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Abstract Automated writing evaluation (AWE) software has received much attention by researchers and practitioners as it has the potential of reducing the time necessary for providing second language (L2) students with written corrective feedback on their writing. While more practitioners are taking advantage of AWE affordances, research has indicated students engaged in untimed writing may still possess reservations about its usefulness as a feedback provider compared to that of L2 writing teachers. As trust affects student writer behavior, it is important to understand how the potential relationship between trust and writing outcomes are related to the source of writing feedback. This is especially important in contexts in which high stakes timed writing is the most frequent type of writing that L2 writers find themselves engaging in. Using a quasi-experimental design, we addressed these issues by examining the effects that perceived feedback source had on two groups of high-intermediate second language writers (n = 61 perceived teacher feedback group; n = 60 perceived AWE feedback group) enrolled in academic reading and writing courses in Northern Taiwan. Both groups received the same type of instruction and feedback for 18 weeks with the only caveat of perceiving the feedback source as coming from only the teacher or the AWE software. Results showed that the perceived AWE feedback group significantly outperformed the perceived teacher feedback group in their L2 writing by the end of the course. In addition, the perceived AWE feedback group put more trust in feedback on grammar rules and lexical choices than the perceived teacher feedback group. This indicates that high-intermediate L2 writers may trust AWE software more for specific types of feedback, such as those related to grammar and vocabulary. These and other results suggest decisions on providing AWE or teacher feedback should be made based on error type.

The tropism of adenoviruses (Ads) is significantly influenced by the binding of various blood factors. To investigate differences in their binding, we conducted cryo-EM analysis on complexes of several human adenoviruses with human platelet factor-4 (PF4), coagulation factors FII (Prothrombin), and FX. While we observed EM densities for FII and FX bound to all the species-C adenoviruses examined, no densities were seen for PF4, even though PF4 can co-pellet with various Ads. Similar to FX, the γ-carboxyglutamic acid (Gla) domain of FII binds within the surface cavity of hexon trimers. While FII binds equally to species-C Ads: Ad5, Ad6, and Ad657, FX exhibits significantly better binding to Ad5 and Ad657 compared to Ad6. Although only the FX-Gla domain is observed at high-resolution (3.7 Å), the entire FX is visible at low-resolution bound to Ad5 in three equivalent binding modes consistent with the 3-fold symmetric hexon. Only the Gla and kringle-1 domains of FII are visible on all the species-C adenoviruses, where the rigid FII binds in an upright fashion, in contrast to the flexible and bent FX. These data suggest that differential binding of FII and FX may shield certain species-C adenoviruses differently against immune molecules, thereby modulating their tropism. The tropism of adenoviruses is influenced by the binding of host blood factors. Here, the authors show the N-terminal non-polar residues of γ-carboxyglutamic acid domains of vitamin K-dependent blood clotting factors interact with the hexon cavities on the surface of species-C adenoviruses. [ABSTRACT FROM AUTHOR]

Background: Vestibular dysfunction causing imbalance affects c. 80% of acute hospitalized traumatic brain injury (TBI) cases. Poor balance recovery is linked to worse return-to-work rates and reduced longevity. We previously showed that white matter network disruption, particularly of right inferior longitudinal fasciculus, mediates the overlap between imbalance and impaired vestibular perception of self-motion (i.e., vestibular agnosia) in acute hospitalized TBI. However, there are no prior reports tracking the acute-longitudinal trajectory of objectively measured vestibular function for hospitalized TBI patients. We hypothesized that recovery of vestibular agnosia and imbalance is linked and mediated by overlapping brain networks. Methods: We screened 918 acute major trauma in-patients, assessed 146, recruited 39 acutely, and retested 34 at 6 months. Inclusion criteria were 18–65-year-old adults hospitalized for TBI with laboratory-confirmed preserved peripheral vestibular function. Benign paroxysmal positional vertigo and migraine were treated prior to testing. Vestibular agnosia was quantified by participants' ability to perceive whole-body yaw plane rotations via an automated rotating-chair algorithm. Subjective symptoms of imbalance (via questionnaires) and objective imbalance (via posturography) were also assessed. Results: Acute vestibular agnosia predicted poor balance recovery at 6 months. Recovery of vestibular agnosia and linked imbalance was mediated by bihemispheric fronto-posterior cortical circuits. Recovery of subjective symptoms of imbalance and objective imbalance were not correlated. Conclusion: Vestibular agnosia mediates balance recovery post-TBI. The link between subjective dizziness and brain injury recovery, although important, is unclear. Therapeutic trials of vestibular recovery post-TBI should target enhancing bi-hemispheric connectivity and linked objective clinical measures (e.g., posturography). [ABSTRACT FROM AUTHOR]

Although the benefits of collaborative learning across disciplines are well-established, its effectiveness hinges on the quality of execution. Motivational beliefs and emotions are crucial in students' engagement and achievement. Yet, a notable gap exists in examining these variables among students with varying proficiency levels in the context of collaborative learning. To address the gap, the present study investigated 289 fourth- and fifth-grade Hong Kong primary students’ motivational beliefs and emotions in ESL collaborative learning and explored the variation across students’ actual and self-perceived English proficiency. The findings revealed an overall high level of motivational beliefs alongside a medium level of anxiety. Structural equation modelling analyses indicated that self-perceived proficiency positively influenced students' motivational beliefs, whereas actual proficiency did not make a unique contribution. Both self-perceived and actual proficiency, as well as their interaction, reduced anxiety. Actual proficiency had a stronger negative impact on anxiety when self-perceived proficiency was high, and the influence of self-perceived proficiency was significant only when actual proficiency was high. Practical implications are discussed. [ABSTRACT FROM AUTHOR]

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Purpose: Germline genetic mutations in women with phyllodes tumors (PT) are understudied, although some describe associations of PT with various mutations. We sought to determine the prevalence of pathogenic/likely pathogenic (P/LP) variants in women with PT. Methods: A 6-site multi-center study of women with a PT was initiated, then expanded nationally through an online "Phyllodes Support Group." All women underwent 84-gene panel testing. We defined eligibility for testing based on select NCCN (National Comprehensive Cancer Network) criteria (v1.2022). Logistic regression was used to estimate the association of covariates with the likelihood of a P/LP variant. Results: 274 women were enrolled: 164 (59.9%) through multi-center recruitment and 110 (40.1%) via online recruitment. 248 women completed testing; overall 14.1% (N = 35) had a P/LP variant, and over half (N = 19) of these individuals had a mutation in genes associated with autosomal dominant (AD) cancer conditions. The most common AD genes with a P/LP variant included CHEK2, ATM, and RAD51D. A quarter of participants (23.8%) met NCCN criteria for testing, but we found no difference in prevalence of a P/LP variant based on eligibility (p = 0.54). After adjustment, the presence of P/LP variants was not associated with age, NCCN testing eligibility, or PT type (all p > 0.05). Conclusion: Our study demonstrates that 7.7% of women with PT harbor germline P/LP variants in genes associated with AD cancer conditions. Early identification of these variants has implications for screening, risk reduction, and/or treatment. National guidelines for women with PT do not currently address germline genetic testing, which could be considered. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to evaluate the safety and efficacy of HoLEP in patients aged > 85 years with indwelling catheter (IDC). Methods: We retrospectively analyzed our bicentric HoLEP database to identify consecutive patients with IDC and trial without catheter (TWOC) failure who underwent surgery between June 2012 and April 2020. Our primary focus was on the population over 85 years of age; Patients under 70 years of age were used as controls. We evaluated the rate of postoperative spontaneous micturition, adverse events and mortality, as well as catheterization duration, hospital stay, and rate of urinary incontinence. Results: In total, 144 patients were included, with 71 (49.3%) and 73 (50.8%) in the ≥ 85 and control group, respectively. The median [IQR] prostatic volume and Charlson score was 90 [70–130] vs. 90 [65–120] mL and 6 [5–7] vs. 3 [2–4] in the ≥ 85 and control groups, respectively. Postoperatively, the rates of major complications (2% vs. 3%) and transfusion (11% vs. 9%) were not significantly different. The median length of stay (2 [1–3] vs. 1 [1–2]; p = 0.03) and rate of TWOC failure during hospitalization (24% vs. 5%, p < 0.001) were significantly higher in the ≥ 85 group. At 3 months and one year follow-up visits, 0 and 10 patients (14.1%) in the ≥ 85 group and 0 and 2 patients (3%) in the control group died, respectively. One year after surgery, 69 (97%) and 73 (100%) (p = 0.2) patients in the ≥ 85 and control groups, respectively, could void spontaneously. Conclusion: HoLEP is a safe and effective procedure for elderly patients with indwelling catheters. At one year, 97% of patients achieved spontaneous voiding, while the urinary incontinence rate was 11%. The 1-year mortality rate was 14%, comparable to that of the general male population of the same age. [ABSTRACT FROM AUTHOR]

The applicability of layered transition-metal dichalcogenides (TMDs) for electrode application in lithium-ion batteries (LIBs) necessitates a fundamental understanding of the ion intercalation/de-intercalation mechanisms to identify the factors that affect the cycling stability and/or degradation behavior of the layers. This paper presents the results of an in-situ study of reactions between Li/Li2O and MoS2 inside the transmission electron microscope (TEM) with the basal plane in the edge-on orientation; this orientation makes it possible to examine directly the microstructural and microchemical changes that occur within the van der Waals (vdW) gaps. The experiments enable the characterization of the nanoscale defects that form in real-time as the Li moves into the gaps. Defects are observed to form along the c-planes of MoS2 during in-situ reaction with Li in the TEM. Energy-filtered TEM (EFTEM) analysis shows that these lines are rich in Li and poorer in Mo and S. Atomic-resolution TEM studies in an aberration-corrected TEM show the different stages of the microstructural evolution along these white-line defects. The formation of these defects during intercalation results in the degradation of the layers as cracks are observed to form at the interfaces between the defects and the matrix when external tensile stresses are applied. This cracking subsequently leads to exfoliation and the structural degradation of the intercalated material. These direct observations complemented by atomistic modeling raise several critical questions concerning the ion intercalation and de-intercalation mechanisms that need to be addressed to understand the factors that affect the safety and reliability of layered TMDs in LIBs. This paper is submitted as part of a special issue honoring the contributions of Kamanio Chattopadhyay to Materials Science and celebrating his 75th birthday. Prof. Chattopadhyay's distinguished career included research on metastable materials, which may have much in common with the materials being studied here, and also served for several years as an Editor of the Journal of Materials Science. [ABSTRACT FROM AUTHOR]

The ore mining sites commonly experience slope instability, which is causing concern for the workers' safety and the operation's stability. Considering the Ziluoyi iron ore mining site as a case study, uniaxial compression strength and shear tests are performed on the lower disk peripheral rock, ore body, and upper disk peripheral rock, leading to the extraction of compressive strength and elastic modulus (lower disk: 77.7 MPa–9.093 GPa; ore body: 19.6 MPa–4.619 GPa; upper disk: 55.47 MPa–5.573 GPa). Further, using the Hoek–Brown criterion in conjunction with the Moher–Columb criterion, the cohesion and internal friction angle of various samples are appropriately determined (lower disk: 21.124 MPa–35.614°; ore body: 21.66 MPa–26.5°; upper disk: 42.916 MPa–25.743°). By employing an appropriate rock mass reduction model, its constants (m and s) and RMR score for the consisting layers (schist layer and ore body) of the three understudy slopes (Slope#1–Slope#3) are evaluated. An effective algorithm based on the Morgenstern–Price method is employed and its effectiveness is also proved by comparing its factor of safety results with those of Geo-Slope for various slope structures subjected to different loads. Subsequently, the stability analyses of various slopes are methodically examined by predicting the factor of safety values under multiple types of loading (i.e., self-weight + groundwater, slope self-weight + groundwater + blasting vibration force, and self-weight + groundwater + seismic force). The factor of safety values of the slopes pertinent to Slope#1/Slope#2/Slope#3 subjected to the above loading conditions are obtained as 1.354/1.273/1.188, 1.326/1.239/1.169, and 1.321/1.232/1.162, respectively. Upon comparing these results with those of a valid homeland specification, it becomes clear that the results are able to meet safety standards and ensure efficient mine operation. [ABSTRACT FROM AUTHOR]

Introduction: Temporomandibular joint (TMJ) septic arthritis is a rare frequently misdiagnosed condition with non-specific symptoms. We present our experience of thirteen cases of TMJ septic arthritis and perform a systematic review of the literature to collate the multiple characteristics of this condition. Material and method: A total of 133 cases of TMJ septic arthritis in humans across 62 studies were analyzed by searching PubMed, Cochrane Library, DOAJ and ClinicalTrials.gov using the following search terms: “TMJ septic arthritis,” “Temporomandibular septic arthritis,” “TMJ infectious arthritis,” and “Temporomandibular infectious arthritis.” Results: We identified three routes of TMJ septic arthritis dissemination: the hematogenous route, direct inoculation, and local contiguity. Joint and rheumatic pathologies and immunomodulatory diseases are risk factors. The most frequently causative bacterial genus is Staphylococcus, followed by Streptococcus. Causative bacteria can be identified by bacteriological analysis. Magnetic resonance imaging, computed tomography (CT), and scintigraphy can be used for diagnosis, but CT is the gold standard in an emergency setting. Blood tests often reveal a high C-reactive protein concentration and high leukocyte counts. Signs and symptoms include preauricular swelling and trismus, and, less commonly, fever, ipsilateral hemifacial pain, joint disorder, and malocclusion with mandibular deviation. Timely treatment is key to avoid short and long-term complications, because proteolytic enzymes from granulocytes can cause irreversible damage within 7 days. Antibiotic therapy, arthroplasty, and physiotherapy are commonly used treatment modalities. Conclusion: TMJ septic arthritis can be misdiagnosed due to its non-specific clinical manifestations. Complications can occur; thus, timely and effective treatment is key. [ABSTRACT FROM AUTHOR]

Toxicological test methods generate raw data and provide instructions on how to use these to determine a final outcome such as a classification of test compounds as hits or non-hits. The data processing pipeline provided in the test method description is often highly complex. Usually, multiple layers of data, ranging from a machine-generated output to the final hit definition, are considered. Transition between each of these layers often requires several data processing steps. As changes in any of these processing steps can impact the final output of new approach methods (NAMs), the processing pipeline is an essential part of a NAM description and should be included in reporting templates such as the ToxTemp. The same raw data, processed in different ways, may result in different final outcomes that may affect the readiness status and regulatory acceptance of the NAM, as an altered output can affect robustness, performance, and relevance. Data management, processing, and interpretation are therefore important elements of a comprehensive NAM definition. We aim to give an overview of the most important data levels to be considered during the development and application of a NAM. In addition, we illustrate data processing and evaluation steps between these data levels. As NAMs are increasingly standard components of the spectrum of toxicological test methods used for risk assessment, awareness of the significance of data processing steps in NAMs is crucial for building trust, ensuring acceptance, and fostering the reproducibility of NAM outcomes. Plain language summary Toxicological test methods initially generate raw data. These need to be further processed to determine a final outcome, such as the classification of test compounds as hits or non-hits. The processing of the raw data is often highly complex and proceeds stepwise. This process generates many layers of data connected by several processing steps. Any change to these processing steps can impact the final output of new approach methods (NAMs). This means that the same raw data, processed in different ways, may result in different final outcomes. Data management, processing and interpretation are therefore considered important elements of a comprehensive NAM definition. We illustrate data processing and evaluation steps that play an important role. Awareness of the significance of data processing steps in NAMs is crucial for building trust, ensuring acceptance, and fostering the reproducibility of NAM outcomes. [ABSTRACT FROM AUTHOR]

Background: Patients with heterozygous familial hypercholesterolemia (HeFH) are at high risk of major adverse cardiovascular events (MACE) and mortality. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), including monoclonal antibodies (alirocumab, evolocumab) and small interfering RNA (inclisiran), substantially reduce lipid levels. This meta-analysis aimed to evaluate the efficacy of both types of PCSK9i specifically in patients with HeFH. Methods: A librarian-assisted systematic search of MEDLINE, Embase, CENTRAL, and ClinicalTrials.gov was performed from 2013 to 2023. Randomized controlled trials of PCSK9i versus control in patients with HeFH were included. No language restrictions were applied. Cochrane Risk-of-Bias tool 2 was used to assess quality of evidence. Meta-analyses were performed using Cochrane ReviewManager. Outcomes included change in atherogenic lipids, MACE, and all-cause death. Results: Seven trials were included (N = 2196). Overall risk of bias was mostly low or with some concerns. Median follow-up was 24 weeks. PCSK9i had an uncertain effect on MACE (odds ratio [OR] 1.25, 95% confidence interval [CI] 0.69–2.26) and all-cause death (OR 2.47, 95% CI 0.33–18.26) due to the low event rate and short follow-up. However, PCSK9i significantly reduced low-density lipoprotein cholesterol (LDL-C) by 54% (95% CI 49–58), apolipoprotein B by 43% (95% CI 37–49), and lipoprotein(a) by 20% (95% CI 13–28). Conclusions: In patients with HeFH, PCSK9i significantly reduced atherogenic lipids (LDL-C, apolipoprotein B, and lipoprotein[a]). Despite this, the effect on MACE or all-cause death was unclear. Larger-scale randomized controlled trials of longer duration are needed to validate whether this short-term reduction in lipid levels translates into a reduction in clinically meaningful outcomes. [ABSTRACT FROM AUTHOR]

A significant limitation of behavioral ecotoxicology is the challenge of obtaining reproducible results due to a wide range of testing conditions. In particular, shoal size affects almost all aspects of fish behavior, but is rarely considered as a factor in ecotoxicological studies. In the present study, we compared the swimming and antipredator responses of different sized shoals of Arabian killifish (Aphaniops stoliczkanus) after exposure to environmentally realistic concentrations of the antidepressant medication sertraline. Groups of fish (1, 3 or 5 individuals) were exposed to either 5 or 50 ng/L sertraline. After 37 days, swimming behavior and responses to a predator alarm were measured. We found that the effects of group size were much stronger than the effects of sertraline on swimming. Group size was also the major factor influencing responses to the predator alarm, with single fish showing the strongest responses. Sertraline directly affected acceleration, turning speed and average distance to the arena wall. For all three parameters, there were significant interactions with shoal size, demonstrating that responses differed depending on the size of the group. We also found that effects of sertraline could still be observed 14 days after cessation of exposure. The study highlights the importance of considering social context and specifically shoal size when designing behavioral studies on chemicals. Failure to consider this may result in over- or under-estimation of risks. [ABSTRACT FROM AUTHOR]

The growing field of psychodermatology examines the interplay between dermatological and psychiatric comorbidities. While current literature recognizes that cutaneous and psychiatric conditions often coexist within patients, the relationship between dysregulated inflammation and depression in patients with inflammatory skin conditions has not been thoroughly explored. This review seeks to describe the connection between cutaneous disease and depression via shared inflammatory cytokine pathways. A review of current literature was conducted, and studies addressing the co-occurrence of depression and inflammatory skin diseases were included. This review focuses on depression in patients with psoriasis, atopic dermatitis, and hidradenitis suppurativa. Studies that focused on the prevalence of depression in these populations, shared inflammatory pathways, and co-management of cutaneous and psychiatric disorders were chosen. The literature revealed a high prevalence of depression in individuals with inflammatory skin conditions compared with those without cutaneous disease. Recent studies described how proinflammatory cytokines in inflammatory skin diseases can elicit inflammation in the brain, leading to depressive symptoms. Certain subsets of cytokines that mediate inflammatory pathways were associated with both cutaneous inflammation and depression, highlighting shared pathology. Antiinflammatory medications targeting shared cytokines found reductions in both cutaneous and depressive symptoms. Practitioners have emphasized interdisciplinary approaches to treating both conditions, including psychotherapy and pharmacological methods. There is a clear association between inflammatory cutaneous diseases and depression. Co-management of these conditions, including interdisciplinary methods, is essential for patients' well-being. Future research addressing similar links between other cutaneous and psychiatric conditions could yield new treatment opportunities as well. [ABSTRACT FROM AUTHOR]

Sands from the dune, berm, and shore environments at Playa las Golondrinas (18° 30′ 51″ N, 67° 3′ 26″) were investigated to explore how beach sands could be applied as a potential environmental (geogenic) background for the local region. Grain size is dominantly unimodal classifying as fine to medium sand. Hydraulic conductivity values range from 1.07 cm/s (berm) to 1.49 cm/s (shoreface). Sample mineralogy as constrained by X-ray diffraction (XRD) reveals a dominance of quartz and feldspar with minor Mg-calcite, pyroxene, and olivine. Light microscopy and scanning electron microscopy-energy dispersive spectroscopy (SEM–EDS) support XRD data and indicate the presence of oxide-bearing lithic fragments in addition to biologic materials (e.g., corals. forams). Reflective spectra are consistent with XRD and microscopy. Bulk element concentrations determined using inductively coupled plasma—mass spectrometry (ICP-MS) are consistent with derivation from the arc-related rocks of Puerto Rico's interior exhibiting LILE enrichment, Pb-enrichment, and associated Nb–Ta depletion. The majority of the bulk elemental concentrations are below those of average upper continental crust (UCC) values and element co-variation trends (e.g., wt. % Fe2O3 vs. As) are interpreted as geogenic in origin. Berm sands are enriched in Fe, Mn, Ni, Cr, V, and As compared to dune and shore samples and this signature is interpreted as being from a wind-driven winnowing effect. The exact form of As (As3+ or As5+) remains unconstrained and thus it is unknown if As is mobile in this environment. Reflective spectra, supported by grain size, mineralogy, and bulk chemistry, enables future remote sensing investigations by providing detailed constraints on sand in environmentally sensitive areas. This study therefore provides local context for metal pollution studies across the region. [ABSTRACT FROM AUTHOR]

Purpose of Review: Voriconazole is a broad-spectrum antifungal agent commonly used to treat severe fungal infections. Significant interindividual variability in drug metabolism can lead to subtherapeutic or toxic serum levels impacting clinical outcomes and risk for adverse effects. This review aims to summarize and evaluate evidence that assesses the impact of voriconazole therapeutic drug monitoring (TDM) on clinical outcomes and adverse effects. Recent Findings: Many factors contribute to variability in serum voriconazole levels, such as CYP2C19 polymorphism, hepatic function, etc. TDM can aid in the management of narrow therapeutic index medications like voriconazole to optimize clinical outcomes. Current literature indicates that TDM improves clinical outcomes and reduces adverse effects by helping achieve therapeutic serum concentrations. Summary: Voriconazole TDM is a valuable tool in optimizing treatment outcomes and minimizing adverse effects. Individualized dosing guided by TDM, helps achieve therapeutic serum levels, particularly in patients with variable metabolism enhancing the efficacy of treatment for invasive fungal infections. [ABSTRACT FROM AUTHOR]

A community-driven effort in Cedar Key, Florida, USA, resulted in the construction of three living shoreline retrofits intended to bolster failing coastal infrastructure and restore habitat functions in Daughtry Bayou. A multi-year monitoring program tracked changes in elevation and vegetation communities across the entire shoreline profile from lower-intertidal to upland/transitional zones and measured wave attenuation during typical and extreme (hurricane) conditions. Overall, these living shoreline retrofits served to soften more than 30% of the bayou’s shoreline, dramatically reducing the extent of armored shoreline in direct contact with tidal influence. The extent of vegetated habitat area has increased at all three sites, despite sediment export from higher elevation zones driven largely by repeated impacts from hurricanes and tropical storms. These living shorelines reduced wave energy by 33 to 79% in typical conditions and by up to 28% in hurricane conditions, consistently outperforming armored shorelines, even during an extreme event (Hurricane Idalia). Our monitoring efforts were sufficient to capture project trajectories and assess performance relative to project goals, but our program had limitations that could have been overcome with additional resources and increased focus on capturing spillover effects. The living shoreline retrofit projects assessed here have persisted through and shown signs of recovery after multiple tropical storms and hurricanes, while providing important energy reduction services. Thus, living shoreline retrofits continue to be a cost-effective shoreline management strategy in the short term for this area. However, our analyses suggest that persistence of these shorelines could be threatened by the combination of sea-level rise (by 2040), upland armoring, and an increasing risk of more intense tropical systems. Therefore, future interventions should more carefully consider these threats in conjunction with habitat enhancement goals. [ABSTRACT FROM AUTHOR]

The pericardium plays an important role in modulating cardiac performance and hemodynamics in patients with heart failure with preserved ejection fraction (HFpEF). Pericardial constraint increases filling pressures in patients with HFpEF, particularly those with the obesity phenotype, atrial myopathy, right ventricular dysfunction, and tricuspid regurgitation. Preclinical and early stage clinical studies indicate that pericardiotomy may become a novel treatment for HFpEF. This review summarizes and discusses the pathophysiology of pericardial restraint and the possibility of pericardiotomy in HFpEF. [ABSTRACT FROM AUTHOR]

Purpose of Review: To describe the current state of gene transfer therapy for inherited cardiomyopathies, focusing on targets, recent experience, limitations, and challenges. Recent Findings: The use of adeno-associated viral vectors with enhanced cardiac tropism has enabled gene transfer therapy for cardiovascular diseases to advance substantially over the past decade. These vectors are now being used to deliver therapeutic genes that potentially can correct specific genetic mutations associated with heart failure, including those involving genes, such as SERCA2a, BAG3, PKP2, LAMP2, MYBPC3 and FXN, that encode proteins that are critical for normal cell function. Experience from recent clinical trials, however, underlines the need for improved methodologies and safety protocols. Despite recent success, there is a need to address existing challenges related to vector delivery, immune responses, and trial design for the field to advance. Summary: Gene transfer therapies present a promising approach for treating genetic cardiomyopathies. Addressing issues related to vector efficiency, immune reactions and trial design is essential to move the field forward. Future research should be aimed at refining existing gene transfer strategies and clinical trial design with the goal of improving outcomes in patients with genetic cardiomyopathies. [ABSTRACT FROM AUTHOR]

Hearing loss (HL) in mid-life has been suggested as a risk factor for cognitive decline. It is unclear whether this relationship is due to deprivation of auditory input alone, degenerative processes, or a combination. Animal models are useful to investigate underlying neural mechanisms as human studies can be confounded by various factors. However, most animal studies use young animals and often exclude females. We used middle-aged guinea pigs of both sexes to investigate whether 8 weeks of auditory deprivation due to conductive HL caused spatial learning and memory impairments. Forty guinea pigs (20 M, 20 F, ~ 12 months) were tested in the Morris Water Maze (MWM) to assess baseline spatial learning and memory. In 20 of these animals (10 M, 10 F) the ear canal was plugged and 8 weeks later, animals were again assessed in MWM. No deficits in spatial learning or memory were observed in either sex. HL caused a small decline in body weight suggesting some stress associated with conductive HL, although adrenal weight, corrected for body weight, did not change. Our data suggest that auditory input deprivation alone does not affect spatial cognition in middle-age, in line with recent human data suggesting that additional risk factors need to be present. [ABSTRACT FROM AUTHOR]

Pulsed Field Ablation (PFA) is a new ablation method being rapidly adopted for treatment of atrial fibrillation, which shows advantages in safety and efficiency over radiofrequency and cryo-ablation. In this study, we used an in vivo swine model (10 healthy and 5 with chronic myocardial infarct) for ventricular PFA, collecting intracardiac electrograms, electro-anatomical maps, native T1-weighted and late gadolinium enhancement MRI, gross pathology, and histology. We used 1000–1500 V pulses, with 1–16 pulse trains to vary PFA dose. Lesions were assessed at 24 h, 7 days, and 6 weeks in healthy and at 48 h in infarcted ventricles. Comparisons of lesion sizes using a numerical model enabled us to determine lethal electric field thresholds for cardiac tissue and its dependence on the number of pulse trains. Similar thresholds were found in normal and infarcted hearts. Numerical modeling and temperature-sensitive MRI confirmed the nonthermal nature of PFA, with less than 2% of a lesion's volume at the highest dose used being attributed to thermal damage. Longitudinal cardiac MRI and histology provide a comprehensive description of lesion maturation. Lesions shrink between 24 h and 7 days post-ablation and then remain stable out to 6 weeks post-ablation. Periprocedural electrograms analysis yields good correlation with lesion durability and size. [ABSTRACT FROM AUTHOR]

Brown rot fungi, the major decomposers in the boreal coniferous forests, cause a unique wood decay pattern but many aspects of brown rot decay mechanisms remain unclear. In this study, decayed wood samples were prepared by cultivation of the brown rot fungi Gloeophyllum trabeum and Coniophora puteana on Japanese coniferous wood of Cryptomeria japonica, and the cutting planes were prepared using broad ion beam (BIB) milling, which enables observation of intact wood, in addition to traditional microtome sections. Samples were observed using field-emission SEM revealing that areas inside the end walls of ray parenchyma cells were the first to be degraded. Osmium reaction precipitates were observed in the degraded regions, as well as in plasmodesmata. In the cell wall where ray parenchyma cells contacted with the tracheids, specific degradation of cross-field pits and hyphal elongation into this area was observed in degradation by both fungi. Other pit types were also degraded as noted in previous studies. Delamination between the S1 and S2 layers of tracheids, and cracks in the tracheid cell walls were observed. These findings provide new insights into the cell wall degradation mechanisms during the incipient stages of brown rot decay. [ABSTRACT FROM AUTHOR]

We present a de novo mitogenome assembly from a specimen of Rhinichthys atratulus, the Eastern Blacknose Dace, collected in the Connecticut River drainage. R. atratulus is a fish species widely distributed across Atlantic slope drainages from Nova Scotia, Canada to the Roanoke River Drainage, Virginia, United States. The assembly has a total length of 16,646 bp; consists of 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and a 974 bp D-loop; and has a GC content of 45.7%. We performed two phylogenetic analyses using the de novo assembly and 28 additional cyprinoid mitochondrial genomes: with and without the D-loop. The resulting phylogenetic trees showed the same branching patterns. However, inclusion of the D-loop resulted in nodes with equal or greater support. The trees largely match previously published analyses, while offering new insights into relationships among leuciscid genera. Our findings indicate that the inclusion of the D-loop in mitogenome phylogenetic analyses can help improve bootstrap support at otherwise unresolved nodes. [ABSTRACT FROM AUTHOR]

In recent decades, drug resistant (DR) strains of Mycobacterium tuberculosis (M.tb), the cause of tuberculosis (TB), have emerged that threaten public health. Although M.tb's complex and protective cell envelope has been widely studied, little is known about how levels of peripheral lipids change in relation to drug resistance. In this study, we examined levels of cell envelope lipids [phthiocerol dimycocerosates (PDIMs)], glycolipids [phosphatidyl-myo-inositol mannosides (PIMs)], and PIMs associated lipoglycans [lipomannan (LM); mannose-capped lipoarabinomannan (ManLAM)] of 22 M.tb strains that ranged in drug resistance profile. We show that the PDIMs:PIMs ratio increases as drug resistance increases, and provide evidence of PDIM isomers only present in the DR-M.tb strains studied. Overall, the LM and ManLAM levels did not differ between drug resistance categories, but ManLAM surface exposure increased with drug resistance. Infection of human macrophages revealed that DR-M.tb strains have decreased association compared to drug susceptible (DS) strains, and that the pre-XDR M.tb strain with the largest PDIMs:PIMs ratio had decreased uptake, but increased intracellular growth at early during infection compared to the DS-M.tb strain H37Rv. These findings suggest that PDIMs may play an important role in drug resistance and that an increase in hydrophobic cell envelope lipids may influence M.tb-host interactions. [ABSTRACT FROM AUTHOR]

The efficiency of gas turbine engines can significantly be enhanced by reducing the clearance between stationary and rotating parts. AlSi-polymer composite abradable coatings are commonly employed for such applications to serve as sacrificial materials while maintaining the pressure within compressors and seals. However, these coatings can face premature failure during operation, particularly due to corrosion and erosion. More specifically, due to the ductile behavior of AlSi-polymer-based abradables, the erosion rates at low impingement angles are particularly high. Thus, there is a strong desire to develop an abradable system capable of maintaining high erosion resistance at various impingement angles while maintaining suitable abradability (i.e., high wear of the abradable during interaction with the blade tip). The main purpose of this study is to critically evaluate the influence of Ni in AlSi-polymer-based abradable coatings on their erosion and tribological performance. The AlSi-polymer powders were mechanically mixed to develop the powders that were subsequently deposited using atmospheric plasma spray (APS). Microstructure analysis using field emission scanning electron microscopy (FESEM) and HR15Y hardness tests was employed to assess the microstructural and mechanical properties of the coating. Ball-on-flat, ball-on-disk, and air jet erosion tests were performed, followed by ex situ surface analysis to elucidate the wear mechanism. The results revealed that the incorporation of Ni preserved the lamellar microstructure characteristic of AlSi and polyester abradable coatings, while concurrently decreasing average wear rates at lower impingement angles, as observed throughout the erosion tests. [ABSTRACT FROM AUTHOR]

Pseudosymmetric hetero-oligomers with three or more unique subunits with overall structural (but not sequence) symmetry play key roles in biology, and systematic approaches for generating such proteins de novo would provide new routes to controlling cell signaling and designing complex protein materials. However, the de novo design of protein hetero-oligomers with three or more distinct chains with nearly identical structures is a challenging unsolved problem because it requires the accurate design of multiple protein-protein interfaces simultaneously. Here, we describe a divide-and-conquer approach that breaks the multiple-interface design challenge into a set of more tractable symmetric single-interface redesign tasks, followed by structural recombination of the validated homo-oligomers into pseudosymmetric hetero-oligomers. Starting from de novo designed circular homo-oligomers composed of 9 or 24 tandemly repeated units, we redesigned the inter-subunit interfaces to generate 19 new homo-oligomers and structurally recombined them to make 24 new hetero-oligomers, including ABC heterotrimers, A2B2 heterotetramers, and A3B3 and A2B2C2 heterohexamers which assemble with high structural specificity. The symmetric homo-oligomers and pseudosymmetric hetero-oligomers generated for each system have identical or nearly identical backbones, and hence are ideal building blocks for generating and functionalizing larger symmetric and pseudosymmetric assemblies. Hetero-oligomeric proteins offer many advantages for bioengineering efforts but are difficult to make from scratch. Here, authors present a simple method for creating pseudosymmetric hetero-oligomers from input symmetrical proteins. [ABSTRACT FROM AUTHOR]

Mutations in the mitochondrial enzyme propionyl-CoA carboxylase (PCC) cause propionic aciduria (PA). Chronic kidney disease (CKD) is a known long-term complication. However, good metabolic control and standard therapy fail to prevent CKD. The pathophysiological mechanisms of CKD are unclear. We investigated the renal phenotype of a hypomorphic murine PA model (Pcca-/-(A138T)) to identify CKD-driving mechanisms. Pcca-/-(A138T) mice show elevated retention parameters and express markers of kidney damage progressing with time. Morphological assessment of the Pcca-/-(A138T) mouse kidneys indicated partial flattening of tubular epithelial cells and focal tubular-cystic dilation. We observed altered renal mitochondrial ultrastructure and mechanisms acting against oxidative stress were active. LC–MS/MS analysis confirmed disease-specific metabolic signatures and revealed disturbances in mitochondrial energy generation via the TCA cycle. Our investigations revealed altered mitochondrial networks shifted towards fission and a marked reduction of mitophagy. We observed a steep reduction of PGC-1-α, the key mediator modulating mitochondrial functions and a counter actor of mitochondrial fission. Our results suggest that impairment of mitochondrial homeostasis and quality control are involved in CKD development in PA. Therapeutic targeting of the identified pathways might help to ameliorate CKD in addition to the current treatment strategies. [ABSTRACT FROM AUTHOR]

Maintaining adequate levels of antiretroviral (ARV) medications is crucial for the efficacy of HIV treatment and prevention regimens. Monitoring ARV levels can predict or prevent adverse health outcomes like treatment failure or drug resistance. However, conventional ARV measurement using liquid chromatography-tandem mass spectrometry (LC–MS/MS) is slow, expensive, and centralized delaying clinical and behavioral interventions. We previously developed a rapid enzymatic assay for measuring nucleotide reverse transcriptase inhibitors (NRTIs) — the backbone of HIV treatment and prevention regimens — based on the drugs' termination of DNA synthesis by HIV reverse transcriptase (RT) enzyme. Here, we expand our work to include non-nucleoside reverse transcriptase inhibitors (NNRTIs) — an ARV class used in established and emerging HIV treatment and prevention regimens. We demonstrate that the REverse Transcriptase ACTivity (REACT) assay can detect NNRTIs including medications used in oral and long-acting/extended-release HIV treatment and prevention. We demonstrate that REACT can measure NNRTIs spiked in either buffer or diluted plasma and that fluorescence can be measured on both a traditional plate reader and an inexpensive portable reader that can be deployed in point-of-care (POC) settings. REACT measured clinically relevant concentrations of five NNRTIs spiked in aqueous buffer. REACT measurements showed excellent agreement between the plate reader and the portable reader, with a high correlation in both aqueous buffer (Pearson's r = 0.9807, P < 0.0001) and diluted plasma (Pearson's r = 0.9681, P < 0.0001). REACT has the potential to provide rapid measurement of NNRTIs in POC settings and may help to improve HIV treatment and prevention outcomes. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a progressive respiratory scarring disease arising from the maladaptive differentiation of lung stem cells into bronchial epithelial cells rather than into alveolar type 1 (AT1) cells, which are responsible for gas exchange. Here, we report that healthy lungs maintain their stem cells through tonic Hippo and β-catenin signaling, which promote Yap/Taz degradation and allow for low-level expression of the Wnt target gene Myc. Inactivation of upstream activators of the Hippo pathway in lung stem cells inhibits this tonic β-catenin signaling and Myc expression and promotes their Taz-mediated differentiation into AT1 cells. Vice versa, increased Myc in collaboration with Yap promotes the differentiation of lung stem cells along the basal and myoepithelial-like lineages allowing them to invade and bronchiolize the lung parenchyma in a process reminiscent of submucosal gland development. Our findings indicate that stem cells exhibiting the highest Myc levels become supercompetitors that drive remodeling, whereas loser cells with lower Myc levels terminally differentiate into AT1 cells. IPF arises from the maladaptive differentiation of lung stem cells into bronchial epithelial cells rather than AT1 cells. Here, Warren, R et al. report that stem cells with the highest Myc levels become supercompetitors that drive remodeling. [ABSTRACT FROM AUTHOR]

Continuous professional development among stakeholders involved in drug safety monitoring and surveillance is imperative in strengthening pharmacovigilance (PV) systems. The "Pharmacovigilance infrastructure and post-marketing surveillance system capacity building for regional medicine regulatory harmonization in East Africa" (PROFORMA) project aims to enhance the national PV infrastructure, post-marketing surveillance systems and clinical trial regulatory capabilities in Ethiopia, Tanzania, Kenya and Rwanda. To achieve this, training, including short-term training (STT) activities, at various levels is required. This article aims to describe the experiences of the authors during the development and implementation of STT in an attempt to improve the PV training landscape of these countries. To identify gaps, a baseline assessment of PV teaching and practices at the national medicines regulatory authorities (NMRAs) and medical universities was conducted. Five successive training sessions, tailored to each country's specific needs and regulatory environments, were conducted; three focusing on fundamental concepts in PV and two dedicated to training-of-trainers courses. The training targeted staff from PV units of the NMRAs and medical universities. Enabling participation from all four countries in the same training fostered cross-country learning and collaboration. The contribution of STT to university education and the operational methodologies within NMRAs are explored, showcasing the impact on knowledge transfer and skill development in each country. In conclusion, by investing strategically in STT activities and fostering partnerships with academic institutions and NMRAs, we demonstrated a sustainable approach to PV capacity strengthening in resource-limited settings. The success of this model underscores its potential for adoption and replication across the African continent, offering a valuable framework for strengthening drug safety regulation and ultimately protecting public health. [ABSTRACT FROM AUTHOR]

The number of disease-modifying therapies (DMTs) approved for the treatment of multiple sclerosis (MS) has greatly increased in recent decades, leading to higher treatment complexity. DMTs can differ in mode and frequency of administration, benefit–risk profile, and associated costs. Patients with MS contend not only with the burden of their chronic disease but also with the treatment burden of their MS therapy. Adhering to dosing schedules and infusion appointments can be difficult for busy, working-age patients or those with limited access to transportation. Patients and healthcare professionals (HCPs) may have differing priorities, concerns, and preferences when selecting treatment, potentially affecting treatment satisfaction and, importantly, adherence. Additionally, patients face direct and indirect costs related to treatment. These factors can all contribute to a high treatment burden on patients, impacting their quality of life and potentially leading to worse patient outcomes. HCPs, patients, and caregivers must work together to alleviate treatment burden through effective communication, shared decision-making, appreciating each other's perspectives, and additional HCP support. Consideration of treatment burden into clinical guidelines is also warranted. In this review, we examine key factors impacting treatment burden for patients with MS, with a focus on the patient perspective as provided by our patient authors, and provide strategies to minimize treatment burden. [ABSTRACT FROM AUTHOR]

Background: Breath testing for small intestinal bacterial overgrowth (SIBO) is typically performed using clinic-based equipment or single-use test kits. Aims: This study aimed to evaluate the utility of a portable, point-of-care breath analysis device (AIRE®, FoodMarble) in patients suspected to have SIBO. A technical assessment including a comparison to existing mail-in kits was first performed. Then, postprandial breath hydrogen levels of patients before and after antibiotic treatment were gathered and compared to levels seen in a healthy cohort. Methods: For the comparison, 50 patients suspected of having SIBO were provided with an AIRE device and performed concurrent LHBTs at-home with a mail-in breath test kit. For the postprandial analysis, twenty-four patients with chronic GI symptoms measured their postprandial hydrogen for 7 days prior to antibiotic treatment and for 7 days after treatment. 10 healthy controls also measured their postprandial hydrogen for 7 days. Results: Substantial agreement was demonstrated between AIRE and the mail-in kits for the performance of lactulose hydrogen breath tests (κ = 0.8). Prior to treatment, patients had significantly greater daily postprandial hydrogen than healthy controls (p < 0.001). The mean postprandial hydrogen of patients reduced significantly after treatment (p < 0.001). Conclusions: Measuring postprandial hydrogen shows potential as a means of differentiating patients with chronic GI symptoms from healthy controls and may be useful in monitoring patients before, during, and after treatment. Future studies could help determine if pre-treatment breath gas levels are predictive of response to antibiotic treatment. [ABSTRACT FROM AUTHOR]

The broom twig miner, Leucoptera spartifoliella (Hübner) is a highly specific biological control agent for the Scotch broom, Cytisus scoparius (L.). Cytisus scoparius has become a major invasive weed spreading in North America, South America, Australia and both the South and North Island of New Zealand, causing a major disturbance to the ecology of the area where it has been established. Currently, there is no tool available to monitor the population density, dispersal, and establishment of L. spartifoliella. This work was undertaken to identify the sex pheromone of L. spartifoliella and develop a monitoring tool for this biological control agent. Analysis of the extract of the female sex pheromone gland by gas chromatography/mass spectrometry and chemical ionization identified a single compound in the extract. Using the mass spectral data and synthesis of candidate compounds, this compound was identified as 5-methylheptadecane. In a field trapping trial, testing various doses (0.01, 0.1 and 1 mg) of 5-methylheptadecane and virgin females as a positive control, the highest male catch obtained was in traps baited with the 1 mg dose. When testing two releasing substrates for the pheromone (i.e. a glass vial containing a cotton ball and another containing white septum), the male catch in a trap baited with a glass vial with the cotton ball was significantly higher than in a trap baited with a white septum. The identification of the sex pheromone of L. spartifoliella will help to detect and determine population densities, distribution, and dispersal of L. spartifoliella. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate ECG-gated retinal vessel calibre as a novel measure of aberrant pulsatile retinal flow in diabetes mellitus. Methods: A novel mydriatic ECG-gated fundoscope was used to acquire retinal vessel calibre measurements at four cardiac cycle time points from end diastole to early diastole. An inhouse software recorded the exact time when an image was captured to corroborate ECG-synchronisation. Arterial applanation tonometry, an alternative method of assessing aberrant blood flow, was used to measure carotid-femoral pulse wave velocity (cPWV) and augmentation index (AIx). The intraclass correlation (ICC) was used to perform intra- and inter-observer reliability analyses. Two reviewers measured the retinal vessel calibre in single retinal arterioles and venules. A receiver operating characteristic curve determined associations with diabetes mellitus. Results: In this study 119 controls and 120 participants with diabetes mellitus were recruited. Mean peak change in retinal arteriolar calibre from baseline was higher in diabetes mellitus compared with controls (controls: 0.92%, IQR 0.63 vs diabetes mellitus: 2.05%, IQR 1.25, p<0.0001). In a subset of 9 controls and 11 participants, the intra-and inter-observer reliability was high (ICC 0.87-0.97) in mean peak changes in retinal vascular responses from baseline. In a subset of 36 controls and 95 participants with diabetes mellitus, diabetes mellitus was more strongly associated with retinal arteriolar pulsatility (AUC 0.85, 95%CI 0.76-0.93) than applanation tonometry (cfPWV AUC 0.72, 95%CI 0.62-0.82 vs AIx AUC 0.56, 95%CI 0.45-0.68). Conclusion: Higher retinal arteriolar pulsatility appears to be more strongly correlated with diabetes mellitus than arterial applanation tonometry. [ABSTRACT FROM AUTHOR]

Food delivery platforms are designed to match on-demand workers with jobs and then manage, monitor, and assess their performance. These platforms provide workers with a digital representation of delivery work. Once a worker accepts a delivery job they need to deal with the complexities of an unsettled urban landscape with varied infrastructures, traffic, and regulations. In particular, the Global South presents a demanding context for this type of work, given less clearly mapped addresses alongside other socio-cultural intricacies. In order to understand how food delivery workers bridge gaps and mismatches between the demands of the app and the realities encountered in situ, for this paper we shadowed six delivery workers over the course of their working day delivering food in Pune, India. The six workers included a complete novice and more experienced riders. We used helmet mounted cameras to record the delivery work, and how our participants managed the extra demands of food delivery work during the COVID-19 pandemic. Our moment-by-moment analysis of the video data is informed by the methodological traditions of ethnomethodology and conversation analysis. While the food delivery platform imposes a detailed workflow expected to be performed alone by the worker, our detailed video analysis reveals the collaborative nature of delivery work. We highlight how workers draw upon their ability to participate in 'fleeting alliances' and produce 'frugal collaboration' with co-located others, such as other delivery workers or security guards. This allows them to resolve everyday troubles, often learning or imparting 'the tricks of the trade' in the process. While gig platforms have commonly been presented as disruptive technologies for coordinating, regulating, and assessing gig workers individually and independently, our findings highlight collaboration as a critically important aspect of food delivery work. [ABSTRACT FROM AUTHOR]

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Schools face an unprecedent demand for mental health services. Student mental health problems can be addressed via a continuum of mental health evidence-based practices (EBPs) integrated within school-wide Positive Behavioral Interventions and Supports (PBIS). However, integrating mental health interventions with PBIS can be challenging. The purpose of this study is to examine the integration of mental health interventions with PBIS in a group of schools in Pennsylvania. We describe the extent to which schools implementing PBIS with fidelity were using mental health EBPs at tiers 2 and 3, examine recommendations about how to achieve further integration, and identify school professional needs for training and support. The study is based on a statewide sample of 48 K-8 schools. Members of the leadership team completed questionnaires and participated in qualitative interviews. Most schools had established advanced tiers of support and offered EBPs for externalizing behavior problems at tier 2. However, few schools reported offering mental health EBPs at tier 3, or interventions for internalizing problems. Qualitative analyses of interview transcripts revealed key recommendations regarding characteristics of interventions students should receive, who should provide the extra supports to students and the type of training that should be made available to school personnel and providers of tier 2 and tier 3 interventions. Participants indicated school mental health personnel did not receive adequate technical assistance to implement EBPs. [ABSTRACT FROM AUTHOR]

Background: Frailty is a risk factor for presentation to the ED, in-hospital mortality, prolonged hospital stays and functional decline at discharge. Profiling the prevalence and level of frailty within the acute hospital setting is vital to ensure evidence-based practice and service development within the construct of frailty. The aim of this cross-sectional study was to establish the prevalence of frailty and co-morbidities among older adults in an acute hospital setting. Methods: Data collection was undertaken by clinical research nurses and advanced nurse practitioners experienced in assessing older adults. All patients aged ≥ 65 years and admitted to a medical or surgical inpatient setting between 08:00 and 20:00 and who attended the ED over a 24-h period were screened using validated frailty and co-morbidity scales. Age and gender demographics, Clinical Frailty Scale (CFS), Charlson Co-morbidity Index (CCI) and admitting specialty (medical/surgical) were collected. Descriptive statistics were used to profile the cohort, and p values were calculated to ascertain the significance of results. Results: Within a sample of 413 inpatients, 291 (70%) were ≥ 65 years and therefore were included in the study. 202 of these 291 older adults (70%) were ≥ 75 years. Frailty was investigated using validated clinical cut-offs on the CFS (not frail < 5; frail ≥ 5). Comorbidities were investigated using the Charlson Comorbidity Index (mild 1–2; moderate 3–4; severe ≥ 5). The median CFS was 6 indicating moderate frailty levels, and the median CCI score was 3 denoting moderate co-morbidity. In the inpatient cohort, 245 (84%) screened positive for frailty, while 223 (75%) had moderate-severe co-morbidity (CCI Mod 3–4, severe ≥ 5). No significant differences were observed across genders for CFS and CCI. In the ED, 81 patients who attended the ED were ≥ 65 years. The median CFS was 6 (moderate frailty), and the median CCI was 5 (severe co-morbidity level). Seventy-four percent (60) of participants screened positively for frailty (CFS ≥ 5), and 31% (25) had a CFS of 7 or greater (severely frail). Ninety-six percent (78) of patients had a moderate-severe level of comorbidity. No significant associations were found between the CFS and CCI and ED participants age, gender, and medical/surgical speciality usage. Conclusion: There is a high prevalence of frailty and co-morbidity among older adults who present to the ED and require inpatient care. This may contribute to increased waiting times, lengths of stay, and the need for specialist intervention. With an increased focus on the integration of care for older adults across care transitions, there is a clear need for expansion of frailty-based services, staff training in frailty care and multidisciplinary team resources across the hospital and community setting. [ABSTRACT FROM AUTHOR]

Background: Approximately 1 in 5 patients with autosomal dominant polycystic kidney disease (ADPKD) will undergo a native nephrectomy in their lifetime. These can be emergent or planned and the indications can range from space for kidney transplant, pain, hematuria and frequent urinary tract infections (UTIs). Due to the diverse nature of presentations, there is a lack of certainty about outcomes and optimal management. Aims: This study aimed to evaluate preoperative indications and perioperative/postoperative complications in this patient cohort. Methods: This retrospective review included 41 patients with ADPKD who underwent unilateral or bilateral nephrectomy in a single hospital between 2010 and 2020. We collected data on patient demographics, surgical indications, histological results and postoperative complications. We sourced this information using the hospital's patient medical records. Results: The main indications for nephrectomy were pain (39.5%) and bleeding (41.8%). Further indications included recurrent UTIs (16.3%), space for transplantation (27.9%), query malignancy (4.7%) and compressive gastropathy (2.3%). With regard to side, 55.8% were right-sided, 23.3% were left-sided, and 20.9% were bilateral. Seven percent of nephrectomy specimens demonstrated malignancy. Postoperative morbidity included requiring blood transfusion and long hospital stay. Thirty-seven percent of patients received a postoperative blood transfusion. There was no immediate or postoperative mortality associated with any of the cases reviewed. Conclusions: In conclusion, this study demonstrates that native nephrectomy remains a safe operation for patients with ADPKD. Although further research is needed into, transfusion protocols, adjunctive therapies, such as TAE and research into timing of nephrectomy are still needed. [ABSTRACT FROM AUTHOR]

Background: Despite developing a polypharmacy core outcome set (COS) in primary care, it is not clear how these outcomes should be measured. Aim: To select outcome measurement instruments (OMIs) for a COS targeting appropriate polypharmacy in older patients in primary care. Method: Following the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) guideline, OMIs were identified from a Cochrane review focusing on appropriate polypharmacy. The quality of OMIs was assessed using a published checklist. Subsequently, two rounds of Delphi questionnaires were conducted via the SoGoSurvey® platform, engaging stakeholders (researchers, clinicians and journal editors specialising in geriatric primary care) to achieve consensus on OMIs using a scale encompassing "agree", "disagree", or "unsure". Consensus was achieved if 70% or more participants chose "agree" and 15% or fewer chose "disagree." Results: The quality of 20 OMIs identified from the Cochrane review was evaluated. Seven OMIs were selected based on meeting the COSMIN guideline's minimum requirements. Out of 188 potential participants, 57 (30.3%) consented to participate. Rounds 1 and 2 of Delphi exercises were completed by 50 respondents, achieving agreement on three OMIs: 'number of serious adverse drug reactions (ADRs)' (98%), 'number of deaths' (76%), and 'number of patients who fell' (70%) for measuring 'serious ADRs,' 'mortality,' and 'falls,' respectively. No agreement was reached for 'medication appropriateness,' 'medication side-effects,' 'quality of life,' and 'medication regimen complexity.' Conclusion: OMIs were selected for a limited number of outcomes in the polypharmacy COS. Future research should identify suitable OMIs for the remaining four outcomes. [ABSTRACT FROM AUTHOR]

Global eradication of peste des petits ruminants (PPR) is planned for 2030 by international animal health organizations in collaboration with national partners. As the deadline approaches, it is fundamental that the PPR status in each country is determined. In addition, the identification of other pathogens of small ruminants that share common geographical locations and can produce similar clinical signs is also important for differential diagnosis. With this in mind, 37 samples collected from goats and sheep presenting respiratory symptoms in Mauritania in 2023 were screened for the presence of PPR virus, Capripoxvirus, Pasteurella multocida and Mycoplasma capricolum subspecies capripneumoniae (Mccp) using a one-step multiplex RT-qPCR assay. None of the samples were positive for Capripoxvirus or P. multocida. Nine of them were positive for PPRV and sequence analysis of a segment of the PPRV nucleoprotein revealed that they belonged to lineage IV and were similar to viruses recently identified in Côte D'Ivoire, Guinea, and Niger indicating transboundary movement. The full genome of one representative virus was also generated. Mccp was identified in eight samples and multi-locus sequence analysis (MLSA) identified them as belonging to MLSA Group 3 together with Mccps identified in China, Tajikistan, Turkey and the United Arab Emirates. This is the first time that such a study has been undertaken in Mauritania and the data generated should be of interest to those involved in the management of goat diseases in Mauritania and neighbouring countries. [ABSTRACT FROM AUTHOR]

Background: Fear of missing out (FoMO) and homesickness have been associated with a variety of negative psychosocial outcomes; however, they have rarely been studied together or with adolescents in residential settings. Objective: This study examined the potential associations of FoMO and homesickness with program outcomes in a sample of adolescents attending a military-style residential program. The residential treatment context inherently involves removal and isolation from an individual's typical living arrangements. Methods: Data were collected from 185 participants (aged 16–18) at three time points (i.e., 2 weeks after entry into the 19-week program; 9 weeks into the program; at week 18 of the program). RESULTS: Overall, FoMO and homesickness declined from initial assessment to midway through the program but rebounded just prior to exit from the program. FoMO and homesickness showed no direct correlations with participant outcomes, although both showed patterns of correlation demonstrating poor adjustment (e.g., low emotion regulation, high loneliness). Decreases in FoMO and homesickness during the program were positively correlated with distress tolerance. Conclusions: Given the negative implications of experiencing FoMO and homesickness, adolescents at risk for emotional distress tolerance may need additional support when initiating participation in residential programs. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a common cancer, with a concerning rise in early-onset CRC cases, signalling a shift in disease epidemiology. Whilst our understanding of the molecular underpinnings of CRC has expanded, the complexities underlying its initiation remain elusive, with emerging evidence implicating the microbiome in CRC pathogenesis. This review synthesizes current knowledge on the intricate interplay between the microbiome, tumour microenvironment (TME), and molecular pathways driving CRC carcinogenesis. Recent studies have reported how the microbiome may modulate the TME and tumour immune responses, consequently influencing cancer progression, and whilst specific bacteria have been linked with CRC, the underlying mechanisms remains poorly understood. By elucidating the functional links between microbial landscapes and carcinogenesis pathways, this review offers insights into how bacteria orchestrate diverse pathways of CRC development, shedding light on potential therapeutic targets and personalized intervention strategies. [ABSTRACT FROM AUTHOR]

Abstract Genetic engineering is a complex topic, even for scientists working in other areas, and even more so for those who lack a formal scientific training. To help gene specialists and affected communities talk with one another, international guidance documents have been published that promote dialogue and exchanges. The current paper explores collaboration among scientists of different disciplines as well as between scientists, the local communities, mediated by theatre actors to develop a conversation about Target Malaria’s work on genetic technologies to modify mosquitoes for malaria elimination in Burkina Faso. It focuses on the co-construction of meaning of key scientific concepts with a view to fostering productive collaboration between scientists and the local community. The community provided feedback on what was shared with them regarding the science being developed in the lab and in the field, which in turn informed aspects of the research itself, and the nature of the collaboration between the scientists and the local community.

Abstract An essential step for SARS‐CoV‐2 infection is the attachment to the host cell receptor by its Spike receptor‐binding domain (RBD). Most of the existing RBD‐targeting neutralizing antibodies block the receptor‐binding motif (RBM), a mutable region with the potential to generate neutralization escape mutants. Here, we isolated and structurally characterized a non‐RBM‐targeting monoclonal antibody (FD20) from convalescent patients. FD20 engages the RBD at an epitope distal to the RBM with a KD of 5.6 nM, neutralizes SARS‐CoV‐2 including the current Variants of Concern such as B.1.1.7, B.1.351, P.1, and B.1.617.2 (Delta), displays modest cross‐reactivity against SARS‐CoV, and reduces viral replication in hamsters. The epitope coincides with a predicted “ideal” vulnerability site with high functional and structural constraints. Mutation of the residues of the conserved epitope variably affects FD20‐binding but confers little or no resistance to neutralization. Finally, in vitro mode‐of‐action characterization and negative‐stain electron microscopy suggest a neutralization mechanism by which FD20 destructs the Spike. Our results reveal a conserved vulnerability site in the SARS‐CoV‐2 Spike for the development of potential antiviral drugs.