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Highly ordered spaced titanium dioxide nanotubes were fabricated via electrochemical anodization and modified with titania nanoparticles and copper oxides. Such materials were rapidly annealed in hydrogen atmosphere or conventionally in a tube furnace in air, in which the temperature slowly increases. Applied synthesis procedure can be considered as simple, cost-effective, and environmentally friendly as it allows for reduction in used materials and enhances sustainable engineering. Manipulating the chemical composition of materials by different thermal treatments resulted in various photoelectrochemical activities and density of CO2 adsorption sites. Rapidly annealed nanotubes decorated by copper oxides exhibit excellent electrochemical properties where one electrode combines both: solar to electricity conversion (photocurrent under visible light 30 µA/cm2) and CO2 adsorption systems (18 times higher current after CO2 saturation). Rapidly thermal hydrogenated TiO2 nanotubes with copper oxides had 17 times higher photocurrent and wider absorption band (380–780 nm) than conventionally annealed ones. Furthermore, the crystal planes such as Cu (111), Cu (220), Cu2O (110), CuO (002) and Cu0, Cu+, Cu2+ oxidation states, and oxygen vacancies were recognized for hydrogenated sample. It should be highlighted that thermal annealing conditions significantly affects ability of copper oxide to CO2 adsorption and CO2 reduction reaction for hydrogenated electrode. [ABSTRACT FROM AUTHOR]

Purpose: Bariatric surgery is considered the main treatment option for patients with severe obesity. The objective of our study is to compare intra- and postoperative outcomes between the robotic and laparoscopic approaches within the sleeve gastrectomy (SG), duodenal switch (DS), and Roux-en-Y gastric bypass (RYGB). Materials and Methods: The data from the MBSAQIP were collected for patients who underwent SG, DS, and RYGB between 2015 and 2021. The postoperative and procedural outcomes including 30-day morbidity and mortality as well as operation length were analyzed using regression models. Results: Our analysis included 1,178,886 surgeries with SG comprising the majority (70%) followed by RYGB (28%) and DS (1%). Other than a higher adjusted risk of unplanned reoperation for robotic RYGB (relative risk (RR) 1.07) and a statistically significant higher rate of postoperative wound disruption in robotic SG for robotic surgery (RR 1.56), there were no statistically significant between-approach differences including infection, wound disruption, death, or reoperation for DS, RYGB, or SG. Our data showed no significant difference in anastomotic leak rate between laparoscopic and robotic approaches in either the DS (p = 0.521) or RYGB (p = 0.800) procedures. Across our study period, the median operation lengths decreased significantly per year for both the robotic SG and DS. Conclusions: Robotic and laparoscopic bariatric surgical procedures have statistically similar 30-day patient outcomes. Robotic bariatric procedures do have significantly longer median operative times than laparoscopic procedures. The decision to use a robotic approach or laparoscopic approach should be made based upon surgeon experience and possibly cost. [ABSTRACT FROM AUTHOR]

Introduction: Informed consent is essential in ensuring patients' understanding of their medical condition, treatment, and potential risks. The objective of this study was to investigate the impact of utilizing a video consent compared to standard consent for patient knowledge and satisfaction in selected general surgical procedures. Methods and procedures: We included 118 patients undergoing appendectomy, cholecystectomy, inguinal hernia repair, and fundoplication at two hospitals in Omaha, NE. Patients were randomized to either a standard consent or a video consent. Outcomes included a pretest and posttest objective knowledge assessment of their procedure, as well as a satisfaction survey which was completed immediately after consent and following discharge. Given the pre-post design, a linear mixed-effect model was estimated for both outcomes. A two-way interaction effect was of primary interest to assess whether pre-to-post change in the outcome differed between patients randomized to standard or video consent. Results: Baseline characteristics were mostly similar between groups except for patient sex, p = 0.041. Both groups showed a statistically significant increase in knowledge from pretest to posttest (standard group: 0.25, 95% CI 0.01 to 0.51, p = 0.048; video group: 0.68, 95% CI 0.36 to 1.00, p < 0.001), with the video group showing significantly greater change (interaction p = 0.043) indicating that incorporating a video into the consent process resulted in a better improvement in patient's knowledge of the proposed procedure. Further, both groups showed a decrease in satisfaction post-discharge, but no statistically significant difference in the magnitude of decrease between the groups (interaction p = 0.309). Conclusion: Video consent lead to a significant improvement in a patient's knowledge of the proposed treatment. Although the patient satisfaction survey didn't show a significant difference, it did show a trend. We propose incorporating videos into the consent process for routine general surgical procedures. [ABSTRACT FROM AUTHOR]

Metallosis is an unusual but consequential complication arising from orthopedic hardware implantation, characterized by the deposition of metallic particles in the periprosthetic soft tissues. The incidence of metallosis associated with shoulder arthroplasties is exceptionally rare since the shoulder is not a weight-bearing joint, making it less susceptible to mechanical wear and, consequently, to conditions like particle disease and metallosis. Nevertheless, anomalous metal-on-metal interactions can develop in total shoulder arthroplasties if the polyethylene component fails due to wear, fracture, or dissociation. If left unaddressed, metallosis can incite an adverse immune-mediated local tissue response, culminating in joint destruction and adjacent soft tissues and muscle necrosis. In this case report, the diagnosis of metallosis was made in a patient with an anatomic total shoulder arthroplasty using a state-of-the-art photon counting detector CT supplemented by post-processing metal artifact reduction algorithms. This advanced imaging approach was effective in discerning the source of implant failure and in identifying manifestations of severe metallosis including osteolysis and pseudotumor formation. Advanced imaging methods can accurately characterize the severity and extent of metallosis, thereby helping guide surgical planning to mitigate serious complications associated with this condition. [ABSTRACT FROM AUTHOR]

Objectives: Clinical trials (CTs) are critical in understanding and managing cancer. However, despite being completed, CT results are often unpublished, compromising the ability to glean useful information from them. This study aimed to evaluate factors influencing the non-publication of urological oncology clinical trials. Methodology: We conducted a comprehensive search of ClinicalTrials.gov to identify CTs focused on urological cancers completed between 2000 and 2020. We used the National Clinical Trial (NCT) identifier number to check whether the trial was published. Results: 9,145 oncology CTs were conducted between 2000 and 2020, of which 8.39% (n = 767) focused on urological cancers, and 47.2% (n = 362) of these trials remained unpublished. Univariable analysis revealed that trials with a sample size of less than 50 and phase 4 were significantly associated with non-publication p < 0.001. In contrast, trials involving triple masking, a higher number of agents, and those conducted in High-Income Countries were associated with a higher likelihood of publication p < 0.05. Multivariable analysis demonstrated that trials enrolling more than 50 patients and employing three or more agents, along with triple and quadruple masking, had higher odds of being published (OR = 1.62; 95%CI (1.22–2.16), 1.89; 95%CI (1.10–3.27), 3.04; 95%CI (1.44–6.44), 5.62; 95%CI (1.72–18.37), and 5.41; 95%CI (1.76–16.67), p < 0.05, respectively). However, trials conducted in low-middle-income Countries had lower odds of publication (OR = 0.26; 95%CI (0.08–0.87), p = 0.02). Conclusion: We found that almost one-half (47.2%) of all completed urologic oncology clinical trials are not published in a PubMed-indexed journal. This non-publication rate represents a significant loss of scientific knowledge and progress. We identified several key variables including sample size. [ABSTRACT FROM AUTHOR]

Purpose of Review: Artificial intelligence (AI) is quickly demonstrating the ability to address problems and challenges in the care of IBD. This review with commentary will highlight today's advancements in AI applications for IBD in image analysis, understanding text, and replicating clinical knowledge and experience. Recent Findings: Advancements in machine learning methods, availability of high-performance computing, and increasing digitization of medical data are providing opportunities for AI to assist in IBD care. Multiple groups have demonstrated the ability of AI to replicate expert endoscopic scoring in IBD, with expansion into automated capsule endoscopy, enterography, and histologic interpretations. Further, AI image analysis is being used to develop new endoscopic scoring with more granularity and detail than is possible using conventional methods. Advancements in natural language processing are proving to reduce laborious tasks required in the care of IBD, including documentation, information searches, and chart review. Finally, large language models and chatbots that can understand language and generate human-like replies are beginning to exhibit clinical intelligence that will revolutionize how we deliver IBD care. Summary: Today, AI is being deployed to replicate expert judgement in specific tasks where disagreement, subjectivity, and bias are common. However, the near future will herald contributions of AI doing what we cannot, including new detailed measures of IBD, enhanced analysis of images, and perhaps even fully automating care. As we speculate on future technologic capabilities that may improve how we care for IBD, this review will also consider how we will implement and fairly use AI in practice. [ABSTRACT FROM AUTHOR]

Purpose of Review: Physical pain is an underrecognized area of dysregulation among those with borderline personality disorder (BPD). Disturbances are observed within the experience of acute, chronic, and everyday physical pain experiences for people with BPD. We aimed to synthesize research findings on multiple areas of dysregulation in BPD in order to highlight potential mechanisms underlying the association between BPD and physical pain dysregulation. Recent Findings: Potential biological mechanisms include altered neural responses to painful stimuli within cognitive-affective regions of the brain, as well as potentially low basal levels of endogenous opioids. Emotion dysregulation broadly mediates dysregulation of physical pain. Certain psychological experiences may attenuate acute physical pain, such as dissociation, whereas others, such as negative affect, may exacerbate it. Social challenges between patients with BPD and healthcare providers may hinder appropriate treatment of chronic pain. Summary: Dysregulated physical pain is common in BPD and important in shaping health outcomes including elevated BPD symptoms, chronic pain conditions, and risk for problematic substance use. [ABSTRACT FROM AUTHOR]

Purpose: Bariatric surgery has been reported to produce durable weight loss in the management of obesity; sleeve gastrectomy (SG) is the most common bariatric procedure. Obesity is a common comorbidity of inflammatory bowel disease (IBD), and the impact of IBD on short-term SG outcomes has not been widely reported. This study assessed whether IBD was associated with adverse post-SG outcomes. Materials and Methods: Hospitalizations of patients undergoing SG in the United States were identified using the 2010–2020 Nationwide Readmissions Database (NRD) and stratified by IBD diagnosis. The SG cohort was propensity-matched based on age, biological sex, body mass index (BMI), comorbid diabetes, hypertension, depression, chronic obstructive pulmonary disease, and discharge in quarter four. Primary aims were to compare in-hospital mortality, post-operative complications, and all-cause 90-day readmission between patients with and without IBD. Secondary outcomes were length of stay (LOS) and total hospital cost. Results: A total of 2030 hospitalizations were matched. The odds of complication were 48% higher for hospitalizations of patients with IBD (11.1% vs. 7.8%; aOR 1.48, aOR 95% CI 1.10–2.00, p =.009). The most common complication was nausea (4.9% vs. 3.7%, p =.187). No statistically significant difference was observed for all-cause 90-day readmissions, LOS, or hospital cost. Conclusion: Hospitalizations of patients with IBD who underwent SG experienced significantly higher post-operative complication rates. However, the similar lengths of stay and readmission rates compared to propensity-matched SG hospitalizations without IBD suggest many complications were minor. SG remains a safe weight loss procedure for patients suffering from IBD and obesity. [ABSTRACT FROM AUTHOR]

Objectives: Parole is an important mechanism for alleviating the extraordinary social and financial costs of mass incarceration. Yet parole boards can also present a major obstacle, denying parole to low-risk inmates who could safely be released from prison. We evaluate a major parole institution, the New York State Parole Board, quantifying the costs of non-risk-based decision-making. Methods: Using ensemble machine Learning, we predict any arrest and any violent felony arrest within three years to generate criminal risk predictions for individuals released on parole in New York from 2012–2015. We quantify the social welfare loss of the Board's non-risked-base decisions by rank ordering inmates by their predicted risk and estimating the crime rates that could have been achieved with counterfactual, risk-based release decisions. We also estimate the release rates that could have been achieved holding arrest rates constant. We attend to the "selective labels" problem in several ways, including by testing the validity of the algorithm for individuals who were denied parole but later released after the expiration of their sentence. Results: We conservatively estimate that the Board could have more than doubled the release rate without increasing the total or violent felony arrest rate, and that they could have achieved these gains while simultaneously eliminating racial disparities in release rates. Conclusions: This study demonstrates the utility of algorithms for evaluating criminal justice decision-making. Our analyses suggest that many individuals are being denied parole and incarcerated past their minimum sentence despite being a low risk to public safety. [ABSTRACT FROM AUTHOR]

The linear production and consumption of plastics today is unsustainable. It creates large amounts of unnecessary and mismanaged waste, pollution and carbon dioxide emissions, undermining global climate targets and the Sustainable Development Goals. This Perspective provides an integrated technological, economic and legal view on how to deliver a circular carbon and plastics economy that minimizes carbon dioxide emissions. Different pathways that maximize recirculation of carbon (dioxide) between plastics waste and feedstocks are outlined, including mechanical, chemical and biological recycling, and those involving the use of biomass and carbon dioxide. Four future scenarios are described, only one of which achieves sufficient greenhouse gas savings in line with global climate targets. Such a bold system change requires 50% reduction in future plastic demand, complete phase-out of fossil-derived plastics, 95% recycling rates of retrievable plastics and use of renewable energy. It is hard to overstate the challenge of achieving this goal. We therefore present a roadmap outlining the scale and timing of the economic and legal interventions that could possibly support this. Assessing the service lifespan and recoverability of plastic products, along with considerations of sufficiency and smart design, can moreover provide design principles to guide future manufacturing, use and disposal of plastics.Four future greenhouse gas emission scenarios for the global plastics system are investigated, with the lead scenario achieving net-zero emissions, and a series of technical, legal and economic interventions recommended. [ABSTRACT FROM AUTHOR]

Biolubricants are bio-based compounds that represent a renewable and biodegradable alternative to petroleum-based lubricants. Although biolubricant applications appear promising, their commercial deployment is still limited. Research in the field of biolubricants is continuously developing to improve their properties as well as their production processes, with the aim of overcoming the current limitations and enhance large-scale application. This review paper aims at reviewing the most recent developments in the ever-evolving field of biolubricant synthesis, focusing on novel feedstocks and catalysts, as well as new chemical modification routes and additive components that aim at further improving their sustainability. Moreover, to bridge the gap between small-scale synthesis and industrial realization, techno-economic and life cycle studies aiming at assessing the feasibility of large-scale biolubricant production are also reviewed. Finally, some considerations and future prospects are discussed based on the key findings of the analysis, which revealed that, while considerable effort is being made to improve the properties and the sustainability of biolubricants, significant work has yet to be done in terms of design and optimization of an industrial-scale process. [ABSTRACT FROM AUTHOR]

Background: Over the past 2 decades, there has been a growing interest in the significance of gender roles in healthcare and several efforts and initiatives have focused on increasing female representation in the medical field. Clinical trials play a very important role in shaping medical practice; moreover, the leaders of clinical trials often represent the upper echelon of researchers in any designated field. Presently, there is no data regarding women’s representation in urological oncology clinical trials leadership. Therefore, the aim of this study is to examine the extent of female representation in leading urological clinical trials. Methodology: To thoroughly examine the representation of females as principal investigators (PIs) in urological cancer clinical trials between 2000 and 2020, we conducted a comprehensive search of completed trials focused on kidney, prostate, and bladder cancer on ClinicalTrials.gov. We extracted relevant information regarding the PIs and analyzed the data using univariate analyses to identify any significant differences between male and female PIs. Results: A total of 9145 cancer clinical trials were conducted over the last 2 decades, and 11.3% (n = 1033) of them were urological cancer clinical trials. We were able to obtain detailed information about the principal investigators (PI) in 79.0% (n = 816) of the clinical trials, and we found that 16.8% (n = 137) of them were led by female investigators. Upon evaluating the characteristics of the PIs, female PIs had a significantly lower median age and median total citations as compared to male PIs (55.0 vs 59.0 and 5333 vs 7902; p-value < 0.001 and 0.006, respectively). However, there was no statistically significant difference between the termination rate, publication rate, funding source, cancer type, and the subject of conducting the clinical trials between male and female PIs. Conclusion: Between 2000 and 2020, only 16.8% of urological cancer clinical trials were led by a female PI, perhaps reflective of a low percentage of senior female researchers in the fields of urology, oncology and radiation oncology. Universities, research institutes and funding agencies should work to improve mentorship, representation and opportunities for female investigators to encourage more involvement for female researchers in these clinical trials. [ABSTRACT FROM AUTHOR]

Purpose of review: Artificial intelligence (AI) is quickly evolving and will be integral to the management of IBD patients. In this review, we provide an overview of technologies powering applications for Crohn's disease and ulcerative colitis, with particular attention to information extraction from imaging and text records. Recent findings: Recent data highlight machine learning capability to replicate expert interpretation and judgment at population scale with accuracy in endoscopic and histology disease grading. Computer vision techniques are also detecting important findings difficult for even expert clinicians to reliably appreciate, including dysplasia on colonoscopy and fibrosis on CT and MRI imaging. Further, segmentation and radiomics can extract more information than manually possible, enabling new possibilities for disease measurement. Finally, natural language processing (NLP) is showing promise automatically extracting IBD-related medical concepts from text and generating conversational responses for both clinicians and patients. Summary: Quickly mounting evidence supports AI reliability grading disease severity in endoscopy, histology, and imaging. In particular use cases, AI can surpass the ability of humans for disease feature detecting and the generation of new measures of IBD activity. Ultimately, AI-powered information extraction will provide significant incremental improvement in the personalization predictions of outcomes and treatment course in IBD. [ABSTRACT FROM AUTHOR]

Purpose of Review: Despite significant negative outcomes, the co-occurrence of personality disorders (PDs) and substance use disorders (SUDs) continues to be underrecognized, and the mechanisms contributing to this co-occurrence remain unclear. This review summarizes recent work on PD-SUD co-occurrence, with a focus on borderline and antisocial PDs, general substance use patterns among those with PDs, and the association of personality traits with SUDs. Recent Findings: The prevalence of co-occurring PD-SUD is generally high, with estimates ranging depending on the type of PD and SUD, the population assessed, and the sampling methods and measures used. Current theoretical explanations for co-occurrence include shared etiology and predisposition models, with research highlighting the importance of transactional processes. Potential underlying mechanisms include personality traits and transdiagnostic characteristics. Summary: Recent research has increased focus on substances besides alcohol, dimensional models of personality pathology, and transactional explanations of co-occurrence, but more research is needed to disentangle the nuanced PD-SUD relationship. [ABSTRACT FROM AUTHOR]

Western, northern, Mexican, and southern corn rootworms (WCR, NCR, MCR, and SCR) are serious corn pests. We evaluated host search behavior of these pests on six plant species using a video tracking system. After a 5-min exposure to plant roots, behavioral parameters were automatically recorded and used to quantify the search behavior. The search behavior was not observed for sorghum since no neonates survived after contacting sorghum roots. After exposures to corn roots, all neonates exhibited the localized search behaviors (i.e., shortening total distance traveled, lowering movement speed, increasing turn angle, moving farther from origin) which are used to stay in and search within root systems. When larvae contacted roots of wheat, barley, oats, soybean, or controls, they expanded the search area by extending the travel path, increasing velocity, and reducing turn angles and total distance moved. The intensity of the search expansion is highly associated with the host preferences known for the four rootworm species and subspecies. Neonates of each corn rootworm exhibited distinct search behaviors. In fact, NCR larvae had the highest speed, the greatest travel path, and the lowest turn angle, whereas MCR larvae had the highest turn angle and moved faster than WCR and SCR larvae. [ABSTRACT FROM AUTHOR]

Introduction: Daptomycin doses 8–12 mg/kg are recommended for susceptible dose-dependent Enterococcus species. However, data remain limited on safety outcomes of such dosing, compared to standard 4–6 mg/kg dosing. Methods: In this retrospective cohort study, patients were stratified into daptomycin standard-dose (≤ 6.5 mg/kg) versus high-dose (≥ 7.5 mg/kg) groups. The primary outcome was daptomycin safety based on a composite of creatine kinase elevation, daptomycin-related peripheral blood eosinophilia, eosinophilic pneumonitis, alanine aminotransferase elevation, and alkaline phosphatase elevation. A secondary aim was to identify risk factors for daptomycin adverse effects. Inclusion criteria were age ≥ 18 years old, daptomycin receipt for ≥ 48 h, and Enterococcus cultures with a daptomycin minimal inhibitory concentration 2–4 mg/L. Results: A total of 119 patients were included for analysis. Median daptomycin doses were 6.0 mg/kg (IQR 5.4, 6.1) and 8.1 mg/kg (IQR 7.9, 9.6) in the standard- and high-dose cohorts, respectively. Median durations were 13.5 days (standard-dose) and 16 days (high-dose) (p = 0.02). The composite safety endpoint occurred in 32.0% of the standard-dose group and 32.5% of the high-dose group (p = 0.96). Daptomycin was dose-reduced or held in 8.1% of patients experiencing an adverse effect. Concurrent antihistamine usage was associated with the composite outcome; however, there was no association with daptomycin dose or concurrent statin use. Conclusion: High-dose daptomycin was not associated with increased laboratory abnormalities or adverse drug reactions compared to standard-dose daptomycin. [ABSTRACT FROM AUTHOR]

Understanding the chemistry underpinning intermetallic synergy and the discovery of generally applicable structure-performances relationships are major challenges in catalysis. Additionally, high-performance catalysts using earth-abundant, non-toxic and inexpensive elements must be prioritised. Here, a series of heterodinuclear catalysts of the form Co(III)M(I/II), where M(I/II) = Na(I), K(I), Ca(II), Sr(II), Ba(II) are evaluated for three different polymerizations, by assessment of rate constants, turn over frequencies, polymer selectivity and control. This allows for comparisons of performances both within and between catalysts containing Group I and II metals for CO2/propene oxide ring-opening copolymerization (ROCOP), propene oxide/phthalic anhydride ROCOP and lactide ring-opening polymerization (ROP). The data reveal new structure-performance correlations that apply across all the different polymerizations: catalysts featuring s-block metals of lower Lewis acidity show higher rates and selectivity. The epoxide/heterocumulene ROCOPs both show exponential activity increases (vs. Lewis acidity, measured by the pKa of [M(OH2)m]n+), whilst the lactide ROP activity and CO2/epoxide selectivity show linear increases. Such clear structure-activity/selectivity correlations are very unusual, yet are fully rationalised by the polymerization mechanisms and the chemistry of the catalytic intermediates. The general applicability across three different polymerizations is significant for future exploitation of catalytic synergy and provides a framework to improve other catalysts. Understanding the intermetallic synergy and the structure-performances relationships of catalysts remains challenging. Here, the authors demonstrate a relationship between both the rates, selectivity and the s-block metal acidity in a series of heterodinuclear catalysts based on Co(III) in combination with alkali and alkaline earth metals for three different polymerization reactios. [ABSTRACT FROM AUTHOR]

This document, titled "Relationship of health-related social needs, social determinants of health, and catheter ablation utilization in atrial fibrillation: Social needs and application of atrial fibrillation ablation," explores the disparities in the utilization of catheter ablation for atrial fibrillation (AF) based on health-related social needs (HRSN) and social determinants of health (SDOH). The study found that individuals with HRSN, such as lower socioeconomic status and limited access to medical care, were less likely to receive AF ablation. Furthermore, patients with HRSN experienced higher rates of readmission, longer hospital stays, and increased hospital costs. The study suggests that further research is needed to address these disparities and improve the management of AF ablation in marginalized populations. [Extracted from the article]

Targeting protein for Xklp2 (TPX2) is a key factor that stimulates branching microtubule nucleation during cell division. Upon binding to microtubules (MTs), TPX2 forms condensates via liquid-liquid phase separation, which facilitates recruitment of microtubule nucleation factors and tubulin. We report the structure of the TPX2 C-terminal minimal active domain (TPX2α5-α7) on the microtubule lattice determined by magic-angle-spinning NMR. We demonstrate that TPX2α5-α7 forms a co-condensate with soluble tubulin on microtubules and binds to MTs between two adjacent protofilaments and at the intersection of four tubulin heterodimers. These interactions stabilize the microtubules and promote the recruitment of tubulin. Our results reveal that TPX2α5-α7 is disordered in solution and adopts a folded structure on MTs, indicating that TPX2α5-α7 undergoes structural changes from unfolded to folded states upon binding to microtubules. The aromatic residues form dense interactions in the core, which stabilize folding of TPX2α5-α7 on microtubules. This work informs on how the phase-separated TPX2α5-α7 behaves on microtubules and represents an atomic-level structural characterization of a protein that is involved in a condensate on cytoskeletal filaments. TPX2 is a key factor stimulating branching microtubule (MT) nucleation. TPX2 forms condensates on MTs critical for branching. In this work, the authors report the atomic-level structure of TPX2 C-terminal minimal active domain on MT lattice and its binding interface, determined by magic-angle-spinning NMR. [ABSTRACT FROM AUTHOR]

Purpose: Robotic-assisted (RA) bariatric surgery has been increasingly used without consistent benefit over a laparoscopic approach (LA). We compared intra- and post-operative complications and 30- and 90-day all-cause readmissions between RA and LA using the Nationwide Readmissions Database (NRD). Materials and Methods: We identified hospitalizations with adult patients who underwent RA or LA bariatric surgery from 2010 to 2019. Primary outcomes included intra- and post-operative complications and 30- and 90-day all-cause readmissions. Secondary outcomes included in-hospital death, length of stay (LOS), cost, and cause-specific readmissions. Multivariable regression models were estimated; analyses accounted for the NRD sampling design. Results: A total of 1,371,778 hospitalizations met inclusion criteria with 7.1% using RA. Patient demographic and clinical characteristics were mostly similar between groups. Adjusted odds of complication were 13% higher for RA (adjusted odds ratio [aOR]: 1.13, 95% CI: 1.03–1.23 p =.008); aORs differed across bariatric procedures. The most common complications included nausea/vomiting, acute blood loss anemia, incisional hernia, and transfusion. Adjusted odds of 30- and 90-day readmission were 10% higher for RA (aOR: 1.10, 95% CI: 1.04–1.17, p =.001 and aOR: 1.10, 95% CI: 1.04–1.16, p <.001, respectively). LOS was similar (1.6 vs. 1.6 days, p =.253); although, hospital costs were 31.1% higher for RA ($15,806 vs. $12,056, p <.001). Conclusion: RA bariatric surgery is associated with 13% higher odds of complication, 10% higher odds of readmission, and 31% hospital costs. Subsequent studies are required using databases that can include additional patient-, facility-, surgery-, and surgeon-specific characteristics. [ABSTRACT FROM AUTHOR]

Proximal spinal muscular atrophy (SMA) is a leading genetic cause for infant death in the world and results from the selective loss of motor neurons in the spinal cord. SMA is a consequence of low levels of SMN protein and small molecules that can increase SMN expression are of considerable interest as potential therapeutics. Previous studies have shown that both 4-phenylbutyrate (4PBA) and trichostatin A (TSA) increase SMN expression in dermal fibroblasts derived from SMA patients. AR42 is a 4PBA-tethered TSA derivative that is a very potent histone deacetylase inhibitor. SMA patient fibroblasts were treated with either AR42, AR19 (a related analogue), 4PBA, TSA or vehicle for 5 days and then immunostained for SMN localization. AR42 as well as 4PBA and TSA increased the number of SMN-positive nuclear gems in a dose-dependent manner while AR19 did not show marked changes in gem numbers. While gem number was increased in AR42-treated SMA fibroblasts, there were no significant changes in FL-SMN mRNA or SMN protein. The neuroprotective effect of this compound was then assessed in SMNΔ7 SMA (SMN2+/+;SMNΔ7+/+;mSmn−/−) mice. Oral administration of AR42 prior to disease onset increased the average lifespan of SMNΔ7 SMA mice by ~ 27% (20.1 ± 1.6 days for AR42-treated mice vs. 15.8 ± 0.4 days for vehicle-treated mice). AR42 treatment also improved motor function in these mice. AR42 treatment inhibited histone deacetylase (HDAC) activity in treated spinal cord although it did not affect SMN protein expression in these mice. AKT and GSK3β phosphorylation were both significantly increased in SMNΔ7 SMA mouse spinal cords. In conclusion, presymptomatic administration of the HDAC inhibitor AR42 ameliorates the disease phenotype in SMNΔ7 SMA mice in a SMN-independent manner possibly by increasing AKT neuroprotective signaling. [ABSTRACT FROM AUTHOR]

Aims: Frontal lobe epilepsy (FLE) is understudied and often misdiagnosed. We sought to comprehensively phenotype FLE and to differentiate FLE from other focal and generalised epilepsy syndromes. Methods: This was a retrospective, observational cohort study of 1078 cases of confirmed epilepsy in a tertiary neurology centre in London. Data sources were electronic health records, investigation reports and clinical letters. Results: 166 patients had FLE based on clinical findings and investigations—97 with identifiable electroencephalography (EEG) foci in frontal areas (definite FLE), while 69 had no frontal EEG foci (probable FLE). Apart from EEG findings, probable and definite FLE did not differ in other features. FLE was distinct from generalized epilepsy, which tended to present with tonic–clonic seizures and be due to genetic causes. FLE and temporal lobe epilepsy (TLE) both featured focal unaware seizures and underlying structural or metabolic aetiology. FLE, TLE and generalized epilepsy differed in their EEG (P = 0.0003) and MRI (P = 0.002) findings, where FLE had a higher rate of normal EEG and abnormal MRI findings compared to TLE. Conclusions: EEG is often normal for FLE, and abnormalities are commonly identified with MRI. There was no difference in the clinical features of definite and probable FLE, suggesting they represent the same clinical entity. The diagnosis of FLE can be made even when scalp EEG is normal. This large medical cohort provides hallmark features of FLE that differentiate it from TLE and other epilepsy syndromes. [ABSTRACT FROM AUTHOR]

Purpose: It is unclear if an elevated tibial tubercle–trochlear groove (TT–TG) distance is a risk factor for poor outcomes following ACLR. Therefore, the purpose of this study was to determine whether patients with an elevated TT–TG have an increased risk of retear following primary ACLR compared to controls with a normal TT–TG. Methods: All patients who underwent primary ACLR between July 2018 and June 2019 with an available preoperative magnetic resonance imaging (MRI) were eligible for inclusion. TT–TG distance was measured on preoperative MRI scans by two independent investigators. Clinical outcomes, return-to-sport rates, and Lysholm scores were compared between patients with a TT–TG < 12.5 mm (normal) and those with a TT–TG ≥ 12.5 mm (elevated). Results: Overall, 159 patients were included, 98 with normal TT–TG distance and 61 with elevated TT–TG distance. Patients with an elevated TT–TG distance had worse post-operative Lysholm scores than patients with a normal TT–TG distance (83.0 vs. 95.0, p = 0.010). In patients who received a bone–patellar tendon–bone (BTB) graft, an elevated TT–TG distance was associated with higher rates of subjective instability (13.0% vs. 3.0%, p = 0.041), reoperation (13.0% vs. 1.5%, p = 0.012), and post-operative complications (25.0% vs. 8.2%, p = 0.026), as well as lower ACL psychological readiness scores (324.1 vs. 446.7, p = 0.015). Conclusion: Patients with an elevated pre-operative TT–TG distance have worse Lysholm scores than patients with normal TT–TG distance. Patients with an elevated pre-operative TT–TG distance who underwent ACLR with BTB grafts had significantly higher rates of subjective instability, reoperation, and post-operative complications. Level of evidence: III. [ABSTRACT FROM AUTHOR]

Background: Dual targeted therapy (DTT) has emerged as an attractive therapeutic option for select patients with active inflammatory bowel disease (IBD) who are unable to achieve remission with biologic or small molecule monotherapy. We conducted a systematic review of specific DTT combinations in patients with IBD. Methods: We conducted a systematic search of MEDLINE, EMBASE, Scopus, CINAHL Complete, Web of Science Core Collection, and Cochrane Library to identify articles related to the use of DTT for the treatment of Crohn Disease (CD) or ulcerative colitis (UC) published before February 2021. Results: Twenty-nine studies were identified comprising 288 patients started on DTT for partially or non-responsive IBD. We identified 14 studies with 113 patients receiving anti-tumor necrosis factor (TNF) and anti-integrin therapies (i.e., vedolizumab and natalizumab), 12 studies with 55 patients receiving vedolizumab and ustekinumab, nine studies with 68 patients receiving vedolizumab and tofacitinib, five studies with 24 patients receiving anti-TNF therapy and tofacitinib, six studies with 18 patients receiving anti-TNF therapy and ustekinumab, and three studies with 13 patients receiving ustekinumab and tofacitinib. Conclusion: DTT is a promising approach to improve IBD treatment for patients with incomplete responses to targeted monotherapy. Larger prospective clinical studies are needed to confirm these findings as is additional predictive modeling to identify the patient subgroups most likely to require and benefit from this approach. [ABSTRACT FROM AUTHOR]

Purpose of Review: Antifungal stewardship has been recognized as a significant component of any antimicrobial stewardship program. In this article, we aim to provide a review of recommendations and antifungal stewardship interventions in hematologic patients. Recent Findings: Core elements of antibiotic stewardship programs can be applied to antifungal stewardship practices. Engagement of high-prescribing specialists, timely access to fungal diagnostics, screening for drug-drug interactions, and therapeutic drug monitoring are recommended practices that specifically pertain to antifungal stewardship. Tools recently developed in assessing adherence to guidelines can prove useful in evaluating prescribing practices. The most common longitudinal metrics are likely to hinge on measuring antifungal consumption. However, many of the parameters to measure antifungal stewardship activity and performance are extremely challenging to obtain. Summary: A multifaceted antifungal stewardship approach is required to improve antifungal use among hematologic patients in an efficient and sustainable manner. [ABSTRACT FROM AUTHOR]

Purpose of Review: To evaluate recent literature regarding the pathways and options for unmatched urology applicants. Recent Findings: Urology remains a competitive surgical sub-specialty with a match process independent of the National Resident Matching Program. Each year a cohort of competitive applicants go unmatched and are faced with the decision to reapply the following cycle while doing a research fellowship or a preliminary internship in the interim or choose a different specialty altogether. In this review, we sought to evaluate the current match process and literature regarding outcomes and options for unmatched applicants as well as to provide future directions for research and improvements to support unmatched urology applicants. Summary: Presently, data regarding outcomes for unmatched applicants is relatively limited. Going forward it is imperative for national urology organizations to create centralized resources for applicants to provide the best possible information for applicants and mentors alike. [ABSTRACT FROM AUTHOR]

Existing antifouling coatings for marine environments rely on the toxicity of copper and small-molecule additives to prevent organism growth. These come with a myriad of environmental and health-related risks, as these additives inevitably leach into seawater. Enzyme-based antifouling polymers have tremendous potential as part of an environmentally innocuous antifouling strategy, but have not yet been commercially realized. Biofouling begins with small molecules and polymers that initiate settlement for larger organisms. Using an enzymatic coating to rapidly hydrolyze these compounds could reduce the surface concentration of these attractive polymers and prevent organism growth. Here, antifouling xylanase and lysing complex enzymes were covalently tethered to surfaces using isoindolinone groups and click chemistry. We found that xylanase and lysing complex continue to hydrolyze xylosidic bonds in hemicellulose polysaccharides after covalent tethering, and the coating maintained activities of > 80% and > 50%, respectively, after 2 months while submerged in artificial seawater, demonstrating this material's potential as an eco-friendly antifouling coating. [ABSTRACT FROM AUTHOR]

The global plastics problem is a trifecta, greatly affecting environment, energy and climate1–4. Many innovative closed/open-loop plastics recycling or upcycling strategies have been proposed or developed5–16, addressing various aspects of the issues underpinning the achievement of a circular economy17–19. In this context, reusing mixed-plastics waste presents a particular challenge with no current effective closed-loop solution20. This is because such mixed plastics, especially polar/apolar polymer mixtures, are typically incompatible and phase separate, leading to materials with substantially inferior properties. To address this key barrier, here we introduce a new compatibilization strategy that installs dynamic crosslinkers into several classes of binary, ternary and postconsumer immiscible polymer mixtures in situ. Our combined experimental and modelling studies show that specifically designed classes of dynamic crosslinker can reactivate mixed-plastics chains, represented here by apolar polyolefins and polar polyesters, by compatibilizing them via dynamic formation of graft multiblock copolymers. The resulting in-situ-generated dynamic thermosets exhibit intrinsic reprocessability and enhanced tensile strength and creep resistance relative to virgin plastics. This approach avoids the need for de/reconstruction and thus potentially provides an alternative, facile route towards the recovery of the endowed energy and materials value of individual plastics.A new compatibilization strategy installs dynamic crosslinkers into several classes of binary, ternary and postconsumer immiscible polymer mixtures in situ, with the resulting compatibilized dynamic thermosets exhibiting intrinsic reprocessability and enhanced tensile strength and creep resistance. [ABSTRACT FROM AUTHOR]

Introduction/aims: There are disparities in the availability of systemic anticancer therapies (SACTs) globally. We set out to investigate the cost and reimbursement of SACTs in the United Kingdom (UK) and the Republic of Ireland (ROI) in conjunction with efficacy and licensing authority decisions in the United States (US) and the European Union (EU). Methods: We sought data pertaining to licensing in the EU, reimbursement in ROI/UK and cost/efficacy of SACTs licensed by the Food and Drug Administration (FDA) between January 2015 and May 2021. Independent samples t tests, chi-square test and Pearson's correlation were used for statistical analysis. Results: We identified that the majority of FDA-approved regimens are licensed by the European Medicines Agency (EMA) (n = 91, 67.9%). However, only a minority of these are currently reimbursed in the UK (n = 60, 45%) or the ROI (n = 28, 21%) as of the 1st of May 2021. In addition, only a minority of regimens have demonstrated a statistically significant OS benefit (n = 54, 40%). There was no association between cost of regimens and either the presence (t = 0.846, p = 0.40) or duration of OS benefit (t = − 0.84, p = 0.64). Conclusions: Our study highlights that many licensed systemic anticancer treatments are not currently reimbursed in ROI/UK. The high cost of these medicines is independent of the presence of an OS benefit. Collaboration between regulatory agencies, governments and industry partners is needed to ensure health expenditure is directed towards the most effective treatments. [ABSTRACT FROM AUTHOR]

The full impacts of the COVID-19 pandemic are yet to be determined. While highly effective vaccines are available to prevent and decrease the severity of COVID-19 infection, significant COVID-19 vaccine hesitancy remains. Understanding motivations, discouraging factors, opinions, and information sources regarding COVID-19 is essential to targeting vaccine hesitancy and improving vaccine uptake. A 25 question survey was administered to the patients of a free clinic in the Midwest to assess patient demographic data, opinions about and experience with COVID-19, the COVID-19 vaccines, and information sources. The main outcome of interest was if vaccination status influenced information sources and opinions regarding COVID-19. This study also analyzed motivating and discouraging factors for vaccination. The study had a total of 104 participants with 7 being excluded. There were a total of 97 survey responses included in this study, there were 79 vaccinated patients and 18 unvaccinated patients. This survey study found differences in information sources between vaccinated and unvaccinated groups. Opinions surrounding the COVID-19 vaccine, public health agencies, and perceived severity of COVID-19 also varied between vaccinated and unvaccinated groups. The differential information sources and opinions between vaccinated and unvaccinated groups emphasizes the importance of access to high-quality sources and educating the community to improve public health. [ABSTRACT FROM AUTHOR]

HIV-1 maturation inhibitors (MIs), Bevirimat (BVM) and its analogs interfere with the catalytic cleavage of spacer peptide 1 (SP1) from the capsid protein C-terminal domain (CACTD), by binding to and stabilizing the CACTD-SP1 region. MIs are under development as alternative drugs to augment current antiretroviral therapies. Although promising, their mechanism of action and associated virus resistance pathways remain poorly understood at the molecular, biochemical, and structural levels. We report atomic-resolution magic-angle-spinning NMR structures of microcrystalline assemblies of CACTD-SP1 complexed with BVM and/or the assembly cofactor inositol hexakisphosphate (IP6). Our results reveal a mechanism by which BVM disrupts maturation, tightening the 6-helix bundle pore and quenching the motions of SP1 and the simultaneously bound IP6. In addition, BVM-resistant SP1-A1V and SP1-V7A variants exhibit distinct conformational and binding characteristics. Taken together, our study provides a structural explanation for BVM resistance as well as guidance for the design of new MIs. HIV maturation inhibitors such as bevirimat (BVM) interfering with Gag processing are emerging as alternative anti-retroviral drug candidates. Here, the authors report structures of assemblies of HIV-1 Gag fragments spanning the CA C-terminal domain and SP1 region bound to BVM. [ABSTRACT FROM AUTHOR]

The traditional view that perceived and archival uncertainty measures are substitutable proxies for "true" environmental (entrepreneurial) uncertainty presumes an "all-seeing eye." Adopting a representationalist epistemology, we distinguish environmental (objective) unpredictability from entrepreneurs' subjective uncertainty, which has so far been theoretically confounded. It is, in fact, possible for an entrepreneur to be highly certain despite excessive unpredictability and vice versa. Theoretically distinguishing these constructs has fundamental implications for entrepreneurial action theory. For example, because intentional action is consciously originated, unpredictability influences action only indirectly, while uncertainty has direct effects. Outcomes, on the other hand, are directly affected by the complexity and dynamism (unpredictability) of things, whereas uncertainty only has an indirect and tenuous role in what occurs. We develop hypotheses along these theoretical lines and test them on a longitudinal sample of new mobile apps and survey responses from their developers. We find, generally, that unpredictability, uncertainty, and their effects on entrepreneurial action are empirically distinct. This provides added impetus for a shift away from positivism and toward a subjectivist approach to entrepreneurship. Plain English Summary: Distinguishing Unpredictability from Uncertainty in Entrepreneurial Action Theory. Entrepreneurship scholarship commonly references a single "entrepreneurial uncertainty" construct in discussing the effects of the unknown on entrepreneurial action. We explain that there are not one but two key constructs at play that should not be confounded: external unpredictability and subjective uncertainty. We explain, and support with evidence from the app development industry, that the unpredictability of a market environment or of entrepreneurial outcomes only has indirect influence on actions. It is the entrepreneur's own uncertainty that drives what actions they will pursue. However, the outcomes that result from action are causally tied to the real unpredictability of the market rather than the entrepreneur's uncertainty of it. As we move into the theory refinement stage of the entrepreneurship discipline, greater care must be taken in referencing one or the other (or both) in entrepreneurship theory. [ABSTRACT FROM AUTHOR]

Purpose of Review: To evaluate recent literature regarding the role of robotic technology in the treatment of nephrolithiasis with particular attention to complex technical procedures. Recent Findings: Robotic platforms including single-port robotics have been widely adopted in urological practice for the treatment of both malignant and benign conditions and has led to an expansion of the utilization of robot-assisted surgery to tackle challenging clinical scenarios such as bladder neck reconstruction, upper urinary tract reconstruction, and more recently complex stone disease. Presently, the American Urological Association guidelines on the surgical management of stones advise against using robotic, open, or laparoscopic techniques as a first-line approach for most patients with stone disease with the exception for patients with anatomical abnormalities, large or complex stones, or patients requiring a concomitant reconstructive operation. Clinicians have demonstrated the safety and feasibility of surgical robotics in the treatment of stone disease for a variety of operations including robotic pyeloplasty, pyelolithotomy, ureterolithotomy, and surgical interventions in urinary diversions as well as novel technologies for robotic ureteroscopy and percutaneous access. Summary: Numerous clinicians have demonstrated the safety and feasibility of using robot-assisted surgery to treat nephrolithiasis, mainly in complex renal anatomy. Further research is necessary to identify the best candidates for utilization of robotics in complex stone disease, and further technological developments will continue to further advance the use of these platforms in the treatment of nephrolithiasis. [ABSTRACT FROM AUTHOR]

Over the past two decades of successive clinical trials in metastatic colorectal cancer (CRC), the median overall survival of both control and experimental arms has steadily improved. However, the incremental change in survival for metastatic CRC patients not treated on trial has not yet been quantified. We performed a retrospective review of 1420 patients with de novo metastatic CRC who received their primary treatment at the University of Texas M.D. Anderson Cancer Center (UTMDACC) from 2004 through 2019. Median OS was roughly stable for patients diagnosed between 2004 and 2012 (22.6 months) but since has steadily improved for those diagnosed in 2013 to 2015 (28.8 months), and 2016 to 2019 (32.4 months). Likewise, 5-year survival rate has increased from 15.7% for patients diagnosed from 2004 to 2006 to 26% for those diagnosed from 2013 to 2015. Notably, survival improved for patients with BRAFV600E mutant as well as microsatellite unstable (MSI-H) tumors. Multivariate regression analysis identified surgical resection of liver metastasis (HR = 0.26, 95% CI, 0.19–0.37), use of immunotherapy (HR = 0.44, 95% CI, 0.29–0.67) and use of third line chemotherapy (regorafenib or trifluridine/tipiracil, HR = 0.74, 95% CI, 0.58–0.95), but not year of diagnosis (HR = 0.99, 95% CI, 0.98–1), as associated with better survival, suggesting that increased use of these therapies are the drivers of the observed improvement in survival. [ABSTRACT FROM AUTHOR]

Background: There are limited real-world data characterizing perianal fistulae in patients with Crohn's disease (CD). Aim: To describe characteristics of patients with CD with and without perianal fistulae. Methods: In this cross-sectional study, characteristics, treatment history, and health outcomes of patients with CD enrolled in the CorEvitas IBD Registry were described according to perianal fistula status (current/previous or none). Results: Eight hundred and seventy-eight patients were included. Compared with patients with no perianal fistulae (n = 723), patients with current/previous perianal fistulae (n = 155) had longer disease duration since CD diagnosis (mean 16.5 vs 12.3 years; difference 4.3 years; 95% CI, 2.0, 6.6) and fewer had Harvey–Bradshaw Index scores indicative of remission (0–4, 56.8% vs 69.6%; difference − 12.9%; 95% CI, − 21.6, − 4.2). More patients with current/previous fistulae reported a history of IBD-related emergency room visits (67.7% vs 56.1%; difference 11.6%; 95% CI, 3.4, 19.8), hospitalizations (76.1% vs 58.4%; difference 17.7%; 95% CI, 10.1, 25.4), and surgeries (59.4% vs 27.7%; difference 31.7%; 95% CI, 23.3, 40.1), and a history of treatment with tumor necrosis factor inhibitors (81.3% vs 60.7%; difference 20.6%; 95% CI, 13.5, 27.7), immunosuppressants (51.6% vs 31.2%; difference 20.4%; 95% CI, 11.9, 29.0), and antibiotics (50.3% vs 23.7%; difference 26.6%; 95% CI, 18.2, 35.1) than patients without perianal fistulae. Conclusions: Patients with CD with current/previous perianal fistulae have more symptomatic experiences of disease, higher medication use, hospitalization rates, and emergency room visits than patients without perianal fistulae. Interventions to prevent/reduce risk of developing fistulae may help improve outcomes in CD. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this work is to describe real-world biologic-experienced psoriasis patients initiating ixekizumab by prior biologic therapy status and compare the effectiveness of ixekizumab between patients who previously failed secukinumab and those who failed other biologics. We hypothesized that (1) clinical outcomes and patient-reported outcomes would improve following a switch to IXE, and (2) there would be no differences in responses between patients who previously failed secukinumab and those who failed other biologics. Methods: Participants (n = 419) included adult psoriasis patients enrolled in the CorEvitas Psoriasis Registry through 9/10/20 who switched to ixekizumab after discontinuing another biologic. Patients were classified by the biologic used immediately prior to ixekizumab and reason for discontinuation: prior secukinumab failure; prior secukinumab non-failure; prior other biologic failure; and prior other biologic non-failure. Discontinuations for efficacy reasons were considered failures; all others were considered non-failures. Baseline descriptive statistics were calculated. Multivariable Poisson regression models estimated the likelihood of response of other failure relative to secukinumab failure. Results: Mean age was 51 years; 48% were women. Psoriasis disease characteristics were similar across prior biologic groups. At 6-month follow-up, disease severity improved for all who initiated ixekizumab after discontinuing another biologic. Secukinumab failure patients who switched to ixekizumab achieved BSA ≤ 1 (49%), BSA ≤ 3 (59%), PASI75 (46%), PASI ≤ 3 (64%), and IGA ≤ 1 (40%). Other failure patients achieved BSA ≤ 1 (55%), BSA ≤ 3 (72%), PASI75 (59%), PASI ≤ 3 (74%), and IGA ≤ 1 (54%). In regression modeling, we observed patients in the other biologics failure group had an increased likelihood of achieving response for BSA ≤ 3, PASI75, PASI90, PASI100, and IGA ≤ 1 compared to patients who failed secukinumab. Conclusions: These findings suggest that patients with psoriasis who switch to ixekizumab after discontinuing another biologic demonstrate improvement in disease severity after six months. Patients who discontinued biologics other than secukinumab may be more likely to respond to ixekiziumab compared to those who switched from secukinumab. [ABSTRACT FROM AUTHOR]

Microtubules (MTs) and their associated proteins play essential roles in maintaining cell structure, organelle transport, cell motility, and cell division. Two motors, kinesin and cytoplasmic dynein link the MT network to transported cargos using ATP for force generation. Here, we report an all-atom NMR structure of nucleotide-free kinesin-1 motor domain (apo-KIF5B) in complex with paclitaxel-stabilized microtubules using magic-angle-spinning (MAS) NMR spectroscopy. The structure reveals the position and orientation of the functionally important neck linker and how ADP induces structural and dynamic changes that ensue in the neck linker. These results demonstrate that the neck linker is in the undocked conformation and oriented in the direction opposite to the KIF5B movement. Chemical shift perturbations and intensity changes indicate that a significant portion of ADP-KIF5B is in the neck linker docked state. This study also highlights the unique capability of MAS NMR to provide atomic-level information on dynamic regions of biological assemblies. In this work the authors report the structure of nucleotide-free kinesin-1 motor domain (apo-KIF5B) in complex with paclitaxel-stabilized microtubules using magic-angle-spinning (MAS) NMR spectroscopy. The study provides insights into the dynamic changes under which the neck linker goes upon binding to ADP. [ABSTRACT FROM AUTHOR]

In the American Midwest, grasslands are highly diverse, endangered ecosystems that require conservation and restoration because they face the threat of plant species invasions. Pyrus calleryana (Decne.; Rosaceae) is a particularly problematic invasive tree in these ecosystems and relatively little is known about the factors that dictate its success. Landscape features regulate the spread of some invasive plants and may play an important role in dictating the vulnerability of grasslands to P. calleryana invasion. Towards developing a predictive framework for grassland invasion, we performed a fine-scale spatial assessment of invaded and uninvaded prairies to determine if landscape characteristics including proximity to forest edge, roads or residences, plant communities or soil characteristics could be used to predict P. calleryana invasion. We found increased invasion near forest edges, likely due to bird dispersal and optimal foraging habitats. Within invaded prairies, P. calleryana was prevalent where there was lower ground cover by grasses and forbs and where there was limited organic matter but increased soil phosphorus, nitrate and micronutrients. This study could not determine if P. calleryana caused these changes or if it established because these parameters were favorable. Our data also indicated an intriguing relationship of increased species richness in P. calleryana invaded sites, potentially because uninvaded sites were characterized by dominant grasses that may reduce available niche space. Taken together, this work suggests that P. calleryana establishment depends on the relative propagule pressure and niche availability and indicates potential for developing a predictive framework for landscape invasion. [ABSTRACT FROM AUTHOR]

Robotic-assisted laparoscopic radical prostatectomy represents one of the most common operations in urologic oncology and involves several critical technical steps including pelvic lymph node dissection, cavernous nerve sparing and vesicourethral anastomosis. The quality of performing these steps is linked to functional and oncological outcomes. Indocyanine green [ICG] is a non-radioactive, water-soluble compound which allows for enhanced visualization with near-infrared fluorescence of both anatomical structures and vasculature during complex abdominal operations such as prostatectomy. During the last decade, several investigators have examined the value and role of ICG fluorescence during prostatectomy. In this review, we sought to evaluate the body of evidence for fluorescence-guided robotic prostatectomy as well as assess potential future areas of investigation with this technology. [ABSTRACT FROM AUTHOR]

Flow is a subjective state characterized by immersion and engagement in one's current activity. The benefits of flow for productivity and health are well-documented, but a rigorous description of the flow-generating process remains elusive. Here we develop and empirically test a theory of flow's computational substrates: the informational theory of flow. Our theory draws on the concept of mutual information, a fundamental quantity in information theory that quantifies the strength of association between two variables. We propose that the mutual information between desired end states and means of attaining them — I (M ; E) — gives rise to flow. We support our theory across five experiments (four preregistered) by showing, across multiple activities, that increasing I (M ; E) increases flow and has important downstream benefits, including enhanced attention and enjoyment. We rule out alternative constructs including alternative metrics of associative strength, psychological constructs previously shown to predict flow, and various forms of instrumental value. Flow is a desired but elusive state characterized by the subjective experience of immersion and engagement in an activity. Here, the authors develop and empirically validate a formal model that specifies variables and computations involved in the subjective experience of flow. [ABSTRACT FROM AUTHOR]

Rationale: Synthetic opioids like fentanyl are contributing to the rise in rates of opioid use disorder and drug overdose deaths. Sleep dysfunction and circadian rhythm disruption may worsen during opioid withdrawal and persist during abstinence. Severe and persistent sleep and circadian alterations are putative factors in opioid craving and relapse. However, very little is known about the impact of fentanyl on sleep architecture and sleep–wake cycles, particularly opioid withdrawal. Further, circadian rhythms regulate sleep–wake cycles, and the circadian transcription factor, neuronal PAS domain 2 (NPAS2) is involved in the modulation of sleep architecture and drug reward. Here, we investigate the role of NPAS2 in fentanyl-induced sleep alterations. Objectives: To determine the effect of fentanyl administration and withdrawal on sleep architecture, and the role of NPAS2 as a factor in fentanyl-induced sleep changes. Methods: Electroencephalography (EEG) and electromyography (EMG) was used to measure non-rapid eye movement sleep (NREMS) and rapid eye movement sleep (REMS) at baseline and following acute and chronic fentanyl administration in wild-type and NPAS2-deficient male mice. Results: Acute and chronic administration of fentanyl led to increased wake and arousal in both wild-type and NPAS2-deficient mice, an effect that was more pronounced in NPAS2-deficient mice. Chronic fentanyl administration led to decreased NREMS, which persisted during withdrawal, progressively decreasing from day 1 to 4 of withdrawal. The impact of fentanyl on NREMS and arousal was more pronounced in NPAS2-deficient mice. Conclusions: Chronic fentanyl disrupts NREMS, leading to a progressive loss of NREMS during subsequent days of withdrawal. Loss of NPAS2 exacerbates the impact of fentanyl on sleep and wake, revealing a potential role for the circadian transcription factor in opioid-induced sleep changes. [ABSTRACT FROM AUTHOR]

Experiences with more subtle racism – which have been called microaggressions – have a host of negative effects on health, mental health, educational performance, and general well-being on people of color. In this study we draw on a longitudinal dataset of Black, Latinx, and Asian students in higher education and use the microaggression framework to distinguish between the types of reported subtle experiences with discrimination, including (1) classroom-based, or perceived discrimination or discomfort in the classroom; (2) microassaults, or verbal assaults; (3) discomfort, or perceived discomfort on campus because of race, (4) criminality, which refers to both being stopped by University police and (5) refusal to acknowledge intra-racial differences, which here describes experiences with intraracial microaggressions. Our findings explore (1) the differential effects of different types of microaggressions on symptoms of depression (2) intergroup differences in effects of microaggressions on depression and (3) the differential effects of different types of microaggressions over time. [ABSTRACT FROM AUTHOR]

The extant literature offers inconsistent predictions and conflicting evidence regarding the relationship between state ownership and the internationalization of emerging market firms (EMFs). Drawing on institutional theory, we examine the moderating roles of political and economic institutions at the subnational and national levels in the link between state ownership and EMFs' outward foreign direct investment (OFDI). Based on a sample of 1421 OFDI projects involving 286 Chinese listed firms in 115 host countries between 2003 and 2016, we find that state ownership can scale up OFDI when Chinese firms are headquartered in subnational regions with high institutional development or low economic development, or when political relationships between home and host countries are amicable or market growth in a host country is slow; otherwise, state ownership hinders OFDI. These findings offer new insights into the relationship between state ownership and the internationalization of EMFs. [ABSTRACT FROM AUTHOR]

The use of selective serotonin reuptake inhibitors (SSRIs) can increase the risk of gastrointestinal (GI) bleeding. Similarly, it is well known that the use of NSAIDs predisposes patients to upper GI bleeding. The aim of this study was to explore if the addition of SSRIs in patients already taking NSAIDs significantly increases their risk for upper GI bleeding. An electronic literature search was conducted using the SCOPUS and MEDLINE databases from inception through September 2020. Cohort and case–control trials that reported patients with upper GI bleeding on NSAIDs with SSRIs, compared to controls on NSAIDs only were included. Newcastle–Ottawa checklist was used to ensure inclusion of high-quality studies. Data was extracted by the lead investigator and cross-checked by the second author. Dichotomous data was pooled to obtain an odds ratio (OR) of the risk of upper GI bleeding in patients on NSAIDs with concomitant SSRI use. The primary endpoint of the study was the risk of upper GI bleeding with SSRIs and NSAIDs compared to NSAIDs alone. A total of 366 citations were reviewed, and 21 were selected for full-text evaluation. 1 cohort and 9 case–control studies were eligible. There was an additional increased risk of upper GI bleeding in patients on NSAIDs with concomitant SSRI use (OR 1.75, 95% CI = 1.32–2.33). In patients already on NSAID therapy, the concomitant use of SSRIs can significantly increase the risk of upper of GI bleeding. [ABSTRACT FROM AUTHOR]

Tryptophan C-mannosylation stabilizes proteins bearing a thrombospondin repeat (TSR) domain in metazoans. Here we show that Plasmodium falciparum expresses a DPY19 tryptophan C-mannosyltransferase in the endoplasmic reticulum and that DPY19-deficiency abolishes C-glycosylation, destabilizes members of the TRAP adhesin family and inhibits transmission to mosquitoes. Imaging P. falciparum gametogenesis in its entirety in four dimensions using lattice light-sheet microscopy reveals defects in ΔDPY19 gametocyte egress and exflagellation. While egress is diminished, ΔDPY19 microgametes still fertilize macrogametes, forming ookinetes, but these are abrogated for mosquito infection. The gametogenesis defects correspond with destabilization of MTRAP, which we show is C-mannosylated in P. falciparum, and the ookinete defect is concordant with defective CTRP secretion on the ΔDPY19 background. Genetic complementation of DPY19 restores ookinete infectivity, sporozoite production and C-mannosylation activity. Therefore, tryptophan C-mannosylation by DPY19 ensures TSR protein quality control at two lifecycle stages for successful transmission of the human malaria parasite. Here, Lopaticki et al. show that Plasmodium falciparum expresses a Dpy19 C-mannosyltransferase in the endoplasmic reticulum that glycosylates TSR domains. Functional characterization shows that PfDpy19 plays a critical role in transmission through mosquitoes as PfDpy19-deficiency abolishes C-glycosylation and destabilizes proteins relevant for gametogenesis and oocyst formation. [ABSTRACT FROM AUTHOR]

Buoyed by recent calls for research to explore micro-level cognitive explanations for ambidexterity, this study examines how individuals' self-efficacy and resilience affect individual ambidexterity across different institutional environments. Building on social cognitive theory, we posit that self-efficacy enhances ambidexterity via resilience and that such relationship varies across economic institutional environments. Our symmetric (PLS-SEM) and configurational (fsQCA) analyses of 1907 knowledge workers in China, New Zealand and Australia provide supportive and complementary evidence for these theoretical arguments. Specifically, PLS-SEM reveals that the mediating effects of resilience on the relationship between self-efficacy and individual ambidexterity are stronger in an environment where economic institutions are weak. fsQCA complements PLS-SEM by showing that individual ambidexterity can be explained by multiple configurations of psychological self-efficacy, resilience, characteristics related to institutions, and personal demographic factors. Taken together, these findings contribute to the international business literature by providing a nuanced understanding of how different psychological resources integrate and interact with institutional factors to enhance individual ambidexterity. [ABSTRACT FROM AUTHOR]

Livestock abortion is an important cause of productivity losses worldwide and many infectious causes of abortion are zoonotic pathogens that impact on human health. Little is known about the relative importance of infectious causes of livestock abortion in Africa, including in subsistence farming communities that are critically dependent on livestock for food, income, and wellbeing. We conducted a prospective cohort study of livestock abortion, supported by cross-sectional serosurveillance, to determine aetiologies of livestock abortions in livestock in Tanzania. This approach generated several important findings including detection of a Rift Valley fever virus outbreak in cattle; high prevalence of C. burnetii infection in livestock; and the first report of Neospora caninum, Toxoplasma gondii, and pestiviruses associated with livestock abortion in Tanzania. Our approach provides a model for abortion surveillance in resource-limited settings. Our findings add substantially to current knowledge in sub-Saharan Africa, providing important evidence from which to prioritise disease interventions. [ABSTRACT FROM AUTHOR]