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Ibrutinib and acalabrutinib are both associated with an increased risk of atrial fibrillation (AF); however, the comparative risk of AF between these 2 BTK inhibitors remains largely unknown. Our primary aim was to evaluate the risk of incident AF in patients exposed to ibrutinib compared to those exposed to acalabrutinib. Using the TriNetX research network database, we established a retrospective cohort of adult patients (≥ 18 years) previously diagnosed with a B-cell malignancy (using ICD-10-CM codes) in whom a first BTKi introduction occurred between January 1st, 2013 (first patient exposed to ibrutinib in TriNetX) and July 1st, 2024. Patients were divided into 2 groups based on their exposure to ibrutinib or acalabrutinib. After propensity score matching (PSM) across 37 covariates, Cox proportional hazard models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) to compare the 2 matched groups. The appropriateness of the proportional hazard assumption was examined and risk differences (RDs) were used if appropriate. Results were summarized with the use of Kaplan–Meier survival curves. Follow-up started from 1 day after first BTKi introduction and continued over a 6-year follow-up period. A cohort of 12,449 patients exposed to ibrutinib and 4,131 to acalabrutinib were included in the study. After PSM, 4,090 patients remained in each group (1:1). During a mean duration of BTKi exposure of 2.3 ± 1.8 years, we found a significantly higher risk of incident AF in the ibrutinib group compared to the acalabrutinib group (RD 0.09, 95% CI 0.07–0.10). This difference was consistent across subgroups (age ≤ or > 75 and lower or higher baseline cardiovascular risk of developing AF). In conclusion, among patients with B-cell malignancies, the risk of developing incident AF is increased when treated with ibrutinib compared to acalabrutinib. Trial registration ClinicalTrial registration number: NCT06561243. [ABSTRACT FROM AUTHOR]

Study Design: Prospective Cohort Study Objectives: The purpose of this study was to prospectively evaluate the impact of preoperative dysphagia on the postoperative incidence and severity of dysphagia in patients undergoing ACDF at multiple institutions. Methods: After IRB approval, patients over 18 years of age who underwent an elective ACDF for degenerative conditions were prospectively enrolled at two academic centers from 2018 to 2021. Preoperative dysphagia was self-reported by patients through a pre-operative questionnaire on a binary basis. Patients completed dysphagia surveys (Bazaz, Dysphagia Short Questionnaire, 10-item Eating Assessment Tool) to assess dysphagia severity during their preoperative visit, and these dysphagia surveys were repeated immediately postoperatively, at two weeks and again at six, 12, and 24 weeks postoperatively. Patients were stratified into three subgroups based on dysphagia status preoperatively and immediately postoperatively and compared using ANOVA tests or Kruskal–Wallis tests for continuous variables and Pearson chi-square analysis or Fisher's Exact test for categorical variables. Results: A total of 168 patients (23 with preoperative dysphagia, 145 without preoperative dysphagia) met study criteria and were enrolled in the study. Patients with preoperative dysphagia had less frequent alcohol consumption (23.8% vs 53.7%, P =.0210), and higher rates of dysphagia at 2-weeks (77.8% vs 38.7%, P =.004) and 24-weeks (43.8% vs 14.8%, P =.010) postoperatively. These patients also had higher severity scores for dysphagia on the Bazaz (P =.001), DSQ (P =.012), EAT10 (P =.022) questionnaires at the 2-week follow-up period, higher DSQ scores (P =.036) at the 6-week follow-up period, higher EAT-10 scores (P =.009) at the 12-week follow-up period, and higher Bazaz (P =.001), DSQ (P =.002), and EAT-10 (P =.005) scores at the 24-week follow-up period. There were no differences in demographic, medical history, surgical variables, rates of ENT consultation, length of stay, or other in-hospital events between groups. Conclusions: Patients undergoing ACDF who had preoperative dysphagia have prolonged postoperative dysphagia and greater dysphagia severity. Surgeons should be aware of the risk of prolonged dysphagia severity that may persist past 24 weeks after surgery when discussing clinical decisions with patients. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) patients represent a clinically complex, heterogeneous population comprising multiple homogeneous cohorts. Purpose: We aimed to identify the common clinical phenotypes of AF patients and compare clinical outcomes between these subgroups. Methods: A 1% representative sample of all AF patients hospitalized between 2010 and 2019 was identified from the French national database. Agglomerative hierarchical cluster analysis was performed using Ward's method and squared Euclidian distance to derive the clusters of patients. Cox regression analyses were used to evaluate outcomes including all-cause death, cardiovascular death, non-cardiovascular death, ischemic stroke, hospitalization for heart failure (HF) and composite of ventricular tachycardia, ventricular fibrillation and cardiac arrest (VT/VF/CA) over a mean follow-up period of 2.0 ± 2.3 years. Results: Four clusters were generated from the 12,688 patients included. Cluster 1 (n = 2375) was younger, low cardiovascular disease (CVD)-risk group with a high cancer prevalence. Clusters 2 (n = 6441) and 3 (n = 1639) depicted moderate-risk groups for CVD. Cluster 3 also had the highest degree of frailty and lung disease while Cluster 4 (n = 2233) represented a high-risk cohort for CVD. After adjusting for confounders, with cluster 1 as the reference, cluster 3 had the highest risk of all-cause death, HR 1.24 (1.09–1.41), ARD (10.3%), cardiovascular death, HR 1.56 (1.19–2.06), ARD (3.3%), non-cardiovascular death, HR 1.20 (1.04–1.38), ARD (6.9%), hospitalization for HF, HR 2.07 (1.71–2.50), ARD (9.1%) and VT/VF/CA, HR 1.74 (1.20–2.53), (ARD 1.3%). Conclusions: Four distinct clusters of AF patients were identified, discriminated by the differential presence of comorbidities. Our findings suggest that hospitalized AF patients with moderate CVD risk may have a poorer prognosis compared to hospitalized AF patients with high CVD risk in the presence of lung pathology and frailty. This subgroup of patients may require more stringent management of existing comorbidities such as chronic obstructive pulmonary disease and sleep apnea, alongside their AF. [ABSTRACT FROM AUTHOR]

Background Myocardial bridging (MB) is considered a frequent and benign condition. However, some patients may experience symptoms. The recent ESC guidelines on sports participation provide guidance on the management of these symptomatic patients with MB but do not provide guidance in the presence of another cardiac pathology. Case summary A 14-year-old-male was admitted for ongoing chest pain and palpitations. He practiced rowing at a competitive level and had an episode of exercise-induced paroxysmal atrial fibrillation (AF) a month ago. A 12-lead electrocardiogram and biomarkers orientated toward an acute coronary syndrome. Transthoracic echocardiography was normal. Cardiac magnetic resonance imaging ruled out the hypothesis of myocarditis and showed no ischemic scar. A coronary computed tomography scan showed a significant MB of the left anterior descending coronary artery. We introduced a beta-blocker and monitored the absence of inducible ischaemia with an exercise echocardiography. Our conclusion was a myocardial infarction with non-obstructive coronary arteries due to MB and adrenergic AF. Return to rowing practice including competitions was allowed under beta-blocker therapy. The 6-year follow-up showed no recurrence of AF under treatment. The patient kept on training and competing, though at a lower level. Discussion This atypical case demonstrates that the so-called benign MB may become malignant, in particular in conjunction with rapid non-physiologic heart rate, and that dealing with this abnormality in athletes remains difficult despite the latest guidelines. Safe return-to-play and competition remain, however, possible under medical therapy if the patient is asymptomatic and has no inducible ischaemia. [ABSTRACT FROM AUTHOR]

Today's political climate is turbulent and polarized. It appears that liberals and conservatives and their respective parties are continuing to grow further apart ideologically, making it increasingly difficult to work together for the good of our country. Marketing researchers use segmentation and positioning analysis to gain a better understanding of consumers' perceptions to increase their success in the marketplace. In this paper, we demonstrate that these same multivariate methods can be used to investigate the current political climate. Across three samples, we find support for political polarization based on voters' views of important political issues. We also find that although the political parties align well with their ideologically typical issues, the presidential candidates (Trump and Biden) do not align well with the issues or their parties. This leads to the conclusion that they may not the best candidates for their parties or the voters. Consumer centric marketers want to help consumers make better decisions so that they are more satisfied with their consumption choices. Ideally, politicians should also want to help voters make better decisions so that voters are more satisfied with their choices of who is best suited to lead our country. The primary contribution of this paper is to demonstrate the application and benefits of using two common marketing analytics methodologies in the investigation of important political issues and voter perceptions. Additionally, this paper also provides practical implications that are applicable to political scientists, political practitioners, and voters. [ABSTRACT FROM AUTHOR]

Aim: To investigate the associations of high‐density lipoprotein (HDL) subfractions and apolipoprotein A‐I (apo A‐I) with fat in the pancreas. Methods: A total of 170 individuals were studied. All participants underwent magnetic resonance imaging on a single 3.0‐Tesla scanner to determine the presence/absence of fatty pancreas. HDL subfractions were measured using a commercially available lipoprotein subfractions testing system and classed as large, intermediate and small HDL. Both unadjusted and adjusted (accounting for demographics, anthropometrics, insulin resistance and other covariates) logistic regression models were built. Results: Individuals with fatty pancreas had significantly lower circulating levels of the large HDL class and apo A‐I. Every unit decrease in the large HDL class was associated with a 93% increase in the likelihood of fatty pancreas in the most adjusted model (P <.001). Every unit decrease in apo A‐I was associated with a 45% increase in the likelihood of fatty pancreas in the most adjusted model (P =.012). The intermediate and small HDL classes were not significantly associated with fatty pancreas. Conclusions: Fat in the pancreas is inversely associated with the circulating levels of large HDL particles and apo A‐I. Purposely designed studies are warranted to investigate the potential of fatty pancreas as an indicator of the risk of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Coulomb explosion is an established momentum imaging technique, where the molecules are ionized multiple times on a femtosecond time scale before breaking up into ionized fragments. By measuring the momentum of all the ions, information about the initial molecular structure is theoretically available. However, significant geometric changes due to multiple ionizations occur before the explosion, posing a challenge in retrieving the ground-state structure of molecules from the measured momentum values of the fragments. In this work, we investigate theoretically and experimentally such a connection between the ground-state geometry of a polyatomic molecule (OCS) and the detected momenta of ionic fragments from the Coulomb explosion. By relying on time-dependent density functional theory (TDDFT), we can rigorously model the ionization dynamics of the molecule in the tunneling regime. We reproduce the energy release and the Newton plot momentum patterns of an experiment in which OCS is ionized to the 6+ charge state. Our results provide insight into the behavior of molecules during strong field multiple ionization, opening a way toward precision imaging of real-space molecular geometries using tabletop lasers. Understanding molecular structure and dynamics through strong-field laser interactions holds great promise. The authors use quantum calculations to show how bonds and angles evolve in an OCS molecule ionized six times by a 7 fs, 800 nm laser pulse, accurately predicting our experimental results. [ABSTRACT FROM AUTHOR]

Coulomb explosion is an established momentum imaging technique, where the molecules are ionized multiple times on a femtosecond time scale before breaking up into ionized fragments. By measuring the momentum of all the ions, information about the initial molecular structure is theoretically available. However, significant geometric changes due to multiple ionizations occur before the explosion, posing a challenge in retrieving the ground-state structure of molecules from the measured momentum values of the fragments. In this work, we investigate theoretically and experimentally such a connection between the ground-state geometry of a polyatomic molecule (OCS) and the detected momenta of ionic fragments from the Coulomb explosion. By relying on time-dependent density functional theory (TDDFT), we can rigorously model the ionization dynamics of the molecule in the tunneling regime. We reproduce the energy release and the Newton plot momentum patterns of an experiment in which OCS is ionized to the 6+ charge state. Our results provide insight into the behavior of molecules during strong field multiple ionization, opening a way toward precision imaging of real-space molecular geometries using tabletop lasers. Understanding molecular structure and dynamics through strong-field laser interactions holds great promise. The authors use quantum calculations to show how bonds and angles evolve in an OCS molecule ionized six times by a 7 fs, 800 nm laser pulse, accurately predicting our experimental results. [ABSTRACT FROM AUTHOR]

Objective: Previous studies have investigated the association between hepatic fat and intrapancreatic fat deposition (IPFD); however, results have been inconclusive. The presence of cardiometabolic factors in certain subpopulations could explain this discrepancy. The aim of the present study was to use moderation analyses to determine the conditions under which hepatic fat is associated with IPFD. Methods: All participants underwent 3T abdominal magnetic resonance imaging (MRI) and spectroscopy. Hepatic fat and IPFD were manually quantified by independent raters. Moderation analyses were performed with adjustment for sex and ethnicity. Results: There were 367 participants included. Adjusted analyses of the overall cohort revealed that age, glycated hemoglobin (HbA1c), low‐density lipoprotein cholesterol (LDL‐C), high‐density lipoprotein cholesterol (HDL‐C), and triglycerides were significant moderators (p < 0.05) of the association between hepatic fat and IPFD. Ranges of significance included age < 61 years, HbA1c < 45 mmol/mol, LDL‐C < 157 mg/dL, HDL‐C > 36 mg/dL, and triglycerides < 203 mg/dL. Conclusions: The association between hepatic fat and IPFD is generally present in young and middle‐aged adults with good cardiometabolic health, whereas the link between the two fat depots becomes uncoupled in older adults or individuals with cardiometabolic risk factors. [ABSTRACT FROM AUTHOR]

Uncultured microorganisms represent a promising and untapped source of antibacterial compounds, crucial in the fight against the significant threat of antimicrobial resistance (AMR). In this study, both traditional and isolation chip (iChip) cultivation techniques were employed to enhance the recovery of known and unknown microorganisms from soils located in Normandy, France. The isolates obtained were identified using 16S rDNA or ITS regions analysis and MALDI-TOF mass spectrometry and were screened for antibacterial activity. A total of 386 isolates, belonging to 6 microbial phyla and distributed across 65 genera, were recovered using both methods. In total, 11 isolates are potentially new bacterial species, and 34 were associated with 22 species described recently. The iChip method yielded a higher diversity of microorganisms (47 genera) than the traditional method (38 genera) and was particularly effective in enriching Actinomycetota. Antibacterial screening against target bacteria showed that 85 isolates (22%) exhibited antibacterial activity. The Streptomyces, Pseudomonas, and Bacillaceae taxa accounted for most antibacterial-producing bacteria with some presenting promising undescribed characteristics. Other active isolates were affiliated with less-known antibacterial producers such as Arthrobacter, Chryseobacterium, Delftia, Ensifer, Flavobacterium, Rahnella, and Stenotrophomonas, among others. These results highlight the potential of our microbial collection as a source of new antibacterial natural products. [ABSTRACT FROM AUTHOR]

Background: People living in precarious socio-economic conditions are at greater risk of developing mental and physical health disorders, and of having complex needs. This places them at risk of health inequity. Addressing social determinants of health (SDH) can contribute to reducing this inequity. Case management in primary care is an integrated care approach which could be an opportunity to better address SDH. The aim of this study is to better understand how case management in primary care may address the SDH of people with complex needs. Methods: A case management program (CMP) for people with complex needs was implemented in four urban primary care clinics. A qualitative study was conducted with semi-structured interviews and a focus group with key informants (n = 24). An inductive thematic analysis was carried out to identify emerging themes. Results: Primary care case managers were well-positioned to provide a holistic evaluation of the person's situation, to develop trust with them, and to act as their advocates. These actions helped case managers to better address individuals' unmet social needs (e.g., poor housing, social isolation, difficulty affording transportation, food, medication, etc.). Creating partnerships with the community (e.g., streetworkers) improved the capacity in assisting people with housing relocation, access to transportation, and access to care. Assuming people provide their consent, involving a significant relative or member of their community in an individualized services plan could support people in addressing their social needs. Conclusions: Case management in primary care may better address SDH and improve health equity by developing a trusting relationship with people with complex needs, improving interdisciplinary and intersectoral collaboration and social support. Future research should explore ways to enhance partnerships between primary care and community organizations. [ABSTRACT FROM AUTHOR]

Background: Non-obese patients with diabetes mellitus (DM) are becoming more prevalent, but their cardiovascular risk (CV) especially when accompanied with cardio-renal-metabolic co-morbidities (hypertension, chronic kidney disease, hyperlipidemia) is not well characterised. The aim of the study was to assess the CV risk among patients with DM in relation to obesity and cardio-renal-metabolic co-morbidities. Materials and methods: This was a cohort study of all patients with DM without a history of major adverse cardiovascular event who were hospitalized for any reason in France in 2013 with at least 5 years of follow-up. They were categorized by the presence of obesity vs no obesity, as well as three cardio–renal–metabolic co-morbidities: hypertension, chronic kidney disease, hyperlipidemia. 'Extremely unhealthy' patients with DM were defined as those having all 3 co-morbidities. Results: There were 196,112 patients (mean age 65.7 (SD 13.7) years; 54.3% males) included into the analysis. During a mean follow-up of 4.69 ± 1.79 years, when adjusted for multiple covariates, the non-obese and 'extremely unhealthy' obese patients had the highest risk of CV death [aHR 1.40 (95% CI, 1.22–1.61) and 1.48 (95% CI, 1.25–1.75), respectively]. The 'extremely unhealthy' obese had the highest risk of MACE-HF [aHR 1.84 (95% CI, 1.72–1.97)] and new-onset AF [aHR 1.64 (95% CI, 1.47–1.83)]. Conclusion: Both non-obese and obese patients with DM with associated cardio-renal-metabolic co-morbidities are an 'extremely unhealthy' phenotype with the highest risk of CV death and CV events. [ABSTRACT FROM AUTHOR]

Background: Atrioventricular node ablation (AVNA) with permanent pacing is an effective treatment of symptomatic atrial fibrillation (AF). Left bundle branch area pacing (LBBAP) prevents cardiac dyssynchrony associated with right ventricular pacing and could prevent worsening of heart failure (HF). Methods: In this retrospective monocentric study, all patients who received AVNA procedure with LBBAP were consecutively included. AVNA procedure data, electrical and echocardiographic parameters at 6 months, and clinical outcomes at 1 year were studied and compared to a matched cohort of patients who received AVNA procedure with conventional pacing between 2010 and 2023. Results: Seventy-five AVNA procedures associated with LBBAP were studied. AVNA in this context was feasible, with a success rate of 98.7% at first ablation, and safe without any complications. There was no threshold rise at follow-up. At 1 year, 6 (8%) patients were hospitalized for HF and 2 (2.7%) were deceased. Patients had a significant improvement in NYHA class and left ventricular ejection fraction (LVEF) (P ≤ 0.0001). When compared to a matched cohort of patients with AVNA and conventional pacing, AVNA data and pacing complications rates were similar. Patients with LBBAP had a better improvement of LVEF (+5.27 ± 9.62% vs. −0.48 ± 14%, P = 0.01), and a lower 1-year rate of composite outcome of hospitalization for HF or death (HR 0.39, 95% CI: 0.16–0.95, P = 0.037), significant on survival analysis (log-rank P-value = 0.03). Conclusion: AVNA with LBBAP in patients with symptomatic AF is feasible, safe, and efficient. Hospitalization for HF or death rate was significantly lower and LVEF improvement was greater. [ABSTRACT FROM AUTHOR]

Questions: How does the type of swamp, that is, riverine vs palustrine, shape understorey and overstorey plant communities? Beyond swamp type, how do spatial, topographic, soil and landscape characteristics determine the taxonomic and functional structure of swamp communities? Location: Southern Québec, Canada. Methods: We sampled riverine and palustrine swamp plant communities in two watersheds within two ecoregions with contrasting land use. At the site scale (n = 56), we analyzed differences between riverine and palustrine swamps in plant richness and cover, species composition, and mean and dispersion values for ecological and morphological traits. At the plot scale (n = 213), we assessed the relative influence of a set of environmental parameters on species richness and cover, as well as on trait values using mixed models and on species composition using redundancy analysis. Results: Species composition and the mean value of traits varied significantly between the two types of swamps. While riverine swamps hosted more non‐native species and were composed of more mesophilic species, shorter in height and with dominant resource acquisition strategies, palustrine swamps sheltered more non‐vascular taxa and tall hygrophilous vascular species with more conservative resource strategies. The surrounding landscape and local microtopography within swamps had a significant effect on plant community structure. Species diversity and trait dispersion increased from agricultural‐dominated to forest‐dominated landscapes, and from homogeneous to heterogeneous substrates. Conclusions: Habitats provided by riverine and palustrine swamps are complementary for wetland biodiversity. Our results underline the need to develop conservation plans to protect a wide variety of freshwater swamp types; for example, management actions that maintain or promote heterogeneous topographic forms at the site scale, and continuity of forest cover at the landscape scale. [ABSTRACT FROM AUTHOR]

Traumatic spinal cord injuries (SCI) result in devastating impairment to an individual's functional ability. The pathophysiology of SCI is related to primary injury but further propagated by secondary reactions to injury, such as inflammation and oxidation. The inflammatory and oxidative cascades ultimately cause demyelination and Wallerian degeneration. Currently, no treatments are available to treat primary or secondary injury in SCI, but some studies have shown promising results by lessening secondary mechanisms of injury. Interleukins (ILs) have been described as key players in the inflammation cascade after neuronal injury; however, their role and possible inhibition in the context of acute traumatic SCIs have not been widely studied. Here, we review the relationship between SCI and IL-6 concentrations in the CSF and serum of individuals after traumatic SCIs. Furthermore, we explore the dual IL-6 signaling pathways and their relevance for future IL-6 targeted therapies in SCI. [ABSTRACT FROM AUTHOR]

Background/Objectives: Diospyros kaki, the most widely cultivated species of persimmon, has been long used in traditional medicine since its leaves' extracts contain high amounts of flavonoids and terpenoids, endowed with several beneficial effects. However, its anticancer activity towards colorectal cancer (CRC) has not been investigated in depth. Methods: The effect of a methanolic extract of D. kaki leaves, rich in kaempferol and quercetin derivatives, have been evaluated on an E705 CRC cell line, representative of most CRC patients, and on SW480 cells, carrying a KRAS-activating mutation. Results: This extract is effective in reducing tumor cells' viability without affecting the healthy mucosa cell line CCD 841. In fact, Western blot experiments showed its ability to induce apoptosis in cancer cells by increasing oxidative stress and disrupting mitochondrial functionality, as shown by reactive oxygen species measurement and Seahorse analysis. Conclusions: With the aim of increasing healthspan, as well as the substantial societal and macroeconomic costs associated with cancer, our results could pave the way to a role for D. kaki extract in both CRC treatment and prevention. [ABSTRACT FROM AUTHOR]

The complexity of cancer requires a comprehensive approach to understand its diverse manifestations and underlying mechanisms. Initially outlined by Hanahan and Weinberg in 2000 and updated in 2010, the hallmarks of cancer provide a conceptual basis for understanding inherent variability in cancer biology. Recent expansions have further elucidated additional hallmarks, including phenotypic plasticity and senescent cells. The International Agency for Research on Cancer (IARC) has identified the key characteristics of carcinogens (KCCs) to evaluate their carcinogenic potential. We analyzed chemicals of concern for environmental exposure that interact with specific receptors to induce genomic instability, epigenetic alterations, immune suppression, and receptormediated effects, thereby contributing to chronic inflammation. Despite their varying degrees of carcinogenicity, these chemicals have similar KCC profiles. Our analysis highlights the pivotal role of receptor binding in activating most other KCCs, underscoring their significance in cancer initiation. Although KCCs are associated with early molecular or cellular events, they do not encompass processes directly linked to full cellular malignancy. Thus, there is a need to integrate clear endpoints that anchor KCCs to the acquisition of a complete malignant phenotype into chemical testing. From the perspective of toxicology and cancer research, an all-encompassing strategy that incorporates both existing and novel KCCs and cancer hallmarks is essential to enable the targeted identification of prevalent carcinogens and facilitate zone-specific prevention strategies. To achieve this goal, collaboration between the KCC and cancer hallmarks communities becomes essential. [ABSTRACT FROM AUTHOR]

Adaptor proteins play central roles in the assembly of molecular complexes and coordinated activation of specific pathways. Through their modular domain structure, the NCK family of adaptor proteins (NCK1 and NCK2) link protein targets via their single SRC Homology (SH) 2 and three SH3 domains. Classically, their SH2 domain binds to phosphotyrosine motif-containing receptors (e.g. receptor tyrosine kinases), while their SH3 domains bind polyproline motif-containing cytoplasmic effectors. Due to these functions being established for both NCK1 and NCK2, their roles were inaccurately assumed to be redundant. However, in contrast with this previously held view, NCK1 and NCK2 now have a growing list of paralog-specific functions, which underscores the need to further explore their differences. Here we review current evidence detailing how these two paralogs are unique, including differences in their gene/protein regulation, binding partners and overall contributions to cellular functions. To help explain these contrasting characteristics, we then discuss SH2/SH3 structural features, disordered interdomain linker regions and post-translational modifications. Together, this review seeks to highlight the importance of distinguishing NCK1 and NCK2 in research and to pave the way for investigations into the origins of their interaction specificity. [ABSTRACT FROM AUTHOR]

Aedes aegypti is an important vector of arboviruses, including dengue, chikungunya and Zika. The application of synthetic insecticides is a frequently used strategy to control this insect. Malathion is an organophosphate insecticide that was widely used in Brazil in the 1980s and 1990s to control the adult form of A. aegypti. In situations where resistance to currently used insecticides is detected, the use of malathion may be resumed as a control measure. Many studies have confirmed resistance to malathion, however, comparative studies of differential gene expression of the entire transcriptome of resistant and susceptible insects are scarce. Therefore, understanding the molecular basis of resistance to this insecticide in this species is extremely important. In this paper, we present the first transcriptomic description of susceptible and resistant strains of A. aegypti challenged with malathion. Guided transcriptome assembly resulted in 39,904 transcripts, where 2133 differentially expressed transcripts were detected, and three were validated by RT-qPCR. Enrichment analysis for these identified transcripts resulted in 13 significant pathways (padj < 0.05), 8 associated with down-regulated and 5 with up-regulated transcripts in treated resistant insects. It was possible to divide the transcripts according to the mechanism of action into three main groups: (i) genes involved in detoxification metabolic pathways; (ii) genes of proteins located in the membrane/extracellular region; and (iii) genes related to DNA integration/function. These results are important in advancing knowledge of genes related to resistance mechanisms in this insect, enabling the development of effective technologies and strategies for managing insecticide resistance. [ABSTRACT FROM AUTHOR]

Background: The role of nonspecific factors, such as treatment credibility, treatment expectancy, and symptom expectancy, may shape the outcomes of the nonoperative treatment of degenerative meniscal tears (DMTs). Purpose/Hypothesis: The purpose of this study was to characterize treatment credibility and expectancy, symptom expectancy, and patient and clinical correlates of these factors among participants before undergoing 4 nonoperative treatment programs for DMTs. It was hypothesized that (1) treatment credibility scores would be similar across patient and baseline clinical subgroups and (2) treatment expectancy and symptom expectancy scores would be lower in older patients and among those reporting a longer pain duration or greater pain intensity. Study Design: Cohort study; Level of evidence, 3. Methods: In 126 participants, validated scales were administered before treatment to assess the credibility of the assigned treatment (possible score of 1-9) as well as the expectations of treatment outcomes (0-100) and symptom improvement (1-5). Patient and clinical characteristics associated with these variables were examined. Results: On average, participants (mean age, 58 years [range, 45-75 years]; 51% female; 94% White) expected the treatment to improve their symptoms by a mean of 68% and expected their symptoms to be "very likely" to improve. Participants with a body mass index (BMI) ≥30 kg/m2 had lower mean treatment credibility (6.09 ± 1.81) and treatment expectancy (64.53 ± 25.16) scores on bivariate analyses than those with a BMI <30 kg/m2 (6.73 ± 1.69 [ P =.045] and 72.86 ± 19.20 [ P =.039], respectively). Participants reporting a pain duration ≥3 months also had lower mean treatment expectancy (63.85 ± 23.83) and symptom expectancy (3.70 ± 0.85) scores compared to those reporting a pain duration <3 months (75.52 ± 18.93 [ P =.003] and 4.16 ± 0.67 [ P =.001], respectively). Conclusion: Most patients about to undergo physical therapy for DMTs considered it to be between "somewhat" and "very" credible and believed that their symptoms, on average, were "very likely" to improve. Although not supported by most evidence, patients with a BMI ≥30 kg/m2 believed physical therapy to be less credible and had lower treatment and symptom expectations, and those with symptoms present for ≥3 months had lower treatment and symptom expectations as well. Whether these nonspecific factors influence outcomes should be considered for further research. [ABSTRACT FROM AUTHOR]

The PROSurvival project aims to improve the prediction of recurrencefree survival in prostate cancer by applying federated machine learning to whole slide images combined with selected clinical data. Both the image and clinical data will be aggregated into an anonymized dataset compliant with the General Data Protection Regulation and published under the principles of findable, accessible, interoperable, and reusable data. The DICOM standard will be used for the image data. For the accompanying clinical data, a human-readable, compact and flexible standard is yet to be defined. From the set of existing standards, mostly extendable with varying degrees of modifications, we chose oBDS as a starting point and modified it to include missing data points and to remove mandatory items not applicable to our dataset. Clinical and survival data from clinic-specific spreadsheets were converted into this modified standard, ensuring on-site data privacy during processing. For publication of the dataset, both image and clinical data are anonymized using established methods. The key challenges arose during the clinical data anonymization and in identifying research repositories meeting all of our requirements. Each clinic had to coordinate the publication with their responsible data protection officers, requiring different approval processes due to the individual states' differing interpretations of the legal regulations. The newly established German Health Data Utilization Act is expected to simplify future data sharing in a responsible and powerful way. [ABSTRACT FROM AUTHOR]

Bactofilins are rigid, nonpolar bacterial cytoskeletal filaments that link cellular processes to specific curvatures of the cytoplasmic membrane. Although homologs of bactofilins have been identified in archaea and eukaryotes, functional studies have remained confined to bacterial systems. Here, we characterize representatives of two families of archaeal bactofilins from the pleomorphic archaeon Haloferax volcanii, halofilin A (HalA) and halofilin B (HalB). HalA and HalB polymerize in vitro, assembling into straight bundles. HalA polymers are highly dynamic and accumulate at positive membrane curvatures in vivo, whereas HalB forms more static foci that localize in areas of local negative curvatures on the outer cell surface. Gene deletions and live-cell imaging show that halofilins are critical in maintaining morphological integrity during shape transition from disk (sessile) to rod (motile). Morphological defects in ΔhalA result in accumulation of highly positive curvatures in rods but not in disks. Conversely, disk-shaped cells are exclusively affected by halB deletion, resulting in flatter cells. Furthermore, while ΔhalA and ΔhalB cells imprecisely determine the future division plane, defects arise predominantly during the disk-to-rod shape remodeling. The deletion of halA in the haloarchaeon Halobacterium salinarum, whose cells are consistently rod-shaped, impacted morphogenesis but not cell division. Increased levels of halofilins enforced drastic deformations in cells devoid of the S-layer, suggesting that HalB polymers are more stable at defective S-layer lattice regions. Our results suggest that halofilins might play a significant mechanical scaffolding role in addition to possibly directing envelope synthesis. [ABSTRACT FROM AUTHOR]

The complexity of cancer requires a comprehensive approach to understand its diverse manifestations and underlying mechanisms. Initially outlined by Hanahan and Weinberg in 2000 and updated in 2010, the hallmarks of cancer provide a conceptual basis for understanding inherent variability in cancer biology. Recent expansions have further elucidated additional hallmarks, including phenotypic plasticity and senescent cells. The International Agency for Research on Cancer (IARC) has identified the key characteristics of carcinogens (KCCs) to evaluate their carcinogenic potential. We analyzed chemicals of concern for environmental exposure that interact with specific receptors to induce genomic instability, epigenetic alterations, immune suppression, and receptormediated effects, thereby contributing to chronic inflammation. Despite their varying degrees of carcinogenicity, these chemicals have similar KCC profiles. Our analysis highlights the pivotal role of receptor binding in activating most other KCCs, underscoring their significance in cancer initiation. Although KCCs are associated with early molecular or cellular events, they do not encompass processes directly linked to full cellular malignancy. Thus, there is a need to integrate clear endpoints that anchor KCCs to the acquisition of a complete malignant phenotype into chemical testing. From the perspective of toxicology and cancer research, an all-encompassing strategy that incorporates both existing and novel KCCs and cancer hallmarks is essential to enable the targeted identification of prevalent carcinogens and facilitate zone-specific prevention strategies. To achieve this goal, collaboration between the KCC and cancer hallmarks communities becomes essential. [ABSTRACT FROM AUTHOR]

Purpose: The utilization of remote patient monitoring (RPM) with home blood pressure monitoring has shown improvement in blood pressure control and adherence with follow-up visits. Patient perceptions regarding its use in the obstetric population have not been widely studied. The aim of this study was to assess patients' knowledge about hypertensive disorders of pregnancy and perceptions and satisfaction of the RPM program. Methods: Descriptive analysis of survey responses of patients with PPHTN enrolled into the RPM program for 6 weeks after delivery between October 2021 and April 2022. Surveys were automatically administered at 1-, 3-, and 6-week postpartum. Responses were further compared between Black and non-Black patient-reported race. Results: 545 patients received the RPM program. Of these, 306 patients consented to data collection. At 1 week, 88% of patients that responded reported appropriately that a blood pressure greater than 160/110 is abnormal. At 3 weeks, 87.4% of patients responded reported they were "very" or "somewhat" likely to attend their postpartum follow-up visits because of RPM. At 6 weeks, 85.5% of the patients that responded were "very" or "somewhat" satisfied with the RPM program. Responses were not statistically different between races. Conclusions: Majority of postpartum patients enrolled in the RPM program had correct knowledge about hypertension. In addition, patients were highly satisfied with the RPM program and likely to attend postpartum follow-up based on responses. Further research is warranted to validate these findings and to address any barriers for patients who did not utilize the program. [ABSTRACT FROM AUTHOR]

Aims In complete atrioventricular block (AVB) with underlying sinus rhythm, it is recommended to implant a dual-chamber pacemaker rather than a single-chamber pacemaker. However, no large-scale study has been able to demonstrate the superiority of this choice on hard clinical criteria such as morbimortality. Methods and results This retrospective observational study included all patients who received a primary pacemaker implantation in the indication of complete AVB with underlying sinus rhythm in France, based on the national administrative database between January 2013 and December 2022. After propensity score matching, we obtained two groups containing 19 219 patients each. The incidence of all-cause mortality was 9.22%/year for the dual-chamber pacemaker group, compared with 11.48%/year for the single-chamber pacemaker group (hazard ratio (HR) 0.807, P < 0.0001]. Similarly, there was a lower incidence of cardiovascular mortality (HR 0.766, P < 0.0001), heart failure (HR 0.908, P < 0.0001), atrial fibrillation (HR 0.778, P < 0.0001), and ischaemic stroke (HR 0.873, P = 0.008) in the dual-chamber pacemaker group than in the single-chamber pacemaker group. Regarding re-interventions and complications, there were fewer upgrades (addition of atrial lead or left ventricular lead) in the dual-chamber group (HR 0.210, P < 0.0001), but more haematomas (HR 1.179, P = 0.006) and lead repositioning (HR 1.123, P = 0.04). Conclusion In the indication of complete AVB with underlying sinus rhythm, our results are consistent with current recommendations to prefer implantation of a dual-chamber pacemaker rather than a single-chamber pacemaker for these patients. Implantation of a dual-chamber pacemaker is associated with a lower risk of mortality, heart failure, atrial fibrillation, and stroke during follow-up. [ABSTRACT FROM AUTHOR]

Understanding the risks in the months following hospital discharge is crucial for healthcare professionals to ensure the need for assistance is met. However, this may be challenging in the case of patients living with a major neurocognitive disorder (PLMNCD). Thus, it is important to incorporate patients' and caregivers' experiences of the transition from hospital to home in the risk assessment. This multiple case study comprised 7 PLMNCD, their caregivers, and occupational therapists. Fifty-four interviews, conducted just before, as well as 3 weeks and 3 to 6 months after hospital discharge, were qualitatively analyzed. Results revealed that risk management during the hospital-to-home transition is a dynamic process aimed at establishing a satisfactory routine while avoiding adverse events. This risk management process, which identifies challenges over time and between stakeholders, involves (a) determining the seriousness and acceptability of risks, (b) reflecting on ways to manage risks, and (c) taking steps to manage risks. This knowledge will help to provide more appropriate care and services that strike a balance between safety and autonomy. [ABSTRACT FROM AUTHOR]

Background: Permanent pacing is often required following valve intervention (either surgical or percutaneous); however, tricuspid interventions pose specific challenges to conventional pacing. Therefore, leadless pacemaker (LP) implantation may be the preferred strategy when permanent pacing is required after tricuspid valve intervention. Purpose: To report periprocedural outcomes and follow-up of patients undergoing implantation of a LP system following tricuspid valve interventions. Methods: Patients with previous tricuspid valve intervention at the time of attempted implantation of a LP (MicraTM, Medtronic, Minneapolis, MN, USA) were included. Results: Between 2019 and 2022, 40 patients underwent LP implantations following tricuspid interventions in 5 large tertiary centers. The mean age was 68.9 ± 13.7 years, and 48% patients were male. The indication for pacing was as following: AVB in 27 (68%) patients, AF with slow ventricular response in 10 (25%) patients, and refractory rapid atrial fibrillation (AF) referred to AV junction ablation in 3 (7%) patients. Most of the patients received Micra VR (78%). The procedure was successful in all patients. The mean procedural time is 58 ± 32 min, and the median fluoroscopy time is 7.5 min. Electrical parameters were within normal range (threshold: 1.35 ± 1.2 V@0.24 ms, impedance: 772 ± 245 Ohm, R-wave: 6.9 ± 5.4 mV). No acute complications were observed. During a mean follow-up of 10 months, electrical parameters remained stable, and 4 deaths were occurred (not related to the procedure). Conclusion: A LP is a safe and efficient option following tricuspid valve interventions. [ABSTRACT FROM AUTHOR]

Background: Pulmonary vein isolation (PVI) is the cornerstone of atrial fibrillation (AF) ablation. Despite promising success rates, redo ablation is sometimes required. At redo, PVs may be found to be isolated (silent) or reconnected. We studied patients with silent vs reconnected PVs at redo and analysed associations with adverse outcomes. Methods: Patients undergoing redo AF ablations between 2013 and 2019 at our institution were included and stratified into silent PVs or reconnected PVs. The primary outcome was a composite of further redo ablation, non-AF ablation, atrioventricular nodal ablation, and death. Secondary outcomes included arrhythmia recurrence. Results: A total of 467 patients were included with mean 4.6 ± 1.7 years follow-up, of whom 48 (10.3%) had silent PVs. The silent PV group had had more often undergone >1 prior ablation (45.8% vs 9.8%; p<0.001), had more persistent AF (62.5% vs 41.1%; p=0.005) and had more non-PV ablation performed both at prior ablation procedures and at the analysed redo ablation. The primary outcome occurred more frequently in those with silent PVs (25% vs 13.8%; p=0.053). Arrhythmia recurrence was also more common in the silent PV group (66.7% vs 50.6%; p=0.047). After multivariable adjustment, female sex (aHR 2.35 [95% CI 2.35–3.96]; p=0.001) and ischaemic heart disease (aHR 3.21 [95% CI 1.56–6.62]; p=0.002) were independently associated with the primary outcome, and left atrial enlargement (aHR 1.58 [95% CI 1.20–2.08]; p=0.001) and >1 prior ablation (aHR 1.88 [95% CI 1.30–2.72]; p<0.001) were independently associated with arrhythmia recurrence. Whilst a finding of silent PVs was not itself significant after multivariable adjustment, this provides an easily assessable parameter at clinically indicated redo ablation which informs the clinician of the likelihood of a worse future prognosis. Conclusions: Patients with silent PVs at redo AF ablation have worse clinical outcomes. [ABSTRACT FROM AUTHOR]

The silkworm Bombyx mori L. converts plant protein into silk. In silk producing countries mulberry leaves are primarily used to feed silkworms, however, recent studies have shown that nutritional supplements in the diet improved the morphological parameters of larvae and cocoons. In the current paper we investigated the effects of whey protein dissolved in water on the larval development of B. mori, cocoon production, mechanical properties of silk threads, silk gland morphology, and mRNA expression of the L-fibroin and sericin-1 genes. The results showed that whey protein supplementation did not affect larval development, and the histological structure of the silk glands remained intact. The water group and whey protein 10% group yielded the highest efficiency of silk protein synthesis. Mechanical testing of silk threads demonstrated that supplementation with whey protein did not affect the quality. The groups fed with whey protein supplements showed similar expression of L-fibroin gene, and higher expression of the sericin-1 gene. Our findings suggest that whey protein does not adversely affect the silk glands and could serve as a basis to produce artificial food for the silkworm. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer care is being increasingly driven by biomarker testing. Many biomarkers are traditionally measured on a sample from a patient tumor such as a biopsy. More recently, "liquid biopsy" has emerged as a blood test to complement or replace traditional tissue-based testing. In this report, we explore one of the first case series of rapid liquid biopsy performed within a hospital setting. The results include a median 3-day time to results, compared to approximately 14 days using traditional centralized reference labs. Additional details of the cohort are shared to highlight the utility of point of care liquid biopsy. Liquid biopsy is rapidly becoming an indispensable tool in the oncologist's arsenal; however, this technique remains elusive in a publicly funded healthcare system, and real-world evidence is needed to demonstrate utility and feasibility. Here, we describe the first experience of an in-house point of care liquid biopsy program at a Canadian community hospital. A retrospective review of consecutive cases that underwent plasma-based next-generation sequencing (NGS) was conducted. Liquid biopsy was initiated at the discretion of clinicians. Sequencing followed a point of care workflow using the Genexus™ integrated sequencer and the Oncomine precision assay, performed by histotechnologists. Results were reported by the attending pathologist. Eligible charts were reviewed for outcomes of interest, including the intent of the liquid biopsy, results of the liquid biopsy, and turnaround time from blood draw to results available. A total of 124 cases, with confirmed or suspected cancer, underwent liquid biopsy between January 2021 and November 2023. The median turnaround time for liquid biopsy results was 3 business days (range 1–12 days). The sensitivity of liquid biopsies was 71%, compared to tissue testing in cases with matched tissue results available for comparison. Common mutations included EGFR (29%), in 86 lung cancer patients, and PIK3CA (22%), identified in 13 breast cancer patients. Healthcare providers ordered liquid biopsies to inform diagnostic investigations and treatment decisions, and to determine progression or resistance mechanisms, as these reasons often overlapped. This study demonstrates that rapid in-house liquid biopsy using point of care methodology is feasible. The technique facilitates precision treatment and offers many additional advantages for cancer care. [ABSTRACT FROM AUTHOR]

Background: The primary objective of this cross-sectional study, conducted in Québec and Bristish Columbia (Canada) between February 2021 and January 2022, was to measure the prevalence of viral RNA in oronasal and rectal swabs and serum antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) amongst cats living in households with at least one confirmed human case. Secondary objectives included a description of potential risk factors for the presence of SARS-CoV-2 antibodies and an estimation of the association between the presence of viral RNA in swabs as well as SARS-CoV-2 antibodies and clinical signs. Oronasal and rectal swabs and sera were collected from 55 cats from 40 households at most 15 days after a human case confirmation, and at up to two follow-up visits. A RT-qPCR assay and an ELISA were used to detect SARS-CoV-2 RNA in swabs and serum SARS-CoV-2 IgG antibodies, respectively. Prevalence and 95% Bayesian credibility intervals (BCI) were calculated, and associations were evaluated using prevalence ratio and 95% BCI obtained from Bayesian mixed log-binomial models. Results: Nine (0.16; 95% BCI = 0.08–0.28) and 38 (0.69; 95% BCI = 0.56–0.80) cats had at least one positive RT-qPCR and at least one positive serological test result, respectively. No risk factor was associated with the prevalence of SARS-CoV-2 serum antibodies. The prevalence of clinical signs suggestive of COVID-19 in cats, mainly sneezing, was 2.12 (95% BCI = 1.03–3.98) times higher amongst cats with detectable viral RNA compared to those without. Conclusions: We showed that cats develop antibodies to SARS-CoV-2 when exposed to recent human cases, but detection of viral RNA on swabs is rare, even when sampling occurs soon after confirmation of a human case. Moreover, cats with detectable levels of virus showed clinical signs more often than cats without signs, which can be useful for the management of such cases. [ABSTRACT FROM AUTHOR]