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Introduction: For advanced osteoarthritis of the knee and hip, the most clinically effective treatment remains total-knee arthroplasty (TKA) and total-hip arthroplasty (THA). Success of these surgeries have traditionally been appraised by economic and volume-based measures. There has been a shift towards the use of patient reported outcome measures (PROMs) to quantify success and guide treatment. The present study provides analysis of three PROMS which have been validated for use in orthopaedic settings; the Oxford Knee Score (OKS), Oxford Hip Score (OHS), Forgotten Joint Score (FJS), and the EuroQol-Visual Analogue Scale (EQ-VAS) - a non-disease specific measure of health. PROMs were completed pre-operatively, 6-weeks, and 1-year after elective TKA and THA undertaken in 2018 in a public teaching hospital in South Australia. Post-operative satisfaction/dissatisfaction was measured using a 5-point Likert scale and was collected at the same 6-week and 1-year points. Results: PROMs were collected from 285 eligible elective knee-arthroplasty, and 205 elective hip-arthroplasty patients. There was significant average improvement, greater than minimal clinical important differences between pre-operative and 1-year post-operative scores for all three PROMs tools. Inter-PROM correlation was strongest between FJS and OKS at 1-year post TKA (rs = 0.722), and between FJS and OHS in post-THA at the same interval (rs = 0.609). TKA patients with higher pre-surgical 10-year mortality were weakly associated with lower pre-operative OKS score (rs = 0.169). BMI was weakly negatively associated with pre-operative and 6-week post-operative EQ-VAS scores (rs = -0.291 and rs = -0.149 respectively). Post-TKA satisfaction was 77.2% at 1-year, and THA 88.5% at the same interval. Conclusion: This study provides an early insight from the use of the OKS, OHS, the EQ-VAS and the FJS as PROMs in primary TKA and THA at our centre. All PROMs demonstrate significant increase (improvement) at both 6-week and 1-year post-operative intervals, relative to pre-operative scores. The FJS demonstrated good sensitivity. Pre-existing co-morbidities do not appear to have any significant relation with post-operative PROMs collected in this study. [ABSTRACT FROM AUTHOR]

To date, little is known about body image and eating concerns among men in midlife. To bridge this gap in the literature, this study tested an adapted and integrated sociocultural model of body image and eating concerns among men in midlife. A sample of men (N = 213) between the ages of 45 and 60 years living in the United States completed an online survey and reported on sociocultural pressures from media, friends, family and partners, body image in younger years, internalization of a youthful lean and muscular ideal, appearance comparison, sexual objectification, body dissatisfaction, attitudes towards muscularity, drive for leanness and thinness, participation in muscularity-oriented behaviors, and restrictive eating. After modification, the final model revealed good fit to the data. Although not all predicted pathways were supported, overall, interpersonal and media pressures were related to internalization of ideals and appearance comparison. In turn, internalization and comparison were related to higher body dissatisfaction, drive for leanness and muscularity, and engagement in muscularity-oriented behaviors and restrictive eating. Findings support the usefulness of an adapted and integrated sociocultural model of body image and eating concerns in midlife men. The model suggests that the pressures that may increase body image and eating concerns in younger men may also be relevant in midlife men. Findings also highlight the usefulness of considering age-specific body-change behaviors and disordered eating in midlife men. [ABSTRACT FROM AUTHOR]

Purpose: Histological grading of tumours is a well-established biomarker used to guide treatment in female breast cancer. However, its significance in male breast cancer remains unclear. This systematic review investigates the prognostic significance of tumour grade in relation to breast cancer-specific survival (BCSS) in male breast cancer patients undergoing surgery. Methods: MEDLINE, PUBMED Central and EMBASE databases were searched to identify randomised trials and observational studies related to male breast neoplasms, tumour grading, recurrence, and survival. Results: A total of fifteen observational type studies were included in the review. A significant association between tumour grade and BCSS was reported in a majority of studies. This association was most evident with regard to high-grade (grade III) compared to low grade (grade I) tumours, with a significant relationship in 4 out of 4 studies. For intermediate-grade II tumours an association was demonstrated in a minority of studies. Conclusions: This study confirms an association between high-grade male breast cancers and poorer disease-specific survival, however, the significance of intermediate-grade tumours remains unclear. Further research is required to investigate the biology of male breast cancer in relation to histological grade and optimally define intermediate-grade disease. [ABSTRACT FROM AUTHOR]

Background: Anemia is one of the most frequent comorbidities in patients with heart failure (HF), which potentially can interfere with the effect of guideline-recommended HF medical therapy and can be associated with the use of neurohormonal blockers. Aim: The aim of this analysis was to determine the prevalence and changes of anemia status in the STRONG-HF study, its association with clinical endpoints, and possible interaction of the presence of anemia with the efficacy and safety of high-intensity HF treatment. Methods: The design and main results of the study have been previously described. Patients were randomized within 2 days prior to anticipated hospital discharge after HF worsening in a 1:1 fashion to either high-intensity care (HIC) or usual care (UC). Baseline characteristics, clinical and safety outcomes, and treatment effect of HIC vs. UC on the primary and secondary outcomes were compared in groups based on baseline anemia. In addition, dynamics of hemoglobin during the study follow-up and predictors of incident anemia at 90 days were investigated. Results: The proportion of anemia in 1077 STRONG-HF patients at enrollment was 27.2%, while at 90 days, it changed to 32.1%. The primary composite outcome occurred in 18.2% of patients without baseline anemia, and 22.5% of patients with baseline anemia (unadjusted HR 1.27; 95% CI 0.90–1.80), a difference that did not reach statistical significance. However, patients with baseline anemia had significantly less improvement of EQ-VAS questionnaire values from baseline to day 90 (adjusted LS-Mean difference −2.34 (−4.37, −0.31), P = 0.02). During the study, anemia developed in 19.4 and 14.6% in HIC and UC groups, respectively. The opposite phenomenon—recovery of anemia—occurred in 27.6 and 28.8% in HIC and UC groups (P = 0.1379). The predictors of incident anemia at 90 days were male sex, geographical region other than Europe, ischemic etiology, higher glucose, and elevated uric acid at baseline. The percentages of optimal doses of renin–angiotensin system inhibitors, beta-blockers, and mineralocorticoid receptor antagonists were not different between anemic and non-anemic patients. High-intensity care strategy did not increase rate of incident anemia at 90 days and reduced the rate of primary and secondary endpoints regardless of baseline hemoglobin. Conclusion: Hemoglobin level and status of anemia have a dynamic nature in the acute HF patients in the post-discharge period dependent on multiple factors. High-intensity HF treatment is safe and beneficial regardless of baseline hemoglobin level and presence of anemia. The improvement of quality of life is significantly lower in anemic HF patients implying specific attention to correction of this condition. [ABSTRACT FROM AUTHOR]

Purpose: To report on the recovery of strength and functional capacity symmetry following multiligament knee surgical reconstruction (MLKR), as well as the capacity of athletes to return to sport. Methods: This prospective cohort study recruited 47 patients undergoing MLKR between February 2018 and July 2021. Forty patients had full outcome assessment postoperatively at 6, 12 and 24 months and were included in the analysis, 75% were knee dislocation one injuries and 60% were injured playing sport. Patient‐reported outcome measures (PROMs) assessed included the International Knee Documentation Committee score, the Knee Outcome Survey, the Lysholm Knee Score and the Tegner Activity Scale (TAS). Patient satisfaction was also assessed. Objective assessment included assessment of active knee flexion and extension range of motion (ROM), the single (single horizontal hop for distance [SHD]) and triple (triple horizontal hop for distance [THD]) hop tests for distance and peak isokinetic knee flexor/extensor torque. Results: All PROMs significantly improved (p < 0.001) from presurgery to 24 months postsurgery. At 24 months, 70% of patients were satisfied with their sports participation. Active knee flexion (p < 0.0001) and extension (p < 0.0001) ROM significantly improved over time, as did the limb symmetry indices (LSIs) for the SHD (p < 0.0001), THD (p < 0.0001), peak knee extensor (p < 0.0001) and flexor (p = 0.012) torque. While LSIs for the SHD, THD and knee flexor strength tended to plateau by 12 months, knee extensor strength continued to improve from 12 to 24 months. Conclusions: The majority of patients undergoing modern MLKR surgical techniques and rehabilitation can achieve excellent knee function, with low complication rates. Level of Evidence: Level IV. [ABSTRACT FROM AUTHOR]

Infections with Enterobacterales (E) are increasingly difficult to treat due to antimicrobial resistance. After ceftriaxone replaced chloramphenicol (CHL) as empiric therapy for suspected sepsis in Malawi in 2004, extended-spectrum beta-lactamase (ESBL)-E rapidly emerged. Concurrently, resistance to CHL in Escherichia coli and Klebsiella spp. decreased, raising the possibility of CHL re-introduction. However, many phenotypically susceptible isolates still carry CHL acetyltransferase (cat) genes. To understand the molecular mechanisms and stability of this re-emerging CHL susceptibility we use a combination of genomics, phenotypic susceptibility assays, experimental evolution, and functional assays for CAT activity. Here, we show that of 840 Malawian E. coli and Klebsiella spp. isolates, 31% have discordant CHL susceptibility genotype–phenotype, and we select a subset of 42 isolates for in-depth analysis. Stable degradation of cat genes by insertion sequences leads to re-emergence of CHL susceptibility. Our study suggests that CHL could be reintroduced as a reserve agent for critically ill patients with ESBL-E infections in Malawi and similar settings and highlights the ongoing challenges in inferring antimicrobial resistance from sequence data. In this work, authors probe the molecular mechanism of re-emerging CHL susceptibility in Malawian Enterobacterales isolates, where they identify a stable truncation of resistance genes by insertion sequences. [ABSTRACT FROM AUTHOR]

The highly pathogenic avian influenza (HPAI) H5N1 virus clade 2.3.4.4b has caused the death of millions of domestic birds and thousands of wild birds in the USA since January 2022 (refs. 1–4). Throughout this outbreak, spillovers to mammals have been frequently documented5–12. Here we report spillover of the HPAI H5N1 virus to dairy cattle across several states in the USA. The affected cows displayed clinical signs encompassing decreased feed intake, altered faecal consistency, respiratory distress and decreased milk production with abnormal milk. Infectious virus and viral RNA were consistently detected in milk from affected cows. Viral distribution in tissues via immunohistochemistry and in situ hybridization revealed a distinct tropism of the virus for the epithelial cells lining the alveoli of the mammary gland in cows. Whole viral genome sequences recovered from dairy cows, birds, domestic cats and a raccoon from affected farms indicated multidirectional interspecies transmissions. Epidemiological and genomic data revealed efficient cow-to-cow transmission after apparently healthy cows from an affected farm were transported to a premise in a different state. These results demonstrate the transmission of the HPAI H5N1 clade 2.3.4.4b virus at a non-traditional interface, underscoring the ability of the virus to cross species barriers.Spillover of the highly pathogenic avian influenza H5N1 virus to dairy cattle and the findings of a clinical, pathological and epidemiological investigation in nine affected farms are reported. [ABSTRACT FROM AUTHOR]

Individuals' abilities to perform goal-directed spatial deployments of attention are distinguishable from their broader preferences for how they use spatial attention when circumstances do not compel a specific deployment strategy. Although these preferences are likely to play a major role in how we interact with the visual world during daily life, they remain relatively understudied. This exploratory study investigated two key questions about these preferences: firstly, are individuals consistent in their preferences for how they deploy their spatial attention when making shifts of attention versus adopting an attentional breadth? Secondly, which other factors are associated with these preferences? Across two experiments, we measured how participants preferred to deploy both attentional breadth (using an adapted Navon task) and eye movements (using a free-viewing task). We also measured participants' working memory capacities (Experiment 1), and their personalities and world beliefs (Experiment 2). In both experiments, there were consistent individual differences in preference for attentional breadth and eye movement characteristics, but these two kinds of preference were unrelated to each other. Working memory capacity was not linked to these preferences. Conversely, the personality trait of Openness to Experience robustly predicted two aspects of eye movement behavior preference, such that higher levels of Openness predicted smaller saccades and shorter scan paths. This suggests that personality dimensions may predict preferences for more absorbed engagement with visual information. However, it appears that individuals' preferences for shifts of attention during scene viewing do not necessarily relate to the breadth of attention they choose to adopt. [ABSTRACT FROM AUTHOR]

This article presents an assemblage of 36 glass samples excavated in the urban site of San Esteban, part of the arrabal of Arrixaca (Murcia) (in al-Andalus, an arrabal was a relatively dense urbanised area outside the city walls) in contexts securely dated to the 12th and early 13th century, spanning the rule of Ibn Mardanīš, and the early period of Almohad domination in the city. The samples were analysed by electron microprobe (EMPA) for major and minor elements and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) for trace elements. The results are examined within the context of glass production, circulation, and consumption in al-Andalus and the Islamicate Mediterranean more broadly. The results show that some of the glasses found in San Esteban-Arrixaca may have been imported from other Islamicate regions (Egypt and Mesopotamia), but that the vast majority can be related to previously recognised compositional Iberian glass groups. At the same time, the identification of several fragments of production waste and raw glass suggest that some glass-working facility may have existed in the vicinity of San Esteban-Arrixaca. The compositional evidence also indicates that recycling (including of imported glass objects) may have been a fairly common practice in Andalusi glassmaking, but it is suggested that some of the usual chemical markers of recycling may, in the case of al-Andalus and perhaps also elsewhere in the medieval Mediterranean, be the result of the cross-breeding of glass- and glaze-making activities. [ABSTRACT FROM AUTHOR]

Sexual consent, or the communication of willingness to participate in sex, is crucial in all sexual interactions. Whereas educators and researchers emphasize an ideal of consent (i.e., "affirmative" consent), lay practices of consent rarely conform to this ideal. In this mixed-methods online study (N = 231), we investigated participants' spontaneous conceptualizations of consent, gender differences in sexual consent conceptualizations, and relations of those conceptualizations to measures of sexual consent attitudes and behaviours. There was considerable variation in the complexity of participants' definitions, which reflected seven core behavioural themes. Certain themes (e.g., articulation of boundaries, consent as a process) aligned with affirmative consent attitudes, but others (e.g., consent as internal desire, lack of coercion) did not. The results suggest that participants have a sophisticated spontaneous understanding of consent, with specific areas that differ from the affirmative consent view. Further, the results suggest some aspects of affirmative consent may not be relevant to all audiences. We discuss the implications of these findings for engaging audiences in sexual consent educational initiatives. [ABSTRACT FROM AUTHOR]

Law enforcement cadets (LECs) complete weeks of subject control technique training. Similar sport-related combat training has been shown to expose participants to head acceleration events (HAEs) that have potential to result in short- and long-term impairments. The purpose of this study was to describe the number and magnitude of HAEs in LECs throughout their training. 37 LECs (7 females; age = 30.6 ± 8.8 years; BMI = 30.0 ± 6.0) were recruited from a law enforcement organization. Participants wore instrumented mouthguards, which recorded all HAEs exceeding a resultant 5 g threshold for training sessions with the potential for HAEs. Participants completed three defensive tactics (DT) training sessions, a DT skill assessment (DTA), and three boxing sessions. Outcome measures included the number of HAEs, peak linear acceleration (PLA), and peak rotational velocity (PRV). There were 2758 true-positive HAEs recorded across the duration of the study. Boxing sessions accounted for 63.7% of all true-positive HAEs, while DT accounted for 31.4% and DTA accounted for 4.9%. Boxing sessions resulted in a higher number of HAEs per session (F2,28 = 48.588, p < 0.001, ηp2 = 0.776), and higher median PLA (F2,28 = 8.609, p = 0.001, ηp2 = 0.381) and median PRV (F2,28 = 11.297, p < 0.001, ηp2 = 0.447) than DT and DTA. The LECs experience a high number of HAEs, particularly during boxing sessions. Although this training is necessary for job duties, HAE monitoring may lead to modifications in training structure to improve participant safety and enhance recovery. [ABSTRACT FROM AUTHOR]

As evidence of global insect declines continues to mount, insect conservationists are becoming increasingly interested in modeling the demographic history of at-risk species from long-term survey data. However, certain entomological survey methods may be susceptible to temporal biases that will complicate these efforts. Entomological light traps, in particular, may catch fewer insects today than they once did due solely to increases in anthropogenic light pollution. Here we investigate this possibility by comparing the demographic histories of corn earworm moths (Helicoverpa zea) estimated from pairs of blacklight and pheromone traps monitored at the same farms. We find a stark decline in blacklight trap efficacy over 25 years of monitoring in Delaware, USA, mirrored over 10 years of monitoring in New Jersey, USA. While the precise causes of this decline remain a subject for discussion, the practical consequences are clear: insect conservationists cannot fully rely on long-term trends from entomological light traps. Implications for insect conservation: H. zea populations appear to have remained largely stable over the past 25 years when assessed using pheromone trap data; when assessed using blacklight trap data, however, they appear to have declined precipitously. This disparity is consistent with a gradual loss in light trap efficacy due to concomitant increases in anthropogenic light pollution. Unfortunately, many nocturnal insects of conservation concern have historically been monitored via light traps alone. Going forward, insect conservationists should seek out alternative sources of monitoring data against which to calibrate estimates of demographic history obtained from light traps. [ABSTRACT FROM AUTHOR]

Predicting ground motions due to induced seismicity is a challenging task owing to the scarcity of data and heterogeneity of the uppermost crust. Dealing with this requires a thorough understanding of the underlying physics and consideration of inter-site variability. The most common ground motion model used in practice is the parametric ground motion prediction equation (GMPE), of which hundreds exist in the literature. However, relatively few are developed with a focus on induced seismicity. Developing GMPEs that are specific to an appropriate magnitude-distance range ( R < 30 km; 2 ≤ M ≤ 6 ) is important for induced seismicity applications. This paper proposes a framework for the development of physically-based GMPEs to provide more accurate and reliable estimates of the potential induced-seismicity ground motion hazard, allowing for better risk assessment and management strategies. To demonstrate this approach, a new set of GMPEs for the 2018-2019 induced seismicity sequence at the Preston New Road (PNR) shale gas site near Blackpool, United Kingdom, is presented. The physically-based GMPE was developed based on a pseudo-finite-fault stochastic ground motion simulation, calibrated with parameters derived from the spectral analysis of weak-motion records from induced seismic events. An optimization-based calibration technique using the area metric (AM) was subsequently performed to calibrate optimal parameters for simulating ground motion at the PNR site. Finally, using a suite of forward simulations for events with 1 ≤ M ≤ 6 recorded at distances up to 30 km, combined with empirical data, a location-specific GMPE was derived through adjustment of an existing model. [ABSTRACT FROM AUTHOR]

Background: Personalising management of primary oesophageal adenocarcinoma requires better risk stratification. Lack of independent validation of proposed imaging biomarkers has hampered clinical translation. We aimed to prospectively validate previously identified prognostic grey-level co-occurrence matrix (GLCM) CT features for 3-year overall survival. Methods: Following ethical approval, clinical and contrast-enhanced CT data were acquired from participants from five institutions. Data from three institutions were used for training and two for testing. Survival classifiers were modelled on prespecified variables ('Clinical' model: age, clinical T-stage, clinical N-stage; 'ClinVol' model: clinical features + CT tumour volume; 'ClinRad' model: ClinVol features + GLCM_Correlation and GLCM_Contrast). To reflect current clinical practice, baseline stage was also modelled as a univariate predictor ('Stage'). Discrimination was assessed by area under the receiver operating curve (AUC) analysis; calibration by Brier scores; and clinical relevance by thresholding risk scores to achieve 90% sensitivity for 3-year mortality. Results: A total of 162 participants were included (144 male; median 67 years [IQR 59, 72]; training, 95 participants; testing, 67 participants). Median survival was 998 days [IQR 486, 1594]. The ClinRad model yielded the greatest test discrimination (AUC, 0.68 [95% CI 0.54, 0.81]) that outperformed Stage (ΔAUC, 0.12 [95% CI 0.01, 0.23]; p =.04). The Clinical and ClinVol models yielded comparable test discrimination (AUC, 0.66 [95% CI 0.51, 0.80] vs. 0.65 [95% CI 0.50, 0.79]; p >.05). Test sensitivity of 90% was achieved by ClinRad and Stage models only. Conclusions: Compared to Stage, multivariable models of prespecified clinical and radiomic variables yielded improved prediction of 3-year overall survival. Clinical relevance statement: Previously identified radiomic features are prognostic but may not substantially improve risk stratification on their own. Key Points: • Better risk stratification is needed in primary oesophageal cancer to personalise management. • Previously identified CT features—GLCM_Correlation and GLCM_Contrast—contain incremental prognostic information to age and clinical stage. • Compared to staging, multivariable clinicoradiomic models improve discrimination of 3-year overall survival. [ABSTRACT FROM AUTHOR]

Physical health habits including physical activity and nutrition are essential for numerous health benefits. However, beginning in childhood, individuals with intellectual disability engage in lower levels of physical activity and healthy nutrition habits compared to individuals without intellectual disability, a trend that carries on into adulthood. Researchers continue to examine the effectiveness of interventions to increase engagement in physical health habits and improve health outcomes for individuals with intellectual disability, with an increased focus on technology-based interventions. This scoping review aimed to describe how technology was being utilized within interventions to improve health-related outcomes for adults with intellectual disability. We described the technology being used, who used the technology, and the feasibility of the interventions. Forty-one studies met criteria, with a total of 698 adult participants with an intellectual disability. While no studies on nutrition were located, technology was used in various physical activity interventions, with the most common being preferred stimulus access, exergaming, and video-based instruction. Most studies took place at day or rehabilitation centers, were implemented by research teams, and either did not discuss cost or were vague in their description related to cost. Implications, limitations, and future research directions are discussed. [ABSTRACT FROM AUTHOR]

Wetlands are important ecosystems for mitigating climate change impacts on the environment and society. Most studies focus on how single environmental factors affect those ecosystems, although several environmental factors may change simultaneously. This study focused on nutrient – water level interaction effects on two different but associated wet grassland species Carex acuta and Glyceria maxima. Biomass allocation and root exudates were measured in a full-factorial mesocosm experiment. Species identity and water level mostly determined total alive biomass and the biomass allocation pattern. Root weight ratio generally increased in C. acuta whereas increased rhizome biomass was associated with G. maxima. Furthermore, increased water levels increased relative aboveground biomass allocation with C. acuta having more leaf and G. maxima having more stem biomass. Surprisingly, fertilisation had little impact on total biomass, but decreased relative biomass allocation to the roots and also strongly suppressed root exudation. There is an apparent nutrient dependent shift in the realised hydrological niche of both plants towards drier conditions. C. acuta behaves similar under all water levels without fertilisation, but thrives best under dry conditions when fertilised. Without fertilisation, G. maxima thrives best under flooded conditions (water level ~ 15 cm above soil surface), but does equally well in saturated water conditions (water level ~ soil surface) when fertilised. [ABSTRACT FROM AUTHOR]

Pornography viewers often report being addicted to pornography even if their behavior does not indicate such addiction. In this study with 1099 participants (52% male), we explored how the specific belief in being addicted to pornography could predict both individual and relational outcomes beyond actual pornography use and reported compulsive pornography use (i.e., considering one's use to be out of control). Using a structural equation model, our results showed that higher agreement with the pornography addiction label, without accounting for compulsivity, was associated with higher depression, suicide ideation, communication discomfort about pornography, and higher odds of having a relationship end solely because of pornography. After accounting for compulsivity, higher agreement with the pornography addiction label was only associated with higher communication discomfort about pornography and higher odds of having a relationship end solely because of pornography. This study highlights that identifying as addicted to pornography may include a stigma that is particularly detrimental to relationship outcomes. [ABSTRACT FROM AUTHOR]

It is estimated that 153,020 cases of CRC per year, with an increase in diagnoses in younger patients. We present a case of a female with an early presentation of Lynch Syndrome and CRC, who, on her third malignant presentation, was re-diagnosed as a constitutional mismatch repair deficiency. [ABSTRACT FROM AUTHOR]

Purpose of Review: We systematically reviewed implementation research conducted in Indigenous communities in the Americas and the Pacific that focused on improving delivery of HIV preventive or treatment services. We highlight strengths and opportunities in the literature and outline principles for Indigenous-led, HIV-related implementation science. Recent Findings: We identified 31 studies, revealing a consistent emphasis on cultural tailoring of services to Indigenous communities. Common barriers to implementation included stigma, geographic limitations, confidentiality concerns, language barriers, and mistrust. Community involvement in intervention development and delivery emerged as a key facilitator, and nearly half of the studies used community-based participatory research methods. While behavioral HIV prevention, especially among Indigenous youth, was a major focus, there was limited research on biomedical HIV prevention and treatment. No randomized implementation trials were identified. Summary: The findings underscore the importance of community engagement, the need for interventions developed within Indigenous communities rather than merely adapted, and the value of addressing the social determinants of implementation success. Aligned to these principles, an indigenized implementation science could enhance the acceptability and reach of critical HIV preventive and treatment services in Indigenous communities while also honoring their knowledge, wisdom, and strength. [ABSTRACT FROM AUTHOR]

Exposure to toxic heavy metals has been associated with the development of attention-deficit/hyperactivity disorder (ADHD). However, fewer studies have examined the associations between abnormal levels of essential trace metals and ADHD, and none have done so using saliva. We investigated whether salivary metals were associated with ADHD in adolescents aged 12 from the Family Life Project (FLP) using a nested case–control study design that included 110 adolescents who met diagnostic criteria for inattentive (ADHD-I), hyperactive-impulsive (ADHD-H), or combined type ADHD (ADHD-C) (cases) and 173 children who did not (controls). We used inductively coupled plasma optical emission spectrophotometry to measure chromium, copper, manganese, and zinc in saliva samples. We employed logistic regression models to examine associations between quartile levels of individual metals and ADHD outcomes by subtype. Salivary copper levels were significantly associated with increased odds of any ADHD diagnosis (OR = 3.31, 95% CI: 1.08–10.12; p = 0.04) and with increased odds of ADHD-C diagnosis (OR = 8.44, 95% CI: 1.58–45.12; p = 0.01). Salivary zinc levels were significantly associated with increased odds of ADHD-C diagnosis (OR = 4.06, 95% CI: 1.21–13.69; p = 0.02). Salivary manganese levels were also significantly associated with increased odds of ADHD-C diagnosis (OR = 5.43, 95% CI: 1.08–27.27, p = 0.04). This is the first study using saliva to assess metal exposure and provide a potential link between salivary levels of copper, manganese, and zinc and ADHD diagnoses in adolescents. Public health interventions focused on metal exposures might reduce ADHD incidence in low-income, minority communities. [ABSTRACT FROM AUTHOR]

We investigate natural selection on polygenic scores in the contemporary US, using the Health and Retirement Study. Across three generations, scores which correlate negatively (positively) with education are selected for (against). However, results only partially support the economic theory of fertility as an explanation for natural selection. The theory predicts that selection coefficients should be stronger among low-income, less educated, unmarried and younger parents, but these predictions are only half borne out: coefficients are larger only among low-income parents and unmarried parents. We also estimate effect sizes corrected for noise in the polygenic scores. Selection for some health traits is similar in magnitude to that for cognitive traits. [ABSTRACT FROM AUTHOR]

Purpose: Although the biliary tract is a common source of invasive infections, the epidemiology of cholangitis- and cholecystitis-associated bloodstream infection (BSI) is not well defined. The objective of this study was to determine the incidence, clinical determinants, microbiology of biliary tract-associated BSI, and predicted adequacy of common empiric therapy regimens. Methods: All biliary tract-associated BSI in Queensland during 2000–2019 were identified using state-wide data sources. Predicted adequacy of empiric antimicrobial therapy was determined according to microbiological susceptibility data. Results: There were 3,698 episodes of biliary tract-associated BSI occurred in 3,433 patients of which 2,147 (58.1%) episodes were due to cholangitis and 1,551 (41.9%) cholecystitis, for age- and sex-standardized incidence rates of 2.7, and 2.0 per 100,000 population, respectively. An increasing incidence of biliary tract-associated BSI was observed over the study that was attributable to an increase in cholangitis cases. There was a significant increased risk for biliary tract-associated BSI observed with advancing age and male sex. Patients with cholangitis were older, more likely to have healthcare associated infection, and have more comorbidities most notably liver disease and malignancies as compared to patients with cholecystitis. The distribution of infecting pathogens was significantly different with polymicrobial aetiologies more commonly observed with cholangitis (18.4% vs. 10.5%; p < 0.001). The combination of ampicillin/gentamicin/metronidazole was predicted to have the overall highest adequacy (96.1%), whereas amoxicillin/clavulanate had the lowest (77.0%). Amoxicillin/clavulanate (75.2% vs. 79.4%, p:0.03) and ceftriaxone/metronidazole (83.4% vs. 89.6%; p < 0.001) showed significantly inferior predicted adequacy for cholangitis as compared to cholecystitis. Conclusions: Bloodstream infections related to cholecystitis and cholangitis exhibit different epidemiology, microbiology, and requirements for empiric therapy. [ABSTRACT FROM AUTHOR]

Purpose: Currently no guidance exists within the literature regarding diagnostic criteria or the long-term outcomes for paediatric patients with acute compartment syndrome (ACS). We conducted a retrospective cohort study reviewing all cases of paediatric ACS managed at a single tertiary referral centre with the aim of characterising the factors responsible for the eventual outcomes. Methods: The patient cohort was identified retrospectively by interrogating the hospital coding system for all paediatric patients between January 2014 and November 2022. The electronic emergency department, inpatient and operative notes as well as clinic letters for each patient were reviewed and data collected regarding presentation, associated injuries, management and subsequent complications plus length of follow-up. The data was analysed to determine if differences in presentation or management affected long term outcome. Results: The final cohort consisted of 34 patients with a mean age of ten years at the time of presentation. The mean time from presentation to fasciotomy was 27.6 h (range 3.0 – 66.6). There was an overall complication rate of 37.5% with a mean follow-up period of 21 months. Patients who had direct closure of their fasciotomy wounds had a significantly lower complications rate and fewer operations compared to those who healed via other wound coverage methods or secondary intention (p < 0.05). Conclusions: Significantly higher complication rates were observed in patients who were unable to have direct wound closure following emergency fasciotomy. This information may be utilised to rationalise long term treatment plans and in counselling of patients and parents. [ABSTRACT FROM AUTHOR]

Children and youth often face barriers that hinder their ability to engage in school, such as poverty, family challenges, and maltreatment. For this reason, children require additional supports if they are to be set up for success in school and life. Collaborative school-community models of wraparound support have been demonstrated as effective approaches for supporting vulnerable children and families to foster positive outcomes. Such models rely on collaborative partnerships between schools and community agencies to coordinate services for children and families. Accordingly, there is a need to understand factors that influence this collaboration in school settings. This study explores partnership collaboration between school and community partners through the case of All in for Youth, a school-based wraparound model of support in western Canada. Focus groups of n = 79 partners across eight schools were analysed, guided by qualitative description methodology. Five essential conditions were identified for partnership collaboration, including value-based training, mutual recognition of expertise, school leadership, established and flexible communication channels, and appropriate staff resources. These conditions can be used to help inform the implementation of similar school-community models of support to foster collaborative partner processes and promote positive outcomes among children, youth, and families. Highlights: Explored factors that impact partnership collaboration in school-community models of support. Focus groups conducted with 79 school-community partners across eight schools. Identified five essential conditions for school-community partnership collaboration. [ABSTRACT FROM AUTHOR]

Background and Objectives: Key opinion leader (KOL) interviews were conducted by the Benefit–Risk Assessment Planning (BRAP) Taskforce to seek expert opinion mainly from industry and regulatory bodies, about the current status and future direction of benefit–risk assessment (BRA) planning in the lifecycle of medical product development. The findings from these interviews are intended to help communication concerning planning for BRA between industry and regulators and shape future guidance. Methods: Key opinion leader interviews consisted of 5 questions related to BRA planning, which were administered to volunteers (mainly clinicians and statisticians) within a pool of experienced pharmaceutical and medical device professionals representing academia, industry, regulatory agencies and a patient group. The interviewees' responses to the 5 questions were summarized. To analyze the qualitative data, a Coding System was developed to label themes arising from the interviews. The key findings from the interviews were summarized into a Master Template. A quantitative analysis based on descriptive statistics was also conducted. Results: Of the 27 interviewees, there were 11 professionals from regulatory agencies, 11 from industry, 4 from academia and 1 from a patient advocacy group. Key findings based on the comments provided by 48% of the interviewees indicated the need of incorporating BRA into other (e.g., existing) processes with the importance of alignment between processes being stressed in the comments provided by 59% of the interviewees. Commencing BRA early in the product lifecycle was emphasized in comments provided by 44% of the interviewees. Among other needs identified were an appropriate contextualization of benefits and risks (based on comments provided by 41% of interviewees) through adoption of an integrated approach with structured support by regulatory agencies and a need for understanding the audience with better communication of benefit–risk (BR) among all stakeholders (based on comments provided by 44% of the interviewees). Almost all comments provided by interviewees (96%) highlighted the importance of utilizing patient experience/preference to guide new product development and BRA. Comments provided by 74% of the interviewees expressed the need to understand patient tolerance for risk and trade-offs, with a majority (78%) of interviewees highlighting how to gather information, and 59% stressing the need for the selection and development of appropriate methodologies as important considerations for enhancing the quality and relevance of the data collected from patients. Conclusions: Interviewees indicated that BRA should commence early in the medical product development and inform decision-making throughout the product lifecycle. Better planning and integration of BRA into existing processes within industry would be valuable. The importance of incorporating the patient voice into BRA and medical product development was emphasized. Other key findings from the KOL interviews included a need for improved communication of BR information, and establishment of methodologies for performing BRA and soliciting patient input. [ABSTRACT FROM AUTHOR]

Summary: Praxelis cleggiae (Compositae: Eupatorieae: Praxeliinae) is described and illustrated from the granite inselbergs (upon which it is most common), and on road crown chippings on old roads, in the Departamento de Santa Cruz, Bolivia; it has a disjunct distribution and is also found on the Serranía San Simón, in the San Ignacio Schist belt, Departamento de Beni. Material of this species was mostly determined as P. insignis (Malme) R.M.King & H.Rob., a Brazilian species, described from the metamorphosed sandstone of what is now the Parque Nacional da Chapada dos Guimarães in Mato Grosso State. The two species have some superficial resemblance, but differ significantly in plant size, internode length (relative to leaf length), branching, leaf shape and size, phyllaries, achenes and pappus. The total number of species of Praxelis recognised in Bolivia is now seven, and 20 species in the genus worldwide. [ABSTRACT FROM AUTHOR]

Purpose: Distal radius fractures are the most common upper limb fractures in adults (up to 18% of all fractures in the Emergency Department). Conservative management is possible for the majority, the preferred surgical technique being volar plate fixation. Dorsal bridge plating (DBP) is an alternative method of treatment for complex fractures. DBP acts as an internal fixator and can be used in patients needing early rehabilitation. This systematic review assesses the demographics, functional and radiological outcomes and complications of using DBP in patients with distal radius fractures compared to volar plate fixation. Methods: A literature search of PubMed, Cochrane, EMBASE and Google Scholar was performed according to PRISMA guidelines. Seven hundred and sixty-one articles were found; 11 articles met the inclusion criteria. Cadaveric studies and case studies of less than five patients were excluded. Primary outcome measures were functional and radiological outcomes. Complications were recorded as secondary outcomes. Results: Three hundred and ninety-four patients were included in the study with an average age of 54.8 years (53.9% male and 46.1% female). Weighted mean follow-up was 55.2 weeks; the mean time to plate removal was 17.3 weeks with a mean DASH score of 25.7. The weighted range of movement was 46.9° flexion, 48.8° extension, 68.4° pronation and 67.5° supination. The radiological parameters show satisfactory outcomes with a mean radial height of 10mm, volar tilt of 3.1°, ulnar variance of 0.5mm and radial inclination of 18.8°. The complication rate was 11.4%. Digital stiffness was the most common complication but improved if tenolysis was performed at plate removal. Conclusions: DBP is a good alternative to volar plating for complex distal radius fractures. The functional outcomes showed a slight loss of range of movement, whereas the radiological outcomes were within recommended limits. A significant disadvantage of the plate is the need for further surgical removal. [ABSTRACT FROM AUTHOR]

Objectives: Corner metaphyseal lesions (CMLs) are specific for child abuse but challenging to detect on radiographs. The accuracy of CT for CML detection is unknown. Our aim was to compare diagnostic accuracy for CML detection on post-mortem skeletal surveys (PMSS, plain radiography) versus post-mortem CT (PMCT). Methods: A 10-year retrospective review was performed at a children's hospital for patients having PMSS, PMCT and histopathological correlation (reference standard) for suspected CMLs. Twenty-four radiologists independently reported the presence or absence of CMLs in all cases in a blinded randomised cross-over design across two rounds. Logistic regression models were used to compare accuracy between modalities. Results: Twenty CMLs were reviewed for each of the 10 subjects (200 metaphyses in all). Among them, 20 CMLs were confirmed by bone histopathology. Sensitivity for these CMLs was significantly higher for PMSS (69.6%, 95% CI 61.7 to 76.7) than PMCT (60.5%, 95% CI 51.9 to 68.6). Using PMSS for detection of CMLs would yield one extra correct diagnosis for every 11.1 (95% CI 6.6 to 37.0) fractured bones. In contrast, specificity was higher on PMCT (92.7%, 95% CI 90.3 to 94.5) than PMSS (90.5%, 95% CI 87.6 to 92.8) with an absolute difference of 2.2% (95% CI 1.0 to 3.4, p < 0.001). More fractures were reported collectively by readers on PMSS (785) than on PMCT (640). Conclusion: PMSS remains preferable to PMCT for CML evaluation. Any investigation of suspected abuse or unexplained deaths should include radiographs of the limbs to exclude CMLs. Clinical relevance statement: In order to avoid missing evidence that could indicate child abuse as a contributory cause for death in children, radiographs of the limbs should be performed to exclude CMLs, even if a PMCT is being acquired. Key Points: • Corner metaphyseal lesions (CMLs) are indicative for abuse, but challenging to detect. Skeletal surveys (i.e. radiographs) are standard practice; however, accuracy of CT is unknown. • Sensitivity for CML detection on radiographs is significantly higher than CT. • Investigation of unexplained paediatric deaths should include radiographs to exclude CMLs even if CT is also being performed. [ABSTRACT FROM AUTHOR]

Previous research on co-development has focused on modeling the relations at the group level; however, how individuals differ in co-development may provide important information as well. Recent work has used vector plots to visually explore individual differences in co-development; however, these judgements were made based on visual inspection of a vector plot rather than the calculation of metrics. Here we propose two metrics that can be used to quantify co-development at the individual level: the co-development change ratio (CCR) and the angle of co-development metric (ACM). CCR provides information about the symmetry of development, examining whether an individual grew at the same pace in one skill relative to peers as compared to growth in the other skill relative to peers. ACM represents the relative amount and direction of change on each skill. This paper provides a tutorial on how to calculate and interpret these two metrics for quantifying co-development at the individual level. [ABSTRACT FROM AUTHOR]

Purpose: The effect of cancellation and postponement of primary total hip arthroplasty (THA) or knee arthroplasty (TKA) on patient outcomes is unclear. The aim was to assess whether cancellation and delay to arthroplasty was associated with worse joint specific function and quality of life (QoL) 1-year postoperatively. Methods: A single centre retrospective case–control study was performed for all patients planned to undergo THA or TKA in 2019. A total of 3133 arthroplasties were scheduled for 2019 (1484 THA, 1649 TKA), of which 344 (11.0%) were cancelled (136 THA [9.2%], 208 TKA [12.6%]). Pre-operative and one-year post-operative EuroQol (EQ-5D) and Oxford hip (OHS) or knee (OKS) scores were collected. Results: The median time between the date of cancellation and the subsequent operation was 46.0 days for TKA and 45.5 days for THA. The cancelled group were more likely to be male (odds ratio [OR] 1.23, p = 0.03), older (mean difference [MD] 1.19, p = 0.03), with a higher ASA grade (OR 1.88 [ASA 3], OR 5.3 [ASA 4], p = 0.001) or planned for a TKA (OR 1.41, p = 0.003). There were no differences in pre-operative OKS (mean difference [MD] 0.19, p = 0.828) or EQ-5D (MD 0.028, p = 0.394) or in the one-year postoperative OKS (MD 1.51, p = 0.064) or EQ-5D (MD 0.041, p = 0.067) between groups undergoing TKA. However, cancelled THA patients had lower pre-operative OHS (MD 2.73, p = 0.018) and EQ-5D (MD 0.134, p = 0.0017) but at one-year postoperatively there was no difference in the absolute OHS (MD 2.07, p = 0.052) or EQ5D (MD 0.04, p = 0.142). The improvement in hip EQ-5D was greater (MD 0.096, p = 0.016) in the cancelled group. Conclusion: Cancellation and short delay did not influence joint specific outcome or QoL following THA or TKA at one-year. Preoperative hip specific pain, function and QoL were worse in cancelled THA patients, suggesting deterioration while waiting for their surgery, but this did not affect their postoperative outcome. [ABSTRACT FROM AUTHOR]

Purpose: We wished to evaluate if an open-source artificial intelligence (AI) algorithm (https://www.childfx.com) could improve performance of (1) subspecialized musculoskeletal radiologists, (2) radiology residents, and (3) pediatric residents in detecting pediatric and young adult upper extremity fractures. Materials and methods: A set of evaluation radiographs drawn from throughout the upper extremity (elbow, hand/finger, humerus/shoulder/clavicle, wrist/forearm, and clavicle) from 240 unique patients at a single hospital was constructed (mean age 11.3 years, range 0–22 years, 37.9% female). Two fellowship-trained musculoskeletal radiologists, three radiology residents, and two pediatric residents were recruited as readers. Each reader interpreted each case initially without and then subsequently 3–4 weeks later with AI assistance and recorded if/where fracture was present. Results: Access to AI significantly improved area under the receiver operator curve (AUC) of radiology residents (0.768 [0.730–0.806] without AI to 0.876 [0.845–0.908] with AI, P < 0.001) and pediatric residents (0.706 [0.659–0.753] without AI to 0.844 [0.805–0.883] with AI, P < 0.001) in identifying fracture, respectively. There was no evidence of improvement for subspecialized musculoskeletal radiology attendings in identifying fracture (AUC 0.867 [0.832–0.902] to 0.890 [0.856–0.924], P = 0.093). There was no evidence of difference between overall resident AUC with AI and subspecialist AUC without AI (resident with AI 0.863, attending without AI AUC 0.867, P = 0.856). Overall physician radiograph interpretation time was significantly lower with AI (38.9 s with AI vs. 52.1 s without AI, P = 0.030). Conclusion: An openly accessible AI model significantly improved radiology and pediatric resident accuracy in detecting pediatric upper extremity fractures. [ABSTRACT FROM AUTHOR]

There are two main families of G protein-coupled receptors that detect odours in humans, the odorant receptors (ORs) and the trace amine-associated receptors (TAARs). Their amino acid sequences are distinct, with the TAARs being most similar to the aminergic receptors such as those activated by adrenaline, serotonin, dopamine and histamine. To elucidate the structural determinants of ligand recognition by TAARs, we have determined the cryo-EM structure of a murine receptor, mTAAR7f, coupled to the heterotrimeric G protein Gs and bound to the odorant N,N-dimethylcyclohexylamine (DMCHA) to an overall resolution of 2.9 Å. DMCHA is bound in a hydrophobic orthosteric binding site primarily through van der Waals interactions and a strong charge-charge interaction between the tertiary amine of the ligand and an aspartic acid residue. This site is distinct and non-overlapping with the binding site for the odorant propionate in the odorant receptor OR51E2. The structure, in combination with mutagenesis data and molecular dynamics simulations suggests that the activation of the receptor follows a similar pathway to that of the β-adrenoceptors, with the significant difference that DMCHA interacts directly with one of the main activation microswitch residues, Trp6.48. Smells are detected in the nose by odorant molecules binding to a specific G protein-coupled receptor on the cell surface. Here, authors have determined the atomic structure of a receptor bound to an odorant molecule that showing how the odorant binds and activates the receptor. [ABSTRACT FROM AUTHOR]

The QUANT study represents the most extensive open-access evaluation of commercial air quality sensor systems to date. This comprehensive study assessed 49 systems from 14 manufacturers across three urban sites in the UK over a three-year period. The resulting open-access dataset captures high time-resolution measurements of a variety of gasses (NO, NO2, O3, CO, CO2), particulate matter (PM1, PM2.5, PM10), and key meteorological parameters (humidity, temperature, atmospheric pressure). The quality and scope of the dataset is enhanced by reference monitors' data and calibrated products from sensor manufacturers across the three sites. This publicly accessible dataset serves as a robust and transparent resource that details the methods used for data collection and procedures to ensure dataset integrity. It provides a valuable tool for a wide range of stakeholders to analyze the performance of air quality sensors in real-world settings. Policymakers can leverage this data to refine sensor deployment guidelines and develop standardized protocols, while manufacturers can utilize it as a benchmark for technological innovation and product certification. Moreover, the dataset has supported the development of a UK code of practice, and the certification of one of the participating companies, underscoring the dataset's utility and reliability. [ABSTRACT FROM AUTHOR]

Purpose: Persistent gastrointestinal (GI) symptoms are frequently experienced by colon cancer survivors and may help identify patients with higher utilization of healthcare services. To assess the relationship between GI symptoms and specialty care utilization among colon cancer survivors. Methods: A prospective longitudinal cohort study at an academic medical center of 126 adults surgically treated for stage I–IV colon cancer between February 2017 and June 2022. Participants reported GI symptoms through the EORTC QLQ-C30 and QLQ-CR29 at enrollment and as frequently as every 6 months for 5 years. Main outcome measures were visits, telephone encounters, and secure messages with a medical provider within specialty oncology clinics within 6 months after each survey completion. Generalized linear mixed regression model for repeated measurements with random trajectory for each participant was performed to estimate the associations between symptoms and healthcare use. Models were adjusted for demographics, clinical and surgical factors, and timing in relation to onset of the COVID-19 pandemic. Results: In the 6 months after each survey time point, patients averaged 1.2 visits, 0.5 telephone encounters, and 3.2 patient-initiated messages. In adjusted models, those with any abdominal pain (RR 1.45; p = 0.002), buttock pain (RR 1.30; p = 0.050), or increased stool frequency (RR 1.26; p = 0.046) had more clinic visits in the following 6 months than those without these symptoms. Including these three symptoms in one model revealed that only abdominal pain was statistically significantly associated with increased clinic visits (RR 1.36; p = 0.016). Patients with any blood or mucus in stool (RR 2.46; p = 0.009) had significantly more telephone encounters, and those with any abdominal pain (RR 1.65; p = 0.002) had significantly more patient-initiated messages than those without these symptoms. Conclusions: Our findings identify GI symptoms associated with increased use of oncologic specialty care among colon cancer survivors, with abdominal pain as an important predictor of utilization. Implications for cancer survivors: Early identification and anticipatory management of colon cancer survivors experiencing abdominal pain may decrease healthcare utilization. [ABSTRACT FROM AUTHOR]

Purpose: Accurate assessment of chronic pain and functional disability in children and adolescents is imperative for guiding pain management interventions. Parents have multifaceted roles in their child’s pain experience and frequently provide parent-proxy reports of pain-related functioning. However, cross-informant variance is often observed with limited understanding of contributing factors. This study aims to examine the degree of alignment between child and parent-proxy reports for Patient-Reported Outcomes Measurement Information System (PROMIS) pain interference domain among children with chronic pain and to identify factors associated with improved child-parent agreement. Methods: This study includes a sample of 127 youth (66.1% female) with mixed etiology chronic pain, ranging in age from 8 to 17 (M = 12.24; SD = 1.598), and their parent. Data was collected at an interdisciplinary pediatric pain clinic and online peer support groups. Measures of demographic, pain intensity, and functioning were collected. Results: Means of parent-proxy reports were significantly lower than child self-reports on the PROMIS (p < 0.05). A statistically significant association between child’s pain intensity (β = 0.953, P < 0.05) and the difference between child self-reported and parent-proxy reported PROMIS functional interference scores was found. Conclusion: Parents underestimated pain-related functional disability relative to children’s self-reports. The difference between the paired child self-report and parent-proxy report of functional disability was significantly associated with greater child self-reported pain intensity. Although parent-proxy reports in pediatric chronic pain is often used in research and practice, findings underscore the importance of incorporating child and adolescent self-report, when possible, to comprehensively capture the child’s pain experience and best inform clinical interventions. [ABSTRACT FROM AUTHOR]

Dengue is a global health concern, and the host-viral interactions that regulate disease severity are largely unknown. Detrimental effects of neutrophils in this disease have been reported, but the precise mechanisms and functional properties of dengue-activated neutrophils are not fully characterised. Here, we measured the effects of dengue virus serotype 3 (DV3) on neutrophil lifespan and functions. We show that DV3 extends neutrophil survival with a significant proportion of cells surviving for 72 h post-incubation. These effects on neutrophil survival were greater than those observed by adding GM-CSF and TNF-α alone, but these cytokines enhanced survival induced by the virus. Enhanced reactive oxygen species (ROS) generation was observed following incubation with DV3 activation and this ROS production was enhanced by co-incubation with priming agents. In addition, DV triggered the enhanced IL-8 expression by the majority of neutrophils and a low percentage of cells were activated to express MCP-1 (CCL2). A low number of neutrophils showed increased co-expression of the migratory markers, CCR7 and CXCR4 which could promote their migration towards lymph nodes. DV3 significantly upregulated the BCL-XL gene at 3, 12, and 24 h, and the Mcl-1 gene at 12 h, following treatment. We also show that DV3 induces the Mcl-1 protein stabilization similar to GM-CSF. This report sheds new light on the mechanisms by which neutrophils may contribute to the pathology of dengue disease via delayed apoptosis and generation of pro-inflammatory molecules, and raises the possibility that dengue-activated neutrophils may play a role in activating cells of adaptive immunity. [ABSTRACT FROM AUTHOR]

This document is a response to a critique of a scientific paper published in Nature Communications. The authors of the response address the criticisms made by Dr. Goldsmith and his colleagues regarding the enzyme activities described in their paper. They clarify that their results were measured using a different method than assumed by Dr. Goldsmith. The authors also present their own experiments that challenge the proposed substrate for one of the enzymes involved in the synthesis of β-ODAP, a compound found in grass peas that can cause a neurodegenerative disorder called lathyrism. They conclude that the synthesis of a key compound involved in β-ODAP synthesis is likely limited in the cytosol of grass pea plants. The article highlights the proposed mechanism for β-ODAP synthesis and provides experimental evidence to support it, while also addressing criticisms and emphasizing the importance of understanding this process for improving the crop. [Extracted from the article]