bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of the COVID Pandemic on STEM Professionals
Authors: Benore Marilee A. , Esquivel Amanda O. , Marincean Simona
Published: May 2022

Early reports indicated that the COVID 19 pandemic negatively impacted STEM professionals' research, resulting in fewer grants, patents, and publications, and disrupted student learning, especially in skills development. More concerning was the prediction that the most severe consequences would be felt by young STEM professionals, or those with family care responsibilities. In order to investigate the impact of the COVID pandemic on STEM professionals in the USA we conducted a survey. Questions included loss of research and lab time, data on papers, grants and publications, and the disruption to personal obligations and work life balance.

The survey, conducted about one year into the pandemic, provided evidence that there were significant differences in productivity and responsibilities, with some differences and work load aligned with gender. Response comments reflected both negative and positive outcomes. This data is consistent with trends observed in other professional fields, as well as those reported in other nations.

This poster will present the results of this research, along with outcomes from other studies. The concerns have spurred several calls to action by professional societies, government agencies and other groups. These recommendations attempt to ensure that STEM professionals can continue to progress in their careers. Strategic planning is necessary in order to ensure that the next generation of STEM researchers are properly supported in order to ensure a diverse workforce.
A Mass Action Model for Heat Shock Induced Enhancer Transcription
Authors: Wang Kiara
Published: May 2022

A proper response to elevated temperature is important for the survival of all organisms. This response is partially achieved through enhancer‐mediated regulation of gene expression. However, the behavior of enhancers during heat shock response is not well understood. Here, we report that binding by heat shock factor 1 (HSF1), the master regulator of heat shock response, leads to upregulation of enhancer transcription. HSF1 bound enhancers also show higher‐than‐expected probability to be near heat induced genes, indicating their potential involvement in the upregulation of these genes. However, the transcriptional upregulation of the majority of enhancers during heat shock is HSF1 independent. To account for this observation, we propose a mass action model of enhancer transcription. Heat shock response results in a global downregulation of gene transcription, which leads to less transcribing RNA polymerase II (Pol II) and more freely diffusing Pol II. Free Pol II can then initiate transcription on accessible chromatin regions driven by the law of mass action.
The Use of Low‐Dose Radiation Pre‐Treatments as a Potential Countermeasure to Galactic Cosmic Radiation Exposure
Authors: Edwards John , Tchernikov Anastasia , Edwards Siena , Hernandez Rachel , Adams Jessica
Published: May 2022

Space exploration involves many dangers, including radiation exposure from galactic cosmic radiation (GCR). This includes high energy protons and heavy ionizing ions such as 56Fe, 28Si, and 16O. NASA has defined GCR as a carcinogenic risk for long‐duration space missions. To date no clear strategy has been developed to counter chronic GCR exposure. We hypothesize that preconditioning cells with low levels of radiation will be protective from subsequent higher radiation exposures. H9C2 cells maintained in culture were pretreated with 0, 0.1, or 0.5 Gy X‐rays using a RadSource 2000 Irradiator. The challenge radiation treatment consisted of either 8 Gy X‐ray or 75cGy of GCR, using a 5 Ion GCRsim protocol. To determine cell health, the cell doubling time assay was used. 10000 cells from each treatment group were put into wells of a 24 well plate and maintained for 48‐72 hours. Following harvest, cells were counted using a flow cytometer. The 8 Gy X‐ray challenge alone significantly (p<.05) increased cell doubling time compared to the no radiation control group. The radiation pre‐treatment groups ameliorated the 8 Gy X‐ray induced increases in cell doubling time and there was no difference compared to the no radiation control group. 75 cGy GCR challenge alone significantly increased cell doubling time compared to the no radiation group. Following the 75cGy challenge, only the 0.5 Gy pre‐treatment ameliorated the 75cGy induced increases in cell doubling time. The cell doubling time protocol measures the amount of time require for a cell to undergo mitosis. It is directly influence by DNA integrity as well as mitochondrial and cellular function. DNA damage or pathologic oxidant stress will delay the replicative functions. As such this is a physiologic measure of the cell wellbeing. Our results suggested that pretreatment with low dose X‐rays enhanced cellular resiliency by inducing an adaptive response which offered a small but significant protection against a following higher radiation challenge. Although perhaps not a practical countermeasure, these findings may serve to offer insight to cell signaling pathways activated in response to low dose irradiation and that might be targeted as a potential countermeasure.
Age‐Related Autophagy Impairment in Cervical and Lumbar Motor Neurons
Authors: Ducaji Emily C. , Sang Julie , Pareja‐Cajiao Miguel , Gransee Heather M. , Sieck Gary C. , Mantilla Carlos B.
Published: May 2022

Neuromuscular dysfunction increases with age and mobility restrictions decrease quality of life for the elderly. A hallmark of aging is the aggregation of proteins and damaged components within a cell, which is especially detrimental to post‐mitotic cells such as motor neurons. Autophagy, a multistep catabolic process, is responsible for the disposal of damaged cellular components. Accumulation of autophagy markers may differ across motor neuron pools consistent with differences in aging effects across muscles. Autophagy is characterized by the elongation of a double‐membrane vacuole around the tagged cargo which fuses with a lysosome and is subsequently degraded. In the present study, expression levels of factors for autophagy initiation (Beclin1), elongation (LC3I, LC3II, the LC3II/I ratio, ATG7, and the ATG5/12 complex), and degradation (p62 clearance) were determined in the cervical (CSC) and lumbar spinal cord (LSC) of male and female C57BL/6 mice at 6, 18, and 24 months of age (n=8/age) using Western blot, spanning a period where aging differences manifest in forelimb vs. hindlimb muscles. A mixed linear model with animal as a random effect was used to compare the effect of age, tissue, sex, and their interaction on the relative expression of each autophagy factor. There was an age*tissue interaction for Beclin1 at 24 mo, with greater Beclin1 expression in LSC than CSC. There was an overall effect of age on LC3I expression, with 24 mo greater than 6 mo, and no changes in LC3II expression. The LC3II/I ratio was significantly different by tissue, whereby CSC had a greater LC3II/I ratio than that of LSC. Expression of ATG7 had a tissue*sex interaction, with ATG7 in females greater in LSC than CSC. There were no changes in ATG5/12 complex. Finally, there was an age and age*tissue interaction in p62 expression. p62 was significantly greater at 24 mo than at 18 mo, and at 18mo the LSC had greater p62 expression than CSC. These results suggest greater impairment of autophagy flux in LSC compared to CSC at comparable ages, consistent with greater susceptibility to aging effects in hindlimb muscles. Future studies will evaluate motor neuron‐specific changes in markers of autophagy elongation (i.e., LC3) and p62 clearance.
T cell differentiation and lineage choice are determined by the TCR
Authors: Miles John , Watkins Thomas , Darko Sam , Wijaya Kuatrinnus , Cooper Martha , Ransier Amy , Waardenberg Ashley , Amante Fiona , Mccarthy James , Price David , Burrows Scott , Doolan Denise , Field Matt , Douek Daniel
Published: May 2022

Next‐generation sequencing technologies have revealed that adaptive immunity is underpinned by a vast array of T cell receptors (TCRs). However, it has proven difficult to interpret these extensive datasets, in part because the field previously lacked a comprehensive and internally controlled reference atlas encompassing the full spectrum of phenotypically defined subsets in each lineage. To address this knowledge gap, we sequenced 74 million TCRs expressed by discrete CD4+ and CD8+ memory T cell populations across genetically unrelated individuals, providing a resource to inform basic and applied studies of repertoire compartmentalisation within the adaptive immune system. Using this resource, we found that T cell differentiation could not be explained solely by the self‐renewing effector model and, unexpectedly, that T cell fate could be predicted by specific genetic and physicochemical features of the TCR.
Shikimate Kinase; Searching for Potential Novel Anti‐Tubercular Agents
Authors: Ogrodniczuk Marcin , Fuanta René
Published: May 2022

Tuberculosis is a respiratory infection with over 10 million reported cases each year. This infection rate is responsible for over two million deaths annually, second only to HIV in fatalities among infectious diseases annually. Studies in the last decade have shown that tuberculosis rates have gradually increased. This observation suggests that there is an alarming increase in the prevalence of drug resistant strains of tuberculosis, thus the need for the discovery of novel antitubercular agents. The shikimate pathway is a seven step metabolic route that produces aromatic amino acids and other cellular metabolites. The target enzyme in this project, Mycobacterium tuberculosis Shikimate Kinase (MtSK), catalyzes the 5th step of this pathway. MtSK converts shikimate to shikimate 3 phosphate. The overall goal of this project is to express and characterize MtSK to screen for potential antitubercular agents. Initial methods included a bacterial transformation of XL1 blue competent E.coli cells. This preliminary transformation was performed using a pET‐21b plasmid with an aroK gene inserted into the multiple cloning site. Successfully transformed XL1 blue cells were cloned and a second transformation of BL21 DE3 competent cells was performed. Initial small scale expression showed the presence of a band around 20 kDa. The theoretical mass of the enzyme is 19.6 kDa which suggests MtSK was successfully expressed. Expression analysis for large scale supported data from small scale as a band of 20 kDa was present. The purity and molecular weight of MtSK were confirmed by nickel affinity chromatography as well as ESI‐LC‐MS. ATP‐dependent kinetic parameters determined via a spectrophotometric coupled assay showed a kcat of 50 ± 6 mM, KM of 0.2 ± 0.04 mM. shikimate dependent kinetic parameters showed a kcat of 55 ± 2 mM, KM of 1.8 ± 0.1 mM. Quenching intrinsic tyrosine fluorescence showed binding affinities similar to ATP and shikimate‐dependent parameters. The marine compound, avarone showed substantial quenching of intrinsic fluorescence. The inhibitory mechanism of avarone on MtSK is currently under investigation.
Polybromo‐1 missense mutations found in renal cancer patients affect bromodomain stability and biological function
Authors: Jiao Guanming , Goetz Christopher , Bursch Karina , Nuñez Raymundo , Olp Michael , Zimmerman Michael , Urrutia Raul , Smith Brian , Dykhuizen Emily
Published: May 2022

Chromatin structure is important in modulating gene expression. A central component of chromatin structure is the covalent post‐translational modification (PTM) of histones. Distinct histone PTMs can determine the accessibility of chromatin and recruit different effector proteins and components of the transcriptional machinery. Histone are modified by “writer” and “eraser” enzymes that can add and remove PTMs, which are recognized by evolutionarily conserved reader domains. Bromodomain is one type of evolutionarily conserved “reader” domain composed of ~110 amino acids, including a conserved asparagine that specifically binds acetylated lysine. There are approximately 80 bromodomains in humans, primarily in chromatin‐associated proteins. Most proteins contain one or two bromodomains. The exception is Polybromo‐1, which contains six tandem bromodomains in addition to two bromo‐adjacent homolog (BAH) domains involved in protein‐protein interactions and a high mobility group (HMG) for interacting with DNA. PBRM1 is a subunit of the polybromo‐associated BAF (PBAF) chromatin remodeling complex, one of three major SWI/SNF subcomplexes found humans. These chromatin remodeling complexes alter chromatin accessibility by evicting, sliding and exchanging nucleosomes on DNA.

In clear cell renal cell cancer carcinoma (ccRCC), the most common subtype of kidney cancer, PBRM1is the second most mutated gene after VHL, with PBRM1mutations found in approximately 40% of ccRCC patients. Mouse models indicate that PBRM1 deletion paired with VHL deletion in the kidney results in tumors, establishing PBRM1 as a bona fide tumor suppressor. While most PBRM1 mutations in patients are also loss of function mutations, ~15‐20% of PBRM1 mutations are missense mutations, with a large portion found at highly conserved residues in the fourth bromodomain (BD4). Using recombinant PBRM1 BD4 mutants, we have assessed how the most common missense mutations found in patients affect the stability and acetyllysine binding of PBRM1 BD4, revealing new insight into bromodomain structure and function. In addition we have expressed a subset of these PBRM1 missense mutations in renal cancer cell lines and assessed how they affect PBRM1 binding to acetyllysine substrates, and subsequent renal cancer growth.
The strength of WWOX binding with protein partners correlates with cancer suppression and potentially with inhibition of Alzheimer's disease progression
Authors: Chang Nan‐Shan
Published: May 2022

Tumor suppressor WW domain‐containing oxidoreductase (WWOX) is one of the risk factors for Alzheimer's disease (AD), a neurodegenerative disease. WWOX binds Tau via its C‐terminal SDR domain and interacts with Tau phosphorylating enzymes ERK, JNK, and GSK‐3β, so as to limit AD progression. Loss of WWOX in newborns leads to severe neural diseases and early death. Gradual loss of WWOX protein in the hippocampus and cortex starting from middle age may slowly induce aggregation of a protein cascade that ultimately causes accumulation of extracellular amyloid beta plaques and intracellular tau tangles, along with reduction in inhibitory GABAergic interneurons, in AD patients over 70 years old. Age‐related increases in pS14‐WWOX accumulation in the brain promotes neuronal degeneration. Suppression of Ser14 phosphorylation by a small peptide Zfra leads to enhanced protein degradation, reduction in NF‐κB‐mediated inflammation, and restoration of memory loss in triple transgenic mice for AD. Intriguingly, tumor suppressors p53 and WWOX may counteract each other in vivo, which leads to upregulation of AD‐related protein aggregation in the brain and lung. WWOX has numerous binding proteins. We reported that the stronger the binding between WWOX and its partners, the better the suppression of cancer growth and reduction in inflammation. Thus, the stronger complex formation between WWOX and partners may provide a better blockade of AD progression.
Role of locus coeruleus expressing angiotensin type 1 receptors (AT1R) neurons in fear learning and stress‐induced anxiety
Authors: Yu Zhe , Marvar Paul
Published: May 2022

Background

The renin‐angiotensin system (RAS) has been implicated in stress‐related disorders, however the central mechanisms responsible for this remains unknown. The locus coeruleus (LC), a major noradrenergic nucleus of the brain, plays a critical role in modulating anxiety‐like behaviors. The LC has also been previously shown to express angiotensinogen (AGT), the pre‐cursor for angiotensin, as well as strong expression of angiotensin II receptors, but its role in stress‐related disorders has not been examined. Using angiotensin II type 1 receptor (AT1R)‐eGFP and Cre mice combined with neuroanatomical and behavioral approaches, we examined the role of LC expressing AT1R in fear‐ and anxiety‐related behavior.

Methods

RNAscope® in situ hybridization assay was used to analyze cellular mRNA expression of AGT in the LC while in vivo chemogenetics combined with behavioral testing in AT1R‐Cre mice mouse was used to examine the role of LC‐AT1R cells in fear memory and stress‐induced anxiety. Further, dual immunohistochemistry plus retrograde tract tracing was used to characterize LC AT1R‐eGFP+ cells and limbic circuit connections.

Results

AGT mRNA and AT1R‐eGFP+ immunoactivity was found localized to the LC. The majority of AT1R‐eGFP+neurons (94%) in LC were co‐localized with tyrosine hydroxylase, a marker for norepinephrine‐containing neurons. Retrograde labeling revealed that some of these AT1R‐eGFP+ neurons send projections to the basolateral amygdala (BLA), an important brain structure for modulating stress induced fear related anxiety responses. Next, the AT1R+ neurons in LC were silenced using Cre‐dependent inhibitory designer receptor exclusively activated by designer drug (hM4Di DREADD) expression followed by Clozapine‐n‐oxide (CNO) administration. Silencing the LC AT1R‐expressing neurons prior to fear extinction training impaired the extinction of learned fear as shown by increased percent freezing during the training (time × drug interaction, F (7, 70) = 3.219, p<0.01, n=6) (Fig 1). Furthermore, restraint stress‐induced anxiety behavior was attenuated by LC AT1R+ neuron inhibition, as shown by increased center entries (22.7 ± 7.3 Saline v.s. 50.5 ± 8.8 CNO, p<0.05, n=6) and % time in center (2.97 ± 1.14 Saline v.s. 8.6 ± 1.4 CNO, p<0.05, n=6) in the open field test, and increased open arm entries (5 ± 1.3 Saline v.s. 12 ± 1.1 CNO, p<0.05, n=6) in the elevated plus maze test (Fig. 2).

Conclusion

These findings provide evidence for a novel angiotensinergic LC cell type and position the LC AT1R as a potential mediator of noradrenergic regulation in learned fear and stress‐induced anxiety. Future studies are needed to fully characterize the underlying neurocircuits and neuropeptide modulators that likely interact with the LC AT1R expressing neurons during stress‐related behaviors.
Synthesis and Characterization of Biopolyol‐based Waterborne Polyurethane Modified through Complexation with Chitosan
Authors: Choi Soonm , Han Sungsoo , Shin Eunjoo
Published: May 2022

In this study, a series of castor oil‐based anionic waterborne polyurethane (CWPU) systems which is suggested as green elastomers with diverse applications in films and coatings, was prepared by modified with O‐carboxymethyl chitosan (CS) as not only a reinforcing filler but a chain‐extender of polyurethane prepolymer to enhance the properties of polyurethanes. Moreover, Not only was the system obtained with castor oil‐based polyol in the absence of a catalyst, but it was maintained with low viscosity by using acetone instead of toxic methyl ethyl ketone (MEK) during the synthesis process. The sizes, zeta potential, chemical formation, and morphology of the CWPU‐CS composites had been investigated by dynamic light scattering (DLS), infrared spectroscopy (IR), and scanning electron microscopy (SEM). Moreover, the results show that the modification allows to enhance storage/loss modulus, tensile properties, thermal stability at high temperature, and biocompatibility of CWPU and CWPU/CS nanocomposites according to various contents of CS.
Using Portfolio in Medical Education: a systematic review
Authors: Barros Mirna D. , Lopes Cristiane , Mendes Carlos J. L. , Tempski Patricia Z.
Published: May 2022

Introduction

The educational landscape of medical courses was transformed by competency based learning, triggering changes in necessities of new and different learning methods and assessment tools. One of these tools was the use of the learning and assessment portfolios. Portfolio is a collection of student work that exhibits the student’s efforts, progress and achievements. In medicine, portfolios are used to study critical thinking and self‐directed learning during the development from student to the professional and the general practitioners.

Objetive

The aim of this review is to answer how and what is the purpose the learning portfolio is applied in medical education

Method

We performed a systematic search of PUBMED electronic database, from 2011 to 2021, resulting in 740 articles. After the inclusion and the exclusion criteria were applied, we extracted and analyzed information from the selected articles. Descriptive statistical tools were used to characterize the profile of the articles.

Results

In total, 48 qualitative studies were included, 75.0%(n=36) about undergraduate and graduate medical students portfolios. The most frequents outcomes were: assessment portfolio and competencies (25.0%), perception, satisfaction and use of portfolio by students (20.8%) and portfolio in reflexive practice and learning self‐regulation (18.8%).

Conclusion

Medical schools, in several countries, use educational portfolio, mostly as an educational tool for undergraduate, graduate (residence) students and, less frequently, for medical professionals for validation or revalidation of diplomas and specialist titles. The main purpose of using portfolios is to draw on student reflection and frequent feedback to assess learning outcomes and the development of skills and competences. The heterogeneity of methods, the lack of control groups and the small number of samples found in articles about the use of the portfolio in Medicine courses were weak points for comparing the outcomes.
The Hsp90 Chaperone Regulates p38 Activation During ER Stress
Authors: Enos Madeleine R. , Brewster Jay L.
Published: May 2022

Diseases such as diabetes, Alzheimer’s disease, and Parkinson’s disease can be characterized by the presence of endoplasmic reticulum stress. The endoplasmic reticulum is an organelle that plays a major role in protein synthesis, but an accumulation of misfolded proteins within the ER lumen causes the organelle to release a stress signal through the unfolded protein response (UPR). Despite being present in many disorders, there are alternative signaling routes within the UPR branches that are not fully understood. Perk dimerization initiates one of three main signaling cascades in the UPR by phosphorylating eIF2α and causing a cell‐wide pause in mRNA translation; however, a study has shown that outside of the established pathway, activation of Perk results in p38 activation, which induces apoptosis during prolonged ER stress. The mechanism responsible for p38 activation is still unknown. One route for elucidating the regulation of p38 activation during ER stress is the Hsp90 chaperone. The Hsp90 chaperone complex sequesters p38 in the cytoplasm and prevents its auto‐activation under normal conditions, so we hypothesized that Perk activation may mediate post‐translational modification of the Hsp90 complex in a manner that would release p38, allowing it to activate. In this study, Tunicamycin‐induced ER stress and Hsp90 inhibition were applied to BHK21 fibroblasts, a cell line in which ER stress has been well characterized, and dissociation of the p38‐Hsp90 complex was measured through immunoblot and co‐immunoprecipitation analysis. Initial immunoblot results from 50nM and 200nM of tunicamycin reconfirm that moderate doses of tunicamycin induced p38 activation in a dose dependent manner. Co‐immunoprecipitation of Hsp90 reconfirmed that tunicamycin‐induced ER stress causes p38 to dissociate from Hsp90. Previous experiments with co‐immunoprecipitation of p38 by Jingyi Chen revealed that treatment with 50nM of tunicamycin resulted in 0.3 decrease in fold induction after 15 minutes. Unexpectedly, we found that inhibition of Hsp90 causes it to exhibit increased binding of p38 with an peak average fold increase of 7 after treatment with 5uM of Hsp90‐I (17‐AAG) for 30 minutes, which suggests Hsp90 as a potential regulator for p38. Because p38 plays an important role in the induction of many intracellular signaling pathways, learning ways to regulate its actions within the context of ER stress may be beneficial in mediating symptoms of disease.
Histological study of a low‐cost embalming technique with preservation for nearly three years at room temperature
Authors: Masuko Telma S. , dos Santos Andrade Lucas , Ottone Nicolás E. , Baptista Carlos A. C. , Barros Mirna D.
Published: May 2022

Introduction

The fixation of cadavers occurs when substances prevent tissue decomposition and is also called embalming. Various techniques for fixing and preserving cadavers, more or less sophisticated, have been described over the last few years. This work is the continuation of a research line on the fixation technique published in 2020 by Masuko & Andrade, that allows the fixation and conservation of a human cadaver at room temperature for a long period (more than two years) with characteristics and mobility similar to those of a fresh corpse.

Materials and Method

In this step we use a donated 14‐years‐old female cat, that was embalmed using a solution published by Masuko & Andrade, in 2020, with peristaltic pump [alcohol 1000ml; phenol 1000mg; glycerin 1000ml; sodium nitrate 1000mg; formaldehyde 2000ml; distilled water 14000ml]. Femoral arterial accesses and complementary injections of formaldehyde were performed in muscles limbs. The cat was maintained at room temperature, ranging from 19.7 to 34.8ºC (67.46–94.64ºF) and the humidity (37–97%) in body bag covered with blackout sheet, without any additional preservation method to mantain the animal. Samples of tissues (skin and subcutaneous tissue, muscle and colon) were collected after 1m175 days of embalming and submitted to histological staining (HE).

Results

This method resulted in a soft and flexible specimen with almost natural colors (Figs. 1, 2). Histological analysis indicated the preservation of tissue and cell structure in the different samples examined, even after 1,175 days of fixation. Epidermis and dermis structure identifiable and preserved, making it possible to visualize attachments such as hair follicles. In dermis, it is possible to identify blood vessels and the general structure of the unmodeled dense connective tissue; muscle tissue is well preserved, with the structure of muscle fibers identifiable both in the longitudinal and transversal sections; the colon presents the general structure of the tunics preserved. It is possible to identify mucosal villi, despite the poor clarity of the already altered lining epithelium, vessels in the submucosal conjunctiva and the smooth musculature of the tunica muscularis.

Discussion

The preservation technique presented in 2020 has low cost and easy execution, being effective in humans and now in animals, maintaining the morphological characteristics of the anatomical specimen for an extended period of time.

Conclusion

We present an alternative anatomical technique for teaching and research in anatomy centers that have to deal with the toxicity of fixation products and the costs of obtaining and maintaining anatomical specimens.
Surgeon Variation in Perioperative Opioid Prescribing and Medium- or Long-term Opioid Utilization after Total Knee Arthroplasty: A Cross-sectional Analysis
Authors: Cen Xi , Jena Anupam B. , Mackey Sean , Sun Eric C.
Published: May 2022

Background

Whether a particular surgeon’s opioid prescribing behavior is associated with prolonged postoperative opioid use is unknown. This study tested the hypothesis that the patients of surgeons with a higher propensity to prescribe opioids are more likely to utilize opioids long-term postoperatively.

Methods

The study identified 612,378 Medicare fee-for-service patients undergoing total knee arthroplasty between January 1, 2011, and December 31, 2016. “High-intensity” surgeons were defined as those whose patients were, on average, in the upper quartile of opioid utilization in the immediate perioperative period (preoperative day 7 to postoperative day 7). The study then estimated whether patients of high-intensity surgeons had higher opioid utilization in the midterm (postoperative days 8 to 90) and long-term (postoperative days 91 to 365), utilizing an instrumental variable approach to minimize confounding from unobservable factors.

Results

In the final sample of 604,093 patients, the average age was 74 yr (SD 5), and there were 413,121 (68.4%) females. A total of 180,926 patients (30%) were treated by high-intensity surgeons. On average, patients receiving treatment from a high-intensity surgeon received 36.1 (SD 35.0) oral morphine equivalent (morphine milligram equivalents) per day during the immediate perioperative period compared to 17.3 morphine milligram equivalents (SD 23.1) per day for all other patients (+18.9 morphine milligram equivalents per day difference; 95% CI, 18.7 to 19.0; P < 0.001). After adjusting for confounders, receiving treatment from a high-intensity surgeon was associated with higher opioid utilization in the midterm opioid postoperative period (+2.4 morphine milligram equivalents per day difference; 95% CI, 1.7 to 3.2; P < 0.001 [11.4 morphine milligram equivalents per day vs. 9.0]) and lower opioid utilization in the long-term postoperative period (–1.0 morphine milligram equivalents per day difference; 95% CI, –1.4 to –0.6; P < 0.001 [2.8 morphine milligram equivalents per day vs. 3.8]). While statistically significant, these differences are clinically small.

Conclusions

Among Medicare fee-for-service patients undergoing total knee arthroplasty, surgeon-level variation in opioid utilization in the immediate perioperative period was associated with statistically significant but clinically insignificant differences in opioid utilization in the medium- and long-term postoperative periods.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Reliability and validity of Vancouver Scar Scale and Withey score after syndactyly release
Authors: Kim Jae Kwang , Park Jin Yeob , Shin Young Ho , Yang Jinseok , Kim Ho Yeon
Published: May 2022

This study aimed to analyze the reliability and validity of the Vancouver Scar Scale (VSS) and the Withey score after syndactyly release. Over a 3-year period, 13 patients who underwent syndactyly release were evaluated. The mean age at the time of syndactyly release was 12 months (range, 8–18 months), and the mean follow-up period was 29 months (range, 17–52 months). We obtained hand photographs and finger motion videos and collected the satisfaction scores for hand function and cosmesis. Three clinicians evaluated the hand photographs and finger motion video of each patient twice using the VSS and the Withey score. The interobserver and intraobserver reliabilities of the VSS and Withey score were determined using intraclass correlation coefficients (ICCs). The validity of the VSS and Withey score was determined using Spearman’s correlation test with the functional and cosmetic satisfaction score. The ICCs for the interobserver reliability of VSS were 0.31 and 0.39 for each measurement, and ICCs for the intraobserver reliability of VSS were 0.46, 0.51, and 0.54 for each observer. The ICCs for the interobserver reliability of the Withey score were 0.74 and 0.70, and the ICCs for the intraobserver reliability of the Withey score were 0.91, 0.74, and 0.96. The Withey score was significantly correlated with the satisfaction score for hand function and hand cosmesis, but the VSS was not. The VSS had poor interobserver reliability and fair intraobserver reliability, whereas the Withey score had good interobserver reliability and excellent intraobserver reliability based on photographic evaluation after syndactyly release.
Pigmented Purpuric Dermatosis of the Hand: Clinicopathologic Analysis of Six Cases With Review of the Literature
Authors: Runge John S. , Nakamura Mio , Sullivan Annette Nichole , Harms Paul W. , Chan May P.
Published: May 2022

Pigmented purpuric dermatosis (PPD) is a group of skin disorders characterized by red, brown, or golden macules and patches with cayenne pepper-like spots. Classic histopathologic features include a perivascular lymphocytic infiltrate with associated erythrocyte extravasation and hemosiderin deposition. Although PPD most commonly affects the lower extremities, upper extremity involvement has been infrequently reported. Cases involving the hands are particularly rare. We present 6 new cases of PPD involving the hand and review 17 previously reported cases in the literature. All cases in our series were unilateral and localized to the dorsum of the hand. PPD was considered clinically in only 2 of these cases. Histopathologic examination revealed hallmark features of PPD, namely a superficial perivascular lymphocytic infiltrate and extravasated erythrocytes. Previous reports of PPD involving the hand described concurrent involvement of other anatomic sites in most cases; only 4 cases (24%) were confined to the hands. Histopathologic descriptions of these reported cases were compatible with PPD. In sum, our series describes a unique and rare clinical presentation of PPD confined to the unilateral dorsal hand. Because of the unusual presentation, biopsy is often required for accurate diagnosis.
A Rare Case of Myxochondroid Metaplasia of the Plantar Foot With Review of Histopathological Mimics
Authors: Alomari Ahmed K. , Warnock Aaron , Cummings Oscar W.
Published: May 2022

Chondromyxoid metaplasia can rarely lead to the formation of a distinctive tumor-like proliferation in the plantar foot. This is thought to represent a reactive or reparative process, possibly due to chronic trauma. For the unwary dermatopathologist, this could represent a diagnostic challenge. Herein, we review the clinical, histopathological, and molecular presentation of an athletic 17-year-old boy with a soft tissue mass arising in the right plantar foot. Microscopic examination showed a relatively circumscribed proliferation of spindle cells with abundant chondromyxoid stroma, hyalinization, and diffuse ERG reactivity. We also review characteristics of this entity that help differentiate it from clinical and histopathologic mimics and postulate possible links with soft tissue chondromas and immature chondroid choristoma.
Primary Care Diagnosis and Treatment of Attention-Deficit/Hyperactivity Disorder in School-Age Children: Trends and Disparities During the COVID-19 Pandemic
Authors: Bannett Yair , Dahlen Alex , Huffman Lynne C. , Feldman Heidi M.
Published: May 2022

Objective:

The aim of this study was to assess rates of primary care provider (PCP) diagnosis and treatment of school-age children with attention-deficit/hyperactivity disorder (ADHD) during the COVID-19 pandemic compared with prepandemic years and to investigate disparities in care.

Method:

We retrospectively analyzed electronic health records from all primary care visits (in-person and telehealth) of children aged 6 to 17 years seen between January 2016 and March 2021 in a community-based primary health care network (n = 77,298 patients). Study outcomes are as follows: (1) number of primary care visits, (2) number of visits with ADHD diagnosis (ADHD-related visits), (3) number of PCP prescriptions for ADHD medications, (4) number of patients with first ADHD diagnoses, and (5) number of first PCP prescriptions of ADHD medications. Interrupted time series analysis evaluated changes in rates of study outcomes during 4 quarters of the pandemic year (March 15, 2020–March 15, 2021) compared with prepandemic years (January 1, 2016–March 14, 2020). Patient demographic characteristics during prepandemic and pandemic years were compared.

Results:

ADHD–related visits dropped in the first quarter of the pandemic year by 33% (95% confidence interval, 22.2%–43.6%), returning to prepandemic rates in subsequent quarters. ADHD medication prescription rates remained stable throughout the pandemic year. Conversely, rates of first ADHD diagnoses and first medication prescriptions remained significantly lower than prepandemic rates. The proportion of ADHD-related visits for patients living in low-income neighborhoods was lower in the pandemic year compared with prepandemic years.

Conclusion:

Ongoing treatment for school-age children with ADHD was maintained during the pandemic, especially in high-income families. Socioeconomic differences in ADHD-related care emphasize the need to improve access to care for all children with ADHD in the ongoing pandemic and beyond.
Physician role differentiation: Patients, practice patterns, and performance
Authors: Comfort Leeann N. , Bambury Elizabeth , Atkinson Mariam Krikorian
Published: May 2022

Background

Multispecialty clinical settings are increasingly prevalent because of the growing complexity in health care, revealing challenges with overlaps in expertise. We study hospitalists and inpatient specialists to gain insights on how physicians with shared expertise may differentiate themselves in practice.

Purpose

The aim of this study was to explore how hospitalists differentiate themselves from other inpatient physicians when treating patient cases in areas of shared expertise, focusing on differences in patient populations, practice patterns, and performance on cost and quality metrics.

Methodology

We use mixed-effects multilevel models and mediation models to analyze medical records and disaggregated billing data for admissions to a large urban pediatric hospital from January 1, 2009, to August 31, 2015.

Results

In areas of shared physician expertise, patients with more ambiguous diagnoses and multiple chronic conditions are more likely to be assigned to a hospitalist. Controlling for differences in patient populations, hospitalists order laboratory tests and medications at lower rates than specialists. Hospitalists’ laboratory testing rate had a significant mediating role in their lower total charges and lower odds of their patients experiencing any nonsurgical adverse events compared to specialists, though hospitalists did not differ from specialists in 30- and 90-day readmission rates.

Practice Implications

Physicians with shared expertise, such as hospitalists and inpatient specialists, differentiate their roles through assignment to ambiguous diagnoses and multisystem conditions, and practice patterns such as laboratory and medication orders. Such differentiation can improve care coordination and establish professional identity when roles overlap.
Cemiplimab for Orbital Squamous Cell Carcinoma in 11 Cases
Authors: Steren Benjamin , Burtness Barbara , Bhatia Aarti , Demirci Hakan , Shinder Roman , Yoo David , Tse Brian , Pointdujour-Lim Renelle
Published: May 2022

Purpose:

To review the demographics, clinical features, and response of orbital squamous cell carcinoma treated with cemiplimab.

Methods:

This is a retrospective multi-institutional series. Patient characteristics, drug dosing, duration, and response to treatment were evaluated.

Results:

The study cohort consisted of 11 patients from 5 institutions. All patients received a regimen of 350 mg q 3 weeks and an average of 11.2 cycles (SD 5.8). No patient experienced significant side effects requiring treatment or cessation of cemiplimab. Complete response was achieved in 9 patients (82%) treated with cemiplimab.

Conclusions:

Immune checkpoint inhibitors, such as cemiplimab provide a globe-sparing option for the treatment of orbital squamous cell carcinoma. It is important to consider these agents especially when orbital exenteration is the alternative.
Emerging roles of circular RNAs in cancer: a narrative review
Authors: Guo Shixiang , Zhang Junfeng , Tao Junyu , Zhu Jinfeng , Zheng Ruixin , Wang Huaizhi
Published: May 2022

Circular RNAs (circRNAs) constitute a novel class of endogenous noncoding RNAs characterized by a covalently closed structure and involved in multiple biological processes. The main biological functions and properties of circRNAs can be defined by five features: a “sponging” effect on other RNA species, post-transcriptional regulation, rolling circle translation, generation of pseudogenes, and splicing interference. Although circRNAs were first detected decades ago, the role of circRNAs and the mechanisms underlying their actions remain incompletely characterized. Recently, circRNAs were reported to play indispensable roles in regulating metabolic and signal transduction events controlling the proliferation, migration, and survival of cells. Importantly, many studies demonstrated that dysregulated circRNA expression is associated with the development of multiple diseases, including cancer. In this review, we summarize current knowledge on the roles and mechanisms of circRNAs in cancer and discuss their functions as oncogenes or tumor suppressors in different tumor types.
Organisational models at the emergency department to reduce hospital admissions among paediatric patients: a systematic literature review
Authors: Detollenaere Jens , Van de Voorde Carine , Van den Heede Koen
Published: May 2022

Paediatric attendances at the emergency department (ED) are often admitted to the hospital less than 24 h to allow time for more extended evaluation. Innovative organisational models could prevent these hospital admissions without compromising safety or quality of delivered care. Therefore, this systematic review identifies evidence on organisational models at the ED with the primary aim to reduce hospital admissions among paediatric patients. Following the PRISMA guidelines, three bibliographic databases (Ovid Medline, Embase, and Cochrane Library) were searched. Studies on organisational models in Western countries, published between January 2009 and January 2021, which applied a comparative design or review and studied at least hospital admission rates, were included. Analyses were mainly descriptive because of the high heterogeneity among included publications. The primary outcome is hospital admission rates. Secondary outcomes are ED length of stay (LOS), waiting time, and patient satisfaction. Sixteen publications described several innovative organisational models ranging from the creation of dedicated units for paediatric patients, innovative staffing models to bringing paediatric critical care physicians to patients at rural EDs. However, the effect on hospital admission rates and other outcomes are inconclusive, and some organisational models may improve certain outcomes in certain settings or vice versa. It appears that a paediatric consultation liaison team has the most consistent effect on hospital admission rates and LOS of paediatric patients presenting with mental problems at the ED. Implementing new innovative organisational models at the ED for paediatric patients could be worthwhile to decrease hospital admissions. However, the existing evidence is of rather weak quality. Future service developments should, therefore, be conducted in a way that allows objective evaluation.
The effect of a home-based coaching program on heart rate variability in subacute stroke patients: a randomized controlled trial
Authors: Guediri Amine , Chaparro David , Borel Benoit , Daviet Jean Christophe , Compagnat Maxence , Mandigout Stéphane
Published: May 2022

Autonomic imbalance in stroke is characterized by increased sympathetic activity and reduced vagal nerve activity. Physical activity could be a strategy to counteract autonomic control impairments after a stroke. The aim of the study was to evaluate the effect on heart rate variability of a 6-month coaching program in a home setting in subacute stroke patients. Eighty-four stroke patients participated in the study. They were randomly assigned to the experimental group or the control group. The intervention was a coaching program, consisting of physical activity, home visits and a weekly phone call. Patients were evaluated after hospital discharge (T0) and at the end of the 6-month period (T1). Heart rate variability measures were recorded in the supine and orthostatic positions. Time and frequency domain values were treated using Kubios. Distance on 6 minutes walking test (6MWT), Barthel and motricity index and modified functional ambulation categories were evaluated. No effects were found on time and frequency domain values in the supine and orthostatic positions in either group. Walking distance on 6MWT increased significantly between T0 and T1 in experimental group (377 ± 141–448 ± 140 m; P < 0.02) with no effects in control group (373.6 ± 150.6–394.6 ± 176.4 m). No other functional effects were found. A coaching program in a home setting had no effect on heart rate variability, probably due to time of recovery and exercise intensity. Future research is needed to understand the lack of changes in heart rate variability by physical activity in subacute stroke patients.
The Mental Effect of Music on the Personal State in Terms of Depressive Personality Disorders
Authors: Zhang Ling
Published: May 2022

The use of music as a basis for overcoming depressive personality disorders is possible only if the individual is ready for this therapy. Music therapy affects, first of all, the very structure of personality, its dynamic filling with current social and political tendencies, and allows to highlight problem areas, which are often viewed as complex in the structure of other psychological problems. The purpose of the current study was the determination and justification of the corresponding criteria in relation to this, as well as the methodology for diagnosing the studied phenomenon. The diagnostics involved five groups of psychologists (in general, 438 persons). The preparedness of therapists for preventive and remedial work with patients with depressive conduct disorder was evaluated. To test the truth of the statistical hypothesis the Wilcoxon-Mann-Whitney criterion was used. The novelty of the article is determined by the fact that the use of music is considered only as a therapeutic measure, and not associated with the use of medication or sedation. The developed system of the use of music therapy can be implemented only under the condition of applying special factors and principles. These factors include, first of all, the ability to respond to the personality and, if necessary, adjust the therapy strategy.