Search

The retinal pigment epithelium (RPE) is vital for the healthy function of the retina. Cellular level changes in the RPE are not visualized with current clinical techniques due to a lack of spatial resolution. Fluorescence adaptive optics scanning light ophthalmoscopy (AOSLO) can image RPE cells by utilizing their intrinsic autofluorescence (AF). The RPE AF has been imaged with only a few discrete excitation and emission bands and the multi-spectral AF has not been interrogated systematically at the level of single cells. In this study, we imaged 16 healthy eyes (ages 20-75) with AOSLO to investigate the multi-spectral AF as a function of age and wavelength with excitation from 650 - 805 nm. Quantitative analysis showed that 720 nm light produced images with the highest SNR (65.0 dB). Spatial AF variability showed a trend to increase with aging, suggesting increased heterogeneity in RPE AF with age. Spatial variability in the multi-spectral fluorescence of RPE cells with age may be a consequence of normal age-related loss of RPE cells. Multi-spectral fluorescence AOSLO provides new insight into aging related changes to RPE cells and may be a useful tool for studying diseases that affect the RPE, such as age-related macular degeneration (AMD). [ABSTRACT FROM AUTHOR]

Purpose: Mohs micrographic surgery (MMS) is a low-risk penile cancer management option. However, contemporary patients' short-term oncologic control and preoperative characteristics predicting reconstruction needs are undefined. This study assesses MMS's oncologic efficacy for low-risk penile cancer and identifies baseline predictors of post-resection reconstruction referral. Methods: We retrospectively reviewed 73 adult males with 78 penile cutaneous malignancies treated with MMS from 2005 to 2019. Patients underwent MMS with or without surgical reconstruction. Demographic information, MMS operative details, lesion pathology, and short-term outcomes were recorded. Descriptive statistics for all variables were calculated, and logistic regression identified predictive factors for urologic referral for complex reconstruction. Results: Seventy-three men with 78 lesions, all staged ≤ cT1a prior to MMS, were identified. Twenty-one men were found to have invasive SCC. Median follow-up was 2.0 years (IQR 0.8–5.2 years). MMS was able to clear the disease in 90.4% of cases. One patient had disease related death following progression. Dermatology closed primarily in 68% of patients. Twenty percent of patients had a complication, most commonly poor wound healing. On univariate and multivariate linear regression analysis, lesion size > 3 cm and involvement of the glans independently predicted the need for referral to a reconstructive surgeon. Conclusions: MMS for penile cancer appears to provide sound oncologic control in the properly selected patient. Involvement of a reconstructive surgeon may be needed for glandular and large lesions, necessitating early referral to a comprehensive multidisciplinary care team. [ABSTRACT FROM AUTHOR]

Despite the great diversity of bats (64 species) in the State of Acre, northwestern Brazil, there are no studies on occurrence and diversity of Bartonella spp. in bats in this region. The present study investigated the occurrence and molecular identity of Bartonella spp. in spleen samples (n = 271) from bats of 30 different species from this region, within the Amazon biome. Twenty-one out of 208 (10.1%) samples positive in the PCR for the mammalian gapdh endogenous genes were positive in the qPCR for Bartonella spp. based on the nuoG gene. The two gltA Bartonella genotypes detected grouped with those previously identified in bats from other locations, expanding the diversity of genotypes associated with bats. This study provided the first molecular evidence of the presence of Bartonella spp. in bats in the state of Acre and in bats of the species Lophostoma silvicolum, Vampyressa thyone, Tonatia saurophila and Phyllostomus elongatus. [ABSTRACT FROM AUTHOR]

Allosteric transcription factors (aTF) regulate gene expression through conformational changes induced by small molecule binding. Although widely used as biosensors, aTFs have proven challenging to design for detecting new molecules because mutation of ligand-binding residues often disrupts allostery. Here, we develop Sensor-seq, a high-throughput platform to design and identify aTF biosensors that bind to non-native ligands. We screen a library of 17,737 variants of the aTF TtgR, a regulator of a multidrug exporter, against six non-native ligands of diverse chemical structures – four derivatives of the cancer therapeutic tamoxifen, the antimalarial drug quinine, and the opiate analog naltrexone – as well as two native flavonoid ligands, naringenin and phloretin. Sensor-seq identifies biosensors for each of these ligands with high dynamic range and diverse specificity profiles. The structure of a naltrexone-bound design shows shape-complementary methionine-aromatic interactions driving ligand specificity. To demonstrate practical utility, we develop cell-free detection systems for naltrexone and quinine. Sensor-seq enables rapid and scalable design of new biosensors, overcoming constraints of natural biosensors. The use of allosteric transcription factors (aTFs) as biosensors has been constrained by their limited natural ligand repertoire. Here, the authors report a method to screen large libraries of aTF variants to develop biosensors with altered specificities to non-native ligands. [ABSTRACT FROM AUTHOR]

The Community Firearm Violence Prevention Network (CFVP Network), funded by the National Institutes of Health (NIH), supports a network of research projects that develop and test interventions through collaborations with community partners to prevent firearm violence, injury, and mortality. The CFVP Network presents a unique opportunity to accelerate the science of preventing firearm injuries. The data harmonization workgroup of the CFVP Network led the process of aligning studies across the three unique inaugural network projects, with particular attention to how the CFVP Network could address current gaps in the science. The goal of the data harmonization workgroup was to align study measures, assessment timelines, and data management and archival processes across projects to enable robust cross-project analyses that accelerate the science of preventing firearm injuries. To accomplish this goal, the workgroup established the infrastructure to facilitate cross-project data collection, data sharing and archiving, and analyses. Among the three inaugural network projects, the workgroup's process resulted in harmonizing two assessment timepoints (baseline and one year post-implementation) and 60 constructs (with 31 identical standardized constructs). These harmonized products provide opportunities for novel analyses across the network projects. We expect that the harmonized study infrastructure developed through this process will catalyze future research focused on preventing firearm injury, including and extending beyond CFVP Network projects. The CFVP data harmonization workgroup's process can serve as a model for future networks that seek to build the science in a particular area. [ABSTRACT FROM AUTHOR]

This research addresses the issue of the heritage preventive conservation in the perspective of energy sustainability, for contributing to the achievement of the Sustainable Development Goals (SDGs) and towards the EU Green Deal. The study analyses and compares four cases associated with different microclimate thresholds as suggested by the standard EN 16893:2018 (Cases 1–3) and as derived from the outputs of three degradation models for preserving paper, wood, and canvas paintings (Case 4). Weather-based indices (degree and gram days) were calculated to estimate trends in the potential energy demand of collection facilities in three European cities belonging to different Köppen-Geiger climate zones (Cfb, Csa, and Dfb), under recent past (1981–2010) and near/far future climate scenarios (2021–2050 and 2071–2100) from two Shared Socioeconomic Pathways (SSP2-4.5 and SSP5-8.5). The findings suggest that adapting facilities' management strategies to focus on collections preservation can facilitate the achievement of 5 out of 17 SDGs, offering a viable alternative to costly energy retrofits and encouraging the development of shared solutions for similar facilities in the same climate zone. The results can contribute to inform the revision of EN 16893 and to face major challenges such as the preservation of paper collections in southern latitudes. [ABSTRACT FROM AUTHOR]

This study investigates various pathological tau isoforms in the retina of individuals with early and advanced Alzheimer's disease (AD), exploring their connection with disease status. Retinal cross-sections from predefined superior-temporal and inferior-temporal subregions and corresponding brains from neuropathologically confirmed AD patients with a clinical diagnosis of either mild cognitive impairment (MCI) or dementia (n = 45) were compared with retinas from age- and sex-matched individuals with normal cognition (n = 30) and non-AD dementia (n = 4). Retinal tau isoforms, including tau tangles, paired helical filament of tau (PHF-tau), oligomeric-tau (Oligo-tau), hyperphosphorylated-tau (p-tau), and citrullinated-tau (Cit-tau), were stereologically analyzed by immunohistochemistry and Nanostring GeoMx digital spatial profiling, and correlated with clinical and neuropathological outcomes. Our data indicated significant increases in various AD-related pretangle tau isoforms, especially p-tau (AT8, 2.9-fold, pS396-tau, 2.6-fold), Cit-tau at arginine residue 209 (CitR209-tau; 4.1-fold), and Oligo-tau (T22+, 9.2-fold), as well as pretangle and mature tau tangle forms like MC-1-positive (1.8-fold) and PHF-tau (2.3-fold), in AD compared to control retinas. MCI retinas also exhibited substantial increases in Oligo-tau (5.2-fold), CitR209-tau (3.5-fold), and pS396-tau (2.2-fold). Nanostring GeoMx analysis confirmed elevated retinal p-tau at epitopes: Ser214 (2.3-fold), Ser396 (2.6-fold), Ser404 (2.4-fold), and Thr231 (1.8-fold), particularly in MCI patients. Strong associations were found between retinal tau isoforms versus brain pathology and cognitive status: a) retinal Oligo-tau vs. Braak stage, neurofibrillary tangles (NFTs), and CDR cognitive scores (ρ = 0.63–0.71), b) retinal PHF-tau vs. neuropil threads (NTs) and ABC scores (ρ = 0.69–0.71), and c) retinal pS396-tau vs. NTs, NFTs, and ABC scores (ρ = 0.67–0.74). Notably, retinal Oligo-tau strongly correlated with retinal Aβ42 and arterial Aβ40 forms (r = 0.76–0.86). Overall, this study identifies and quantifies diverse retinal tau isoforms in MCI and AD patients, underscoring their link to brain pathology and cognition. These findings advocate for further exploration of retinal tauopathy biomarkers to facilitate AD detection and monitoring via noninvasive retinal imaging. [ABSTRACT FROM AUTHOR]

Purpose: Glucagon-like receptor agonists (GLP1-RAs) have raised peri-procedural concerns due to their potential to delay gastric emptying. The American Association of Anesthesiologists has advised pausing a single dose before elective endoscopy. However, a subsequent directive from multiple gastroenterology societies underscored the need for further assessment to substantiate this practice. We aimed to evaluate the frequency of serious adverse events and retained gastric products during endoscopic sleeve gastroplasty (ESG) with uninterrupted GLP1-RA use. Materials and Methods: We conducted a retrospective evaluation of all patients undergoing ESG while on GLP1-RAs at three centers from August 2022 to February 2024. Per standard protocol, all patients had refrained from solid foods for at least 24 h and maintained nil per os for 12 h preceding their ESG. Records were reviewed for patient characteristics and medication type and doses. Primary outcomes included serious adverse events and retained gastric products based on patient records, procedure reports, and procedural videos. Results: Fifty-seven consecutive adults (89.5% women, mean age of 44 ± 9 years, mean BMI of 40.1 ± 8.1 kg/m2, 35.1% with T2DM, and 26.3% with pre-T2DM) underwent ESG without stopping GLP1-RAs, which included semaglutide (45.6%), liraglutide (19.3%), dulaglutide (22.8%), and tirzepatide (12.3%). During intubation, endoscopy, and recovery, there were no instances of retained gastric solids, pulmonary aspiration, gastroesophageal regurgitation, or hypoxia. Conclusion: A ≥ 24-h pre-endoscopy liquid-only diet with ≥ 12-h pre-endoscopy fast may negate the need for GLP1-RA interruption for routine upper endoscopy in adults with native gastric anatomy. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate factors associated with differences in intraocular pressure (IOP) readings between iCare and Goldmann applanation tonometry (GAT) in established glaucoma patients. Methods: This retrospective comparative study included clinical data of 350 eyes from 350 established glaucoma patients who had iCare and GAT IOP measured by an ophthalmic technician and a glaucoma specialist, respectively. The main outcome measure was the difference in IOP measurements of the right eyes with iCare and GAT. Results: The intraclass correlation coefficient (ICC) between GAT and iCare was 0.90. The mean IOP difference between tonometers was − 0.18 ± 2.89 mmHg. Bland–Altman plots indicated a 95% limit of agreement of − 5.8 to 5.5 mmHg. Central corneal thickness (CCT) and age were significantly correlated with the difference in IOPs of the iCare and GAT. GAT-IOP and age were significantly associated with the absolute difference in measured IOP of the two tonometers. The difference in measurements was not significantly associated with prior glaucoma surgery, average global index of optical coherence tomography, axial length, technician years of experience and certification, and IOP range. Conclusion: Although there is good agreement between the iCare and GAT mean values, these devices are not interchangeable in glaucoma patients due to the wide range of the limit of agreement. [ABSTRACT FROM AUTHOR]

A significant number of wind bracings in existing railway transom top bridges are numerically assessed deficient against the assessment nosing load recommended by the AS5100, where in almost all cases, there is no observed evidence of wind bracings being overloaded. This paper estimates the nosing load applied by various trains to a couple of random spans of an existing railway transom top bridge. Firstly, field testing of this bridge is conducted and the measured stresses at the mid-center of girders and wind bracings are collected during various normal train operations to validate the developed Finite Element (FE) models of this bridge. Then, the nosing loads due to different trains are estimated using the validated FE model through a two-staged validation approach, including automatic FE stress intensity optimization and rigorous manual FE model sensitivity analysis while transoms in various conditions are also incorporated in the FE model. Results demonstrate that the nosing load is significantly less than the required load in the AS5100 with magnitudes ranging between 8.6% to 9.4% of the maximum vertical axle load of the passed trains; suggesting that the AS5100 assessment nosing load should be revised to avoid unnecessary expensive upgrades of numerically assessed deficient wind bracings. [ABSTRACT FROM AUTHOR]

Immense pressure is being put on criminal justice agencies to adopt and implement evidence-based practices (EBP). Empirical evidence highlights the need for leadership support to make agencies more evidence-based. The current study is an empirical examination of how criminal justice leaders understand EBP and its correlates or predictors in the domains of agency characteristics, individual characteristics, and openness to research partnerships. Data were collected through a statewide survey of police chiefs and chief probation/parole officers in Pennsylvania. Using a multinomial logistic regression model and a binary logistic regression model, correlates and predictors of familiarity and accuracy with EBP were identified. About 32% had never heard of EBP, 27% were familiar with it but did not define it correctly, and 41% held some knowledge of it. Results showed that EBP training may have introduced EBPs to leaders, but it failed to teach them what EBP actually is, and their lack of knowledge of EBP may be contributing to their lack of participation in research partnerships. By providing recommendations based on findings related to EBP training and research partnerships, the current research contributes to the ongoing discussion regarding challenges associated with EBP implementation and acceptance of EBPs among criminal justice practitioners. [ABSTRACT FROM AUTHOR]

Microbial protein, produced by fermentation of Fusarium venenatum is a promising candidate alternative protein source. Previous study has demonstrated its ability to improve hyperlipidemia in rats, yet the related mechanism remains unclear. In this study, we aimed to evaluate the potential of F. venenatum as an alternative protein source and its impact on lipid metabolism using multi-omics analysis. Initial experiments with Caenorhabditis elegans revealed that F. venenatum enhanced longevity, improved immune responses, and reduced lipid metabolism by downregulating fat synthesis-related genes. Subsequently, we conducted experiments with mice on a high-fat diet to confirm the anti-obesity effects of F. venenatum. The groups fed F. venenatum showed improved lipid profiles and reduced hepatic fat accumulation. Furthermore, fecal metabolomic analysis showed higher excretion of primary bile acid and cholesterol in the groups fed F. venenatum which might lead to a decrease in lipid digestion and hepatic fat accumulation. Collectively, this series of experiments revealed the potential of F. venenatum as a sustainable alternative protein and its application as an anti-obesity supplement. Fusarium venenatum is a potential protein source in Caenorhabditis elegans and mice that exhibits anti-obesity properties by improving lipid profiles and reducing fat accumulation. [ABSTRACT FROM AUTHOR]

Researchers and policymakers have proposed systems to detect novel pathogens earlier than existing surveillance systems by monitoring samples from hospital patients, wastewater, and air travel, in order to mitigate future pandemics. How much benefit would such systems offer? We developed, empirically validated, and mathematically characterized a quantitative model that simulates disease spread and detection time for any given disease and detection system. We find that hospital monitoring could have detected COVID-19 in Wuhan 0.4 weeks earlier than it was actually discovered, at 2,300 cases (standard error: 76 cases) compared to 3,400 (standard error: 161 cases). Wastewater monitoring would not have accelerated COVID-19 detection in Wuhan, but provides benefit in smaller catchments and for asymptomatic or long-incubation diseases like polio or HIV/AIDS. Air travel monitoring does not accelerate outbreak detection in most scenarios we evaluated. In sum, early detection systems can substantially mitigate some future pandemics, but would not have changed the course of COVID-19. Monitoring samples from hospital patients, wastewater, or air travel may enable early detection of pathogens. Here, the authors assess how these surveillance systems could have impacted detection of COVID-19 and their potential benefits for detection of other emerging pathogens. [ABSTRACT FROM AUTHOR]

Introduction : The performance characteristics of endoscopic sleeve gastroplasty (ESG) for weight recurrence after intragastric balloon (IGB) are unknown. Methods: This is a retrospective propensity score matched study of ESG after IGB (IGB-to-ESG) vs ESG without prior IGB (ESG-only). The primary outcome was total weight loss (TWL) at 12 months. Secondary outcomes included TWL at 3 and 6 months, 12-month excess weight loss (EWL), procedural characteristics, and safety. Results: Thirty-nine adults underwent ESG from August 2020 to September 2022 after IGB explantation a median of 24 months (range 2–56 months) prior and a median post-IGB nadir weight increase of 100.0% (range 0 to 3200%). An ESG-only 2:1 age- sex- and BMI- propensity score matched cohort was derived from 649 patients (Pearson's goodness-of-fit: 0.86). TWL for IGB-to-ESG vs. ESG-only was 12.3 ± 13.5% vs. 12.4 ± 3.7% at 3 months (p = 0.97), 10.1 ± 7.1% vs. 15.4 ± 4.6% at 6 months (p < 0.001), and 8.7 ± 7.7% vs. 17.1 ± 5.7% at 12 months (p < 0.001). Twelve-month EWL for IGB-to-ESG vs ESG-only was 27.8 ± 46.9% vs 62.0 ± 21.0% (p < 0.001). There was no difference in mean procedural duration of ESG; however, more sutures were used with IGB-to-ESG vs. ESG-only (7 vs. 6, p < 0.0002). There were no serious adverse events in either cohort. Conclusion: ESG after IGB produces safe, acceptable weight loss but with an attenuated effect compared to ESG alone. Further study is required to understand the factors driving this discrepancy. [ABSTRACT FROM AUTHOR]

Surgical site infection in colorectal surgery is prevalent compared to other surgeries due to colonic bacterial load. This has serious implication on recovery, length of stay, readmission, mortality and duration to oncological treatment. We hypothesized that mechanical bowel preparation and oral antibiotics (MBP + OA) reduces surgical site infection in patients undergoing colorectal resection. Our institution introduced MBP + OA for elective colorectal surgeries in 2020. Inclusion criteria were as follows: (1) open colorectal resection, (2) low rectal resection with defunctioning ileostomy and (3) resection of locally advanced colorectal tumour requiring laparoscopically assisted approach. All patients who met these criteria were enrolled. Characteristics and outcomes were compared with control population from previous year that met the criteria but did not receive MBP + OA. 148 patients were studied between January 2019 and June 2021. 68 received MBP + OA; 80 did not. The MBP + OA group had a lower surgical site infection rate of 8.8% vs. 25.0% in the control group (p = 0.018). Multivariate analysis revealed that MBP + OA is an independent protective factor for surgical site infection (odds ratio = 0.30, confidence interval 0.106–0.851; p = 0.024) while open approach is an independent predictor for surgical site infection (odds ratio = 7.435, confidence interval 1.863–29.666; p = 0.004). There was no difference in anastomotic leak rate (p = 0.45). With regards to ERAS-specific outcomes, the MBP + OA group had higher rate of establishing solid diet by POD2 (57.4% vs. 33.8%, p = 0.0067) and shorter day to bowel opening (1.88SD1.08 vs. 2.39SD1.79). MBP + OA is effective in reducing surgical site infection and complements ERAS. This is one of the first studies to be conducted in the Asian population. [ABSTRACT FROM AUTHOR]

The auditory brainstem implant (ABI) is an auditory neuroprosthesis that provides hearing by electrically stimulating the cochlear nucleus (CN) of the brainstem. Our previous study (McInturff et al., 2022) showed that single-pulse stimulation of the dorsal (D)CN subdivision with low levels of current evokes responses that have early latencies, different than the late response patterns observed from stimulation of the ventral (V)CN. How these differing responses encode more complex stimuli, such as pulse trains and amplitude modulated (AM) pulses, has not been explored. Here, we compare responses to pulse train stimulation of the DCN and VCN, and show that VCN responses, measured in the inferior colliculus (IC), have less adaption, higher synchrony, and higher cross-correlation. However, with high-level DCN stimulation, responses become like those to VCN stimulation, supporting our earlier hypothesis that current spreads from electrodes on the DCN to excite neurons located in the VCN. To AM pulses, stimulation of the VCN elicits responses with larger vector strengths and gain values especially in the high-CF portion of the IC. Additional analysis using neural measures of modulation thresholds indicate that these measures are lowest for VCN. Human ABI users with low modulation thresholds, who score best on comprehension tests, may thus have electrode arrays that stimulate the VCN. Overall, the results show that the VCN has superior response characteristics and suggest that it should be the preferred target for ABI electrode arrays in humans. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic may have a compounding effect on the substance use of American veterans with posttraumatic stress disorder (PTSD). This study investigated the relationship between PTSD and current reactions to COVID-19 on alcohol and cannabis use among veterans who completed a survey 1 month prior to the pandemic in the USA and a 6-month follow-up survey. We hypothesized that veterans with PTSD would experience more negative reactions to COVID-19 and increased alcohol and cannabis use behaviors over those without PTSD. Veterans with PTSD prior to the pandemic, relative to those without, endorsed poorer reactions, greater frequency of alcohol use, and greater cannabis initiation and use during the pandemic. Veterans with PTSD may use substances to manage COVID-related stress. Clinicians may see an increase in substance use among this group during and after the pandemic and may need to implement specific behavioral interventions to mitigate the negative effects of COVID-19. [ABSTRACT FROM AUTHOR]

The development of stable sorbent materials to deliver reversible adsorption of ammonia (NH3) is a challenging task. Here, we report the efficient capture and storage of NH3 in a series of robust microporous aluminium-based metal-organic framework materials, namely MIL-160, CAU-10-H, Al-fum, and MIL-53(Al). In particular, MIL-160 shows high uptakes of NH3 of 4.8 and 12.8 mmol g−1 at both low and high pressure (0.001 and 1.0 bar, respectively) at 298 K. The combination of in situ neutron powder diffraction, synchrotron infrared micro-spectroscopy and solid-state nuclear magnetic resonance spectroscopy reveals the preferred adsorption domains of NH3 molecules in MIL-160, with H/D site-exchange between the host and guest and an unusual distortion of the local structure of [AlO6] moieties being observed. Dynamic breakthrough experiments confirm the excellent ability of MIL-160 to capture of NH3 with a dynamic uptake of 4.2 mmol g−1 at 1000 ppm. The combination of high porosity, pore aperture size and multiple binding sites promotes the significant binding affinity and capacity for NH3, which makes it a promising candidate for practical applications. Porous sorbents capable of high ammonia (NH3) uptake capacities are of great interest for ammonia storage for industry, as well as for the environmental remediation of this toxic and corrosive gas. Here, NH3 adsorption is investigated in four robust aluminium-based metal–organic frameworks, and in situ neutron powder diffraction, synchrotron IR micro-spectroscopy and 27Al solid-state NMR studies show that the pore geometries, framework rigidity, and nature of the host–guest binding sites together dictate the high NH3 capture and storage capacity. [ABSTRACT FROM AUTHOR]

Investors use heuristics and biases which may disproportionately impact entrepreneurial teams with women when hearing pitches and evaluating early-stage ventures. However, merely entertaining a pitch is not enough—the tone of the conversation also matters. To investigate, we explore non-rationality in the funding process by applying Natural Language Processing (NLP) to Shark Tank: a high-impact television program fosr entrepreneurial pitching. Using sentiment analysis, we show that male judges react more positively to pitches from entrepreneurial teams with women. Importantly, these positive reactions are not indicative of increased deal flow. The opposite is true for female judges who, while no more likely to react positively to teams with female entrepreneurs, are significantly more likely to ink a deal when they do. By showing how non-rational thinking and biases impact both the pitch narrative and the likelihood of securing funding, our findings have important implications regarding heuristic formation and gender bias in early-stage investment. Plain English Summary: Despite the positive reaction from male judges in pitch competitions, teams with female entrepreneurs are less likely to ink a deal. However, female judges are more likely to fund teams with female entrepreneurs, regardless of reaction sentiment. To evaluate, we explore non-rationality in the funding process by applying Natural Language Processing (NLP) to Shark Tank: a high impact television program for entrepreneurial pitching. Using sentiment analysis, we show that male judges react more positively to pitches from entrepreneurial teams with women. Importantly, these positive reactions are not indicative of increased deal flow. Interestingly, the opposite is true for female judges who are no more likely to react positively to female entrepreneurs, but when they do, are significantly more likely to ink a deal. Our findings have important implication regarding the heuristic formation and gender bias in early-stage investment. [ABSTRACT FROM AUTHOR]

Purpose: To assess real-world effectiveness and tolerability of fixed-dose combination netarsudil 0.02%/latanoprost 0.005% (FCNL) in management of glaucoma patients in a tertiary eye care center. Methods: This retrospective cohort study included glaucoma patients initiated on FCNL from January 2018 to July 2021 with at least 1-month follow-up. Demographic and clinical data were collected at baseline and at follow-up visits through 12 months. Patient-solicited side effects were recorded at each visit. Maximum glaucoma pharmacotherapy was defined as surgery/laser being the next treatment option following an intensive pharmacotherapy regimen, or when pharmacotherapy could not be increased due to allergy/intolerance or all pharmacologic mechanisms already being in use. Results: Seventy-nine eyes of 47 patients were included. Mean age was 67.7 ± 14.7 years. Baseline IOP was 18.7 ± 4.9 mmHg; mean change in IOP (∆IOP) each study visit compared to baseline ranged from − 1.6 ± 3.5 to − 4.4 ± 4.1 mmHg (all p < 0.05). The eyes on maximum glaucoma pharmacotherapy (73.4%) had similar ∆IOP compared to those on non-maximal therapy at each visit (p > 0.2 for all). Forty-three (54.4%) eyes were switched from a prostaglandin analog alone, producing a 1-month IOP reduction of − 4.7 ± 3.9 mmHg at 1 month which remained significant at each visit for the 12-month study period (all p < 0.05). Across all study visits, conjunctival hyperemia was documented in 26 (32.9%) eyes. Subjective blurry vision was reported in 22 (27.8%) eyes without significant worsening of visual acuity at any visit (all p > 0.05). Six (7.6%) and 7 (8.9%) eyes required further medical or surgical/laser intervention, respectively. Kaplan–Meier analysis revealed no significant difference in the need for subsequent medical or surgical intervention between those on maximum and non-maximal pharmacotherapy (p > 0.4). Conclusion: FCNL was well-tolerated and demonstrated a significant and sustained reduction in IOP, even as last-line therapy before incisional or laser surgery in those on maximum glaucoma pharmacotherapy. FCNL is a viable treatment option for glaucomatous eyes before consideration of surgical intervention. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) continues to significantly impact the global population, thus countermeasure platforms that enable rapid development of therapeutics against variants of SARS-CoV-2 are essential. We report use of a phage display human antibody library approach to rapidly identify neutralizing antibodies (nAbs) against SARS-CoV-2. We demonstrate the binding and neutralization capability of two nAbs, STI-2020 and STI-5041, against the SARS-CoV-2 WA-1 strain as well as the Alpha and Beta variants. STI-2020 and STI-5041 were protective when administered intravenously or intranasally in the golden (Syrian) hamster model of COVID-19 challenged with the WA-1 strain or Beta variant. The ability to administer nAbs intravenously and intranasally may have important therapeutic implications and Phase 1 healthy subjects clinical trials are ongoing. [ABSTRACT FROM AUTHOR]

A major informatic challenge in single cell RNA-sequencing analysis is the precise annotation of datasets where cells exhibit complex multilayered identities or transitory states. Here, we present devCellPy a highly accurate and precise machine learning-enabled tool that enables automated prediction of cell types across complex annotation hierarchies. To demonstrate the power of devCellPy, we construct a murine cardiac developmental atlas from published datasets encompassing 104,199 cells from E6.5-E16.5 and train devCellPy to generate a cardiac prediction algorithm. Using this algorithm, we observe a high prediction accuracy (>90%) across multiple layers of annotation and across de novo murine developmental data. Furthermore, we conduct a cross-species prediction of cardiomyocyte subtypes from in vitro-derived human induced pluripotent stem cells and unexpectedly uncover a predominance of left ventricular (LV) identity that we confirmed by an LV-specific TBX5 lineage tracing system. Together, our results show devCellPy to be a useful tool for automated cell prediction across complex cellular hierarchies, species, and experimental systems. A major informatic challenge in single cell RNA-sequencing analysis is the precise annotation of datasets where cells exhibit complex multilayered identities or transitory states. Here the authors present devCellPy, a Python-based package that enables the automated prediction of cell types across complex cellular hierarchies, species, and experimental systems with high accuracy, particularly for developmental scRNA-seq datasets. [ABSTRACT FROM AUTHOR]

Introduction: We hypothesized that the cranial phenotype influences the shape of the posterior cranial fossa and the relative position of the sigmoid sinus. Materials and methods: The topography of the sigmoid sinus was studied on 26 magnetic resonance venograms and 35 embalmed cadavers by morphometric analysis, dissection, and photo modeling techniques. Results: The data show that the transverse diameter of the posterior cranial fossa correlates positively with the laterolateral diameter of the skull. The majority of cases with the low-anterior position of the sigmoid sinus were recorded in the brachycephalic group (82%), while the high-posterior localization of the sigmoid sinus was typical for the dolichocephalic patients (63%). The results of the ANOVA test confirm the significance of differences. Conclusions: The shape of the skull reflects the morphology of the posterior cranial fossa and influences the topographic characteristics of the sigmoid sinus that must be considered in the selection of surgical approach to the inner ear and pontocerebellar angle. [ABSTRACT FROM AUTHOR]

Fate-determining transcription factors (TFs) can promote lineage-restricted transcriptional programs from common progenitor states. The inner cell mass (ICM) of mouse blastocysts co-expresses the TFs NANOG and GATA6, which drive the bifurcation of the ICM into either the epiblast (Epi) or the primitive endoderm (PrE), respectively. Here, we induce GATA6 in embryonic stem cells–that also express NANOG–to characterize how a state of co-expression of opposing TFs resolves into divergent lineages. Surprisingly, we find that GATA6 and NANOG co-bind at the vast majority of Epi and PrE enhancers, a phenomenon we also observe in blastocysts. The co-bound state is followed by eviction and repression of Epi TFs, and quick remodeling of chromatin and enhancer-promoter contacts thus establishing the PrE lineage while repressing the Epi fate. We propose that co-binding of GATA6 and NANOG at shared enhancers maintains ICM plasticity and promotes the rapid establishment of Epi- and PrE-specific transcriptional programs. The authors show that the transcription factors NANOG and GATA6 co-bind the same enhancers in common progenitors before divergent epiblast and primitive endoderm lineages emerge. This may help maintain plasticity at early stages and facilitate bifurcation into distinct lineages [ABSTRACT FROM AUTHOR]

A comprehensive characterization of epigenomic organization in the embryonic mouse forebrain will enhance our understanding of neurodevelopment and provide insight into mechanisms of neurological disease. Here we collected single-cell chromatin accessibility profiles from four distinct neurogenic regions of the embryonic mouse forebrain using single nuclei ATAC-Seq (snATAC-Seq). We identified thousands of differentially accessible peaks, many restricted to distinct progenitor cell types or brain regions. We integrated snATAC-Seq and single cell transcriptome data to characterize changes of chromatin accessibility at enhancers and promoters with associated transcript abundance. Multi-modal integration of histone modifications (CUT&Tag and CUT&RUN), promoter-enhancer interactions (Capture-C) and high-order chromatin structure (Hi-C) extended these initial observations. This dataset reveals a diverse chromatin landscape with region-specific regulatory mechanisms and genomic interactions in distinct neurogenic regions of the embryonic mouse brain and represents an extensive public resource of a 'ground truth' epigenomic landscape at this critical stage of neurogenesis. The authors took a multimodal approach to characterize the differential transcriptome and epigenetic landscape between distinct regions of the embryonic mouse forebrain, revealing many unexplored presumptive promoter-enhancer interactions. [ABSTRACT FROM AUTHOR]

Classic lifespan developmental theory describes emerging adulthood and the transition to adulthood as important periods for thinking about one's future life trajectory. Today, youth are facing far-reaching changes to daily life due to COVID-19. This may have negative effects on their future outlook, and the extent of such effects may be related to personality. This study examined emerging adults' (N = 195, Mage = 20.58, SD = 3.98) multidimensional personality profiles in relation to the extent that they hold a positive outlook on their future at the outset of the COVID-19 pandemic. Quantitative and brief narrative measures of future outlook were collected. Hierarchical cluster analysis and Latent Profile Analysis revealed two clear personality profiles, labeled Reflectors (n = 106) and Forgers (n = 89). Forgers demonstrated robust personality characteristics indicative of psychologically 'pushing forward' through pandemic-related challenges. Reflectors demonstrated more pandemic reactivity including higher stress but also more psychological integration of the pandemic experience into their sense of self. In terms of future outlook, Forgers reported a positive and expansive outlook on the future across multiple measures. In contrast, Reflectors held more negative, restricted views of what future life might hold. Results are discussed in terms of the role of multi-level personality in dictating emerging adults' future perspectives in the wake of life challenges. Ideas are presented about how to best support young people as they transition into the future, into adulthood, while grappling with the challenges of the pandemic. [ABSTRACT FROM AUTHOR]

The auditory brainstem implant (ABI) is an auditory neuroprosthesis that provides hearing to deaf patients by electrically stimulating the cochlear nucleus (CN) of the brainstem. Whether such stimulation activates one or the other of the CN's two major subdivisions is not known. Here, we demonstrate clear response differences from the stimulation of the dorsal (D) vs. ventral (V) subdivisions of the CN in a mouse model of the ABI with a surface-stimulating electrode array. For the DCN, low levels of stimulation evoked multiunit responses in the inferior colliculus (IC) that were unimodally distributed with early latencies (avg. peak latency of 3.3 ms). However, high levels of stimulation evoked a bimodal distribution with the addition of a late latency response peak (avg. peak latency of 7.1 ms). For the VCN, in contrast, electrical stimulation elicited multiunit responses that were usually unimodal and had a latency similar to the DCN's late response. Local field potentials (LFP) from the IC showed components that correlated with early and late multiunit responses. Surgical cuts to sever the output of the DCN, the dorsal acoustic stria (DAS), gave insight into the origin of these early and late responses. Cuts eliminated early responses but had little-to-no effect on late responses. The early responses thus originate from cells that project through the DAS, such as DCN's pyramidal and giant cells. Late responses likely arise from the spread of stimulation from a DCN-placed electrode array to the VCN and could originate in bushy and/or stellate cells. In human ABI users, the spread of stimulation in the CN may result in abnormal response patterns that could hinder performance. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy and safety profile of netarsudil 0.02% ophthalmic solution in a tertiary glaucoma referral center. Methods: This retrospective cohort study included patients with glaucoma initiated on netarsudil 0.02% at a single institution from November 2017 to September 2018. Demographic and clinical data were collected, including intraocular pressure (IOP) and drug side effects at baseline and 1-, 3-, and 6-month follow-up visits. Results: A total of 340 eyes of 233 patients were included; mean ± SD patient age was 69.1 ± 12.5 years. One hundred twenty (48%) eyes experienced ≥ 20% decreases in IOP at the 1-month study visit; this effect was maintained through the 6-month visit. IOP-lowering effects in patients using ≥ 3 topical glaucoma medications were similar (all p > 0.1). Eighteen (7.4%) and 7 (2.9%) patients experienced increases in IOP of ≥ 3 and ≥ 5 mmHg, respectively. Across all study visits, conjunctival hyperemia was noted at a rate of 27.6%, and though frequently reported, complaints of blurred vision (31.1%) did not manifest in significant worsening of visual acuity. The rate of drug discontinuation due to insufficient IOP-lowering and side effects was 15.6% and 24.8%, respectively. Twenty-nine (11.4%) and 82 (32.3%) eyes required additional medical and surgical/laser intervention, respectively. Conclusion: Commonly used as the last-line medical therapy in this case series, netarsudil safely and significantly reduced IOP in patients with glaucoma, even in those using ≥ 3 glaucoma medications. Increases in IOP of ≥ 3 mmHg occurred in a small number of patients. Subjective vision changes and conjunctival hyperemia were the most frequently reported side effects. [ABSTRACT FROM AUTHOR]

C-terminal cleaved tau at D421 (∆D421-tau) accumulates in the brains of Alzheimer's disease (AD) patients. However, it is unclear how tau truncation, an understudied tau post-translational modification, contributes to AD pathology and progression. Utilizing an adeno-associated virus (AAV) gene delivery-based approach, we overexpressed full-length tau (FL-tau) and ∆D421-tau in 4- and 12-month-old mice for 4 months to study the neuropathological impact of accumulation in young adult (8-month) and middle-aged (16-month) mice. Overall, we show that independent of the tau species, age was an important factor facilitating tau phosphorylation, oligomer formation, and deposition into silver-positive tangles. However, mice overexpressing ∆D421-tau exhibited a distinct phosphorylation profile to those overexpressing FL-tau and increased tau oligomerization in the middle-age group. Importantly, overexpression of ∆D421-tau, but not FL-tau in middle-aged mice, resulted in pronounced cognitive impairments and hippocampal long-term potentiation deficits. While both FL-tau and ∆D421-tau induced neuronal loss in mice with age, ∆D421-tau led to significant neuronal loss in the CA3 area of the hippocampus and medial entorhinal cortex compared to FL-tau. Based on our data, we conclude that age increases the susceptibility to neuronal degeneration associated with ΔD421-tau accumulation. Our findings suggest that ΔD421-tau accumulation contributes to synaptic plasticity and cognitive deficits, thus representing a potential target for tau-associated pathologies. [ABSTRACT FROM AUTHOR]

The recent detection of potent carcinogenic nitrosamine impurities in several human medicines has triggered product recalls and interrupted the supply of critical medications for hundreds of millions of patients, illuminating the need for increased testing of nitrosamines in pharmaceutical products. However, the development of analytical methods for nitrosamine detection is challenging due to high sensitivity requirements, complex matrices, and the large number and variety of samples requiring testing. Herein, we report an analytical method for the analysis of a common nitrosamine, N-nitrosodimethylamine (NDMA), in pharmaceutical products using full evaporation static headspace gas chromatography with nitrogen phosphorous detection (FE-SHSGC-NPD). This method is sensitive, specific, accurate, and precise and has the potential to serve as a universal method for testing all semi-volatile nitrosamines across different drug products. Through elimination of the detrimental headspace-liquid partition, a quantitation limit of 0.25 ppb is achieved for NDMA, a significant improvement upon traditional LC-MS methods. The extraction of nitrosamines directly from solid sample not only simplifies the sample preparation procedure but also enables the method to be used for different products as is or with minor modifications, as demonstrated by the analysis of NDMA in 10+ pharmaceutical products. The in situ nitrosation that is commonly observed in GC methods for nitrosamine analysis was completely inhibited by the addition of a small volume solvent containing pyrogallol, phosphoric acid, and isopropanol. Employing simple procedures and low-cost instrumentation, this method can be implemented in any analytical laboratory for routine nitrosamine analysis, ensuring patient safety and uninterrupted supply of critical medications. [ABSTRACT FROM AUTHOR]

Scissor structures can meet different performance goals by actively changing their geometric configurations. This paper focuses on the inverse design problem of planar scissor structures with end constraints to obtain various forms without changing the span. Two strategies are proposed, one based on adding hinges and the other based on telescopic rods. The corresponding geometrical principles and constraint conditions are formulated. An inverse design framework from two predefined target shapes to design parameters is established, which consist of geometry optimization and mobility assessment. Seven case studies are used to illustrate the design method based on the two strategies. Results show potential for application of morphing planar scissor structure in practice. [ABSTRACT FROM AUTHOR]

Background: While ultrasound is often the preferred imaging modality for suspected acute cholecystitis (AC), CT is often the first line study when patients are being evaluated for abdominal pain. The diagnostic value of CT in the setting of AC is controversial, given the prevalent use of additional imaging. Purpose: To evaluate the positive predictive value (PPV) of CT for diagnosing acute cholecystitis (AC) when used as a first line imaging study for evaluating abdominal pain and assess if additional imaging with ultrasound studies provides additional clinically useful information. Materials and methods: Abnormal gallbladder findings in CT imaging studies were queried in a retrospective study over a 25-month period within a large urban health system. Sonographic (US) studies performed within 72 h of the initial CT were also included. Outcomes were determined by surgical pathology, fluid analysis, and clinical outcomes. Cases were stratified by the interpreting radiologist's subjective confidence level of diagnosing AC, and the PPVs were compared between cases using CT without US and cases with both CT and US. Results: Of the 468 CT studies meeting criteria, 192 were read as concerning for AC. PPV of CT was 44.7% without US and 50.5% when US was positive, which amounted to an insignificant gain (p = 0.41). When subdividing by confidence level, high-confidence positive CTs demonstrated no significant difference without ultrasound (80%) compared to with ultrasound (75%). Less confident reads in CT demonstrated potential gain from ultrasound; in the case of a "probable" CT impression, PPV increased from 45% without US to 90% with a high-confidence ultrasound impression. Conclusion: Based on current practice within a large health system, CT examinations with high suspicion for AC demonstrated little gain from follow-up ultrasound. However, ultrasound may be of benefit when CT interpretations are less confident but still suspicious for AC. [ABSTRACT FROM AUTHOR]

Background: Primary repair or resection with anastomosis (PR/A) has been gaining increasing recognition for traumatic colonic injuries, with the need for faecal diversion (FD) especially those of penetrating etiology being questioned. However, the role of PR/A in critically ill patients is still controversial with concerns pertaining to safety and anastomotic leak. Aims and methods: We performed a systemic review of studies comparing outcomes of FD versus PR/A in traumatic colonic injuries. A systematic review was performed as per PRISMA guidelines utilizing three electronic databases: Pubmed, EMBASE, and Cochrane Library resources. Mortality and anastomotic leak rates are identified as the primary and secondary outcomes, respectively. Data extracted include mortality rates, type of surgical intervention, surgical complications, and need for DC (damage control) surgery. Results: Fourteen studies were identified comprising 11 retrospective, 2 prospective cohort and 1 randomized trial with a total of 2071 patients. Six studies included patients that underwent DC surgery. The overall mortality rate was 3.77% and was higher in the FD group compared to PR/A group (5.38% vs 2.49%, p = 0.07). 71.3% of patients underwent PR/A with an overall leak rate of 4.63%. There was no difference in intra-abdominal collections between the PR/A and FD groups. In the subgroup analysis, anastomotic leak rate was significantly higher in the DC group compared to non-DC group (16.7% vs 3.2%, p = 0.003). Conclusions: This meta-analysis supports PR/A in stable patients with traumatic colonic injuries. FD should be considered in critically ill patients who require DC surgery as leak rates are significantly higher. [ABSTRACT FROM AUTHOR]

Notably, refractory AML patients with MCL-1 dependence had a CRc rate of 52% compared with 38% in refractory AML patients without MCL-1 dependence (Supplemental Fig. A comparison of clinical outcomes among patients with MCL-1-dependent R/R AML and non-MCL-1-dependent R/R AML patients is outlined in Supplemental Tables 3-5. Eighty-two patients were enrolled onto one of the five cohorts: (1) MCL-1 <15% ( I n i = 15), (2) MCL-1: 15-<30% ( I n i = 14), (3) MCL-1: 30-<40% ( I n i = 14), (4) MCL-1: >=40% ( I n i = 25), and (5) NDHR AML with MCL-1 >=40% ( I n i = 14). [Extracted from the article]

We aim to investigate the role of medication adherence history in treatment needed diabetic retinopathy (TNDR). We conducted a retrospective nested case–control study using 3 population-based databases in Taiwan. The major one was the 2-million-sample longitudinal health and welfare population-based database from 1997 to 2017, a nationally representative random sample of National Health Insurance Administration enrolled beneficiaries in 2010 (LHID2010). The national death registry and national cancer registry were also checked to verify the information. The outcome was defined as the TNDR. The Medication possession ratio (MPR) was defined as the ratio of total days of diabetes mellitus (DM) medication supply divided by total observation days. MPR ≥ 80% was proposed as good medication adherence. The association of MPR and the TNDR was analyzed. Other potential confounders and MPR ratio were also evaluated. A total of (n = 44,628) patients were enrolled. Younger aged, male sex and patients with less chronic illness complexity or less diabetes complication severity tend to have poorer medication adherence. Those with severe comorbidity or participating pay-for-performance program (P4P) revealed better adherence. No matter what the characteristics are, patients with good MPR showed a significantly lower likelihood of leading to TNDR after adjustment with other factors. The protection effect was consistent for up to 5 years. Good medication adherence significantly prevents treatment needed diabetic retinopathy. Hence, it is important to promote DM medication adherence to prevent risks of diabetic retinopathy progression, especially those who opt to have low medication adherence. [ABSTRACT FROM AUTHOR]

Determining the nature and extent of covalency of early actinide chemical bonding is a fundamentally important challenge. Recently, X-ray absorption, electron paramagnetic, and nuclear magnetic resonance spectroscopic studies have probed actinide-ligand covalency, largely confirming the paradigm of early actinide bonding varying from ionic to polarised-covalent, with this range sitting on the continuum between ionic lanthanide and more covalent d transition metal analogues. Here, we report measurement of the covalency of a terminal uranium(VI)-nitride by 15N nuclear magnetic resonance spectroscopy, and find an exceptional nitride chemical shift and chemical shift anisotropy. This redefines the 15N nuclear magnetic resonance spectroscopy parameter space, and experimentally confirms a prior computational prediction that the uranium(VI)-nitride triple bond is not only highly covalent, but, more so than d transition metal analogues. These results enable construction of general, predictive metal-ligand 15N chemical shift-bond order correlations, and reframe our understanding of actinide chemical bonding to guide future studies. Determining the covalency of actinide chemical bonding is a fundamentally important challenge. Here, the authors report a 15N nuclear magnetic resonance spectroscopy study of a terminal uranium-nitride, revealing exceptional NMR properties and covalency that redefine 15N NMR parameter space and actinide chemical bonding. [ABSTRACT FROM AUTHOR]

Purpose: To investigate sports compression garment (CG)-induced recovery hemodynamics and their potential impact on subsequent cycling performance.Methods: In a randomized crossover design, 13 physically active men (20.9 ± 1.4 years; 65.9 ± 7.8 kg; 173.3 ± 4.8 cm; peak power output 254.2 ± 27.2 W) underwent 2 experimental trials. During each experimental trial, the subjects performed 20-min fatiguing preload cycling followed by 60-min passive recovery wearing either a sports CG (28.6 ± 9.4 mmHg) or gymnastic pants (CON). A 5-min all-out cycling performance test was subsequently conducted and power output and cadence were recorded. Cardiac output (CO) and stroke volume (SV) were measured using Doppler ultrasound (USCOM®). Heart rate (HR), blood lactate [BLa-], ratings of perceived exertion (RPE), leg muscle soreness (LMS), mean arterial pressure (MAP) and systemic vascular resistance (SVR) were monitored at 5, 15, 30, 45, 60 min during passive recovery.Results: During the subsequent 5-min all-out cycling performance test, power output (215.2 ± 24.0 vs. 210.8 ± 21.5 W, CG vs. CON) and cadence (72.5 ± 3.8 vs. 71.2 ± 4.8 rpm, CG vs. CON) were higher in CG than CON (P < 0.05). SV was higher at 15, 30 and 45 min (P < 0.05), CO was higher at 5 and 45 min (P < 0.05), HR was lower at 15 and 30 min (P < 0.05) and [BLa-] was lower at 5 and 15 min (P < 0.05) during passive recovery, while LMS was lower at all time-points (P < 0.05) compared with CON.Conclusion: Sports CG improves subsequent cycling performance by enhancing hemodynamic responses and attenuating perceived muscle soreness during passive recovery in physically active men. [ABSTRACT FROM AUTHOR]

The highly infectious nature of SARS-CoV-2 necessitates the use of widespread testing to control the spread of the virus. Presently, the standard molecular testing method (reverse transcriptase-polymerase chain reaction, RT-PCR) is restricted to the laboratory, time-consuming, and costly. This increases the turnaround time for getting test results. This study sought to develop a rapid, near-patient saliva-based test for COVID-19 (Saliva-Dry LAMP) with similar accuracy to that of standard RT-PCR tests. A lyophilized dual-target reverse transcription-loop-mediated isothermal amplification (RT-LAMP) test with fluorometric detection by the naked eye was developed. The assay relies on dry reagents that are room temperature stable. A device containing a centrifuge, heat block, and blue LED light system was manufactured to reduce the cost of performing the assay. This test has a limit of detection of 1 copy/µL and achieved a positive percent agreement of 100% [95% CI 88.43% to 100.0%] and a negative percent agreement of 96.7% [95% CI 82.78–99.92%] relative to a reference standard test. Saliva-Dry LAMP can be completed in 105 min. Precision, cross-reactivity, and interfering substances analysis met international regulatory standards. The combination of ease of sample collection, dry reagents, visual detection, low capital equipment cost, and excellent analytical sensitivity make Saliva-Dry LAMP particularly useful for resource-limited settings. [ABSTRACT FROM AUTHOR]

The load a tephra fall deposit applies to an underlying surface is a key factor controlling its potential to damage a wide range of assets including buildings, trees, crops and powerlines. Though it has long been recognised that loading can increase when deposits absorb rainfall, few efforts have been made to quantify likely load increases. This study builds on previous theoretical work, using an experimental approach to quantify change in load as a function of grainsize distribution, rainfall intensity and duration. A total of 20 laboratory experiments were carried out for ~ 10-cm thick, dry tephra deposits of varying grainsize and grading, taken to represent different eruptive scenarios (e.g. stable, waxing or waning plume). Tephra was deposited onto a 15° impermeable slope (representing a low pitch roof) and exposed to simulated heavy rainfalls of 35 and 70 mm h−1 for durations of up to 2 h. Across all experiments, the maximum load increases ranged from 18 to 30%. Larger increases occurred in fine-grained to medium-grained deposits or in inversely graded deposits, as these retained water more efficiently. The lowest increases occurred in normally graded deposits as rain was unable to infiltrate to the deposit's base. In deposits composed entirely of coarse tephra, high drainage rates meant the amount of water absorbed was controlled by the deposit's capillary porosity, rather than its total porosity, resulting in load increases that were smaller than expected. These results suggest that, for low pitch roofs, the maximum deposit load increase due to rainfall is around 30%, significantly lower than the oft-referenced 100%. To complement our experimental results, field measurements of tephra thickness should be supplemented with tephra loading measurements, wherever possible, especially when measurements are made at or near the site of observed damage. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of tube shunt type [Ahmed (AGV) versus Baerveldt (BGI)] on the frequency of tube-cornea touch and corneal decompensation after tube shunt surgery. Methods: This retrospective comparative study included 145 eyes of 130 patients with uveitic glaucoma who underwent AGV (75 eyes) or BGI (70 eyes) implantations. Electronic medical records were reviewed to document demographic factors, intraocular pressure (IOP) reduction, frequency of tube-cornea touch, corneal decompensation, and need for subsequent corneal transplantation. Results: The mean follow-up was 27.7±3.3 months for AGV and 32.8±3.8 months for BGI (p=0.30). Tube-cornea touch was observed in 5 eyes after BGI and 1 eye in the AGV group (p=0.08). The BGI group reported a significantly higher rate of corneal decompensation (9 versus 0; p=0.001) and transplantation (6 versus 0; p=0.01) compared to the AGV group. Previous trabeculectomy was a significant risk factor for corneal complications in eyes undergoing BGI implantation (odds ratio [OR]= 8.17, 95% confidence interval [CI]=1.78–37.45, p=0.007). Conclusion: Similar rates of tube-cornea touch were observed in both shunt types; BGI shunts were associated with a greater incidence of corneal complications and transplantation as compared to AGV in this retrospective series of uveitic glaucoma cases. [ABSTRACT FROM AUTHOR]

Pancreatic islets adapt to insulin resistance of pregnancy by up regulating β-cell mass and increasing insulin secretion. Previously, using a transgenic mouse with global, heterozygous deletion of prolactin receptor (Prlr+/−), we found Prlr signaling is important for this adaptation. However, since Prlr is expressed in tissues outside of islets as well as within islets and prolactin signaling affects β-cell development, to understand β-cell-specific effect of prolactin signaling in pregnancy, we generated a transgenic mouse with an inducible conditional deletion of Prlr from β-cells. Here, we found that β-cell-specific Prlr reduction in adult mice led to elevated blood glucose, lowed β-cell mass and blunted in vivo glucose-stimulated insulin secretion during pregnancy. When we compared gene expression profile of islets from transgenic mice with global (Prlr+/−) versus β-cell-specific Prlr reduction (βPrlR+/−), we found 95 differentially expressed gene, most of them down regulated in the Prlr+/− mice in comparison to the βPrlR+/− mice, and many of these genes regulate apoptosis, synaptic vesicle function and neuronal development. Importantly, we found that islets from pregnant Prlr+/− mice are more vulnerable to glucolipotoxicity-induced apoptosis than islets from pregnant βPrlR+/− mice. These observations suggest that down regulation of prolactin action during pregnancy in non-β-cells secondarily and negatively affect β-cell gene expression, and increased β-cell susceptibility to external insults. [ABSTRACT FROM AUTHOR]

Many phenomena in the Sun's atmosphere are magnetic in nature and study of the atmospheric magnetic field plays an important part in understanding these phenomena. Tools to study solar magnetic fields include magnetic topology and features such as magnetic null points, separatrix surfaces, and separators. The theory of these has most robustly been developed under magnetic charge topology, where the sources of the magnetic field are taken to be discrete, but observed magnetic fields are continuously distributed, and reconstructions and numerical simulations typically use continuously distributed magnetic boundary conditions. This article investigates the pitfalls in using continuous-source descriptions, particularly when null points on the z = 0 plane are obscured by the continuous flux distribution through, e.g., the overlap of non-point sources. The idea of null-like points on the boundary is introduced where the parallel requirement on the field B ∥ = 0 is retained but the requirement on the perpendicular component is relaxed, i.e. B ⊥ ≠ 0 . These allow the definition of separatrix-like surfaces which are shown (through use of a squashing factor) to be a class of quasi-separatrix layer, and separator-like lines which retain the x-line structure of separators. Examples are given that demonstrate that the use of null-like points can reinstate topological features that are eliminated in the transition from discrete to continuous sources, and that their inclusion in more involved cases can enhance understanding of the magnetic structure and even change the resulting conclusions. While the examples in this article use the potential approximation, the definition of null-like points is more general and may be employed in other cases such as force-free field extrapolations and MHD simulations. [ABSTRACT FROM AUTHOR]

It is becoming increasingly difficult for game developers to manage the cost of developing a game, while meeting the high expectations of gamers. One way to balance the increasing gamer expectation and development stress is to build an active modding community around the game. There exist several examples of games with an extremely active and successful modding community, with the Minecraft game being one of the most notable ones. This paper reports on an empirical study of 1,114 popular and 1,114 unpopular Minecraft mods from the CurseForge mod distribution platform, one of the largest distribution platforms for Minecraft mods. We analyzed the relationship between 33 features across 5 dimensions of mod characteristics and the popularity of mods (i.e., mod category, mod documentation, environmental context of the mod, remuneration for the mod, and community contribution for the mod), to understand the characteristics of popular Minecraft mods. We firstly verify that the studied dimensions have significant explanatory power in distinguishing the popularity of the studied mods. Then we evaluated the contribution of each of the 33 features across the 5 dimensions. We observed that popular mods tend to have a high quality description and promote community contribution. [ABSTRACT FROM AUTHOR]

Purpose of Review: To review the evidence regarding the usage of suprapubic tube (SPT) versus indwelling urethral catheter (IUC) after robot-assisted radical prostatectomy (RARP). Recent Findings: Available data on the use of SPT for urinary drainage after RARP is somewhat limited mostly because of the variations of study designs and non-standardized outcomes. Although it may provide some mild benefit in terms of catheter-related pain and discomfort, the benefit seems not to be clinically significant. Summary: The evidence in the literature so far does not support routine usage of SPT as the primary urinary drainage method after RARP. Further higher-quality studies that can show clinically significant advantages over IUC are still needed to justify its usage. [ABSTRACT FROM AUTHOR]

Prior work has shown that gamer loyalty is important for the sales of a developer's future games. Therefore, it is important for game developers to increase the longevity of their games. However, game developers cannot always meet the growing and changing needs of the gaming community, due to the often already overloaded schedules of developers. So-called modders can potentially assist game developers with addressing gamers' needs. Modders are enthusiasts who provide modifications or completely new content for a game. By supporting modders, game developers can meet the rapidly growing and varying needs of their gamer base. Modders have the potential to play a role in extending the life expectancy of a game, thereby saving game developers time and money, and leading to a better overall gaming experience for their gamer base. In this paper, we empirically study the metadata of 9,521 mods that were extracted from the Nexus Mods distribution platform. The Nexus Mods distribution platform is one of the largest mod distribution platforms for PC games at the time of our study. The goal of our paper is to provide useful insights about mods on the Nexus Mods distribution platform from a quantitative perspective, and to provide researchers a solid foundation to further explore game mods. To better understand the potential of mods to extend the longevity of a game we study their characteristics, and we study their release schedules and post-release support (in terms of bug reports) as a proxy for the willingness of the modding community to contribute to a game. We find that providing official support for mods can be beneficial for the perceived quality of the mods of a game: games for which a modding tool is provided by the original game developer have a higher median endorsement ratio than mods for games that do not have such a tool. In addition, mod users are willing to submit bug reports for a mod. However, they often fail to do this in a systematic manner using the bug reporting tool of the Nexus Mods platform, resulting in low-quality bug reports which are difficult to resolve. Our findings give the first insights into the characteristics, release schedule and post-release support of game mods. Our findings show that some games have a very active modding community, which contributes to those games through mods. Based on our findings, we recommend that game developers who desire an active modding community for their own games provide the modding community with an officially-supported modding tool. In addition, we recommend that mod distribution platforms, such as Nexus Mods, improve their bug reporting system to receive higher quality bug reports. [ABSTRACT FROM AUTHOR]

Background: Robot-assisted radical prostatectomy (RARP) can generally be performed with 1–2 nights of postoperative monitoring before discharge from the hospital. Little is known about what causes individual patients to remain in hospital beyond the second postoperative day. Methods: Data for RARPs performed between 2013 and 2015 were extracted from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database. The fraction of cases with prolonged length of stay (PLOS) that can be reasonably attributed to complications was examined. Logistic regression was performed to identify risk factors for PLOS in the overall population and separately in the population of patients with PLOS without any perioperative complications. Results: Of 11,440 patients, 10,342 (90.4%) were discharged on postoperative days 0–2; 80.6% (887/1101) of patients with PLOS did not experience any perioperative complications. The most common complication was bleeding requiring transfusion, but this was present in only 5.6% (62/1101) of patients with PLOS. Logistic regression identified predictors of PLOS as age, race, wound class, American Society of Anesthesiologists class, smoking, diabetes, dyspnea, dependent functional health status, congestive heart failure, operative time, and pelvic lymph node dissection. Results of this regression were insensitive to the exclusion of patients who experienced no perioperative complications. Conclusions: This study utilizes logistic regression on NSQIP data to identify risk factors for PLOS after RARP and, in particular, to evaluate the role of postoperative complications in PLOS. The analysis shows that postoperative complications account for a small minority of cases of PLOS after RARP. [ABSTRACT FROM AUTHOR]

Purpose of Review: Surgeons have played a significant role in the current opioid epidemic through overprescribing practices in the postoperative setting. However, contemporary efforts have helped to decrease opioid excess, particularly in the field of urology. Minimally invasive surgery offers a unique avenue to address overuse of narcotics in the postoperative period given its emphasis on enhanced recovery. Recent Findings: Historically, the majority of the literature characterizing postoperative opioid use and its reduction has focused on non-urological surgery. However, recent studies have shown that patients undergoing urologic procedures are prescribed opioids in a similar manner as patients in other surgical specialties. Reduction strategies have been implemented through the use of regional anesthesia, enhanced recovery after surgery pathways, and the development of procedure-specific opioid prescription recommendations. Summary: Patients undergoing urologic surgery experience the same risk of opioid misuse and abuse as patients undergoing other types of surgery. However, the wide use of minimally invasive urological surgeries including robotic surgery offers a unique opportunity to reduce postoperative opioid use through multimodal and interdisciplinary protocols and standardizing guidelines. [ABSTRACT FROM AUTHOR]

Benign prostatic hyperplasia (BPH), a nonmalignant enlargement of the prostate, is among the most common diseases affecting aging men, but the underlying molecular features remain poorly understood, and therapeutic options are limited. Here we employ a comprehensive molecular investigation of BPH, including genomic, transcriptomic and epigenetic profiling. We find no evidence of neoplastic features in BPH: no evidence of driver genomic alterations, including low coding mutation rates, mutational signatures consistent with aging tissues, minimal copy number alterations, and no genomic rearrangements. At the epigenetic level, global hypermethylation is the dominant process. Integrating transcriptional and methylation signatures identifies two BPH subgroups with distinct clinical features and signaling pathways, validated in two independent cohorts. Finally, mTOR inhibitors emerge as a potential subtype-specific therapeutic option, and men exposed to mTOR inhibitors show a significant decrease in prostate size. We conclude that BPH consists of distinct molecular subgroups, with potential for subtype-specific precision therapy. Benign prostatic hyperplasia (BPH) is one of the most common diseases affecting aging men with limited therapeutic options. In this study, the authors describe the molecular characterization of BPH performing genomic, transcriptomic and epigenetic analysis of 18 BPH cases. [ABSTRACT FROM AUTHOR]