Identifying the effects of scaffolding on learners' temporal deployment of self-regulated learning operations during game-based learning using multimodal data.

Introduction: Self-regulated learning (SRL), or learners' ability to monitor and change their own cognitive, affective, metacognitive, and motivational processes, encompasses several operations that should be deployed during learning including Searching, Monitoring, Assembling, Rehearsing, and Translating (SMART). Scaffolds are needed within GBLEs to both increase learning outcomes and promote the accurate and efficient use of SRL SMART operations. This study aims to examine how restricted agency (i.e., control over one's actions) can be used to scaffold learners' SMART operations as they learn about microbiology with Crystal Island, a game-based learning environment. Methods: Undergraduate students (N = 94) were randomly assigned to one of two conditions: (1) Full Agency, where participants were able to make their own decisions about which actions they could take; and (2) Partial Agency, where participants were required to follow a pre-defined path that dictated the order in which buildings were visited, restricting one's control. As participants played Crystal Island, participants' multimodal data (i.e., log files, eye tracking) were collected to identify instances where participants deployed SMART operations. Results: Results from this study support restricted agency as a successful scaffold of both learning outcomes and SRL SMART operations, where learners who were scaffolded demonstrated more efficient and accurate use of SMART operations. Discussion: This study provides implications for future scaffolds to better support SRL SMART operations during learning and discussions for future directions for future studies scaffolding SRL during game-based learning.

Assessing Content of Accredited Colon and Rectal Surgery Fellowship Websites: Is there Adequate Information for Applicants?

Electronic information is a vital resource used by fellowship applicants. This study aimed to assess the completeness of colon and rectal surgery (CRS) fellowship program online information. Program information on the Association of Program Directors for Colon and Rectal Surgery (APDCRS) website as well as each institutional website was evaluated based on templated criteria. Sixty-eight accredited fellowship programs were identified. Six (9%) programs had complete profiles on the APDCRS platform, with an average of 3.5 details completed per program. Sixty-two (91%) websites were easily accessible. None of these contained all 28 criteria assessed and 47 (69%) contained less than half of assessed content. The most common data point was fellowship program description (96%), while board pass rate (1%) was the least common. Most CRS fellowship websites were grossly incomplete. Electronically available information is vital to fellowship applicants, and programs should try to provide easily accessible information about their program.

Natural history and outcomes of patients with liver cirrhosis complicated by hepatic hydrothorax.

BACKGROUND: Hepatic hydrothorax (HH) is an uncommon and difficult-to-manage complication of cirrhosis with limited treatment options. AIM: To define the clinical outcomes of patients presenting with HH managed with current standards-of-care and to identify factors associated with mortality. METHODS: Cirrhotic patients with HH presenting to 3 tertiary centres from 2010 to 2018 were retrospectively identified. HH was defined as pleural effusion in the absence of cardiopulmonary disease. The primary outcomes were overall and transplant-free survival at 12-mo after the index admission. Cox proportional hazards analysis was used to determine factors associated with the primary outcomes. RESULTS: Overall, 84 patients were included (mean age, 58 years) with a mean model for end-stage liver disease score of 29. Management with diuretics alone achieved long-term resolution of HH in only 12% patients. At least one thoracocentesis was performed in 73.8% patients, transjugular intrahepatic portosystemic shunt insertion in 11.9% patients and 33% patients received liver transplantation within 12-mo of index admission. Overall patient survival and transplant-free survival at 12 mo were 68% and 41% respectively. At multivariable analysis, current smoking [hazard ratio (HR) = 8.65, 95% confidence interval (CI): 3.43-21.9, P < 0.001) and acute kidney injury (AKI) (HR = 2.91, 95%CI: 1.21-6.97, P = 0.017) were associated with a significantly increased risk of mortality. CONCLUSION: Cirrhotic patients with HH are a challenging population with a poor 12-mo survival despite current treatments. Current smoking and episodes of AKI are potential modifiable factors affecting survival. HH is often refractory of diuretic therapy and transplant assessment should be considered in all cases.

Keep it SIMPL: Improved Feedback After Implementation of an App-Based Feedback Tool.

BACKGROUND: Data defining the utility of the system for improving and measuring procedural learning (SIMPL) in surgical education is limited. The aim of this pilot study is to describe the impact of SIMPL on resident and faculty perspectives regarding operative feedback. METHODS: Residents and faculty were surveyed prior to and 6 months after SIMPL implementation. Associations were analyzed using χ2 for categorical and Student's t-test for continuous variables. Statistical significance was defined as P-value < .05. RESULTS: The proportion of residents receiving intraoperative feedback at least once/day increased significantly (35% to 73%, P = .025); there was a trend toward increased postoperative feedback (15% to 33%, P = .201). Faculty reported an increase in intraoperative (55% to 91%, P = .041) and postoperative feedback (21% to 64%, P = .020). Satisfaction with intraoperative feedback improved from a score of 3.50 ± 1.05 to 3.93 ± .62, although not statistically significant (P = .181). Satisfaction with postoperative feedback improved significantly from 2.85 ± .93 to 3.50 ± .65 (P = .032). The proportion of faculty who felt they were providing effective feedback increased (53% to 91%, P = .032). The proportion of residents who perceived that feedback enhanced their surgical skill increased as well (65% to 93%, P = .048). DISCUSSION: Despite a modest increase in frequency of postoperative feedback, perceived quality of feedback improved substantially after implementation of SIMPL. Introduction of SIMPL also increased the amount of feedback provided by faculty intraoperatively. SIMPL, via direct and indirect effects, has a positive impact on the resident operative learning environment. Further work is necessary to examine the influence this may have on resident operative skill and patient outcomes.

Malnutrition and low muscle strength are independent predictors of clinical outcomes and healthcare costs after liver transplant.

BACKGROUND & AIMS: Malnutrition and sarcopenia are associated with increased morbidity and mortality in cirrhosis but conflicting data are reported after liver transplantation (LT), with little known about the economic burden of malnutrition at LT. This study aims to investigate the impact of pre-transplant malnutrition and muscle strength on post-transplant clinical outcomes and healthcare costs. METHODS: Pre-transplant nutritional status (via subjective global assessment, SGA) and handgrip strength (HGS) were assessed in patients transplanted from 2009-2017. Descriptive statistics and regression analysis were used to analyse the association between nutrition and muscle function with post-LT clinical outcomes and hospital costs. RESULTS: 373 patients (70% male, median age 55 [IQR: 47, 60]) were transplanted, with 79% malnourished and mean HGS 31.4 ± 9.35 kg for males and 17.6 ± 5.78 kg for females. Malnutrition and reduced HGS independently predicted adverse post-transplant outcomes. ICU length of stay (LOS) was associated with severe malnutrition (HR (time to discharge (TTD)) 0.706, p = 0.014) and low HGS (HR (TTD) 0.692, p = 0.003); hospital LOS with severe malnutrition (HR (TTD) 0.759, p = 0.049) and low HGS (HR (TTD) 0.730, p = 0.011), and post-transplant infection with severe malnutrition (OR 1.76, p = 0.042) and low HGS (OR 1.83, p = 0.015). Accordingly, hospital costs were 30% higher in severely malnourished compared to well-nourished recipients (p = 0.012). Neither malnutrition or impaired HGS were associated with post-transplant mortality. CONCLUSIONS: This large cohort study demonstrates malnutrition and muscle weakness are independently associated with early post-transplant morbidity, namely infection and ICU and hospital LOS; with significantly increased hospital costs. Strategies to combat malnutrition and deconditioning pre-transplant may improve patient and health system outcomes after LT.

Interactome analysis illustrates diverse gene regulatory processes associated with LIN28A in human iPS cell-derived neural progenitor cells.

A single protein can be multifaceted depending on the cellular contexts and interacting molecules. LIN28A is an RNA-binding protein that governs developmental timing, cellular proliferation, differentiation, stem cell pluripotency, and metabolism. In addition to its best-known roles in microRNA biogenesis, diverse molecular roles have been recognized. In the nervous system, LIN28A is known to play critical roles in proliferation and differentiation of neural progenitor cells (NPCs). We profiled the endogenous LIN28A-interacting proteins in NPCs differentiated from human induced pluripotent stem (iPS) cells using immunoprecipitation and liquid chromatography-tandem mass spectrometry. We identified over 500 LIN28A-interacting proteins, including 156 RNA-independent interactors. Functions of these proteins span a wide range of gene regulatory processes. Prompted by the interactome data, we revealed that LIN28A may impact the subcellular distribution of its interactors and stress granule formation upon oxidative stress. Overall, our analysis opens multiple avenues for elaborating molecular roles and characteristics of LIN28A.

Cortical organoids model early brain development disrupted by 16p11.2 copy number variants in autism.

Reciprocal deletion and duplication of the 16p11.2 region is the most common copy number variation (CNV) associated with autism spectrum disorders. We generated cortical organoids from skin fibroblasts of patients with 16p11.2 CNV to investigate impacted neurodevelopmental processes. We show that organoid size recapitulates macrocephaly and microcephaly phenotypes observed in the patients with 16p11.2 deletions and duplications. The CNV dosage affects neuronal maturation, proliferation, and synapse number, in addition to its effect on organoid size. We demonstrate that 16p11.2 CNV alters the ratio of neurons to neural progenitors in organoids during early neurogenesis, with a significant excess of neurons and depletion of neural progenitors observed in deletions. Transcriptomic and proteomic profiling revealed multiple pathways dysregulated by the 16p11.2 CNV, including neuron migration, actin cytoskeleton, ion channel activity, synaptic-related functions, and Wnt signaling. The level of the active form of small GTPase RhoA was increased in both, deletions and duplications. Inhibition of RhoA activity rescued migration deficits, but not neurite outgrowth. This study provides insights into potential neurobiological mechanisms behind the 16p11.2 CNV during neocortical development.

Love at First Click: Surgery Residency Websites in the Virtual Era.

INTRODUCTION: Frequently, a residency program's website is the first interaction students interested in surgery have with the program. In the setting of virtual interviews for residency in 2020, the online availability of program information is of heightened importance. We sought to assess how academic versus community-based general surgery residency programs compared with respect to certain details on their websites. METHODS: A total of n = 268 surgery residency programs were investigated. Our database of website characteristics included: direct link to residency website from the American Council on Graduate Medical Education (ACGME) program page, resident research requirement, listing of residents' publications, availability of residents' demographic information, program alumni information, board pass rates, attrition rate, detail of educational/academic activities, residents' evaluation methods, diversity, and mentorship. Inter-group analyses between academic and community-based programs were performed using Pearson's Chi-squared test. RESULTS: Academic and community-based general surgery residency program websites were compared based on twelve (12) different parameters. Statistically significant differences were observed for eight of these comparisons: direct website access from ACGME (p = 0.007), research highlighted (p < 0.001), resident research requirement (p = 0.002), resident demographic information available (p=0.004), alumni information (p = 0.005), resident evaluation methods (p = 0.016), diversity (p < 0.001), and mentorship (p = 0.012). Across these domains, academic programs had more information available on their websites than the community programs did. The program websites did not differ significantly based on the frequency of mentioning resident publications, board pass rate, attrition rate, or resident education. CONCLUSION: Many general surgery programs are lacking detailed information on their websites. The amount of website information available on general surgery residency programs differs when comparing academic and community-based programs.

Pharmacological reversal of synaptic and network pathology in human MECP2-KO neurons and cortical organoids.

Duplication or deficiency of the X-linked MECP2 gene reliably produces profound neurodevelopmental impairment. MECP2 mutations are almost universally responsible for Rett syndrome (RTT), and particular mutations and cellular mosaicism of MECP2 may underlie the spectrum of RTT symptomatic severity. No clinically approved treatments for RTT are currently available, but human pluripotent stem cell technology offers a platform to identify neuropathology and test candidate therapeutics. Using a strategic series of increasingly complex human stem cell-derived technologies, including human neurons, MECP2-mosaic neurospheres to model RTT female brain mosaicism, and cortical organoids, we identified synaptic dysregulation downstream from knockout of MECP2 and screened select pharmacological compounds for their ability to treat this dysfunction. Two lead compounds, Nefiracetam and PHA 543613, specifically reversed MECP2-knockout cytologic neuropathology. The capacity of these compounds to reverse neuropathologic phenotypes and networks in human models supports clinical studies for neurodevelopmental disorders in which MeCP2 deficiency is the predominant etiology.

Understanding the Well-Being of General Surgery Residents.

BACKGROUND: In 2017, the Accreditation Council for Graduate Medical Education program guidelines changed to include a section that requires programs to optimize resident and faculty member well-being. There is still a poor understanding of general surgery resident wellness, and there are few well-established wellness programs. METHODS: We created a novel 50-question anonymous survey to assess burnout, depression, and wellness that was distributed to the general surgery residents as part of a pilot study. Univariate analysis was performed to assess wellness and wellness changes. Bivariate analysis was performed to determine the association between wellness variables and gender, age, and postgraduate year (PGY) level. RESULTS: Thirty-five of 55 residents participated in the survey. Over half of the residents (54%) reported gaining weight during residency. Nearly 70% reported working while having an ongoing family issue, and 77% worked at least once while ill. Fourteen residents (40%) reported that their wellness worsened over the previous academic year, while 7 (20%) reported that it remained the same, and 11 (31%) reported that it improved. These changes varied significantly by the PGY level (P < .01). Age (younger vs older than 30) and sex were found to be effective measure modifiers of the association between wellness change and PGY level. DISCUSSION: The overall wellness of the general surgery residents at our institution varies greatly. Poor wellness may lead to inferior patient care, burnout and depression, and negative resident morale. Residency programs need to implement programming to address wellness deficiencies.

USMLE Step 1 Is Pass/Fail - Should the ABSITE Follow Suit?

The United States Medical Licensing Examination (USMLE) Step 1 was recently made pass/fail. This decision was controversial largely because of the reliance on USMLE Step 1 scores in resident selection. However, these scores do not correlate with resident ability. In this manuscript, we consider if the American Board of Surgery In-Training Examination (ABSITE) should be pass/fail as well. The ABSITE has been used for "high-stakes" purposes, such as preliminary resident advancement and prospective fellow evaluation, for which it was not intended. Moreover, similar to the USMLE Step 1 exam, ABSITE scores have demonstrated no correlation with clinical ability. A pass/fail ABSITE would return the exam to its original purpose and minimize an over-reliance on scores. Moving forward, new objective measures will need to be developed to assess surgical trainees in a more holistic manner.

Drowning Prevention in Pediatrics.

Drowning contributes significantly to morbidity and mortality in the pediatric population but it is largely preventable through judicious use of safety measures. To affect outcomes surrounding drowning, pediatricians need to understand the most updated terminology, the basic resuscitation protocols, and the assessment and management of a drowning victim. Most importantly, pediatricians must appreciate the importance of properly counseling patients and families about drowning prevention. Effective preventive measures supported by the literature include constant and reliable adult supervision, swim instruction for most children older than age 4 years, pool isolation fencing, and the proper use of personal floatation devices. [Pediatr Ann. 2018;47(3):e112-e117.].

The American Board Style Practice In-Training Examination as a Predictor of Performance on the American Board of Surgery In-Training Examination.

BACKGROUND: The American Board of Surgery In-Training Examination (ABSITE), is an annual 250 question, multiple-choice test that assesses residents' surgical knowledge in preparation for board examinations. At our program, we developed a Surgical Council on Resident Education-based American Board Style Practice In-Training Examination: The ABSPITE. The 40-question examination was designed to help with test preparation. The purpose of this study was to evaluate the ABSPITE's predictive value on ABSITE performance. METHODS: From 2013 to 2016, the ABSPITE was administered to residents at our program. Performances (N = 134) were graded based on a standardized scale to determine resident percent and percentile performance, then compared to average ABSITE performance. RESULTS: Combined analysis showed a statistically significant positive correlation between average ABSITE and ABSPITE percentages and percentiles. This held true when categorical and preliminary residents were compared. When stratified by resident PGY level, the same results were seen for PGY 1 and PGY 2 residents but correlations failed to reach statistical significance for higher resident training levels. CONCLUSIONS: The practice ABSPITE examination strongly correlates with ABSITE performance among junior residents at our program, and may be a valuable tool to predict ABSITE performance and guide review efforts.

Antibiotic Susceptibility Monitoring of Neisseria gonorrhoeae in Bacolod City, Philippines.

A local study was conducted to monitor the antibiotic susceptibility of N. gonorrhoeae in Bacolod City, Philippines. A total of 88 isolates were taken during the period of 1 January 2015 to 30 June 2017, from male patients ages 12 to 72 years. The highest incidence of gonorrhea infection was in the group aged 20⁻24 years (34.09%). The susceptibility pattern to antibiotics was as follows: ceftriaxone 100%, cefixime 82.6%, spectinomycin 92.1%, ciprofloxacin 4.9%, tetracycline 5.1%, and penicillin G with 0%. All isolates were noted to produce beta-lactamase, which can be attributed to plasmid-mediated penicillin resistance. These findings indicate that the resistance rates of N. gonorrhoeae to most commonly-used antibiotics are increasing, and that ceftriaxone remains an effective antibiotic in treating gonorrhea infections locally.

A human neurodevelopmental model for Williams syndrome.

Williams syndrome is a genetic neurodevelopmental disorder characterized by an uncommon hypersociability and a mosaic of retained and compromised linguistic and cognitive abilities. Nearly all clinically diagnosed individuals with Williams syndrome lack precisely the same set of genes, with breakpoints in chromosome band 7q11.23 (refs 1-5). The contribution of specific genes to the neuroanatomical and functional alterations, leading to behavioural pathologies in humans, remains largely unexplored. Here we investigate neural progenitor cells and cortical neurons derived from Williams syndrome and typically developing induced pluripotent stem cells. Neural progenitor cells in Williams syndrome have an increased doubling time and apoptosis compared with typically developing neural progenitor cells. Using an individual with atypical Williams syndrome, we narrowed this cellular phenotype to a single gene candidate, frizzled 9 (FZD9). At the neuronal stage, layer V/VI cortical neurons derived from Williams syndrome were characterized by longer total dendrites, increased numbers of spines and synapses, aberrant calcium oscillation and altered network connectivity. Morphometric alterations observed in neurons from Williams syndrome were validated after Golgi staining of post-mortem layer V/VI cortical neurons. This model of human induced pluripotent stem cells fills the current knowledge gap in the cellular biology of Williams syndrome and could lead to further insights into the molecular mechanism underlying the disorder and the human social brain.

The Brazilian Zika virus strain causes birth defects in experimental models.

Zika virus (ZIKV) is an arbovirus belonging to the genus Flavivirus (family Flaviviridae) and was first described in 1947 in Uganda following blood analyses of sentinel Rhesus monkeys. Until the twentieth century, the African and Asian lineages of the virus did not cause meaningful infections in humans. However, in 2007, vectored by Aedes aegypti mosquitoes, ZIKV caused the first noteworthy epidemic on the Yap Island in Micronesia. Patients experienced fever, skin rash, arthralgia and conjunctivitis. From 2013 to 2015, the Asian lineage of the virus caused further massive outbreaks in New Caledonia and French Polynesia. In 2013, ZIKV reached Brazil, later spreading to other countries in South and Central America. In Brazil, the virus has been linked to congenital malformations, including microcephaly and other severe neurological diseases, such as Guillain-Barré syndrome. Despite clinical evidence, direct experimental proof showing that the Brazilian ZIKV (ZIKV(BR)) strain causes birth defects remains absent. Here we demonstrate that ZIKV(BR) infects fetuses, causing intrauterine growth restriction, including signs of microcephaly, in mice. Moreover, the virus infects human cortical progenitor cells, leading to an increase in cell death. We also report that the infection of human brain organoids results in a reduction of proliferative zones and disrupted cortical layers. These results indicate that ZIKV(BR) crosses the placenta and causes microcephaly by targeting cortical progenitor cells, inducing cell death by apoptosis and autophagy, and impairing neurodevelopment. Our data reinforce the growing body of evidence linking the ZIKV(BR) outbreak to the alarming number of cases of congenital brain malformations. Our model can be used to determine the efficiency of therapeutic approaches to counteracting the harmful impact of ZIKV(BR) in human neurodevelopment.

Synergistic induction of apoptosis by a polo-like kinase 1 inhibitor and microtubule-interfering drugs in Ewing sarcoma cells.

Since polo-like kinase 1 (PLK1) is highly expressed in Ewing sarcoma (ES), we evaluated the therapeutic potential of the PLK1 inhibitor BI 6727. Here, we identify a synergistic induction of apoptosis by BI 6727 and several microtubule-interfering drugs in ES cells, including vincristine (VCR), vinblastine (VBL), vinorelbine (VNR) and eribulin. Synergistic drug interaction is confirmed by calculation of combination index (CI). Also, BI 6727 and VCR act in concert to reduce long-term clonogenic survival. Mechanistically, BI 6727/VCR co-treatment cooperates to trigger mitotic arrest, phosphorylation of BCL-2 and BCL-XL and downregulation of MCL-1. This inactivation of anti-apoptotic BCL-2 family proteins in turn promotes activation of BAX and BAK, activation of caspase-9 and -3 and caspase-dependent apoptosis. Overexpression of BCL-2 or simultaneous knockdown of BAX and BAK significantly rescue BI 6727/VCR-induced apoptosis, indicating that engagement of the mitochondrial pathway is critical for BI 6727/VCR-mediated apoptosis. The clinical relevance of PLK1 inhibitor-based combination therapies is underscored by the fact that BI 6727 is currently evaluated in phase I clinical trials in childhood cancer. In conclusion, PLK1 inhibitors such as BI 6727 may provide a new strategy to chemosensitize ES.