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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

Abstract Objective While risk factors for osteoarthritis (OA) are well known, it is not well understood why certain individuals maintain high mobility and joint health throughout their life while others demonstrate OA at older ages. The purpose of this study was to assess which demographic, clinical and MRI quantitative and semi-quantitative factors are associated with preserving healthy knees in older individuals. Methods This study analyzed data from the OA Initiative (OAI) cohort of individuals at the age of 65 years or above. Participants without OA at baseline (BL) (Kellgren-Lawrence (KL) ≤ 1) were followed and classified as incident cases (KL ≥ 2 during follow-up; n = 115) and as non-incident (KL ≤ 1 over 96-month; n = 391). Associations between the predictor-variables sex, age, BMI, race, clinical scoring systems, T2 relaxation times and Whole-Organ Magnetic Resonance Imaging-Score (WORMS) readings at BL and the preservation of healthy knees (KL ≤ 1) during a 96-month follow-up period were assessed using logistic regression models. Results Obesity and presence of pain showed a significant inverse association with maintaining radiographically normal joints in patients aged 65 and above. T2 relaxation times of the lateral femur and tibia as well as the medial femur were also significantly associated with maintaining radiographically normal knee joints. Additionally, absence of lesions of the lateral meniscus and absence of cartilage lesions in the medial and patellofemoral compartments were significantly associated with maintaining healthy knee joints. Conclusion Overall, this study provides protective clinical parameters as well as quantitative and semi-quantitative MR-imaging parameters associated with maintaining radiographically normal knee joints in an older population over 8 years.

Abstract Synthetic biology allows us to reuse, repurpose, and reconfigure biological systems to address society’s most pressing challenges. Developing biotechnologies in this way requires integrating concepts across disciplines, posing challenges to educating students with diverse expertise. We created a framework for synthetic biology training that deconstructs biotechnologies across scales—molecular, circuit/network, cell/cell-free systems, biological communities, and societal—giving students a holistic toolkit to integrate cross-disciplinary concepts towards responsible innovation of successful biotechnologies. We present this framework, lessons learned, and inclusive teaching materials to allow its adaption to train the next generation of synthetic biologists.

Abstract Individuals in isolated and extreme environments can experience debilitating side-effects including significant decreases in fat-free mass (FFM) from disuse and inadequate nutrition. The objective of this study was to determine the strengths and weaknesses of three-dimensional optical (3DO) imaging for monitoring body composition in either simulated or actual remote environments. Thirty healthy adults (ASTRO, male = 15) and twenty-two Antarctic Expeditioners (ABCS, male = 18) were assessed for body composition. ASTRO participants completed duplicate 3DO scans while standing and inverted by gravity boots plus a single dual-energy X-ray absorptiometry (DXA) scan. The inverted scans were an analog for fluid redistribution from gravity changes. An existing body composition model was used to estimate fat mass (FM) and FFM from 3DO meshes. 3DO body composition estimates were compared to DXA with linear regression and reported with the coefficient of determination (R 2 ) and root mean square error (RMSE). ABCS participants received only duplicate 3DO scans on a monthly basis. Standing ASTRO meshes achieved an R 2 of 0.76 and 0.97 with an RMSE of 2.62 and 2.04 kg for FM and FFM, while inverted meshes achieved an R 2 of 0.52 and 0.93 with an RMSE of 2.84 and 3.23 kg for FM and FFM, respectively, compared to DXA. For the ABCS arm, mean weight, FM, and FFM changes were −0.47, 0.06, and −0.54 kg, respectively. Simulated fluid redistribution decreased the accuracy of estimated body composition values from 3DO scans. However, FFM stayed robust. 3DO imaging showed good absolute accuracy for body composition assessment in isolated and remote environments.

This study investigates the innovation efficiency of listed companies in the Beijing-Tianjin-Hebei region from 2015 to 2021. Various models are applied to analyze the data and identify factors affecting innovation efficiency. The findings show that, after adjusting the data, most listed companies' scale efficiency decreases significantly. Pure technical efficiency also decreases, but not to a substantial degree. These changes lead to an overestimation of innovation efficiency. The analysis reveals that the business environment influences the innovation index of listed companies. Additionally, there is a positive relationship between enterprise nature, equity concentration, urban financial expenditure, and innovation efficiency. Longer-established companies face challenges in improving their innovation efficiency. Most companies demonstrate improvements in technical efficiency, indicating relatively high levels of technical efficiency. However, continuous technological progress is crucial. The paper suggests that policymakers and company management should prioritize the enterprise's nature, equity concentration, and urban financial expenditure to cultivate innovation efficiency.

Abstract While alterations in nucleus size, shape, and color are ubiquitous in cancer, comprehensive quantification of nuclear morphology across a whole-slide histologic image remains a challenge. Here, we describe the development of a pan-tissue, deep learning-based digital pathology pipeline for exhaustive nucleus detection, segmentation, and classification and the utility of this pipeline for nuclear morphologic biomarker discovery. Manually-collected nucleus annotations were used to train an object detection and segmentation model for identifying nuclei, which was deployed to segment nuclei in H&E-stained slides from the BRCA, LUAD, and PRAD TCGA cohorts. Interpretable features describing the shape, size, color, and texture of each nucleus were extracted from segmented nuclei and compared to measurements of genomic instability, gene expression, and prognosis. The nuclear segmentation and classification model trained herein performed comparably to previously reported models. Features extracted from the model revealed differences sufficient to distinguish between BRCA, LUAD, and PRAD. Furthermore, cancer cell nuclear area was associated with increased aneuploidy score and homologous recombination deficiency. In BRCA, increased fibroblast nuclear area was indicative of poor progression-free and overall survival and was associated with gene expression signatures related to extracellular matrix remodeling and anti-tumor immunity. Thus, we developed a powerful pan-tissue approach for nucleus segmentation and featurization, enabling the construction of predictive models and the identification of features linking nuclear morphology with clinically-relevant prognostic biomarkers across multiple cancer types.

Abstract Selective serotonin reuptake inhibitors (SSRIs) are widely used for depression based on the monoamine deficiency hypothesis. However, the clinical use of these agents is controversial, in part because of their variable clinical efficacy and in part because of their delayed onset of action. Because of the complexities involved in replicating human disease and clinical dosing in animal models, the scientific community has not reached a consensus on the reasons for these phenomena. In this work, we create a theoretical hippocampal model incorporating escitalopram’s pharmacokinetics, pharmacodynamics (competitive and non-competitive inhibition, and serotonin transporter (SERT) internalization), inflammation, and receptor dynamics. With this model, we simulate chronic oral escitalopram in mice showing that days to weeks are needed for serotonin levels to reach steady-state. We show escitalopram’s chemical efficacy is diminished under inflammation. Our model thus offers mechanisms for how chronic escitalopram affects brain serotonin, emphasizing the importance of optimized dose and time for future antidepressant discoveries.

Summary: Although cancer cachexia is classically characterized as a systemic inflammatory disorder, emerging evidence indicates that weight loss also associates with local tissue inflammation. We queried the regulation of this inflammation and its causality to cachexia by exploring skeletal muscle, whose atrophy strongly associates with poor outcomes. Using multiple mouse models and patient samples, we show that cachectic muscle is marked by enhanced innate immunity. Nuclear factor κB (NF-κB) activity in multiple cells, including satellite cells, myofibers, and fibro-adipogenic progenitors, promotes macrophage expansion equally derived from infiltrating monocytes and resident cells. Moreover, NF-κB-activated cells and macrophages undergo crosstalk; NF-κB+ cells recruit macrophages to inhibit regeneration and promote atrophy but, interestingly, also protect myofibers, while macrophages stimulate NF-κB+ cells to sustain an inflammatory feedforward loop. Together, we propose that NF-κB functions in multiple cells in the muscle microenvironment to stimulate macrophages that both promote and protect against muscle wasting in cancer.

Summary: Background: Contemporary surgical practices for traumatic brain injury (TBI) remain unclear. We describe the clinical profile of an 18-centre US TBI cohort with cranial surgery. Methods: The prospective, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study (2014–2018; ClinicalTrials.gov #NCT02119182) enrolled subjects who presented to trauma centre and received head computed tomography within 24-h (h) post-TBI. We performed a secondary data analysis in subjects aged ≥17-years with hospitalisation. Clinical characteristics, surgery type/timing, hospital and six-month outcomes were reported. Findings: Of 2032 subjects (age: mean = 41.4-years, range = 17–89-years; male = 71% female = 29%), 260 underwent cranial surgery, comprising 65% decompressive craniectomy, 23% craniotomy, 12% other surgery. Subjects with surgery (vs. without surgery) presented with worse neurological injury (median Glasgow Coma Scale = 6 vs. 15; midline shift ≥5 mm: 48% vs. 2%; cisternal effacement: 61% vs. 4%; p

Abstract Lyme disease, the most prevalent tick‐borne disease in North America, is caused by the bacterium Borrelia burgdorferi, and in the eastern and central United States, it is spread to humans by the black‐legged tick (Ixodes scapularis). Due to the complex, multiyear and multihost life cycle of this species, a matrix modeling approach is needed to effectively estimate subseasonal, multistage survival and transition dynamics in order to better understand and predict when population growth is high. Of the three questing tick life stages (larvae, nymphs, and adults), nymphs are most often associated with transmitting the bacteria to humans, and previous work suggests a mix of abiotic and biotic drivers are associated with nymph abundance. However, understanding tick population growth requires understanding mortality and transition probabilities for each stage and each stage may be individually and uniquely impacted by climate and host availability. A larval tick, for example, may experience warming temperatures differently than nymph or adults, because they are present on the landscape at different times. Here, we describe and validate a model that accounts for field sampling design and evaluates abiotic (temperature, relative humidity, precipitation) and biotic (host abundance) drivers of variation in tick population growth. To account for the drivers of subseasonal and interannual variability in demography, phenology, and population density, we built stage‐structured population models that account for variability in meteorology and host population abundance throughout the full tick lifecycle. Our model is fit and validated with 11 years of tick and host data from the northeastern United States. In this context, we found that a four‐stage model that includes unique transitions to and from a dormant, overwintering nymph state outperforms a model that only includes the three questing stages, and that incorporating the abundance of the predominant host species, Peromyscus leucopus, and weather variables improved predictions and model fit. Additionally, the model accurately predicted all three questing stages at sites different than where they were calibrated, showing that this model structure is generally transferable. Overall, this model lays a foundation for the real‐time iterative forecasting of tick populations needed to effectively protect public health.

Abstract Objective The present study objectived to investigate the influence of Ramadan fasting (RF) on olfactory function. Methods Sixty‐two participants were included in the current prospective study. The odor threshold and identification performances were determined by using the Connecticut Chemosensory Clinical Research Center (CCCRC) test initially (day 0) and on the first and last day (30th) of RF. Body weight (BW)s were measured initially and at the end of the study. The results were analyzed statistically. Results The average of baseline and last‐day BWs were 78.38 ± 12.96 and 78.36 ± 12.39 kg, respectively. No significant difference was determined in terms of BWs (p = .932, p > .05). In the evaluation of CCCRC test outcomes, significant differences were observed in the scores of butanol thresholds (p = .0001), odor identification (p = .0001), food‐related odors identification (p = .0001), and the number of normosmic individuals (p = .0001) at different times (p

Abstract Objectives This study aims to better understand the perspectives of emergency medicine physicians’ on the role that state‐mandated, topic‐specific continuing medical education (CME) plays in addressing knowledge gaps, its relevance to current emergency practice, its reported burden and costs of CME activities to emergency physicians, and its perceived improvement in patient care. Methods A cross‐sectional survey was designed by the Coalition of Board‐Certified Emergency Physicians (COBCEP) and distributed in February 2023 to all American Board of Emergency Medicine (ABEM)‐certified physicians. Statistical tests of significance (Pearson's chi‐square and Fisher's exact test) assessed the cost and time spent on CME as well as the perceived value placed on CME by ABEM‐certified physicians to improve patient care. Data were summarized using descriptive statistics. Results There were 5562 (13.0%) responses from the 43656 physicians who received the survey—5506 responses were included for analysis. Over half of the physicians (53.0%) had more than 15 years of post‐residency practice experience. Most physicians (57.3%) spent less than $5,000 per year on obtaining CME. Most physicians practicing in states with state‐mandated, topic‐specific CME requirements believed that participation in ABEM continuing certification could be used to reduce the need for state‐mandated, topic‐specific CME requirements (83.6%) and state‐mandated, topic‐specific requirements were believed to be unlikely to improve patient care (70.8%). Conclusions Although well‐intended, state CME requirements may lack relevancy and can, at times, place an undue burden on emergency physicians. Tailoring CME requirements to increase relevance to their patient populations and reduce barriers to completing CME could enhance knowledge translation and improve patient outcomes.

Proper derivation of CH3NH3PbX3 (MAPbX3; where X = Cl−, Br−, I−) optical constants is a critical step toward the development of high‐performance perovskite devices. To date, the optical dispersions at all wavelengths have been inconsistently characterized by under‐approximating or omitting anomalous spectral features. Herein, a rigorous optical dispersion data analysis of single‐crystal MAPbBr3 involving variable‐angle spectroscopic ellipsometry data appended with transmission intensity data is presented. This approach yields a more robust derivation of the refractive index and extinction coefficient for both anomalous (absorptance) and normal (no absorptance) optical dispersion regimes. Using the derived optical constants, illustrative modeled perovskite solar cell device designs are presented in relation to nonrealistic designs prepared using representative optical constants reported in the literature. In comparison, the derived optical constants enables the modeling of layer thicknesses to maximize absorption by the active layer (MAPbBr3) and minimize parasitic optical absorptance by the nonactive layers at broad angles of incidence (≈0°–70°). This robust derivation of MAPbBr3 optical constants is expected to impact the optical dispersion data analysis of all perovskite analogs and expedite targeted development of, for example, solar cell, light‐emitting diode, photo‐ and X‐ray/γ‐ray detector, and laser system technologies.

Background: Atherosclerotic cardiovascular disease (ASCVD) risk estimation based on the pooled cohort equation (PCE) overestimates in population-based cohorts. Whether it performs equally across disaggregated demographics in health care populations is less known. Objectives: The purpose of the study was to recalibrate PCE and rederive prevention thresholds in a contemporary health care system and evaluate its performance across sociodemographics. Methods: We retrospectively inspected electronic health records between 2010 to 2012 and 2020 to 2022 within Mass General Brigham health care in New England region. We compared performance of the original vs recalibrated PCE measured by calibration, discrimination, reclassification rate, and net benefit among 160,926 patients aged 40 to 79 years and without prior ASCVD or lipid-lowering medication. Results: Of the 160,926 patients (mean age: 54.6 ± 8.6 years; 61.4% female), 20,373 (12.7%) developed ASCVD over 10 years. The original PCE globally underestimated ASCVD risk (observed vs predicted incidence rate: 0.13 vs 0.05). Recalibration upclassified risk primarily among individuals with low-to-borderline risk by the original PCE and additionally identified 40% of patients who had undergone ASCVD events yet deemed statin-ineligible based on the original PCE. Treatment thresholds yielding the greatest net benefit were ≥24.0% for women (+23.3%) vs ≥26.0% for men (+18.7%), whereas ≥26.0% for White or other race (+24.7%) vs ≥14.0% Black or African American (+12.5%), respectively. Specifically, Hispanic or Latino and non-Hispanic Black patients conferred the greatest sensitivity improvement at ≥12.3% threshold compared to higher ≥23.6% among non-Hispanic Asian or Pacific Islanders. Generally, lower thresholds earlier in life were optimal. Conclusions: Recalibration and personalized treatment thresholds derived within a health system may improve prevention treatment allocation efficiency.

Complex endovascular aortic repair (EVAR) requires the use of multiple small sheath cannulation inside a large sheath. Because the large sheath is not designed for multiple small sheath cannulation, large amounts of blood loss can be encountered in complex EVARs. Cell Saver can be used effectively in complex EVARs using a modified draping technique, allowing for increased cell salvage and autogenous transfusions as needed.

Summary: Nuclear pore complexes (NPCs) regulate nucleocytoplasmic transport and are anchored in the nuclear envelope by the transmembrane nucleoporin NDC1. NDC1 is essential for post-mitotic NPC assembly and the recruitment of ALADIN to the nuclear envelope. While no human disorder has been associated to one of the three transmembrane nucleoporins, biallelic variants in AAAS, encoding ALADIN, cause triple A syndrome (Allgrove syndrome). Triple A syndrome, characterized by alacrima, achalasia, and adrenal insufficiency, often includes progressive demyelinating polyneuropathy and other neurological complaints. In this report, diagnostic exome and/or RNA sequencing was performed in seven individuals from four unrelated consanguineous families with AAAS-negative triple A syndrome. Molecular and clinical studies followed to elucidate the pathogenic mechanism. The affected individuals presented with intellectual disability, motor impairment, severe demyelinating with secondary axonal polyneuropathy, alacrima, and achalasia. None of the affected individuals has adrenal insufficiency. All individuals presented with biallelic NDC1 in-frame deletions or missense variants that affect amino acids and protein domains required for ALADIN binding. No other significant variants associated with the phenotypic features were reported. Skin fibroblasts derived from affected individuals show decreased recruitment of ALADIN to the NE and decreased post-mitotic NPC insertion, confirming pathogenicity of the variants. Taken together, our results implicate biallelic NDC1 variants in the pathogenesis of polyneuropathy and a triple A-like disorder without adrenal insufficiency, by interfering with physiological NDC1 functions, including the recruitment of ALADIN to the NPC.