bluuebunny/crossref_metadata_2025_split huggingface dataset:
Current opinion of presentation of dysphagia and dysphonia in patients with coronavirus disease 2019
Authors: Miles Anna , Brodsky Martin B. 
Published: August 2022

Purpose of review
Dysphagia and dysphonia are common presentations of both acute and long coronavirus disease 2019 (COVID-19). The majority of peer-reviewed publications in 2020 and early 2021 were expert guidance and consensus statements to support dysphagia management in multidisciplinary teams while protecting clinicians and patients from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. This review discusses dysphagia and dysphonia primary data published in 2021–2022, focusing on patient presentations, pathophysiology, and evidence for interventions.

Recent findings
Clinicians and researchers amassed knowledge of the cross-system presentation of dysphagia and dysphonia in patients with COVID-19, from severe disease requiring ICU stays to those with mild-to-moderate disease presenting to outpatient clinics. Pre-COVID-19 health status, hospitalization experience, presence of neurological symptoms, and impact of the virus to the upper aerodigestive and respiratory system need consideration in patient management. Long-term dysphagia and dysphonia manifested from COVID-19 require otolaryngologist and speech-language pathologist input.

Summary
Changes in immunity through population vaccination and variations in COVID-19 from SARS-CoV-2 mutations means prevalence data are challenging to interpret. However, there is no doubt of the presence of long-term dysphagia and dysphonia in our clinics. Long-term dysphagia and dysphonia are complex and a multidisciplinary team with a tailored approach for each patient is required.
Oropharyngeal reconstruction after transoral robotic surgery
Authors: Silverman Dustin A. , Birkeland Andrew C. , Bewley Arnaud F. 
Published: August 2022

Purpose of review
Transoral robotic surgery (TORS) has experienced an evolution in recent years. This technique has proved to be a safe and effective method for extirpation of select oropharyngeal tumors. Advances in technology as well as improved surgeon experience allow for the resection of larger, more complex cancers. Although healing by secondary intention remains the current standard for limited oropharyngeal defects, larger resections demand reconstruction with vascularized tissue to minimize morbidity and optimize functional outcomes. The objective of this review is to evaluate recent literature regarding oropharyngeal reconstruction after TORS.

Recent findings
A variety of reconstructive options to manage oropharyngeal defects exist. Several reconstructive algorithms have been suggested; however, careful consideration must be used to select the most ideal flap type. Locoregional flaps have shown excellent functional outcomes with limited morbidity. An increase in free flap reconstruction has been demonstrated, particularly among patients with larger TORS defects and following chemoradiation therapy. Despite limited data, robotic-assisted flap inset and microvascular anastomosis has recently shown promise.

Summary
Reconstruction and flap selection following TORS should be tailored to the patient and unique oropharyngeal defect. Functional outcomes are promising with low complication rates among these patients.
Pleomorphic Liposarcoma
Authors: Gjorgova Gjeorgjievski Sandra , Thway Khin , Dermawan Josephine K. , John Ivy , Fisher Cyril , Rubin Brian P. , Jenkins Sarah , Thangaiah Judith J. , Folpe Andrew L. , Fritchie Karen J. 
Published: August 2022

Pleomorphic liposarcoma (PLPS) is a highly aggressive sarcoma comprising variable numbers of pleomorphic lipoblasts mixed with undifferentiated pleomorphic sarcoma (UPS)-like areas. Morphologic variants, such as myxofibrosarcoma-like or epithelioid, may cause diagnostic confusion, especially on a core biopsy, but there are few data on the prognostic significance of these features. A total of 120 PLPS biopsies and resection specimens were reviewed and catalogued based on the presence of myxofibrosarcoma-like, UPS-like, and epithelioid foci, in 10% increments. The clinical parameters were collected. Cases occurred in 75 males and 45 females, ranging from 8 to 98 years (median, 62.5 y). Cases arose in the extremities (n=72), trunk (n=32), head/neck (n=10), bone (n=4), mediastinum (n=1), or viscera (colon polyp, n=1). Of those with known depth (n=81), 40 were intramuscular, 34 were subcutaneous, and 7 arose in the dermis. Their sizes ranged from 1 to 24.5 cm (median, 7 cm). Of the patients with ≥1 month of follow-up (n=70), 5 had recurrence and 15 had metastasis. The 5-year overall survival and event-free survival rates were 66.2% and 63.1%, respectively. Tumors ≥5 cm had inferior overall survival compared with tumors <5 cm. The presence of epithelioid areas was also statistically significant in terms of poorer overall survival and event-free survival, while tumors with ≥50% undifferentiated pleomorphic-like areas had better overall survival. There was a trend towards poorer outcomes in tumors with necrosis (≥1%). PLPS is an aggressive adipocytic malignancy that is most commonly present in the extremities of older adults. The morphologic features of these tumors are diverse, and they may be mistaken for UPS or myxofibrosarcoma, carcinoma, and melanomas, particularly on biopsies. Tumor size, necrosis, and epithelioid morphology are associated with adverse prognosis.
Opioids alter paw placement during walking, confounding assessment of analgesic efficacy in a postsurgical pain model in mice
Authors: Brings Victoria E. , Payne Maria A. , Gereau Robert W. 
Published: August 2022

Abstract

Introduction:
Hind paw–directed assays are commonly used to study the analgesic effects of opioids in mice. However, opioid-induced hyperlocomotion can obscure results of such assays.

Objectives:
We aimed to overcome this potential confound by using gait analysis to observe hind paw usage during walking in mice.

Methods:
We measured changes in the paw print area after induction of postsurgical pain (using the paw incision model) and treatment with oxycodone.

Results:
Paw incision surgery reduced the paw print area of the injured hind paw as mice avoided placing the incised section of the paw on the floor. Surprisingly, oxycodone caused a tiptoe-like gait in mice, reducing the paw print area of both hind paws. Further investigation of this opioid-induced phenotype revealed that analgesic doses of oxycodone or morphine dose-dependently reduced the hind paw print area in uninjured mice. The gait changes were not dependent on opioid-induced increases in the locomotor activity; speed and paw print area had no correlation in opioid-treated mice, and other analgesic compounds that alter locomotor activity did not affect the paw print area.

Conclusion:
Unfortunately, the opioid-induced “tiptoe” gait phenotype prevented gait analysis from being a viable metric for demonstrating opioid analgesia in injured mice. However, this work reveals an important, previously uncharacterized effect of treatment with analgesic doses of opioids on paw placement. Our characterization of how opioids affect gait has important implications for the use of mice to study opioid pharmacology and suggests that scientists should use caution when using hind paw–directed nociceptive assays to test opioid analgesia in mice.
Adverse Cardiovascular Outcomes Among Older Adults With Primary Hyperparathyroidism Treated With Parathyroidectomy Versus Nonoperative Management
Authors: Seib Carolyn D. , Meng Tong , Cisco Robin M. , Suh Insoo , Lin Dana T. , Harris Alex H.S. , Trickey Amber W. , Tamura Manjula K. , Kebebew Electron 
Published: August 2022

Objective:The authors sought to compare the incidence of adverse cardiovascular (CV) events in older adults with primary hyperparathyroidism (PHPT) treated with parathyroidectomy versus nonoperative management.Background:PHPT is a common endocrine disorder that is associated with increased CV mortality, but it is not known whether parathyroidectomy reduces the incidence of adverse CV events.Methods:The authors conducted a population-based, longitudinal cohort study of Medicare beneficiaries diagnosed with PHPT (2006–2017). Multivariable, inverse probability weighted Cox proportional hazards regression was used to determine the associations of parathyroidectomy with major adverse cardiovascular events (MACEs), CV disease-related hospitalization, and CV hospitalization-associated mortality.Results:The authors identified 210,206 beneficiaries diagnosed with PHPT from 2006 to 2017. Among 63,136 (30.0%) treated with parathyroidectomy and 147,070 (70.0%) managed nonoperatively within 1 year of diagnosis, the unadjusted incidence of MACE was 10.0% [mean follow-up 59.1 (SD 35.6) months] and 11.5% [mean follow-up 54.1 (SD 34.0) months], respectively. In multivariable analysis, parathyroidectomy was associated with a lower incidence of MACE [hazard ratio (HR): 0.92; 95% confidence interval (95% CI): 0.90–0.94], CV disease-related hospitalization (HR: 0.89; 95% CI: 0.87–0.91), and CV hospitalization-associated mortality (HR: 0.76; 95% CI: 0.71–0.81) compared to nonoperative management. At 10 years, parathyroidectomy was associated with adjusted absolute risk reduction for MACE of 1.7% (95% CI: 1.3%–2.1%), for CV disease-related hospitalization of 2.5% (95% CI: 2.1%–2.9%), and for CV hospitalization-associated mortality of 1.4% (95% CI: 1.2%–1.6%).Conclusions:In this large, population-based cohort study, parathyroidectomy was associated with a lower long-term incidence of adverse CV outcomes when compared with nonoperative management for older adults with PHPT, which is relevant to surgical decision making for patients with a long life expectancy.
EEG Pattern With Spectral Analysis Can Prognosticate Good and Poor Neurologic Outcomes After Cardiac Arrest
Authors: Qing Kurt Y. , Forgacs Peter B. , Schiff Nicholas D. 
Published: August 2022

Purpose:
To investigate the prognostic value of a simple stratification system of electroencephalographical (EEG) patterns and spectral types for patients after cardiac arrest.

Methods:
In this prospectively enrolled cohort, using manually selected EEG segments, patients after cardiac arrest were stratified into five independent EEG patterns (based on background continuity and burden of highly epileptiform discharges) and four independent power spectral types (based on the presence of frequency components). The primary outcome is cerebral performance category (CPC) at discharge. Results from multimodal prognostication testing were included for comparison.

Results:
Of a total of 72 patients, 6 had CPC 1–2 by discharge, all of whom had mostly continuous EEG background without highly epileptiform activity at day 3. However, for the same EEG background pattern at day 3, 19 patients were discharged at CPC 3 and 15 patients at CPC 4–5. After adding spectral analysis, overall sensitivity for predicting good outcomes (CPC 1–2) was 83.3% (95% confidence interval 35.9% to 99.6%) and specificity was 97.0% (89.5% to 99.6%). In this cohort, standard prognostication testing all yielded 100% specificity but low sensitivity, with imaging being the most sensitive at 54.1% (36.9% to 70.5%).

Conclusions:
Adding spectral analysis to qualitative EEG analysis may further improve the diagnostic accuracy of EEG and may aid developing novel measures linked to good outcomes in postcardiac arrest coma.
Nirmatrelvir/ritonavir and molnuipiravir in the treatment of mild/moderate COVID-19: results of a real-life study
Authors: Gentile Ivan , Scotto Riccardo , Moriello Nicola Schiano , Pinchera Biagio , Villari Riccardo , Trucillo Emilia , Ametrano Luigi , Fusco Ludovica , Castaldo Giuseppe , Buonomo Antonio Riccardo ,   Federico II COVID team
Published: August 2022

AbstractMolnupiravir and Nirmatrelvir are the first available oral antivirals (OA) active against SARS-CoV-2. However, the trials evaluating the efficacy of OAs involved patients unvaccinated and infected with variants different from those currently circulating. The purpose of this study is to provide real-life data on the efficacy and safety of OAs during the omicron surge of COVID-19 pandemic in a cohort of mostly vaccinated patients.We conducted a retrospective study on patients with confirmed SARS-CoV-2 infection treated with OAs during the omicron surge in Italy.We enrolled 257 patients. Of these, 146 (56.8%) were treated with molnupiravir and 111 (43.2%) with nirmatrelvir/ritonavir. Patients in molnupiravir group were older, had a lower body mass index, and a higher rate of chronic heart disease than those treated with nirmatrelvir/ritonavir.During the 14-day follow-up, four hospitalizations were recorded (1.6%), three in molnupiravir (2.1%) and 1 in nirmatrelvir/ritonavir (0.9%) group. Only one patient (who had received molnupiravir) died. Median time-to-negativity of nasal swab was 8 days (8 days in nirmatrelvir/ritonavir vs. 10 days in molnupiravir group, p<0.01).Globally, we recorded 37 adverse drug reactions (mainly dysgeusia, diarrhea, and nausea) in 31 of 257 individuals (12.1%). Only two patients (0.8%), both receiving molnupiravir, terminated treatment due to the development of adverse drug reactions.In conclusion, during the omicron surge, in a population of mostly vaccinated patients treated with molnupiravir or nirmatrelvir/ritonavir, we observed a low rate of hospitalization, death, and adverse drug reactions. These rates were even lower than those reported in pivotal trials.
Visual Outcome of Anti-Vascular Endothelial Growth Factor Injection at the University of Gondar Hospital Tertiary Eye Care and Training Centre, North-West Ethiopia
Authors: Endale Kassahun , Tsegaw Asamere 
Published: August 2022

ABSTRACTBackgroundThe management of macular edema and ocular neovascularization is changing and includes a new group of drugs called anti-vascular endothelial growth factor (anti-VEGF). Intra-vitreal injection of anti-VEGF agents has become the new standard of care for macular edema. However, data on their real world effectiveness and safety of these drugs in African eye care settings are very scarce.ObjectiveTo assess the visual outcome of intravitreal Avastin (IVA) injection at University of Gondar hospital tertiary eye-care and training center.MethodsA retrospective analysis of medical records of patients who received IVA at the center was done. The main outcome measure was visual acuity (VA).ResultsThe study included 37 eyes of 34 study participants with macular edema secondary to diabetic retinopathy, retinal vein occlusions, and neovascular age related macular degeneration (AMD). Mean VA improved from 6/60 (approximate 35 ETDRS letters) at baseline to 6/24 (approximate 55 ETDRS letters) at 2 months follow-up (p=0.0045) and this improvement was maintained at 6 months of follow up. This happened after mean injection of 2.5 times per eye over 6 months period. No major ocular or systemic treatment related adverse events were observed.ConclusionPatients who received IVA as initial therapy for macular edema from diabetic retinopathy, retinal vein occlusions, and neovascular AMD has a significant mean VA improvement which was maintained up to 6 months. Short term results show that IVA is effective and safe.
KCNH2encodes a nuclear-targeted polypeptide that mediates hERG1 channel gating and expression
Authors: Jain Abhilasha , Stack Olivia , Ghodrati Saba , Sanchez-Conde Francisco G. , Ukachukwu Chiamaka , Salwi Shreya , Jimenez-Vazquez Eric N. , Jones David K. 
Published: August 2022

ABSTRACTKCNH2encodes hERG1, the voltage-gated potassium channel that conducts the rapid delayed rectifier potassium current (IKr) in human cardiac tissue. hERG1 is one of the first channels expressed during early cardiac development, and its dysfunction is associated with intrauterine fetal death, sudden infant death syndrome, cardiac arrhythmia, and sudden cardiac death. Here, we identified a novel hERG1 polypeptide (hERG1NP) that is targeted to the nuclei of immature cardiac cells, including hiPSC-CMs and neonatal rat cardiomyocytes. The nuclear hERG1NP immunofluorescent signal is diminished in matured hiPSC-CMs and absent from adult rat cardiomyocytes. Antibodies targeting distinct hERG1 channel epitopes demonstrated that the hERG1NP signal maps to the hERG1 distal C-terminal domain.KCNH2deletion using CRISPR simultaneously abolished IKr and the hERG1NP signal in hiPSC-CMs. We then identified a putative nuclear localization sequence (NLS) within the distal hERG1 C-terminus, 883-RQRKRKLSFR-892. Interestingly, the distal C-terminal domain was targeted almost exclusively to the nuclei when overexpressed HEK293 cells. Conversely, deleting the NLS from the distal peptide abolished nuclear targeting. Similarly, blocking α or β1 karyopherin activity diminished nuclear targeting. Finally, overexpressing the putative hERG1NP peptide in the nuclei of HEK cells significantly reduced hERG1a current density, compared to cells expressing the NLS-deficient hERG1NP or GFP. These data identify a developmentally regulated polypeptide encoded byKCNH2, hERG1NP, whose presence in the nucleus indirectly modulates hERG1 current magnitude and kinetics.
Structures of chloramphenicol acetyltransferase III and E. coli β-ketoacylsynthase III co-crystallized with partially hydrolysed acetyl-oxa(dethia)CoA
Authors: Benjamin Aaron B. , Stunkard Lee M. , Ling Jianheng , Nice Jaelen N. , Lohman Jeremy R. 
Published: August 2022

AbstractAcetyl-CoA is a reactive metabolite that non-productively hydrolyzes in a number of enzyme active sites on the crystallization time frame. In order to elucidate enzyme:acetyl-CoA interactions leading to catalysis, acetyl-CoA substrate analogs are needed. One possible analog for use in structural studies is acetyl-oxa(dethia)CoA (AcOCoA), where the thioester sulfur of CoA is replaced by an oxygen. Here we present structures of chloramphenicol acetyltransferase III (CATIII) and E. coli ketoacylsynthase III (FabH) from crystals grown in the presence of partially hydrolyzed AcOCoA and the respective nucleophile. Based on the structures, the behaviour of AcOCoA differs between the enzymes, with FabH reacting with AcOCoA and CATIII being unreactive. The structure of CATIII reveals insight into the catalytic mechanism, with one active site of the trimer having relatively clear electron density for AcOCoA and chloramphenicol, and the other active sites having weaker density for AcOCoA. One FabH structure has a hydrolyzed AcOCoA product oxa(dethia)CoA (OCoA) and the other FabH structure has an acyl-enzyme intermediate with OCoA. Together these structures provide preliminary insight into the use of AcOCoA for enzyme structure-function studies with different nucleophiles.SynopsisStable analogs of acetyl-CoA are needed to support structure-function studies of acetyltransferase enzymes. We report structures of two enzymes in the presence of an acetyl-CoA analog where the thioester is replaced by an ester.
A mathematical model of calcium signals around laser-induced epithelial wounds
Authors: Stevens Aaron C. , O’Connor James T. , Pumford Andrew D. , Page-McCaw Andrea , Hutson M. Shane 
Published: August 2022

AbstractCells around epithelial wounds must first become aware of the wound’s presence in order to initiate the wound healing process. An initial response to an epithelial wound is an increase in cytosolic calcium followed by complex calcium signaling events. While these calcium signals are driven by both physical and chemical wound responses, cells around the wound will all be equipped with the same cellular components to produce and interact with the calcium signals. Here, we have developed a mathematical model in the context of laser-ablation of theDrosophilapupal notum that integrates tissue-level damage models with a cellular calcium signaling toolkit. The model replicates experiments in the contexts of control wounds as well as knockdowns of specific cellular components, but it also provides new insights that are not easily accessible experimentally. The model suggests that cell-cell variability is necessary to produce calcium signaling events observed in experiments, it quantifies calcium concentrations during wound-induced signaling events, and it shows that intercellular transfer of the molecule IP3is required to coordinate calcium signals across distal cells around the wound. The mathematical model developed here serves as a framework for quantitative studies in both wound signaling and calcium signaling in theDrosophilasystem.
Enhancing the perceived organizational support, perceived ethical-philanthropic CSR and subjective well-being: the role of ethical leadership
Authors: Ilyas Sehrish , Abid Ghulam , Ashfaq Fouzia 
Published: August 2022

PurposeThis study aims to examine the impact of ethical leadership style on the subjective well-being of health-care workers by examining the sequential mediating effects of perceived organizational support and perceived ethical-philanthropic corporate social responsibility (CSR).Design/methodology/approachData were collected from frontline health-care workers (i.e. doctors and nurses). Further, to cope with the response burden during the acute wave of the coronavirus pandemic, this study used split-questionnaire design for data collection.FindingsThis study’s findings fully support the hypothesized framework of the study, illustrating that ethical leadership positively influenced the subjective well-being of health-care workers. Moreover, this study found that the ethical leadership and well-being relationship is sequentially mediated by perceived organizational support and perceived ethical-philanthropic CSR.Practical implicationsThis study possesses practical implications for health-care institutions to encompass the agenda of developing ethically appropriate conduct in their administration and become genuinely concerned about health-care workers and society as well.Social implicationsBy highlighting the role of ethical leadership in participating in ethical and philanthropic CSR activities, this study possesses social implications for the well-being of health-care workers and society at large.Originality/valueA positive and strong chain of perceptions about organizational support accorded to employees specifically and society at large emerges as an important sequential mediating mechanism that helps ethical leaders in hospital administration in building subjective well-being in their followers amid the COVID-19 pandemic.