The Open Force Field Initiative: Open Software and Open Science for Molecular Modeling.

Force fields are a key component of physics-based molecular modeling, describing the energies and forces in a molecular system as a function of the positions of the atoms and molecules involved. Here, we provide a review and scientific status report on the work of the Open Force Field (OpenFF) Initiative, which focuses on the science, infrastructure and data required to build the next generation of biomolecular force fields. We introduce the OpenFF Initiative and the related OpenFF Consortium, describe its approach to force field development and software, and discuss accomplishments to date as well as future plans. OpenFF releases both software and data under open and permissive licensing agreements to enable rapid application, validation, extension, and modification of its force fields and software tools. We discuss lessons learned to date in this new approach to force field development. We also highlight ways that other force field researchers can get involved, as well as some recent successes of outside researchers taking advantage of OpenFF tools and data.

MARK2/MARK3 kinases are catalytic co-dependencies of YAP/TAZ in human cancer.

The Hippo signaling pathway is commonly dysregulated in human cancer, which leads to a powerful tumor dependency on the YAP/TAZ transcriptional coactivators. Here, we used paralog co-targeting CRISPR screens to identify the kinases MARK2/3 as absolute catalytic requirements for YAP/TAZ function in diverse carcinoma and sarcoma contexts. Underlying this observation is direct MARK2/3-dependent phosphorylation of NF2 and YAP/TAZ, which effectively reverses the tumor suppressive activity of the Hippo module kinases LATS1/2. To simulate targeting of MARK2/3, we adapted the CagA protein from H. pylori as a catalytic inhibitor of MARK2/3, which we show can regress established tumors in vivo. Together, these findings reveal MARK2/3 as powerful co-dependencies of YAP/TAZ in human cancer; targets that may allow for pharmacology that restores Hippo pathway-mediated tumor suppression.

Risk of Pancreatitis After Endoscopic Ultrasound-Guided Fine-Needle Aspiration of Pancreatic Cystic Lesions: A Systematic Review and Meta-Analysis.

INTRODUCTION: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is frequently used to risk-stratify pancreatic cystic lesions (PCLs). Rising PCL incidence and developments in tissue acquisition and specimen analysis necessitate updated appraisal of EUS-FNA safety, particularly the risk of postprocedure pancreatitis, the most common EUS-FNA-related adverse event. Our systematic review aims to accurately quantify the risk of EUS-FNA-related pancreatitis to best inform decisions regarding EUS-FNA's optimal role in PCL workup. METHODS: We performed systematic searches in 4 databases from inception to April 2024 for original English-language studies investigating EUS-FNA-related pancreatitis. We extracted data on demographics and EUS-FNA-related pancreatitis risk, severity, and risk factors. These were meta-analyzed through the DerSimonian Laird Method using a random-effects model. Meta-regression of pancreatitis risk was performed to delineate associations with clinical and procedural characteristics. RESULTS: Sixty-four studies comprised 8,086 patients and reported 110 EUS-FNA-related pancreatitis events. Pooled risk of EUS-FNA-related pancreatitis was 1.4% (95% confidence intervals, -0.8% to 3.5%; I2 = 0.00), which was predominantly of mild severity (67%) and uniformly nonfatal. Pancreatitis risk lacked significant association with sample size, age, sex, cyst size, needle caliber, or passes, although we noted trends toward higher risk in studies published after 2015, those using higher gauge needles (19 G vs 22 G/25 G), and those performing EUS-guided through-the-needle biopsy. DISCUSSION: We note with high certainty that pancreatitis after EUS-FNA of PCLs is infrequent and mild in severity with no mortality in the included cohort. EUS-guided through-the-needle biopsy may serve as a significant risk factor for EUS-FNA-related pancreatitis risk; however, further studies are needed to delineate other predisposing characteristics.

Stroke Severity, Caregiver Feedback, and Cognition in the REGARDS-CARES Study.

BACKGROUND: Cognitive impairment after stroke is common and is present in up to 60% of survivors. Stroke severity, indicated by both volume and location, is the most consequential predictor of cognitive impairment, with severe strokes predicting higher chances of cognitive impairment. The current investigation examines the associations of 2 stroke severity ratings and a caregiver-report of poststroke functioning with longitudinal cognitive outcomes. METHODS AND RESULTS: One hundred fifty-seven caregivers and stroke survivor dyads participated in the CARES (Caring for Adults Recovering From the Effects of Stroke) project, an ancillary study of the REGARDS (Reasons for Geographic and Racial Differences in Stroke) national cohort study. The Glasgow Outcome Scale and modified Rankin Scale scores collected at hospitalization discharge were included as 2 primary predictors of cognitive impairment. The number of caregiver-reported problems and impairments at 9 months following stroke were included as a third predictor. Cognition was measured using a biennial telephone battery and included the domains of learning, memory, and executive functioning. Multiple cognitive assessments were analyzed up to 5 years poststroke, controlling for prestroke cognition and demographic variables of the stroke survivor. Separate mixed models showed significant main effects of the Glasgow Outcome Scale (b=0.3380 [95% CI, 0.14-0.5]; P=0.0009), modified Rankin Scale (b=-0.2119 [95% CI, -0.32 to -0.10]; P=0.0002), and caregiver-reported problems (b=-0.0671 [95% CI, -0.09 to -0.04]; P<0.0001) on longitudinal cognitive scores. In a combined model including all 3 predictors, only caregiver-reported problems significantly predicted cognition (b=-0.0480 [95% CI, -0.08 to -0.03]; P<0.0001). CONCLUSIONS: These findings emphasize the importance of caregiver feedback in predicting cognitive consequences of stroke.

Aberrant bowel movement frequencies coincide with increased microbe-derived blood metabolites associated with reduced organ function.

Bowel movement frequency (BMF) directly impacts the gut microbiota and is linked to diseases like chronic kidney disease or dementia. In particular, prior work has shown that constipation is associated with an ecosystem-wide switch from fiber fermentation and short-chain fatty acid production to more detrimental protein fermentation and toxin production. Here, we analyze multi-omic data from generally healthy adults to see how BMF affects their molecular phenotypes, in a pre-disease context. Results show differential abundances of gut microbial genera, blood metabolites, and variation in lifestyle factors across BMF categories. These differences relate to inflammation, heart health, liver function, and kidney function. Causal mediation analysis indicates that the association between lower BMF and reduced kidney function is partially mediated by the microbially derived toxin 3-indoxyl sulfate (3-IS). This result, in a generally healthy context, suggests that the accumulation of microbiota-derived toxins associated with abnormal BMF precede organ damage and may be drivers of chronic, aging-related diseases.

The Influence of Disagreements over COVID-19 Preventive Measures on Stress and Sleep Quality.

In this paper we reported the rate of disagreements and their effect on stress levels and sleep quality. Data was collected from 573 South Dakota residents. We estimated two ordinary least squares regressions using stress and sleep quality due to COVID-19 as outcome variables. A high percentage (62.1%) of the participants reported disagreements over COVID-19 with friends and family members. Disagreements over COVID-19 were associated with a higher level of stress (ß = 1.001, p = .000) and a lower level of sleep quality (ß = -.431, p = .039). The results of this study should serve as a reminder to researchers to consider the impact of interpersonal conflict over public health measures with family and friends on mental health.

Differential Target Multiplexed Spinal Cord Stimulation for the Treatment of Chronic Intractable Upper Limb Pain: 12-Month Results From a Prospective, Multicenter Study.

OBJECTIVES: This prospective, open-label, single-arm, multicenter study evaluated the use of differential target multiplexed (DTM) spinal cord stimulation (SCS) therapy for chronic upper limb pain (ULP). MATERIALS AND METHODS: A total of 58 candidates for SCS who had chronic ULP were enrolled at 11 sites in the USA. The safety and effectiveness of DTM SCS for treating chronic intractable ULP were evaluated over 12 months. The primary end point was the percentage of responders (≥50% ULP relief versus baseline) to treatment at three months after device activation. This study also evaluated the extent of disability, patient satisfaction, and patient global impression of change with DTM SCS therapy. RESULTS: The mean baseline pain score (10-cm visual analog scale [VAS-10]) for ULP was 7.2 cm, with a mean age of 56 years and mean ULP duration of ten years; 47 subjects were assessed at the primary end point. The percentage of ULP responders was 92% at three months, which was consistent at six (91%) and 12 months (86%). Significant ULP relief (81% reduction in VAS-10) was observed at the primary end point and sustained throughout the study duration. Significant improvements in disability in addition to high levels (>95%) of satisfaction and feelings of improvement were reported. Frequency of study-related anticipated adverse events was in line with expectations of SCS therapy. CONCLUSION: In this patient population with difficult-to-treat conditions with limited clinical evidence of the effectiveness of SCS, subjects reported significant reduction in chronic ULP in response to treatment with DTM SCS.

Dystrophin deficiency impairs cell junction formation during embryonic myogenesis from pluripotent stem cells.

Mutations in the DMD gene lead to Duchenne muscular dystrophy (DMD), a severe neuromuscular disorder affecting young boys as they acquire motor functions. DMD is typically diagnosed at 2-4 years of age, but the absence of dystrophin has negative impacts on skeletal muscles before overt symptoms appear in patients, which poses a serious challenge in current standards of care. Here, we investigated the consequences of dystrophin deficiency during skeletal muscle development. We used single-cell transcriptome profiling to characterize the myogenic trajectory of human pluripotent stem cells and showed that DMD cells bifurcate to an alternative branch when they reach the somite stage. Dystrophin deficiency was linked to marked dysregulations of cell junction proteins involved in the cell state transitions characteristic of embryonic somitogenesis. Altogether, this work demonstrates that in vitro, dystrophin deficiency has deleterious effects on cell-cell communication during myogenic development, which should be considered in future therapeutic strategies for DMD.

Beriberi following sleeve gastrectomy.

Bariatric surgery is being undertaken more frequently in response to rising levels of obesity but is increasingly also requested as a cosmetic choice. Nutritional deficiencies are a recognised consequence of gastrectomy, with potentially severe and permanent neurological sequelae. We present two cases of acute, severe polyneuropathy following sleeve gastrectomy. Severe thiamine deficiency was considered in both cases but with delayed proof and a significant initial differential diagnosis. Neurologists must have a high index of suspicion for the peripheral as well as central presentations of thiamine deficiency to avoid permanent disability. We also call for explicit information resources warning of the risk and signs of thiamine deficiency to be provided routinely to patients after gastrectomy.

Preventing loss of sirt1 lowers mitochondrial oxidative stress and preserves C2C12 myotube diameter in an in vitro model of cancer cachexia.

Cancer cachexia is a multifactorial syndrome associated with advanced cancer that contributes to mortality. Cachexia is characterized by loss of body weight and muscle atrophy. Increased skeletal muscle mitochondrial reactive oxygen species (ROS) is a contributing factor to loss of muscle mass in cachectic patients. Mice inoculated with Lewis lung carcinoma (LLC) cells lose weight, muscle mass, and have lower muscle sirtuin-1 (sirt1) expression. Nicotinic acid (NA) is a precursor to nicotinamide dinucleotide (NAD+) which is exhausted in cachectic muscle and is a direct activator of sirt1. Mice lost body and muscle weight and exhibited reduced skeletal muscle sirt1 expression after inoculation with LLC cells. C2C12 myotubes treated with LLC-conditioned media (LCM) had lower myotube diameter. We treated C2C12 myotubes with LCM for 24 h with or without NA for 24 h. C2C12 myotubes treated with NA maintained myotube diameter, sirt1 expression, and had lower mitochondrial superoxide. We then used a sirt1-specific small molecule activator SRT1720 to increase sirt1 activity. C2C12 myotubes treated with SRT1720 maintained myotube diameter, prevented loss of sirt1 expression, and attenuated mitochondrial superoxide production. Our data provides evidence that NA may be beneficial in combating cancer cachexia by maintaining sirt1 expression and decreasing mitochondrial superoxide production.

Characterization of highly pathogenic avian influenza virus in retail dairy products in the US.

In March 2024, clade 2.3.4.4b H5N1 highly pathogenic avian influenza virus (HPAIV) was detected in dairy cattle in the US, and it was discovered that the virus could be detected in raw milk. Although affected cow's milk is diverted from human consumption and current pasteurization requirements are expected to reduce or eliminate infectious HPAIV from the milk supply, a study was conducted to characterize whether the virus could be detected by quantitative real-time RT-PCR (qrRT-PCR) in pasteurized retail dairy products and, if detected, to determine whether the virus was viable. From 18 April to 22 April 2024, a total of 297 samples of Grade A pasteurized retail milk products (23 product types) were collected from 17 US states that represented products from 132 processors in 38 states. Viral RNA was detected in 60 samples (20.2%), with qrRT-PCR-based quantity estimates (non-infectious) of up to 5.4log1050% egg infectious doses per mL, with a mean and median of 3.0log10/mL and 2.9log10/mL, respectively. Samples that were positive for type A influenza by qrRT-PCR were confirmed to be clade 2.3.4.4 H5 HPAIV by qrRT-PCR. No infectious virus was detected in any of the qrRT-PCR-positive samples in embryonating chicken eggs. Further studies are needed to monitor the milk supply, but these results provide evidence that the infectious virus did not enter the US pasteurized milk supply before control measures for HPAIV were implemented in dairy cattle.IMPORTANCEHighly pathogenic avian influenza virus (HPAIV) infections in US dairy cattle were first confirmed in March 2024. Because the virus could be detected in raw milk, a study was conducted to determine whether it had entered the retail food supply. Pasteurized dairy products were collected from 17 states in April 2024. Viral RNA was detected in one in five samples, but infectious virus was not detected. This provides a snapshot of HPAIV in milk products early in the event and reinforces that with current safety measures, infectious viruses in milk are unlikely to enter the food supply.

Cerium- and samarium-nitrate interaction and accumulation on human dentin.

OBJECTIVE: To investigate the accumulation of cerium-nitrate and samarium-nitrate on dentin without or with smear-layer and to test their antibacterial activity. DESIGN: 24 dentin-enamel slices were cut from 24 extracted molars. 12 slices underwent smear-layer creation (320 grit, 200 g, 5 s), the other 12 smear-layer removal (20 % EDTA, 300 s). Slices were halved to 48 semilunar-shaped specimens. One specimen per tooth was treated with either Ce(NO3)3 (50 wt% aqueous solution; pH = 1.29; n = 6) or Sm(NO3)3 (50 wt% aqueous solution; pH = 1.88; n = 6). The other specimen served as control (A. demin). After water rinsing, elemental composition (Ce, Sm, Ca, P, O, N, Na, Mg, C) was measured (EDX; EDAX Octane-Elect, APEX v2.5, low-vacuum) in dentin. Atomic percent (At%), Ca/P- and Ca/N-ratios were calculated and analyzed non-parametrically (α = 0.05, error rates method). Additionally, antibacterial activity (2 min exposure) of Ce(NO3)3 and Sm(NO3)3 against Streptococcus mutans, Actinomyces naeslundii, Schaalia odontolytica, and Enterococcus faecalis was determined (colony forming units) after anaerobic incubation at 37 °C for 24 h (control: 0.2 % CHX). RESULTS: At% (median) of Ce and Sm were as follows: Ce(NO3)3 3.4 and 0.9 At%Ce with and without smear-layer, respectively; Sm(NO3)3 2.4 and 1.3 At%Sm with and without smear-layer, respectively. Ce(NO3)3 and Sm(NO3)3-application significantly decreased Ca/P-ratios (1.22 - 1.45; p ≤ 0.02) compared to controls (1.47 - 1.63). With smear-layer, significantly higher Ca/N-ratios (5.1 - 29.3) could be detected across all groups (p ≤ 0.004) compared to specimens without smear-layer (0.37 - 0.48). Ce(NO3)3 and Sm(NO3)3 showed reduction rates of up to ≥ 5 log10 steps for S. mutans, A. naeslundii, and S. odontolytica. CONCLUSIONS: Cerium and samarium nitrate showed accumulation on dentin and certain antibacterial activity and could therefore be identified as potential compounds to treat and prevent dentin and root caries and dentin hypersensitivity.

Lysine Methyltransferase 2D Regulates Immune Response and Metastasis in Head and Neck Cancer.

BACKGROUND/AIM: The most frequently altered epigenetic modifier in head and neck squamous carcinoma (HNSC) is the histone methyltransferase KMT2D. KMT2D catalyzes methylation of histone H3K4 resulting in open chromatin and the activation of target genes. Tumor-associated macrophages (TAMs) promote cancer growth by causing T lymphocyte exhaustion. C-C motif chemokine ligand 2 (CCL2) is a potent TAM chemotactic factor. In HNSC, TAMs have been associated with unfavorable patient outcomes and metastasis. The aim of this study was to determine the role of KMT2D in HNSC using genetically engineered in vivo models. MATERIALS AND METHODS: KMT2D protein expression was correlated with lymph node metastasis in human HNSC using immunohistochemistry. Genetically engineered KMT2D and CCL2 knockout models of HNSC were created in vivo. HNSC was characterized using qRT-PCR, histopathology, and immunohistochemistry/immunofluorescence microscopy. We also analyzed the effects of KMT2D expression on the proliferation and migration of human HNSC lines. The regulation of the CCL2 gene by KMT2D was characterized using chromatin immunoprecipitation-sequencing assay of transposase accessible chromatin-sequencing, and chromatin conformation capture-sequencing. RESULTS: Human HNSC cases with high KMT2D expression exhibited significantly increased lymph node metastasis. Reduced KMT2D expression in our genetically engineered model correlated with reduced lymph node metastasis, longer latency, and slow tumor growth. CCL2 expression was decreased in KMT2D deficient HNSC, which correlated with a reduced TAM gene expression signature. Genomic experiments demonstrated that KMT2D directly targeted the CCL2 gene. A new genetically engineered in vivo model of CCL2-null HNSC was created, recapitulating the KMT2D deficient phenotype and showing a decreased T lymphocyte exhaustion signature. CONCLUSION: KMT2D regulates CCL2-mediated immune response and metastasis in HNSC.

Advancing Genetic Testing in Kidney Diseases: Report From a National Kidney Foundation Working Group.

About 37 million people in the United States have chronic kidney disease, a disease that encompasses diseases of multiple causes. About 10% or more of kidney diseases in adults and about 70% of selected chronic kidney diseases in children are expected to be explained by genetic causes. Despite the advances in genetic testing and an increasing understanding of the genetic bases of certain kidney diseases, genetic testing in nephrology lags behind other medical fields. More understanding of the benefits and logistics of genetic testing is needed to advance the implementation of genetic testing in chronic kidney diseases. Accordingly, the National Kidney Foundation convened a Working Group of experts with diverse expertise in genetics, nephrology, and allied fields to develop recommendations for genetic testing for monogenic disorders and to identify genetic risk factors for oligogenic and polygenic causes of kidney diseases. Algorithms for clinical decision making on genetic testing and a road map for advancing genetic testing in kidney diseases were generated. An important aspect of this initiative was the use of a modified Delphi process to reach group consensus on the recommendations. The recommendations and resources described herein provide support to nephrologists and allied health professionals to advance the use of genetic testing for diagnosis and screening of kidney diseases.

The LTAR Grazing Land Common Experiment at the Central Plains Experimental Range: Collaborative adaptive rangeland management.

Semiarid rangelands throughout the western Great Plains support livestock production and many other ecosystem services. The degree to which adaptive multi-paddock (AMP) grazing management approaches can help achieve desired ecosystem services remains unclear. At the Central Plains Experimental Range in northeastern Colorado, a management-science partnership with a diverse stakeholder group is comparing collaborative adaptive rangeland management (CARM), designed to incorporate AMP principles, to traditional rangeland management (TRM), consisting of season-long grazing during the growing season. Each treatment was implemented on a set of 10, 130-ha pastures paired by soils, topography, and plant communities to evaluate how CARM affects vegetation (composition and production), livestock production (steer weight gain), and wildlife habitat (vegetation structure for grassland birds). For the first 5 years of the experiment, CARM cattle were managed as a single herd using AMP grazing with planned year-long rest in 20% of the pastures. Relative to TRM, CARM enhanced heterogeneity in vegetation structure across the landscape, benefiting two grassland bird species. However, this came at the cost of 12%-16% lower steer weight gains in CARM versus TRM and declining populations of a third bird species of conservation concern in both treatments. Here we discuss how increased understanding of ecological and social processes during the experiment's first 5 years led to changes in the CARM treatment and management objectives during the next 5 years. We also discuss how innovations in remote sensing, environmental sensors, ecosystem modeling, social learning, and economic analyses are being integrated into and supported by the CARM experiment.

Cross-Validation of Lipid Structure Assignment Using Orthogonal Ion Activation Modalities on the Same Mass Spectrometer.

The onset and progression of cancer is associated with changes in the composition of the lipidome. Therefore, better understanding of the molecular mechanisms of these disease states requires detailed structural characterization of the individual lipids within the complex cellular milieu. Recently, changes in the unsaturation profile of membrane lipids have been observed in cancer cells and tissues, but assigning the position(s) of carbon-carbon double bonds in fatty acyl chains carried by membrane phospholipids, including the resolution of lipid regioisomers, has proven analytically challenging. Conventional tandem mass spectrometry approaches based on collision-induced dissociation of ionized glycerophospholipids do not yield spectra that are indicative of the location(s) of carbon-carbon double bonds. Ozone-induced dissociation (OzID) and ultraviolet photodissociation (UVPD) have emerged as alternative ion activation modalities wherein diagnostic product ions can enable de novo assignment of position(s) of unsaturation based on predictable fragmentation behaviors. Here, for the first time, OzID and UVPD (193 nm) mass spectra are acquired on the same mass spectrometer to evaluate the relative performance of the two modalities for lipid identification and to interrogate the respective fragmentation pathways under comparable conditions. Based on investigations of lipid standards, fragmentation rules for each technique are expanded to increase confidence in structural assignments and exclude potential false positives. Parallel application of both methods to unsaturated phosphatidylcholines extracted from isogenic colorectal cancer cell lines provides high confidence in the assignment of multiple double bond isomers in these samples and cross-validates relative changes in isomer abundance.

Hepatitis B Virus in People who Inject Drugs and Men who Have Sex With Men With HIV in India: A Cross-sectional Study.

Background: People with HIV (PWH) who are coinfected with hepatitis B virus (HBV) have a higher risk of mortality compared with PWH alone. Populations such as people who inject drugs (PWID) and men who have sex with men (MSM) are particularly at high risk for HBV acquisition; yet, limited epidemiological data from these populations exist on HBV prevalence from low- and middle-income country settings (LMICs). Methods: We characterized the prevalence and correlates of HBV serological markers in a sample of PWID and MSM with HIV recruited across 15 Indian cities using hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), and hepatitis B surface antibody (anti-HBs). Testing of stored specimens for the presence of these markers was performed on the Abbott ARCHITECT i1000 as per the manufacturer's instructions. Correlates of ever being infected with HBV (reactive for anti-HBc and/or HBsAg) and chronic HBV (reactive for HBsAg) among those ever infected were assessed using univariable and multivariable multilevel logistic regression models accounting for site-level clustering. Results: A total of 2198 (95%) of the 2314 participants recruited for the trial were screened for HBV markers. The median age among the PWID and MSM participants was 30 and 32 years, respectively. The prevalence of ever being infected with HBV was 75.6% vs 46.9% in PWID vs MSM, respectively (P < .01); prevalence of chronic infection was also higher in PWID vs MSM (14.1% vs 9.5%; P < .01). Correlates of ever being infected with HBV among PWID included unstable housing (adjusted odds ratio [aOR], 5.02) and sharing injection paraphernalia (aOR, 2.70), and among MSM, correlates included history of injection drug use (aOR, 4.87) and gender identity. The prevalence of isolated core (anti-HBc in the absence of anti-HBs) was 34.7% vs 29.4% in PWID vs MSM (P < .05). Vaccination serostatus was <10% in both populations. Conclusions: In this large sample of PWID and MSM with HIV, we observed a high prevalence of serology consistent with HBV infection and low vaccination, highlighting the need for routine screening and catch-up vaccination. The high prevalence of isolated anti-HBc reactivity highlights the need to understand the risk of reactivation with this serological pattern.

Methods to Screen the Adhesion of Fish Cells on Plant-, Algal- and Fungal-Derived Biomaterials.

Cellular agriculture, an alternative and innovative approach to sustainable food production, has gained momentum in recent years. However, there is limited research into the production of cultivated seafood. Here, we investigated the ability of fish mackerel cells (Scomber scombrus) to adhere to plant, algal and fungal-based biomaterial scaffolds, aiming to optimize the cultivation of fish cells for use in cellular agriculture. A mackerel cell line was utilized, and metabolic assays and confocal imaging were utilized to track cell adhesion, growth, and differentiation on the different biomaterials. The mackerel cells adhered and grew on gelatin (positive control), zein, and soy proteins, as well as on alginate, chitosan, and cellulose polysaccharides. The highest adhesion and growth were on the zein and chitosan substrates, apart from the gelatin control. These findings provide a blueprint to enhance scaffold selection and design, contributing to the broader field of cellular agriculture through the development of scalable and eco-conscious solutions for meeting the growing global demand for seafood.

A Nationwide Analysis of Complications, Reoperations and Cost of Wide-Awake Flexor Tendon Repairs.

INTRODUCTION: Some papers suggest that wide-awake flexor tendon repair (FTR) may reduce rates of postoperative tendon gapping and rupture due to improved intraoperative testing of the repair. The current study is a nationwide cohort study comparing FTRs performed wide-awake and with traditional anesthesia. METHODS: Patients undergoing zone II FTR between 2010-2022 were identified in PearlDiver. Exclusion criteria were other tendon repairs, concomitant treatment for vascular injury, fracture, dislocation or amputation, inpatient or office surgery, age <18 years and <1 year of follow-up. Patients were stratified by anesthesia technique: traditional anesthesia (general anesthesia, monitored anesthesia care, regional blocks) or wide-awake. Patients were matched based on age, sex, Elixhauser Comorbidity Index (ECI) score, geographical region, insurance coverage, number of tendon repairs and presence of concomitant nerve repair. 30-day wound complications, emergency department visits and readmissions and 1-year reoperations were identified. Total reimbursement for surgery was determined. RESULTS: Each matched cohort included 2,563 patients. Wide-awake patients had fewer 30-day emergency department visits (2.7% vs 4.8%). There were no differences in 30-day wound complications or readmissions. There was no difference in 1-year reoperations for rupture or for stiffness. Multivariable linear regression identified wide-awake surgery to be a significantly associated with lower total reimbursement. CONCLUSIONS: Performing digital FTR using wide-awake techniques can reduce costs, but the hypothesis that wide-awake repairs may reduce rates of tendon rupture was not supported by the current study.