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Neuropsychiatric adverse reactions of leukotriene receptor antagonist, antihistamine...
Sainan Bian
Lisha Li

Sainan Bian

and 8 more

January 30, 2024
Background There are limited real-world studies about the differences of leukotriene receptor antagonist (LTRA), antihistamine and inhaled corticosteroid (ICS) associated neuropsychiatric events. We aimed in this study to summarize the clinical characteristics of drug associated neuropsychiatric events and compare the differences between different drug categories. Methods Disproportionality analysis and Bayesian analysis were used in data mining to screen the suspected neuropsychiatric events with LTRA, antihistamine and ICS based on the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) from January 2004 to September 2020. Results A total of 9475 neuropsychiatric events were identified. Neuropsychiatric events related to LTRA, antihistamine and ICS were 5201 (54.89%), 3226 (34.05%), and 1048 (11.06%), respectively. LTRA related neuropsychiatric events were more common in patients aged from 4 to 6 years old (18.66%), while antihistamine and ICS related neuropsychiatric events were more common in patients with 18 to 44 years old (29.92%) and older than 65 years old (30.60%), respectively. Montelukast was considered to have the tightest relationship to neuropsychiatric events, followed by the first generation of antihistamine. Most neuropsychiatric symptoms occurred within the first 10 days after drug initiation. Death rate due to neuropsychiatric events of antihistamine was significantly higher than LTRA and ICS (p<0.001). Conclusions LTRA associated neuropsychiatric events was most frequent in 4 to 6-year old children and most cases occurred with the first 10 days after drug initiation. Fatality rate due to antihistamine associated neuropsychiatric events was higher than LTRA and ICS.
LNCRNA expression landscape and specificity between brain regions
Adewale Ogunleye
Umair Ali

Adewale Ogunleye

and 1 more

January 30, 2024
Long noncoding RNAs (lncRNAs) are transcribed into low potential protein coding RNA molecules, which account for over 70% of mammalian transcriptional products. The role of lncRNAs and their expression is still largely unknown, and the subject of recent investigations. Here, we used bulk RNA sequencing data from the Genotype-Tissue Expression (GTEx) project to investigate the occurrence and specificity of lncRNAs in 13 brain regions (1000 samples). These highly specific lncRNA were co-expressed with previously known mRNA markers in different regions of the brain. Further investigation revealed that splicing could influence the divergent biogenesis and enrichment of lncRNA alleles in different regions. Overall, we demonstrate the use of lncRNA as a potential tool for deconvolving brain regions and further highlights its use for cell-type identification from bulk transcriptome data.
Responses of gut microbiota in moose (Alces alces) populations with different migrati...
Shiyu Chen
Marcel Holyoak

Shiyu Chen

and 7 more

January 30, 2024
The implications of migration for gut microbial community composition and function, and effects on population health of host animals are poorly known. In this study, we quantified migration patterns and gene flow for moose populations in northeast China and tested their relationships to recent climate warming. And we then characterized moose gut microbial composition and tested its relationships to moose migration patterns. We found that moose populations increasingly moved northward or to higher latitude due to late spring warming. Migratory and isolated moose populations differed in their gut microbe composition and frequency of different functional groups of bacteria that relate to digestion and diet composition. Gut microbe composition was also related to different environmental variables in isolated vs. migratory moose populations. Our results suggested that gut microbes of isolated moose populations were only related to altitude, whereas those in migratory moose populations were related to temperature, precipitation, longitude and latitude. We believe that differences in the taxonomic and functional composition of gut microbiota relating to digestion are adaptive. Consequently, this study highlights that special attention should be placed on isolated populations of moose, and ecological corridors or translocation of individuals may be needed for moose conservation to allow persistence in the face of global warming.
Compliance and challenges of Transmission Based Precaution Practices among Nurses in...
Ahmed Al-Smadi
Salam Banihani

Ahmed Al-Smadi

and 3 more

January 30, 2024
Background: Standard precautions (SPs) practices are of crucial management skills among Health Care Workers (HCWs) including nurses against the highly infectious novel virus SARS-CoV-2. Aim of the study: The study aimed to assess level of nurse’s compliance with SPs, and identify the main challenges that experienced by nurses during their work with infected SARS-CoV-2 patient’s. Methods: A cross-sectional survey design was used. The study was conducted in different sectors that represent the health care sector in Jordan. 386 nurses recruited from the different sectors. Results: Data were collected from 386 participants. 66.8% of the participants were female. Most of them revealed that they were dealt previously SARS-CoV-2 patients (73.6%). Generally, nurses demonstrated good level of compliance with SPs practices (71%). The staff reported that they mostly adhere with performing hand hygiene after all procedures (65.8%). On the other hand, they were least adherence with maintaining a physical distance of patient and staff of at least 6ft apart (28.5%). conclusion: It was concluded that nurses have a good level of SPs practices. Many challenges were experienced by nurses while caring of SARS-CoV-2 patients.
Hermite-Hadamard type inequalities involving $s$-convex function in the first sense
Gültekin Tınaztepe
SINEM SEZER EVCAN

Gültekin Tınaztepe

and 3 more

January 30, 2024
In this paper we extend some estimates of a Hermite-Hadamard type inequality for functions whose absolute values of the first derivatives are $s$-convex in the first sense. By means of the obtained inequalities, some bound functions involving beta functions and digamma function are derived as applications. Furthermore, they are used to obtain an error bound in numerical integration of certain $s$-convex functions by composite trapezoid rule.
THERMOELASTIC ANALYSIS OF FUNCTIONALLY GRADED ANNULAR ROTATING DISC
Pooja Rani
Kuldip Singh

Pooja Rani

and 2 more

January 30, 2024
This study deals with thermoelastic analysis of annular rotating disc made of functionally graded materials. Material properties are assumed to vary along radial direction according to power-law function, and the Poisson's ratio is constant. A gradient parameter is chosen between -0.5 to 0.5. When gradient parameter equals to zero, the disc becomes isotropic disc case. The distributions of radial and tangential stresses on the disc are obtained for various gradient parameter by means of the diverse elasticity modulus, thermal conductivity, thermal expansion coefficient and density.
Discovery of Hysteresis Models Through the Symmetry Principle
BASSIROU DIATTA
Celestin Wafo Soh

BASSIROU DIATTA

and 2 more

January 30, 2024
We employ the symmetry principle to obtain rate-independent hysteresis operators associated with a nonlinear diffusion equation. The direct Lie approach to this problem leads to an overdetermined system of equations for symmetries that are extremely difficult to analyze. To mitigate this problem, we employ the classification of low-dimensional Lie algebra following the suggestion of Lahno \textit{et al.} (Journal of Physics A: Mathematical and General \textbf{32} (42) (1999): 7405). After excluding linear models, we obtain a one-dimensional principal symmetry Lie algebra, seven symmetry Lie algebras of dimension two, twenty-six symmetry Lie algebras of dimension three, and two symmetry Lie algebras of dimension four. The curves of invariant solutions for symmetry Lie algebras of dimensions three and four are exhibited in three forms. Under appropriate selection of parameters, all invariant solutions show one-to-many relationships between inputs and outputs, except for one in dimension three.
Title: A Study on the Stability Analysis of Mathematical Model leading to the Star Fo...
Sanjeev Kumar
Dr.A.K.Awasthi

Sanjeev Kumar

and 1 more

January 30, 2024
Abstract It takes millions of years for a star to get formed. This paper deals with the stability analysis of mathematical model which governs star formation. Variation matrix or Jacobian Matrix is developed out of differential equation which arises from three component of galactic region i.e. atomic, molecular and stellar components. Mathematical Model is the best way to explore and explain the system of three components in the galactic region. In fact, Mathematical Modelling- is the main, if not the only way one, way for theoretical research of astrophysical processes and objects [6]. Various examples has been taken for comparative studies and computational purposes Keywords: Galactic region, interstellar medium, giant molecular mass, stellar evolution, galaxy, star formation.
The Association of Otalgia with Nasal Septum Deviation: A Prospective Study
Alex Wright
Joshua Kay

Alex Wright

and 4 more

January 30, 2024
Objectives: There has been anecdotal evidence that otalgia and ear fullness are associated with a deviated nasal septum (DNS). The goal of this novel, pilot study is to evaluate if eustachian tube dysfunction (ETD) is associated with a DNS and improved following septoplasty. Design: Prospective comparative pilot study Setting: Tertiary hospital at an academic institution Participants: Twenty-five patients with septal deviations (16 with otalgia and 9 controls) underwent septoplasty with inferior turbinate reduction between November 2016 and May 2018. Main Outcome Measures: ETDQuestionnaire (ETDQ-7), Sino-nasal Outcome Test (SNOT-22), and Nasal Obstruction Symptom Evaluation (NOSE) assessed quality of life pre and post operation. Results: Mean SNOT-22 scores decreased significantly for both groups (p< 0.05). The results of the ETDQ-7 showed aural symptoms significantly decreased for case patients at 6 weeks (-17.4, p=0.016) which continued through week 12. Symptoms of ear fullness and pain were significantly reduced in the case group (p<0.05). With both groups experienced a reduction in all questionnaires, decreased SNOT-22 scores correlated with ETDQ-7 (p=0.0012) and NOSE (p<0.036) improvements while the control group did not see test correlations. Conclusions: Overall, our study demonstrated otalgia or ear fullness could be associated with a DNS. The data suggests significant correlations between all three questionnaires in evaluating patients with nasal obstruction and aural symptoms, and that they are reasonable tools in evaluating ETD outcomes concerning septoplasty. Thus, we propose that nasal septum deviation be evaluated and included in any algorithm for the diagnosis and management of patients with ETD.
Treatment of B-cell Lymphoma, Unclassifiable, with Features Intermediate Between Diff...
Egor Volchkov
Mariia Senchenko

Egor Volchkov

and 8 more

January 30, 2024
B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma (DLBCL) and classical Hodgkin’s lymphoma (cHL) is a rare malignant disease that develops from mature B cells. This disease was first recognized as a distinct entity in 2008. It is most common in the 20 to 40 age group and rare in children. Currently, there are no clear criteria for diagnosis and standard therapy for such patients. According to the literature, it is possible to use treatment regimens applied for both aggressive B-cell lymphomas and Hodgkin’s lymphoma. The addition of anti-CD20/CD30 targeted agent to standard therapy may be effective, given the expression of these markers by tumor cells. In this article, we present the clinical and morphological characteristics of patients with unclassifiable B-cell lymphoma with features intermediate between diffuse large B-cell lymphoma and cHL, diagnosed at our center, including 4 patients at the onset of the disease in childhood
LOW RISK PEDIATRIC FOOT SYNOVIAL SARCOMA: PROLONGED OVERALL SURVIVAL WITH AN EXCLUSIV...
Gabriela  Gonzalez Diaz
Estefania Rossetti

Gabriela Gonzalez Diaz

and 5 more

January 30, 2024
Synovial sarcoma (SS) constitutes an aggressive tissue sarcoma that can affect all age groups but is frequently observed in children and adolescents. Although a multimodal strategy with surgery, chemotherapy and radiotherapy tends to be the treatment of choice, adequate risk stratification has allowed to separate a low-risk group of SS, with long term survival with an exclusive surgical approach. We report a case of a pediatric patient with a low-risk foot SS, that achieved prolonged event free survival and overall survival with exclusive surgical treatment, minimizing long-term morbidity of chemo and radiotherapy.
Resilience and Emotions of Frontline Obstetrics and Gynaecology Healthcare Workers Du...
Hester Lau
Ni Ni Soe

Hester Lau

and 4 more

January 30, 2024
Objective: To explore impact of COVID-19 outbreak on resilience and emotions of frontline healthcare workers (HCW) during the pandemic Design: Cross-sectional retrospective descriptive study Setting: KK Women and Children’s Hospital, Singapore, Department of Obstetrics and Gynaecology, between 7 February to 30 April 2020 Population: One hundred and one (101) HCW who worked in COVID-19 screening facilities and wards Methods: The participants were given a survey designed to understand their emotions when caring for patients with suspected or confirmed COVID-19, and how their various aspects of health were affected. The Brief Resilience Scale (BRS) was used to evaluate their resilience. Results: Normal resilience scores were found in 72.6% of HCW, 11.3% had high resilience scores while 16.1% had low resilience scores. Doctors had higher resilience scores than nurses (3.8 vs 3.3, p-value 0.017). HCWs perceived their mental health was most affected, followed by social and physical health as a result of COVID-19 related work. The main stressors faced were related to their personal safety and that of their family. A positive attitude at work with good teamwork, time away from routine clinical work and appreciation received helped to relieve the emotional and psychological stress faced. Conclusion: It is essential to explore appropriate interventions for HCW with low resilience to better assist the coping mechanism during this pandemic. Stressors identified and feedback received through this study are useful for implementing supportive workforce resources during an infectious disease outbreak.
Aerosol generation during coughing - Quantitative definition for aerosol generating p...
Enni Sanmark
Lotta-Maria Oksanen

Enni Sanmark

and 7 more

January 30, 2024
Aim: The aim of the study was to determine the quantitative value of high-risk aerosol generation during surgery. Background: Coughing is commonly used as a reference of high-risk aerosol generation during surgeries and other clinical procedures. Those procedures during which aerosol generation exceeds the amount of aerosol produced by coughing are referred to as high-risk AGPs. However, no golden standard about quantitative levels of high-risk aerosol generation exists. Methods: 37 healthy volunteers recruited to cough in the operating room. Aerosol particles, with the size of 0.3-10 µm, generated during coughing were measured with Optical Particle Sizer from 40cm, 70cm and 100cm distances. The distances reflected to potential distance where the staff is working during surgeries. Volitional coughs were compared to involuntary coughs measured with same set up during extubations. Results: A total of 306 coughs were measured. Total aerosol concentration during coughing averaged 1.706 ± 10.802 (range 0.000 – 88.157). Highest aerosol concentrations were measured furthest from the source. No difference between volitional and involuntary coughs were observed. Discussion: The aerosol concentrations, measured in this study can be used as a reference level for high-risk aerosol generation in the operating room environment when assessing the risk of operating room staff´s exposure for aerosol particles
Establishment of a diagnostic model to distinguish Coronavirus Disease 2019 from infl...
Dongyang Xing
Suyan Tian

Dongyang Xing

and 6 more

January 30, 2024
Background: Coronavirus disease 2019 (COVID-19) and Influenza A are common disease caused by viral infection. The clinical symptoms and transmission routes of the two diseases are similar. This study established a model of laboratory findings to distinguish COVID-19 from influenza A perfectly. Methods: In this study, 56 COVID-19 patients and 54 influenza A patients were included. Laboratory findings, epidemiological characteristics and demographic data were obtained from electronic medical record databases. Elastic network models, followed by a stepwise logistic regression model were implemented to identify indicators capable of discriminating COVID-19 and influenza A. Results: A monogram is diagramed to show the resulting discriminative model. The majority of hematological and biochemical parameters in COVID-19 patients were significantly different from those in influenza A patients. In the final model, albumin/globulin, total bilirubin and erythrocyte specific volume were selected as predictors. This model has been demonstrated to have a satisfactory predictive performance to discriminate between COVID-19 and influenza A (AUC=0.844) using an external validation set. Conclusion: The establishment of a diagnostic model on laboratory findings is of great significance for the identification of COVID-19 and influenza A.
Pterostilbene inhibits influenza virus infection through interaction with NS1 protein
Wenjiao Wu
Yilu Ye

Wenjiao Wu

and 7 more

January 30, 2024
With the prevalence of novel influenza strain and drug resistance virus, it is urgent to develop effective and low-toxicity anti-influenza therapeutics. Here we found that pterostilbene effectively inhibited influenza A virus infection. Mechanism study demonstrated that pterostilbene inhibited virus infection through interaction with influenza non-structural protein 1 (NS1), in turn promoted the induction of antiviral type I interferon and impeded the pro-viral PI3K/Akt pathway activation during influenza virus infection, inducing a synergistic inhibitory effect against influenza virus infection. Thus, pterostilbene can be a promising anti-influenza agent for the future antiviral drug exploitation.
Predicting the severity of disease progression in COVID-19 at the individual and popu...
Narendra Chirmule
Pradip Nair

Narendra Chirmule

and 5 more

January 30, 2024
The impact of COVID-19 disease on health and economy has been global, and the magnitude of devastation is unparalleled in modern history. Any potential course of action to manage this complex disease requires the systematic and efficient analysis of data that can delineate the underlying pathogenesis. We have developed a mathematical model of disease progression to predict the clinical outcome, utilizing a set of causal factors known to contribute to COVID-19 pathology such as age, comorbidities, and certain viral and immunological parameters. Viral load and selected indicators of a dysfunctional immune response, such as cytokines IL-6 and IFN which contribute to the cytokine storm and fever, parameters of inflammation d-dimer and ferritin, aberrations in lymphocyte number, lymphopenia, and neutralizing antibodies were included for the analysis. The model provides a framework to unravel the multi-factorial complexities of the immune response manifested in SARS-CoV-2 infected individuals. Further, this model can be valuable to predict clinical outcome at an individual level, and to develop strategies for allocating appropriate resources to mitigate severe cases at a population level.
Nosocomial Covid-19 Infection in Women Undergoing Elective Cesarean Sections: A prosp...
Aaron Nizam
Michael Nimaroff

Aaron Nizam

and 5 more

January 30, 2024
Objectives: To determine the nosocomial infection rate in women undergoing elective cesarean section Design: Non-randomized prospective cohort trial Setting: Two large-volume obstetrical units at academic institutions Population: Women undergoing elective cesarean section during the reopening phase of the Covid-19 pandemic in New York State Methods: Eligible patients with negative pre-operative Covid-19 reverse transcriptase-polymerase chain reaction test and IgG antibody test were re-tested 6-9 days after discharge. Main Outcome Measures: The primary objective was the Covid-19 test conversion rate defined as a positive PCR test after discharge with a negative pre-operative test. This was used as a proxy for the nosocomial infection rate. Results: No patients with a negative PCR test pre-operatively had a positive PCR test for the Covid-19 virus postoperatively. Conclusions: With a strict and methodical perioperative and postpartum protocol, we can limit nosocomial Covid-19 infections in women undergoing elective cesarean section. Funding: No external funding was obtained for this study Keywords: Covid-19, Cesarean Section, Nosocomial Infection
Remote and rural mothers’ perceptions of risks and safety of intrapartum care: a qual...
Verity Watson
Helen Bryers

Verity Watson

and 5 more

January 30, 2024
The views of mothers are important in shaping policy and practice regarding options for intra-partum care. The aim of this study was to assess the trade-offs that remote and rural women make regarding intrapartum care. Methods Qualitative telephone interviews were undertaken, transcribed and analysed for themes by two researchers. A diagrammatic analysis was then derived to illustrate the relationship between the themes. Results 13 interviews were undertaken with women who had young children and one who was pregnant. All were from the north of Scotland. Key themes identified related to: risk/safety, distance, travel, weather, antenatal care, intervention, type and place of care, the possibility of intra-partum and postnatal transfer, and support by different professional groups. Discussion and Conclusion This in-depth study provides insight into the factors that women living in remote and rural areas consider when making choices regarding intrapartum care. These views should be incorporated into policy development and inform antenatal discussion with pregnant women.
Multi-enzyme-producing extremophile isolated from food waste under fluctuating enviro...
Van Hong Thi Pham
Jeongyoon Ahn

Van Hong Thi Pham

and 5 more

January 30, 2024
Well-adapted bacteria under wide extreme conditions of acidic/alkaline pH and hot/cold temperatures play a significant role in degradation efficiency and in eliminating the cost of waste treatment processes in large areas. Extremozymes isolated by these organisms are resistant to extraordinary properties of salt allowance, cold adaptivity, and thermostability. In this study, we aimed to assess the isolation of protease-, amylase-, cellulase-, and lignin peroxidase-producing bacteria using a wide range of physical parameters to select suitable isolates and investigate their functions and enzyme activities. The bacterial strain FW2 was isolated from food waste and screened the growth and the degradation of organic compounds under fluctuating temperatures, different pH values, and high salinity concentrations. This strain was able to degrade organic compounds at temperatures from –6℃ to 75°C (weak at 80°C) under a wide pH range of 4.5–12, and in a sodium chloride (NaCl) concentration of 0–35%. Maximum enzyme production was obtained at 1200 U/mL for protease, 2400 U mL-1 for amylase, 920 U/mL for CMCase, 1300 U/mL for Avicelase, and 0.165 U/mL for Lignin peroxidase at pH 7–7.5, 40–45°C, and 0–10% NaCl. With these valuable characteristics, strain FW2 may be a potential contributor to waste degradation under fluctuating environmental conditions.
Patient’s experience with Arabin cervical pessary during pregnancy: a questionnaire s...
Viola Seravalli
Noemi Strambi

Viola Seravalli

and 6 more

January 30, 2024
Objective To investigate women’s experience with the cervical pessary for prevention of preterm birth. Design: Retrospecitve questionnaire study. Setting: Tertiary care hospital in Italy. Population: 166 pregnant women treated with Arabin cervical pessary within one center. Methods: A questionnaire was administered to all women after delivery. Main outcome measures: Data about patient’s experience before the insertion (adequacy of the information received), during treatment (follow-up, impact on daily life, perceived discomfort, side effects) and at the time of removal (pain, patient’s expectation met regarding the treatment) were analysed. Results: Information received before the insertion of Arabin pessary was considered adequate in 163/166 (98.2%). An increase of vaginal discharge was experienced by 70/166 (42.2%) women. Discomfort or other side effects were reported in 13.8% and 16.3% of cases, respectively. Overall, 77% of women reported an improved quality of life and 94% considered the follow-up during pregnancy adequate. Removal was moderately painful for 58/166 (35%) of women. Patient’s expectations regarding the treatment were exceeded in the majority of cases (75.3%). In a final step, we compared our results to previous studies suggesting that clinical experience of the health care specialists in charge may explain why the discrepancy of results. Conclusion: Although some trials report high rates of non-compliant patients, this could not be confirmed by our study. In contrast, most women reported a positive experience and were motivated to continue the treatment when they were continuously followed by experienced clinicians.
Comparison of surgery resection, transcatheter arterial chemoembolization and local a...
luke Zhou
Jian Chen

luke Zhou

and 5 more

January 30, 2024
Objectives: To determine surgery resection (SR), the use of transcatheter arterial chemoembolization (TACE) and the use of local ablation, which is more effective for patients with primary large hepatocellular carcinoma (HCC). Methods: We assessed clinical trials through PubMed, Medline, Embase and the Cochrane Library up to March 2020. The basic data and the overall survival (OS) were recorded. The primary outcome was short-term and long-term survival. Results: A total of 23 researches including 2849 patients were enrolled in the meta-analysis. The meta-analysis indicated a significant improvement in the 1-year OS (HR=2.71, 95% CI 1.75–4.22, P < 0.01), 2-year OS (HR = 2.51, 95% CI 1.59–3.96, P < 0.01) favoring combination therapy over monotherapy. A significant improvement in the 1-year (HR = 3.38, 95% CI 1.90–6.01, P <0.01) and 2-year (HR = 1.96, 95% CI 1.25–3.07, P =0.003) OS favoring TACE + SR over TACE therapy. The pooled outcome indicated that three-year OS rate (HR = 3.11, 95% CI 1.49–6.49, P =0.002) and 5-year OS (HR = 2.95, 95% CI 1.30–6.66, P =0.009) was higher in the SR group than in the TACE group. Meta-analysis indicated that TACE+ ablation therapy was superior to other therapy (P<0.01) except when compared with TACE+SR/ SR (P>0.01). Conclusions: In patients with large hepatocellular carcinoma, SR is the preferred treatment. For those patients who cannot be operated or lack of surgical opportunity, TACE combined with local ablation therapy may achieve better therapeutic effect.
Use of inhaled corticosteroids on an intermittent or as-needed basis in pediatric ast...
Carlos Rodriguez-Martinez
Monica Sossa-Briceño

Carlos Rodriguez-Martinez

and 2 more

January 30, 2024
Objectives: The aim of the present study was to summarize the principal findings of all available studies that have evaluated the use of ICS on an intermittent or as-needed basis as an add-on therapy to short-acting β2-agonists (SABAs) or fast-acting β2-agonists (FABAs), given alone or in addition to daily controller therapy, in pediatric asthmatic patients. Methods: Studies published by February 2021 that evaluate the use of ICS on an intermittent or as-needed basis as an add-on therapy to SABAs or FABAs given alone or in addition to daily controller therapy in pediatric asthma were identified. The quality of the studies was assessed using the Cochrane Risk of Bias and the AMSTAR 2 tools. Results: Of 294 references identified, 14 studies were included. The use of ICS on an intermittent or as-needed basis (as an add-on therapy to SABAs) has been shown to be more effective than treatment with SABA alone and to be similarly or less effective compared to regular daily ICS administration. Furthermore, strategies involving increasing the dose of ICS only when needed (as an add-on therapy to FABAs such as formoterol) and keeping it low during stable stages of the disease have been shown to be similarly or more effective than comparators. Conclusion: The use of ICS on an intermittent or as-needed basis as an add-on therapy to SABAs or FABAs, given alone or in addition to daily controller therapy in pediatric asthmatic patients, is an effective and well-tolerated treatment strategy.
Suspected drug induced liver injury due to 6-mercaptopurine with a superimposed Sars-...
Kory Cablay
Violet Borowicz

Kory Cablay

and 2 more

January 30, 2024
6-Mercaptopurine (6-MP) is a chemotherapeutic drug that exhibits hepatotoxic effects due to its toxic metabolites. This report describes a case of suspected drug induced liver injury exacerbated by a Sars-Cov-2 infection. A 16-year-old male with VHR B-ALL was admitted for hyperbilirubinemia two months after a 6-MP dosage increase and found to have an active Sars-Cov-2 infection. Liver function improved throughout hospitalization and the patient was discharged on allopurinol. Following liver function after a dosage increase of hepatoxic chemotherapy and in a pediatric oncology patient with an active Sars-Cov-2 infection undergoing treatment is vital due to potential liver impact.
Mechanistic modeling of a novel oncolytic virus, V937, to describe viral kinetic and...
Zinnia P Parra Guillen
Tomoko Freshwater

Zinnia P Parra Guillen

and 7 more

January 30, 2024
V937 is an investigational novel oncolytic, non-genetically modified Kuykendall strain of Coxsackievirus A21 which is in clinical development for the treatment of advanced solid tumor malignancies. V937 infects and lyses tumor cells expressing the intercellular adhesion molecule I (ICAM-I) receptor. We integrated in vitro and in vivo data from six different preclinical studies to build a mechanistic model that allowed a quantitative analysis of the biological processes of V937 viral kinetics and dynamics, viral distribution to tumor, and anti-tumor response to V937 in human xenograft models in immunodeficient mice following intratumoral and intravenous administration. Estimates of viral infection and replication which were calculated from in vitro experiments were successfully used to describe the tumor response in vivo under various experimental conditions. Despite the predicted high clearance rate of V937 in systemic circulation (t1/2=4.3 min), high viral replication was observed in immunodeficient mice which resulted in tumor shrinkage with both intratumoral and intravenous administration. The described framework represents a step towards the quantitative characterization of viral distribution, replication, and oncolytic effect of a novel oncolytic virus following intratumoral and intravenous administrations in the absence of an immune response. This model may further be expanded to integrate the role of the immune system on viral and tumor dynamics to support the clinical development of oncolytic viruses.
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