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Objective: The management of preoperative medications is an essential component of perioperative care for the cardiac surgical patient. This turnkey order set is part of a series created by the Enhanced Recovery After Surgery Cardiac Society, first presented at the Annual Meeting of The American Association for Thoracic Surgery in 2023. Numerous guidelines and expert consensus documents have been published to provide guidance in preoperative medication management. Our objective is to integrate these documents into an evidence-based order set that will facilitate standardized implementation of best practices for preoperative medication management for nonemergent adult cardiac surgery. Methods: Subject matter experts were consulted to translate existing guidelines and peer reviewed literature into a sample turnkey order set for the preoperative management of patients’ medications. Orders derived from consistent Class I, IIA, or equivalent recommendations across referenced guidelines and consensus manuscripts appear in the order set in bold type. Selected orders that were inconsistently Class I or IIA, Class IIB, or supported by published evidence, were also included in italicized type. Results: Holding antiplatelet and anticoagulant medications before nonemergent cardiac surgical procedures may reduce the risk of bleeding. Sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 agonists should also be discontinued to prevent acidosis and aspiration, respectively. Specific guidance for frequently used medications are complied within the manuscript, less frequently used medications are listed seperately. Conclusions: Despite strong recommendations from major guidelines and consensus manuscripts, variation exists in preoperative medication orders, with limited availability of succinct implementation tools. This turnkey order set may facilitate standardized comprehensive preoperative medication management before nonemergent cardiac surgery.

Objective: Optimal perioperative pain management is an essential component of perioperative care for the cardiac surgical patient. This turnkey order set is part of a series created by the Enhanced Recovery After Surgery Cardiac Society, first presented at the Annual Meeting of The American Association for Thoracic Surgery in 2023. Several guidelines and expert consensus documents have been published to provide guidance on pain management and opioid reduction in cardiac surgery. Our objective is to consolidate that guidance into an evidence-based order set that will assist in the implementation of a comprehensive multimodal approach to pain management. Methods: Subject matter experts were consulted to translate existing guidelines and peer-reviewed literature into a sample turnkey order set for pain management. Orders derived from consistent Class I, IIA, or equivalent recommendations across referenced guidelines and consensus manuscripts appear in the order set in bold type. Selected orders that were inconsistently Class I or IIA, Class IIB, or supported by published evidence, were also included in italicized type. Results: Opioid-based analgesia is associated with delayed recovery and opioid-related adverse events. Several multimodal medications have been shown to reduce reliance upon opioids. These include the scheduled use of acetaminophen, gabapentinoids, and nonsteroidal anti-inflammatory drugs. In addition, intravenous analgesics such as dexmedetomidine, ketamine, magnesium, and lidocaine have been shown to both complement the maintenance of anesthesia as well as optimize pain control postoperatively. Long-acting opioids remain a key component of pain management when provided to reduce the overall use of short-acting synthetic opioids or in direct response to break though pain after exhausting other alternatives. When applied in a bundled fashion, several studies have demonstrated a reduction in overall opioid administration and improved rates of postoperative recovery. Conclusions: There has been increased awareness regarding the potential short- and long-term adverse effects of both inadequate analgesia and excessive opioid administration after cardiac surgery. This turnkey order set aims to facilitate implementation of a comprehensive approach toward provision of multimodal, opioid-sparing medications to optimize pain management in cardiac surgery.

Abstract This research quantitatively evaluates the natural radioactivity levels and geological radiation hazard parameters of soil and rock specimens obtained from mining locations in North-Eastern Nigeria, by means of grammar-ray spectroscopy. There have been potential public health risks associated with the use of soil and rock from mining locations in North-Eastern Nigeria, specifically the study areas. A total of twenty-eight samples were systematically gathered from Nahuta and Kashere locations. Through gamma spectrometry employing a NaI (TI) detector, the natural radioactivity levels of 238U, 232Th and 40 K were determined for each and every sample. The findings indicated that the mean activity concentrations of 226Ra, 232Th, and 40 K in Nahuta are 46.13 ± 4.78 Bq/Kg, 34.10 ± 3.02 Bq/Kg and 473.94 ± 5.41 Bq/Kg for the soil samples respectively, and 32.91 ± 0.49 Bq/Kg, 40.70 ± 0.41 Bq/Kg, and 578.18 ± 4.28 Bq/Kg for the rock samples respectively. The corresponding mean activity concentrations of 226Ra, 232Th, and 40 K in kashere are 17.99 ± 4.18 Bq/Kg, 23.73 ± 1.78 Bq/Kg, and 191.65 ± 3.15 Bq/Kg, for the soil samples, and 20.24 ± 3.72 Bq/Kg, 29.09 ± 1.78 Bq/Kg, and 148.36 ± 3.15 Bq/Kg, for the rock samples respectively. An analysis of radiation risk parameters (D, AEDE, Raeq, Hex, Hin, AGDE and ELCR) has been conducted and findings explored. While the samples from the kashere region fall within the international recommended levels, elevated readings of certain radiation health parameters are observed in the Nahuta region, posing serious public health risk due to utilization of the soil and rock from this area in construction activities.

Abstract Recent advances in DNA barcoding have immeasurably advanced global biodiversity research in the last two decades. However, inherent limitations in barcode sequences, such as hybridization, introgression or incomplete lineage sorting can lead to misidentifications when relying solely on barcode sequences. Here, we propose a new Niche‐model‐Based Species Identification (NBSI) method based on the idea that species distribution information is a potential complement to DNA barcoding species identifications. NBSI performs species membership inference by incorporating niche modelling predictions and traditional DNA barcoding identifications. Systematic tests across diverse scenarios show significant improvements in species identification success rates under the newly proposed NBSI framework, where the largest increase is from 4.7% (95% CI: 3.51%–6.25%) to 94.8% (95% CI: 93.19%–96.06%). Additionally, obvious improvements were observed when using NBSI on potentially ambiguous sequences whose genetic nearest neighbours belongs to another species or more than two species, which occurs commonly with species represented by single or short DNA barcodes. These results support our assertion that environmental factors/variables are valuable complements to DNA sequence data for species identification by avoiding potential misidentifications inferred from genetic information alone. The NBSI framework is currently implemented as a new R package, ‘NicheBarcoding’, that is open source under GNU General Public Licence and freely available from https://CRAN.R‐project.org/package=NicheBarcoding.

Abstract Background Homo- and heteromerization of G protein-coupled receptors (GPCRs) plays an important role in the regulation of receptor functions. Recently, we demonstrated an interaction between the serotonin receptor 7 (5-HT7R), a class A GPCR, and the cell adhesion molecule CD44. However, the functional consequences of this interaction on 5-HT7R-mediated signaling remained enigmatic. Methods Using a quantitative FRET (Förster resonance energy transfer) approach, we determined the affinities for the formation of homo- and heteromeric complexes of 5-HT7R and CD44. The impact of heteromerization on 5-HT7R-mediated cAMP signaling was assessed using a cAMP responsive luciferase assay and a FRET-based cAMP biosensor under basal conditions as well as upon pharmacological modulation of the 5-HT7R and/or CD44 with specific ligands. We also investigated receptor-mediated G protein activation using BRET (bioluminescence resonance energy transfer)-based biosensors in both, homo- and heteromeric conditions. Finally, we analyzed expression profiles for 5-HT7R and CD44 in the brain during development. Results We found that homo- and heteromerization of the 5-HT7R and CD44 occur at similar extent. Functionally, heteromerization increased 5-HT7R-mediated cAMP production under basal conditions. In contrast, agonist-mediated cAMP production was decreased in the presence of CD44. Mechanistically, this might be explained by increased Gαs and decreased GαoB activation by 5-HT7R/CD44 heteromers. Unexpectedly, treatment of the heteromeric complex with the CD44 ligand hyaluronic acid boosted constitutive 5-HT7R-mediated cAMP signaling and receptor-mediated transcription, suggesting the existence of a transactivation mechanism. Conclusions Interaction with the hyaluronan receptor CD44 modulates both the constitutive activity of 5-HT7R as well as its agonist-mediated signaling. Heteromerization also results in the transactivation of 5-HT7R-mediated signaling via CD44 ligand.

Abstract Mutations in the RNA helicase DDX3X, implicated in various cancers and neurodevelopmental disorders, often impair RNA unwinding and translation. However, the mechanisms underlying the impairment and the differential interactions of DDX3X mutants with wild-type (WT) X-linked DDX3X and Y-linked homolog DDX3Y remain elusive. This study reveals that specific DDX3X mutants more frequently found in disease form distinct hollow condensates in cells. Using a combined structural, biochemical, and single-molecule microscopy study, we show that reduced ATPase and RNA release activities contribute to condensate formation and these catalytic deficits result from inhibiting the catalytic cycle at multiple steps. Proteomic investigations further demonstrate that these hollow condensates sequester WT DDX3X/DDX3Y and other proteins crucial for diverse signaling pathways. WT DDX3X enhances the dynamics of heterogeneous mutant/WT hollow condensates more effectively than DDX3Y. These findings offer valuable insights into the catalytic defects of specific DDX3X mutants and their differential interactions with wild-type DDX3X and DDX3Y, potentially explaining sex biases in disease.

A 68-year-old male with liver cirrhosis presented with dizziness and dyspnea two days after endoscopic Histoacryl occlusion of gastric varicses. Imaging revealed a large endovascular embolization of Histoacryl glue, spanning from porto-caval collaterals via the inferior vena cava to the right atrium, partially occluding right atrial inflow. This case report describes the successful removal of this large net-like mass of Histoacryl glue using thrombectomy devices from the inferior vena cava and the right atrium. Postprocedure imaging showed near-complete clearance with residual fragments in the superior mesenteric vein and small emboli in the pulmonary arteries. The patient was discharged in stable condition. Histoacryl glue can cause severe complications if embolized. This case highlights the potential of advanced thrombectomy devices for managing embolic complications from endovascular treatments.

Abstract Megachile is one of the largest bee genera, including nearly 1,500 species, but very few chromosome-level assemblies exist for this group or the family Megachilidae. Here, we report the chromosome-level genome assembly of Megachile lagopoda collected from Xizang, China. Using PacBio CLR long reads and Hi-C data, we assembled a genome of 256.83 Mb with 96.08% of the assembly located on 16 chromosomes. Our assembly contains 266 scaffolds, with a scaffold N50 length of 15.6 Mb, and BUSCO completeness of 99.20%. We masked 27.10% (69.61 Mb) of the assembly as repetitive elements, identified 459 non-coding RNAs, and predicted 11,157 protein-coding genes. This high-quality genome of M. lagopoda represents an important step forward for our knowledge of megachilid genomics and bee evolution overall.

Abstract The increasing availability of biobanks is changing the way individuals are identified for genomic research. This study assesses the validity of a self-reported clinical diagnosis of schizophrenia. The study included 1744 clinically-ascertained participants with schizophrenia or schizoaffective disorder depressed-type (SA-D) diagnosed by self-report and/or research interview and 1453 UK Biobank participants with self-reported and/or medical record diagnosis of schizophrenia or SA-D. Unaffected controls included a total of 501,837 participants. We assessed the positive predictive values (PPV) of self-reported clinical diagnoses against research interview and medical record diagnoses. Polygenic risk scores (PRS) and phenotypes relating to demographics, education and employment were compared across diagnostic groups. The variance explained (r2) in schizophrenia PRS for each diagnostic group was compared to samples in the Psychiatric Genomics Consortium (PGC). In the clinically-ascertained participants, the PPV of self-reported schizophrenia for a research diagnosis of schizophrenia was 0.70, which increased to 0.81 after expanding the research diagnosis to schizophrenia or SA-D. In UK Biobank, the PPV of self-reported schizophrenia for a medical record diagnosis was 0.74. Compared to participants who self-reported, participants with a clinically-ascertained research diagnosis were younger and more likely to have a high school qualification. Participants with a medical record diagnosis in UK Biobank were less likely to be employed or have a high school qualification than those who self-reported. Schizophrenia PRS did not differ between participants that had a diagnosis from self-report, research diagnosis or medical records. Polygenic liability r2, for all diagnosis definitions, fell within the distribution of PGC schizophrenia cohorts. Self-reported measures of schizophrenia are justified in genomic research to maximise sample size and reduce the burden of in-depth interviews on participants, although within sample validation of diagnoses is recommended.

There have been potential public health risks associated with the use of soil and rock from mining locations in North-Eastern Nigeria. This research evaluates the natural hazard parameters of soil and rock specimens obtained from mining locations in North-Eastern Nigeria, using grammar-ray spectroscopy. A total of twenty-eight samples were systematically gathered from Nahuta and Kashere locations. Through gamma spectrometry employing a NaI (TI) detector, the natural radioactivity levels of 238U, 232Th and 40K were determined for each sample. The findings indicated that the mean activity concentrations of 226Ra, 232Th, and 40K in Nahuta are 46.13±4.78 Bq/Kg, 34.10±3.02 Bq/Kg and 473.94±5.41 Bq/Kg for the soil samples respectively, and 32.91±0.49 Bq/Kg, 40.70±0.41 Bq/Kg, and 578.18±4.28 Bq/Kg for the rock samples respectively. The corresponding mean activity concentrations of 226Ra, 232Th, and 40K in Kashere are 17.99±4.18 Bq/Kg, 23.73±1.78Bq/Kg, and 191.65±3.15 Bq/Kg, for the soil samples, and 20.24±3.72 Bq/Kg, 29.09±1.78 Bq/Kg, and 148.36±3.15 Bq/Kg, for the rock samples respectively. An analysis of radiation risk parameters (D, AEDE, Raeq, Hex, Hin, AGDE, and ELCR) has been explored. While the samples from the Kashere region fall within the international recommended levels, elevated readings of certain radiation health parameters are observed in the Nahuta region, posing serious public health risks due to the utilization of the soil and rock from this area in construction activities.

Abstract Background NPM1‐mutated acute myeloid leukemia (AML) is the most frequent AML subtype. As wild‐type NPM1 is known to orchestrate ribosome biogenesis, it has been hypothesized that altered translation may contribute to leukemogenesis and leukemia maintenance in NPM1‐mutated AML. However, this hypothesis has never been investigated. We reasoned that if mutant NPM1 (NPM1c) directly impacts translation in leukemic cells, loss of NPM1c would result in acute changes in the ribosome footprint. Methods Here, we performed ribosome footprint profiling (Ribo‐seq) and bulk messenger RNA (mRNA) sequencing in two NPM1‐mutated cell lines engineered to express endogenous NPM1c fused to the FKBP (F36V) degron tag (degron cells). Results and discussion Incubation of degron cells with the small compound dTAG‐13 enables highly specific degradation of NPM1c within 4 hours. As expected, RNA‐sequencing data showed early loss of homeobox gene expression following NPM1c degradation, confirming the reliability of our model. In contrast, Ribo‐seq data showed negligible changes in the ribosome footprint in both cell lines, implying that the presence of NPM1c does not influence ribosome abundance and positioning on mRNA. While it is predictable that NPM1c exerts its leukemogenic activity at multiple levels, ribosome footprint does not seem influenced by the presence of mutant NPM1.

Abstract One Health aims to achieve optimal health outcomes for people, animals, plants, and shared environments. We describe a multisector effort to understand and mitigate SARS-CoV-2 transmission risk to humans via the spread among and between captive and wild white-tailed deer. We first framed a One Health problem with three governance sectors that manage captive deer, wild deer populations, and public health. The problem framing included identifying fundamental objectives, causal chains for transmission, and management actions. We then developed a dynamic model that linked deer herds and simulated SARS-CoV-2. Next, we evaluated management alternatives for their ability to reduce SARS-CoV-2 spread in white-tailed deer. We found that single-sector alternatives reduced transmission, but that the best-performing alternative required collaborative actions among wildlife management, agricultural management, and public health agencies. Here, we show quantitative support that One Health actions outperform single-sector responses, but may depend on coordination to track changes in this evolving system.

Abstract Prior studies have shown strong genetic effects on cortical thickness (CT), structural covariance, and neurodevelopmental trajectories in childhood and adolescence. However, the importance of genetic factors on the induction of spatiotemporal variation during neurodevelopment remains poorly understood. Here, we explore the genetics of maturational coupling by examining 308 MRI-derived regional CT measures in a longitudinal sample of 677 twins and family members. We find dynamic inter-regional genetic covariation in youth, with the emergence of regional subnetworks in late childhood and early adolescence. Three critical neurodevelopmental epochs in genetically-mediated maturational coupling were identified, with dramatic network strengthening near eleven years of age. These changes are associated with statistically-significant (empirical p-value

Abstract Background Harmful algal bloom occurrences have been increasingly reported globally and over time. Exposure to the variety of toxins and co-contaminants that may be present in harmful algal blooms can cause illness and even death. Poison control data is a valuable public health information source that has been used to characterize many types of toxin exposures, including harmful algal blooms. Prior studies have been limited by location and time, and knowledge gaps remain regarding cyanobacteria harmful algal bloom (cyanoHAB) exposure circumstances, and the breadth and severity of associated clinical effect. Methods The objective of this study was to characterize epidemiologic and clinical features of cyanoHAB exposure cases reported to 55 US poison control centers and available in the National Poison Data System (NPDS). We identified 4260 NPDS cyanoHAB exposure cases reported from 2010 to 2022, including symptomatic exposure cases with and without clinical effects related to the exposure and asymptomatic exposure cases. We assessed demographics; exposure routes, locations, chronicity; clinical effects; and medical outcomes. We calculated case rates annually and 13-year case rates by US geographic division. Results Over half of cyanoHAB exposure cases were children

Objective: To investigate the efficacy of elagolix plus add-back therapy (estradiol [1 mg] and norethindrone acetate [0.5 mg] once daily) on patient-reported nonbleeding symptoms and menstrual bleeding associated with uterine fibroids (UFs) across different subpopulations. Design: Post hoc analysis of two phase 3 clinical trials—Elaris UF-1 and UF-2. Setting: A total of 76 (UF-1) and 77 (UF-2) US clinical sites. Patient(s): Women (N = 591) with UFs and heavy menstrual bleeding. Intervention(s): Elagolix (300 mg) twice daily with add-back therapy (the indicated dose for UF-associated heavy menstrual bleeding) vs. placebo for 6 months. Main Outcome Measure(s): “Very much improved” or “much improved” change in nonbleeding symptoms (abdominal/pelvic pain, abdominal/pelvic pressure/cramping, back pain, and abdominal bloating) and menstrual bleeding measured using a Patient Global Impression of Change scale. Improvements were assessed in subpopulations stratified using baseline characteristics (age, race [self-reported], body mass index, and International Federation of Gynecology and Obstetrics fibroid classification). Result(s): Across subpopulations, differences favored elagolix plus add-back therapy (vs. placebo) for most symptoms at month 1 and all symptoms at months 3 as well as 6. In patients with characteristics commonly associated with high disease burden (age >40 years, Black/African American), those treated with elagolix plus add-back therapy reported significantly greater improvements vs. placebo at months 1–6 (P

Abstract The Neuronal alpha-Synuclein Disease (NSD) biological definition and Integrated Staging System (NSD-ISS) provide a research framework to identify individuals with Lewy body pathology and stage them based on underlying biology and increasing degree of functional impairment. Utilizing data from the PPMI, PASADENA, and SPARK studies, we developed and applied biologic and clinical data-informed definitions for the NSD-ISS across the disease continuum. Individuals enrolled as Parkinson’s disease, Prodromal, or Healthy Controls were defined and staged based on biological, clinical, and functional anchors at baseline. Across the three studies 1741 participants had SAA data and of these 1030 (59%) were S+ consistent with NSD. Among sporadic PD, 683/736 (93%) were NSD, and the distribution for Stages 2B, 3, and 4 was 25%, 63%, and 9%, respectively. Median (95% CI) time to developing a clinically meaningful outcome was 8.3 (6.2, 10.1), 5.9 (4.1, 6.0), and 2.4 (1.0, 4.0) years for baseline stage 2B, 3, and 4, respectively. We propose pilot biologic and clinical anchors for NSD-ISS. Our results highlight the baseline heterogeneity of individuals currently defined as early PD. Baseline stage predicts time to progression to clinically meaningful milestones. Further research on validation of the anchors in longitudinal cohorts is necessary.

Abstract Background Falls are the leading cause of injury related morbidity and mortality in older adults. Primary and secondary prevention strategies that address modifiable risk factors are critically important to reduce the number of falls and fall related injuries. A number of evidence-based fall prevention programs are available, but few offer potential for broad dissemination and public health impact due to implementation barriers, such as a need for trained program leaders and clinicians. Methods The study will use a randomized controlled trial design to evaluate incorporating physical therapy exercises (primary prevention strategy) within an existing intervention called Walk with Ease. While Walk with Ease has an established evidence-base related to the management of arthritis pain and symptoms, the present study will determine the potential to also reduce falls and fall risk in community-dwelling older adults. The integrated process and outcome evaluation will determine the relative effectiveness of individually-prescribed exercises (compared to standardized exercises) as well as the potential of ‘habit training’ resources (relative to generic behavior prompts) to improve compliance with exercises in this population. Discussion The study, conducted through a local clinical-community partnership will advance both the science and practice of community-based fall prevention programming, while also informing implementation strategies needed to promote broader dissemination. Trial registration ClinicalTrials.gov, NCT05693025, Registered January 20, 2023, Updated March 1, 2023.

A new species of bumble bee-mimicking brood parasitic bee, Tetralonioidella mimetica Orr & Zhu, sp. nov., is described from China. The systematic placement of this species was initially challenging but was resolved using a combination of phylogenomic and COI barcode analyses, which strongly support the new species as a member of the genus Tetralonioidella Strand. Interestingly, the new species mimics the color pattern of both a bumble bee (Bombus Latreille), and its host Habropoda Smith species, a mimicry format previously unknown for bees. A review of the other Tetralonioidella species revealed three additional bee mimics, including two further likely model-host-brood parasite mimicry complexes. To our knowledge, these represent the first documented three-tiered mimetic systems in bees. Several additional taxonomic actions recently became necessary in these and related taxa: Tetralonioidella meghalayensis Dohling & Dey, 2024 is synonymized syn. nov. with Habropoda radoszkowskii (Dalla Torre, 1896) and Varthemapistra Engel, stat. rev. is again synonymized with Habrophorula Lieftinck. Our results also highlight issues with the generic classification of the tribe Melectini as currently used, as Melecta Latreille was found paraphyletic in relation to the remaining melectine genera. As a first step toward resolving this issue, we return the Melecta subgenus Eupavlovskia Popov, stat. rev. to genus level and discuss the ongoing systematic uncertainties regarding melectine taxonomy.

Abstract A seminal component of systems thinking is the application of an advanced technology in one domain to solve a challenging problem in a different domain. This article introduces a method of using advanced computer vision to solve the challenging signal processing problem of specific emitter identification. A one-dimensional signal is sampled; those samples are transformed into to two-dimensional images by computing a bispectrum; those images are evaluated using advanced computer vision; and the results are statistically combined until any user-selected level of classification accuracy is obtained. In testing on a published DARPA challenge dataset, for every eight additional signal samples taken from a candidate signal (out of many thousands), classification error decreases by an entire order of magnitude.

Abstract Background In Germany, around 2.250 children and adolescents are diagnosed with cancer each year. Despite generally positive long-term survival rates, many patients must cope with late effects of the disease and its treatment. This highlights the need for a well-structured, long-term approach addressing both physical and mental health issues. Currently, the German healthcare system lacks such comprehensive structures. Our study aims to evaluate the effectiveness of a structured, multidisciplinary long-term approach compared to conventional “treatment as usual” (TAU). Methods A prospective, multicenter study with ten pediatric university clinics in Germany will be conducted. The cluster-randomization takes place at the clinic level. Children and adolescents who completed their cancer treatment at least five years ago and their parents will be eligible to participate. While the control group (CG) receives TAU, the intervention group (IG) participates in a structured program. This program includes risk-based medical treatment and psychosocial interventions tailored to each patient’s individual needs within a two-month timeframe. The primary outcome is the improvement of self-efficacy. Secondary outcomes are satisfaction with health care, improvement of health-related quality of life (HRQoL), reduction of mental health problems, and improvement of transition readiness. Discussion This approach has the potential to optimize the health care for individuals who survived cancer during childhood or adolescence. It addresses the challenges of overuse, underuse, and misuse of health care resources. By considering both medical and psychosocial factors and promoting increased self-efficacy, independent from parental involvement, it may facilitate a smoother transition to adult medicine and enhance adherence to lifelong aftercare. If proven successful, this approach will contribute to the integration of multidisciplinary strategies into standard healthcare practice. Trial registration German Clinical Trials Register DRKS00029269. Registered on December 23, 2022.

Abstract Clonal hematopoiesis of indeterminate potential (CHIP) is linked to diverse aging-related diseases, including hematologic malignancy and atherosclerotic cardiovascular disease (ASCVD). While CHIP is common among older adults, the underlying factors driving its development are largely unknown. To address this, we performed whole-exome sequencing on 8,374 blood DNA samples collected from 4,187 Atherosclerosis Risk in Communities Study (ARIC) participants over a median follow-up of 21 years. During this period, 735 participants developed incident CHIP. Splicing factor genes (SF3B1, SRSF2, U2AF1, and ZRSR2) and TET2 CHIP grow significantly faster than DNMT3A non-R882 clones. We find that age at baseline and sex significantly influence the incidence of CHIP, while ASCVD and other traditional ASCVD risk factors do not exhibit such associations. Additionally, baseline synonymous passenger mutations are strongly associated with CHIP status and are predictive of new CHIP clone acquisition and clonal growth over extended follow-up, providing valuable insights into clonal dynamics of aging hematopoietic stem and progenitor cells. This study also reveals associations between germline genetic variants and incident CHIP. Our comprehensive longitudinal assessment yields insights into cell-intrinsic and -extrinsic factors contributing to the development and progression of CHIP clones in older adults.

Invasive wood-boring insects are a major economic and ecological concern worldwide as they impact native woody plant populations. These pest species are increasing in prevalence, with devastating impact, as global trade leads to higher rates of introduction and establishment. The emerald ash borer (Agrilus planipennis; EAB) is one such species, which has caused widespread damage across much of the United States and is now spreading across Europe. Non-indigenous woodborers such as EAB are difficult to detect at early stages of invasion, which is when management and eradication efforts are most effective and cost efficient. Environmental DNA (eDNA) surveys have demonstrated power in detecting invasive species when rare in the landscape due to their ability to detect trace amounts of DNA and identify to species. Here, we trialled a novel eDNA method for collecting environmental samples within host trees where invasive pest larvae are feeding, using EAB as a case study. We extracted tree cores approximately 1 cm in length using an increment hammer to assess detectability of eDNA from larvae feeding under the bark. In trees visibly infested with EAB, we observed a seasonal peak in EAB DNA detection probability (~ 64%; towards the end of the growing season), indicating a potential impact of ash tree phenology or EAB phenology on detection. When we trialled the method in a site with ash trees of low or uncertain EAB abundance, we did not record positive EAB eDNA detections. This outcome may have resulted from differing EAB phenology at the northern latitude of this survey site or because larval galleries were less numerous causing EAB DNA to be scarcer within the tree. Our results, however, provide preliminary evidence that increment hammer tree cores can be used to detect eDNA of EAB and, perhaps, other wood-boring pests. Further work is needed to clarify false negative survey detections at ash trees showing little to no signs or symptoms of infestation, as well as investigating the deposition, transport and persistence dynamics of EAB eDNA within trees.

We investigate the contrasting realities of the pandemic on psychosocial experiences and ways of coping among American Voices Project respondent surveys (N = 720) and interviews (N = 172). Despite similar levels of distress early in the pandemic, by late 2020 clear differences across education, race and ethnicity, and gender emerged, both quantitatively and qualitatively. Those with structural advantages reported greater gains from the pandemic, including self-improvement opportunities like therapy and time outdoors. In contrast, respondents without college degrees, Black and Hispanic individuals, and women reported experiencing greater psychosocial shocks into the later months of 2020 and feeling disproportionately undervalued, socially disconnected, and stressed, respectively. The former two groups also systematically differed in their coping strategies, which included hard work, emotion suppression, and faith.

Background: Phase 3 PRIME/PRIME2 trials independently demonstrated efficacy and an acceptable safety profile of dupilumab adults with moderate-to-severe prurigo nodularis. Objective: To obtain a more precise estimate of onset and magnitude of treatment effect using PRIME/PRIME2 pooled data. Methods: In PRIME/PRIME2, patients were randomized to dupilumab or placebo for 24 weeks. Pooled analysis assessed proportion of patients achieving clinically meaningful improvement in itch, clear/almost-clear skin, or both; at weeks 12 and 24; overall and by demographic subgroups and changes from baseline to week 24 in symptoms, signs, and quality of life. Results: Patients receiving dupilumab (n = 153) vs placebo (n = 158) experienced significant improvements in all tested endpoints. At week 24, 90 (58.8%) dupilumab-treated vs 30 (19.0%) placebo-treated patients achieved clinically meaningful improvement in itch, 71 (46.4%) vs 27 (17.1%) clear/almost clear skin, and 54 (35.3%) vs 14 (8.9%) achieved both (P

Abstract Understanding individuals’ distinct movement patterns is crucial for health, rehabilitation, and sports. Recently, we developed a machine learning-based framework to show that “gait signatures” describing the neuromechanical dynamics governing able-bodied and post-stroke gait kinematics remain individual-specific across speeds. However, we only evaluated gait signatures within a limited speed range and number of participants, using only sagittal plane (i.e., 2D) joint angles. Here we characterized changes in gait signatures across a wide range of speeds, from very slow (0.3 m/s) to exceptionally fast (above the walk-to-run transition speed) in 17 able-bodied young adults. We further assessed whether 3D kinematic and/or kinetic (ground reaction forces, joint moments, and powers) data would improve the discrimination of gait signatures. Our study showed that gait signatures remained individual-specific across walking speeds: Notably, 3D kinematic signatures achieved exceptional accuracy (99.8%, confidence interval (CI) 99.1–100%) in classifying individuals, surpassing both 2D kinematics and 3D kinetics. Moreover, participants exhibited consistent, predictable linear changes in their gait signatures across the entire speed range. These changes were associated with participants’ preferred walking speeds, balance ability, cadence, and step length. These findings support gait signatures as a tool to characterize individual differences in gait and predict speed-induced changes in gait dynamics.

Abstract Objective Past decades of research into contrast media injections and optimization thereof in radiology clinics have focused on scan acquisition parameters, patient-related factors, and contrast injection protocol variables. In this review, evidence is provided that a fourth bucket of crucial variables has been missed which account for previously unexplained phenomena and higher-than-expected variability in data. We propose how these critical factors should be considered and implemented in the contrast-medium administration protocols to optimize contrast enhancement. Methods This article leverages a combination of methodologies for uncovering and quantifying confounding variables associated with or affecting the contrast-medium injection. Engineering benchtop equipment such as Coriolis flow meters, pressure transducers, and volumetric measurement devices are combined with small, targeted systematic evaluations querying operators, equipment, and the physics and fluid dynamics that make a seemingly simple task of injecting fluid into a patient a complex and non-linear endeavor. Results Evidence is presented around seven key factors affecting the contrast-medium injection including a new way of selecting optimal IV catheters, degraded performance from longer tubing sets, variability associated with the mechanical injection system technology, common operator errors, fluids exchanging places stealthily based on gravity and density, wasted contrast media and inefficient saline flushes, as well as variability in the injected flow rate vs. theoretical expectations. Conclusion There remain several critical, but not commonly known, sources of error associated with contrast-medium injections. Elimination of these hidden sources of error where possible can bring immediate benefits and help to drive standardized and optimized contrast-media injections. Critical relevance statement This review brings to light the commonly neglected/unknown factors negatively impacting contrast-medium injections and provides recommendations that can result in patient benefits, quality improvements, sustainability increases, and financial benefits by enabling otherwise unachievable optimization. Key Points How IV contrast media is administered is a rarely considered source of CT imaging variability. IV catheter selection, tubing length, injection systems, and insufficient flushing can result in unintended variability. These findings can be immediately addressed to improve standardization in contrast-enhanced CT imaging. Graphical Abstract

Abstract Background Cigarette smoking has major detrimental effects on oral health. Tobacco interventions in dental settings are effective, but rarely delivered. The American Dental Hygienists Association recommends that oral health providers: Ask patients about tobacco use, Advise quitting tobacco use, and Refer to state quitlines (Ask-Advise-Refer; AAR). While AAR connects patients to counseling, it does not directly connect patients to medication. Nicotine replacement therapy sampling (NRTS) is an empirically supported intervention to provide starter packs of nicotine replacement therapy (NRT) to people who smoke. NRTS combined with AAR could be an effective tobacco treatment intervention for dental settings. Methods This manuscript describes the study protocol for the Free Samples for Health (FreSH) study, a group randomized clinical trial testing the effectiveness of NRTS + AAR vs. AAR alone on long-term smoking abstinence. Fifty dental practices in the Midwest and Northeast nodes of the National Dental Practice-Based Research Network are randomly assigned to provide AAR and either a 2-week supply of 14-mg nicotine patches and 4-mg nicotine lozenges (NRTS condition) or an electric toothbrush (ET condition). Approximately 1,200 patients who currently smoke—regardless of interest in quitting— are recruited during dental visits. Participants complete a baseline survey in-person, then after visit, 1-, 3-, and 6-month follow-up surveys remotely. The primary outcome is carbon monoxide-confirmed 7-day point prevalence abstinence from combustible tobacco measured at 6 months post-enrollment. Secondary outcomes include: 24-h intentional quit attempts, change in cigarettes smoked per day, NRT utilization, attitudes toward NRT, intention to use NRT, and intention to quit smoking. A key informant process evaluation and cost effectiveness analysis will provide information for future implementation of NRTS. Discussion This is the first clinical trial to assess the effectiveness of NRTS on promoting smoking cessation in dental settings. If effective, this treatment could be implemented to increase the provision of smoking cessation interventions in dental settings to provide an additional treatment access point for people who smoke. Trial Registration. Registered at ClincalTrials.gov (NCT05627596) on 11/25/2022.

Abstract Histone deacetylases (HDACs) have a wide range of targets and can rewire both the chromatin and lipidome of cancer cells. In this study, we show that valproic acid (VPA), a brain penetrant anti-seizure medication and histone deacetylase inhibitor, inhibits the growth of IDH1 mutant tumors in vivo and in vitro, with at least some selectivity over IDH1 wild-type tumors. Surprisingly, genes upregulated by VPA showed no enhanced chromatin accessibility at the promoter, but there was a correlation between VPA-downregulated genes and diminished promoter chromatin accessibility. VPA inhibited the transcription of lipogenic genes and these lipogenic genes showed significant decreases in promoter chromatin accessibility only in the IDH1 MT glioma cell lines tested. VPA inhibited the mTOR pathway and a key lipogenic gene, fatty acid synthase (FASN). Both VPA and a selective FASN inhibitor TVB-2640 rewired the lipidome and promoted apoptosis in an IDH1 MT but not in an IDH1 WT glioma cell line. We further find that HDACs are involved in the regulation of lipogenic genes and HDAC6 is particularly important for the regulation of FASN in IDH1 MT glioma. Finally, we show that FASN knockdown alone and VPA in combination with FASN knockdown significantly improved the survival of mice in an IDH1 MT primary orthotopic xenograft model in vivo. We conclude that targeting fatty acid metabolism through HDAC inhibition and/or FASN inhibition may be a novel therapeutic opportunity in IDH1 mutant gliomas.

Abstract Background Older adult women often do not engage in sufficient physical activity (PA) and can encounter biological changes that exacerbate the negative effects of inadequate activity. Wearable activity monitors can facilitate PA initiation, but evidence of sustained behavior change is lacking. Supplementing wearable technologies with intervention content that evokes enjoyment, interest, meaning, and personal values associated with PA may support long term adherence. In this paper, we present the protocol of an NIA-funded study designed to evaluate the efficacy of CHALLENGE for increasing step count and motivation for PA in insufficiently active older women (Challenges for Healthy Aging: Leveraging Limits for Engaging Networked Game-based Exercise). CHALLENGE uses social media to supplement wearable activity monitors with the autonomy-supportive frame of a game. We hypothesize that CHALLENGE will engender playful experiences that will improve motivation for exercise and lead to sustained increases in step count. Methods We will recruit 300 healthy, community dwelling older adult women on a rolling basis and randomize them to receive either the CHALLENGE intervention (experimental arm) or an activity monitor-only intervention (comparison arm). Participants in both groups will receive a wearable activity monitor and personalized weekly feedback emails. In the experimental group, participants will also be added to a private Facebook group, where study staff will post weekly challenges that are designed to elicit playful experiences while walking. Assessments at baseline and 6, 12, and 18 months will measure PA and motivation-related constructs. We will fit linear mixed-effects models to evaluate differences in step count and motivational constructs, and longitudinal mediation models to evaluate if interventional effects are mediated by changes in motivation. We will also conduct thematic content analysis of text and photos posted to Facebook and transcripts from individual interviews. Discussion By taking part in a year-long intervention centered on imbuing walking behaviors with playful and celebratory experiences, participating older adult women may internalize changes to their identity and relationship with PA that facilitate sustained behavior change. Study results will have implications for how we can harness powerful and increasingly ubiquitous technologies for health promotion to the vast and growing population of older adults in the U.S. and abroad. Trial registration ClinicalTrials.gov Identifier NCT04095923. Registered September 17th, 2019.

Abstract The mechanisms underlying the selective regional vulnerability to neurodegeneration in Huntington’s disease (HD) have not been fully defined. To explore the role of astrocytes in this phenomenon, we used single-nucleus and bulk RNAseq, lipidomics, HTT gene CAG repeat-length measurements, and multiplexed immunofluorescence on HD and control post-mortem brains. We identified genes that correlated with CAG repeat length, which were enriched in astrocyte genes, and lipidomic signatures that implicated poly-unsaturated fatty acids in sensitizing neurons to cell death. Because astrocytes play essential roles in lipid metabolism, we explored the heterogeneity of astrocytic states in both protoplasmic and fibrous-like (CD44+) astrocytes. Significantly, one protoplasmic astrocyte state showed high levels of metallothioneins and was correlated with the selective vulnerability of distinct striatal neuronal populations. When modeled in vitro, this state improved the viability of HD-patient-derived spiny projection neurons. Our findings uncover key roles of astrocytic states in protecting against neurodegeneration in HD.

Abstract Equitable and accessible education in life sciences, bioengineering, and synthetic biology is crucial for training the next generation of scientists, fostering transparency in public decision-making, and ensuring biotechnology can benefit a wide-ranging population. As a groundbreaking technology for genome engineering, CRISPR has transformed research and therapeutics. However, hands-on exposure to this technology in educational settings remains limited due to the extensive resources required for CRISPR experiments. Here, we develop CRISPRkit, an affordable kit designed for gene editing and regulation in high school education. CRISPRkit eliminates the need for specialized equipment, prioritizes biosafety, and utilizes cost-effective reagents. By integrating CRISPRi gene regulation, colorful chromoproteins, cell-free transcription-translation systems, smartphone-based quantification, and an in-house automated algorithm (CRISPectra), our kit offers an inexpensive (~$2) and user-friendly approach to performing and analyzing CRISPR experiments, without the need for a traditional laboratory setup. Experiments conducted by high school students in classroom settings highlight the kit’s utility for reliable CRISPRkit experiments. Furthermore, CRISPRkit provides a modular and expandable platform for genome engineering, and we demonstrate its applications for controlling fluorescent proteins and metabolic pathways such as melanin production. We envision CRISPRkit will facilitate biotechnology education for communities of diverse socioeconomic and geographic backgrounds.

Abstract Images collected during NASA’s Double Asteroid Redirection Test (DART) mission provide the first resolved views of the Didymos binary asteroid system. These images reveal that the primary asteroid, Didymos, is flattened and has plausible undulations along its equatorial perimeter. At high elevations, its surface is rough and contains large boulders and craters; at low elevations its surface is smooth and possesses fewer large boulders and craters. Didymos’ moon, Dimorphos, possesses an intimate mixture of boulders, several asteroid-wide lineaments, and a handful of craters. The surfaces of both asteroids include boulders that are large relative to their host body, suggesting that both asteroids are rubble piles. Based on these observations, our models indicate that Didymos has a surface cohesion ≤ 1 Pa and an interior cohesion of ∼10 Pa, while Dimorphos has a surface cohesion of

Abstract Oculopharyngodistal myopathy (OPDM) is an inherited myopathy manifesting with ptosis, dysphagia and distal weakness. Pathologically it is characterised by rimmed vacuoles and intranuclear inclusions on muscle biopsy. In recent years CGG • CCG repeat expansion in four different genes were identified in OPDM individuals in Asian populations. None of these have been found in affected individuals of non-Asian ancestry. In this study we describe the identification of CCG expansions in ABCD3, ranging from 118 to 694 repeats, in 35 affected individuals across eight unrelated OPDM families of European ancestry. ABCD3 transcript appears upregulated in fibroblasts and skeletal muscle from OPDM individuals, suggesting a potential role of over-expression of CCG repeat containing ABCD3 transcript in progressive skeletal muscle degeneration. The study provides further evidence of the role of non-coding repeat expansions in unsolved neuromuscular diseases and strengthens the association between the CGG • CCG repeat motif and a specific pattern of muscle weakness.

Abstract Human cytomegalovirus (CMV) is a highly prevalent herpesvirus that is often transmitted to the neonate via breast milk. Postnatal CMV transmission can have negative health consequences for preterm and immunocompromised infants, but any effects on healthy term infants are thought to be benign. Furthermore, the impact of CMV on the composition of the hundreds of bioactive factors in human milk has not been tested. Here, we utilize a cohort of exclusively breastfeeding full-term mother-infant pairs to test for differences in the milk transcriptome and metabolome associated with CMV, and the impact of CMV in breast milk on the infant gut microbiome and infant growth. We find upregulation of the indoleamine 2,3-dioxygenase (IDO) tryptophan-to-kynurenine metabolic pathway in CMV+ milk samples, and that CMV+ milk is associated with decreased Bifidobacterium in the infant gut. Our data indicate two opposing CMV-associated effects on infant growth; with kynurenine positively correlated, and CMV viral load negatively correlated, with infant weight-for-length at 1 month of age. These results suggest CMV transmission, CMV-related changes in milk composition, or both may be modulators of full-term infant development.

Abstract Chimeric antigen receptor (CAR) T-cells targeting Fibroblast Growth Factor Receptor 4 (FGFR4), a highly expressed surface tyrosine receptor in rhabdomyosarcoma (RMS), are already in the clinical phase of development, but tumour heterogeneity and suboptimal activation might hamper their potency. Here we report an optimization strategy of the co-stimulatory and targeting properties of a FGFR4 CAR. We replace the CD8 hinge and transmembrane domain and the 4-1BB co-stimulatory domain with those of CD28. The resulting CARs display enhanced anti-tumor activity in several RMS xenograft models except for an aggressive tumour cell line, RMS559. By searching for a direct target of the RMS core-regulatory transcription factor MYOD1, we identify another surface protein, CD276, as a potential target. Bicistronic CARs (BiCisCAR) targeting both FGFR4 and CD276, containing two distinct co-stimulatory domains, have superior prolonged persistent and invigorated anti-tumor activities compared to the optimized FGFR4-specific CAR and the other BiCisCAR with the same 4-1BB co-stimulatory domain. Our study thus lays down the proof-of-principle for a CAR T-cell therapy targeting both FGFR4 and CD276 in RMS.

Abstract Neuroendocrine (NE) transformation is a mechanism of resistance to targeted therapy in lung and prostate adenocarcinomas leading to poor prognosis. Up to date, even if patients at high risk of transformation can be identified by the occurrence of Tumor Protein P53 (TP53) and Retinoblastoma Transcriptional Corepressor 1 (RB1) mutations in their tumors, no therapeutic strategies are available to prevent or delay histological transformation. Upregulation of the cell cycle kinase Cell Division Cycle 7 (CDC7) occurred in tumors during the initial steps of NE transformation, already after TP53/RB1 co-inactivation, leading to induced sensitivity to the CDC7 inhibitor simurosertib. CDC7 inhibition suppressed NE transdifferentiation and extended response to targeted therapy in in vivo models of NE transformation by inducing the proteasome-mediated degradation of the MYC Proto-Oncogen (MYC), implicated in stemness and histological transformation. Ectopic overexpression of a degradation-resistant MYC isoform reestablished the NE transformation phenotype observed on targeted therapy, even in the presence of simurosertib. CDC7 inhibition also markedly extended response to standard cytotoxics (cisplatin, irinotecan) in lung and prostate small cell carcinoma models. These results nominate CDC7 inhibition as a therapeutic strategy to constrain lineage plasticity, as well as to effectively treat NE tumors de novo or after transformation. As simurosertib clinical efficacy trials are ongoing, this concept could be readily translated for patients at risk of transformation.

Abstract Impervious surface data are increasingly important for research and planning. Despite the availability of global and local urban land cover maps, regional data are lacking in Africa. We generated annual 30 m impervious cover data from 2001–2020 for Ghana, Togo, Benin, and Nigeria using the Landsat archive. We used random forest to predict impervious cover using 11 spectral indices and applied pixel-level temporal segmentation with the LandTrendr algorithm. Processing with LandTrendr improved the accuracy of the random forest predictions, with higher predicted-observed r2 (0.81), and lower mean error (−0.03), mean absolute error (5.73%), and root mean squared error (9.93%). We classified pixels >20% impervious as developed and

Abstract There is much interest in targeting the activity in the oxytocin system to regulate social bonding. However, studies with exogenous administration of oxytocin face the caveats of its low stability, poor brain permeability and insufficient receptor specificity. The use of a small-molecule oxytocin receptor-specific agonist could overcome these caveats. Prior to testing the potential effects of a brain-penetrant oxytocin receptor agonist in clinical settings, it is important to assess how such an agonist would affect social bonds in animal models. The facultatively monogamous prairie voles (Microtus ochrogaster), capable of forming long-term social attachments between adult individuals, are an ideal rodent model for such testing. Therefore, in a series of experiments we investigated the effects of the recently developed oxytocin receptor-specific agonist LIT-001 on the acquisition and expression of partner preference, a well-established model of pair bonding, in prairie voles. LIT-001 (10 mg/kg, intraperitoneal), as expected, facilitated the acquisition of partner preference when administered prior to a 4hr cohabitation. In contrast, while animals injected with vehicle after the 4hr cohabitation exhibited significant partner preference, animals that were injected with LIT-001 did not show such partner preference. This result suggests that OXTR activation during expression of pair bonding can inhibit partner preference. The difference in effects of LIT-001 on acquisition versus expression was not due to basal differences in partner preference between the experiments, as LIT-001 had no significant effects on expression of partner preference if administered following a shorter (2hr-long) cohabitation. Instead, this difference agrees with the hypothesis that the activation of oxytocin receptors acts as a signal of presence of a social partner. Our results indicate that the effects of pharmacological activation of oxytocin receptors crucially depend on the phase of social attachments.

Abstract Background Leveraging Alzheimer’s disease (AD) imaging biomarkers and longitudinal cognitive data may allow us to establish evidence of cognitive resilience (CR) to AD pathology in-vivo. Here, we applied latent class mixture modeling, adjusting for sex, baseline age, and neuroimaging biomarkers of amyloid, tau and neurodegeneration, to a sample of cognitively unimpaired older adults to identify longitudinal trajectories of CR. Methods We identified 200 Harvard Aging Brain Study (HABS) participants (mean age = 71.89 years, SD = 9.41 years, 59% women) who were cognitively unimpaired at baseline with 2 or more timepoints of cognitive assessment following a single amyloid-PET, tau-PET and structural MRI. We examined latent class mixture models with longitudinal cognition as the dependent variable and time from baseline, baseline age, sex, neocortical Aβ, entorhinal tau, and adjusted hippocampal volume as independent variables. We then examined group differences in CR-related factors across the identified subgroups from a favored model. Finally, we applied our favored model to a dataset from the Alzheimer’s Disease Neuroimaging Initiative (ADNI; n = 160, mean age = 73.9 years, SD = 7.6 years, 60% women). Results The favored model identified 3 latent subgroups, which we labelled as Normal (71% of HABS sample), Resilient (22.5%) and Declining (6.5%) subgroups. The Resilient subgroup exhibited higher baseline cognitive performance and a stable cognitive slope. They were differentiated from other groups by higher levels of verbal intelligence and past cognitive activity. In ADNI, this model identified a larger Normal subgroup (88.1%), a smaller Resilient subgroup (6.3%) and a Declining group (5.6%) with a lower cognitive baseline. Conclusion These findings demonstrate the value of data-driven approaches to identify longitudinal CR groups in preclinical AD. With such an approach, we identified a CR subgroup who reflected expected characteristics based on previous literature, higher levels of verbal intelligence and past cognitive activity.

Background: While studies have assessed comparative rates of restoration of shoulder function and alleviation of symptoms, comparative systemic postoperative complication rates between biceps tenotomy and tenodesis have yet to be assessed. The purpose of the present study was to use a national administrative database to perform a comprehensive investigation into 30-day complication rates after biceps tenotomy versus tenodesis, thus providing valuable insights for informed decision-making by clinicians and patients regarding the optimal surgical approach for pathologies of the long head of the biceps tendon. Methods: The National Surgical Quality Improvement Program database was queried to analyze postoperative complication rates and metrics associated with biceps tenotomy and tenodesis. Patient data spanning from 2012 to 2021 was extracted, with relevant variables assessed to identify and compare these two surgical approaches. Adjusted and unadjusted analyses were utilized to analyze patient demographics, comorbidities, operative times, lengths of stay, readmissions, adverse events, and yearly surgical volume, along with trends in usage, across cohorts. Results: Of 11,527 total patients, 264 (2.29%), 6826 (59.22%), and 4437 (38.49%) underwent tenotomy, tenodesis with open repair, and tenodesis with arthroscopic repair, respectively. Tenotomy operative times ([mean ± SD]: 66.25 ± 44.76 minutes) were shorter than those for open tenodesis (78.83 ± 41.82) and arthroscopic tenodesis (75.98 ± 40.16). Conversely, tenotomy patients had longer hospital days (0.88 ± 4.86 days) relative to open tenodesis (.08 ± 1.55) and arthroscopic tenodesis (.12 ± 2.70). Multivariable logistic regression controlling for demographics and comorbidities demonstrated that patients undergoing tenodesis were less likely to be readmitted (adjusted odds ratio [AOR]: 0.42, 95% confidence interval [CI]: 0.17-0.98, P = .050) or sustain serious adverse events (AOR: 0.27, 95% CI: 0.13-0.57, P

Background: The current standard-of-care pathology report relies only on lengthy written text descriptions without a visual representation of the resected cancer specimen. This study demonstrates the feasibility of incorporating virtual, three-dimensional (3D) visual pathology reports to improve communication of final pathology reporting. Materials and methods: Surgical specimens are 3D scanned and virtually mapped alongside the pathology team to replicate grossing. The 3D specimen maps are incorporated into a hybrid visual pathology report which displays the resected specimen and sampled margins alongside gross measurements, tumor characteristics, and microscopic diagnoses. Results: Visual pathology reports were created for 10 head and neck cancer cases. Each report concisely communicated information from the final pathology report in a single page and contained significantly fewer words (293.4 words) than standard written pathology reports (850.1 words, p

In plant breeding and genetics, predictive models traditionally rely on compact representations of high-dimensional data, often using methods like Principal Component Analysis (PCA) and, more recently, Autoencoders (AE). However, these methods do not separate genotype-specific and environment-specific features, limiting their ability to accurately predict traits influenced by both genetic and environmental factors. We hypothesize that disentangling these representations into genotype-specific and environment-specific components can enhance predictive models. To test this, we developed a compositional autoencoder (CAE) that decomposes high-dimensional data into distinct genotype-specific and environment-specific latent features. Our CAE framework employed a hierarchical architecture within an autoencoder to effectively separate these entangled latent features. Applied to a maize diversity panel dataset, the CAE demonstrated superior modeling of environmental influences and out-performs PCA (principal component analysis), PLSR (Partial Least square regression) and vanilla autoencoders by 7 times for ‘Days to Pollen’ trait and 10 times improved predictive performance for ‘Yield’. By disentangling latent features, the CAE provided a powerful tool for precision breeding and genetic research. This work has significantly enhanced trait prediction models, advancing agricultural and biological sciences.

Background selection, by which selection on deleterious alleles reduces diversity at linked neutral sites, influences patterns of total neutral diversity, πT, and genetic differentiation, FST, in structured populations. The theory of background selection may be split into two regimes: the background selection regime, where selection pressures are strong and mutation rates are sufficiently low such that deleterious alleles are at a deterministic mutation-selection balance, and the interference selection regime, where selection pressures are weak and mutation rates are sufficiently high that deleterious alleles accumulate and interfere with another, leading to selective interference. Previous work has quantified the effects of background selection on πT and FST only for deleterious alleles in the background selection regime. Furthermore, there is evidence to suggest that migration reduces the effects of background selection on FST, but this has not been fully explained. Here, we derive novel theory to predict the effects of migration on background selection experienced by a subpopulation and extend previous theory from the interference selection regime to make predictions in an island model. Using simulations, we show that this theory best predicts FST and πT. Moreover, we demonstrate that background selection may generate minimal increases in FST under sufficiently high migration rates, because migration reduces correlated effects on fitness over generations within subpopulations. However, we show that background selection may still cause substantial reductions in πT, particularly for metapopulations with a larger effective population size. Our work further extends the theory of background selection into structured populations, and suggests that background selection will minimally confound locus-to-locus FST scans.

Background: The recently published WHO classification of central nervous system (CNS) tumours recognizes DNA methylation profiling as a desirable and, for some diagnoses, essential diagnostic tool adjunctive to conventional histopathology. DNA methylation profiling is not routinely available in many countries, including Greece. Methods: In this collaborative study, we report the DNA methylation results in a series of children and adolescents with CNS tumours in Greece (2018–2023). In total, 130 tumour samples were analyzed using the latest applicable version of the Heidelberg brain tumour classifier. Results: Upon initial analysis, 80 % (104/130) achieved calibrated scores (Cs) ≥ 0.9 and matched an established methylation class family/subclass. Among them, methylation results confirmed (90/104, 86.5 %), refined (50/104, 48 %) or changed (10/104, 9.6 %) the histological diagnosis. Only four results were regarded as non-contributing (4/104, 3.9 %). Twenty-six tumour samples received Cs < 0.9. Despite low scores, methylation results supported the initial diagnosis with lower confidence in 38.5 % (10/26) and established the diagnosis in two tumours with non-conclusive histopathology. Additional t-distributed stochastic neighbour embedding (t-SNE) analysis allowed the possible classification of twelve tumours. Nine more samples reached high Cs using the newer brain tumour classifiers, since available. Samples co-tested in Greece demonstrated excellent test reproducibility, supporting the analysis' local implementation. Methylome profiling impacted the clinical management of 40 % of patients, modifying stratification, prognosis, or treatment approach. Conclusions: This study supports the need to integrate methylome analysis into routine diagnostics in our country and highlights the importance of collaboration between European pediatric oncology centres.

Background: Intrinsic foot muscle weakness has been implicated in a wide range of forefoot conditions and is typically measured by the paper grip test. The proposed “knuckle test” is intended to evaluate intrinsic foot muscle function, in which active flexion of toes makes the metatarsal heads (“knuckles”) prominent in the forefoot. This study seeks to compare prevalence of negative knuckle test results and intrinsic muscle weakness in patients, primarily by association with a positive paper grip test result and secondarily with presence of toe deformities. Methods: Ninety-eight patients, 55 with toe deformity and 43 without, were evaluated for ability to flex their toes to the extent of knuckle prominence (knuckle test) and grip paper on the ground with their toes (paper grip test). Variables were compared between those with positive and negative knuckle test results. Results: A negative knuckle test result is significantly associated with the inability to grip a paper strip ( P

There are a limited number of case reports describing the division of a horseshoe kidney (HSK) during trans- peritoneal repair of an abdominal aortic aneurysm (AAA). We present case of a juxta-renal AAA overlaid by an L shaped HSK, repaired trans- peritoneal with division of the isthmus. This was complicated by post-operative urinoma which was successfully treated interventionally.This approach was chosen due to the presence of the juxta-renal AAA with the majority of the HSK being perfused by a large left renal artery originating at the neck of the AAA. Temporary bilateral ureteral stents were placed. The isthmus of the HSK was divided followed by open tube graft repair of the AAA. Postoperative workup revealed an abdominal urinoma, which was successfully treated by urinary diversion and selective renal arterial branch embolization. Two years later, patient remains well with no evidence of hydronephrosis or graft infection.

This study investigated the pathogenic mechanisms of Aeromonas veronii in macrophages. THP-1 derived macrophages were used as a human macrophage model and were treated with A. veronii strain AS1 isolated from intestinal biopsies of an IBD patient, or Escherichia coli strain K-12. RNA was extracted and subjected to RNA sequencing and comparative transcriptomic analyses. Protein levels of IL-8, IL-1β, IL-18, and TNFα were measured using ELISA, and apoptosis was assessed using caspase 3/7 assays. Both A. veronii AS1 and E. coli K-12 significantly upregulated the expression of many genes involving inflammation. At the protein level, A. veronii AS1 induced significantly higher levels of IL-8, TNFα, mature IL-18 and IL-1β than E. coli K-12, and led to greater elevation of caspase 3/7 activities. Both A. veronii AS1 and E. coli K-12 upregulated the expression of CASP5, but not other caspase genes. A. veronii AS1 significantly downregulated the expression of 20 genes encoding histone proteins that E. coli K-12 did not. The more profound pathogenic effects of A. veronii in inducing inflammation and apoptosis in macrophages than E. coli K-12, are consistent with its role as a human enteric pathogen. The upregulated expression of CASP5 and increased release of IL-1β and IL-18, support the role of CASP5 in activation of non-canonical inflammasome. The downregulation of histone genes by A. veronii suggests a unique impact on host cell gene expression, which may represent a novel virulence strategy. These findings advance the understanding of pathogenic mechanisms of the emerging human enteric pathogen A. veronii.

Summary: Neural representations for visual stimuli typically emerge with a bilateral distribution across occipitotemporal cortex (OTC)? Pediatric patients undergoing unilateral OTC resection offer an opportunity to evaluate whether representations for visual stimulus individuation can sufficiently develop in a single OTC. Here, we assessed the non-resected hemisphere of patients with pediatric resection within (n = 9) and outside (n = 12) OTC, as well as healthy controls’ two hemispheres (n = 21). Using functional magnetic resonance imaging, we mapped category selectivity (CS), and representations for visual stimulus individuation (for faces, objects, and words) with repetition suppression (RS). There were no group differences in CS or RS. However, OTC resection patients’ accuracy on face and object (but not word) recognition was lower than controls’. The neuroimaging results highlight neural resilience following damage to the contralateral homologue. Critically, however, a single OTC does not suffice for typical behavior, and, thereby, implicates the necessary contributions of bilateral OTC for visual recognition.

Abstract Louisiana surveys waterfowl hunters every 5 years to assess hunter effort, harvest success, demographics, and preferences for proposed regulations and management practices. The 2020 Survey of Louisiana Waterfowl Hunters addressed hunter satisfaction patterns, hunter perceptions on waterfowl migration, associations of field experiences to satisfaction, associations among distribution waves, the efficacy of sample coverage by an email survey, and allowed comparison with hunter satisfaction with surveys in 2005, 2010, and 2015. We distributed a 31‐question survey by email to 73,554 Louisiana waterfowl hunters following the 2019–2020 season. We received 13,483 total responses, of which 8,218 were usable (licensed respondents actively hunting waterfowl during the 2019–2020 season), resulting in a qualified response rate of 12.0%. We compared qualified respondents to the overall population of Harvest Information Program registrants (169,891) and found no significant differences for age class, geographic distribution, and license type. Our results indicated that surveys should be distributed in 3 waves, as the number of days hunted would be overestimated by 7% (mean of 15 days [95% confidence interval = 14.7–15.7] compared to a mean of 14 days [95% confidence interval = 13.7–14.4]) by a single survey. Hunters' satisfaction was independent of which geographic zone they hunted, whether they were members of conservation organizations, or how many waterfowl were seen. Our results also indicated that the probability of greater hunter satisfaction was increased by 98% as the number of waterfowl harvested surpassed 57, by 68% for respondents reporting that their actual harvest exceeded expected harvest by at least one bird, and by 61% for respondents reporting that their actual days hunted exceeded expected days hunted by at least one day.

Background: The role of medical therapy for heart failure with reduced ejection fraction (HFrEF) in subjects with end-stage renal disease receiving renal transplantation (RT) is understudied. Here, we describe post-RT HFrEF medical management practices at a single urban, academic tertiary care center. Methods: RT recipients between January 1, 2015 and November 30, 2020 with history of ejection fraction (EF)