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The design and implementation of successful rotational flaps of the scalp remains a complex process. There are several described techniques, all of which are based on a two-dimension surface, absent consideration of the convexity, and thereby three-dimensional nature of the scalp. This has contributed to flaps that are either too small or unnecessarily large in a bid to compensate. Mathematical analysis using trigonometric and algebraic formulas was used to derive the relationship between the defect, triangulation, the contour of the scalp, the radius of the arc of rotation for the flap, and scalp skin tension. Polyurethane models were used to test the applicability of the resultant formula, and a consecutive clinical case series is presented. Rotation flap dimensions were calculated using an apex angle of 30° depicted as a two-dimensional construct. The contour of the defect was then measured as the depth of depression with radius of the rotation flap calculated based on the changes in flap surface area across the defect. Finite element analysis was used to measure redistribution of tension along the flap reconstructing the defect, and the efficacy of the approach was confirmed in the consecutive clinical series. This study provides a reliable flap design based on mathematical analysis, with evidence-based application to the clinical setting.

Abstract Results of the impact of reading books and viewing television on neurodevelopment have been mixed, without definitive evaluation to date. Using data from 11,875 US adolescents in the Adolescent Brain and Cognitive Development (ABCD) study, we investigated the associations between reading and television viewing on brain morphology and neurocognitive performance. After quality control, 8,125 participants’ MRI scans and cognitive tests were analyzed in relation to their reading and TV habits. Greater reading time was associated with higher cognitive performance and regionally-selective increases in cortical area, while greater TV viewing had a much smaller association with lower cognitive performance and decreased cortical area. Regionally, areas of spatial overlap in associations included the lateral temporal, inferior parietal, and inferior frontal lobes, while significant associations in the ventral and inferior temporal cortex and cingulate cortex were unique to reading habits. These relationships persisted after adjusting for demographics, socioeconomic factors, genetic ancestry, and imaging factors. The magnitude of reading associations exceeded those of TV viewing and was similar to established contributions of parental income and education on neurodevelopment. This study provides a comprehensive evaluation of how these behaviors correlate with early adolescent brain development across a large diverse population.

Abstract The PEAK family of pseudokinases, comprising PEAK1-3, play oncogenic roles in several poor prognosis human cancers, including triple negative breast cancer (TNBC). However, therapeutic targeting of pseudokinases is challenging due to their lack of catalytic activity. To address this, we screen for PEAK1 effectors and identify calcium/calmodulin-dependent protein kinase 2 (CAMK2)D and CAMK2G. PEAK1 promotes CAMK2 activation in TNBC cells via PLCγ1/Ca2+ signalling and direct binding to CAMK2. In turn, CAMK2 phosphorylates PEAK1 to enhance association with PEAK2, which is critical for PEAK1 oncogenic signalling. To achieve pharmacologic targeting of PEAK1/CAMK2, we repurpose RA306, a second generation CAMK2 inhibitor. RA306 inhibits PEAK1-enhanced migration and invasion of TNBC cells in vitro and significantly attenuates TNBC xenograft growth and metastasis in a manner mirrored by PEAK1 ablation. Overall, these studies establish PEAK1 as a critical cell signalling nexus that integrates Ca2+ and tyrosine kinase signals and identify CAMK2 as a therapeutically ‘actionable’ target downstream of PEAK1.

In this paper, we present the implementation of the Cha-Cheon Identity-Based Signature (IBS) scheme to enhance secure data transfer in cloud computing environments. Cloud computing rely on traditional Public Key Infrastructure (PKI) systems, which is burdened by certificate management infrastructure. The primary focus of this research to simplify key and certificate management by leveraging identity-based elliptic curve cryptography (ECC) within the Cha-Cheon IBS framework. We show that the proposed IBS solution integrates seamlessly with Amazon Web Services (AWS), utilizing services like S3 for secure data storage and KMS for key management. By applying ECC, the Cha-Cheon scheme achieves efficient cryptographic operations with smaller key sizes, resulting in reduced computational overhead, faster key generation, signature creation, and verification times compared to RSA-based systems. We conducted extensive performance evaluations to compare the Cha-Cheon IBS scheme with traditional PKI-based systems. The results demonstrate that our implementation significantly outperforms RSA in terms of key generation, encryption, and signature verification times, especially under increased user loads and data sizes. Moreover, the security analysis confirms the robustness of the Cha-Cheon IBS against key compromise, offering strong resistance to unauthorized access and key revocation issues. The scheme also scales efficiently as the number of users increases, making it ideal for large-scale cloud infrastructures. This research highlights the potential of IBS as a viable alternative to PKI systems, providing a more streamlined and efficient approach to secure data transfers in cloud environments.

Use of 10-valent pneumococcal conjugate vaccine in Kenya has led to substantial reductions in vaccine-type pneumococcal carriage and invasive pneumococcal disease. However, analysis of recent surveillance data indicates an outbreak of vaccine-type serotype 1 in 2023 in Kibera, Kenya. Continued monitoring of invasive pneumococcal disease in Kenya is warranted.

Abstract Pulsed radio frequency energy (PRFE) therapy is a non-invasive, electromagnetic field-based treatment modality successfully used in clinical applications. However, conventional PRFE devices are often bulky, expensive, and require extended treatment durations, limiting patient adherence and efficacy. Here, we present a lightweight, cost-effective wearable PRFE system consisting of a flexible electronic bandage and a smartphone. The bandage, mainly composed of an NFC Frequency Doubler (NFD) and a Radiofrequency Energy Radiator (RER), is powered and administered by the smartphone to generate 27.12 MHz radio wave pulses, for simplified, smartphone-enabled PRFE therapy. Its ultra-flexible, battery-free design supports personalized wound care at a low-cost (

Abstract A collection of datasets describing six years of experiments on maize (Zea mays, L.) (corn) is presented (1989, 1990, 1994, 2013, 2016, and 2018). Four weighing lysimeters were used to determine crop evapotranspiration (ET). In-soil and above ground microclimate and ET data are presented on a 15-minute interval as are weather data for all days of the year. Data analysis determined ET, precipitation, irrigation, and dew and frost accumulation on a 15-minute basis from lysimeter mass data. Soil water content data from calibrated neutron probe readings is presented on a periodic basis. Crop planting, harvest, fertilization, pest control, and other agronomic information are presented in agronomic calendars by day of year. Crop growth data are presented on a periodic basis throughout the growing season, as are final crop biomass and yield data. The data are suitable for analysis of effects of irrigation and other agronomic decisions on crop yield and water productivity in the Southern High Plains region of the USA, for model calibration and testing, and for model improvement.

Abstract Understanding how the traits of lineages are related to diversification is key for elucidating the origin of variation in species richness. Here, we test whether traits are related to species richness among lineages of trees from all major biogeographical settings of the lowland wet tropics. We explore whether variation in mortality rate, breeding system and maximum diameter are related to species richness, either directly or via associations with range size, among 463 genera that contain wet tropical forest trees. For Amazonian genera, we also explore whether traits are related to species richness via variation among genera in mean species-level range size. Lineages with higher mortality rates—faster life-history strategies—have larger ranges in all biogeographic settings and have higher mean species-level range sizes in Amazonia. These lineages also have smaller maximum diameters and, in the Americas, contain dioecious species. In turn, lineages with greater overall range size have higher species richness. Our results show that fast life-history strategies influence species richness in all biogeographic settings because lineages with these ecological strategies have greater range sizes. These links suggest that dispersal has been a key process in the evolution of the tropical forest flora.

Abstract Phase transitions in the mantle control its internal dynamics and structure. The post-spinel transition marks the upper–lower mantle boundary, where ringwoodite dissociates into bridgmanite plus ferropericlase, and its Clapeyron slope regulates mantle flow across it. This interaction has previously been assumed to have no lateral spatial variations, based on the assumption of a linear post-spinel boundary in pressure and temperature. Here we present laser-heated diamond anvil cell experiments with synchrotron X-ray diffraction to better constrain this boundary, especially at higher temperatures. Combining our data with results from the literature, and using a global analysis based on machine learning, we find a pronounced nonlinearity in the post-spinel boundary, with its slope ranging from –4 MPa/K at 2100 K, to –2 MPa/K at 1950 K, and to 0 MPa/K at 1600 K. Changes in temperature over time and space can therefore cause the post-spinel transition to have variable effects on mantle convection and the movement of subducting slabs and upwelling plumes.

Abstract Bacterial transcription activator-like effectors (TALEs) promote pathogenicity by activating host susceptibility (S) genes. To understand the pathogenicity and host adaptation of Xanthomonas citri pv. malvacearum (Xcm), we assemble the genome and the TALE repertoire of three recent Xcm Texas isolates. A newly evolved TALE, Tal7b, activates GhSWEET14a and GhSWEET14b, different from GhSWEET10 targeted by a TALE in an early Xcm isolate. Activation of GhSWEET14a and GhSWEET14b results in water-soaked lesions. Transcriptome profiling coupled with TALE-binding element prediction identify a pectin lyase gene as an additional Tal7b target, quantitatively contributing to Xcm virulence alongside GhSWEET14a/b. CRISPR-Cas9 gene editing supports the function of GhSWEETs in cotton bacterial blight and the promise of disrupting the TALE-binding site in S genes for disease management. Collectively, our findings elucidate the rapid evolution of TALEs in Xanthomonas field isolates and highlight the virulence mechanism wherein TALEs induce multiple S genes to promote pathogenicity.

Middle East respiratory syndrome coronavirus (MERS-CoV) circulates in dromedary camels in the Arabian Peninsula and occasionally causes spillover infections in humans. MERS-CoV diversity is poorly understood because of the lack of sampling during the COVID-19 pandemic. We collected 558 swab samples from dromedary camels in Saudi Arabia during November 2023–January 2024. We found 39% were positive for MERS-CoV RNA by reverse transcription PCR. We sequenced 42 MERS-CoVs and 7 human 229E-related coronaviruses from camel swab samples by using high-throughput sequencing. Sequences from both viruses formed monophyletic clades apical to recently available genomes. MERS-CoV sequences were most similar to B5 lineage sequences and harbored unique genetic features, including novel amino acid polymorphisms in the spike protein. Further characterization will be required to understand their effects. MERS-CoV spillover into humans poses considerable public health concerns. Our findings indicate surveillance and phenotypic studies are needed to identify and monitor MERS-CoV pandemic potential.

Using a prion amplification assay, we identified prions in tissues from wild pigs (Sus scrofa) living in areas of the United States with variable chronic wasting disease (CWD) epidemiology. Our findings indicate that scavenging swine could play a role in disseminating CWD and could therefore influence its epidemiology, geographic distribution, and interspecies spread.

Abstract: Activated protein C (APC) is a pleiotropic plasma protease with diverse functions derived from its anticoagulant, anti-inflammatory, and cytoprotective activities. The selective uncoupling and/or modulation of these APC activities by antibodies may have therapeutic benefit in diseases such as traumatic bleeding, hemophilia, sepsis, and ischemia. TPP-26870 is an antibody that targets a nonactive site of APC for the selective modulation of APC activities. To optimize the potency of TPP-26870, variants with single amino acid mutation in the complementarity-determining regions (CDRs) were screened, and 21 variants with improved affinity constant were identified. Interestingly, the affinity maturation of TPP-26870 did not merely generate a panel of variants with higher potency in functional assays. Functional data demonstrated that the pleiotropic functions of APC were very sensitive to epitope-CDR interactions. Single amino acid mutations within the CDRs of TPP-26870 were sufficient to elicit divergent antagonistic and agonistic effects on the various APC functional activities. These include prolonged in vitro APC plasma half-life, increased inhibition of anticoagulant activity, and agonistic enhancement of histone H3 cleavage, while having less impact on protease-activated receptor 1 cleavage, compared with TPP-26870. This study illustrates that APC is highly sensitive to non–active site targeting that can lead to unpredictable changes in its activity profile of this pleiotropic enzyme. Furthermore, this study demonstrates the ability to modify APC functions to advance the potential development of APC-targeted antibodies as therapeutics for the treatment of diseases including trauma bleeding, hemophilia, ischemia, and sepsis.

Abstract Shock waves, the interface of supersonic and subsonic plasma flows, are the primary region for charged particle acceleration in multiple space plasma systems, including Earth’s bow shock, which is readily accessible for in-situ measurements. Spacecraft frequently observe relativistic electron populations within this region, characterized by energy levels surpassing those of solar wind electrons by a factor of 10,000 or more. However, mechanisms of such strong acceleration remain elusive. Here we use observations of electrons with energies up to 200 kiloelectron volts and a data-constrained model to reproduce the observed power-law electron spectrum and demonstrate that the acceleration by more than 4 orders of magnitude is a compound process including a complex, multi-step interaction between more commonly known mechanisms and resonant scattering by several distinct plasma wave modes. The proposed model of electron acceleration addresses a decades-long issue of the generation of energetic (and relativistic) electrons at planetary plasma shocks. This work may further guide numerical simulations of even more effective electron acceleration in astrophysical shocks.

Lysine deacetylases (KDACs or HDACs) are metal‐dependent enzymes that regulate lysine acetylation, a post‐translational modification that is present on thousands of human proteins, essential for many cellular processes, and often misregulated in diseases. The selective inhibition of KDACs would allow for understanding of the biological roles of individual KDACs and therapeutic targeting of individual enzymes. Recent studies have suggested that purportedly specific KDAC inhibitors have significant off‐target binding, but the biological consequences of off‐target binding were not evaluated. We compared the effects of treatment with two of the reportedly most KDAC‐selective inhibitors, Tubastatin A and PCI‐34051, in HT1080 cells in which the endogenous KDAC6 or KDAC8 gene has been mutated to inactivate enzyme catalysis while retaining enzyme expression. Genetic inactivation results in much stronger deacetylation defects on known targets compared to inhibitor treatment. Gene expression analysis revealed that both inhibitors have extensive and extensively overlapping off‐target effects in cells, even at low inhibitor doses. Furthermore, Tubastatin A treatment led to increased histone acetylation, while inactivation of KDAC6 or KDAC8 did not. Genetic inactivation of KDAC6, but not KDAC8, impaired tumor formation in a xenograft model system, in contrast to previous reports with KDAC inhibitors suggesting the reverse. We conclude that the majority of observed biological effects of treatment with KDAC inhibitors are due to off‐target effects rather than the intended KDAC inhibition. Developing a truly specific KDAC6 inhibitor could be a promising therapeutic avenue, but it is imperative to develop new inhibitors that selectively mimic genetic inactivation of individual KDACs.

Abstract Background Glycogen storage disease (GSD) Ia is an ultra-rare inherited disorder of carbohydrate metabolism. Patients often present in the first months of life with fasting hypoketotic hypoglycemia and hepatomegaly. The diagnosis of GSD Ia relies on a combination of different biomarkers, mostly routine clinical chemical markers and subsequent genetic confirmation. However, a specific and reliable biomarker is lacking. As GSD Ia patients demonstrate altered lipid metabolism and mitochondrial fatty acid oxidation, we built a machine learning model to identify GSD Ia patients based on plasma acylcarnitine profiles. Methods We collected plasma acylcarnitine profiles from 3958 patients, of whom 31 have GSD Ia. Synthetic samples were generated to address the problem of class imbalance in the dataset. We built several machine learning models based on gradient-boosted trees. Our approach included hyperparameter tuning and feature selection and generalization was checked using both nested cross-validation and a held-out test set. Results The binary classifier was able to correctly identify 5/6 GSD Ia patients in a held-out test set without generating significant amounts of false positive results. The best model showed excellent performance with a mean received operator curve (ROC) AUC of 0.955 and precision-recall (PR) curve AUC of 0.674 in nested CV. Conclusions This study demonstrates an innovative approach to applying machine learning to ultra-rare diseases by accurately identifying GSD Ia patients based on plasma free carnitine and acylcarnitine concentrations, leveraging subtle acylcarnitine abnormalities. Acylcarnitine features that were strong predictors for GSD Ia include C16-carnitine, C14OH-carnitine, total carnitine and acetylcarnitine. The model demonstrated high sensitivity and specificity, with selected parameters that were not only robust but also highly interpretable. Our approach offers potential prospect for the inclusion of GSD Ia in newborn screening. Rare diseases are underrepresented in machine learning studies and this work highlights the potential for these techniques, even in ultra-rare diseases such as GSD Ia.

Abstract Background This study aimed to investigate which basic psychological needs profile, based on different levels of autonomy, competence, and relatedness, could exhibit higher student engagement and favorable attitudes toward interprofessional education (IPE). Methods A total of 341 undergraduate and postgraduate health and social care students enrolled in an IPE simulation participated in this study. Data were analyzed using a person-centered approach using a two-step cluster analysis, multiple analysis of variance, and bootstrapped independent t-tests. The participants completed the self-report scales such as the basic psychological needs in general questionnaire, interprofessional attitudes scale, and engagement versus disaffection with learning scale. Results Two basic psychological needs profiles emerged from the cluster analysis: a high basic psychological needs profile (i.e., high autonomy, moderately high competence, and very high relatedness) and a low basic psychological needs profile (i.e., low autonomy, moderately low competence, and very low relatedness). Students with high basic psychological needs profiles (n = 140; 41%) had more positive attitudes about IPE and were more behaviorally and emotionally engaged in participating in IPE tasks than students with low basic psychological needs profiles (n = 201; 59%). Conclusions Findings suggest that health and social care students’ engagement and attitudes toward interprofessional education differed based on their basic psychological needs profiles. Health professions educators can leverage students’ basic psychological needs in designing interventions and simulation activities to promote students’ engagement and collaborative outcomes in IPE. Enhancing students’ basic psychological needs could be crucial in fostering greater behavioral and emotional engagement and positive attitudes in participating in IPE.

Background: Optimum efficiency and responsiveness to callers of mental health helplines can only be achieved if call priority is accurately identified. Currently, call operators making a triage assessment rely heavily on their clinical judgment and experience. Due to the significant morbidity and mortality associated with mental illness, there is an urgent need to identify callers to helplines who have a high level of distress and need to be seen by a clinician who can offer interventions for treatment. This study delves into the potential of using machine learning (ML) to estimate call priority from the properties of the callers’ voices rather than evaluating the spoken words. Method: Phone callers’ speech is first isolated using existing APIs, then features or representations are extracted from the raw speech. These are then fed into a series of deep learning neural networks to classify priority level from the audio representation. Results: Development of a deep learning neural network architecture that instantly determines positive and negative levels in the input speech segments. A total of 459 call records from a mental health helpline were investigated. The final ML model achieved a balanced accuracy of 92% correct identification of both positive and negative instances of call priority. Conclusions: The priority level provides an estimate of voice quality in terms of positive or negative demeanor that can be simultaneously displayed using a web interface on a computer or smartphone.

Abstract Phytophthora blight caused by Phytophthora capsici is a serious disease affecting a wide range of plants. Biochar as a soil amendment could partially replace peat moss and has the potential to suppress plant diseases, but its effects on controlling phytophthora blight of container-grown peppers have less been explored, especially in combination of biological control using Trichoderma. In vitro (petri dish) and in vivo (greenhouse) studies were conducted to test sugarcane bagasse biochar (SBB) and mixed hardwood biochar (HB) controlling effects on pepper phytophthora blight disease with and without Trichoderma. Sugarcane bagasse biochar and HB were blended with the commercial substrate (CS, peat-based) at 10% (SBB10, by volume), and 10%, 30%, 50%, 70% (HB10, HB30, HB50, and HB70, by volume), respectively, and CS (CS100) was used as the control. Both in vitro and in vivo studies used randomized complete block design with three treatment factors: pathogen (without or with inoculation of P. capsici), biochar (different biochar treatments), and Trichoderma (without or with inoculation). In vitro results showed that Trichoderma inhibited P. capsici growth while biochar did not have significant beneficial effects. In vivo results showed that plants grown in HB30 and HB50 had similar or higher plant growth index and shoot dry weight than the control regardless of pathogen presence. In the presence of the pathogen, plants grown in HB30, HB50, and HB70 had significantly lower disease severity, and disease incidence ratings than the control, while Trichoderma did not show beneficial effects on controlling the disease. In conclusion, HB replacing 30% and 50% peat moss in substrate could reduce pepper blight disease caused by P. capsici without negatively affecting plant growth.

Abstract Sodium butyrate (NaBu), well-known as a histone deacetylase inhibitor and for its capacity to impede cell growth, can enhance the production of a specific protein, such as an antibody, in recombinant Chinese hamster ovary (CHO) cell cultures. In this study, two CHO cell lines, namely K1 and DG44, along with their corresponding mAb-producing lines, K1-Pr and DG44-Pr, were cultivated with or without NaBu. A SWATH-based profiling method was employed to analyze the proteome. Cells cultured in the presence of NaBu exhibited a reduction in mitosis and gene expression, supported by their culture data demonstrating growth inhibition. The presence of NaBu corresponded to upregulation of intracellular trafficking and secretion pathways, aligned with an observed increase in mAb production, and was associated with an elevated glycosylation pathway and a slight alteration in the glycosylation profile of the mAbs. Increased fatty acid oxidation, redox interactions, and lipid biosynthesis were also observed and are likely attributable to the metabolism of NaBu. A comprehensive understanding of the systemic effects of NaBu will facilitate the discovery of strategies to enhance or prolong the productivity of CHO cells. Graphical Abstract

Abstract Objectives The objective of this study is to compare the early oncological outcomes of delayed (>90 days) versus scheduled (≤90 days) radical prostatectomy (RP). Patients and methods Patients with prostate cancer due to undergo surgery between March 2020 and June 2020 who were enrolled in the COVIDSurg‐Cancer international, observational study were prospectively followed up for 1 year. Time to surgery was defined as the difference between the operation date and the multi‐disciplinary team decision to offer surgery. The primary outcome was the positive surgical margin (PSM) rate. Biochemical recurrence (BCR), upgradation and upstaging were secondary oncological outcomes. The Independent t‐test and Mann Whitney U test were used to compare means between groups and regression models and were used to investigate factors associated with the primary outcome. Results Four hundred seventy‐six (78.7%) patients underwent RP from 605 that were eligible. Three hundred seven (64.5%) patients underwent scheduled RP, and 169 (35.5%) underwent delayed RP. A small proportion of men (n = 35, 6.8%) did not undergo RP within the 1‐year follow‐up period. More men with high‐risk disease (72.8%) underwent scheduled RP compared to men with intermediate‐risk disease (60.2%) (p

Abstract Background Some children and young people (CYP) infected with SARS-COV-2 experience impairing symptoms post-infection, known as post-COVID-19 condition (PCC). Using data from the National Long COVID in Children and Young People (CloCk) study, we report symptoms and their impact up to 24-months post-infection. Methods CloCk is a cohort of CYP in England aged 11-to-17-years when they had a SARS-CoV-2 PCR-test (between September 2020 and March 2021). Of 31,012 eligible CYP 24-months post-PCR test, 12,632 participated (response = 40.7%). CYP were grouped by infection status: ‘initial test-negatives; no subsequent positive-test’ (NN); ‘initial test-negatives; subsequent positive-test’ (NP); ‘initial test-positives; no reported re-infection’ (PN); and ‘initial test-positives; reported re-infection’ (PP). The Delphi research definition of PCC in CYP was operationalised; symptom severity/impact and validated scales (e.g., Chalder Fatigue Scale) were recorded. We examine symptom profiles 24-month post-index-test by infection status. Results 7.2% of CYP consistently fulfil the PCC definition at 3-, 6-, 12- and 24-months. These CYPs have a median of 5-to-6 symptoms at each time-point. Between 20% and 25% of all infection status groups report 3+ symptoms 24-months post-testing; 10–25% experience 5+ symptoms. The reinfected group has more symptoms than the other positive groups; the NN group has the lowest symptom burden (p

ABSTRACT Objectives Understanding the patterns and implications of coexisting musculoskeletal conditions is crucial for developing effective management strategies and improving care for older adults. This study aimed to examine the associations between musculoskeletal multimorbidity burden and trajectory and holistic well‐being among middle‐aged and older adults. Methods This prospective study employed data from nine consecutive waves of the English Longitudinal Study of Aging (ELSA), spanning 2002–2018. We used latent class trajectory models (LCTM) to identify groups based on changes in musculoskeletal multimorbidity status. Subsequently, we employed linear mixed models to investigate the associations between musculoskeletal disease burden, trajectory groups, and seven dimensions of holistic well‐being: Activities of Daily Living (ADLs), Instrumental Activities of Daily Living (IADLs), depression, memory, loneliness, social interactions, and life satisfaction. Results In total, 5272 participants (mean age: 71.9 years; SD: 8.9) were included in the final analysis. Four distinct trajectories were identified: a low‐burden group (48.37%), an emerging group (14.76%), a moderate‐burden group (26.00%), and a persistent burden group (10.87%). After adjustment, the findings demonstrate that the musculoskeletal disorder burden significantly impacts ADLs, depression, memory, social interactions, and life satisfaction in middle‐aged and older adults, with minor effects on IADLs and loneliness. Moreover, with the escalation of the burden, its impact significantly intensifies (p for trend is

N-glycosylation can have a profound effect on the quality of mAb therapeutics. In biomanufacturing, one of the ways to influence N-glycosylation patterns is by altering the media used to grow mAb cell expression systems. Here, we explore the potential of machine learning (ML) to forecast the abundances of N-glycan types based on variables related to the growth media. The ML models exploit a dataset consisting of detailed glycomic characterisation of Anti-HER fed-batch bioreactor cell cultures measured daily under 12 different culture conditions, such as changes in levels of dissolved oxygen, pH, temperature, and the use of two different commercially available media. By performing spent media quantitation and subsequent calculation of pseudo cell consumption rates (termed media markers) as inputs to the ML model, we were able to demonstrate a small subset of media markers (18 selected out of 167 mass spectrometry peaks) in a Chinese Hamster Ovary (CHO) cell cultures are important to model N-glycan relative abundances (Regression - correlations between 0.80–0.92; Classification - AUC between 75.0–97.2). The performances suggest the ML models can infer N-glycan critical quality attributes from extracellular media as a proxy. Given its accuracy, we envisage its potential applications in biomaufactucuring, especially in areas of process development, downstream and upstream bioprocessing.

Abstract Background Most Canadians receive their care in community hospitals, yet most clinical research is conducted in academic hospitals. This study aims to compare patients with community acquired pneumonia (CAP) treated in academic and community hospitals with respect to their demographics, clinical characteristics, treatments and outcomes. Methods This nested observational cohort substudy of the Community Acquired Pneumonia: Toward InnoVAtive Treatment (CAPTIVATE) trial included 1,329 hospitalized adults with CAP recruited between March 1st, 2018 and September 31st, 2023 from 15 Canadian hospitals. Unadjusted and adjusted analyses for age, sex and co-morbidities using logistic, Cox and censored quantile regressions were conducted. Results Patients in community hospitals were older (mean [SD] 75.0 [15.7] years vs. 68.3 [16.2] years; p

Abstract Background Understanding environmental correlates of sedentary behaviour (SB) among young people is important as such data can identify approaches to limit sedentary time. This paper estimates associations of parent-reported neighbourhood and adolescent-reported home environments with SB among adolescents aged 11–19 years from 14 countries. Methods In the International Physical activity and the Environment Network (IPEN) Adolescent Study (an observational, cross-sectional multi-country study), adolescents wore a triaxial accelerometer for seven days that assessed sedentary time (ST). Adolescents completed survey measures of sedentary behaviour (SB) related to recreational screen time and sitting time in motor vehicles. Parents and adolescents completed surveys assessing neighbourhood and home environments. Accelerometer based ST was available in 3,982 adolescents while survey data were available for 6,302 dyads. We estimated the total and direct effects of each environmental attribute on ST and SB. Sex of the adolescent and city/country were examined as moderators. Results The average ST in adolescents from 14 countries ranged from 7.8 to 10.5 h/day. Personal social media was the only significant correlate of total ST across both sexes. With respect to self-reported SB, adolescents accumulated an average of 3.8 h of non-school screen time per day and nearly 40 min of transport-related sitting time. Screen time was associated with all home environment variables, including social media account, as well as land use mix—diversity, traffic safety, and crime safety. Transport-related sitting time was related to land use mix—diversity, recreation facilities, walking facilities, and pedestrian infrastructure, but no home environment variables. City/country and sex were significant moderators of several associations. Conclusions Both home and neighbourhood environment features were related to ST and SB. Having social media accounts emerged as a major contributor towards sedentarism in adolescents.

Background: Metastatic gastroenteropancreatic neuroendocrine neoplasms (GEPNEN) can cause ectopic Cushing’s syndrome (ECS). ECS is highly morbid and medical therapy is complex and can be ineffective. Patients unsuitable for bilateral adrenalectomy (BA) have dismal outcomes. Peptide receptor radionuclide therapy (PRRT) is a rational option for hormone and disease control in ECS caused by NEN with high somatostatin receptor (SSTR) expression. Aim: To describe the characteristics and outcomes of patients with ECS treated with PRRT. Methods: Single-centre, retrospective analysis of imaging, biochemistry and outcomes of seven consecutive patients with ECS caused by metastatic GEPNEN treated with PRRT from 2006 to 2023. Results: Patients were aged 17–75 (female n = 6). The primary site was the pancreas (5/7) and rectum (2/7). Six patients were on medical therapy for ECS at baseline (one had a previous BA). A median of 34.4 GBq of [177Lu]Lu-DOTA-octreotate was given. [90Y]Y-DOTA-octreotate (one patient) and [111In]In-octreotide (one patient) were also used. Five patients had radiosensitising chemotherapy. Five patients had a flare of ECS within 1 week of PRRT cycle 1 (PRRT-C1). Following PRRT-C1, 5/7 patients had complete biochemical resolution of ECS at 1.5–6 months (four ongoing; one recurred after 12 months and had elective BA at 18 months). Best metabolic response on [18F]F-FDG PET/CT: Four patients had a complete metabolic response (CMR), and one had a partial metabolic response. PFS was 3–208 months. Two patients progressed at the first follow-up. The longest ECS remission and CMR continues at >17 years. Conclusion: PRRT can be effective for ECS caused by metastatic SSTR-positive GEPNEN and should be considered in its treatment algorithm.

Abstract Background Reliability of echocardiographic calculations for stroke volume and mitral regurgitant fraction (RFMR) are affected by observer variability and lack of a gold standard. Variability is used to calculate critical change values (CCVs) that are thresholds representing real change in a measure not associated with observer variability. Hypothesis Observed intra‐ and interobserver accuracy and variability in healthy dogs help model CCV for RFMR. Animals Reliability cohort of 34 healthy dogs; allometric scaling cohort of 99 dogs with heart disease and 25 healthy dogs. Methods Accuracy, variability, and CCV of 2 observers using geometric and flow‐based echocardiography were prospectively compared against a standard of RFMR = 0% and extrapolated across a range of expected RFMR values in the reliability cohort partly derived from cardiac dimensions predicted by the allometric cohort. Results Accuracy of methods to determine RFMR in descending order was 4‐chamber bullet (Bullet4CH), mitral inflow, cube formula, and Simpson's method of disks. Intraobserver variability was relatively high. The CCV for RFMR ranged from 28% to 88% and was inversely related to RFMR when extrapolated for use in affected dogs. For both observers, the Bullet4CH method had the lowest intraobserver CCV (Operator 1:28%, Operator 2:41%). Interobserver strength of agreement was low with intraclass correlation coefficients ranging from 0.210 to 0.413. Conclusions and Clinical Importance Echocardiographic volumetric methods used to calculate stroke volume and RFMR have low accuracy and high variability in healthy dogs. Extrapolation of observed CCV to a range of expected RFMR suggests observers and methods are not interchangeable and variability might hinder routine clinical usage. Individual observers should be aware of their own variability and CCV.

Abstract This case study examined how the Kingdom of Saudi Arabia (KSA) managed the 2018 Hajj season, one of the largest worldwide gatherings, to identify prominent communication strategies utilised in a large event. The two-way symmetrical communication and the renewal discourse theory served as theoretical frameworks. A thematic analysis was utilised to analyse communication content, news articles, and tweets. It is almost impossible to know whether the KSA intentionally applied Grunig’s two-way symmetrical communications theory; nevertheless, the results suggested that KSA operated in a way that followed Grunig’s theory. The findings showed how the KSA learned from past mistakes and incorporated Grunig’s two-way symmetrical communication model to implement best public relations practices for a successful 2018 Hajj season. This case study provided various perspectives on how employing communication strategies can help manage a significant event successfully.

Abstract Background Depression is among the leading causes of the global burden of disease and is associated with substantial morbidity in old age. The importance of providing timely intervention, particularly those with subclinical symptoms, has thus increasingly been emphasised. Despite their overall effectiveness, a small but notable subgroup tends to be less responsive to interventions. Identifying predictors of non-remission and non-response is critical to inform future strategies for optimising intervention outcomes. Methods A total of 4153 older adults aged 60 years and above with subclinical depressive symptoms (Patient Health Questionnaire-9 [PHQ-9] = 5–19) were recruited from JC JoyAge, a large-scale collaborative stepped-care intervention service across Hong Kong. A wide range of clinical and modifiable risk and protective factors at baseline were assessed, including depressive symptoms, anxiety symptoms, loneliness, suicidal ideation, cognitive capacity, multimorbidity, chronic pain, need for informal care due to mental health reasons, history of abuse, and sociodemographic characteristics. Separate multivariable logistic regression models were applied to identify predictors of non-remission (PHQ-9 ≥ 5) and non-response (

Abstract Neuromodulation by vagus nerve stimulation (VNS) provides therapeutic benefits in multiple medical conditions, including epilepsy and clinical depression, but underlying mechanisms of action are not well understood. Cervical vagus nerve biopsies were procured from transplant organ donors for high resolution light microscopy (LM) and transmission electron microscopy (TEM) to map the human fascicular and sub-fascicular organization. Cervical vagal segments show laterality with right sided dominance in fascicle numbers and cross-sectional areas as well as sexual dimorphism with female dominance in fascicle numbers. The novel and unprecedented detection of numerous small fascicles by high resolution LM and TEM expand the known fascicle size range and morphological diversity of the human vagus nerve. Ground truth TEM quantification of all myelinated and unmyelinated axons within individual nerve fascicles show marked sub-fascicular heterogeneity of nerve fiber numbers, size, and myelination. A heuristic action potential interpreter (HAPI) tool predicts VNS-evoked compound nerve action potentials (CNAPs) generated by myelinated and unmyelinated nerve fibers and validates functional dissimilarity between fascicles. Our findings of laterality, sexual dimorphism, and an expanded range of fascicle size heterogeneity provide mechanistic insights into the varied therapeutic responses and off-target effects to VNS and may guide new refinement strategies for neuromodulation.

The US Food and Drug Administration recognizes the unmet medical need for antibacterial drugs to treat serious bacterial diseases caused by resistant pathogens for which effective therapies are limited or lacking. The agency also recognizes that designing and conducting clinical trials to assess the safety and efficacy of drugs to treat resistant infections is challenging, especially for drugs only active against a single or a few bacterial species, and that a more flexible development program might be appropriate. In this article, we discuss several regulatory considerations for flexible development programs for antibacterial drugs intended to meet an unmet medical need. As an example, we use the recent approval of sulbactam for injection and durlobactam for injection (XACDURO) for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia caused by susceptible isolates of Acinetobacter baumannii-calcoaceticus complex.

Abstract Objective The objective of this study was to report the 12‐month oncological outcomes for patients with non‐muscle‐invasive bladder cancer (NMIBC) within the prospective, international COVIDSurg Cancer study. Patients and methods Eligible patients were aged ≥18 years and scheduled for elective surgical management of NMIBC with curative intent (transurethral resection of bladder tumour [TURBT] or bladder biopsy) from 21 January to 14 April 2020. The primary outcome was disease recurrence within 12 months of previous elective TURBT/bladder biopsy. Secondary outcomes included disease progression within 12 months of previous elective TURBT/bladder biopsy, site‐declared delay to surgery from diagnosis as a consequence of COVID‐19 and deviation in standard care due to COVID‐19. Comparisons were made to cohorts from the pre‐pandemic era. Results Bladder cancer accounted for 2.2% (n = 446) of patients in the COVIDSurg Cancer study, with data contributed by 27 centres across 12 countries internationally. Within this included cohort, 229 patients had NMIBC and 12‐month follow‐up data available. On application of National Institute for Health and Care Excellence (NICE) criteria, 47.2% were classified as having high‐risk disease. Overall disease recurrence and progression rates were 29.3% and 9.7% at 12 months, respectively. In purely high‐risk pre‐pandemic cohorts, the International Bladder Cancer Group (IBCG) estimates a recurrence rate of 25% at 12 months, and the European Association of Urology (EAU) NMIBC 2021 scoring model estimates a 12‐month progression rate of 3.5%. As a consequence of the COVID‐19 pandemic, 10.9% of patients had site‐declared delay to TURBT/bladder biopsy; 7.4% did not undergo intravesical therapy or had early discontinuation of this; 9.2% did not undergo early repeat resection for high‐risk disease; and 18.3% had a delay to cystoscopic follow‐up surveillance. Conclusions This prospective study indicates that there were widespread deviations in usual care for NMIBC during the pandemic and that 12‐month oncological outcomes appear to be impaired compared to published pre‐pandemic outcomes.

Abstract Doberman Pinschers are known for their increased susceptibility to dilated cardiomyopathy (DCM) relative to other domestic dogs. This makes the Doberman Pinscher a key model for gene-disease investigations. We conducted a genome-wide association study (GWAS) leveraging a database of genetic profiles obtained through collaboration with the Doberman Diversity Project (DDP). We worked in parallel to increase the depth and power of the DDP database. We exchanged direct correspondences with listed breeders and owners to establish health updates for participant dogs. In total, our study included data on 216, 184 single nucleotide polymorphisms (SNPs) in 46 cases and 3226 population control Doberman Pinschers. Using a generalized linear mixed model and saddlepoint approximation to correct for unbalanced group sizes, we identified a cluster of SNPs associated with DCM on chromosome 16.

Abstract The species-specific character of sounds in the animal kingdom has been extensively documented, yet research on fishes has predominantly focused on a limited number of species, overlooking the potential of acoustic signals to reflect broader taxonomic ranks. In this study, we analyzed acoustic data of hand-held sounds from 388 specimens spanning 5 genera and 33 species within the family Holocentridae, with the objective of evaluating the use of sound characteristics for taxonomic discrimination across various levels (subfamily, genus, species). Sounds could be indicative of grouping. Taxa discriminability depends on taxonomic level; the higher the taxonomic level, the better the discrimination of taxa based on sounds. Analogous to the role of morphological traits in taxonomic delineation, this research corroborates the utility of acoustic features in identifying fish taxa across multiple hierarchical levels. Remarkably, certain holocentrid species have evolved complex sound patterns characterized by unique temporal arrangements where pulses are not continuous but emitted in blocks, facilitating the exploitation of the acoustic space.

Abstract Fasting hypoglycemia is a severe and incompletely understood symptom of various inborn errors of metabolism (IEM). Precision-cut liver slices (PCLS) represent a promising model for studying glucose production ex vivo. This study quantified the net glucose production of human and murine PCLS in the presence of different gluconeogenic precursors. Dihydroxyacetone-supplemented slices from the fed mice yielded the highest rate, further stimulated by forskolin and dibutyryl-cAMP. Moreover, using 13C isotope tracing, we assessed the contribution of glycogenolysis and gluconeogenesis to net glucose production over time. Pharmacological inhibition of the glucose 6-phosphate transporter SLC37A4 markedly reduced net glucose production and increased lactate secretion and glycogen storage, while glucose production was completely abolished in PCLS from glycogen storage disease type Ia and Ib patients. In conclusion, this study identifies PCLS as an effective ex vivo model to study hepatic glucose production and opens opportunities for its future application in IEM research and beyond.

Abstract Motile cilia are critical structures that regulate early embryonic development and tissue homeostasis through synchronized ciliary motility. The formation of motile cilia is dependent on precisely controlled sequential processes including the generation, migration, and docking of centrioles/basal bodies as well as ciliary growth. Using the published proteomics data from various organisms, we identified proliferation-associated 2G4 as a novel regulator of ciliogenesis. Loss-of-function studies using Xenopus laevis as a model system reveal that Pa2G4 is essential for proper ciliogenesis and synchronized movement of cilia in multiciliated cells (MCCs) and the gastrocoel roof plate (GRP). Pa2G4 morphant MCCs exhibit defective basal body docking to the surface as a result of compromised Rac1 activity, apical actin network formation, and immature distal appendage generation. Interestingly, the regions that include the RNA-binding domain and the C-terminus of Pa2G4 are necessary for ciliogenesis in both MCCs and GRP cells. Our findings may provide insights into motile cilia-related genetic diseases such as Primary Ciliary Dyskinesia.

Abstract Introduction The ACCESS trial showed that those who received a copayment elimination benefit had a modest improvement in their adherence to medications, but no improvement in clinical outcomes. This is consistent with other studies that have demonstrated that time-limited copayment elimination was welcomed by participants. However, the removal of such benefits can be problematic, as participants may have become accustomed to receiving the benefit, and made changes to their spending that would need to be reconsidered. We aimed to explore participants’ experience with resuming cost sharing for their medications at the end of the ACCESS trial and if this experience influenced their willingness to participate in future trials like ACCESS. Methods We conducted semi-structured interviews with 21 former participants of the ACCESS trial who were receiving the copayment elimination intervention, with discussions focused on the loss of the copayment elimination. The interviews were recorded, transcribed, and analyzed in duplicate using thematic analysis. Results Four primary themes emerged from the analysis, including emotionality regarding loss of benefits; notification of benefit termination, describing tangible losses from coverage ending, but resistance to acknowledging negative impacts; and acceptability of receiving a temporary financial benefit. Many participants described negative emotions around the loss of coverage and concern about affording care for their chronic diseases. Despite negative emotions about the end of their study benefit, participants generally had a positive view of the study and would participate again in a future study of this nature. Conclusion The positive tangible and emotional benefits of the copayment elimination over 3 years outweighed the negative emotions and impacts associated with having to become reaccustomed to life without it. Patient and public contribution Within the ACCESS trial, participants were involved in the design, modification, and implementation of the program using multiple focus groups. The current study aimed to engage patients to provide input on their experience and engagement with the copayment elimination program.

Background/Objectives: Rehabilitation helps reduce disability in dementia. The Australian National Dementia Action Plan identifies a gap in clear treatment pathways post-diagnosis, affecting the quality of life for those with dementia. This study assessed the impact of a one-day dementia training course and follow-up on GPs’ and practice nurses’ knowledge, attitudes, and confidence regarding dementia rehabilitation. Methods: The training, led by two experienced GPs and an academic physiotherapist, covered dementia diagnosis, allied health roles, care planning, and referrals. The follow-up involved applying the learnt material and completing a reflective task. Three longitudinal surveys (Dementia Knowledge Assessment Scale—DKAS, General Practitioners’ Attitudes and Confidence towards Dementia Survey—GPACS-D, and Dementia Rehabilitation Scale) and Likert-scale statements were conducted pre-course, post-course, and at four-month follow-up, alongside a focus group. Descriptive and regression analyses were applied to survey data, and content analysis was used for focus group data. Results: Seventeen participants (14 GPs, 3 nurses) completed the pre–post-course survey, with eight (6 GPs, 2 nurses) participating in follow-up and focus group discussions. Post-course, DKAS scores increased by 12.1%, GPACS-D by 10.1%, and the dementia rehabilitation scale by 9.4%. Likert-scale statements improved by 8–79%. At the four-month follow-up, there was a slight, non-significant decline in most measures. Focus groups highlighted the training’s impacts, useful components, barriers, and suggestions for improvement. Conclusion: Training GPs and practice nurses in dementia rehabilitation enhances knowledge, awareness, and confidence. Ongoing efforts are needed to sustain benefits and address referral barriers for better access to dementia rehabilitation services.

The purpose of the study is to investigate the notion of Necessity-driven Entrepreneurs (NDEs) and Opportunity-driven Entrepreneurs (ODEs) among IME (Immigrant Micro Enterprise) owners in the hospitality industry and how changes in motivational traits influence business practices, innovation, and growth aspirations. In many geographical contexts, the ever-challenging hospitality industry is dominated by businesses that are immigrant-owned and of micro sizes that experience additional challenges compared to their native and large counterparts. Through qualitative research and interviews with 18 owners of restaurants and eateries in the IME category in eastern Norway, the study found that while NDE traits are dominant during start-ups, ODE traits also exist, revealing a dynamic relationship between the two and thus problematic to classify hospitality IMEs as either NDE or ODE. Experiences and close customer interactions rather than formal R&D activities inspire changes and innovations in business practices, growth aspirations, and perceptions of success. This study offers new insights into hospitality IME owners’ motivations and goals, which may be relevant in other similar industries and geographical contexts. It underscores the importance of understanding the interplay of NDE and ODE traits among IME owners and their impact on business success in the challenging industry in which they operate.

Abstract Background Point-of-care ultrasound (POCUS) has emerged as an essential bedside tool for clinicians, but lack of access to ultrasound equipment has been a top barrier to POCUS use. Recently, several handheld ultrasound devices (“handhelds”) have become available, and clinicians are seeking data to guide purchasing decisions. Few comparative studies of different handhelds have been done. We conducted a cross-sectional study comparing 6 handhelds readily available in the United States (Butterfly iQ + ™ by Butterfly Network Inc.; Clarius™ by Clarius Mobile Health; Kosmos™ by EchoNous; TE Air™ by Mindray; Vscan Air™ SL and CL by General Electric; and Lumify™ by Philips Healthcare). A multi-specialty group of physician POCUS experts (n = 35) acquired three standard ultrasound views (abdominal right upper quadrant, cardiac apical 4-chamber, and superficial neck and lung views) in random order on the same standardized patients and rated the image quality. Afterward, a final survey of the overall ease of use, image quality, and satisfaction of each handheld was completed. Results Thirty-five POCUS experts specializing in internal medicine/hospital medicine, critical care, emergency medicine, and nephrology acquired and rated right upper quadrant, apical 4-chamber, and superficial neck and lung views with 6 different handhelds. For image quality, the highest-rated handhelds were Vscan Air™ for the right upper quadrant view, Mindray TE Air™ for the cardiac apical 4-chamber view, and Lumify™ for superficial views of the neck and lung. Overall satisfaction with image quality was highest with Vscan Air™, Lumify™, and Mindray, while overall satisfaction with ease of use was highest with Vscan Air™. The 5 most desirable characteristics of handhelds were image quality, ease of use, portability, probe size, and battery life. Ultimately, all 6 handhelds had notable advantages and disadvantages, with no single device having all desired qualities or features. Conclusions The overall satisfaction with image quality was rated highest with Vscan Air™, Lumify™, and Mindray TE Air™when acquiring right upper quadrant, apical 4-chamber, and superficial neck and lung views. No single handheld was perceived to be superior in image quality for all views. Vscan Air™ was rated highest for overall ease of use and was the most preferred handheld for purchase by POCUS experts.

Abstract This report describes the development and characterization of a comprehensive collection of CHO cell glycosylation mutants with significant potential for advancing glycobiology and biotechnology. EPO-Fc and trastuzumab, two model molecules, were produced using these mutants to assess the effects of mutated glycogenes, and LC-MS/MS analysis was employed to quantitatively analyse their N-glycans. EPO-Fc exhibited exclusively homogeneous Man9 glycans only when nearly all α-mannosidases in the genome were inactivated, except lysosomal MAN2B1. Some mutants lacking GnT-I activity produce mostly Man5 N-glycans, while their O-glycan and glycolipid profiles can differ due to other mutations in the cell. GnT-II deficiency prevents GnT-V from adding GlcNAc to the core N-glycan, resulting in branches attaching solely to the α1,3-linked mannose, leaving the α1,6-linked mannose free. The mutant-produced antibody’s single-branched glycan contains more sialic acid than the dual-branched glycans produced in CHO-K1 cells. Trastuzumab produced in these mutants provided insights into how Fc N-glycans impact the antibody’s interaction with FcγR1 and FcγR2a, FcγR3a, and their influence on antibody-dependent cellular cytotoxicity (ADCC). In the study of Fc glycans in Fc-FcγR1 and FcγR2a interactions, we observed a consistent glycan-related impact on binding to both receptors, indicating a common interaction mechanism between Fc glycans and both FcγRI and FcγRIIa. CHO mutants produced trimeric gp120 demonstrated distinct reactivity with multiple broadly neutralizing anti-HIV antibodies, confirming the involvement of gp120 glycans in interactions with specific broadly neutralizing antibodies. Finally, one of the mutants produced human β-glucocerebrosidase with uniform Man5 N-glycans, showcasing its potential for glycoengineered production and enhancement in therapeutic efficacy.

Abstract We describe the geographical variation in tree species composition across Amazonian forests and show how environmental conditions are associated with species turnover. Our analyses are based on 2023 forest inventory plots (1 ha) that provide abundance data for a total of 5188 tree species. Within-plot species composition reflected both local environmental conditions (especially soil nutrients and hydrology) and geographical regions. A broader-scale view of species turnover was obtained by interpolating the relative tree species abundances over Amazonia into 47,441 0.1-degree grid cells. Two main dimensions of spatial change in tree species composition were identified. The first was a gradient between western Amazonia at the Andean forelands (with young geology and relatively nutrient-rich soils) and central–eastern Amazonia associated with the Guiana and Brazilian Shields (with more ancient geology and poor soils). The second gradient was between the wet forests of the northwest and the drier forests in southern Amazonia. Isolines linking cells of similar composition crossed major Amazonian rivers, suggesting that tree species distributions are not limited by rivers. Even though some areas of relatively sharp species turnover were identified, mostly the tree species composition changed gradually over large extents, which does not support delimiting clear discrete biogeographic regions within Amazonia.

The presence of fog in offshore regions poses significant hazards to navigation and aviation, making fog nowcasting indispensable for various industries, including oil and gas. This study presented a novel approach utilizing Recurrent Neural Networks (RNN) within a deep learning framework to address this need. Leveraging geostationary GOES-16 satellite data from the summers of 2018 and 2019, fog maps were generated as input. The model incorporated Convolutional Long Short-Term Memory (ConvLSTM) layers and was trained with a unique loss function combining Minimum Squared Error (MSE) and structural DISSIMilarity (DSSIM) metrics. Validation results demonstrated an approximate 60% accuracy for both two-hour and three-hour nowcasting. Furthermore, evaluation against in-situ data from an offshore platform revealed a Probability of Detection (PoD) of 0.75 and False Alarm Rate (FAR) of 0.14 for two-hour nowcasting, PoD of 0.75 and FAR of 0.20 for three-hour nowcasting, and PoD of 0.70 and FAR of 0.20 for six-hour nowcasting. These findings suggested the operational viability of the proposed method for short-term fog forecasting in offshore environments.

Abstract Background Subway systems are becoming increasingly common worldwide transporting large populations in major cities. PM2.5 concentrations have been demonstrated to be exceptionally high when underground, however. Studies on the impact of subway PM exposure on cardiopulmonary health in the United States are limited. Methods Healthy volunteers in New York City were exposed to a 2-h visit on the 9th Street Station platform on the Port Authority Trans-Hudson train system. Blood pressure, heart rate variability (HRV), spirometry, and forced impulse oscillometry were measured, and urine, blood spot, and nasal swab biosamples were collected for cytokine analysis at the end of the 2-h exposure period. These endpoints were compared against individual control measurements collected after 2-h in a “clean” control space. In addition to paired comparisons, mixed effects models with subject as a random effect were employed to investigate the effect of the PM2.5 concentrations and visit type (i.e., subway vs. control). Results Mean PM2.5 concentrations on the platform and during the control visit were 293.6 ± 65.7 (SD) and 4.6 ± 1.9 µg/m3, respectively. There was no change in any of the health metrics, but there was a non-significant trend for SDNN to be lower after subway exposure compared to control exposure. Total symptomatic scores did increase post-subway exposure compared to reported values prior to exposure or after the control visit. No significant changes in cytokine concentrations in any specimen type were observed. Mixed-effects models mostly corroborated these paired comparisons. Conclusions Acute exposures to PM on a subway platform do not cause measurable cardiopulmonary effects apart from reductions in HRV and increases in symptoms in healthy volunteers. These findings match other studies that found little to no changes in lung function and blood pressure after exposure in underground subway stations. Future work should still target potentially more vulnerable populations, such as individuals with asthma or those who spend increased time underground on the subway such as transit workers.

Abstract The anti-stigma Opening Minds initiative (Mental Health Commission of Canada) identified the workplace as one of four critical areas for stigma evaluation and programming. Researchers found, however, that no validated tool to measure stigma in this context existed at the time. The purpose of the current research was to develop and assess the psychometric properties of a multi-component quantitative measure of public stigma towards mental illnesses in the workplace: Opening Minds Scale for Workplace Attitudes (OMS-WA). Three studies are discussed. Study 1 outlines the initial development of the OMS-WA, finding a five-factor structure with 23 items (EFA analysis; N = 207). Study 2 utilized employees from various businesses to further validate the OMS-WA, (N = 107), finding good internal consistency and good convergent/divergent validity. Study 3 utilized baseline data from two national large-scale stigma reduction and resiliency programs (first responders and general workplaces) to confirm the factor structure, finding good model fit and reliability with both samples (N = 5385; N = 1207). Together, these results provide strong evidence of the OMS-WA. Its use in measuring workplace stigma related to mental illness is recommended. Considerable future evaluation is warranted, and directions for generalizability studies, as well as suggestions for using the OMS-WA in intervention trials, are provided.

Abstract Phenotypes play a fundamental role in medical genetics, serving as external manifestations of underlying genotypes. Deep phenotyping, a cornerstone of precision medicine, involves precise multi-system phenotype assessments, facilitating disease subtyping and genetic understanding. Despite their significance, the field lacks standardized protocols for accurate phenotype evaluation, hindering clinical comprehension and research comparability. We present a comprehensive workflow of deep phenotyping for rare bone diseases from the Genetics Clinic of Skeletal Deformity at Peking Union Medical College Hospital. Our workflow integrates referral, informed consent, and detailed phenotype evaluation through HPO standards, capturing nuanced phenotypic characteristics using clinical examinations, questionnaires, and multimedia documentation. Genetic testing and counseling follow, based on deep phenotyping results, ensuring personalized interventions. Multidisciplinary team consultations facilitate comprehensive patient care and clinical guideline development. Regular follow-up visits emphasize dynamic phenotype reassessment, ensuring treatment strategies remain responsive to evolving patient needs. In conclusion, this study highlights the importance of deep phenotyping in rare bone diseases, offering a standardized framework for phenotype evaluation, genetic analysis, and multidisciplinary intervention. By enhancing clinical care and research outcomes, this approach contributes to the advancement of precision medicine in the field of medical genetics.