In this paper, we establish a new post quantum integral identity for twice $(p,q)$-differentiable convex functions. Then, we use this result to derive some new post quantum Ostrowski-type inequalities for twice $(p,q)$-differentiable convex functions involving $(p,q)_a$- and $(p,q)^b$-integrals. The newly established results are also proven to be generalizations of some existing results in the field of integral inequalities of already published ones.

Objective: The objective of this study is to identify the effects of Coronavirus Disease 2019 (COVID-19) on liver enzymes in pregnant patients and to determine the significance of transaminitis as a predictor of worse clinical outcomes. Design: Case series. Setting: Tertiary care medical center. Population: 31 pregnant patients with a positive COVID-19 polymerase chain reaction (PCR) test and 20 infants who presented during March 25, 2020, to May 26, 2020. Methods: Maternal and neonatal outcomes were compared between patients with transaminitis and without transaminitis using one tailed Mann-Whitney test for nonparametric data and the fisher’s exact test for categorical data. Main outcome measures: Worse maternal outcomes between the groups were defined as need for intubation, oxygen supplementation, intensive care unit (ICU) admission, maternal death, and length of hospital stay. Results: Of the 31 patients with COVID-19, 10/29 (34.5%) were found to have transaminitis. The patients with transaminitis had increased oxygen requirements, increased rate of intubation and ICU admissions. Neonatal outcomes in patients with transaminitis included earlier gestational age at delivery and lower birth weights, but neither were statistically significant. Conclusion: Our study revealed that patients with COVID-19 and concomitant transaminitis had worse clinical outcomes in the mother when compared to those without transaminitis. Further studies should be conducted to explore this link between abnormal liver studies and poor outcomes in pregnant patients diagnosed with COVID-19. Keywords: Coronavirus, COVID-19, transaminitis, pregnancy Tweetable abstract: Pregnant patients with COVID-19 and transaminitis had worse outcomes than ones without transaminitis.

Objective - To compare neonatal magnesemia in the first fifteen days of neonatal life between three groups: a control group not exposed to MgSO4, a neuroprotection group, and an eclampsia prevention group, and to explore its’ associations with child outcomes. Design - Retrospective single-centre cohort study. Setting - Tertiary care setting. Population - Infants admitted at the neonatal intensive care unit born between 24 and 32 weeks’ gestation, regardless of etiology of preterm birth. Methods - Linear mixed regression of neonatal magnesemia on exposure group and day of life. Generalised estimating equations models of child outcomes on neonatal magnesemia according to exposure group and day of life. Main outcome measures - Neonatal magnesemia (mmol/l). Results - Neonatal magnesemia is significantly higher in the preeclampsia group compared to the control and neuroprotection group. On the day of birth, this is irrespective of maternal magnesemia (preeclampsia vs control group), and the maternal total dose or duration of MgSO4 administration (preeclampsia vs neuroprotection group). No differences were found in short-term composite outcome between the three groups. Conclusions - We found mean differences in neonatal magnesemia between children not exposed to MgSO4 antenatally, children exposed for fetal neuroprotection, and children exposed for maternal eclampsia prevention. A 4g loading and 1g/h maintenance dose, for fetal neuroprotection and eclampsia prevention, appears to be safe on the short term for the neonate. Funding - Isabelle Dehaene is funded by a scholarship of FWO (1700520N) Keywords - neonatal magnesemia, neuroprotection, preeclampsia, preterm birth

Background: Cold exposure can trigger asthma attacks. However, the underlying mechanism is yet to be elucidated. We hypothesize that low temperature reduces occludin expression and compromises airway epithelial barrier function, which, in turn, results in asthma exacerbation. Methods: We examined occludin expression in Beas-2B cells exposed to either 29 °C or 37 °C. The following drugs were administered prior to cold treatment: MG132 (a proteasome inhibitor), cycloheximide (a protein synthesis inhibitor), HC-067047 plus GSK2193874 (transient receptor potential vanilloid 4 [TRPV4] antagonists), or C4-ceramide (an SGK1 activator). siNedd4-2 was transfected into Beas-2B cells to investigate the role of Nedd4-2 in mediating cold-induced occludin instability. In animal experiments, we treated ovalbumin (OVA)-induced asthmatic mice with either a thermoneutral temperature of 30 °C or repeated cold stress (10 °C, 6 h/day) for 2 weeks. Either GSK2193874 or C4-ceramide was administered during the cold treatment. After a final OVA challenge, pulmonary permeability, serum IgE levels, and lung inflammation were assessed. Results: Treatment at 29 °C for 1−9 h significantly reduced Beas-2B cell occludin expression, which was rescued upon treatment with MG132, HC-067047 plus GSK2193874, C4-ceramide, or the Nedd4-2 knockdown. Notably, low temperatures affected occludin stability through SGK1/Nedd4-2-dependent proteolysis. In vivo analyses revealed that repeated cold exposure compromised the airway epithelial barrier function and exacerbated lung inflammation in mice, which was partially attenuated by the GSK2193874 or C4-ceramide injection. Conclusions: We identified a new mechanism underlying cold-induced asthma exacerbation that may involve SGK1/Nedd4-2-mediated occludin proteolysis, resulting in epithelial barrier dysfunction.

Background: The information received by patients with cancer and the consequent satisfaction are main components of the evaluation of quality of care. We aim to validate the Mexican-Spanish version of the QLQ-INFO25 in patients with gastrointestinal cancer. Methods: Patients included responded the QLQ-INFO25 instrument at a cancer center. The usual psychometric tests were performed. Results: 70 female and 66 males were included (mean age 56.2); 111 were colorectal and 25 gastroesophageal cancer. Questionnaire compliance rates were high and the instrument was well accepted. No missing values were found. Convergent item correlation was 0.008 to 0.768 and divergent item correlation was from 0.014 to 0.662. Cronbach’s α coefficients of multi-item scales were >0.7 (range, 0.655–0.905). Four scales distinguished among esophagogastric or colorectal cancer, and four scales were associated with overall survival. Conclusion: The Mexican-Spanish version of the questionnaire is reliable and valid to be used in clinical trials.

This study aimed to investigate the relationship between job stress, burnout and intention to leave, moderated by emotional and cognitive empathy. Data were collected via the Maslach Burnout Inventory (MBI-HSS), “Interpersonal Reactivity Index” (IRI) measuring perspective-taking and empathic concern, Spielberger’s “Professional Stress Questionnaire”, and a questionnaire measuring “Intention to leave”. Medical doctors, nurses and psychologists working in addiction facilities were surveyed. Data processing showed that independently, job stress increases burnout and intention to leave. Also, either cognitive or emotional factors of empathy prevent burnout and intention to leave, but in interaction with each other they reduce each other’s preventing effect. Moreover, perspective-taking enhances the effect of job stress on intention to leave. This twofold effect of empathy for burnout and intention to leave provides practical implications for healthcare professionals. Key words: burnout; empathy; job stress; intention to leave.

Evidence suggests that guard cells have higher rate of phosphoenolpyruvate carboxylase (PEPc)-mediated dark CO2 assimilation than mesophyll cells. However, it is unknown which metabolic pathways are activated following dark CO2 assimilation in guard cells. Furthermore, it remains unclear how the metabolic fluxes throughout the tricarboxylic acid (TCA) cycle and associated pathways are regulated in illuminated guard cells. Here we used 13C-HCO3 labelling of tobacco guard cells harvested under continuous dark or during the dark-to-light transition to elucidate principles of metabolic dynamics downstream of CO2 assimilation. Most metabolic changes were similar between dark-exposed and illuminated guard cells. However, illumination increased the 13C-enrichment in sugars and metabolites associated to the TCA cycle. Sucrose was labelled in the dark, but light exposure increased the 13C-labelling into this metabolite. Fumarate was strongly labelled under both dark and light conditions, while illumination increased the 13C-enrichment in pyruvate, succinate and glutamate. Only one 13C was incorporated into malate and citrate in either dark or light conditions. Our results collectively suggest that the PEPc-mediated CO2 assimilation provides carbons for gluconeogenesis, the TCA cycle and glutamate synthesis and that previously stored malate and citrate are used to underpin the specific metabolic requirements of illuminated guard cells.

Abstract ( n=254/250 words)   Background: The Janssen-Ad26.COV2.S vaccine is authorised for use in several countries with more than 30 million doses administered. Mild and severe allergic adverse events following immunisation(AEFI) have been reported. The aim of this report is to detail allergic reactions reported during the Sisonke phase 3B study in South Africa. Methods: A single-dose of the Ad26.COV2.S vaccine was administered to 477234 South African Healthcare Workers between 17 February and 17 May 2021. Monitoring of adverse events used a combination of passive reporting and active case finding. Telephonic contact was attempted for all adverse events reported as “allergy”. Anaphylaxis adjudication was performed using the Brighton Collaboration (BCC) and NIAID case definitions.  Results: A large cohort of South African healthcare workers received the Ad26.COV2.S vaccination. Only 250(0.052%) patients reported any allergic-type reaction(less than 1 in 2000), with four cases of adjudicated anaphylaxis (BCC level 1, n=3)(prevalence of 8.4 per million doses). All anaphylaxis cases had a prior history of drug or vaccine-associated anaphylaxis. Cutaneous allergic reactions were the commonest non-anaphylatic reactions and included: self-limiting, transient/localised rashes requiring no healthcare contact(n=91); or isolated urticaria and/or angioedema[n=70 median  onset 48(IQR 11.5-120) hours post vaccination] that necessitated healthcare contact(81%), antihistamine(63%), and/or systemic/topical corticosteroid(16%). All immediate (including adjudicated anaphylaxis) and the majority of delayed AEFI(65/69) cases resolved completely.   Conclusions: Allergic AEFI are rare following a single-dose of Ad26.COV with complete resolution in  all cases of anaphylaxis. Though rare, isolated, delayed onset urticaria and/or angioedema was the commonest allergic AEFI requiring treatment, with nearly half occurring in participants without known atopic disease.   Keywords: allergic reaction, anaphylaxis, COVID19 adenovirus vaccine; Janssen-Ad26.COV2.S vaccine, urticaria

Objectives：The median effective concentration of ropivacaine in interscalene brachial plexus block for postoperative analgesia after arthroscopic rotator cuff repair(ARCR) has not been determined. Design: this is a prospective double blinded study. Method: This study was conducted on 40 patients with ASA grade I or II who had selective ARCR. A concentration of 10mL ropivacaine administered for the Interscalene brachial plexus block(ISBPB) was determined using the up-and-down sequential. The initial concentration of ropivacaine 0.3%. After a successful or unsuccessful postoperative analgesia, the concentration of ropivacaine was decreased or increased by 0.05% in the next patient, respectively. We defined successful postoperative analgesia as a visual analogue scale(VAS)score＜4 at rest or activity within initial 8 hours after ISBPB. VAS score≥4 was defined as unsuccessful analgesia. The analytic techniques of linear, linear-logarithmic, exponential regressions and centered isotonic regression were used to determine the EC50 of ropivacaine and the residual standard errors were calculated for the comparison of “goodness of fit” among the different models. Results: The concentration of local anesthetic ropivacaine administered ranged from 0.1% to 0.35%. The EC50 (95% confidence interval) from 4 different statistical approaches (linear, linear-logarithmic, exponential regressions and centred isotonic regression) were 0.207% (0.168%, 0.355%), 0.182% (0.165%, 0.353%), 0.196% (0.154%, 0.356%), and 0.163%, respectively. Among all of the 4 models, the exponential regression had the least residual standard error (0.0990). Conclusion: The EC50 derived from four statistical models for 10ml ropivacaine in ultrasound-guided interscalene brachial plexus block for postoperative analgesia was distributed in a narrow range of 0.163%–0.207%.

Cryptococcus spp. are basidiomycete fungi with a unique phenotypic peculiarity, the mucopolysaccharide capsule that circulate all the cell body. Cryptococcus spp. are broadly found in the environment, but there are two species are associated to disease in humans and other animals: Cryptococcus neoformans and Cryptococcus gattii complexes. Experimental studies on cryptococcosis in mammal animal model have demonstrated the occurrence of CNS infection and similarities in the fungal pathogenicity with clinical and immunological features of the human infection. There is still a lack of studies involving pharmacokinetics and pharmacodynamics (PK/PD) in animal models of cryptococcosis in the literature and these experimental models are useful to understand this mycosis and antifungal effectiveness for improving the therapeutic schemes. The scope of this review is to describe and discuss the main mammal animal models for PK/PD studies of antifungals used in the cryptococcosis treatment. Alternative models and computational methods are also addressed. Therefore, all approaches to PK/PD studies are relevant to investigate the drug-infection interaction and consequently to improve the cryptococcosis therapy.

Background: Persistence of protective immunity for SARS-CoV-2 is important against reinfection. Knowledge on SARS-CoV-2 immunity in pediatric patients is currently lacking. We opted to assess the SARS-CoV-2 adaptive immunity in recovered children and adolescents, addressing the pediatrics specific immunity towards COVID-19. Method: Two independent assays were performed to investigate humoral and cellular immunological memory in pediatric convalescent COVID-19 patients. Specifically, RBD IgG, CD4+, and CD8+ T cell responses were identified and quantified in recovered children and adolescents. Results: SARS-CoV-2-specific RBD IgG detected in recovered patients had a half-life of 121.6 days and estimated duration of 7.9 months compared with baseline levels in controls. The specific T cell response was shown to be independent of recovery time. Both CD4+ and CD8+ T cells showed robust responses not only to spike (S) peptides (a main target of vaccine platforms) but were also similarly activated when stimulated by membrane (M) and nuclear (N) peptides. Importantly, we found the differences in the adaptive responses were correlated with the age of the recovered patients. The CD4+ T cell response to SARS-CoV-2 S peptide in children aged <12 years correlated with higher SARS-CoV-2 RBD IgG levels, whereas higher level of CD8+ T cells in children aged ≥12 years, suggesting the importance of a T cell-dependent humoral response in younger children under 12 years. Conclusion: Both cellular and humoral immunity against SARS-CoV-2 infections can be induced in pediatric patients. Our important findings provide fundamental knowledge on the immune memory responses to SARS-CoV-2 in recovered pediatric patients.

The KCC-Jacobi method has been used for analyzing Garner cancerous model. The KCC theory is based on the assumption that the second-order dynamical system and geodesics equation, in associated Finsler space, are topologically equivalent. The stability (Jacobi stability) based on KCC theory and linear stability of the model are discussed in detail. Further, the effect of parameters on stability and presence of chaos in the model are investigated. The asymptotic behavior of stabilities of model are investigated. This investigation will be helpful in cancer therapy. The numerical examples of particular interest have been taken to compare Jacobi and linear stability and it has been found that Jacobi stability on the basis of KCC theory is global than the linear stability.

In this work, we prove a generalized version of Hermite-Hadamard-Mercer type inequalities using the Beta function. Moreover, we prove some new trapezoidal type inequalities involving Beta functions for differentiable convex functions. The main advantage of these inequalities is that these can be converted into similar classical integral inequalities, Riemann-Liouville fractional integral inequalities and $k$-Riemann-Liouville fractional integral inequalities. Finally, we give applications to special means of real numbers for newly established inequalities.

Coronaviruses infect lungs leading to death due to asphyxiation. SARS-CoV-2 is treated by targeting symptoms, repurposing drugs and plasma therapy. Several synthetic drugs are being prescribed that cause major side effects in liver, kidney and heart. Therefore new compounds with low toxicity must be investigated. We have identified antiviral compounds like Eritadenine, Gallic Acid, Ergosterol Peroxide and Pleuran from various edible mushrooms such as Lentinula edodes, Agaricus bisporus, Pleutorus ostreatus and Hericium erinaceus with evidence of literature review. The docking and simulation studies with the targets of SARS-CoV-2 such as Main Protease (M Pro) and Spike Protein were highly successful. In silico ADMET studies further proved that these compounds are druggable with low toxicity. These compounds have potential to prevent the cellular entry to prohibit assembly of new viruses inside the cell. But further studies are required to substantiate their bioactivity claim by in vitro and in vivo assay methods.

Tolerance to exogenously added ROS examined for correlation to enhanced specific growth rates of A. platensis

Background: Considering the role of higher blood urea nitrogen and lower serum albumin (SA) levels in deceased COVID-19 patients, increased blood urea nitrogen to SA (B/A) ratio may help to determine those at higher risk of becoming critically ill. This study evaluated the association of SA level and B/A ratio with disease severity and 30–day mortality and also their predictive value for disease severity in COVID–19 patients. Methods: 433 adult patients with COVID–19, admitted to a referral medical center in Tehran, Iran, from February to May 2020 were included. The laboratory markers were measured on admission. Disease severity was categorized into mild disease, severe pneumonia, acute respiratory distress syndrome (ARDS), sepsis, and septic shock. The mortality was followed up for thirty days after admission. Results: Thirty–day mortality rate was 27.25%. The frequency of mild, severe pneumonia, ARDS, sepsis, and septic shock was 30.72%, 36.95%, 24.02%, 6.00%, and 2.31%, respectively. Mean B/A ratio was different among different disease severities. The odds of thirty-day mortality increased by 16% by each unit increase in B/A ratio and decreased by 57% by each unit increase in SA level. B/A ratio had the AUC of 0.45 for disease severity prediction with 71% sensitivity and 22% specificity. Conclusion: The results showed that B/A ratio and SA levels are associated with mortality in COVID–19 patient, while they had low predictive value for disease severity. High B/A ratio is, additionally, associated with disease severity. Therefore, we suggest to use this marker for clinical assessment of patients with COVID–19.

Here we report a boy with disseminated choroid plexus carcinoma diagnosed at an age of 2 years 9 months on the background of de novo germline mutation in ТР53. The patient received 3 cycles of high-dose methotrexate-based chemotherapy and 4 cycles of alternating carboplatin/cyclophosphamide chemotherapy, followed by craniospinal proton beam irradiation. To date, the patient lives with neither progression of the disease nor other extracranial neoplasms for 6 years from the diagnosis. This is the first successful experience of proton irradiation therapy affording long-term survival in a child with Li-Fraumeni syndrome-associated choroid plexus carcinoma.

Continuous cropping (CC) obstacles resulting from the increase in planting frequency restrict the sustainable development of the vegetable industry. To understand the mechanisms causing continuous cropping obstacles in-depth, we analyzed pepper (Capsicum annuum L.) rhizosphere soils. Samples were collected using a new type of in situ sampler composed of microporous ceramic tubes. After elution, the samples were qualitatively and quantitatively analyzed via gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC). Then, the effects of the main possible allelochemicals on sensitive plants were investigated. Fourteen chemicals, including 2,4-di-tert-butyl-phenol (2,4-DTBP), diisobutyl adipate (DIBA), dibutyl phthalate (DBP) ，and limonene, were detected with GC-MS. The measured concentration of 2,4-DTBP increased with pepper growth. The results based on seed toxicity revealed that low-concentration (<50 mg·L-1) 2,4-DTBP improved lettuce seed germination rates and that high-concentration (>300 mg·L-1) 2,4-DTBP had significant (p<0.05) inhibitory effects. The results obtained from sensitive cucumber plants showed that the average plant height in the treatments containing 2,4-DTBP was lower (p<0.05). Significant increases in reactive oxygen species (ROS) levels and reductions in the photosynthetic rate (Pnet) were also detected (p<0.05). Leaf transpiration (Tr), stomatal conductance (Gs) and root activity also decreased significantly compared with those of the control. The comparison results between the 2,4-DTBP treatment and the pepper CC treatment showed that the cucumber was more significantly damaged in the latter. Similar trends also occurred in pepper. Our results indicate that the in situ sampler in this study can reflect the actual concentrations of possible allelochemicals in rhizosphere soil. 2,4-DTBP is one of the most important allelochemicals in pepper, and the accumulation of 2,4-DTBP may be an important factor inducing continuous cropping obstacles in pepper.

Species richness pattern along the elevation gradient forms precious tools in understanding diversity gradients and their principal mechanisms. Himachal Pradesh, one of the hubs of biological diversity has congenial atmospheric conditions and is homeland for large number of insects. Despite being one of the major biodiversity hotspots several insect families remain poorly studied in the state including, Cicadellidae: Hemiptera. A total of 85 leafhoppers species belonging to 61 genera of 12 subfamilies of Cicadellidae were recorded from all the 12 districts of the state covering 25 locations. Four species, Gurawa monorcephala Pruthi, Leofa pulchellus Distant, Olidiana kirkaldyi (Walker) and Paralimnellus cingulatus (Dlabola) appeared to be new records from Himachal Pradesh and one species, Pseudosubhimalus sp. Nov was new from India. Species richness as well as diversity increased with rising altitude from Sub-mountain low hills zone I (350-650m amsl) with a hump at mid hills zone II (651-1800m amsl) following a declining trend towards high hills wet temperate zone III (1801-2200m amsl) and high hills dry temperate zone IV (above 2200m amsl). This elevational disparity in species richness might be due to variations in the physiological requirements, host preference and changing climate. Abundance of leafhopper species as observed in temperate regions is of serious concern of global warming, due to their job in transmission of plant viruses and phytoplasmas, of which the world has still no control, therefore the future of food security lies in the paradigm of uncertainty.

BACKGROUND: IgE and High-affinity IgE receptor (FcεRI) expression on basophils has been scarcely explored in patients with chronic inducible urticaria (CIndU). OBJECTIVES: To investigate baseline serum IgE and FcεRI expression on blood basophils in a large cohort of CIndU patients and its relationship to treatment response. METHODS: Baseline total serum IgE and basophil FcεRI expression measured by flow cytometry in 165 patients with CIndU was studied. The relationship of both parameters with the response to antihistamine and anti-IgE (omalizumab) treatment was considered in a subsample of CIndU patients. FcεRI expression in basophils was assessed by mean fluorescence intensity (MFI) and basophil FcεRI standardized density (receptors/cell). RESULTS: The median FcεRI expression standardized per density in blood basophils was found significantly higher in patients with CIndU compared to HCs. A positive correlation was found between IgE serum levels and basophil FcεRI expression. Basal FcεRI expression was not related to antihistamine treatment response. However, it was related to omalizumab, and patients responding to omalizumab showed higher basal basophil expression of FcεRI levels. Non-responders to the antihistamine showed significantly higher IgE serum levels. CONCLUSIONS: FcεRI receptor overexpression in patients with CIndU shows almost the same pattern than Chronic Spontaneous Urticaria. It seems to be independent of CIndU subtypes. Although additional studies would be welcome, our work highlights the relevance of FcεRI receptor regulation in CIndU supporting the autoimmune pathogenesis and suggest that CIndU patients benefit from anti-IgE therapy.

Objective, To evaluate clinical features of children with Deep venous thrombosis (DVT) associated with acute hematogenous osteomyelitis (AHO) caused by Staphylococcus aureus. Method, We reviewed a 4-year medical records of patients with DVT of AHO conclusive caused by Staphylococcus aureus (S. aureus) retrospectively and we compared clinical and laboratory characteristics of AHO with or without DVT, and patients whose DVT dissolved within or more than 3 weeks. Results, 87 AHO patients were admitted during four years period. Nineteen of 87 (22%) patients had DVT. For DVT patients, median age was 9 years (range, 6 mouths-15 years). 74% (14/19) patients were boys. Methicillin-susceptible Staphylococcus aureus (MSSA) accounted for 58% (11/19). All DVT occurred adjacent to the infection site. Femoral vein and common femoral vein were both the two most affected vein (9 cases, respectively). Eighteen (95%) patients received anticoagulation therapy with low molecular weight heparin. Seven of the 13 (54%) with available data had complete resolution of DVT within three weeks of anticoagulation therapy. None of patients required rehospitalization for bleeding or recurrent of DVT. Comparative analysis found patients with DVT were older. C-reactive protein, procalcitonin, D-dimer, fibrinogen, positive blood culture and incidence of intensive care unit admission, multifocal, the length of hospital stay were higher in patients with DVT. Conclusion, More than twenty percent of patients with S. aureus AHO developed DVT in present study. MSSA accounted more than half. More than half cases had complete resolution of DVT within three weeks of anticoagulation therapy without complications afterwards.

objectives: Logistic regression analysis has widespread applications in clinical disease diagnosis, but it has not yet been applied to assess the acceptance of radiotherapy and chemotherapy in patients with lung cancer. A prediction model was established to investigate the influencing factors of radiotherapy and chemotherapy in lung cancer. Methods: A sample was admitted of lung cancer patients to Binzhou Medical University Hospital stays from January 2020 to June 2021. After investigating doctors, nurses, patients, managers and conducting expert demonstration, the questionnaire was formed. The questionnaire was filled out by the patient or the patient’s family members. The factors in the questionnaire data of patients accepting and not accepting radiotherapy and chemotherapy were compared for monofactor analysis, and the significantly different single factor were analyzed by multifactor logistic regression analysis, explored the influencing factors of radiotherapy and chemotherapy in lung cancer patients established a predictive model and drew the receiver operating characteristic curve. Results: The factors of two groups had statistically significant differences or no statistically significant differences. After multifactor logistic regression analysis was conducted, own personality, self-care ability, disease course classification, own attitude towards disease treatment, and family attitude towards disease treatment were included in the influencing factors of radiotherapy and chemotherapy in patients with lung cancer. Then, a predictive model was established. The area under the ROC curve of the predicted model was 0.973, the 95% confidence interval was 0.952-0.995, the optimal critical value was 0.832, the sensitivity was 91.84%, the specificity was 89.09%, and the accuracy was 90.85%. Conclusions: Based on logistic regression analysis, the prediction model could predict the extent of accepting radiotherapy and chemotherapy in patients with lung cancer. Understanding the factors related to patients with lung cancer accepting radiotherapy and chemotherapy could provide useful information for the targeted and effective treatment by clinicia

Background: The introduction of antiretroviral therapy (ART) significantly decreases the incidence of tuberculosis (TB) in Human Immunodeficiency Virus ( HIV) positive individuals during their follow-up. However, a considerable proportion is still co-infected with TB after ART initiation. Thus, this study aimed to assess the determinants of TB incidence among HIV-positive individuals during their ART follow-up in Addis Ababa, Ethiopia. Methods: A nested case-control study was conducted among HIV-positive individuals who were enrolled in ART clinics in Addis Ababa, Ethiopia from 2013 up to 2018. Cases were tuberculosis co-infected HIV positive individuals who were taking antiretroviral treatment, while controls were TB free HIV positive individuals who were taking antiretroviral treatment. The cases and controls are matched exactly in age and sex. Data were entered in EpiInfo version 7.1 and analyzed using SPSS version 20. Bivariable and multivariable conditional logistic regression were employed along with 95% CI. A P-value <0.05 in the multivariable analysis was considered statistically significant. Results: Fifty-seven cases were compared with 114 controls pair-matched exactly in age and sex. Accordingly, previous TB history (X 2; 13.790 , P<0.001), baseline functional status (X 2; 9.120 , P=0.010), baseline WHO clinical stage (X 2; 10.083 , P=0.001), baseline hemoglobin value (X 2; 6.985 , P=0.008), baseline body mass index (X 2; 3.873 , P=0.049), isoniazid preventive treatment intake status (X 2; 8.047 , P=0.005), baseline CD4 value (X 2; 12.741 , P<0.001) and length of stay on ART (X 2; 53.359 , P<0.001) were associated with TB infection. Length of stay on ART was found to be the statistically significant determinant of TB infection after ART initiation (aOR=5.925, 95%CI=2.649-13.250). Conclusion: Advanced clinical stages at the baseline, previous TB history, and not taking IPT were associated with TB infection. The long term ART exposure significantly decreases tuberculosis incidence in HIV patients. Screening HIV-positive patients for tuberculosis throughout their ART follow-up would be important early detection and treatment of tuberculosis.

Background and Purpose: Ritonavir-boosted lopinavir and chloroquine were withdrawn for COVID-19 treatment according to WHO recommendation. However, lopinavir is still being used for COVID-19 treatment in a clinical practice guideline without supportive evidence. We demonstrated the utility of physiologically-based pharmacokinetic (PBPK)/pharmacodynamic (PD) models to support clinical use of lopinavir and the withdrawal of chloroquine for COVID-19 treatment. Experimental approach: The developed whole-body PBPK models were validated against clinical data. Model validation was performed using acceptable methods. The inhibitory effect (%E) was calculated to demonstrate drug efficacy. The recommended drug regimen for COVID-19 was the combination of 400/100 mg lopinavir/ritonavir given twice daily and 300 mg base chloroquine given twice daily for 14 days. Key Results: This study successfully developed whole-body PBPK models (AAFEs of 1.2-fold). For patients with a 70 kg body weight, %E for chloroquine in epithelial lining fluid (ELF) and bronchial epithelial cells (BEC) were about 2% and 12%, respectively. The corresponding values for lopinavir were 66% and 87.4%, respectively. With the increased body weight to 90 kg, %E for lopinavir in BEC dramatically dropped to lower than 60%, while that in ELF was slightly decreased (86.87%). Conclusion and Implications: The results support the decision of withdrawing chloroquine and using lopinavir in asymptomatic (with positive antigen kit test) or mild COVID-19 cases. In addition, results support the administration of antiviral drugs within the ten days of infection to prevent treatment failure.