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Abstract The physical appearance of date palm (Phoenix dactylifera) fruit (dates) is important for its market value. Many date-producing countries experience significant financial losses due to the poor appearance of the fruit, skin separation or puffiness being a major reason. Previous research showed evidence linking the skin separation phenotype to environmental conditions. To investigate this further, a genome-wide association study was conducted using genome data from 199 samples collected from 14 countries. Here, we identified nine genetic loci associated with this phenotype and investigated genes in these regions that may contribute to the phenotype overall. Multiple genes in the associated regions have functional responses to growth regulators and are involved in cell wall development and modification. Analysis of gene expression data shows many are expressed during fruit development. We show that there are both environmental and genetic contributions to the fruit skin separation phenotype. Our results indicate that different date cultivars exhibit varying degrees of skin separation despite genetic similarities or differences. However, genetically different cultivars show extreme differences compared to the phenotype variation between genetically similar cultivars. We demonstrate that beyond environmental factors, genetics is a strong contributor to the most extreme skin separation in some cultivars. Identifying the genetic factors may help better understand the biology and pathways that lead to the environmental effects on skin separation and improve commercial date production. In conclusion, our key finding is that both environmental and genetic factors contribute to skin separation variation, and improvements in environmental factors alone cannot overcome the extreme level of variation observed in some cultivars.

Abstract Pregenomic hepatitis B virus RNA (HBV pgRNA) is a potential biomarker in the management of HBV infected patients. However, prior to the use in routine clinical practice potential confounders of test results need to be identified. This study investigates the stability of HBV pgRNA under various storage conditions. HBV-RNA level of 26 HBV patients were determined using the Roche cobas® 6800/8800 investigational HBV-RNA assay. Plasma and serum were stored for 6,48,169 h at 4,25 and 42 °C, respectively. Additionally, 10 serum and plasma samples underwent 4 or 11 cycles of freezing (−80 °C) and thawing (25 °C). A significant decline in mean pgRNA concentration compared to baseline was observed after storage for 48 h at 25 °C as well as after 6 h of storage at 42 °C. Accordingly, sub-analyses of predefined pgRNA baseline concentrations (≤ 10 cp/mL, > 10–100 cp/ml, > 100 cp/mL) revealed significant changes in pgRNA level after storage at 25 and 42 °C. No effect of freezing and thawing on pgRNA level was observed. A qualitative detection of HBV pgRNA is feasible in samples with > 100 cp/mL up to 48 h under storage temperatures of 4–42 °C. For most stable quantitative HBV pgRNA values storage at 4 °C should be preferred.

Protein–ligand interactions (PLIs) determine the efficacy and safety profiles of small molecule drugs. Existing methods rely on either structural information or resource-intensive computations to predict PLI, casting doubt on whether it is possible to perform structure-free PLI predictions at low computational cost. Here we show that a light-weight graph neural network (GNN), trained with quantitative PLIs of a small number of proteins and ligands, is able to predict the strength of unseen PLIs. The model has no direct access to structural information about the protein–ligand complexes. Instead, the predictive power is provided by encoding the entire chemical and proteomic space in a single heterogeneous graph, encapsulating primary protein sequence, gene expression, the protein–protein interaction network, and structural similarities between ligands. This novel approach performs competitively with, or better than, structure-aware models. Our results suggest that existing PLI prediction methods may be improved by incorporating representation learning techniques that embed biological and chemical knowledge.

Pemakaian mesin pintas jantung paru (PJP) dalam operasi coronary artery bypass graft (CABG) dapat meningkatkan kebutuhan transfusi darah. Tujuan penelitian ini untuk mengetahui efektivitas retrograde autologous priming (RAP) dalam menurunkan volume transfusi sel darah merah/packed red cell (PRC) pada pasien bedah jantung koroner dengan mesin PJP. Penelitian ini melibatkan 52 pasien yang dijadwalkan menjalani operasi coronary artery bypass graft (CABG). RAP dimulai selama bypass dalam satu kelompok dengan mengalirkan larutan kristaloid dari jalur arteri dan vena ke dalam kantong penampung dengan volume penarikan RAP yang dimaksudkan dan disesuaikan untuk setiap pasien. Non-RAP menggunakan teknik konvensional PJP. 52 pasien (RAP = 26; kontrol = 26) dilibatkan dalam analisis. Pasien dalam kelompok RAP menerima volume transfusi PRC intraoperatif yang jauh lebih rendah dibanding dengan pasien pada kelompok non-RAP (median, 0 mL vs 205 mL, p=0,014). Analisis regresi linier berganda menunjukkan bahwa prosedur RAP mempengaruhi secara signifikan (p

Abstract Background Current literature presents mixed effects of the COVID-19 pandemic on Indigenous communities. We aim to highlight potential disparities and temporal shifts in both the impact of COVID-19 and vaccine uptake among hospitalized Indigenous populations in Chile. Methods We conducted an observational analysis utilizing 1,598,492 hospitalization records from 2020 to 2021 based on publicly accessible hospital discharge data spanning 65 healthcare facilities of medium and high complexity funded through the Diagnosis-Related Groups (DRG) mechanism in Chile, representing roughly 70% of the country’s total hospitalizations. This was supplemented with publicly available municipal data on COVID-19 vaccinations and socio-demographic variables. We performed logistic regression analysis at 0.05 level of significance to assess the bivariate and multivariable association of Indigenous status with COVID-19 diagnosis and COVID-19 deaths among hospitalized populations. We also performed univariate and multiple linear regression to assess the association of COVID-19 vaccination rate and Indigenous status at the municipality level. In addition, we report the distribution of top 10 secondary diagnoses among hospitalized COVID-19 cases and deaths separately for Indigenous and non-Indigenous populations. Results Indigenous populations displayed lower adjusted odds for both COVID-19 diagnosis (OR: 0.76, 95% CI: 0.74, 0.77) and death (OR: 0.91, 95% CI: 0.85, 0.97) when compared to non-Indigenous groups. Notably, the adjusted odds ratio for COVID-19 diagnosis in Indigenous populations rose from 0.59 (95% CI: 0.57, 0.61) in 2020 to 1.17 (95% CI: 1.13, 1.21) in 2021. Factors such as the significantly higher median age and greater number of comorbidities in the non-Indigenous hospitalized groups could account for their increased odds of COVID-19 diagnosis and mortality. Additionally, our data indicates a significantly negative adjusted association between COVID-19 vaccination rates and the proportion of Indigenous individuals. Conclusion Although Indigenous populations initially showed lower odds of COVID-19 diagnosis and mortality, a marked rise in diagnosis odds among these groups in 2021 underscores the urgency of targeted interventions. The observed negative association between the proportion of Indigenous populations and vaccination rates further underscores the necessity to tackle vaccine access barriers and work towards equitable distribution.

Composites are synthesized by combining different materials, resulting in properties suitable for use as adsorbents due to the combination of pores and functional groups within the constituent materials. This study developed a silica-biochar composite to serve as an adsorbent for rhodamine B dye, utilizing silica derived from red mud and biochar obtained from oil palm empty fruit bunches (OPEFB). This research focused on analyzing the characteristics and effectiveness of the composite as an adsorbent by varying its composition. Silica from red mud exhibited a purity of 80.05% and possessed silanol (Si-OH) and siloxane (Si-O-Si) functional groups on its surface, whereas biochar from OPEFB had a carbon content of 95.91% and included functional groups such as -OH, C=O, C=C, C-H, and C-O. The combination of silica and biochar yielded a composite surface consisting of -OH, C=O, C=C, C-O, C-H, and Si-O-Si functional groups. The silica-biochar composite demonstrated a greater surface area than its individual components, with silica at 69.824 m²/g and biochar at 95.452 m²/g. The composite with a 1:2 (% w/w) ratio exhibited the largest surface area at 102.371 m²/g, achieving a maximum adsorption capacity of 1.550 mg/g and an efficiency of 88.463%. The adsorption process encompasses physical interactions via pore diffusion and chemical interactions through functional groups.

Sepsis, a severe medical condition, signifies the systemic immune response to infection, often leading to organ dysfunction and mortality. Escherichia coli is a significant contributor to sepsis cases, particularly in gastrointestinal disorders. This study aimed to investigate the histopathological changes in the gastric tissue of mice induced by Escherichia coli infection and evaluate the protective effects of kentut leaf extract (Paederia foetida L.). Histopathological analysis revealed distinct alterations in the gastric tissue among different treatment groups. While normal mouse treatment showed no significant changes, negative control (K-) and positive control (K+) groups exhibited inflammation and hyperemia of the gastric mucosa, characterized by necrosis, degeneration, and inflammatory cell infiltration. Treatment with kentut leaf extract (P1, P2, and P3) resulted in milder inflammation compared to controls, indicating a protective effect against gastric mucosal damage induced by Escherichia coli infection. This protective mechanism is attributed to the anti-inflammatory properties of saponins, flavonoids, and essential oils present in kentut leaf extract. These findings underscore the potential therapeutic benefits of kentut leaf extract in mitigating gastric mucosal injury associated with bacterial infection.

Metal plating frequently employs nickel (Ni) and copper (Cu) as anodes. Cu/ Cu-Ni film formed has many advantages, such as better corrosion resistance and high hardness characteristics. This study aims to assess the properties of Cu/Cu-Ni film, such as phase, surface morphology, crystallographic orientation, hardness, corrosion analysis, and contact angle, which were fabricated using electrodeposition with various Ni salt additions (0.3, 0.5 and 0.7 M). In addition, the cathode current efficiency (CCE) and deposition rate of the Cu/Cu-Ni electrodeposition were also investigated. An increase in Ni salt in the plating bath could enhance the pH, promoting higher CCE and depleting hydrogen evolution at the cathode, leading to the presenting Ni phase in the alloy. The higher concentration of Ni salt in the solution could also enhance the deposition rate due to a shift to a pH value, which affects the roughening of the surface morphology, promoting a higher contact angle. All crystal structures generated by Cu/Cu-Ni electrodeposition were FCC, with the preferred orientation of the (111) plane. Crystallite size and lattice strain depend on the deposition rate. Less crystallite size and lattice strain affect the film’s hardness and corrosion resistance. Moreover, the third bath had the resulting Cu-Ni layer with the best hardness and corrosion rate of around 136 HV and 0.081 mmpy.

IntroductionPrimary care settings present an opportunity for alcohol and substance use disorder (A/SUD) screening and treatment referral. However, there are recognized deficiencies in widely used treatment referral approaches, including acute care connections, vs. those that can support longer-term recovery. Recovery Management Checkups for Primary Care (RMC-PC) is an intervention with an evidence base for improving treatment referral and subsequent recovery for primary care patients; however, the intervention has never been fully implemented outside of a research context. We conducted a feasibility study to inform a future hybrid study of RMC-PC that will test the implementation and effectiveness of the intervention in primary care practice.MethodWe used a convergent mixed method design. The study’s setting was a Federally Qualified Health Center (FQHC) located in a large midwestern city. RMC-PC linkage services were administered by one of two treatment linkage managers: an FQHC linkage manager (F-LM) and a research staff linkage manager (R-LM). Quantitative data included (a) rates of positive A/SUD screening among a group of FQHC patients and (b) linkage manager service data (e.g., rate of successful meeting completion and days to completing of key events). Qualitative data included (c) an assessment of linkage manager’s motivational interviewing performance and (d) a focus group with FQHC staff focused on their perspectives on RMC-PC implementation determinants. Quantitative data were summarized using descriptive statistics, and linkage manager performance was compared. Qualitative data were analyzed using a hybrid deductive-inductive process.ResultsFifty percent of patients screened met moderate-high A/SUD risk. Eleven of 16 recruited patients completed at least one linkage manager meeting, with 63% completing both meetings. The F-LM delivered RMC-PC services alongside other duties successfully; however, three primary barriers to FQHC implementation were identified (difficulties applying motivational interviewing, incompatibilities of screening with FQHC technology and workflow, and lack of billing mechanism to support services).ConclusionRMC-PC is feasible for FQHC staff to deliver, though issues identified must be considered to ensure successful and sustainable implementation. Knowledge gained will inform a packaged implementation strategy that will be used in a future hybrid trial.

Objective Hypertrophic cardiomyopathy (HCM), including obstructive HCM (oHCM), is the most common inherited cardiomyopathy causing lifestyle-limiting symptoms. Data are lacking about patients’ perspectives on the daily impact of their symptoms. This qualitative interview study was conducted to better understand patients’ experiences with oHCM.Methods In October 2019, telephone interviews were conducted with 20 US adults with oHCM identified by the Hypertrophic Cardiomyopathy Association. Using a semi-structured interview guide, key symptoms, impacts of oHCM and oHCM treatment goals were discussed.Results Median age was 54 years (range 29–78), 55% were women, 85% were white and 15% were Hispanic or Latino. Median time since diagnosis was 3 years. Symptoms included shortness of breath, dizziness/light-headedness, heart palpitations/fluttering (all 95%), fatigue (90%) and chest pain/pressure (80%). All participants reported limitations in physical functioning/activities; most reported additional impacts (emotional stress (80%), fear of dying (55%)). Shortness of breath and fatigue were among their most bothersome symptoms; an effective oHCM treatment would need to improve ≥1 of these symptoms (allowing increased physical/social activity).Conclusions Patients with oHCM experience a high symptom burden and psychosocial impacts, affecting health status. Improved shortness of breath, fatigue and physical functioning are highly valued by patients and represent important treatment goals.

Abstract Background Estimating program costs when planning community-based mental health programs can be burdensome. Our aim was to retrospectively document the cost for the first year of planning and implementing Healthy Minds Healthy Communities (HMHC), a mental health promotion and prevention multi-level intervention initiative. This Program is among the first to use the Community Initiated Care (CIC) model in the US and is aimed at building community resilience and the capacity for communities to provide mental health support, particularly among those disproportionately impacted by COVID-19. Our objective is to share our methods for costing a program targeting 10 zip codes that are ethnically and linguistically diverse and provide an example for estimating the cost of a mental health prevention and promotion programs consisting of multiple evidence-based interventions. Methods We used a semi-structured interview process to collect cost data through the first year of program planning, start-up and initial implementation from key staff. We calculated costs for each activity, grouped them by major project categories, and identified the cost drivers of each category. We further validated cost estimates through extensive literature review. The cost analysis was done from the provider’s perspective, which included the implementing agency and its community partners. We delineated costs that were in-kind contributions to the program by other agency, and community partners. Sensitivity analyses were conducted to estimate uncertainty around parameters. Results For the first year of the development and implementation of the program, (funded through program and in-kind) is estimated at $1,382,669 (2022 US$). The costs for the three main activity domains for this project are: project management $135,822, community engagement $364,216 and design and execution $756,934. Overall, the cost drivers for the first year of this intervention were: hiring and onboarding staff, in-person community building/learning sessions, communications and marketing, and intervention delivery. Conclusion Implementation of community-based mental health promotion and prevention programs, when utilizing a participatory approach, requires a significant amount of upfront investment in program planning and development. A large proportion of this investment tends to be human capital input. Developing partnerships is a successful strategy for defraying costs.

Abstract Molecular responses to alcohol consumption are dynamic, context-dependent, and arise from a complex interplay of biological and external factors. While many have studied genetic risk associated with drinking patterns, comprehensive studies identifying dynamic responses to pharmacologic and psychological/placebo effects underlying binge drinking are lacking. We investigated transcriptome-wide response to binge, medium, and placebo alcohol consumption by 17 healthy heavy social drinkers enrolled in a controlled, in-house, longitudinal study of up to 12 days. Using RNA-seq, we identified 251 and 13 differentially expressed genes (DEGs) in response to binge drinking and placebo, respectively. Eleven protein-coding DEGs had very large effect sizes in response to binge drinking (Cohen’s d > 1). Furthermore, binge dose significantly impacted the Cytokine-cytokine receptor interaction pathway (KEGG: hsa04060) across all experimental sequences. Placebo also impacted hsa04060, but only when administered following regular alcohol drinking sessions. Similarly, medium-dose and placebo commonly impacted KEGG pathways of Systemic lupus erythematosus, Neutrophil extracellular trap formation, and Alcoholism based on the sequence of drinking sessions. These findings together indicate the “dose-extending effects” of placebo at a molecular level. Furthermore, besides supporting alcohol dose-specific molecular changes, results suggest that the placebo effects may induce molecular responses within the same pathways regulated by alcohol.

Abstract Background Policymaking is quickly gaining focus in the field of implementation science as a potential opportunity for aligning cross-sector systems and introducing incentives to promote population health, including substance use disorders (SUD) and their prevention in adolescents. Policymakers are seen as holding the necessary levers for realigning service infrastructure to more rapidly and effectively address adolescent behavioral health across the continuum of need (prevention through crisis care, mental health, and SUD) and in multiple locations (schools, primary care, community settings). The difficulty of aligning policy intent, policy design, and successful policy implementation is a well-known challenge in the broader public policy and public administration literature that also affects local behavioral health policymaking. This study will examine a blended approach of coproduction and codesign (i.e., Policy Codesign), iteratively developed over multiple years to address problems in policy formation that often lead to poor implementation outcomes. The current study evaluates this scalable approach using reproducible measures to grow the knowledge base in this field of study. Methods This is a single-arm, longitudinal, staggered implementation study to examine the acceptability and short-term impacts of Policy Codesign in resolving critical challenges in behavioral health policy formation. The aims are to (1) examine the acceptability, feasibility, and reach of Policy Codesign within two geographically distinct counties in Washington state, USA; (2) examine the impact of Policy Codesign on multisector policy development within these counties using social network analysis; and (3) assess the perceived replicability of Policy Codesign among leaders and other staff of policy-oriented state behavioral health intermediary organizations across the USA. Discussion This study will assess the feasibility of a specific approach to collaborative policy development, Policy Codesign, in two diverse regions. Results will inform a subsequent multi-state study measuring the impact and effectiveness of this approach for achieving multi-sector and evidence informed policy development in adolescent SUD prevention and treatment.

Abstract High hospital occupancy degrades emergency department performance by increasing wait times, decreasing patient satisfaction, and increasing patient morbidity and mortality. Late discharges contribute to high hospital occupancy by increasing emergency department (ED) patient length of stay (LOS). We share our experience with increasing and sustaining early discharges at a 650-bed academic medical center in the United States. Our process improvement project followed the Institute of Medicine Model for Improvement of successive Plan‒Do‒Study‒Act cycles. We implemented multiple iterative interventions over 41 months. As a result, the proportion of discharge orders before 10 am increased from 8.7% at baseline to 22.2% (p

Abstract Background Biliary tract cancers (BTCs) are rare and lethal cancers, with a 5-year survival inferior to 20%(1–3). The only potential curative treatment is surgical resection. However, despite complex surgical procedures that have a remarkable risk of postoperative morbidity and mortality, the 5-year survival rate after radical surgery (R0) is 20–40% and recurrence rates are up to ~ 75%(4–6). Up to ~ 40% of patients relapse within 12 months after resection, and half of these patient will recur systemically(4–6). There is no standard of care for neoadjuvant chemotherapy (NAC) in resectable BTC, but retrospective reports suggest its potential benefit (7, 8). Methods PURITY is a no-profit, multicentre, randomized phase II/III trial aimed at evaluating the efficacy of the combination of gemcitabine, cisplatin and nabpaclitaxel (GAP) as neoadjuvant treatment in patients with resectable BTC at high risk for recurrence. Primary objective of this study is to evaluate the efficacy of neoadjuvant GAP followed by surgery as compared to upfront surgery, in terms of 12-month progression-free survival for the phase II part and of progression free survival (PFS) for the phase III study. Key Secondary objectives are event free survival (EFS), relapse-free survival, (RFS), overall survival (OS), R0/R1/R2 resection rate, quality of life (QoL), overall response rate (ORR), resectability. Safety analyses will include toxicity rate and perioperative morbidity and mortality rate. Exploratory studies including Next-Generation Sequencing (NGS) in archival tumor tissues and longitudinal ctDNA analysis are planned to identify potential biomarkers of primary resistance and prognosis. Discussion Considering the poor prognosis of resected BTC experiencing early tumor recurrence and the negative prognostic impact of R1/R2 resections, PURITY study is based on the rationale that NAC may improve R0 resection rates and ultimately patients’ outcomes. Furthermore, NAC should allow early eradication of microscopic distant metastases, undetectable by imaging but already present at the time of diagnosis and avoid mortality and morbidity associated with resection for patients with rapid progression or worsening general condition during neoadjuvant therapy. The randomized PURITY study will evaluate whether patients affected by BTC at high risk from recurrence benefit from a neoadjuvant therapy with GAP regimen as compared to immediate surgery. Trial registration PURITY is registered at ClinicalTrials.gov (NCT06037980) and EuCT(2023–503295-25–00).

The leukocyte count examination in tuberculosis infection serves to monitor the inflammation caused by Mycobacterium tuberculosis. An increasing leukocyte count can lead to complications such as pleuritis. The purpose of this study was to determine the total leukocyte count of pulmonary tuberculosis patients at RSUD Gambiran, Kediri City, based on gender and age. This research was a descriptive retrospective study. Data analysis was conducted using Microsoft Excel and presented in the form of tables and diagrams. The results of this study showed that pulmonary tuberculosis infection was more prevalent in males, with 26 individuals (62%) affected. In terms of age groups, the highest infection rate was in the 21-60 years age range, with 30 individuals (71%) affected. As for leukocyte count elevation (leukocytosis), it was more commonly observed in males with a count of 14.57 µL. In terms of age groups, leukocytosis was frequently observed in the 21-60 years age range, with a count of 48.66 µL. Out of the 42 samples, 19 individuals had a normal leukocyte count, while the remaining 23 individuals experienced leukocytosis. From the results of the study, it can be concluded that not all pulmonary tuberculosis patients experience leukocytosis; some patients maintain a normal leukocyte count.

Abstract Background Pharmacists remain an underutilized resource in the treatment of opioid use disorder (OUD). Although studies have engaged pharmacists in dispensing medications for OUD (MOUD), few studies have evaluated collaborative care models in which pharmacists are an active, integrated part of a primary care team offering OUD care. Methods This study seeks to implement a pharmacist integrated MOUD clinical model (called PrIMO) and evaluate its feasibility, acceptability, and impact across four diverse primary care sites. The Consolidated Framework for Implementation Research is used as an organizing framework for study development and interpretation of findings. Implementation Facilitation is used to support PrIMO adoption. We assess the primary outcome, the feasibility of implementing PrIMO, using the Stages of Implementation Completion (SIC). We evaluate the acceptability and impact of the PrIMO model at the sites using mixed-methods and combine survey and interview data from providers, pharmacists, pharmacy technicians, administrators, and patients receiving MOUD at the primary care sites with patient electronic health record data. We hypothesize that it is feasible to launch delivery of the PrIMO model (reach SIC Stage 6), and that it is acceptable, will positively impact patient outcomes 1 year post model launch (e.g., increased MOUD treatment retention, medication regimen adherence, service utilization for co-morbid conditions, and decreased substance use), and will increase each site’s capacity to care for patients with MOUD (e.g., increased number of patients, number of prescribers, and rate of patients per prescriber). Discussion This study will provide data on a pharmacist-integrated collaborative model of care for the treatment of OUD that may be feasible, acceptable to both site staff and patients and may favorably impact patients’ access to MOUD and treatment outcomes. Trial registration: The study was registered on Clinicaltrials.gov (NCT05310786) on April 5, 2022, https://www.clinicaltrials.gov/study/NCT05310786?id=NCT05310786&rank=1

We prove the existence of generalized solutions of the Monge–Kantorovich equations with fractional [Formula: see text]-gradient constraint, [Formula: see text], associated to a general, possibly degenerate, linear fractional operator of the type, ℒsu = −Ds ⋅ (ADsu + bu) + d ⋅ Dsu + cu, with integrable data, in the space [Formula: see text], which is the completion of the set of smooth functions with compact support in a bounded domain [Formula: see text] for the [Formula: see text]-norm of the distributional Riesz fractional gradient [Formula: see text] in [Formula: see text] (when [Formula: see text], [Formula: see text] is the classical gradient). The transport densities arise as generalized Lagrange multipliers in the dual space of [Formula: see text] and are associated to the variational inequalities of the corresponding transport potentials under the constraint [Formula: see text]. Their existence is shown by approximating the variational inequality through a penalization of the constraint and nonlinear regularization of the linear operator [Formula: see text]. For this purpose, we also develop some relevant properties of the spaces [Formula: see text], including the limit case [Formula: see text] and the continuous embeddings [Formula: see text], for [Formula: see text]. We also show the localization of the nonlocal problems ([Formula: see text]), to the local limit problem with classical gradient constraint when [Formula: see text], for which most results are also new for a general, possibly degenerate, partial differential operator [Formula: see text] with coefficients only integrable and bounded gradient constraint.

Background: Neonatal intensive care units (NICU) outbreaks caused by methicillin-susceptible Staphylococcus aureus (MSSA) are less commonly reported than outbreaks caused by methicillin-resistant S. aureus. We report an unusual outbreak of MSSA skin and soft tissue infections (SSTIs) in a level IV NICU investigated by whole genome sequencing (WGS) and molecular typing. Methods: An investigation was initiated in a 56-single-bed NICU after four patients developed MSSA SSTIs in Week 1. Case-patients had positive MSSA cultures identified by clinical cultures or surveillance sampling (bilateral nares, axillae, umbilicus, and groin), and antibiotic susceptibility testing was performed. WGS and assessment of isolate relatedness through mutation event analysis and multi-locus sequence typing (MLST) was performed by the NYS DOH. Demographic and isolate characteristics were compared using Wilcoxon rank sum test, Fisher’s exact test and Pearson’s Chi-squared test, as appropriate. Results: From Week 2 to Week 32, 9 rounds of surveillance for MSSA colonization were conducted. In all, 30 case-patients had MSSA colonization and 16 infants developed infections including impetigo (n=7), pustules (n=5), staphylococcal scalded skin syndrome (SSSS, n=2), abscess (n=1), and bacteremia (n=1). All SSTI cases presented on infants’ faces, all of whom were on non-invasive respiratory support. MLST identified 4 distinct types including MLST 121 (n=12), MLST 398 (n=10), MLST 30 (n=6), and MLST 15 (n=6). Eight isolates were unrelated to other isolates. MLST 398 and MLST 30 included isolates not closely related (>9 mutation events). The 12 MLST 121 isolates were closely related (≤9 mutational events between all isolates), harbored the mupA gene, and were mupirocin-resistant (MIC>1024 ug/ml). Clinical infection and mupirocin resistance were associated with MLST 121 (Table 1). Multiple infection control measures were implemented, including increased availability of alcohol-based hand sanitizers, introducing bare-below-the-elbows practice for staff, contact precautions for case-patients, decolonization with mupirocin and chlorhexidine baths, environmental cleaning/disinfection, and removing excess equipment and supplies. No new cases of mupirocin-resistant or MLST 121 SSTIs occurred after Week 25. Conclusion: We report a MSSA outbreak associated with multiple MLST types and a predominant mupirocin-resistant strain. This report highlights the ability of molecular typing to characterize strains causing infections versus colonization and the potential loss of mupirocin as a control measure when outbreaks are caused by mupirocin-resistant strains. WGS analysis allows for increased discrimination of mutation events allowing for improved resolution of case relatedness compared to other typing methods. Successful control of this outbreak was achieved with a multitude of infection prevention and control.

Background: Measures against COVID-19 in nursing homes affected not only clients but also staff. However, staff perspectives on the importance of these measures remain underexplored. Objective: To investigate measures related to staff during the COVID-19 pandemic, staff perspectives of important measures and the involvement of staff in deciding on these measures. Design: A qualitative study. Setting(s): We analysed minutes of nursing home outbreak teams in the Netherlands and conducted group meetings with Dutch nursing home staff in different positions, prioritizing measures and discussing staff’ involvement in deciding on the measures. Participants were recruited purposefully. Participants: The minutes of 41 nursing home organizations were collected during March–November, 2020. Four group meetings were organized in the same period, each with 5 to 7 participants, resulting in 23 participants. Methods: The meeting minutes were analysed using qualitative content analysis, whereas reflexive thematic analysis was used for the group meeting data. The group meetings were conducted online and structured by the Nominal Group Technique to discuss the importance of measures for staff. Results: Measures implemented for staff focused on prevention of COVID-19 transmission, (suspension of) educational activities, testing, additional tasks and staffing capacity, promoting well-being, and other means of support. The implemented measures overlapped with the measures considered important by staff. In addition, staff considered measures on decision-making support and communication to be important. Staff prioritized the measures in the group meetings because they affected their well-being, workforce scheduling, decision-making, or infection prevention. Furthermore, the group meetings revealed that decision-making shifted from mainly implementing national measures to more context-adjusted decision-making in the staff's or clients’ situations. Conclusions: We showed that although nursing home staff were not always involved in decision-making during the first COVID-19 wave, there was overlap between the measures implemented by the organizations and measures considered important by staff. We suggest that organizations should be encouraged to explore ways of promoting timely involvement of staff in decision-making; for example, through monitoring staff needs and well-being and giving staff more autonomy to deviate from standard measures during future outbreaks or medical emergencies.

Abstract Background Cross-system interventions that integrate health, behavioral health, and social services can improve client outcomes and expand community impact. Successful implementation of these interventions depends on the extent to which service partners can align frontline services and organizational operations. However, collaboration strategies linking multiple implementation contexts have received limited empirical attention. This study identifies, describes, and specifies multi-level collaboration strategies used during the implementation of Ohio Sobriety Treatment and Reducing Trauma (Ohio START), a cross-system intervention that integrates services across two systems (child welfare and evidence-based behavioral health services) for families that are affected by co-occurring child maltreatment and parental substance use disorders. Methods In phase 1, we used a multi-site qualitative design with 17 counties that implemented Ohio START. Qualitative data were gathered from 104 staff from child welfare agencies, behavioral health treatment organizations, and regional behavioral health boards involved in implementation via 48 small group interviews about collaborative approaches to implementation. To examine cross-system collaboration strategies, qualitative data were analyzed using an iterative template approach and content analysis. In phase 2, a 16-member expert panel met to validate and specify the cross-system collaboration strategies identified in the interviews. The panel was comprised of key child welfare and behavioral health partners and scholars. Results In phase 1, we identified seven cross-system collaboration strategies used for implementation. Three strategies were used to staff the program: (1) contract for expertise, (2) provide joint supervision, and (3) co-locate staff. Two strategies were used to promote service access: (4) referral protocols and (5) expedited access agreements. Two strategies were used to align case plans: (6) shared decision-making meetings, and (7) sharing data. In phase 2, expert panelists specified operational details of the cross-system collaboration strategies, and explained the processes by which strategies were perceived to improve implementation and service system outcomes. Conclusions We identified a range of cross-system collaboration strategies that show promise for improving staffing, service access, and case planning. Leaders, supervisors, and frontline staff used these strategies during all phases of implementation. These findings lay the foundation for future experimental and quasi-experimental studies that test the effectiveness of cross-system collaboration strategies.

Abstract Creating durable, eco-friendly coatings for long-term corrosion protection requires innovative strategies to streamline design and development processes, conserve resources, and decrease maintenance costs. In this pursuit, machine learning emerges as a promising catalyst, despite the challenges presented by the scarcity of high-quality datasets in the field of corrosion inhibition research. To address this obstacle, we have created an extensive electrochemical library of around 80 inhibitor candidates. The electrochemical behaviour of inhibitor-exposed AA2024-T3 substrates was captured using linear polarisation resistance, electrochemical impedance spectroscopy, and potentiodynamic polarisation techniques at different exposure times to obtain the most comprehensive electrochemical picture of the corrosion inhibition over a 24-h period. The experimental results yield target parameters and additional input features that can be combined with computational descriptors to develop quantitative structure–property relationship (QSPR) models augmented by mechanistic input features.

Background: Intake of potassium iodide (KI) reduces the accumulation of radioactive iodine in the thyroid gland in the event of possible contamination by radioactive iodine released from a nuclear facility. The World Health Organization (WHO) has stated the need for research for optimal timing, appropriate dosing regimen, and safety for repetitive iodine thyroid blocking (ITB). The French PRIODAC project, addressed all these issues, involving prolonged or repeated releases of radioactive iodine. Preclinical studies established an effective dose through pharmacokinetic modeling, demonstrating the safety of repetitive KI treatment without toxicity. Summary: Recent preclinical studies have determined an optimal effective dose for repetitive administration, associated with pharmacokinetic modeling. The results show the safety and absence of toxicity of repetitive treatment with KI. Good laboratory practice level preclinical studies corresponding to individuals >12 years have shown a safety margin established between animal doses without toxic effect. After approval from the French health authorities, the market authorization of the two tablets of KI, 65 mg/day, was defined with a new dosing scheme of a daily repetitive intake of the treatment up to 7 days unless otherwise instructed by the competent authorities for all categories of population except pregnant women and children under the age of 12 years. Conclusion: This new marketed authorization resulting from scientific-based evidence obtained as part of the PRIODAC project may serve as an example to further harmonize the application of KI for repetitive ITB in situations of prolonged radioactive release at the European and international levels, under the umbrella of the WHO.

The facultative intracellular pathogen Shigella flexneri invades non-phagocytic epithelial gut cells. Through a syringe-like apparatus called type 3 secretion system, it injects effector proteins into the host cell triggering actin rearrangements leading to its uptake within a tight vacuole, termed the bacterial-containing vacuole (BCV). Simultaneously, Shigella induces the formation of large vesicles around the entry site, which we refer to as infection-associated macropinosomes (IAMs). After entry, Shigella ruptures the BCV and escapes into the host cytosol by disassembling the BCV remnants. Previously, IAM formation has been shown to be required for efficient BCV escape, but the molecular events associated with BCV disassembly have remained unclear. To identify host components required for BCV disassembly, we performed a microscopy-based screen to monitor the recruitment of BAR domain-containing proteins, which are a family of host proteins involved in membrane shaping and sensing (e.g. endocytosis and recycling) during Shigella epithelial cell invasion. We identified endosomal recycling BAR protein Sorting Nexin-8 (SNX8) localized to IAMs in a PI(3)P-dependent manner before BCV disassembly. At least two distinct IAM subpopulations around the BCV were found, either being recycled back to cellular compartments such as the plasma membrane or transitioning to become RAB11A positive “contact-IAMs” involved in promoting BCV rupture. The IAM subpopulation duality was marked by the exclusive recruitment of either SNX8 or RAB11A. Hindering PI(3)P production at the IAMs led to an inhibition of SNX8 recruitment at these compartments and delayed both, the step of BCV rupture time and successful BCV disassembly. Finally, siRNA depletion of SNX8 accelerated BCV rupture and unpeeling of BCV remnants, indicating that SNX8 is involved in controlling the timing of the cytosolic release. Overall, our work sheds light on how Shigella establishes its intracellular niche through the subversion of a specific set of IAMs.

Introduction: Spontaneous coronary artery dissection (SCAD) is a rare cause of myocardial infarction. Patients suffering SCAD are often young women without typical risk factors for atherosclerotic heart disease. Clinicians should maintain a high index of suspicion for SCAD. Case series: We report three cases of patients with SCAD from a single physician in a six-month period. Each case is unique and highlights the varied presentations and epidemiological risk factors associated with this condition. Discussion: We believe these cases are unique in that they provide insights into the variable presentations and conditions frequently associated with SCAD and will help clinicians maintain a high index of suspicion for this difficult to diagnose and rare cause of type 2 myocardial infarction. We discuss differences in interventional techniques and medical management.

ZIKV has been found in the cerebrospinal fluid (CSF) and brains of adults infected with viruses that manifest neurological disorders. ZIKV is a mosquito-borne single-stranded RNA virus, which belongs to the family Flaviviridae. The efforts of the scientific community have rapidly increased knowledge about this virus. However, understanding the complexities of ZIKV infection, transmission and pathogenesis remains an urgent challenge. Therefore, it is critical to study competent vectors and natural reservoirs for ZIKV, viral genetic diversity and flavivirus coinfection. Due to the great challenges to develop a ZIKV vaccine, it is still not possible to be immunized against ZIKV infection and related pathologies. The methods are nucleotide search for the Zika virus was carried out in silico, using the NCBI bioinformatics application by providing access to biomedical and genomic information. /H. sapiens-tc/THA/2006/CVD_06-020, the complete genome was then searched for FASTA, then prediction of vaccine epitope using the IEDB. The vaccine candidate peptides were analyzed for their antigenicity using VaxiJen. Proteins were classified by AllerTop to known allergenicity, then ToxinPred to predict and design toxic/non-toxic peptides. There are 30 peptide sequences are predicted to be a candidate of peptides B-cell epitope zika virus vaccine design using “zika virus isolate zika virus/H. sapiens-tc/THA/2006/CVD_06-020, complete genome”.

Typhoid fever is an acute systemic infectious disease that is related to poor personal hygiene and environmental sanitation. The diagnosis of typhoid fever is established through laboratory examinations, including serological, hematological, and bacteriological tests. This research aims to determine the correlation between the Widal diagnostic test and the total leukocyte count and platelet count in suspected typhoid fever patients at RS Aura Syifa Kediri. The study design used in this research is quantitative descriptive analysis with a cross-sectional approach. The data was collected retrospectively from secondary sources, specifically medical records of patients from August 1, 2021, to March 31, 2022, at RS Aura Syifa Kediri. The total population comprised 157 patients, and a purposive sampling method was used to select 41 patients who met the inclusion and exclusion criteria. The statistical analysis using the Spearman correlation test resulted in p-values ≥ α = 0.05 for the following correlations: Widal test O with leukocytes (0.538 ≥ 0.05), Widal test H with leukocytes (0.915 ≥ 0.05), Widal test O with platelets (0.476 ≥ 0.05), and Widal test H with platelets (0.965 ≥ 0.05). These findings indicate that there is no significant correlation between the Widal test O and H with the platelet count in patients with typhoid fever. Therefore, it can be concluded that there is no significant relationship between the Widal test O and H results and the platelet count in typhoid fever patients.

Komitmen dalam organisasi bisa diartikan sebagai sikap atau perilaku yang ditampilkan seseorang terhadap organisasi dengan membuktikan loyalitas untuk mencapai visi, misi, nilai, dan tujuan organisasi. Komitmen organisasi karyawan dipengaruhi oleh banyak hal, salah satunya adalah Quality of Work Life. Penelitian ini bertujuan untuk mengetahui apakah terdapat hubungan antara komitmen organisasi dan quality of work life pada karyawan PT. Majuperkasa Indonesia. Pengambilan data menggunakan dua skala, yaitu Skala Komitmen Organisasi 33 aitem (α= 0,929) dan Skala Quality of Work Life 51 aitem (α= 0,935). Subjek adalah karyawan PT. Majuperkasa Indonesia dengan jumlah subjek 160 orang dengan penentuan sampel menggunakan nonprobability sampling dengan cara random sampling. Berdasarkan analisis data pada penelitian ini melalui pengujian statistik, dapat ditarik kesimpulan bahwa terdapat hubungan dengan arah yang positif dan signifikan antara komitmen organisasi dan quality of work life pada karyawan. Hal ini terlihat dari hasil yang ditunjukkan pada uji korelasi Pearson (r) = 0,569 dengan p = 0,000 ( 0,05) yang berarti terdapat hubungan positif dan signifikan antara komitmen organisasi dengan quality of work life pada karyawan di PT. Majuperkasa Indonesia.

Abstract Background On December 29, 2021, during the delta wave of the Coronavirus Disease 2019 (COVID-19) pandemic, the stock of premanufactured solutions used for continuous kidney replacement therapy (CKRT) at the University of New Mexico Hospital (UNMH) was nearly exhausted with no resupply anticipated due to supply chain disruptions. Within hours, a backup plan, devised and tested 18 months prior, to locally produce CKRT dialysate was implemented. This report describes the emergency implementation and outcomes of this on-site CKRT dialysate production system. Methods This is a single-center retrospective case series and narrative report describing and reporting the outcomes of the implementation of an on-site CKRT dialysate production system. All adults treated with locally produced CKRT dialysate in December 2021 and January 2022 at UNMH were included. CKRT dialysate was produced locally using intermittent hemodialysis machines, hemodialysis concentrate, sterile parenteral nutrition bags, and connectors made of 3-D printed biocompatible rigid material. Outcomes analyzed included dialysate testing for composition and microbiologic contamination, CKRT prescription components, patient mortality, sequential organ failure assessment (SOFA) scores, and catheter-associated bloodstream infections (CLABSIs). Results Over 13 days, 22 patients were treated with 3,645 L of locally produced dialysate with a mean dose of 20.0 mL/kg/h. Fluid sample testing at 48 h revealed appropriate electrolyte composition and endotoxin levels and bacterial colony counts at or below the lower limit of detection. No CLABSIs occurred within 7 days of exposure to locally produced dialysate. In-hospital mortality was 81.8% and 28-day mortality was 68.2%, though illness severity was high, with a mean SOFA score of 14.5. Conclusions Though producing CKRT fluid with IHD machines is not novel, this report represents the first description of the rapid and successful implementation of a backup plan for local CKRT dialysate production at a large academic medical center in the U.S. during the COVID-19 pandemic. Though conclusions are limited by the retrospective design and limited sample size of our analysis, our experience could serve as a guide for other centers navigating similar severe supply constraints in the future.

Abstract Background The COVID-19 pandemic has become one of the most devastating worldwide crises. The pandemic has heavily affected the most vulnerable groups, including Indigenous communities. Our study aimed to evaluate the attitudes and behaviors relating to care and prevention of COVID-19 in a predominantly Indigenous university population in Mexico. Methods A cross-sectional descriptive study was conducted in early February 2022 focused on university students in a predominantly Indigenous community in central Mexico. The survey addressed prevention, vaccination, anthropometric data, and food intake. Results We obtained a high response rate of 71.6%, with 981 students (41.2%) identifying as belonging to an Indigenous group. In the sample, 3.1% (95% CI 2.07, 4.33) of the Indigenous group reported COVID-19 deaths among family members older than 18 years; this rate was 3% (95% CI 2.17, 4.03) in the non-Indigenous group. Whereas most of the students [98% (95% CI 97.62, 98.72)] reported having received COVID-19 vaccines, 36.6% (95% CI 33.57, 39.70) and 39.9% (95% CI (37.32, 42.52) of the Indigenous and non-Indigenous respondents, respectively, reported that their parents were fully vaccinated against COVID-19. Finally, we found important differences in weight and Body Mass Index (BMI) between pre-pandemic baseline and two years after confinement in the general population as well as between Indigenous and non-Indigenous: general BMI increased from 22.9 ± 4.1 kg/m2 to 23.6 ± 4.1 kg/m2 (Wilcoxon test; P

Abstract Background Most implementations fail before the corresponding services are ever delivered. Measuring implementation process fidelity may reveal when and why these attempts fail. This knowledge is necessary to support the achievement of positive implementation milestones, such as delivering services to clients (program start-up) and competency in treatment delivery. The present study evaluates the extent to which implementation process fidelity at different implementation stages predicts achievement of those milestones. Methods Implementation process fidelity data—as measured by the Stages of Implementation Completion (SIC)—from 1287 implementing sites across 27 evidence-informed programs were examined in mixed effects regression models with sites nested within programs. Implementation process fidelity, as measured by the proportion of implementation activities completed during the three stages of the SIC Pre-Implementation phase and overall Pre-Implementation (Phase 1) and Implementation (Phase 2) proportion scores, was assessed as a predictor of sites achieving program start-up (i.e., delivering services) and competency in program delivery. Results The predicted probability of start-up across all sites was low at 35% (95% CI [33%, 38%]). When considering the evidence-informed program being implemented, that probability was nearly twice as high (64%; 95% CI [42%, 82%]), and 57% of the total variance in program start-up was attributable to the program. Implementation process fidelity was positively and significantly associated with achievement of program start-up and competency. The magnitude of this relationship varied significantly across programs for Pre-Implementation Stage 1 (i.e., Engagement) only. Compared to other stages, completing more Pre-Implementation Stage 3 (Readiness Planning) activities resulted in the most rapid gains in probability of achieving program start-up. The predicted probability of achieving competency was very low unless sites had high scores in both Pre-Implementation and Implementation phases. Conclusions Strong implementation process fidelity—as measured by SIC Pre-Implementation and Implementation phase proportion scores—was associated with sites’ achievement of program start-up and competency in program delivery, with early implementation process fidelity being especially potent. These findings highlight the importance of a rigorous Pre-Implementation process.

Abstract Background The RPGR gene has been associated with X‐linked cone‐rod dystrophy. This report describes a variant in RPGR detected with exome sequencing (ES). Genes like RPGR have not always been included in panel‐based testing and thus genome‐wide tests such as ES may be required for accurate diagnosis. Methods The Texome Project is studying the impact of ES in medically underserved patients who are in need of genomic testing to guide diagnosis and medical management. The hypothesis is that ES could uncover diagnoses not made by standard medical care. Results A 58‐year‐old male presented with retinitis pigmentosa, sensorineural hearing loss, and a family history of retinal diseases. A previous targeted gene panel for retinal disorders had not identified a molecular cause. ES through the Texome Project identified a novel, hemizygous variant in RPGR (NM_000328.3: c.1302dup, p.L435Sfs*18) that explained the ocular phenotype. Conclusions Continued genetics evaluation can help to end diagnostic odysseys of patients. Careful consideration of genes represented when utilizing gene panels is crucial to ensure an accurate diagnosis. Medically underserved populations are less likely to receive comprehensive genetic testing in their diagnostic workup. Our report is an example of the medical impact of genomic medicine implementation.

ObjectiveMulti-center implementation of rapid whole genome sequencing with assessment of the clinical utility of rapid whole genome sequencing (rWGS), including positive, negative and uncertain results, in admitted infants with a suspected genetic disease.Study designrWGS tests were ordered at eight hospitals between November 2017 and April 2020. Investigators completed a survey of demographic data, Human Phenotype Ontology (HPO) terms, test results and impacts of results on clinical care.ResultsA total of 188 patients, on general hospital floors and intensive care unit (ICU) settings, underwent rWGS testing. Racial and ethnic characteristics of the tested infants were broadly representative of births in the country at large. 35% of infants received a diagnostic result in a median of 6 days. The most common HPO terms for tested infants indicated an abnormality of the nervous system, followed by the cardiovascular system, the digestive system, the respiratory system and the head and neck. Providers indicated a major change in clinical management because of rWGS for 32% of infants tested overall and 70% of those with a diagnostic result. Also, 7% of infants with a negative rWGS result and 23% with a variant of unknown significance (VUS) had a major change in management due to testing.ConclusionsOur study demonstrates that the implementation of rWGS is feasible across diverse institutions, and provides additional evidence to support the clinical utility of rWGS in a demographically representative sample of admitted infants and includes assessment of the clinical impact of uncertain rWGS results in addition to both positive and negative results.

Abstract Introduction: Demonstrating the impact of implementation science presents a new frontier for the field, and operationalizing downstream impact is challenging. The Translational Science Benefits Model (TSBM) offers a new approach for assessing and demonstrating research impact. Here we describe integration of the TSBM into a mentored training network. Methods: Washington University’s Clinical and Translational Science Awards TSBM team collaborated with a National Institute of Mental Health-supported training program, the Implementation Research Institute (IRI), a 2-year training institute in mental health implementation science. This partnership included three phases: (1) introductory workshop on research impact, (2) workshop on demonstrating impact, and (3) sessions to guide dissemination, including interactive tools and consultation with the TSBM research team. Fifteen IRI alumni were invited to participate in the pilot; six responded agreeing to participate in the training, develop TSBM case studies, and provide feedback about their experiences. Participants applied the tools and gave feedback on design, usability, and content. We present their case studies and describe how the IRI used the results to incorporate TSBM into future trainings. Results: The case studies identified 40 benefits spanning all four TSBM domains, including 21 community, 11 policy, five economic, and three clinical benefits. Participants reported that TSBM training helped them develop a framework for talking about impact. Selecting benefits was challenging for early-stage projects, suggesting the importance of early training. Conclusions: The case studies showcased the institute’s impact and the fellows’ work and informed refinement of tools and methods for incorporating TSBM into future IRI training.

Our reliance on agriculture for sustenance, healthcare, and resources has been essential since the dawn of civilization. However, traditional agricultural practices are no longer adequate to meet the demands of a burgeoning population amidst climate-driven agricultural challenges. Microalgae emerge as a beacon of hope, offering a sustainable and renewable source of food, animal feed, and energy. Their rapid growth rates, adaptability to non-arable land and non-potable water, and diverse bioproduct range, encompassing biofuels and nutraceuticals, position them as a cornerstone of future resource management. Furthermore, microalgae’s ability to capture carbon aligns with environmental conservation goals. While microalgae offers significant benefits, obstacles in cost-effective biomass production persist, which curtails broader application. This review examines microalgae compared to other host platforms, highlighting current innovative approaches aimed at overcoming existing barriers. These approaches include a range of techniques, from gene editing, synthetic promoters, and mutagenesis to selective breeding and metabolic engineering through transcription factors.

Introduction: Due to the radiation-sparing effects on salivary gland acini, changes in the composition of the oral microbiome may be a driver for improved outcomes in patients receiving proton radiation with potentially worse outcomes in patients exposed to photon radiation therapy. To date, a head-to-head comparison of oral microbiome changes at a metagenomic level with longitudinal sampling has yet to be performed in these patient cohorts. Methods and Materials: To comparatively analyze oral microbiome shifts during head and neck radiation therapy, a prospective pilot cohort study was performed at the Maryland Proton Treatment Center (MPTC) and the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center. A longitudinal metagenomic comparative analysis of oral microbiome shifts was performed at three-time points (pre-radiation, during radiation, and immediately post-radiation). Head and neck cancer patients receiving proton radiation (n=4) were compared to photon radiation (n=4). Additional control groups included healthy age- and sex-matched controls (n=5), head and neck cancer patients who never received radiation therapy (n=8), and patients with oral inflammatory disease (n=3). Results: Photon therapy patients presented with a lower microbial alpha diversity at all timepoints and there was a trend towards reduced species richness as compared with proton therapy. Healthy controls and proton patients exhibited overall higher and similar diversity. A more dysbiotic state was observed in patients receiving photon therapy as compared to proton therapy in which oral microbial homeostasis was maintained. Mucositis was observed in 3/4 photon patients and was not observed in any proton patients during radiation therapy. Bacterial de novo pyrimidine biosynthesis pathway and nitrate reduction V pathway were comparatively higher following photon exposure. These functional changes in bacterial metabolism may suggest that photon exposure produces a more permissive environment for proliferation of pathogenic bacteria. Conclusion: Oral microbiome dysbiosis in patients receiving photon radiation may be associated with increased mucositis occurrence. Proton radiation therapy for head and neck cancer demonstrates a safer side effect profile in terms of oral complications, oral microbiome dysbiosis, and functional metabolic status.

1,3-β-d-Glucan (BDG) is commonly used for diagnosing invasive fungal infections (IFIs). While exposure to cellulose-based hemodialyzers is known to cause false-positive BDG results, the impact of modern hemofilters used in continuous renal replacement therapy (CRRT) remains unclear. This retrospective, single-center cohort study aimed to evaluate the effect of CRRT on BDG levels in critically ill patients. We included adult intensive care unit (ICU) patients with ≥1 BDG measurement between December 2019 and December 2020. The primary outcome was the rate of false-positive BDG results in patients exposed to CRRT compared to unexposed patients. Propensity score analysis was performed to control for confounding factors. A total of 103 ICU patients with ≥1 BDG level were identified. Most (72.8%) were medical ICU patients. Forty patients underwent CRRT using hemofilter membranes composed of sodium methallyl sulfonate copolymer (AN 69 HF) (82.5%) and of polyarylethersulfone (PAES) (17.5%). Among the 91 patients without proven IFI, 31 (34.1%) had false-positive BDG results. Univariable analysis showed an association between CRRT exposure and false-positive BDG results. However, the association between CRRT exposure and false-positive BDG results was no longer significant across three propensity score models employed: 1:1 match (n = 32) (odds ratio (OR) 1.65, p = .48), model-adjusted (n = 91) (OR 1.75, p = .38), quintile-adjusted (n = 91) (OR 1.78, p = .36). In this single-center retrospective analysis, exposure to synthetic CRRT membranes did not independently increase the risk of false-positive BDG results. Larger prospective studies are needed to further evaluate the association between CRRT exposure and false-positive BDG results in critically ill patients with suspected IFI.

ABSTRACTBackground Mycobacterium abscessus subspecies massiliense (M. massiliense) is increasingly recognized as an emerging bacterial pathogen, particularly in cystic fibrosis (CF) patients and CF centres’ respiratory outbreaks. We characterized genomic and phenotypic changes in 15 serial isolates from two CF patients (1S and 2B) with chronic pulmonary M. massiliense infection leading to death, as well as four isolates from a CF centre outbreak in which patient 2B was the index case.Results Comparative genomic analysis revealed the mutations affecting growth rate, metabolism, transport, lipids (loss of glycopeptidolipids), antibiotic susceptibility (macrolides and aminoglycosides resistance), and virulence factors. Mutations in 23S rRNA, mmpL4, porin locus and tetR genes occurred in isolates from both CF patients. Interestingly, we identified two different spontaneous mutation events at the mycobacterial porin locus: a fusion of two tandem porin paralogs in patient 1S and a partial deletion of the first porin paralog in patient 2B. These genomic changes correlated with reduced porin protein expression, diminished 14C-glucose uptake, slower bacterial growth rates, and enhanced TNF-α induction in mycobacteria-infected THP-1 human cells. Porin gene complementation of porin mutants partly restored 14C-glucose uptake, growth rate and TNF-α levels to those of intact porin strains.Conclusions We hypothesize that specific mutations accumulated and maintained over time in M. massiliense, including mutations shared among transmissible strains, collectively lead to more virulent, host adapted lineages in CF patients and other susceptible hosts.

ABSTRACTThe 1918–20 pandemic influenza killed 50–100 million people worldwide, but mortality varied by ethnicity and geography. In Norway, areas dominated by Sámi experienced 3–5 times higher mortality than the country’s average. We here use data from burial registers and censuses to calculate all-cause excess mortality by age and wave in two remote Sámi areas of Norway 1918–20. We hypothesise that geographic isolation, less prior exposure to seasonal influenza, and thus less immunity led to higher Indigenous mortality and a different age distribution of mortality (higher mortality for all) than was typical for this pandemic in non-isolated majority populations (higher young adult mortality & sparing of the elderly). Our results show that in the fall of 1918 (Karasjok), winter of 1919 (Kautokeino), and winter of 1920 (Karasjok), young adults had the highest excess mortality, followed by also high excess mortality among the elderly and children. Children did not exhibit excess mortality in the second wave in Karasjok in 1920. It was not the young adults alone who produced the excess mortality in Kautokeino and Karasjok. We conclude that geographic isolation caused higher mortality among the elderly in the first and second waves, and among children in the first wave.

Abstract Uncontrolled human and industrial activities lead to the increase in demand for selective gas sensors for detection of poisonous gases in our environment. Conventional resistive gas sensors suffer from predetermined sensitivity and poor selectivity among gases. This paper demonstrates curcumin reduced graphene oxide-silk field effect transistor for selective and sensitive detection of ammonia in air. The sensing layer was characterized by X-ray diffraction, FESEM and HRTEM to confirm its structural and morphological features. Raman spectroscopy, Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy was carried out to analyze the functional moieties present in the sensing layer. Curcumin reduced graphene oxide introduces sufficient hydroxyl groups in the sensing layer to provide high degree of selectivity towards ammonia vapors. The performance of the sensor device was evaluated at positive, negative and zero gate voltage. Carrier modulation in the channel through gate electrostatics revealed that the minority carriers (electrons) in p-type reduced graphene oxide plays a pivotal role in enhancement of sensitivity of the sensor device. The sensor response was enhanced to 634% for 50 ppm ammonia at 0.6 V gate voltage compared to 23.2% and 39.3% at 0 V and − 3 V respectively. The sensor exhibited faster response and recovery at 0.6 V owing to higher mobility of electrons and quick charge transfer mechanism. The sensor exhibited satisfactory humidity resistant characteristics and high stability. Hence, curcumin reduced graphene oxide-silk field effect transistor device with proper gate bias elucidates excellent ammonia detection and may be a potential candidate for future room temperature, low power, portable gas detection system.

Abstract Objective This study describes the development of an intervention to increase the frequency of audiologists’ asking about and providing information regarding mental wellbeing within adult audiology services. Design The Behaviour Change Wheel (BCW), an eight-step systematic process, was followed to develop the intervention. Reports describing the first four steps are published elsewhere. This report describes the final four steps and details the intervention developed. Results A multifaceted intervention was developed to change audiologists’ behaviours relating to providing mental wellbeing support to adults with hearing loss. Specifically, three behaviours were targeted: (1) asking clients about their mental wellbeing, (2) providing general information on the mental wellbeing impacts of hearing loss, and (3) providing personalised information on managing the mental wellbeing impacts of hearing loss. A variety of intervention functions and behaviour change techniques were incorporated into the intervention, including instruction and demonstration, information about others approval, adding objects to the environment, use of prompts/cues, and endorsement from credible sources. Conclusion This study is the first to use the Behaviour Change Wheel to develop an intervention targeting mental wellbeing support behaviours in audiologists and confirms the usability and usefulness of the approach in a complex area of clinical care. The systematic development of the Ask, Inform, Manage, Encourage, Refer (AIMER) intervention will facilitate a thorough evaluation of its effectiveness in the next phase of this work.

Latar belakang. Anak periode prasekolah menurut Center for disease Control and Prevention adalah anak yang berusia antara 3 – 5 tahun. Pada periode ini terjadi perkembangan personal sosial yang pesat. Saat ini ditemukan peningkatan durasi penggunaan media layar pada anak usia prasekolah dari tahun ke tahun yang cukup signifikan, terlebih pada saat pandemi COVID-19 akibat adanya kebijakan Pembeljaran Jarak Jauh. Penggunaan media layar yang berlebihan pada anak dapat menimbulkan permasalahan kesehatan salah satunya gangguan pola tidur pada anak. Tujuan. Mengetahui hubungan antara durasi penggunaan media layar dengan gangguan pola tidur yang terjadi pada anak periode prasekolah selama masa pandemi COVID-19 Metode. Penelitian ini menggunakan desain penelitian cross sectional pada 86 anak usia 3-5 tahun di Kota Depok Hasil penelitian diuji dengan uji chi square dengan bantuan software SPSS 24.0. Hasil. Analisis univariat menujukan bahwa durasi penggunaan media layar rata – rata harian anak pada hari sekolah (Senin – Jumat) sebesar 3,9 jam /hari, sedangkan pada hari libur (Sabtu - Minggu dan Hari Libur lainnya) sebesar 5,1 jam/hari dengan media layar yang paling banyak digunakan adalah televisi (87,2%) dan smartphone (80,2%). Analisis bivariat menujukan bahwa secara statistik terdapat hubungan bermakna antara durasi penggunaan media layarber lebih dengan gangguan pola tidur (p : 0,013) Kesimpulan. Secara statistik didapatkan hubungan antara durasi penggunaan media layar dengan pola tidur pada anak usia 3 – 5 tahun di masa pandemi COVID-19.

One of Indonesia's leading exports from the manufacturing industry is the furniture sector. Yogyakarta is one of the regions with the largest furniture exports in Indonesia. CV. CA is one of the creative economy actors in the craft sub-sector who has succeeded in creating a variety of simple and elegant products with quality and certified wood raw materials. This research method uses qualitative and quantitative approaches. CV CA develops products and carries out a level of readiness for innovation and competes with similar competitors. Based on the results of this study, CV CA's business processes are proven in the field and pass the competency. Therefore, through this research, we can find out what CV CA has implemented so that it can penetrate the export market and revive the SME’s of the creative economy industry.

Crossing over is the occurrence of disconnection and reconnection followed by a reciprocal exchange between the two chromatids in a bivalent form. The crossing event will produce parental type and recombinant type. In the event of crossing over, various factors can influence it. These factors can be due to internal and external. Recently, various factors have been reported that influence the incidence of crossing over. These factors include age, temperature, radiation, and changes in chromosome structure. This research is a type of experimental research that uses a randomized block design. Randomized block design by crossing D. melanogaster strains ?N>< ?bcl and ?N>< ?ym and their reciprocals. From the results of this cross (F1) then cross again ?N with the recessive male (from stock) then observe the phenotype of the offspring (F2) and calculate the results of the offspring. The F2 ?N crosses were treated with age variations, namely 0, 3, 6, 9, 12, 15, and 18 days. Based on the results of these crosses, the derived strains that appeared in the F2 crosses showed the phenomenon of crossing over with the influence of the age of the female and the type of strain on crossing events. the frequency or value of crossing over (formation of recombinants) decreased with the increasing age of the female. If the age of the female affects the frequency of crossing over, then the older the female, the more likely the frequency of crossing over will decrease. However, because the data obtained were incomplete, it was not possible to know the effect of female age on the frequency of crossing over of D. melanogaster crosses ?N>< ? bcl and ?N >< ?ym and their reciprocals. The condition for crossing over is the formation of a synaptonemal complex. Age of D. melanogaster females has an effect on the frequency of crossing over in crosses N? >< bcl?, N? >< ym?, and their reciprocals. The older Drosophila melanogaster is, the lower the frequency of crossing over will occur. Based on this, it was necessary to cross D. melanogaster with strains N, bcl, and ym. A cross consists of ?N >ym and their reciprocals. By crossing ?N with a recessive male from the stock, then observing the F2 phenotype, it is hoped that crossing over will occur. So that you can better understand by doing the practice directly. In this case, the effect of crossing over is seen from the age of the female and the type of strain.

Abstract Transcriptome profiling of human whole blood is used to discover biomarkers of diseases and to assess phenotypic traits. Recently, finger-stick blood collection systems have allowed a less invasive and quicker collection of peripheral blood. Such non-invasive sampling of small volumes of blood offers practical advantages. The quality of gene expression data is strictly dependent on the steps used for the sample collection, extraction, preparation and sequencing. Here we have: (i) compared the manual and automated RNA extraction of small volumes of blood using the Tempus Spin RNA isolation kit and the MagMAX for Stabilized Blood RNA Isolation kit , respectively; and (ii) assessed the effect of TURBO DNA Free treatment on the transcriptomic data of RNA isolated from small volumes of blood. We have used the QuantSeq 3′ FWD mRNA-Seq Library Prep kit to prepare RNA-seq libraries, which were sequenced on the Illumina NextSeq 500 system. The samples isolated manually displayed a higher variability in the transcriptomic data as compared to the other samples. The TURBO DNA Free treatment affected the RNA samples negatively, decreasing the RNA yield and reducing the quality and reproducibility of the transcriptomic data. We conclude that automated extraction systems should be preferred over manual extraction systems for data consistency, and that the TURBO DNA Free treatment should be avoided when working on RNA samples isolated manually from small volumes of blood.