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Adaptive optics (AO) systems correct optical phase aberrations of the incoming light generated by the atmosphere. To do so simultaneous estimators of the atmospheric turbulence parameters are required. For the family of wide-field AO (WFAO) systems, this information must be stratified in altitude. Among these vectorized estimations, wind profiling in altitude is needed for the reduction of temporal errors in AO loops or for the estimation of turbulence coherence time. This paper proposes a turbulence wind profiler called image processing based peak tracking algorithm (ipta). ipta is an image-processing based approach that automatically and reliably estimates wind velocity for several turbulent layers along the line of sight. The estimation of each wind layer is achieved by tracking peaks produced in cross-correlation maps from pairs of wavefront sensors (WFSs) slopes using the technique known as SLODAR (slope detection and ranging). Results for simulated and on-sky WFS data sets demonstrate that ipta outperforms one of the state of the art wind profiler methods [the profiler covariance parametrization of wind velocity (CAW)] in terms of accuracy and speed. Results also show that, in terms of execution time, our method scales better when the number of WFS lenslets is increased. Being an open source and reliable tool, we believe ipta can be a useful wind profiler for the AO community. [ABSTRACT FROM AUTHOR]

Background: Current guidelines recommend resection with primary anastomosis with diverting loop ileostomy over Hartmann's procedure if deemed safe for acute diverticulitis. The primary objective of the current study was to compare the utilization of these strategies and describe nationwide ostomy closure patterns and readmission outcomes within 1 year of discharge. Methods: This was a retrospective, population-based, cohort study of United States Hospitals reporting to the Nationwide Readmissions Database from January 2011 to December 2019. There were 35,774 patients identified undergoing non-elective primary anastomosis with diverting loop ileostomy or Hartmann's procedure for acute diverticulitis. Rates of ostomy closure, unplanned readmissions, and complications were compared. Cox proportional hazards and logistic regression models were used to control for patient and hospital-level confounders as well as severity of disease. Results: Of the 35,774 patients identified, 93.5% underwent Hartmann's procedure. Half (47.2%) were aged 46–65 years, 50.8% female, 41.2% publicly insured, and 91.7% underwent open surgery. Primary anastomosis was associated with higher rates of 1-year ostomy closure (83.6% vs. 53.4%, p < 0.001) and shorter time-to-closure [median 72 days (Interquartile range 49–103) vs. 115 (86–160); p < 0.001]. Primary anastomosis was associated with increased unplanned readmissions [Hazard Ratio = 2.83 (95% Confidence Interval 2.83–3.37); p < 0.001], but fewer complications upon stoma closure [Odds Ratio 0.51 (95% 0.42–0.63); p < 0.001]. There were no differences in complications between primary anastomosis and Hartmann's procedure during index admission [Odds Ratio = 1.13 (95% Confidence Interval 0.96–1.33); p = 0.137]. Conclusion: Patients who undergo primary anastomosis for acute diverticulitis are more likely to undergo ostomy reversal and experience fewer postoperative complications upon stoma reversal. These data support the current national guidelines that recommend primary anastomosis in appropriate cases of acute diverticulitis requiring operative treatment. [ABSTRACT FROM AUTHOR]

Computers became more standard in the early 1980s, and science and technology were influencing artists like the author. He began using a supercomputer and FORTRAN 77 software to define a non-Euclidean geometry model using conformal mapping to create art. A series of twisted and curved space images was manifested, reflective of Albert Einstein's theories of general and special relativity. It was the author's encounter with Edward Teller, "father of the H-bomb," that led the author to artist Francis Bacon. It was a private lesson with the artist that forced the author out of the box and into his own visual world. [ABSTRACT FROM AUTHOR]

A case-control study examined the connection between pyoderma gangrenosum (PG) and mental health conditions in adults. Using the All of Us (AoU) database, researchers identified patients with PG and compared them to controls. The study found that adults with PG had a higher prevalence of new-onset depression and anxiety compared to the controls. Demographic information about the PG cases, such as age, gender, race/ethnicity, and education level, was also provided. The study suggests the need for increased mental health assessments and attention to patient quality of life in PG care, but acknowledges limitations such as low patient numbers and reliance on administrative data. Further research is necessary to fully understand the relationship between PG and mental health. [Extracted from the article]

In a previous work, we introduced, in the context of gravitational wave science, an initial study on an automated domain-decomposition approach for a reduced basis through hp-greedy refinement. The approach constructs local reduced bases of lower dimensionality than global ones, with the same or higher accuracy. These "light" local bases should imply both faster evaluations when predicting new waveforms and faster data analysis, particularly faster statistical inference (the forward and inverse problems, respectively). In this approach, however, we have previously found important dependence on several hyperparameters, which do not appear in a global reduced basis. This naturally leads to the problem of hyperparameter optimization (HPO), which is the subject of this paper. Here, we compare the efficiency of the Bayesian approach against grid and random searches, which are two order of magnitude slower. Then, we tackle the problem of HPO through Bayesian optimization.We find that, for the cases studied here of gravitational waves from the collision of two spinning but non-precessing black holes, for the same accuracy, local hp-greedy reduced bases with HPO have a lower dimensionality of up to 4×, depending on the desired accuracy. This factor should directly translate into a parameter estimation speedup in the context of reduced order quadratures, for instance. Such acceleration might help in the near real-time requirements for electromagnetic counterparts of gravitational waves from compact binary coalescences. The code developed for this project is available open source from public repositories. This paper is an invited contribution to the Special Issue "Recent Advances in Gravity: A Themed Issue in Honor of Prof. Jorge Pullin on his 60th Anniversary". [ABSTRACT FROM AUTHOR]

Fatigue and musculoskeletal pain are also frequent in patients with psoriasis without psoriatic arthritis (PsA). The current study aimed to assess the impact of an intervention program based on aerobic training to reduce fatigue and musculoskeletal pain in patients with psoriasis without PsA. A total of 118 male patients with poriasis volunteered in the current interventional study and were randomly allocated to the experimental (n=59) or control group (n=59). The intervention consisted of a 16-week aerobic training program on a treadmill, three sessions per week, consisting of a warm-up, 35- to 50-minute treadmill exercise (increasing by 5 minutes/4 weeks) at a work intensity of 50 to 65 percent of peak heart rate (increasing by 5%/4 weeks), and cool-down. The Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-Fatigue), Health Assessment Questionnaire-Disability Index (HAQ-DI), and visual analog scale (VAS) were compared pre- and postintervention. Nutritional intake, maximal aerobic power, lipid profile, serum markers of muscle damage, and body composition were also assessed. When compared to baseline, FACIT-Fatigue, HAQ-DI, and VAS scores were significantly improved without increasing markers of muscle damage. Fat mass percentage, lipid profile, and maximal oxygen consumption were also improved. In conclusion, a 16-week aerobic training program at moderate intensity was safe, well tolerated, and effective in patients with psoriasis without PsA. Long-term follow-up studies are required to examine whether these promising results may improve clinical outcomes. [ABSTRACT FROM AUTHOR]

This study examines how tree‐like fins can be used to improve the phase‐change process of Latent Heat Storage (LHS) systems. ANSYS‐Fluent was utilized to predict the temperature distribution and the time‐evolution of the phase‐change process. A Heat Transfer Fluid (HTF) at 353 K was used for the charging, and 293 K for the discharging process in a shell and tube configuration. Results showed that tree‐like fins provide superior thermal performance compared to straight fins (base case) for both charging and discharging. The thermal performance is enhanced when employing short fin lengths relative to their maximum size at each branch (small αn values). This reduces the temperature gradients within the PCM without increasing the volume occupied by the fins within the LHS system. In addition, decreasing αn values increases the heat transfer area between the fins and Phase‐Change Material (PCM). Designs with two bifurcations achieved a notable increase in their heat transfer area, accelerating the phase‐change process compared to the base case. [ABSTRACT FROM AUTHOR]

Objective: Genomic profiling previously classified melanoma into distinct subtypes based on the presence or absence of mutations in driver genes, but metabolic differences between and within these groups have yet to be thoroughly analyzed. Thus, the objective of the present study is to provide the first effort to holistically characterize the metabolic landscape of qualified melanoma genomic subtypes at single-cell resolution. Methods: Expression data for a total of 1145 malignant cells sourced from NRAS(Q61L), BRAF(V600E), and NRAS/BRAF WT melanomas were retrieved from the Broad Single Cell Portal. Metabolic activity was interrogated by pathway scoring and gene set enrichment analysis. Results: A total of 53 metabolic pathways were differentially regulated in at least one melanoma genomic subtype. Some notable findings include: BRAF/NRAS WT cells were enriched for fatty acid biosynthesis and depleted for metabolism of alanine, aspartate, and glutamate; BRAF(V600E) melanoma cells were enriched for beta-alanine metabolism and depleted for phenylalanine metabolism; NRAS(Q61L) melanoma cells were enriched for steroid biosynthesis and depleted for linoleic acid metabolism. Conclusion: Primary limitations include the total quantity of single cells and breadth of available genomic subtypes plus inherent noisiness of the applied methodologies. Nonetheless, these findings nominate novel, testable therapeutic targets. [ABSTRACT FROM AUTHOR]

The Hyperphagia Questionnaire for Clinical Trials (HQ-CT) is an observer-reported outcome measure that has been widely used in interventional studies to assess changes in hyperphagic behaviors in individuals with Prader-Willi syndrome (PWS). However, HQ-CT scores in the wider PWS population and the general population have not been reported. Here we report HQ-CT scores from more than 400 individuals with PWS and 600 typical individuals, aged 5–26. Overall, HQ-CT scores were significantly higher in those with PWS compared to typically developing individuals at all ages evaluated. In addition, while HQ-CT scores in the typically developing population decreased with age, scores increased with age in PWS. To further understand the variability of HQ-CT scores in the PWS population, semi-structured interviews were conducted with caregivers of a small subset of adults with PWS who had unexpectedly low HQ-CT scores. These caregivers reported that strict adherence to a food routine, food security measures and supervised food preparation reduced the frequency and intensity of hyperphagic behaviors measured by HQ-CT. Thus, hyperphagic behaviors are captured by the HQ-CT for most individuals with PWS, but for some individuals residing in settings with highly structured food routines, HQ-CT scores may not fully reflect the extent of PWS-associated hyperphagia. [ABSTRACT FROM AUTHOR]

Deep learning models are seeing increased use as methods to predict mutational effects or allowed mutations in proteins. The models commonly used for these purposes include large language models (LLMs) and 3D Convolutional Neural Networks (CNNs). These two model types have very different architectures and are commonly trained on different representations of proteins. LLMs make use of the transformer architecture and are trained purely on protein sequences whereas 3D CNNs are trained on voxelized representations of local protein structure. While comparable overall prediction accuracies have been reported for both types of models, it is not known to what extent these models make comparable specific predictions and/or generalize protein biochemistry in similar ways. Here, we perform a systematic comparison of two LLMs and two structure-based models (CNNs) and show that the different model types have distinct strengths and weaknesses. The overall prediction accuracies are largely uncorrelated between the sequence- and structure-based models. Overall, the two structure-based models are better at predicting buried aliphatic and hydrophobic residues whereas the two LLMs are better at predicting solvent-exposed polar and charged amino acids. Finally, we find that a combined model that takes the individual model predictions as input can leverage these individual model strengths and results in significantly improved overall prediction accuracy. [ABSTRACT FROM AUTHOR]

With the advent of large collections of adaptive immune receptor recombination reads representing cancer, there is the opportunity to further investigate the adaptive immune response to viruses in the cancer setting. This is a particularly important goal due to longstanding but still not well-resolved questions about viral etiologies in cancer and viral infections as comorbidities. In this report, we assessed the T cell receptor complementarity determining region-3 (CDR3) amino acid (AA) sequences, for blood-sourced TCRs from neuroblastoma (NBL) cases, for exact AA sequence matches to previously identified anti-viral TCR CDR3 AA sequences. Results indicated the presence of anti-viral TCR CDR3 AA sequences in the NBL blood samples highly significantly correlated with worse overall survival. Furthermore, the TCR CDR3 AA sequences demonstrating chemical complementarity to many cytomegalovirus antigens represented cases with a worse outcome, including cases where such CDR3s were obtained from tumor samples. Overall, these results indicate a significant need for, and provide a novel strategy for assessing viral infection complications in NBL patients. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disorder characterized by inflammatory arthritis and periarticular structural damage. Available evidence suggests that RA results from complex interactions between genetic susceptibility (e.g., HLA-DRB1), environmental factors (e.g., smoking), and immune dysregulation. Alongside joint-related symptoms, individuals with RA may also experience a wide array of skin issues, including the development of nodules, neutrophilic dermatoses, vasculitis, and vasculopathy. Treatment strategies for these manifestations vary but routinely involve corticosteroids, disease-modifying anti-rheumatic drugs, and biologics, with individualized approaches guided by disease severity. In this review, we provide comprehensive insights into the skin-related issues associated with RA, outlining their clinical characteristics and histopathological findings. Our aim is to facilitate early diagnosis and personalized treatment to improve the quality of life of affected individuals. [ABSTRACT FROM AUTHOR]

In this study, we use nationwide all-payer ED data to assess the patient and hospital factors that influence inpatient admission rates for HS. Keywords: Hidradenitis suppurativa; Inpatient admission; Emergency department; NEDS; HCUP; Bed management EN Hidradenitis suppurativa Inpatient admission Emergency department NEDS HCUP Bed management 2999 3001 3 11/02/23 20231201 NES 231201 To the Editor, Hidradenitis suppurativa (HS) is a recurring inflammatory disease characterized by inflamed nodules, abscesses, tunneled tracts, and scars typically located in the axilla, inframammary folds, and groin [[1]]. Taken together, these data suggest that interventions targeting these demographics may reduce ED utilization and hospital admissions among HS patients. [Extracted from the article]

HS patients more frequently utilized emergency department (ED) services relative to psoriasis patients in a cohort cost-identification study assessing all-cause utilization outpatient costs (7.4 vs. 4.2%, I P i < 0.0001) [[2]]. Therefore, we aimed to assess patient characteristics and ED charges for HS treatment using nationwide, all-payer ED data. Targeted interventions may reduce ED utilization among HS patients and mitigate financial burden among HS patient subgroups more vulnerable to increased healthcare costs. [Extracted from the article]

We conducted a morphological analysis of the spiral structure in two isolated spiral galaxies: NGC 2756 and NGC 2776. The primary objective of this research is to gain a deeper understanding of how spiral structure is distributed in disk galaxies. To achieve this, we employed the two-dimensional fast Fourier transform method and conducted a comprehensive analysis of the Fourier spectra and radial density functions (RDF) to examine their patterns and characteristics. The results indicate that the main mode of the spiral structure is m = 2. However, using RDFs, we identified that other modes may be relevant in certain regions of the galactic disk, such as m = 3. This result suggests the existence of multiple spiral structures depending on the analyzed region. [ABSTRACT FROM AUTHOR]

This research focused on the study of multiple spiral structures in galaxies undergoing various types of interactions, with a specific emphasis on galaxies NGC 4254 and NGC 5985. Using the two-dimensional Fourier transform, the study provides insights into the complex morphological features of these galaxies. NGC 4254, classified as SA(s)c, reveals prominent m = 1 and m = 2 modes in the Fourier analysis, indicating continuous spiral structures extending from the nucleus to the outer regions. In the case of NGC 5985, classified as SAB(r)b, the dominant Fourier modes are m = 1 and m = 2. The study measured the length of the bar to be 3.9 kpc and a ring with a radius of 10.9 kpc. The presence of discontinuous spiral structures is attributed to numerous bifurcations in the spiral arms. In summary, this research provides valuable insights into the nature of multiple spiral structures in interacting galaxies. The two-dimensional Fourier transform proves to be a valuable tool for uncovering morphological details, offering key insights into the evolutionary histories and environmental influences of NGC 4254 and NGC 5985. [ABSTRACT FROM AUTHOR]

BACKGROUND: Surgical rescue (SR) is the recovery of patients with surgical complications. Patients transferred (TP) for surgical diagnoses to higher-level care or inpatients (IP) admitted to nonsurgical services may develop intra-abdominal infection (IAI) and require emergency surgery (ES). The aims were to characterize the SR population by the site of ES consultation, open abdomen (OA), and risk of mortality. STUDY DESIGN: This was an international, multi-institutional prospective observational study of patients requiring ES for IAI. Laparotomy before the transfer was an exclusion criterion. Patients were divided into groups: clinic/ED (C/ED), IP, or TP. Data collected included demographics, the severity of illness (SOI), procedures, OA, and number of laparotomies. The primary outcome was mortality. Multivariable logistic regression models were constructed. RESULTS: There were 752 study patients (C/ED 63.8% vs TP 23.4% and IP 12.8%), with a mean age of 59 years and 43.6% women. IP had worse SOI scores (Charlson Comorbidity Index, American Society of Anesthesiologists Physical Status Classification System, and Sequential Organ Failure Assessment). The most common procedures were small and large bowel (77.3%). IP and TP had similar rates of OA (IP 52.1% and TP 52.3 %) vs C/ED (37.7%, p < 0.001), and IP had more relaparotomies (3 or 4). The unadjusted mortality rate was highest in IP (n = 24, 25.0%) vs TP (n = 29, 16.5%) and C/ED (n = 68, 14.2%, p = 0.03). Adjusting for age and SOI, only SOI had an impact on the risk of mortality (area under the curve 86%). CONCLUSIONS: IP had the highest unadjusted mortality after ES for IAI and was followed by the TP; SOI drove the risk of mortality. SR must be extended to IP for timely recognition of the IAI. [ABSTRACT FROM AUTHOR]

Warm-mix asphalt (WMA) is a group of technologies focused on reducing the viscosity of the asphalt binder (or binder) to produce asphalt mixtures at a reduced temperature compared with that specified for conventional hot-mix asphalt mixtures. The WMA technologies include two main groups: foaming and additives. The additives can be classified as synthetic-chemical or natural-based. This study aims at assessing the feasibility of optimizing the WMA additives dose by maximizing the adhesion between the asphalt binder and the aggregate at their interface in WMA mixtures. Adhesion is quantified using energy parameters derived from surface-free energy measurements (SFE), including three WMA additives (Carnauba wax, a natural-based warm-mix additive, Sasobit, and Evotherm). Accomplishing this objective required measurements of SFE for four different asphalt binders, and corresponding WMA-modified asphalt binders were performed. The results suggest the possibility of identifying a WMA-additive dose that maximizes adhesion at the binder–aggregate interface in terms of resistance to fracture (i.e., adhesive failure) and moisture damage, and the wettability of the binder. In addition, the results showed that the inclusion of Carnauba wax as a warm-mix additive yielded equivalent adhesion at the binder–aggregate interface compared with the response of the other commercially available WMA additives evaluated (i.e., Sasobit and Evotherm). Additional studies at the mixture level are recommended to validate further the conclusions obtained in this study. [ABSTRACT FROM AUTHOR]

Professor Rutger Rosenberg, a pioneering marine ecologist, passed away on January 6, 2024, at the age of 81. He received his PhD in 1973 and went on to publish over 250 papers and reports, becoming one of the most cited marine biologists. His research focused on the response of benthic communities to organic enrichment, pollution, and low dissolved oxygen. Rosenberg also made significant contributions to the study of hypoxia and developed novel methods for studying marine coastal sediments. He was known for his collaborative approach and mentored numerous students and researchers throughout his career. [Extracted from the article]

Introduction: Cutaneous melanoma remains a leading cancer with sobering post-metastasis mortality rates. To date, the ligand-receptor interactome of melanomas remains weakly studied despite applicability to anti-cancer drug discovery. Here we leverage established crosstalk methodologies to characterize important ligand-receptor pairs in primary and metastatic cutaneous melanoma. Methods: Bulk transcriptomic data, representing 470 cutaneous melanoma samples, was retrieved from the Broad Genome Data Analysis Center Firehose portal. Tumor and stroma compartments were computationally derived as a function of tumor purity estimates. Identification of preferential ligand-receptor interactions was achieved by relative crosstalk scoring of 1380 previously established pairs. Results: Metastatic cutaneous melanoma uniquely enriched PTH2-PTH1R for tumor-to-stroma signaling. The Human R-spondin ligand family was involved in 4 of the 15 top-scoring stroma-to-tumor interactions. Receptor ACVR2B was involved in 3 of the 15 top-scoring tumor-to-tumor interactions. Conclusions: Numerous gene-level differences in ligand-receptor crosstalk between primary and metastatic cutaneous melanomas. Further investigation of notable pairings is warranted. [ABSTRACT FROM AUTHOR]

Malaria is an infectious disease that can cause severe sickness and death if not diagnosed and treated in a timely manner. The current gold standard technique for malaria diagnosis is microscopy, which requires a dedicated laboratory setting and trained personnel and can have a long time to result. These requirements can be alleviated using paper-based diagnostic devices that enable rapid and inexpensive diagnosis at the point of care, which can allow patients to receive treatment before their symptoms progress when used for early detection of diseases. The lateral-flow immunoassay (LFA) is one such device, but currently available LFAs are susceptible to false negative results caused by low parasite density. To improve sensitivity and detection, we utilized the aqueous two-phase system (ATPS) to concentrate and purify the sample, and nanozyme signal enhancement to increase the intensity of the visible signal on the test strip. We were able to achieve a limit of detection (LOD) of 0.01 ng/mL for the malaria biomarker Plasmodium lactate dehydrogenase (pLDH) in human serum using a multi-step assay combining the LFA format with the ATPS and nanozyme signal enhancement. [ABSTRACT FROM AUTHOR]

Purpose: It is unknown whether the trend of rising incisional hernia (IH) repair (IHR) incidence and costs until 2011 currently persists. We aimed to evaluate how the IHR procedure incidence, cost and patient risk-profile have changed over the last decade relative to all abdominal surgeries (AS).Methods: Repeated cross-sectional analysis of 38,512,737 patients undergoing inpatient 4AS including IHR within the 2008-2018 National Inpatient Sample. Yearly incidence (procedures/1,000,000 people [PMP]), hospital costs, surgical and patient characteristics were compared between IHR and AS using generalized linear and multinomial regression.Results: Between 2008-2018, 3.1% of AS were IHR (1,200,568/38,512,737). There was a steeper decrease in the incidence of AS (356.5 PMP/year) compared to IHR procedures (12.0 PMP/year) which resulted in the IHR burden relative to AS (2008-2018: 12,576.3 to 9,113.4 PMP; trend difference P < 0.01). National costs averaged $47.9 and 1.7 billion/year for AS and IHR, respectively. From 2008-2018, procedure costs increased significantly for AS (68.2%) and IHR (74.6%; trends P < 0.01). Open IHR downtrended (42.2%), whereas laparoscopic (511.1%) and robotic (19,301%) uptrended significantly (trends P < 0.01). For both AS and IHR, the proportion of older (65-85y), Black and Hispanic, publicly-insured, and low-income patients, with higher comorbidity burden, undergoing elective procedures at small- and medium-sized hospitals uptrended significantly (all P < 0.01).Conclusion: IH persists as a healthcare burden as demonstrated by the increased proportion of IHR relative to all AS, disproportionate presence of high-risk patients that undergo these procedures, and increased costs. Targeted efforts for IH prevention have the potential of decreasing $17 M/year in costs for every 1% reduction. [ABSTRACT FROM AUTHOR]

Background: National and international guidelines support early cholecystectomy after mild gallstone pancreatitis but a recent nationwide study suggested these recommendations are not universally followed. Our study sought to quantify the national utilization of same hospitalization cholecystectomy versus non-operative management (NOM) and its association with pancreatitis recurrence, readmissions, and costs after mild gallstone pancreatitis (GP). Methods: Adult patients admitted with mild GP were identified from the Nationwide Readmission Database 2010–2015. Primary outcomes included the rate of cholecystectomy during the index admission as well as pancreatitis recurrence and readmission at 30 and 180 days (30d, 180d) comparing NOM to same hospitalization cholecystectomy. Mortality upon readmission, total length of stay (LOS), and total costs (combined index-readmission hospital costs) were also explored. Cox proportional hazards regression and generalized linear models controlled for patient/hospital confounders. Results: Among the 65,067 patients identified, 30% underwent cholecystectomy. The NOM cohort was older (58 vs. 50 years), had more comorbidities (Charlson index > 2, 23.5% vs. 11.5%), fewer female patients (56.7% vs. 67%) and less discharge-to-home (84.9% vs. 94.4%) (all p < 0.001). NOM was associated with increase in recurrence and unplanned readmissions at 30d [Hazard Ratio 3.53 (95% CI 2.92–4.27), 2.41 (2.11–2.74), respectively], and 180d [4.27 (3.65–4.98), 2.78 (2.54–3.04), respectively], as well as increased mortality during 180d readmission 1.88 (1.06–3.35). This approach was also associated with significant increase in LOS [predicted mean difference 2.79 days (95% CI 2.46–3.12)] and total costs [$2507.89 ($1714.4–$3301.4)]. Conclusions: In the USA, most patients presenting with mild GP do not undergo same hospitalization cholecystectomy. This strategy results in higher recurrent pancreatitis, mortality during readmission, and an additional $4.85 M/year in hospital costs nationwide. These data support same hospitalization cholecystectomy as the gold standard for mild GP. [ABSTRACT FROM AUTHOR]

The public health implications of the COVID-19 pandemic reach beyond those of the disease itself. Various centers have anecdotally reported increases in the incidence of dog bite injuries which predominate in pediatric populations. The reasons for this increase are likely multifactorial and include an increase in canine adoptions, remote learning, and psychosocial stressors induced by lockdowns. We hypothesized that there was a significant increase in the proportion of dog bite injuries at our institution and within a nationally representative cohort. We queried our electronic health record and the National Electronic Injury Surveillance System (NEISS) for all records pertaining to dog bites between 2015 and 2020, and the annual incidence was calculated. Poisson regression was then used to estimate whether there was a significant difference in the adjusted risk ratio for each year. The institutional and national cohorts revealed relative increases in the incidence of dog bite injury of 243 and 147.9 per 100,000 over the study period, respectively. Both cohorts observed significant increases of 44% and 25% in the annual incidence relative to 2019, respectively. Poisson regression revealed a significantly elevated adjusted relative risk in the institutional cohort for 2020 (2.664, CI: 2.076-3.419, P < 0.001). The national cohort also revealed an increase (1.129, CI: 1.091-1.169, P < 0.001). A nationwide increase in the incidence of dog bite injuries among children was observed during COVID-19 in 2020. These findings suggest that dog bites remain a public health problem that must be addressed by public health agencies. [ABSTRACT FROM AUTHOR]

Background: Despite the fact that only modest adaptive immune system related approaches to treating Alzheimer's disease (AD) are available, an immunogenomics approach to the study of AD has not yet substantially advanced.Objective: Thus, we sought to better understand adaptive immune receptor chemical features in the AD setting.Methods: We characterized T-cell receptor alpha (TRA) complementarity determining region-3 (CDR3) physicochemical features and identified TRA CDR3 homology groups, represented by TRA recombination reads extracted from 2,665 AD-related, blood- and brain-derived exome files.Results: We found that a higher isoelectric value for the brain TRA CDR3s was associated with a higher (clinically worse) Braak stage and that a number of TRA CDR3 chemical homology groups, in particular representing bloodborne TRA CDR3s, were associated with higher or lower Braak stages. Lastly, greater chemical complementarity of both blood- and brain-derived TRA CDR3s and tau, based on a recently described CDR3-candidate antigen chemical complementarity scoring process (https://adaptivematch.com), was associated with higher Braak stages.Conclusion: Overall, the data reported here raise the questions of (a) whether progression of AD is facilitated by the adaptive immune response to tau; and (b) whether assessment of such an anti-tau immune response could potentially serve as a basis for adaptive immune receptor related, AD risk stratification? [ABSTRACT FROM AUTHOR]

Background: Volume expansion and vasopressors for the treatment of shock is an intensive process that requires frequent assessments and adjustments. Strict blood pressure goals in multiple physiologic states of shock (traumatic brain injury, sepsis, and hemorrhagic) have been associated with improved outcomes. The availability of continuous physiologic data is amenable to closed-loop automated critical care to improve goal-directed resuscitation. Methods: Five adult swine were anesthetized and subjected to a controlled 30% estimated total blood volume hemorrhage followed by 30 min of complete supra-celiac aortic occlusion and then autotransfusion back to euvolemia with removal of aortic balloon. The animals underwent closed-loop critical care for 255 min after removal of the endovascular aortic balloon. The closed-loop critical care algorithm used proximal aortic pressure and central venous pressure as physiologic input data. The algorithm had the option to provide programmatic control of pumps for titration of vasopressors and weight-based crystalloid boluses (5 ml/kg) to maintain a mean arterial pressure between 60 and 70 mmHg. Results: During the 255 min of critical care the animals experienced hypotension (< 60 mmHg) 15.3% (interquartile range: 8.6–16.9%), hypertension (> 70 mmHg) 7.7% (interquartile range: 6.7–9.4%), and normotension (60–70 mmHg) 76.9% (interquartile range: 76.5–81.2%) of the time. Excluding the first 60 min of the critical care phase the animals experienced hypotension 1.0% (interquartile range: 0.5–6.7%) of the time. Median intervention rate was 8.47 interventions per hour (interquartile range: 7.8–9.2 interventions per hour). The proportion of interventions was 61.5% (interquartile range: 61.1–66.7%) weight-based crystalloid boluses and 38.5% (interquartile range: 33.3–38.9%) titration of vasopressors. Conclusion: This autonomous critical care platform uses critical care adjuncts in an ischemia–reperfusion injury model, utilizing goal-directed closed-loop critical care algorithm and device actuation. This description highlights the potential for this approach to deliver nuanced critical care in the ICU environment, thereby optimizing resuscitative efforts and expanding capabilities through cognitive offloading. Future efforts will focus on optimizing this platform through comparative studies of inputs, therapies, and comparison to manual critical care. [ABSTRACT FROM AUTHOR]

Background: Volume expansion and vasopressors for the treatment of shock is an intensive process that requires frequent assessments and adjustments. Strict blood pressure goals in multiple physiologic states of shock (traumatic brain injury, sepsis, and hemorrhagic) have been associated with improved outcomes. The availability of continuous physiologic data is amenable to closed-loop automated critical care to improve goal-directed resuscitation. Methods: Five adult swine were anesthetized and subjected to a controlled 30% estimated total blood volume hemorrhage followed by 30 min of complete supra-celiac aortic occlusion and then autotransfusion back to euvolemia with removal of aortic balloon. The animals underwent closed-loop critical care for 255 min after removal of the endovascular aortic balloon. The closed-loop critical care algorithm used proximal aortic pressure and central venous pressure as physiologic input data. The algorithm had the option to provide programmatic control of pumps for titration of vasopressors and weight-based crystalloid boluses (5 ml/kg) to maintain a mean arterial pressure between 60 and 70 mmHg. Results: During the 255 min of critical care the animals experienced hypotension (< 60 mmHg) 15.3% (interquartile range: 8.6–16.9%), hypertension (> 70 mmHg) 7.7% (interquartile range: 6.7–9.4%), and normotension (60–70 mmHg) 76.9% (interquartile range: 76.5–81.2%) of the time. Excluding the first 60 min of the critical care phase the animals experienced hypotension 1.0% (interquartile range: 0.5–6.7%) of the time. Median intervention rate was 8.47 interventions per hour (interquartile range: 7.8–9.2 interventions per hour). The proportion of interventions was 61.5% (interquartile range: 61.1–66.7%) weight-based crystalloid boluses and 38.5% (interquartile range: 33.3–38.9%) titration of vasopressors. Conclusion: This autonomous critical care platform uses critical care adjuncts in an ischemia–reperfusion injury model, utilizing goal-directed closed-loop critical care algorithm and device actuation. This description highlights the potential for this approach to deliver nuanced critical care in the ICU environment, thereby optimizing resuscitative efforts and expanding capabilities through cognitive offloading. Future efforts will focus on optimizing this platform through comparative studies of inputs, therapies, and comparison to manual critical care. [ABSTRACT FROM AUTHOR]

Base editing can be applied to characterize single nucleotide variants of unknown function, yet defining effective combinations of single guide RNAs (sgRNAs) and base editors remains challenging. Here, we describe modular base-editing-activity 'sensors' that link sgRNAs and cognate target sites in cis and use them to systematically measure the editing efficiency and precision of thousands of sgRNAs paired with functionally distinct base editors. By quantifying sensor editing across >200,000 editor-sgRNA combinations, we provide a comprehensive resource of sgRNAs for introducing and interrogating cancer-associated single nucleotide variants in multiple model systems. We demonstrate that sensor-validated tools streamline production of in vivo cancer models and that integrating sensor modules in pooled sgRNA libraries can aid interpretation of high-throughput base editing screens. Using this approach, we identify several previously uncharacterized mutant TP53 alleles as drivers of cancer cell proliferation and in vivo tumor development. We anticipate that the framework described here will facilitate the functional interrogation of cancer variants in cell and animal models. Improved base editing libraries enable high-throughput functional analysis of single-nucleotide variants in cancer. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has resulted in an unprecedented global demand for in vitro diagnostic reagents. Supply shortages and hoarding have impacted testing capacity which has led to inefficient COVID-19 case identification and transmission control, predominantly in developing countries. Traditionally, RNA extraction is a prerequisite for conducting SARS-CoV-2 nucleic acid amplification tests (NAAT); however, simplified methods of sample processing have been successful at bypassing typical nucleic acid extraction steps, enabling extraction-free SARS-CoV-2 NAAT workflows. These methods involve chemical and physical approaches that are inexpensive and easily accessible alternatives to overcome extraction kit supply shortages, while offering acceptable test performance. Here we provide an overview of three main sample preparation strategies that have been shown to facilitate extraction-free SARS-CoV-2 NAATs. [ABSTRACT FROM AUTHOR]

Background: Data on duration of antibiotics in patients managed with an open abdomen (OA) due to intra-abdominal infection (IAI) are scarce. We hypothesized that patients with IAI managed with OA rather than closed abdomen (CA) would have higher rates of secondary infections (SIs) independent of the duration of the antibiotic treatment.Methods: This was an observational, prospective, multicenter, international study of patients with IAI requiring laparotomy for source control. Demographic and antibiotic duration values were collected. Primary outcomes were SI (surgical site, bloodstream, pneumonia, urinary tract) and mortality. Statistical analysis included ANOVA, chi-square/Fisher's exact test, and logistic regression.Results: Twenty-one centers contributed 752 patients. The average age was 59.6 years, 43.6% were women, and 43.9% were managed with OA. Overall mortality was 16.1%, with higher rates among OA patients (31.6% vs 4.4%, p < 0.001). OA patients had higher Sequential Organ Failure Assessment (4.7 vs 1.8, p < 0.001), American Society of Anesthesiologists Physical Status (3.6 vs 2.7, p < 0.001), and APACHE II scores (16.1 vs 9.4, p < 0.001). The mean duration of antibiotics was 6.5 days (8.0 OA vs 5.4 CA, p < 0.001). A total of 179 (23.8%) patients developed SI (33.1% OA vs 16.8% CA, p < 0.001). Longer antibiotic duration was associated with increased rates of SI: 1 to 2 days, 15.8%; 3 to 5 days, 20.4%; 6 to 14 days, 26.6%; and more than 14 days, 46.8% (p < 0.001).Conclusions: Patients with IAI managed with OA had higher rates of SI and increased mortality compared with CA. A prolonged duration of antibiotics was associated with increased rates of SI. Increased antibiotic duration is not associated with improved outcomes in patients with IAI and OA. [ABSTRACT FROM AUTHOR]

Although assimilation theories acknowledge that the host society adopts aspects of migrant culture, empirical work continues to focus on the assimilation trajectories of immigrants. This study represents the first effort to investigate, on a national level, whether Asians and Hispanics exert a cultural influence on local populations. We assess this possibility by using ethnic restaurants – both national chain and local establishments – as a test case. County-level data is pooled from the decennial U.S. Census, the American Community Survey, the Economic Research Service, the Voting and Elections Collection from CQ Press, and Reference U.S.A. to investigate the association of interest; Nielsen Marketing data is used to further supplement analyses. Results indicate that Asians and Hispanics may indeed influence local community expressions of culture – both in terms of restaurant availability and the extent to which those outside of the co-ethnic community engage in restaurant ownership. Moreover, we find compelling evidence that assimilation may be stronger in locations with advantaged majority populations. In combination, this manuscript offers innovative theoretical perspectives as well as preliminary evidence to suggest assimilation is indeed a multidirectional process. [ABSTRACT FROM AUTHOR]

Introduction: Heterosexual couples are at high risk for HIV acquisition in sub-Saharan Africa, and HIV self-testing (HST) is an additional approach to expand access to HIV testing services. However, it is not well known how gender equality is associated with HST. Methods: We used intervention-arm data from a cluster-randomised controlled HST intervention trial (N = 1 618) conducted in Uganda to determine the association between attitudes towards intimate partner violence (IPV), decision-making power and male partner's uptake of HST among heterosexual couples expecting a child in south-central Uganda. The original study question was to assess the impact of providing pregnant women with HST kits to improve male partner's HIV testing rates. For this analysis, the primary exposures were gender equality (measured by male partner's and female partner's attitudes towards IPV and the female partner's household decision-making power), and the primary outcome was the male partner's uptake of HST. Multivariate logistic regression was used for analysis. Results: We found that male partner HST uptake did not vary depending on male partner's attitudes towards IPV or decision-making power; however, male partner HST uptake did depend on the female partner's attitude towards IPV, with 1.76 times more testing (95% CI 1.06–2.92) in couples where the woman had "medium" versus "high" acceptance of IPV, and 1.82 times more testing (95% CI 1.08–3.08) in couples where the woman had "low" versus "high" acceptance of IPV. Conclusions: This study shows the importance of appropriate negative attitudes by women to IPV in increasing male partner's HST uptake to integrate HST into national health care policies. [ABSTRACT FROM AUTHOR]

One fundamental problem of protein biochemistry is to predict protein structure from amino acid sequence. The inverse problem, predicting either entire sequences or individual mutations that are consistent with a given protein structure, has received much less attention even though it has important applications in both protein engineering and evolutionary biology. Here, we ask whether 3D convolutional neural networks (3D CNNs) can learn the local fitness landscape of protein structure to reliably predict either the wild-type amino acid or the consensus in a multiple sequence alignment from the local structural context surrounding site of interest. We find that the network can predict wild type with good accuracy, and that network confidence is a reliable measure of whether a given prediction is likely going to be correct or not. Predictions of consensus are less accurate and are primarily driven by whether or not the consensus matches the wild type. Our work suggests that high-confidence mis-predictions of the wild type may identify sites that are primed for mutation and likely targets for protein engineering. [ABSTRACT FROM AUTHOR]

Healthcare researchers are showing renewed interest in the utilization of N-of-1 clinical trials for the individualization of pharmacological treatments. Here, we propose a frequentist approach to conducting treatment individualization in N-of-1 trials that we call "partial empirical Bayes." We infer the most beneficial treatment for the patient from combining the information provided by a previously conducted population crossover trial with individual patient data. We propose a method for estimating an optimal number of treatment cycles and investigate the statistical conditions under which N-of-1 trials are more beneficial than traditional clinical approaches. We represent the patient population with a random-coefficients linear model and calculate estimators of posttreatment individual disease severities. We show the estimators' consistency under the most common N-of-1 designs and examine their prediction errors and performance with small numbers of patient's responses. We demonstrate by simulating new patients that our approach is equivalent or superior to both the common clinical practice of recommending the on-average best treatment for all patients and the common individualization method that simply compares average responses to the tested treatments. We conclude that some situations exist in which individualization with N-of-1 trials is highly beneficial while other situations exist in which individualization may be unfruitful. [ABSTRACT FROM AUTHOR]

Consensus on the safety and efficacy of various types of mesh in reconstructing the abdomen has yet to be reached. Hybrid mesh products have been designed to address the need for a cost-effective mesh leveraging the tensile strength of a synthetic mesh while minimizing the prosthetic footprint within the abdominal wall through resorbable materials. In this study we evaluate early clinical outcomes and health related quality of life (HR-QOL) of a new Hybrid mesh, SynecorTM, for Ventral Hernia Repair (VHR). Adult (>18 y old) patients undergoing VHR with SynecorTM mesh by a single surgeon between 2017-2019 with ≥1-y follow-up were identified. We analyzed a composite of postoperative outcomes as well as the incidence of hernia recurrence, readmissions, mortality, and HR-QOL. Thirty-five patients were included in our analysis with a median follow up of 2.1 y. The median age and BMI were 54.1 y and 33.2 kg/m2, respectively. The rate of surgical site occurrences was 37.1%, with only one patient (2.9%) requiring surgical intervention. No patients developed a hernia recurrence. Overall HR-QOL improved significantly (preoperative mean 2.5 [SD 0.7] versus postoperative 3.4 [0.4]; P < 0.01), particularly in regards to pain, functional status, self-esteem and body image (all P < 0.05). Abdominal reinforcement with SynecorTM mesh at the time of VHR results in promising early recurrence rates, an acceptable safety risk profile, and an improvement in overall HR-QOL. [ABSTRACT FROM AUTHOR]

Introduction: Patients infected with SARS-Cov-2, the causative virus behind the coronavirus disease-19 (COVID-19) pandemic, have been increasing rapidly in New York City. New York City has the highest incidence in the United States and fully 45% of all deaths from COVID-19. Our medical center is located within a high-density region of cases in south Brooklyn and, in fact, three of our neighborhood zip codes are in the top seven in New York in incidence. As a result, our center has experienced a dramatic increase in hospitalizations, particularly respiratory distress secondary to COVID-19, which rapidly exceeded the capacity of our internal medicine service. This necessitated the formation of new COVID-19 units throughout the hospital, replacing all former service lines. These units employed management teams composed of residents from many medical and surgical disciplines, including general surgery residents. Methods: Our general surgery residency program established a surgical COVID-19 (SCOVID) management team. Initially, 4 surgical residents (2 senior and 2 junior), 1 attending surgeon, and 1 attending internal medicine physician were allocated to the initial SCOVID team. On day 3 of implementation, to achieve more rapid competence in the complex management of these patients, a senior medicine resident with direct experience in the care of COVID-19 patients was added in an advisory capacity. Results: The addition of an experienced senior medical resident and attending allowed for the quick adoption of uniform management protocols by surgical residents and attendings. Discussion: We describe a protocol for the establishment of COVID-19 management teams staffed with general surgical residents, as well as a strategy for the achievement of rapid increases in competency. The addition of a senior internal medicine resident and attending to our SCOVID team allowed for rapid achievement of competency in the care of COVID-19 patients in our large institution at the epicenter of the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Introduction E-cigarettes and heated tobacco products (HTPs) may serve as potential options for harm reduction for smokers if they possess reward profiles similar to cigarettes. Little is known about the abuse liability of HTPs and e-cigarettes versus cigarettes in racial/ethnic minority smokers. Aims and Methods Twenty-two nicotine-deprived people who smoke (black [ n  = 12] and white [ n  = 10]) completed three visits that included a standardized 10-puff bout followed by a 50-minute ad libitum use assessment with their usual brand cigarette (UBC), an e-cigarette, and HTP. Visits were completed in a randomized crossover design and were separated by a minimum 48-hour washout period. Assessments included plasma nicotine, Cmax, and reductions in craving and withdrawal. Results UBC delivered significantly greater levels of nicotine compared to the e-cigarette (p  < .001) and HTP (p  < .01) during both the standardized and ad libitum sessions. HTP delivered more nicotine than the e-cigarette during the standardized puffing session (p  = .047) but not the ad libitum session. Only craving during the standardized puffing session and not the ad libitum session showed significant differences across products (p  < .001) such that UBC resulted in the greatest reduction followed by HTP and e-cigarette. Conclusions Despite greater nicotine delivery from the UBC compared to e-cigarette and HTP, participants reported reductions in craving and withdrawal across products, particularly following ad libitum use. Implications Use of participant's UBCs (UBC) resulted in greater nicotine delivery compared to both the e-cigarette and HTP. Despite this relative difference in nicotine delivery, participants reported reductions in craving and withdrawal across products, particularly following ad libitum use. These findings suggest that in this sample of black and white people who smoke, HTPs and e-cigarettes provided significant relief from negative symptoms that maintain smoking. [ABSTRACT FROM AUTHOR]

This paper explores the effect of the amplitude ratio of the higher to the fundamental eigenmode in bimodal atomic force microscopy (AFM) on the phase contrast and the dissipated power contrast of the higher eigenmode. We explore the optimization of the amplitude ratio in order to maximize the type of contrast that is most relevant to the particular study. Specifically, we show that the trends in the contrast range behave differently for different quantities, especially the dissipated power and the phase, with the former being more meaningful than the latter (a similar analysis can be carried out using the virial, for which we also provide a brief example). Our work is based on numerical simulations using two different conservative-dissipative tip-sample models, including the standard linear solid and the combination of a dissipation coefficient with a conservative model, as well as experimental images of thin film Nafion ® proton exchange polymers. We focus on the original bimodal AFM method, where the higher eigenmode is driven with constant amplitude and frequency (i.e., in "open loop"). [ABSTRACT FROM AUTHOR]

Within the framework of a derivable construction of QED, a formulation of nonlinear axion-electrodynamics is investigated. This approach is intended to predict possible strong-QED processes with a discussion of the role of axion-like particles that might be significant in nonlinear electrodynamics (NLED). We introduce a nonlinear model of axion-electrodynamics with remaining questions to be further explored. [ABSTRACT FROM AUTHOR]

Child maltreatment (CM) is a serious and prevalent public health problem in the United States (U.S.) yet programming to combat the issue often overlooks high school aged youth (those aged 14–17). In 2017, over 90,000 youth in the U.S. experienced CM during their high school years (U.S. Department of Health and Human Services 2019). This manuscript will highlight the importance of prevention programs for youth affected by child maltreatment and report the findings of a pilot study that examined the effectiveness of the Childhelp Speak Up Be Safe Prevention Education Curriculum among high school students. The purpose of the pilot study was to determine if the revised and expanded curriculum for grades 9–12 was feasible and to examine the validity of the new survey items, including the RESIST strategy questions. The pilot study utilized a two-phase non-probability convenience sample to evaluate high school student gains in knowledge of safety related resistance strategies. High school students (N = 269) attending one urban charter public high school (grades 9–12) in the Southwest who completed pre- and post-survey RESIST strategy items participated in the pilot. The results indicated that students receiving the Childhelp Speak Up Be Safe Prevention Education Curriculum increased their identification and knowledge of safety related resistance strategies. [ABSTRACT FROM AUTHOR]

Purpose: Poor health literacy and awareness are thought to be some of the major contributors to existing racial/ethnic disparities in access to breast reconstruction after mastectomy. This study aimed to determine whether physician led, community-based educational symposium improves understanding of breast cancer care and breast reconstruction in underserved populations.Methods: Annual educational symposiums were held between 2017 and 2019 in underserved communities in the greater Philadelphia area. The symposium consisted of a series of short lectures on breast health, cancer screening, surgical management and reconstruction, patient testimonials, a Q&A panel, and an exhibitor fair. Attendees were given pre- and post-symposium surveys that evaluated knowledge of breast cancer care and reconstruction on a 0-100 scale based on percentage of correct answers.Results: Of 169 individuals, 92%, 91%, and 83% completed pre-symposium, post-symposium, and both surveys, respectively. Median age was 60 years, and 92% were Black. Knowledge/understanding survey scores significantly improved after the symposium (50 vs. 87, p < 0.01). Of all respondents, 92% found the symposium to be useful, 89% were introduced to resources that they were not previously aware of, 90% would recommend the symposium to others, and 91% would pass along the information they learned.Conclusion: This study presents an effective and reproducible strategy to increase community awareness and understanding of general breast cancer concepts and breast reconstruction options. Through community outreach and education, physicians can help underserved populations have a better understanding of their potential options for breast reconstruction and ultimately reduce this well documented but inadequately addressed disparity in cancer care. [ABSTRACT FROM AUTHOR]

Museums usually exhibit thousands of artworks, and nowadays, they often have their collections online for visitors. In these collections, the curators are responsible for organizing the artworks seeking a delicate balance between emotion and reason. Given an initial artwork, however, a visitor is likely to select and admire a set of related artworks that match her interests. This setting can be seen as a recommendation problem in the art domain. Although image recommendation systems have been previously developed, considering the artwork nature is a fundamental aspect when designing a recommender system in this domain. Thus, we propose a hybrid recommendation approach that combines deep autoencoders with a social influence graph in order to capture the visual aspects and context of artworks (represented by images). These mechanisms inform the generation of rankings of related artworks. In this context, we report on a case-study with a group of art experts who assessed the rankings of artworks recommended by our approach. Although preliminary, the results showed a better precision than traditional strategies based solely on image features or metadata. Furthermore, the recommendations exhibited diversity properties, avoiding typical over-specialization problems of content-based techniques. • We propose an artwork recommendation approach that combines deep autoencoders with a social influence graph. • Visual-content features and context features are jointly used to improve the recommendation. • The performance of the proposed approach is evaluated with a group of art experts and compared against a content-based approach. [ABSTRACT FROM AUTHOR]

Several psychiatric disorders are linked with an increased risk of developing type 2 diabetes (T2D), but the mediating mechanisms are unclear. We aimed to investigate health behaviors, obesity, psychotropic medication use, and comorbidity as potential mediating mechanisms explaining these associations. We combined data from a large population-based survey with register-based data and followed a sample of 250,013 Danes (≥16 years) for up to 8.9 years. We conducted mediation analyses investigating 10 potential mediators of the associations between psychiatric disorders and incident T2D. Individuals with a substance use disorder, schizophrenia, mood disorder, neurotic disorder, eating disorder, or a personality disorder had a significantly higher risk of developing T2D. Organic disorders, intellectual disabilities, developmental and behavioral disorders were not associated with T2D-risk. For all psychiatric disorders significantly associated with T2D, the use of antidepressant medication had the largest proportional mediating effect on the association (13–32 %). Use of antidepressant medication had the largest contribution to the associations between psychiatric disorders and incident T2D. Future epidemiological studies and prevention studies should focus on optimizing the use of antidepressant medication with minimal side effects, and the promotion of health behaviors in individuals with a psychiatric disorder to prevent T2D. • For most of the investigated psychiatric disorders, we found an increased risk of incident T2D. • The use of antidepressant medication had the largest proportional mediating effect (13-32%). • Future studies should focus on optimizing the use of antidepressant medication and the promotion of health behaviors. [ABSTRACT FROM AUTHOR]

The nuclear protein CCCTC-binding factor (CTCF) has diverse roles in chromatin architecture and gene regulation. Functionally, CTCF associates with thousands of genomic sites and interacts with proteins, such as cohesin, or non-coding RNAs to facilitate specific transcriptional programming. In this study, we examined CTCF during the cellular stress response in human primary cells using immune-blotting, quantitative real time-PCR, chromatin immunoprecipitation-sequence (ChIP-seq) analysis, mass spectrometry, RNA immunoprecipitation-sequence analysis (RIP-seq), and Airyscan confocal microscopy. Unexpectedly, we found that CTCF is exquisitely sensitive to diverse forms of stress in normal patient-derived human mammary epithelial cells (HMECs). In HMECs, a subset of CTCF protein forms complexes that localize to Serine/arginine-rich splicing factor (SC-35)-containing nuclear speckles. Upon stress, this species of CTCF protein is rapidly downregulated by changes in protein stability, resulting in loss of CTCF from SC-35 nuclear speckles and changes in CTCF-RNA interactions. Our ChIP-seq analysis indicated that CTCF binding to genomic DNA is largely unchanged. Restoration of the stress-sensitive pool of CTCF protein abundance and re-localization to nuclear speckles can be achieved by inhibition of proteasome-mediated degradation. Surprisingly, we observed the same characteristics of the stress response during neuronal differentiation of human pluripotent stem cells (hPSCs). CTCF forms stress-sensitive complexes that localize to SC-35 nuclear speckles during a specific stage of neuronal commitment/development but not in differentiated neurons. We speculate that these particular CTCF complexes serve a role in RNA processing that may be intimately linked with specific genes in the vicinity of nuclear speckles, potentially to maintain cells in a certain differentiation state, that is dynamically regulated by environmental signals. The stress-regulated activity of CTCF is uncoupled in persistently stressed, epigenetically re-programmed "variant" HMECs and certain cancer cell lines. These results reveal new insights into CTCF function in cell differentiation and the stress-response with implications for oxidative damage-induced cancer initiation and neuro-degenerative diseases. Author summary: Our tissues are subject to chronic physiological and environmental damage, yet little is known about how healthy human cells normally respond to stress. We examined the effect of damage on cells obtained from breast tissue of disease-free women. Unexpectedly, we identified a well-known protein regulator of chromosomal function, CTCF, as a robust target of stress signals. In normal mammary cells, a pool of CTCF is localized to large "depots" within the nucleus that regulate RNA processing. Upon cellular damage, CTCF rapidly disappears from nuclear "depots" by stress-inducible protein degradation while genome occupancy by CTCF is relatively unaffected. We observe the same phenomenon in neuronal progenitors differentiated from human pluripotent stem cells. We propose that in specific cell types, stress-sensitive forms of CTCF exist that have a unique function in RNA metabolism potentially by fine-tuning gene expression near nuclear speckles, which may maintain cells in a progenitor or adaptive state. Upon stress, this particular CTCF function is rapidly disabled, which may change the identity of cells most vulnerable to disease in order to safeguard them from becoming dysfunctional. Persistently stressed cells have lost this CTCF function, which may facilitate the genesis of damage-induced cancer initiation and neuro-degeneration. [ABSTRACT FROM AUTHOR]

Background: Early cholecystectomy (E-CCY; 8 weeks or less) after percutaneous cholecystostomy tube (PCT) placement has been associated with increased postoperative complications, but this finding has not been validated at a national level and PCT-related complications and interventions (PCT-RCIs) were not evaluated.Study Design: Adults with PCT for acute cholecystitis subsequently undergoing CCY were identified within the Nationwide Readmission Database (2010-2015) and our institution (2017-2019). Adjusted relative risks (aRRs) of postoperative complications were estimated using Poisson regression comparing E-CCY with delayed cholecystectomy (D-CCY; more than 8 weeks) within the nationwide cohort. Institutional PCT-RCIs, operative data, and postoperative outcomes were compared between E-CCY and D-CCY using chi-square and Kruskal-Wallis tests.Results: Of 6,145 patients from the Nationwide Readmission Database, 32.9% were D-CCY. Risk-adjusted analysis identified no differences between E-CCY and D-CCY in complications (aRR 0.98; 95% CI, 0.89 to 1.07), mortality (aRR 0.88; 95% CI, 0.43 to 1.81), or 30-day readmissions (aRR 1.04; 95% CI, 0.85 to 1.27). Risk-adjusted analyses assessing the association of time to interval cholecystectomy (IC) with morbidity indicated an increased risk of surgical complications in the first month after PCT placement (aRR 1.17; 95% CI, 1.08 to 1.33). In the institutional cohort (E-CCY, n = 23; D-CCY, n = 45), there were no statistically significant differences found in estimated blood loss, length of stay, and postoperative complications. There were increased PCT-RCIs in the D-CCY group (26.9% E-CCY vs 69% D-CCY; p < 0.01) based on our unadjusted analysis.Conclusions: Increased operative complications when IC is performed within 1 month of PCT placement and increased PCT-RCIs when IC is performed 8 weeks after PCT placement suggest that the most favorable timing for IC is between 4 and 8 weeks after PCT placement. [ABSTRACT FROM AUTHOR]

Most data on health care utilization after incisional hernia (IH) repair are limited to 30-days and are not nationally representative. We sought to describe nationwide 1-year readmission burden after IH repair (IHR). Patients undergoing elective IHR discharged alive were identified using the 2010-2014 Nationwide Readmission Database. Transfers and incomplete follow-up were excluded. Descriptive statistics were used to describe rates of 1-year readmission, IH recurrence, and bowel obstruction. Cox regression allowed identification of factors associated with 1-year readmissions. Generalized linear models were used to estimate predicted mean difference in cumulative costs/year, which allowed estimation of IHR readmission costs/year nationwide. Of 15,935 identified patients, 19.35% were readmitted within 1 y. Patients who were readmitted differed by insurance, Charlson index, illness severity, smoking status, disposition, and surgical approach compared with those who were not (P < 0.05). Of readmitted patients, 39.3% returned within 30 d; 50.9% and 25.6% were due to any and infectious complications, respectively; 25.6% presented to a different hospital; 35.4% required reoperation; 5.4% experienced bowel obstruction; and 5% had IHR revision. Factors associated with readmissions included Medicare (hazard ratio [HR] 1.46 [95% confidence interval 1.19-1.8]; P < 0.01) or Medicaid (HR 1.42 [1.12-1.8], P < 0.01); chronic pulmonary disease (1.38 [1.17-1.64], P < 0.01), and anemia (1.36, [1.05-1.75], P = 0.02). Readmitted patients had higher 1-year cumulative costs (predicted mean difference $12,190 [95% CI: 10,941-13,438]; P < 0.01). Nationwide cost related to readmissions totaled $90,196,248/y. One-year readmissions after IHR are prevalent and most commonly due to postoperative complications, especially infections. One-third of readmitted patients require a subsequent operation, and 5% experience IH recurrence, intensifying the burden to patients and on the health care system. [ABSTRACT FROM AUTHOR]