Miracle-dz/UniFAR-FTUs huggingface dataset:
Postdocs’ lab engagement predicts trajectories of PhD students’ skill development

Significance Conventional wisdom in the laboratory sciences suggests that PhD students develop their research skills as a function of mentorship from their faculty advisors (i.e., principal investigators; PIs). However, no prior research has identified empirically a relationship between specific PI practices and the development of research skills. Here we show that PIs’ laboratory and mentoring activities do not significantly predict students’ skill development trajectories, but the engagement of postdocs and senior graduate students in laboratory interactions do. These findings support the practice of “cascading mentorship” as differentially effective and identify a critical but previously unrecognized role for postdocs in the graduate training process. They also illustrate both the importance and the feasibility of identifying evidence-based practices in graduate education. The doctoral advisor—typically the principal investigator (PI)—is often characterized as a singular or primary mentor who guides students using a cognitive apprenticeship model. Alternatively, the “cascading mentorship” model describes the members of laboratories or research groups receiving mentorship from more senior laboratory members and providing it to more junior members (i.e., PIs mentor postdocs, postdocs mentor senior graduate students, senior students mentor junior students, etc.). Here we show that PIs’ laboratory and mentoring activities do not significantly predict students’ skill development trajectories, but the engagement of postdocs and senior graduate students in laboratory interactions do. We found that the cascading mentorship model accounts best for doctoral student skill development in a longitudinal study of 336 PhD students in the United States. Specifically, when postdocs and senior doctoral students actively participate in laboratory discussions, junior PhD students are over 4 times as likely to have positive skill development trajectories. Thus, postdocs disproportionately enhance the doctoral training enterprise, despite typically having no formal mentorship role. These findings also illustrate both the importance and the feasibility of identifying evidence-based practices in graduate education.
A Reliability Analysis of Entrustment-Derived Workplace-Based Assessments

Purpose To examine the reliability and attributable facets of variance within an entrustment-derived workplace-based assessment system. Method Faculty at the University of Cincinnati Medical Center internal medicine residency program (a 3-year program) assessed residents using discrete workplace-based skills called observable practice activities (OPAs) rated on an entrustment scale. Ratings from July 2012 to December 2016 were analyzed using applications of generalizability theory (G-theory) and decision study framework. Given the limitations of G-theory applications with entrustment ratings (the assumption that mean ratings are stable over time), a series of time-specific G-theory analyses and an overall longitudinal G-theory analysis were conducted to detail the reliability of ratings and sources of variance. Results During the study period, 166,686 OPA entrustment ratings were given by 395 faculty members to 253 different residents. Raters were the largest identified source of variance in both the time-specific and overall longitudinal G-theory analyses (37% and 23%, respectively). Residents were the second largest identified source of variation in the time-specific G-theory analyses (19%). Reliability was approximately 0.40 for a typical month of assessment (27 different OPAs, 2 raters, and 1–2 rotations) and 0.63 for the full sequence of ratings over 36 months. A decision study showed doubling the number of raters and assessments each month could improve the reliability over 36 months to 0.76. Conclusions Ratings from the full 36 months of the examined program of assessment showed fair reliability. Increasing the number of raters and assessments per month could improve reliability, highlighting the need for multiple observations by multiple faculty raters.
A functional enrichment test for molecular convergent evolution finds a clear protein-coding signal in echolocating bats and whales

Significance Echolocation is a prime example of convergent evolution, the independent gain of similar features in species of different lineages. Is phenotypic convergence driven by underlying molecular convergence? If so, could molecular convergence include contributions from highly constrained, often-pleotropic, coding regions? We develop a generalizable test that offers a resounding “yes” to both extensively debated questions. Our test highlights molecular convergence in genes regulating the cochlear ganglion of echolocating bats and whales, the skin of aquatic mammals, and the lung of high-altitude mammals. Importantly, the approach correctly dismisses confounding convergence-like patterns, such as those from sequence decay of vision genes in blind subterranean species, and is readily applicable to the thousands of genomes sequenced across the tree of life. Distantly related species entering similar biological niches often adapt by evolving similar morphological and physiological characters. How much genomic molecular convergence (particularly of highly constrained coding sequence) contributes to convergent phenotypic evolution, such as echolocation in bats and whales, is a long-standing fundamental question. Like others, we find that convergent amino acid substitutions are not more abundant in echolocating mammals compared to their outgroups. However, we also ask a more informative question about the genomic distribution of convergent substitutions by devising a test to determine which, if any, of more than 4,000 tissue-affecting gene sets is most statistically enriched with convergent substitutions. We find that the gene set most overrepresented (q-value = 2.2e-3) with convergent substitutions in echolocators, affecting 18 genes, regulates development of the cochlear ganglion, a structure with empirically supported relevance to echolocation. Conversely, when comparing to nonecholocating outgroups, no significant gene set enrichment exists. For aquatic and high-altitude mammals, our analysis highlights 15 and 16 genes from the gene sets most affected by molecular convergence which regulate skin and lung physiology, respectively. Importantly, our test requires that the most convergence-enriched set cannot also be enriched for divergent substitutions, such as in the pattern produced by inactivated vision genes in subterranean mammals. Showing a clear role for adaptive protein-coding molecular convergence, we discover nearly 2,600 convergent positions, highlight 77 of them in 3 organs, and provide code to investigate other clades across the tree of life.
Efficacy of therapeutic plasma exchange in reducing the incidence of recurrent pancreatitis related to familial chylomicronemia

Familial chylomicronemia syndrome (FCS) is caused by a genetic defect in triglyceride (TG) metabolism that leads to severe hypertriglyceridemia, which in turn is associated with multiple morbidities and may cause severe pancreatitis that is both recurrent and progressive. Management of hypertriglyceridemia in FCS is challenging, as both dietary and medical interventions are often ineffective. Therapeutic plasma exchange (TPE) has been shown to rapidly decrease circulating levels of chylomicrons and TGs in patients presenting with acute hypertriglyceridemic‐associated pancreatitis. Conversely, limited evidence exists to suggest that prophylactic use of TPE is effective at preventing recurrence of acute pancreatitis.
Prevalence of Psychological Frailty in Japan: NCGG-SGS as a Japanese National Cohort Study

There has been less research conducted on the psychological aspects of frailty than on the physical and cognitive characteristics of frailty. Thus, we aimed to define psychological frailty, clarify its prevalence, and investigate the relationship between psychological frailty and lifestyle activity or disability incidence in older adults in Japan. The participants in our study were 4126 older adults (average age 71.7 years) enrolled in the National Center for Geriatrics and Gerontology-i87uStudy of Geriatric Syndromes (NCGG-SGS). We characterized physical frailty of the following as ≥ 3: slow walking speed, muscle weakness, exhaustion, low physical activity, and weight loss. We used the Geriatric Depression Scale 15 items version (GDS-15) to screen for depressive mood, indicated by 5 points or more on the scale. The co-presence of physical frailty and depressive mood was defined as psychological frailty. The incidence of disability was determined using data from the Japanese long-term care insurance system over 49 months. We found that the prevalence of physical frailty, depressive mood, and psychological frailty were 6.9%, 20.3%, and 3.5%, respectively. Logistic regression indicated that the odds ratios for loss of lifestyle activities were significantly higher in participants with psychological frailty for going outdoors using the bus or train, driving a car, using maps to go to unfamiliar places, reading books or newspapers, cognitive stimulation, culture lessons, giving advice, attending community meetings, engaging in hobbies or sports, house cleaning, fieldwork or gardening, and taking care of grandchildren or pets. During the follow-up period, 385 participants (9.3%) developed a disability. The incidence of disability was associated with both physical and psychological frailty in the fully adjusted model. However, no significant association between disability and depressive mood was found. We conclude that individuals with psychological frailty had the highest risk of disability. Future policies should implement disability prevention strategies among older adults with psychological frailty.
Review on Centration, Astigmatic Axis Alignment, Pupil Size and Optical Zone in SMILE

Abstract The advent of “flapless” small-incision lenticule extraction (SMILE), employing all-in-one technology, has resulted in a revolutionary breakthrough in refractive surgeries. SMILE has been gaining popularity due to fewer potential complications, such as postoperative dry eyes and greater biomechanical stability, etc. However, attention must be given to 1) the centration on the corneal vertex, 2) the proper alignment of the astigmatic axis, and 3) the relationship between pupil size and treatment diameter, to achieve good SMILE results. There is no pupil-tracking system to ascertain the accuracy of centration during the SMILE surgery. To improve the centration accuracy, our center uses two corneal topographers (Pentacam and Sirius) to measure and determine corneal vertex. Proper predicted optical zone diameter is not clearly defined yet in SMILE. Some scholars insist that mesopic pupil size should be taken into consideration when setting the predicted optical zone. Meanwhile, the issue of “functional optical zone” still has many unresolved issues and warrants further studies.
Systematic evaluation of PAXgene® tissue fixation for the histopathological and molecular study of lung cancer

Whilst adequate for most existing pathological tests, formalin is generally considered a poor DNA preservative and use of alternative fixatives may prove advantageous for molecular testing of tumour material; an increasingly common approach to identify targetable driver mutations in lung cancer patients. We collected paired PAXgene® tissue‐fixed and formalin‐fixed samples of block‐sized tumour and lung parenchyma, Temno‐needle core tumour biopsies and fine needle tumour aspirates (FNAs) from non‐small cell lung cancer resection specimens. Traditionally processed formalin fixed paraffin wax embedded (FFPE) samples were compared to paired PAXgene® tissue fixed paraffin‐embedded (PFPE) samples. We evaluated suitability for common laboratory tests (H&E staining and immunohistochemistry) and performance for downstream molecular investigations relevant to lung cancer, including RT‐PCR and next generation DNA sequencing (NGS). Adequate and comparable H&E staining was seen in all sample types and nuclear staining was preferable in PAXgene® fixed Temno tumour biopsies and tumour FNA samples. Immunohistochemical staining was broadly comparable. PFPE samples enabled greater yields of less‐fragmented DNA than FFPE comparators. PFPE samples were also superior for PCR and NGS performance, both in terms of quality control metrics and for variant calling. Critically we identified a greater number of genetic variants in the epidermal growth factor receptor gene when using PFPE samples and the Ingenuity® Variant Analysis pipeline. In summary, PFPE samples are adequate for histopathological diagnosis and suitable for the majority of existing laboratory tests. PAXgene® fixation is superior for DNA and RNA integrity, particularly in low‐yield samples and facilitates improved NGS performance, including the detection of actionable lung cancer mutations for precision medicine in lung cancer samples.
Outcomes of Infants Supported With Extracorporeal Membrane Oxygenation Using Centrifugal Versus Roller Pumps: An Analysis From the Extracorporeal Life Support Organization Registry.

OBJECTIVES To determine whether mortality differs between roller and centrifugal pumps used during extracorporeal membrane oxygenation in infants weighing less than 10 kg. DESIGN Retrospective propensity-matched cohort study. SETTING All extracorporeal membrane oxygenation centers reporting to the Extracorporeal Life Support Organization. PATIENTS All patients less than 10 kg supported on extracorporeal membrane oxygenation during 2011-2016 within Extracorporeal Life Support Organization Registry. INTERVENTIONS Centrifugal and roller pump recipients were propensity matched (1:1) based on predicted probability of receiving a centrifugal pump using demographic variables, indication for extracorporeal membrane oxygenation, central versus peripheral cannulation, and pre-extracorporeal membrane oxygenation patient management. MEASUREMENTS AND MAIN RESULTS A total of 12,890 patients less than 10 kg were supported with extracorporeal membrane oxygenation within the Extracorporeal Life Support Organization registry during 2011-2016. Patients were propensity matched into a cohort of 8,366. Venoarterial and venovenous extracorporeal membrane oxygenation runs were propensity matched separately. The propensity-matched cohorts were similar except earlier year of extracorporeal membrane oxygenation (standardized mean difference, 0.49) in the roller pump group. Within the propensity-matched cohort, survival to discharge was lower in the centrifugal pump group (57% vs 59%; odds ratio, 0.91; 95% CI, 0.83-0.99; p = 0.04). Hemolytic, infectious, limb injury, mechanical, metabolic, neurologic, pulmonary, and renal complications were more frequent in the centrifugal pump group. Hemorrhagic complications were similar between groups. Hemolysis mediated the relationship between centrifugal pumps and mortality (indirect effect, 0.023; p < 0.001). CONCLUSIONS In this propensity score-matched cohort study of 8,366 extracorporeal membrane oxygenation recipients weighing less than 10 kg, those supported with centrifugal pumps had increased mortality and extracorporeal membrane oxygenation complications. Hemolysis was evaluated as a potential mediator of the relationship between centrifugal pump use and mortality and met criteria for full mediation.
Proteasome Inhibitors Suppress ErbB Family Expression through HSP90-Mediated Lysosomal Degradation

Although dual EGFR/HER2 tyrosine kinase inhibitor lapatinib has provided effective clinical benefits for HER2-positive breast cancer patients, acquired resistance to this drug remains a major concern. Thus, the development of alternative therapeutic strategies is urgently needed for patients who failed lapatinib treatment. Proteasome inhibitors have been reported to possess high anti-tumor activity to breast cancer cells. Therefore, this study aims to examine whether and how proteasome inhibitor bortezomib can overcome lapatinib resistance. Treatments with several proteasome inhibitors, including Bortezomib, MG132, and proteasome inhibitor I (PSI), as well as the viabilities of both HER2-positive breast cancer cell lines and their lapatinib-resistant clones, were inhibited. Importantly, the expressions of ErbB family were downregulated at both transcriptional and translational levels. Also, our results further indicated that proteasome inhibitors decreased ErbB family expression through lysosomal degradation pathway in a heat shock protein 90 (HSP90)-dependent manner. In this study, our data supported a potential approach to overcome the acquired resistance of HER2-overexpressing breast cancer patients to lapatinib using proteasome inhibitors.
PECS II block is associated with lower incidence of chronic pain after breast surgery

Background Breast cancer is complicated by a high incidence of chronic postoperative pain (25%–60%). Regional anesthesia might play an important role in lowering the incidence of chronic pain; however it is not known if the pectoral nerve block (PECS block), which is commonly used for breast surgery, is able to prevent this complication. Our main objective was therefore to detect any association between the PECS block and chronic pain at 3, 6, 9, and 12 months in patients undergoing breast surgery. Methods We conducted a prospective, monocentric, observational study. We enrolled 140 consecutive patients undergoing breast surgery and divided them in patients receiving a PECS block and general anesthesia (PECS group) and patients receiving only general anesthesia (GA group). Then we considered both intraoperative variables (intravenous opioids administration), postoperative data (pain suffered by the patients during the first 24 postoperative hours and the need for additional analgesic administration) and development and persistence of chronic pain (at 3, 6, 9, and 12 mo). Results The PECS group had a lower incidence of chronic pain at 3 months (14.9% vs. 31.8%, P = 0.039), needed less intraoperative opioids (fentanyl 1.61 μg/kg/hr vs. 3.3 μg/kg/hr, P < 0.001) and had less postoperative pain (3 vs. 4, P = 0.017). Conclusions The PECS block might play an important role in lowering incidence of chronic pain, but further studies are needed.
Pathogenicity of a QX-like avian infectious bronchitis virus isolated in China

ABSTRACT Avian infectious bronchitis is a serious and highly contagious disease caused by infectious bronchitis virus (IBV). We isolated a highly virulent IBV strain (CK/CH/JS/TAHY) from kidneys of diseased chickens. Phylogenetic analysis based on the S1 gene revealed that CK/CH/JS/TAHY clustered with the QX-like type. The S1 gene has 1,620 nucleotides and encoded a polypeptide of 540 amino acids with typical coronavirus cleavage recognition sites of HRRR. About 1-day-old specific pathogen-free White Leghorn chickens inoculated with CK/CH/JS/TAHY at 105.5 EID50 exhibited clinical signs including coughing, sneezing, nasal discharge, and tracheal vocalization accompanied by depression with 84% mortality and 100% morbidity. The kidneys of dead birds were swollen and pale and exhibited severe urate deposition. Histopathological examination revealed kidney hemorrhages, multifocal necrosis of the renal tubules and trachea with cilia loss, sloughing of epithelial cells, and edema of the lamina propria. IBV-specific antibodies appeared at 10 D post-infection. Chickens vaccinated with a CK/CH/JS/TAHY oil-emulsion vaccine showed 26.7% morbidity and 3% mortality indicating a protective effect. In conclusion, the IBV strain is a virulent avian IBV and that exhibited severe pathogenicity in chickens and is a vaccine candidate to prevent infection by Chinese QX-like nephropathogenic IBV strains.
Anti-Thymocyte Globulin versus Interleukin-2 Receptor Antagonist in Kidney Transplant Recipients with Hepatitis C Virus.

BACKGROUND Hepatitis C virus-positive (HCV+) kidney transplant (KT) recipients are at increased risks of rejection and graft failure. The optimal induction agent for this population remains controversial, particularly regarding concerns that anti-thymocyte globulin (ATG) might increase HCV-related complications. METHODS Using SRTR and Medicare claims data, we studied 6780 HCV+ and 139,681 HCV- KT recipients in 1999-2016 who received ATG or interleukin-2 receptor antagonist (IL2RA) for induction. We first examined the association of recipient HCV status with receiving ATG (vs. IL2RA) using multilevel logistic regression. Then, we studied the association of ATG (vs. IL2RA) with KT outcomes (rejection, graft failure, and death) and hepatic complications (liver transplant registration and cirrhosis) among HCV+ recipients using logistic and Cox regression. RESULTS HCV+ recipients were less likely to receive ATG than HCV- recipients (living donor, aOR=0.640.770.91; deceased donor, aOR=0.710.810.92). In contrast, HCV+ recipients who received ATG were at lower risk of acute rejection compared to those who received IL2RA (1-year crude incidence=11.6% vs. 12.6%; aOR=0.680.820.99). There was no significant difference in the risks of graft failure (aHR=0.861.001.17), death (aHR=0.850.951.07), liver transplant registration (aHR=0.580.971.61), and cirrhosis (aHR=0.730.921.16). CONCLUSIONS Our findings suggest that ATG, as compared to IL2RA, may lower the risk of acute rejection without increasing hepatic complications in HCV+ KT recipients. Given the higher rates of acute rejection in this population, ATG appears to be safe and reasonable for HCV+ recipients.
Isolation, Identification, and Characterization of Pectinolytic Yeasts for Starter Culture in Coffee Fermentation

This experiment was carried out to identify and select pectinolytic yeasts that have potential use as a starter culture for coffee fermentation during wet processing. The coffee fruit was fermented for 48 h at 28 °C and a sample was taken from the fermented solution and spread onto yeast extract-peptone-dextrose agar (YPDA) media and incubated at 28 °C. A total of 28 yeasts were isolated, eight of which had the ability to produce pectinase enzymes. The species of those eight yeasts were molecularly identified and confirmed. These yeasts are Wickerhamomyces anomalus (strain KNU18Y3), Saccharomycopsis fibuligera (strain KNU18Y4), Papiliotrema flavescens (strain KNU18Y5 and KNU18Y6), Pichia kudriavzevii (strain KNU18Y7 and KNU18Y8), and Saccharomyces cerevisiae (strain KNU18Y12 and KNU18Y13). The pectin degradation index of S. fibuligera (strain KNU18Y4), W. anomalus (strain KNU18Y3), and P. flavescens (strain KNU18Y6) were higher compared to the others, at 178%, 160%, and 152%, respectively. The pectinase enzyme assays were made on two growth media: coffee pulp media (CPM) and synthetic pectin media (SPM). S. fibuligera (strain KNU18Y4) and W. anomalus (strain KNU18Y3) had great potential in producing polygalacturonase (PG) and pectin lyase (PL) compared to others in both media. However, S. cerevisiae strains (KNU18Y12 and KNU18Y13) produced higher pectin methylesterase (PME). Using MEGA 6 software, the phylogenetic trees were constructed to determine the evolutionary relationship of newly identified yeasts from our experiment and previously published yeast species. The sequences of the yeasts were deposited in the National Center for Biotechnology Information (NCBI) database.