bluuebunny/crossref_metadata_2025 huggingface dataset:
Pyroptosis patterns influence the clinical outcome and immune microenvironment characterization in HPV-positive head and neck squamous cell carcinoma
Authors: Li Doudou , Ma Dong , Hou Yuxia
Published: May 2023

Background

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous tumor with diverse molecular pathological profiles. Recent studies have suggested the vital role of pyroptosis in tumor microenvironment. However, the expression patterns of pyroptosis in HPV-positive HNSCC are still unclear.

Methods

Unsupervised clustering analysis was used to identify the pyroptosis patterns based on the RNA-sequencing data of 27 pyroptosis-related genes (PRGs) in HPV-positive HNSCC samples. Random forest classifier and artificial neural network were performed to screen the signature genes associated with pyroptosis, which were verified in two independent external cohorts and qRT-PCR experiment. Principal component analysis was used to develop a scoring system, namely Pyroscore.

Results

The expression variations of 27 PRGs in HPV-positive HNSCC patients were analyzed from genomic and transcriptional domains. Two pyroptosis-related subtypes with distinct clinical outcomes, enrichment pathways and immune characteristics were identified. Next, six signature genes (GZMB, LAG3, NKG7, PRF1, GZMA and GZMH) associated with pyroptosis were selected for prognostic prediction. Further, a Pyroscore system was constructed to determine the level of pyroptosis in each patient. A low Pyroscore was featured by better survival time, increased immune cell infiltration, higher expression of immune checkpoint molecules and T cell-inflamed genes, as well as elevated mutational burden. The Pyroscore was also related to the sensitivity of chemotherapeutic agents.

Conclusions

The pyroptosis-related signature genes and Pyroscore system may be reliable predictors of prognosis and serve as mediators of immune microenvironment in patients with HPV-positive HNSCC.
PD-L1 expression, morphology, and molecular characteristic of a subset of aggressive uterine tumor resembling ovarian sex cord tumor and a literature review
Authors: Xiong Si-Ping , Luo Rong-Zhen , Wang Fang , Yang Xia , Lai Jun-Peng , Zhang Chao , Liu Li-Li
Published: May 2023

Background

Uterine tumors resembling ovarian sex cord tumor (UTROSCT) is a rare neoplasm of unknown etiology and has undetermined malignant potential. The emergence of recurrent UTROSCT case reports has led to its initial identification as a tumor of low malignancy potential. Owing to its low incidence, we currently lack any in-depth studies regarding the subset of UTROSCTs that may be aggressive in nature. Here, we sought to identify unique characteristics in aggressive UTROSCT.

Methods

19 cases of UTROSCT were collected. Their histologic and tumor immune microenvironment were evaluated by three gynecologic pathologists. The gene alteration was also detected by RNA sequencing. For later analyses regarding differences between benign and malignant tumors, we supplemented our 19 included cases with additional reports from the literature.

Results

Interestingly, we found PD-L1 expression in stromal tumor-infiltrating immune cells (stromal PD-L1) was markedly higher in aggressive UTROSCT. Patients with high stromal PD-L1 (≥ 22.5 cells/mm2) had worse prognosis. When our cases were added with previous cases identified in the literature, we discovered that aggressive UTROSCT was more likely to have significant mitotic activity and NCOA2 gene alterations than benign UTROSCT. Consistence with those results, patients with significant mitotic activity and gene alteration of NCOA2 had worse prognoses.

Conclusions

Collectively, high expression of stromal PD-L1, significant mitotic activity, and gene alteration of NCOA2 may be useful markers to predict aggressive UTROSCT.
Vascular response patterns to targeted therapies in murine breast cancer models with divergent degrees of malignancy
Authors: Hoffmann Emily , Gerwing Mirjam , Krähling Tobias , Hansen Uwe , Kronenberg Katharina , Masthoff Max , Geyer Christiane , Höltke Carsten , Wachsmuth Lydia , Schinner Regina , Hoerr Verena , Heindel Walter , Karst Uwe , Eisenblätter Michel , Maus Bastian , Helfen Anne , Faber Cornelius , Wildgruber Moritz
Published: May 2023

Background

Response assessment of targeted cancer therapies is becoming increasingly challenging, as it is not adequately assessable with conventional morphological and volumetric analyses of tumor lesions. The tumor microenvironment is particularly constituted by tumor vasculature which is altered by various targeted therapies. The aim of this study was to noninvasively assess changes in tumor perfusion and vessel permeability after targeted therapy in murine models of breast cancer with divergent degrees of malignancy.

Methods

Low malignant 67NR or highly malignant 4T1 tumor-bearing mice were treated with either the multi-kinase inhibitor sorafenib or immune checkpoint inhibitors (ICI, combination of anti-PD1 and anti-CTLA4). Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with i.v. injection of albumin-binding gadofosveset was conducted on a 9.4 T small animal MRI. Ex vivo validation of MRI results was achieved by transmission electron microscopy, immunohistochemistry and laser ablation-inductively coupled plasma-mass spectrometry.

Results

Therapy-induced changes in tumor vasculature differed between low and highly malignant tumors. Sorafenib treatment led to decreased tumor perfusion and endothelial permeability in low malignant 67NR tumors. In contrast, highly malignant 4T1 tumors demonstrated characteristics of a transient window of vascular normalization with an increase in tumor perfusion and permeability early after therapy initiation, followed by decreased perfusion and permeability parameters. In the low malignant 67NR model, ICI treatment also mediated vessel-stabilizing effects with decreased tumor perfusion and permeability, while ICI-treated 4T1 tumors exhibited increasing tumor perfusion with excessive vascular leakage.

Conclusion

DCE-MRI enables noninvasive assessment of early changes in tumor vasculature after targeted therapies, revealing different response patterns between tumors with divergent degrees of malignancy. DCE-derived tumor perfusion and permeability parameters may serve as vascular biomarkers that allow for repetitive examination of response to antiangiogenic treatment or immunotherapy.
The Ras small GTPase RSR1 regulates cellulase production in Trichoderma reesei
Authors: Li Ni , Qiu Zhouyuan , Cai Wanchuan , Shen Yaling , Wei Dongzhi , Chen Yumeng , Wang Wei
Published: May 2023

Background

Lignocellulose is the most abundant renewable resource in the world and has attracted widespread attention. It can be hydrolyzed into sugars with the help of cellulases and hemicellulases that are secreted by filamentous fungi. Several studies have revealed that the Ras small GTPase superfamily regulates important cellular physiological processes, including synthesis of metabolites, sporulation, and cell growth and differentiation. However, it remains unknown how and to what extent Ras small GTPases participate in cellulase production.

Results

In this study, we found that the putative Ras small GTPase RSR1 negatively regulated the expression of cellulases and xylanases. Deletion of rsr1 (∆rsr1) significantly increased cellulase production and decreased the expression levels of ACY1-cAMP-protein kinase A (PKA) signaling pathway genes and the concentration of intracellular cyclic adenosine monophosphate (cAMP). Loss of acy1 based on ∆rsr1 (∆rsr1∆acy1) could further increase cellulase production and the expression levels of cellulase genes, while overexpression of acy1 based on ∆rsr1 (∆rsr1-OEacy1) significantly reduced cellulase production and transcriptional levels of cellulase genes. In addition, our results revealed that RSR1 negatively controlled cellulase production via the ACY1-cAMP-PKA pathway. Transcriptome analysis revealed significantly increased expression of three G-protein coupled receptors (GPCRs; tre62462, tre58767, and tre53238) and approximately two-fold higher expression of ACE3 and XYR1, which transcriptionally activated cellulases with the loss of rsr1. ∆rsr1∆ tre62462 exhibited a decrease in cellulase activity compared to ∆rsr1, while that of ∆rsr1∆tre58767 and ∆rsr1∆tre53238 showed a remarkable improvement compared to ∆rsr1. These findings revealed that GPCRs on the membrane may sense extracellular signals and transmit them to rsr1 and then to ACY1-cAMP-PKA, thereby negatively controlling the expression of the cellulase activators ACE3 and XYR1. These data indicate the crucial role of Ras small GTPases in regulating cellulase gene expression.

Conclusions

Here, we demonstrate that some GPCRs and Ras small GTPases play key roles in the regulation of cellulase genes in Trichoderma reesei. Understanding the roles of these components in the regulation of cellulase gene transcription and the signaling processes in T. reesei can lay the groundwork for understanding and transforming other filamentous fungi.
Comparison of 6-min walk test distance vs. estimated maximum oxygen consumption for predicting postoperative pulmonary complications in patients undergoing upper abdominal surgery: a prospective cohort study
Authors: Yin Xin , Wang Jingwen , Xu Zhibo , Qian Fuyong , Liu Songbin , Cai Yuxi , Jiang Zhaoshun , Zhang Xixue , Gu Weidong
Published: May 2023

Objective

The present study aims to evaluate the predictive ability of estimated maximum oxygen consumption (e$$\dot{V}$$

V
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O2max) and 6-min walk distance (6MWD) for postoperative pulmonary complications (PPCs) in adult surgical patients undergoing major upper abdominal surgery.

Method

This study was conducted by collecting data prospectively from a single center. The two predictive variables in the study were defined as 6MWD and e$$\dot{V}$$

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O2max. Patients scheduled for elective major upper abdominal surgery from March 2019 to May 2021 were included. The 6MWD was measured for all patients before surgery. e$$\dot{V}$$

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O2max was calculated using the regression model of Burr, which uses 6MWD, age, gender, weight, and resting heart rate (HR) to predict aerobic fitness. The patients were categorized into PPC and non-PPC group. The sensitivity, specificity, and optimum cutoff values for 6MWD and e$$\dot{V}$$

V
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O2max were calculated to predict PPCs. The area under the receiver operating characteristic curve (AUC) of 6MWD or e$$\dot{V}$$

V
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O2max was constructed and compared using the Z test. The primary outcome measure was the AUC of 6MWD and e$$\dot{V}$$

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O2max in predicting PPCs. In addition, the net reclassification index (NRI) was calculated to assess ability of e$$\dot{V}$$

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O2max compared with 6MWT in predicting PPCs.

Results

A total of 308 patients were included 71/308 developed PPCs. Patients unable to complete the 6-min walk test (6MWT) due to contraindications or restrictions, or those taking beta-blockers, were excluded. The optimum cutoff point for 6MWD in predicting PPCs was 372.5 m with a sensitivity of 63.4% and specificity of 79.3%. The optimum cutoff point for e$$\dot{V}$$

V
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O2max was 30.8 ml/kg/min with a sensitivity of 91.6% and specificity of 79.3%. The AUC for 6MWD in predicting PPCs was 0.758 (95% confidence interval (CI): 0.694–0.822), and the AUC for e$$\dot{V}$$

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O2max was 0.912 (95%CI: 0.875–0.949). A significantly increased AUC was observed in e$$\dot{V}$$

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O2max compared to 6MWD in predicting PPCs (P < 0.001, Z = 4.713). And compared with 6MWT, the NRI of e$$\dot{V}$$

V
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O2max was 0.272 (95%CI: 0.130, 0.406).

Conclusion

The results suggested that e$$\dot{V}$$

V
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O2max calculated from the 6MWT is a better predictor of PPCs than 6MWD in patients undergoing upper abdominal surgery and can be used as a tool to screen patients at risk of PPCs.
Amino acid profile, physico-chemical properties and fatty acids composition of some fruit seed kernels after detoxification
Authors: Mustafa Mustafa Abdel-Moneim , Sorour Mohamed Abdel-Hamid , Mehanni Abul-Hamd El‐Sayed , Hussien Saleh Mahmoud
Published: May 2023

Background

The use of food processing wastes and by-products, as well as the under-utilization of agricultural products, have recently received increased attention. Mango, apricot and peach are the three most significant fruits grown and processed in Egypt.

Results

This work aimed to evaluate the amino acid composition, physio-chemical properties and fatty acids content of mango, apricot, and peach seed kernels after removal antinutritional components. According to the results, mango kernel flour contained all the essential amino acids with levels higher than those of the FAO/WHO reference protein. In addition, total essential amino acids were 28.88, 26.78 and 36.46 g/100 g protein for apricot, peach and mango kernel flours, respectively. The highest essential amino acids value was leucine, while the highest non-essential amino acids value was glutamic in all kernel protein. All kernel oils showed adequate values for acid and peroxide value. The main unsaturated fatty acids in all kernel oils were oleic and linoleic acids. Oleic acid contents ranged between 41.76% and 59.87%. On the other hand, linoleic acid contents varied between 5.25% and 26.61%.

Conclusions

Mango, apricot, and peach kernels are by-products that present a novel potential source of excellent protein and oil that might be used for food and other industrial applications after reduction of antinutritional matter. As a result, detoxified kernel flour might be used to enhance high-value food products with economical, high-quality sources of protein and oil.

Graphical Abstract
Acetate and propionate effects in response to LPS in a porcine intestinal co-culture model
Authors: Andrani Melania , Borghetti Paolo , Ravanetti Francesca , Cavalli Valeria , Ferrari Luca , De Angelis Elena , Martelli Paolo , Saleri Roberta
Published: May 2023

Background

The interest in acetate and propionate as short chain fatty acids (SCFA) derives from research on alternative strategies to the utilization of antibiotics in pig farms. SCFA have a protective role on the intestinal epithelial barrier and improve intestinal immunity by regulating the inflammatory and immune response. This regulation is associated with an increase in intestinal barrier integrity, mediated by the enhancement of tight junction protein (TJp) functions, which prevent the passage of pathogens through the paracellular space. The purpose of this study was to evaluate the effect of in vitro supplementation with SCFA (5 mM acetate and 1 mM propionate) on viability, nitric oxide (NO) release (oxidative stress), NF-κB gene expression, and gene and protein expression of major TJp (occludin [OCLN], zonula occludens-1 [ZO-1], and claudin-4 [CLDN4]) in a porcine intestinal epithelial cell (IPEC-J2) and peripheral blood mononuclear cell (PBMC) co-culture model upon LPS stimulation, through which an acute inflammatory state was simulated.

Results

Firstly, the inflammatory stimulus induced by LPS evaluated in the IPEC-J2 monoculture was characterized by a reduction of viability, gene expression of TJp and OCLN protein synthesis, and an increase of NO release. The response evaluated in the co-culture showed that acetate positively stimulated the viability of both untreated and LPS-stimulated IPEC-J2 and reduced the release of NO in LPS-stimulated cells. Acetate also promoted an increase of gene expression of CLDN4, ZO-1, and OCLN, and protein synthesis of CLDN4, OCLN and ZO-1 in untreated and LPS-stimulated cells. Propionate induced a reduction of NO release in both untreated and LPS-stimulated IPEC-J2. In untreated cells, propionate induced an increase of TJp gene expression and of CLDN4 and OCLN protein synthesis. Contrarily, propionate in LPS-stimulated cells induced an increase of CLDN4 and OCLN gene expression and protein synthesis. PBMC were influenced by acetate and propionate supplementation, in that NF-κB expression was strongly downregulated in LPS-stimulated cells.

Conclusions

The present study demonstrates the protective effect of acetate and propionate upon acute inflammation by regulating epithelial tight junction expression and protein synthesis in a co-culture model, which simulates the in vivo interaction between epithelial intestinal cells and local immune cells.
Results from a randomised controlled pilot study of the Better Conversations with Primary Progressive Aphasia (BCPPA) communication partner training program for people with PPA and their communication partners
Authors: Volkmer A , Walton H , Swinburn K , Spector A , Warren J. D , Beeke S
Published: May 2023

Background

There has been a growing focus on functional communication interventions for primary progressive aphasia (PPA). These interventions aim to support individuals to participate in life situations. One such intervention, communication partner training (CPT) aims to change conversation behaviours in both the person with PPA and their communication partner (CP). CPT has a growing evidence base in stroke aphasia; however, these programmes are not designed to meet the needs of people with progressive communication difficulties. To address this, the authors developed a CPT program entitled Better Conversations with PPA (BCPPA) and undertook a pilot trial to establish for a future full trial; predicted recruitment rates, acceptability, an assessment of treatment fidelity and an appropriate primary outcome measure.

Methodology

This was a single-blind, randomised controlled pilot study comparing BCPPA to no treatment, delivered across 11 National Health Service Trusts in the UK. A random sample of eight recordings of local collaborators delivering the intervention were analysed to examine fidelity. Participants completed feedback forms reporting on acceptability. Pre- and post-intervention measures targeted conversation behaviours, communication goals and quality of life.

Results

Eighteen people with PPA and their CPs (9 randomised to BCPPA, 9 randomised to no treatment) completed the study. Participants in the intervention group rated BCPPA positively. Treatment fidelity was 87.2%. Twenty-nine of 30 intervention goals were achieved or over-achieved and 16 of 30 coded conversation behaviours demonstrated change in the intended direction. The Aphasia Impact Questionnaire was identified as the preferred outcome measure.

Conclusion

The first randomised controlled UK pilot study of a CPT program for people with PPA and their families demonstrates BCPPA is a promising intervention. The intervention was acceptable, treatment fidelity high and an appropriate measure identified. Results of this study indicate a future RCT of BCPPA is feasible.

Trial registration

Registered 28/02/2018 ISRCTN10148247.
Access to cardiovascular medicines in low- and middle-income countries: a mini review
Authors: Harrison Mark Amankwa , Marfo Afia Frimpomaa Asare , Annan Augustine , Ankrah Daniel Nii Amoo
Published: May 2023

Background

Many cardiovascular (CV) medicines are required for long term. However, with their limited resources, low- and middle-income countries (LMICs) may have challenges with access to cardiovascular medicines. The aim of this review was to provide a summary of available evidence on access to cardiovascular medicines in LMICs.

Methods

We searched PubMed and Google scholar for English language articles on access to cardiovascular medicines for the period 2010–2022. We also searched for articles reporting measures for challenges in access to CV medicines from 2007 to 2022. Studies conducted in LMICs, and reporting availability and affordability were included for review. We also reviewed studies reporting affordability or availability using the World Health Organisation/Health Action International (WHO/HAI) method. Levels of affordability and availability were compared.

Results

Eleven articles met the inclusion criteria for review on availability and affordability. Although availability appears to have improved, many countries did not meet the availability target of 80%. Between economies and within countries, there are equity gaps in access to CV medicines. Availability is lower in public health facilities than private facilities. Seven out of 11 studies reported availability less than 80%. Eight studies which investigated availability in the public sector reported less than 80% availability. Overall, CV medicines, especially combined treatments are not affordable in the majority of countries. Simultaneous achievement of availability and affordability target is low. In the studies reviewed, less than 1–53.5 days wages were required to purchase one month supply of CV medicines. Failure to meet affordability was 9–75%. Five studies showed that, on average 1.6 days’ wages of the Lowest-Paid Government Worker (LPGW) was required to purchase generic CV medicines in the public sector. Efficient forecasting and procurement, increased public financing and policies to improve generic use, among others are measures for improving availability and affordability.

Conclusions

Significant gaps exist in access to cardiovascular medicines in LMICs, and in many low—and lower middle—income countries access to cardiovascular medicines is low. To improve access and achieve the Global Action Plan on non-communicable diseases in these countries, policy interventions must be urgently instituted.
Mucormycosis in post-COVID patients: loose cannon waiting to fire at the anaesthesiologist
Authors: Prakash Avinash , Yadav Anita , Raipure Amrusha , Baghel Jyoti
Published: May 2023

Background

Recently, several cases of mucormycosis in people with coronavirus disease 2019 (COVID-19) have been increasingly reported worldwide, in particular from India. As an increasing number of post-COVID patients with mucormycosis are presenting for surgical management, the onus is on the anaesthesiologists to adequately evaluate and optimise such patients.

Case presentation

We present three cases to highlight the anaesthetic challenges in patients undergoing functional endoscopic sinus surgery (FESS) with debridement surgery for mucormycosis through a series of three cases. In our manuscript, two cases had comorbidities as a challenge uncontrolled diabetes and hypertension. The third case had difficult intubation due to a small mouth opening which was probably due to swelling and tenderness as a result of rhino orbital mucormycosis.

Conclusions

Proper anticipation, optimization and timed promptness to deal with the anaesthetic challenges pertaining to the multisystemic involvement and sequelae of mucormycosis should be done.
Assessment of estimated low-density lipoprotein-cholesterol (LDL-c) equations: a systematic review and meta-analysis
Authors: Ephraim Richard K. D. , Ativi Emmanuel , Ashie Samuel A. , Abaka-Yawson Albert , Darkwah Kwame Osei
Published: May 2023

Background

Low-density lipoprotein cholesterol (LDL-c) is the major determinant of cardiovascular disease burden. This study critically reviewed the published literature and performed a meta-analysis to compare and to determine which other equations provide the best means of estimating LDL-c in clinical settings.

Method

English articles indexed in PubMed, Science Open, Biomed central and SpringerLink databases were searched with searches being conducted in or after 2001 up to date. According to the predefined inclusion and exclusion criteria, 22 articles out of the 17,970 retrieved were eligible for quantitative analysis. Data were pooled and meta-analysis performed using a random-effects model, and the results are described as event rates (pooled correlation coefficient).

Main body of the abstract

All the twelve equations showed positive correlation with the respective direct low-density lipoprotein-cholesterol measurements. The pooled estimates showed a stronger positive correlation between Martin’s low-density lipoprotein-cholesterol equation and the direct low-density lipoprotein-cholesterol measurement [0.96 (95% CI 0.94–0.98)] as compared to Friedewald’s equation and the direct method [0.94 (95% CI 0.92–0.96)]. At triglycerides levels > 400 mg/dl, Martin’s low-density lipoprotein-cholesterol equation established better performance (77.78%) than the Friedewald’s equation. In studies where triglycerides levels > 400 mg/dl were excluded Martin’s low-density lipoprotein-cholesterol equation still established better performance (83.33%) than the Friedewald’s equation.

Short conclusion

Our data suggest that Martin’s equation showed a better performance than Friedewald equation. Martin’s equation can serve as a more accurate method to estimate low-density lipoprotein cholesterol as compared to Friedewald’s equation especially in situations of the same racial background.
Video-assisted thoracic surgery is associated with faster delivery to adjuvant chemotherapy after lung resection in patients with lung cancer
Authors: Batıhan Güntuğ , Ceylan Kenan Can , Kaya Şeyda Örs
Published: May 2023

Background

Rapid recovery after surgery is especially important for patients who are scheduled for adjuvant therapy.

This study aimed to investigate the effect of video-assisted thoracic surgery (VATS) on chemotherapy referral time and chemotherapy tolerance in patients who underwent lung resection for non-small cell lung cancer.

Methods

The data of 612 patients who underwent lung resection with the diagnosis of non-small cell lung cancer in our clinic between January 2014 and December 2021 were reviewed. Patients who underwent lobectomy or bilobectomy with systematic mediastinal lymph node dissection and who received at least one cycle of adjuvant chemotherapy were included in the study. The characteristics of the patients, pathological data, postoperative follow-up findings, and the time between the operation and adjuvant chemotherapy were recorded.

Results

A total of 144 patients who met the criteria were included in the study. The mean age was 61.6 ± 7.9 years. The mean visual analogue scale scores were found to be lower, and the length of hospital stay was found to be shorter in the VATS group compared to thoracotomy.

The mean time (days) to initiate chemotherapy after surgery was statistically shorter in the VATS group (48.9 ± 17.6 vs 58.1 ± 27.6, p = 0.049). However, there weren't seen any statistical differences between VATS and thoracotomy groups in terms of mean cycle completed, percentage of planned regimen received, and grade ≥ 3 toxicity rates (p = 0.16, p = 0.18, and p = 0.22, respectively).

Conclusions

VATS provides faster recovery compared to open surgery and shortens the time for patients to refer to adjuvant chemotherapy.
Epstein–Barr virus and cytomegalovirus coinfection in Egyptian COVID-19 patients
Authors: Barakat Eman F , Sherief Ahmed F , Elsheikh Nesma G , Khalifa Mai Mohi M. El-Metwaly
Published: May 2023

Background

Reactivation of herpesviruses such as Epstein–Barr virus (EBV) and cytomegalovirus (CMV) in COVID-19 patients reported in many studies in different countries during the pandemic. We aimed to measure prevalence of this coinfection in Egyptian COVID-19 patients with elevated liver enzymes and its relation to the severity and the outcome of COVID-19 infection in those patients.

Methods

A cross-sectional study was carried out on 110 COVID-19 patients with elevated liver enzymes regardless the severity of COVID-19 disease. All patients were subjected to medical history, clinical examination, laboratory investigations, high-resolution computed tomography chest (HRCT chest). Epstein–Barr virus (EBV) and Human cytomegalovirus (HCMV) were determined by VCA IgM and CMV IgM respectively by enzyme-linked immunosorbent assay (ELISA).

Results

Of the included 110 patients with COVID-19 illness, 5 (4.5%) were Epstein–Barr virus seropositive and 5 (4.5%) were human cytomegalovirus seropositive. Regarding the symptoms, the incidence of fever in the EBV and CMV seropositive group was apparently higher than that in the EBV and CMV seronegative group. In lab tests, the platelets and albumin of EBV and CMV seropositive group decreased more significantly than EBV and HCMV seronegative group, and serum ferritin, D-dimer, and C-reactive protein show higher values in seropositive group than in seronegative group but not statistically significant. Seropositive group had received higher doses of steroids than seronegative group. The median of hospital stay in seropositive group was (15 days) nearly double that of seronegative group with statistically significant difference between both groups.

Conclusion

Coinfection of EBV and CMV in COVID-19 Egyptian has no effect on the disease severity or the clinical outcome of the disease. But those patients had higher hospital stay duration.
The role of video-fluoroscopy in the assessment of obstructive sleep apnea patients: comparative study
Authors: Baz Hemmat , Abdalgalil Amera Ahmed , Zayed Ahmed Mohamed , Morsy Nesreen Elsayed , Elsobki Ahmed , Amer Ayman
Published: May 2023

Background

Pre-operative imaging tools play a crucial role in the anatomic assessment of the upper airway and adjacent structures in obstructive sleep apnea patients. The current study was aimed at comparing and correlating the results of videofluoroscopy in evaluating upper airway obstruction in surgically fit obstructive sleep apnea “OSA” patients with fiberoptic nasoendoscopic examination during the awake “Muller’s maneuver” and during sleep induced with propofol for better selection of the suitable surgical maneuver. The present study was an observational cross-sectional study of 69 surgically fit OSA patients (36 males and 33 females); their ages ranged between 29 and 65 years with mean age of 45.87 ± 9.68 years. The patients were selected from otorhinolaryngology, phoniatric, and pulmonology outpatient clinics during the period from February 2019 to January 2020.

Results

The present study demonstrated that no statistically significant difference was found between the three techniques (video-fluoroscopy, awake fiber-optic nasoendoscopy, and drug-induced sleep nasoendoscopy “DISE”) as regards the shape of upper airway collapse at retropalatal, retroglossal, and hypopharyngeal levels in OSA patient (P: 0.621, 0.669, and 1.0 respectively). Statistically, a significant difference was observed between video-fluoroscopy, awake fiber-optic nasoendoscopy on one hand, and DISE on the other one regarding the grade of upper airway collapse at all levels (P: 0.006, 0.037, and 0.003). It was a mild significant difference in favor of DISE.

Conclusion

Video-fluoroscopy is a good, reliable complementary preoperative assessment tool to identify obstruction patterns of the upper airway in OSA patients with quantitative measurements.
Impact of Prior Authorization on Patient Access to Cancer Care
Authors: Trapani Dario , Kraemer Lianne , Rugo Hope S. , Lin Nancy U.
Published: May 2023

Prior authorization (PA) is a type of utilization review that health insurers apply to control service delivery, payments, and reimbursements of health interventions. The original stated intent of PA was to ensure high-quality standards in treatment delivery while encouraging evidence-based and cost-effective therapeutic choices. However, as currently implemented in clinical practice, PA has been shown to affect the health workforce, adding administrative burden to authorize needed health interventions for patients and often requiring time-consuming peer-to-peer reviews to challenge initial denials. PA is presently required for a wide range of interventions, including supportive care medicines and other essential cancer care interventions. Patients who are denied coverage are commonly forced to receive second-choice options, including less effective or less tolerable options, or are exposed to financial toxicity because of substantial out-of-pocket expenditures, affecting patient-centric outcomes. The development of tools informed by national clinical guidelines to identify standard-of-care interventions for patients with specific cancer diagnoses and the implementation of evidence-based clinical pathways as part of quality improvement efforts of cancer centers have improved patient outcomes and may serve to establish new payment models for health insurers, thereby also reducing administrative burden and delays. The definition of a set of essential interventions and guidelines- or pathways-driven decisions could facilitate reimbursement decisions and thus reduce the need for PAs. Structural changes in how PA is applied and implemented, including a redefinition of its real need, are needed to optimize patient-centric outcomes and support high-quality care of patients with cancer.
Effects of nonlinear membrane capacitance in the Hodgkin-Huxley model of action potential on the spike train patterns of a single neuron
Authors: Kumar Jitender , Das Gupta Patrick , Ghosh Subhendu
Published: May 2023

The membrane capacitance has been shown to have a nonlinear dependence on the cell membrane potential in various types of cells. But the role of the nonlinear membrane capacitance in neurons has not been studied in detail. Herein, by considering the membrane capacitance to be a nonlinear parameter, we have explored the behavior of the cell membrane in three different types of neurons,i.e., squid giant neuron, rodent hippocampal interneuron, and rodent cortical neuron. The Hodgkin-Huxley equation of action potential was modified accordingly and simulated computationally. Our simulated results suggest that the action potential amplitude of a neuron almost remains the same for some duration when the voltage dependence parameter of the nonlinear capacitance increases up to a certain range, the initiation of the next action potential is delayed and the reduction in spike frequencies occurs in comparison to constant membrane capacitance. This indicates the importance of nonlinearity in membrane capacitance. Simultaneously the inter-spike interval (ISI) changes with the nonlinear membrane capacitance parameter. The gating dynamics show changes mainly in theactivation current while the membrane capacitance is considered to be nonlinear. The above-mentioned computational results are primarily predictive pending experimental verification.
Early Detection of Adrenal Insufficiency: The Impact of Newborn Screening for Adrenoleukodystrophy
Authors: Ramirez Alcantara Jonanlis , Grant Natalie R , Sethuram Swathi , Nagy Amanda , Becker Catherine , Sahai Inderneel , Stanley Takara , Halper Alyssa , Eichler Florian S
Published: May 2023

Context

Males with adrenoleukodystrophy (ALD) have an 80% lifetime risk of developing adrenal insufficiency (AI), which can be life-threatening when undetected. Newborn screening (NBS) for ALD has been implemented in 29 states, yet the impact of NBS upon clinical management has not been reported.

Objective

To investigate whether the implementation of NBS has altered the time to diagnosis of AI in children with ALD.

Design

We conducted a retrospective medical chart review of pediatric patients with ALD.

Setting

All patients were seen in a leukodystrophy clinic in an academic medical center.

Patients

We included all pediatric patients with ALD who were seen between May 2006 and January 2022. We identified 116 patients (94% boys).

Main Outcome Measures

We extracted information about ALD diagnosis in all patients and AI surveillance, diagnosis, and treatment in boys with ALD.

Results

Thirty-one (27%) patients were diagnosed with ALD by NBS, and 85 (73%) were diagnosed outside the newborn period. The prevalence of AI among boys in our patient population was 74%. AI diagnosis was made significantly earlier in boys diagnosed with ALD by NBS than in boys diagnosed outside the newborn period (median [IQR] age of diagnosis = 6.7 [3.9, 12.12] months vs 6.05 [3.74, 8.35] years) (P < .001). When maintenance dose of glucocorticoids were initiated, there were significant differences in ACTH and peak cortisol levels in patients diagnosed by NBS and outside the newborn period.

Conclusions

Our results suggest that implementing NBS for ALD leads to significantly earlier detection of AI and earlier initiation of glucocorticoid supplementation in boys affected by ALD.
China in Tax Havens
Authors: Clayton Christopher , Coppola Antonio , Dos Santos Amanda , Maggiori Matteo , Schreger Jesse
Published: May 2023

We document the rise of China in offshore capital markets. Chinese firms use global tax havens to access foreign capital in both equity and bond markets. In the last 20 years, China's presence went from raising a negligible amount of capital in these markets to accounting for more than half of equity issuance and around a fifth of global corporate bonds outstanding in tax havens. Using rich micro data, we show that a range of Chinese firms, including both tech giants and state-owned enterprises, use these offshore centers. We conclude by discussing the macroeconomic and financial stability implications of these patterns.
The Stock Connect to China
Authors: He Zhiguo , Wang Yuehan , Zhu Xiaoquan
Published: May 2023

As a bridge between Chinese mainland and international financial markets, the Stock Connect program allows investors on both sides to gain mutual access. By analyzing how cross-border flows respond to macro-related shocks, we show that compared with possibly homemade foreign investors, genuine foreign investors are more likely affected by the US monetary shocks, the exchange rate risk, the US market performance, and the cross-market valuation disparity. The paper highlights the importance of profiling different groups of cross-border participants over market integration.
Emotional and Behavioral Impacts of Telementoring and Homeschooling Support on Children
Authors: Hassan Hashibul , Islam Asad , Siddique Abu , Wang Liang Choon
Published: May 2023

We examine the emotional and behavioral impacts of a randomized telementoring intervention on Bangladeshi primary school-aged children during COVID-19 school closures. We measured the prevalence of emotional, conduct, hyperactivity/inattention, and peer-relation problems among children twice. We found significant reductions in conduct and hyperactivity problems among the treated one month after the intervention ended. However, these impacts disappeared after one year. We also observed significant deterioration in the mental health problems of all children. These results highlight that remote learning can prevent mental health problems among children in the short term, but sustained support is necessary to effectively address the problems.
Interest Rates and World Trade: An “Austrian” Perspective
Authors: Antràs Pol
Published: May 2023

I develop a framework to study the interplay between world trade and interest rates. The model incorporates an explicit notion of time and production length, in the “Austrian” tradition of Bohm-Bawerk (1889). Changes in the interest rate affect production lengths, labor productivity, and the financial costs of exporting. I decompose the response of the volume of world trade to changes in the interest rate into four components: a labor productivity effect, a “propensity to consume out of labor income” effect, a “temporal dimension of variable trade costs” effect, and a “selection into exporting” effect.
Technologies That Replace a “Central Planner”
Authors: Townsend Robert M. , Zhang Nicolas X.
Published: May 2023

Contracting possibilities are endogenous to the technologies on which the negotiation and the trading environments are built. Here we review how different technologies allow different implementations of the “central planner” and gradually abstract this centralized role away into the technological environment. We emphasize that the “central planner” construct should no longer remain an abstract invocation in the literature and that it already is concretely deployed to implement optimized solutions to bilateral and multiagent mechanism design problems. We hope to provide methods for economic, business, and policy designers to leverage the right technological tools for the different problems they are facing.
How Should Sanctions Account for Bystander Countries?
Authors: Sturm John
Published: May 2023

Neutral “bystander countries” have profoundly shaped the impact of trade sanctions imposed on Russia following its invasion of Ukraine. How should sanctions account for the presence of such bystanders? I study this question in a simple trade model where a sanctioning country places tariffs on imports from a sanctioned country in the presence of a neutral third country. Optimal tariffs-as-sanctions are lower on goods that the sanctioner can import from bystanders. On goods that the sanctionee can export to bystanders, tariffs-as-sanctions are higher given an elasticity of (excess) supply to the sanctioner but lower given a total elasticity of supply.
Anxiety, Test-Taking Aid, and Test Scores: Evidence from Economics Classes
Authors: Cannonier Colin , Burke Monica Galloway
Published: May 2023

Using data collected over five years for an introductory economics course, this study investigates the relationship between anxiety, test-taking aid, and test performance. The results show that test aid is associated with a 0.21 standard deviation increase in test scores. Although anxiety decreases test performance, accounting for anxiety does not eliminate the significant impact of test aid. The positive impact of test aid has heterogenous effects. Test aids play a moderating role in reducing unwanted stress while maintaining test integrity. Our results suggest that the effect of high anxiety may have implications for a student's academic trajectory.
Timely Business Dynamics Using Google Places
Authors: Duprey Thibaut , Rigobon Daniel E. , Kotlicki Artur , Schnattinger Philip
Published: May 2023

We introduce a new real-time method to measure business opening and closure rates by relying on Google Places, the data behind the Google Maps platform. We collect data on establishments of customer-facing industries (food, retail, accommodation) and provide evidence that the opening and closure rates reflect well the temporary closures and reopening during the pandemic. We find that the operational or closed status of establishments is correlated with business reviews: fewer reviews are associated with impending business exit, and more reviews are associated with expanding businesses posting new job vacancies.
Payroll Employment at the Weekly Frequency
Authors: Cajner Tomaz , Crane Leland D. , Decker Ryan A. , Hamins-Puertolas Adrian , Kurz Christopher
Published: May 2023

Nontraditional data can provide critical economic insights in real time. We document the development of weekly employment indexes based on microdata from the payroll processor ADP. These data have provided insights into labor market developments in the fast-moving pandemic environment of recent years, as well as in more quiescent periods. We describe processes for weighting and benchmarking, seasonally adjusting weekly data, and ultimately combining the signals from ADP and official data. Finally, we show how the weekly employment indexes have fared during the pandemic jobs recovery, focusing on revisions to official data for the second half of 2021.
Hormone Therapy, Suicidal Risk, and Transgender Youth in the United States
Authors: Campbell Travis , Mann Samuel , Nguyen Duc Hien , Rodgers Yana van der Meulen
Published: May 2023

This study uses the 2015 US Transgender Survey to test how initiation of hormone replacement therapy (HRT) affects the risk of attempting suicide among transgender individuals. We constructed a retrospective panel and employed a stacked event study design to demonstrate that HRT is associated with a substantially lower risk of suicide attempt. The average treatment effect on the treated is a decrease of 5.7 percentage points in the risk of ever attempting suicide if HRT is started between the ages of 14 and 17, which amounts to a 14.4 percent reduction in the risk of attempting suicide relative to the pretreatment mean.
The Impact of COVID-19 on Access to Mental Health Care Services
Authors: Harrell Benjamin , Fumarco Luca , Button Patrick , Schwegman David J. , Denwood Kyla
Published: May 2023

The COVID-19 pandemic increased the rate of mental health disorders, as well as demand for mental health services. It remains unclear, however, the extent to which it impacted access to mental health care. Using data from an audit field experiment, which ran from January to May 2020 and overlapped with the onset of the COVID-19 pandemic, we examine the impact of COVID-19 on access to mental health care appointments in the United States. We find that increased intensity of COVID-19–measured by daily cases, daily fatalities, and weekly excess deaths–is associated with decreased access to mental health care appointments.
Has Consumer Acceptance of Electric Vehicles Been Increasing? Evidence from Microdata on Every New Vehicle Sale in the United States
Authors: Gillingham Kenneth T. , van Benthem Arthur A. , Weber Stephanie , Saafi Mohamed Ali , He Xin
Published: May 2023

Electric vehicle (EV) sales have been rapidly growing around the world, spurred by technology advances and policy actions. This study leverages rich data on all individual new light-duty vehicles sold in the United States from 2014 to 2020. We examine how EV attributes, prices, and sales have evolved, exploring substantial heterogeneity across geography, vehicle class, price range, and demographics. We use a matching analysis to compare EVs to similar conventional vehicles to find that EVs have been surprisingly competitive in very recent years. This suggests that constrained supply is an important determinant of the low overall EV market share.
The Impact of Distance in Retail Markets
Authors: Edgel Danny , Houde Jean-François , Newberry Peter , Seim Katja
Published: May 2023

We examine the demand-side implications of Amazon's distribution and logistics investments. Our results indicate that online demand–transactions at Amazon and its competitors–does not respond to the consumer's proximity to Amazon's upstream fulfillment distribution facilities, suggesting that their densification did not differentially improve local shipping times and on-time delivery. Instead, we find that investments in last-mile delivery facilities and services allow the company to improve shipping times more directly in the urban markets served by these facilities, simultaneously increasing demand through the rollout of same-day service options and reducing the visits to traditional brick-and-mortar retail.
Do Tax Increases Tame Inflation?
Authors: Cloyne James , Martinez Joseba , Mumtaz Haroon , Surico Paolo
Published: May 2023

The answer is “yes” for personal income taxes but “no” for corporate income taxes. Using narrative-identified US federal tax changes post-World War II and disaggregated sectoral data on consumer and producer prices, we show that higher average personal income tax rates lower prices across a broad range of sectors, but higher average corporate tax rates do not. There is also significant sectoral heterogeneity in the size of the effects. Finally, only personal tax increases lower inflation expectations, while corporate tax increases lead to persistent declines in stock prices. Our results are consistent with personal taxes affecting aggregate demand and corporate taxes persistently affecting supply conditions.
The Importance of Fed Chair Speeches as a Monetary Policy Tool
Authors: Swanson Eric T.
Published: May 2023

I estimate the effects of Federal Open Market Committee (FOMC) announcements, post-FOMC press conferences, and speeches and Congressional testimony by the Fed chair on stock prices, Treasury yields, and interest rate futures from 1988 to 2019. I show that for all but the very shortest-maturity interest rate futures, Fed chair speeches are more important than FOMC announcements. My results suggest that the previous literature's focus on FOMC announcements has ignored the most important source of variation in US monetary policy.