bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Influence of Relationship-Centered Coaching on Physician Perceptions of Peer Review in the Context of Mandated Regulatory Practices
Authors: Arabsky Sherylyn , Castro Nadya , Murray Michael , Bisca Ioana , Eva Kevin W. 
Published: August 2020

Purpose
Medical regulatory authorities are legally mandated to protect patients by monitoring the practice of medicine. While principally a matter of public safety, many pursue this mission by establishing quality improvement initiatives that prioritize professional development for all rather than identification of substandard performers. Engaging practitioners in directed learning opportunities, however, is rife with challenge given inherent social complexities. This study was run to explore whether relationship-centered coaching could improve physicians’ perceptions of the value of engaging with College-mandated peer review.

Method
A quasi-experimental analysis was performed on physician ratings of the effectiveness of peer assessor interactions and assessment processes during 3 time periods: (1) an historical control (March 2016–December 2016; n = 296); (2) a period after assessors were trained to deliver feedback using relationship-centered coaching (December 2016–March 2017; n = 96); and (3) after physicians were given more capacity to choose patient records for peer review and engage in discussion about multisource feedback results (March 2017–December 2018; n = 448).

Results
Psychometric analyses supported the aggregation of survey items into assessor interaction and assessment process subscores. Training assessors to engage in relationship-centered coaching was related with higher assessor interaction scores (4.64 vs 4.47; P < .05; d = 0.37). Assessment process scores did not increase until after additional program enhancements were made in period 3 (4.33 vs 4.17, P < .05, d = 0.29).

Conclusions
Despite peer interactions being inherently stressful for physicians when they occur in the context of regulatory authority visits, efforts to establish a quality improvement culture that prioritizes learning can improve physicians’ perceptions of peer review.
Fat Grafting as a Novel Treatment for Xerostomia
Authors: Bamba Ravinder , Shadfar Scott , Van Natta Bruce W. 
Published: August 2020

Purpose:
Within the context of xerostomia, there is evidence that adipose-derived stem cells (ASCs) can differentiate into salivary gland cells in the appropriate environment. The purpose of this study was to preliminarily investigate whether fat grafting as practiced in the United States would be an effective treatment for xerostomia.

Methods:
Patients were selected for the study if they were seeking treatment for xerostomia after radiation treatment to the head and neck for cancer treatment. Fat grafting was performed in bilateral parotid and submandibular glands. Visual Analog Scale (VAS) of xerostomia was used both preoperatively and postoperatively to assess the effect upon xerostomia symptoms.

Results:
Nine patients were included in this study. All patients had complaints of long-standing xerostomia. The average preoperative VAS score was 9.1. All patients tolerated all rounds of fat grafting with no complications. The average postoperative VAS score was 6.0. Compared to preoperative scores, all patients had improvement in VAS scores. The decrease in average VAS score postoperatively (9.1 versus 6.0) was statistically significant (P = 0.007).

Conclusions:
Our study showed that there was improvement in xerostomia symptoms with autologous fat transfer alone. This is a novel finding for fat grafting demonstrating regenerative potential. There has been extensive basic research that has shown that adipose-derived mesenchymal stem cells can have a protective and restorative role after salivary gland radiation damage. Our case series is the first report of fat grafting having a similar reported outcome.
Level of Evidence: 4
Upper Airway Changes Following Different Orthognathic Surgeries, Evaluated by Cone Beam Computed Tomography: A Systematic Review and Meta-analysis
Authors: Shokri Abbas , Ramezani Kousar , Afshar Arghavan , Poorolajal Jalal , Ramezani Navid 
Published: August 2020

Purpose:
This study sought to assess the upper airway changes following different orthognathic surgeries using cone-beam computed tomography.

Methods:
An electronic search of the literature was conducted in major electronic databases including Medline (PubMed), Web of Science, Scopus, and Open Grey for articles published up to January 20, 2018. Human studies that evaluated the changes in the volume and minimum cross-sectional area of the upper airway or its subdivisions in patients who had undergone orthognathic surgery by use of cone-beam computed tomography were included. Manual search of the bibliographies of the included articles was also conducted. The included studies underwent risk of bias assessment.

Results:
A total of 1330 articles were retrieved. After excluding the duplicates and irrelevant articles, 41 studies fulfilled the eligibility criteria for this systematic review; out of which, 30 entered the meta-analysis. The majority of studies had a medium risk of bias. Mandibular setback, and maxillary advancement + mandibular setback decreased the volume of the upper airway (−6042.87 mm3 and −1498.78 mm3, respectively) and all its subdivisions in long-term (>3 months), except for the nasopharynx, the volume of which increased following maxillary advancement + mandibular setback. Mandibular advancement and maxillomandibular advancement both increased the upper airway volume in long-term (7559.38 mm3 and 7967.06 mm3, respectively); however, only the changes after the former procedure were significant. The minimum cross-sectional area increased after maxillomandibular advancement (161.43 mm2), and decreased following maxillary advancement + mandibular setback (−23.79 mm2) in long-term.

Conclusion:
There is moderate evidence to suggest that mandibular advancement is the only orthognathic movement that provides a statistically significant change in long-term upper airway volume.
SARS-CoV-2 surveillance in decedents in a large, urban medical examiner’s office
Authors: Brouwer Andrew F. , Myers Jeffrey L. , Martin Emily T. , Konopka Kristine E. , Lauring Adam S. , Eisenberg Marisa C. , Lephart Paul R. , Nguyen Teresa , Jaworski Andrea , Schmidt Carl J. 
Published: August 2020

AbstractBackgroundSARS-CoV-2 has become a global pandemic. Given the challenges in implementing widespread SARS-CoV-2 testing, there is increasing interest in alternative surveillance strategies.MethodsWe tested nasopharyngeal swabs from 821 decedents in the Wayne County Medical Examiner’s office for SARS-CoV-2. All decedents were assessed by a COVID-19 checklist, and decedents flagged by the checklist (237) were preferentially tested. A random sample of decedents not flagged by the checklist were also tested (584). We statistically analyzed the characteristics of decedents (age, sex, race, and manner of death), differentiating between those flagged by the checklist and not and between those SARS-CoV-2 positive and not.ResultsDecedents were more likely to be male (70% vs 48%) and Black (55% vs 36%) than the catchment population. Seven-day average percent positivity among flagged decedents closely matched the trajectory of percent positivity in the catchment population, particularly during the peak of the outbreak (March and April). After a lull in May to mid-June, new positive tests in late June coincided with increased case detection in the catchment. We found large racial disparities in test results: despite no statistical difference in the racial distribution between those flagged and not, SARS-CoV-2 positive decedents were substantially more likely to be Black (89% vs 51%). SARS-CoV-2 positive decedents were also more likely to be older and to have died of natural causes, including of COVID-19 disease.ConclusionsDisease surveillance through medical examiners and coroners could supplement other forms of surveillance and may serve as a possible early outbreak warning sign.
Association of mental disorders with SARS-CoV-2 infection and severe health outcomes: a nationwide cohort study
Authors: Jeon Ha-Lim , Kwon Jun Soo , Park So-Hee , Shin Ju-Young 
Published: August 2020

ABSTRACTBackgroundNo epidemiological data exists for the association between mental disorders and the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) severity.AimsTo evaluate the association between mental disorders and the risk of SARS-CoV-2 infection and severe outcomes following COVID-19.MethodsWe performed a cohort study using the Korean COVID-19 patient database based on the national health insurance data. Each patient with a mental or behavioral disorder (diagnosed during six months prior to the first SARS-CoV-2 test) was matched by age, sex, and Charlson comorbidity index with up to four patients without mental disorders. SARS-CoV-2 positivity risk and risk of death or severe events (intensive care unit admission, use of mechanical ventilation, and acute respiratory distress syndrome) post-infection were calculated using conditional logistic regression analysis.ResultsAmong 230,565 patients tested for SARS-CoV-2, 33,653 (14.6%) had mental disorders, 928/33,653 (2.76%) tested positive, and 56/928 (6.03%) died. In multivariate analysis with the matched cohort, there was no association between mental disorders and SARS-CoV-2 positivity risk (odds ratio [OR], 1.02; 95% confidence interval [CI], 0.92-1.12); however, a higher risk was associated with schizophrenia-related disorders (OR, 1.36; 95% CI, 1.02-1.81). Among confirmed cases, mortality risk significantly increased in patients with mental disorders (OR, 1.84, 95% CI, 1.07-3.15).ConclusionMental disorders are likely contributing factors of mortality following COVID-19. Although the infection risk did not increase in overall mental disorders, patients with schizophrenia-related disorders were more vulnerable to the infection.
Thermodynamics of DNA Hybridization from Atomistic Simulations
Authors: Zerze Gül H. , Stillinger Frank H. , Debenedetti Pablo G. 
Published: August 2020

AbstractStudying the DNA hybridization equilibrium via brute force molecular dynamics (MD) or commonly used advanced sampling approches is notoriously difficult at atomistic lengthscale. However, besides providing a more realistic modeling of this microscopic phenomenon, atomistic resolution is a necessity for some fundamental research questions, such as the ones related to DNA’s chirality. Here, we describe an order parameter-based advanced sampling technique to calculate the free energy surface of hybridization and estimate melting temperature of DNA oligomers at atomistic resolution, using a native topology-based order parameter. We show that the melting temperatures estimated from our atomistic simulations follow an order consistent with the predictions from melting experiments and those from the nearest neighbor model, for a range of DNA sequences of different GC content. Moreover, free energy surfaces and melting temperatures are calculated to be identical for D- and L-enantiomers of Drew-Dickerson dodecamer.Abstract FigureGraphical TOC Entry
Antisense oligonucleotides against monoacylglycerol acyltransferase 1 (Mogat1) improve glucose metabolism independently ofMogat1
Authors: Lutkewitte Andrew J. , Singer Jason M. , Shew Trevor M. , Martino Michael R. , Hall Angela M. , Finck Brian N. 
Published: August 2020

ABSTRACTObjectiveMonoacylglycerol acyltransferase (MGAT) enzymes catalyze the synthesis of diacylglycerol from monoacylglycerol. Previous work has suggested the importance of MGAT activity in the development of obesity-related hepatic insulin resistance. Indeed, antisense oligonucleotide (ASO)-mediated knockdown of the gene encoding MGAT1,Mogat1, reduced hepatic MGAT activity and improved glucose tolerance and insulin resistance in high fat diet (HFD) fed mice. However, recent work has suggested that some ASOs may have off-target effects on body weight and metabolic parameters via activation of the interferon alpha/beta receptor 1 (IFNAR-1) pathway.MethodsMice with whole-bodyMogat1knockout or a floxed allele forMogat1to allow for liver-specificMogat1-knockout (by either a liver-specific transgenic or adeno-associated virus-driven Cre recombinase) were generated. These mice were placed on a high fat diet and glucose metabolism and insulin sensitivity was assessed after 16 weeks on diet. In some experiments, mice were treated with control orMogat1or control ASOs in the presence or absence of IFNAR-1 neutralizing antibody.ResultsGenetic deletion of hepaticMogat1, either acutely or chronically, did not improve hepatic steatosis, glucose tolerance, or insulin sensitivity in HFD-fed mice. Furthermore, constitutiveMogat1knockout in all tissues actually exacerbated HFD-induced weight gain, insulin resistance, and glucose intolerance on a HFD. Despite markedly reducedMogat1expression, liver MGAT activity was unaffected in all knockout mouse models.Mogat1overexpression hepatocytes increased liver MGAT activity and TAG content in low-fat fed mice, but did not cause insulin resistance. Interestingly,Mogat1ASO treatment improved glucose tolerance in both wild-type andMogat1null mice, suggesting an off target effect. Inhibition of IFNAR-1 did not block the effect ofMogat1ASO on glucose homeostasis.ConclusionThese results indicate that genetic loss ofMogat1does not affect hepatic MGAT activity or metabolic homeostasis on HFD and show thatMogat1ASOs improve glucose metabolism through effects independent of targetingMogat1or activation of IFNAR-1 signaling.Abstract FigureHighlightsMogat1 liver-specific KO or KD does not improve metabolism in HFD fed mice.Whole-body Mogat1-deletion impairs insulin tolerance in HFD fed mice.Mogat1 ASOs improves whole body metabolism independently of gene knockdown.Blockade of the INFR response does not prevent off-target effects of Mogat1 ASOs.
MeCP2 deficiency exacerbates the neuroinflammatory setting and autoreactive response during an autoimmune challenge: implications for Rett Syndrome
Authors: Zalosnik MI , Fabio MC , Bertoldi ML , Castañares CL , Degano AL 
Published: August 2020

ABSTRACTBackgroundRett syndrome is a severe and progressive neurological disorder linked to mutations in the MeCP2 gene located on the X chromosome. So far it has not been established how the presence of a mutant form of MeCP2 can maintain essential regulation of immune responses to support the normal homeostasis of individuals. Since MeCP2 is mostly expressed as a “partially functional” protein in humans with RTT, the aim of our work was to evaluate whether a mutation in MeCP2 interferes with the induction of neuroinflammatory responses in real time.MethodsWe used MeCP2308/ymouse model (MUT) and exposed it to an autoimmune challenge, experimental autoimmune encephalomyelitis (EAE). WT and MUT mice were immunized with CFA-MOG or CFA alone (control) and clinical scores were evaluated daily. Animals were sacrificed at either 12 days post-induction (dpi, acute stage) or 30 dpi (chronic stage) and spleen and spinal cord were collected from individual mice for further studies. Cellular infiltration and microgliosis was evaluated by IHC. Cytokine production was assessed in spinal cord and in cultured splenocytes after MOG activation ex-vivo by cytometry and real time RT-PCR.ResultsOur results showed that MeCP2 deficiency increased the susceptibility to develop EAE, along with a defective induction of anti-inflammatory responses and an exacerbated MOG-specific reactivity with high IFNγ expression in peripheral immune sites. During the chronic stage, an increase in gene expression of pro-inflammatory cytokines (IFNγ, TNFα and IL-1β) and downregulation of genes relevant for immune regulation (IL-10, FoxP3 and CX3CR1) was found in MUT-EAE spinal cords.ConclusionsThis is the first study performed in a MeCP2 mutant mouse model that explores the pathophysiology and neuroinflammation in the context of an autoimmune challenge. We could establish that an MeCP2 mutation act intrinsically affecting neuroimmune interactions by promoting an inflammatory environment and a deficient immune regulatory setting. These results are relevant for understanding the consequences of MeCP2 mutations on immune homeostasis in MeCP2-related disorders, as well as setting the bases for further therapeutic interventions that consider the immune status in patients.
Rodent mnemonic similarity task performance requires the prefrontal cortex
Authors: Johnson Sarah A. , Zequeira Sabrina , Turner Sean M. , Maurer Andrew P. , Bizon Jennifer L. , Burke Sara N. 
Published: August 2020

AbstractMnemonic similarity task performance, in which a known target stimulus must be distinguished from similar lures, is supported by the hippocampus and perirhinal cortex and is known to decline in advanced age. Interestingly, disrupting hippocampal activity leads to mnemonic discrimination impairments when lures are novel, but not when they are familiar. This observation suggests other brain structures can support discrimination abilities as stimuli are learned. The prefrontal cortex (PFC) is critical for retrieval of remote events and executive functions, such as working memory, and is also particularly vulnerable to dysfunction in aging. Importantly, the medial PFC is reciprocally connected to the perirhinal cortex and neuron firing in this region coordinates communication between lateral entorhinal and perirhinal cortices to presumably modulate hippocampal activity. This anatomical organization and function of the medial PFC suggests that it contributes to mnemonic discrimination; however, this notion has not been empirically tested. In the current study, young adult male and female F344 x Brown Norway F1 hybrid rats were trained on a rodent object-based mnemonic similarity task, and surgically implanted with guide cannulae targeting prelimbic and infralimbic regions of the medial PFC. Prior to mnemonic discrimination tests, rats received PFC infusions of the GABAAagonist muscimol. Analyses of expression of the neuronal activity-dependent immediate-early geneArcin medial PFC and adjacent cortical regions confirmed muscimol infusions led to neuronal inactivation in the infralimbic and prelimbic cortices. Moreover, muscimol infusions in PFC impaired mnemonic discrimination performance relative to the vehicle control across all testing blocks when lures shared 50-90% feature overlap with the target. Thus, in contrast to prior results from rats given hippocampal muscimol infusions, PFC inactivation impaired target-lure discrimination regardless of the novelty or familiarity of the lures. These findings indicate the PFC plays a critical role in mnemonic similarity task performance, but the time course of PFC involvement is dissociable from that of the hippocampus.
IL-4 receptor targeting as an effective immunotherapy against triple-negative breast cancer
Authors: Parveen Sadiya , Siddharth Sumit , Cheung Laurene S , Kumar Alok , Murphy John R , Sharma Dipali , Bishai William R 
Published: August 2020

ABSTRACTIn many solid tumors including triple-negative breast cancer (TNBC), IL-4 receptor (IL-4R) upregulation has been shown to promote cancer cell proliferation, apoptotic resistance, metastatic potential and a Th2 response in the tumor microenvironment (TME). Immunosuppressive cells in the TME including myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) also express the IL4-R. We hypothesized that selective depletion of IL4-R bearing cells in TNBC may have dual cytotoxic and immunotherapeutic benefit. To selectively target IL-4R+cells, we genetically constructed, expressed and purified DABIL-4, a fusion protein toxin consisting of the catalytic and translocation domains of diphtheria toxin fused to murine IL-4. We found that DABIL-4 has potent and specific cytotoxic activity against TNBC cellsin vitro. In murine TNBC models, DABIL-4 significantly reduced tumor growth, splenomegaly and lung metastases, and this was associated with reductions in MDSC, TAM and regulatory T-cells (Tregs) populations with a concomitant increase in the proportion of IFNγ+CD8 T-cells. The anti-tumor activity of DABIL-4 was absent in IL-4R KO mice directly implicating IL-4R directed killing as the mechanism of anti-tumor activity. Moreover, NanoString analysis of DABIL-4 treated TNBC tumors revealed marked decline in mRNA transcripts that promote tumorigenesis and metastasis. Our findings demonstrate that DABIL-4 is a potent targeted antitumor agent which depletes both IL-4R bearing tumor cells as well as immunosuppressive cell populations in the TME.STATEMENT OF SIGNIFICANCEIn solid tumors like breast cancer, Interleukin-4 receptor (IL-4R) expression in the tumor microenvironment aids tumor growth and metastasis. IL-4R expression upon host immune cells further dampens antitumor immunity. In this study, we have genetically constructed a fusion protein toxin, DABIL-4, composed of the catalytic and translocation domains of diphtheria toxin and murine IL-4. DABIL-4 showed specific cytotoxicity against triple-negative breast cancer (TNBC) cells in vitro. DABIL-4 also markedly inhibited TNBC tumor growth and metastasis in vivo. The primary activity of DABIL-4 was found to be depletion of IL-4R+ immune cells in combination with direct elimination of tumor cells. In conclusion, DABIL-4 targeting of both tumor and immunosuppressive host cells is a versatile and effective treatment strategy for TNBC.