF) and autism spectrum disorder (ASD) are life-long conditions with intense treatment burdens for patients and families. Patients with a concurrent diagnosis (CF-ASD) experience unique obstacles to CF care. This study describes the experiences of our multidisciplinary CF team in caring for patients with CF-ASD and provides insight into provider and parental perspectives on clinical management.This is a three-part qualitative study involving 1) retrospective chart review of patients with CF-ASD, 2) surveys with multi-disciplinary care team members, and 3) semi-structured interviews with caregivers of patients with CF-ASD. Challenges in clinical management of this specific cohort were compiled using data from chart review and care team surveys. Strategies to address these concerns were identified and rated by individual families based on relevance and practicality.Within our CF center, 12 patients have an official diagnosis of ASD. Median age of patients with CF-ASD was 8.5 years (range 3-20 years), 67% were male, and 83% were on highly effective modulator therapy. Clinical barriers included sensory processing issues, environmental overstimulation, intolerance to procedures and to disrupted routines. Potentially impactful strategies include patient-specific coping plans, guided behavioral interventions, parental advocacy, and improved communication between the family and multidisciplinary team.Children with CF-ASD face extraordinary challenges beyond the experience of neurotypical children with CF. Increased awareness of this complex dual diagnosis will help providers be sensitive to the unique needs of these patients, help build consistent and trustworthy relationships with their families and deliver effective clinical care despite limitations. This article is protected by copyright. All rights reserved.

The Centers for Disease Control and Prevention reported a sharp increase in overdose deaths from illicitly manufactured fentanyls (IMFs) occurring between 2020 and 2021 in the United States. Approximately 4 in 10 drug overdose deaths involved opioids and stimulants. Fentanyl test strips (FTS), used to test drug product before use, can be a powerful harm reduction tool to promote safer use behaviors.This pilot study assessed treatment-seeking service users' knowledge and understanding of IMFs and motivation to use FTS to prevent overdose.Clients receiving residential-based or office-based substance use treatment services were recruited from a community mental health center in the midwestern United States to complete a harm reduction-focused survey. Eligibility criteria included clients aged 18-89 years with self-reported drug use in the past year. A 20-question survey was administered verbally, both in person and via phone to assess knowledge of IMFs and FTS.Of respondents (N = 30), 80% agreed that IMFs cause more overdoses than heroin. Most (73%) indicated concern about a friend overdosing owing to IMFs, and half (53%) expressed concern about personal risk of overdose. Most (73%) would like to be able to detect whether there is fentanyl in their drug before use, but only 17% indicated that they feel confident in their ability to use FTS.Many respondents who were receiving services for past-year substance use lacked understanding of how to use FTS for harm reduction. Clients who primarily use nonopioid (stimulant) drug products are at even greater risk of IMF overdose and would benefit the most from increased access and education surrounding the use of FTS. Our health care system must rapidly continue to explore and expand on overdose prevention efforts, including access to FTS, given that urgent action is needed to reduce the continued rise in overdose deaths in the United States.

Wild mushrooms are extensively gathered by rural communities throughout the uplands of northern Vietnam and nearby countries for food and medicine. These non-wood forest products are important for the livelihood of numerous rural communities. Many of these fungi form symbiotic relationships with the roots of certain species of forest trees, and the fruiting bodies can not be produced in artificial media. In the northeast region of the country, an edible red Russula (Nấm chẹo or Nấm hồng cô) has been harvested from under wild Castanopsis, Engelhardia and Lithocarpus trees by local people for a long time. However, the identity of this Russula is unknown. We collected basidiomes of this edible Russula in Cao Bang, Bac Giang and Quang Ninh provinces and described its morphological features. We used ITS rDNA and LSU rDNA sequence analysis to compare with other similar taxa in GenBank. Morphological and molecular analysis identified the taxon as Russula griseocarnosa, previously described from southern Yunnan, China. There is strong interest by local governments to commercialize R. griseocarnosa in Vietnam. However, over-harvesting could have detrimental effects on the population of this edible species. Therefore, further studies are needed to quantify the ecological requirements and to develop sustainable harvesting protocols of this edible species in Vietnam.

Mangroves can play a major role in efforts to mitigate climate change through two pathways. These are (1) carbon sequestration following reforestation of areas where mangroves previously existed, and (2) protection of existing carbon stores in intact mangrove forests. There is considerable international interest in carbon mitigation by governments and businesses as a way of meeting emissions reduction targets, and this could result in significant investment in mangrove restoration and protection. This is likely to have positive benefits in terms of coastal protection, biodiversity protection and new economic activity. This project examined three aspects of mangroves related to the emerging carbon economy. There has been considerable (0.2 million hectares) mangrove restoration in Vietnam and this activity provides insights into the causes of project success or failure. A review of this restoration concluded that the failure of several past restoration projects in Vietnam could be attributed to poor species and site selection and lack of incentives to engage residents in long-term management. The economic, environmental and social aspects of mangrove-shrimp farming or aquaculture (MAS) systems in Ca Mau Province, Vietnam, were examined, and it was concluded that this approach allows the achievement of these multiple objectives. Whereas, most of the discussion around mangroves and their role in carbon management is at the international and national levels, implementation occurs at the local level. It was found that whereas local stakeholders had a reasonable understanding of climate change, they were less clear about carbon markets and the role that mangroves can play. This points to the need for new educational programmes. The study concluded that monitoring and verification systems for both carbon and biodiversity are essential to allow the resultant multiple benefits of carbon mitigation projects to be realised.

Allometric models play an undeniable role for estimating hard-to-measure quantities such as volume, biomass and carbon stock in forests. However, so far there has been limited model development for native forests in Vietnam. Therefore, this study was conducted to build and analyze the effectiveness of nonlinear and mixed models for secondary and old-growth forests in Gia Lai, Vietnam. The study measured diameter at breast height, total height, commercial height and crown width of forest trees in 20 plots (10 plots for each forest stage). The results showed that diameter had the strongest relationship with height. In the secondary forest, the Power, Korf and Ratskowky models were the best for pairs of variables, while Prodan, Weibull and Power models were the best fit in the old-growth forest. The nonlinear mixed-effect models were better than classic nonlinear models in both forest stages. Fixed and mixed models developed in this study are very valuable for estimating difficult-to-measure quantities and contribute to effective forest management in the study region.

This paper provides a brief introduction to the secret level of Tibetan spiritual biographies (gsang ba’i rnam thar) and autobiographies (gsang ba’i rang rnam) with a focus on visions in meditation and dreams. In the analysis section, some appropriately selected episodes of such secret aspects taken from one of the spiritual autobiographies of the Second Pawo, Tsuklak Trengwa (dpa’ bo gtsug lag phreng ba; 1504–1566), called The Mirror Reflecting the Illusory Countenance (‘khrul pa’i bzhin ras ‘char ba’i me long) are presented and interpreted.

The circadian rhythm generates out-of-equilibrium metabolite oscillations that are controlled by feedback loops under light/dark cycles. Here we describe a non-equilibrium nanosystem comprising a binary population of enzyme-containing polymersomes capable of light-gated chemical communication, controllable feedback and coupling to macroscopic oscillations. The populations consist of esterase-containing polymersomes functionalized with photo-responsive donor–acceptor Stenhouse adducts (DASA) and light-insensitive semipermeable urease-loaded polymersomes. The DASA–polymersome membrane becomes permeable under green light, switching on esterase activity and decreasing the pH, which in turn initiates the production of alkali in the urease-containing population. A pH-sensitive pigment that absorbs green light when protonated provides a negative feedback loop for deactivating the DASA–polymersomes. Simultaneously, increased alkali production deprotonates the pigment, reactivating esterase activity by opening the membrane gate. We utilize light-mediated fluctuations of pH to perform non-equilibrium communication between the nanoreactors and use the feedback loops to induce work as chemomechanical swelling/deswelling oscillations in a crosslinked hydrogel. We envision possible applications in artificial organelles, protocells and soft robotics.

Within the Marispace-X project, a digital maritime data space based on data sovereignty, security, interoperability, and modularity according to the Gaia-X concept should be created. The article provides an overview of the envisioned Marispace-X digital infrastructure, a decentralized maritime data ecosystem, followed by exemplary applications for hydrographic surveys and some of the use cases defined in the Marispace-X project. These exemplary applications are related to data management, sharing and processing services that can be performed on a cloud infrastructure. This digital infrastructure should simplify data handling of all the different data types and formats that exist in the maritime domain.

This article examines the racial dimensions of UFO abduction narratives by comparing the structural elements of these narratives with historical accounts of African enslavement. It is suggested that UFO abduction narratives from White Americans, which make up an overwhelming majority of such accounts, comes from collective feelings of widespread culpability for the enslavement and profiting from African persons. It is suggested that the UFO abduction experience is a way to overcome such pervasive feelings of guilt by establishing a new power dynamic that reverses the roles of victim and victimizer and mirrors closely historical accounts of abduction. Furthermore, it seeks to add to the discourse surrounding race and the conception of the extraterrestrial.

Ko te tino kaupapa o te tuhinga nei hei whakaatu i ngā rautaki a te Maori mō ngā rākau taketake e kainga ana e te ngāngara. Kua whakaputaina mai ngā rautaki e rima nei; pūrākau, rāhui, karakia, tohu, me te mahitahi. I ahu mai ngā rautaki katoa i te mātauranga Māori. Ahakoa, he rerekē ētahi o ngā āhuatanga mō ia rautaki, kotahi noa te whakaakoranga ka puta i ngā rautaki katoa—ko te hononga o ngā mea katoa. Koirā te kitenga matua o te rangahau. Nā te mea, ko tātou ngā tāngata o te ao tūroa, ngā tamariki o te moana, o ngā roto, o ngā awa, o ngā ngahere hoki.

Resumo O Programa Educacional de Resistência às Drogas (PROERD) é o programa escolar de prevenção mais disseminado no Brasil, seu atual currículo é baseado no programa norte-americano Keepin’it REAL (kiR). Não há na literatura evidência de efetividade do PROERD na prevenção ao uso de drogas, sendo necessários estudos complementares que auxiliem a compreensão desses achados. O objetivo do presente estudo é realizar uma síntese das evidências do efeito do currículo que deu origem ao PROERD: o kiR. Através de revisão sistemática encontrou-se 17 estudos que reportaram resultados de efeito de diferentes versões do kiR no uso de drogas e/ou violência. Com exceção do estudo brasileiro, não foram encontrados estudos que avaliassem o efeito no uso de drogas da versão aplicada por policiais (DARE-kiR), a mesma implementada pelo PROERD. Foram encontradas evidências favoráveis do kiR na prevenção ao uso de drogas para o currículo do 7º ano, que contrariam os resultados de efeito nulo do PROERD. Não foram encontradas evidências internacionais do efeito do kiR no currículo do 5º ano, assim como o estudo do PROERD. Sugere-se que revisões no currículo do 7º ano do PROERD para que ele possa refletir os resultados internacionais e que o currículo do 5º ano posso ser repensado considerando as evidências negativas internacionais. Abstract The Drug Resistance Educational Program (PROERD) is Brazil’s most widespread school-based prevention program; its current curriculum is based on the North American Keepin’ it REAL (kiR) program. There is no evidence of the effectiveness of PROERD in preventing drug use, pointing to the need for further studies to understand these findings. The aim of the study was to synthesis the evidence of the effect of the kiR curriculum (PROERD) through a systematic review. We found 17 studies that reported the effects of different versions of kiR on drug use and/or violence. Except for the Brazilian study, no studies were found that assessed the effect on drug use of the version applied by police officers (DARE-kiR), the same one implemented by PROERD. Favorable evidence of kiR in drug use prevention was found for the 7th-grade curriculum, which contradicts the PROERD’s null-effect results. No international evidence of the effect of kiR was found in the 5th-grade curriculum, in the same line as the PROERD’s study. It is suggested that PROERD’s 7th-grade curriculum should be revised to reflect international results and that the 5th-grade curriculum should be reconsidered in light of the negative international evidence.