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1.
preprints.org; 2023.
Preprint in English | PREPRINT-PREPRINTS.ORG | ID: ppzbmed-10.20944.preprints202309.1815.v1

ABSTRACT

Self-selecting the intensity of aerobic training is a perspective that allows practitioners to develop autonomy (choice of pace), improve physical fitness and achieve weight loss. To compare the effect of four aerobic training protocols on cardiometabolic and psycho-affective responses in physically inactive adult men and women. The sample consisted of 11 individuals aged 56 ± 10 years and BMI 29.2 ± 2.4 kg/m2 performed four different treadmill aerobic training protocols, including: 1-individual with self-selected intensity (ISS), 2-individual with prescribed intensity (IPI) (64-76% of HR max), 3-small group with self-select. selected intensity (SGS) and 4-small group prescribed intensity (SGP) (64-76% of HR max). Heart rate (HR), lactate (LACT), perceived exertion (RPE), affective response (FS), activation scale (FAS), enjoyment (PACES) and intention to repeat the session (INT) were analyzed. Statistical analysis used ANOVA with Tukey's post hoc test (p<0.05). HR, LACT and RPE analyzes did not show significant differences between protocols. The FS showed a smaller decline in the SI protocol (p<0.05), and the intention to repeat the training session was greater in the SI protocol (p<0.05). Conclusion: The data allow us to conclude that the SI training protocol produced superior results in affective response, pleasure and intention to repeat the session.


Subject(s)
Weight Loss , Seizures
2.
biorxiv; 2023.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2023.09.26.559599

ABSTRACT

Background: The covid-19 pandemic brought negative impacts in almost every country in the world. These impacts were observed mainly in the public health sphere, with a rapid raise and spread of the disease and failed attempts to restrain it while there was no treatment. However, in developing countries, the impacts were severe in other aspects such as the intensification of social inequality, poverty and food insecurity. Specifically in Brazil, the miscommunication among the government layers conducted the control measures to a complete chaos in a country of continental dimensions. Brazil made an effort to register granular informative data about the case reports and their outcomes, while this data is available and can be consumed freely, there are issues concerning the integrity and inconsistencies between the real number of cases and the number of notifications in this dataset. Results: We projected and implemented four types of analysis to explore the Brazilian public dataset of Severe Acute Respiratory Syndrome (srag dataset) notifications and the google dataset of community mobility change (mobility dataset). These analysis provides some diagnosis of data integration issues and strategies to integrate data and experimentation of surveillance analysis. The first type of analysis aims at describing and exploring the data contained in both datasets, starting by assessing the data quality concerning missing data, then summarizing the patterns found in this datasets. The Second type concerns an statistical experiment to estimate the cases from mobility patterns organized in periods of time. We also developed, as the third analysis type, an algorithm to help the understanding of the disease waves by detecting them and compare the time periods across the cities. Lastly, we build time series datasets considering deaths, overall cases and residential mobility change in regular time periods and used as features to group cities with similar behavior. Conclusion: The exploratory data analysis showed the under representation of covid-19 cases in many small cities in Brazil that were absent in the srag dataset or with a number of cases very low than real projections. We also assessed the availability of data for the Brazilian cities in the mobility dataset in each state, finding out that not all the states were represented and the best coverage occurred in Rio de Janeiro state. We compared the capacity of place categories mobility change combination on estimating the number of cases measuring the errors and identifying the best components in mobility that could affect the cases. In order to target specific strategies for groups of cities, we compared strategies to cluster cities that obtained similar outcomes behavior along the time, highlighting the divergence on handling the disease. Availability: https://github.com/YasCoMa/dashboard-srag-mobility


Subject(s)
Respiratory Insufficiency , Severe Acute Respiratory Syndrome , COVID-19
3.
preprints.org; 2023.
Preprint in English | PREPRINT-PREPRINTS.ORG | ID: ppzbmed-10.20944.preprints202309.1520.v1

ABSTRACT

Polycystic ovary syndrome (PCOS) is a prevalent condition characterized by manifestations that can influence self-image and potentially result in psychological distress; however, data from literature on sexual function (SF) in PCOS women are contradictory. We aimed to evaluate sexual dysfunction (SD) in PCOS women by carrying out a systematic review and meta-analysis, using the gold-standard assessment tool SD-diagnosis (Female Sexual Function Index:FSFI). Seven databases were analyzed until August-2023; study quality was assessed by risk of bias and Newcastle Ottawa Scale. Our analysis encompassed 25 case-control studies (9933 women). PCOS group presented significantly lower scores in arousal (MD= -0.36 CI95%-0.60;-0.11), lubrication (MD= -0.52 CI95%-0.75;-0.28), orgasm (MD= -0.39 CI95%-0.57;-0.20), satisfaction (MD= -0.32 CI95%-0.50;-0.14) and pain subdomains (MD= -0.46 CI95%-0.75;-0.16), as in overall FSFI score (MD= -2.27 CI95%-3.23;-1.31). Overweight/obese (OW/O) patients exhibited significantly higher overall FSFI than OW/O controls (MD=1.98 CI95%0.68;3.27), particularly in lubrication (MD= -0.34), orgasm (MD= -0.26) and satisfaction (MD= -0.25) subdomains. These findings offer insights regarding SD in PCOS women and emphasize the need to incorporate SF assessment into multidisciplinary care. By this way, PCOS can be also considered a gateway diagnosis to other long-term consequences. Further research should focus on controlling variables, as ethnicity, culture, religion and economic disparities.


Subject(s)
Sexual Dysfunction, Physiological , Obesity , Pain , Polycystic Ovary Syndrome
4.
preprints.org; 2023.
Preprint in English | PREPRINT-PREPRINTS.ORG | ID: ppzbmed-10.20944.preprints202309.1415.v1

ABSTRACT

Background: The global pandemic of coronavirus disease 2019 (COVID-19) resulted to many deaths from fulminant respiratory failure. Chronic obstructive pulmonary disease (COPD) is the leading cause of morbidity and mortality worldwide. There has been great concern regarding the impact of COPD on COVID-19 illness. Methods: Data from the Philippine CORONA Study were analyzed to determine the association of COPD and COVID-19 in terms of mortality, disease severity, respiratory failure, mechanical ventilation, and lengths of stay in the intensive care unit (ICU) and hospital. The influence of smoking on COVID-19 disease severity and mortality were also reviewed. Results: A total of 10,881 patients were included in the study and 156 (1.4%) patients had been diagnosed with COPD. Majority of COVID-19 patients with COPD had other existing comorbidities: hypertension, diabetes mellitus, chronic cardiac disease, and chronic kidney disease. COPD patients more commonly present with severe or critical COVID-19. COPD patients with COVID-19 were at higher risk to experience in-hospital mortality, respiratory failure, and to be admitted in the ICU. Smokers were more likely to present with higher COVID-19 severity and experience in-hospital mortality. Conclusion: Our study supports that the growing evidence that COPD among COVID-19 patients is a risk for higher mortality, more severe form of COVID-19, higher ICU admission, and higher respiratory failure needing ventilatory support. Smoking increases risk for developing severe COVID-19 and mortality.


Subject(s)
Heart Diseases , COVID-19 , Renal Insufficiency, Chronic , Respiratory Insufficiency , Diabetes Mellitus , Pulmonary Disease, Chronic Obstructive , Hypertension
5.
preprints.org; 2023.
Preprint in English | PREPRINT-PREPRINTS.ORG | ID: ppzbmed-10.20944.preprints202309.1151.v1

ABSTRACT

Castor oil may be differentiated from other non-edible vegetable oils because of its main composition of hydroxylated fatty acids. Ricinoleic acid comprises 80–90% wt. of fatty acids in castor oil (Ricinus communis). In this study, the thermo-oxidative stability and tribological behavior of bio-based lubricant samples synthesized from castor oil using isoamyl alcohol were evaluated. Initially, the compositional and physicochemical properties of the obtained samples were assessed using 1H NMR, FTIR, and ASTM methods. Oxidative stability of the samples was evaluated using Rancimat method at 110 °C under air flow. The final biolubricant sample (BL2), obtained after esterification, epoxidation, and oxirane rings opening reactions, presented an oxidation stability time (OST) of 14.3 h. The thermal stability was also evaluated by thermogravimetry (TG) from the mass variations under inert and oxidative atmosphere. BL2 showed higher thermal stability compared to the other samples, demonstrating higher decomposition temperatures in both inert (339.04 °C) and oxidative (338.47 °C) atmospheres, for a mass loss of 50%. The tribological properties of the samples were evaluated using a four-ball tribometer configuration. The BL1 and BL2 samples exhibited lower friction coefficients than the mineral oil sample (MOS) by 21.5% and 43.1%, respectively. Regarding wear, the observed wear scar diameter (WSD) was also lower in BL1 and BL2 compared to MOS by 5.2% and 40.4%, respectively. The results of the tribological evaluation suggest that both samples obtained in this study have promising potential for applications in lubricating machines and mechanical systems.

6.
preprints.org; 2023.
Preprint in English | PREPRINT-PREPRINTS.ORG | ID: ppzbmed-10.20944.preprints202309.1048.v1

ABSTRACT

Idiosyncratic drug induced liver injury (DILI) is an unpredictable reaction of exposed individual on a certain drug, and the drug-induced autoimmune hepatitis (DIAIH) presents a DILI phenotype that mimics idiopathic autoimmune hepatitis (AIH) when considering the clinical, biochemical, serological and histological parameters. We present a case of a 48-year-old male that was hospitalized due to severe hepatocellular liver injury two months after the self-treatment with the muscle-building dietary supplement based on arginine-alpha-ketoglutarate, L-citrulline, L tyrosine, creatine malate and beet extract. His immunology panel was positive with increased IgG levels, and the radiologic methods showed no signs of chronic liver disease. He underwent corticosteroid treatment with adequate response. After the therapy withdrawal, a clinical relapse occurred. Seven months after the initial presentation liver MR suggested the initial cirrhotic changes of the right liver lobe. Liver biopsy revealed abundant lymphoplasmacytic infiltrate with piecemeal necrosis and grade 2 fibrosis. He responded well on the corticosteroid treatment again, and was further treated with low dose prednisone without additional relapses. Several years later, further management confirmed presence of liver cirrhosis with no histological or biochemical signs of the disease activity. DIAIH is a DILI phenotype difficult to distinguish from idiopathic AIH despite a wide armamentarium of diagnostic methods. Regular patient monitoring and clinical open-mindedness with the adjustment of therapeutic approaches according to the disease course are more important than strict labelling of the disease.


Subject(s)
Necrosis , Fibrosis , Autoimmune Diseases , End Stage Liver Disease , Liver Cirrhosis , Chemical and Drug Induced Liver Injury
7.
preprints.org; 2023.
Preprint in English | PREPRINT-PREPRINTS.ORG | ID: ppzbmed-10.20944.preprints202309.0727.v1

ABSTRACT

Concatemeric viral DNA is packaged into Bacteriophage P22 procapsids via a headful packaging mechanism mediated by a molecular machine consisting of small (gp3) and large (gp2) terminase subunits. Although a negative stain reconstruction exists for the terminase holoenzyme, it is not clear how this complex binds dodecameric portal protein located at a 5-fold mismatch vertex. Herein, we describe new assemblies for the holoenzyme. Both native mass spectrometry and transmission electron microscopy reveal that the P22 terminase complex adopts three main assemblies, which include a nonameric S-terminase bound to two L-terminase 1(gp3)9:2(gp2), two nonameric S-terminase bound to five L-terminase 2(gp3)9:5(gp2), and three nonameric S-terminase bound to seven L-terminase 3(gp3)9:7(gp2). Native agarose gel electrophoresis shows that the terminase complex interacts with procapsid with mild crosslinking. These results herein illustrate the P22 terminase complex can adopt a variety of confirmations and assembly states.

8.
biorxiv; 2023.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2023.09.07.556636

ABSTRACT

In September 2023, the SARS-CoV-2 XBB descendants, such as XBB.1.5 and EG.5.1 (originally XBB.1.9.2.5.1), are predominantly circulating worldwide. Unexpectedly, however, a lineage distinct from XBB was identified and named BA.2.86 on August 14, 2023. Notably, BA.2.86 bears more than 30 mutations in the spike (S) protein when compared to XBB and the parental BA.2, and many of them are assumed to be associated with immune evasion. Although the number of reported cases is low (68 sequences have been reported as of 7 September 2023), BA.2.86 has been detected in several continents (Europe, North America and Africa), suggesting that this variant may be spreading silently worldwide. On 17 August 2023, the WHO designated BA.2.86 as a variant under monitoring. Here we show evidence suggesting that BA.2.86 potentially has greater fitness than current circulating XBB variants including EG.5.1. The pseudovirus assay showed that the infectivity of BA.2.86 was significantly lower than that of B.1.1 and EG.5.1, suggesting that the increased fitness of BA.2.86 is not due to the increased infectivity. We then performed a neutralization assay using XBB breakthrough infection sera to address whether BA.2.86 evades the antiviral effect of the humoral immunity induced XBB subvariants. The 50% neutralization titer of XBB BTI sera against BA.2.86 was significantly (1.4-fold) lower than those against EG.5.1. The sera obtained from individuals vaccinated with 3rd-dose monovalent, 4th-dose monovalent, 4th-dose BA.1 bivalent, and 4th-dose BA.5 bivalent mRNA vaccines exhibited very little or no antiviral effects against BA.2.86. Moreover, the three monoclonal antibodies (Bebtelovimab, Sotrovimab and Tixagevimab), which worked against the parental BA.2, did not exhibit antiviral effects against BA.2.86. These results suggest that BA.2.86 is one of the most highly immune evasive variants ever.


Subject(s)
Seizures
9.
preprints.org; 2023.
Preprint in English | PREPRINT-PREPRINTS.ORG | ID: ppzbmed-10.20944.preprints202309.0304.v1

ABSTRACT

This study presents a novel polyurethane-activated carbon composite (PACC) as an effective and sustainable adsorbent for treating lead-ion-contaminated waters. The PACC was characterized using SEM-EDX, FTIR, BET, XRD, and TGA to evaluate its physicochemical and thermal properties. Furthermore, the PACC was employed in an experimental column adsorption setup to investigate its adsorption performance and to develop a dynamic method suitable for industrial implementation. Parameters such as bed height (50, 100, 150 mm), flow rate (4, 6, 8 mL min-1), pH (2, 4, 6), and initial metal ion concentrations (10, 50, 100 mg L-1) were examined. The experimental data exhibited strong agreement with the Thomas and Yoon-Nelson models (R2 ≥ 0.96), indicating efficient adsorption mechanisms. Remarkably, the depleted adsorbent has the potential for facile regeneration without substantial loss in capacity. The PACC demonstrated excellent adsorption performance for lead ions in aqueous solutions in a fixed-bed column system. Thus, the novel PACC material holds potential for scalable application in industrial settings to address water pollution challenges, especially in regions with uncontrolled effluent discharge.


Subject(s)
Breakthrough Pain , Composite Lymphoma
10.
medrxiv; 2023.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2023.09.01.23293947

ABSTRACT

Background: We previously conducted a Phase IIa randomized placebo-controlled trial of 40 subjects to assess the efficacy and safety of dupilumab use in those hospitalized with COVID-19 (NCT04920916). Based on our pre-clinical data suggesting downstream pulmonary dysfunction with COVID-19 induced type 2 inflammation, we contacted patients from our Phase IIa study at 1 year for assessment of Post Covid-19 Conditions (PCC). Methods: Subjects at 1 year after treatment underwent pulmonary function testing (PFTs), high resolution computed tomography (HRCT) imaging, symptom questionnaires, neurocognitive assessments, and serum immune biomarker analysis, with subject survival also monitored. The primary outcome was the proportion of abnormal PFTs, defined as an abnormal diffusion capacity for carbon monoxide (DLCO) or 6-minute walk testing (6MWT) at the 1-year visit. Results: Sixteen of the 29 one-year survivors consented to the follow up visit. We found that subjects who had originally received dupilumab were less likely to have abnormal PFTs compared to those who received placebo (Fishers exact p=0.011, adjusted p=0.058). We additionally found that 3 out of 19 subjects (16%) in the dupilumab group died by 1 year compared to 8 out of 21 subjects (38%) in the placebo group (log rank p=0.12). We did not find significant differences in neurocognitive testing, symptoms or CT chest imaging between treatment groups but observed evidence of reduced type 2 inflammation in those who received dupilumab. Conclusions: We observed evidence of reduced long-term morbidity and mortality from COVID-19 with dupilumab treatment during acute hospitalization when added to standard of care regimens.


Subject(s)
Inflammation , COVID-19 , Lung Diseases
11.
preprints.org; 2023.
Preprint in English | PREPRINT-PREPRINTS.ORG | ID: ppzbmed-10.20944.preprints202308.2074.v1

ABSTRACT

Existence of hybrid electric vehicles nowadays is one of the emerging technologies worldwide. Different countries are using this technology on their transportation, and nowadays, a lot of other countries are gradually adapting on using this kind of innovation in their transport system. Philippines is among these countries which aims to have a sustainable mobility by embracing the use of hybrid - electric vehicles but still lots of consumers are lacking awareness on this technology. Lack of information on the social, environmental, and economic potential benefits are among the main issues of Philippines consumers that really affect its uptake. The goal of this study was to evaluate the consumer’s perception and purchase intention on the transition of hybrid - electric vehicles for sustainable mobility and transportation here in the Philippines. It aimed to assess consumer awareness with hybrid - electric vehicles and its potential benefits to human beings in terms of social, environmental, and economic aspects. The study also gauged the impact of this perception on consumer’s purchase intention on hybrid - electric vehicles. These objectives were attained using the Descriptive Statistics and Correlation Analysis. Using these methods, the results revealed that majority of the consumers believed on the positive benefits of transitioning to hybrid - electric vehicles in terms of social, environmental, and economic aspects. This study also showed that these benefits have high impact on the consumer’s intention of buying or having a hybrid – electric vehicle. Electric vehicle is one of the most effective measure of decarbonizing the transport system. Furthermore, government and automotive businesses must strengthen their drive in spreading awareness of hybrid – electric vehicle’s benefits to consumers to further support country’s effort for development.

12.
preprints.org; 2023.
Preprint in English | PREPRINT-PREPRINTS.ORG | ID: ppzbmed-10.20944.preprints202308.2026.v1

ABSTRACT

I. Introduction: Adherence to ART reduces morbidity and mortality among PLHIV by suppression of viral replication, restoration and preservation of immune function. However, poor adherence may lead to treatment failure and death. PLHIV have high probability of treatment interruptions due to lockdowns related to COVID-19 protocol. Mortality rate is higher among COVID-19 patients with HIV than those with COVID-19 only. This led to determination of the barriers to antiretroviral medication adherence in PLHIV at the time of COVID-19 pandemic and seek significant association between identified HIV treatment barriers and socio-demographic characteristics. II. Methods: A cross-sectional study using online survey questionnaire was distributed via social media. Sample size was computed using Open Epi software. Data was analyzed using Stata software. Categorical variables and quantitative data were summarized using frequencies and percentages, and mean and standard deviation respectively. Chi-square test or Fisher’s exact test, whichever is more appropriate, was used to determine association between socio-demographic characteristics and HIV treatment barriers. III. Results: There is a total of 116 respondents, 115 were males, homosexual (59.5%), with mean age of 30.25 years old (SD = 6.22) and majority (53.4%) were from NCR. The most common HIV treatment barriers reported by PLHIV in accessing treatment and care were unavailability of transportation and cost of courier services for ARV delivery (62.1%), location of treatment hubs (52.6%) and financial assistance (37.9%). IV. Conclusion: There is significant association between location of treatment hubs and respondents who finished college/graduate studies; checkpoints and crossing borders and: 1. respondents from Northern Luzon, 2. unemployment; financial assistance and: 1. Respondents 18 to 25 years old, 2. unemployment, 3. respondents who finished elementary/high school; psychosocial support and: 1. Respondents from NCR, 2. Respondents 26 to 30 years old;


Subject(s)
COVID-19
13.
preprints.org; 2023.
Preprint in English | PREPRINT-PREPRINTS.ORG | ID: ppzbmed-10.20944.preprints202308.1903.v1

ABSTRACT

This study presents a methodology to fabricate Ti6Al4V cylindrical compacts with a highly porous core and dense shell with the purpose to mimic the bone microstructure. Compacts with different core diameters were obtained by conventionally press and sintering. Large pores were created with the aid of pore formers. Sintering kinetics was determined by dilatometry, whereas characterization was performed by X-ray computed tomography. Also, permeability was evaluated on the 3D microstructure and the mechanical strength was evaluated by compression tests. Results indicated that sintering is constraint by the different densification rates of the porous and dense layers. Nonetheless, defectless compacts were obtained due to neck bonding between Ti6Al4V particles. Large pores were located in the designed core with similar pore size distribution. Permeability increased following a power law as a function of the pore volume fraction. Stiffness of bilayer components was driven by the porous core, meanwhile, the strength resulted from the combination of both layers. Bilayer materials obtained showed a permeability and mechanical properties, as well as admissible strain (σy /E) similar to those of human bones.

14.
medrxiv; 2023.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2023.08.25.23294606

ABSTRACT

Waning antibody responses after COVID-19 vaccination combined with the emergence of the SARS-CoV-2 Omicron lineage led to reduced vaccine effectiveness. As a countermeasure, bivalent mRNA-based booster vaccines encoding the ancestral spike protein in combination with that of Omicron BA.1 or BA.5 were introduced. Since then, BA.2-descendent lineages have become dominant, such as XBB.1.5 or BA.2.86. Here, we assessed how different COVID-19 priming regimens affect the immunogenicity of the recently used bivalent booster vaccinations and breakthrough infections. BA.1 and BA.5 bivalent vaccines boosted neutralizing antibodies and T-cells up to 3 months after boost; however, cross-neutralization of XBB.1.5 was poor. Interestingly, different combinations of prime-boost regimens induced divergent responses: participants primed with Ad26.COV2.S developed lower binding antibody levels after bivalent boost while neutralization and T-cell responses were similar to mRNA-based primed participants. In contrast, the breadth of neutralization was higher in mRNA-primed and bivalent BA.5 boosted participants. Combined, we highlight important "lessons learned" from the employed COVID-19 vaccination strategies. Our data further support the use of monovalent vaccines based on circulating strains when vaccinating risk groups, as recently recommended by the WHO. We emphasize the importance of the continuous assessment of immune responses targeting circulating variants to guide future COVID-19 vaccination policies.


Subject(s)
Protein S Deficiency , COVID-19 , Breakthrough Pain
15.
medrxiv; 2023.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2023.08.22.23294439

ABSTRACT

IntroductionThe MMR vaccine has been shown by several studies over the years to have a potent effect on heterologous immunity. The reduction in mortality and respiratory and gastrointestinal diseases in childhood has been consolidated with recent studies demonstrating a better evolution of COVID-19 with the use of this vaccine. Stimulation of innate immunity by the MMR vaccine can be very useful, both used alone or in association with other vaccines, especially those for COVID-19. ObjectivesTo evaluate the decrease in the incidence of infection or severity of COVID-19 with the use of the MMR vaccine before and after the use of specific vaccines against COVID-19. MethodsThis extension analysis followed 120 volunteer healthcare professionals aged 18 to 60 who received the MMR vaccine before the specific COVID-19 vaccine and 73 volunteers who used the MMR vaccine after the COVID-19 vaccine. Visits to the Research Center were carried out at an average interval of 4 weeks for 12 weeks. The diagnosis of COVID-19 was performed using the RT-PCR technique for the SARS-CoV-2 virus. ResultsThe most used vaccine against COVID-19 was Coronavac in 59.1%. A total of 44 cases of COVID-19 were diagnosed (20% of the sample), the vast majority of which were mild cases (70.5%). There was no difference in the incidence and severity of COVID-19 in health professionals who used the MMR vaccine before or after the specific vaccine against the SARS-CoV-2 virus (Coronavirus or AstraZeneca). ConclusionThe incidence and severity of COVID-19 does not differ with the use of the MMR vaccine before or after the specific vaccine against COVID-19.


Subject(s)
Gastrointestinal Diseases , COVID-19
16.
biorxiv; 2023.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2023.08.20.554012

ABSTRACT

Background: Deconvolution is used to estimate the proportion of mixed cell types from tissue or blood samples based on genomic profiling. DNA methylation is commonly used because specific CpG positions reflect cell type identity and can be accurately measured at either the population or single-molecule level. Methylation sequencing techniques can profile multiple individual CpGs on a single DNA molecule, but few deconvolution models have been developed to exploit these single-molecule methylation haplotypes for cell type deconvolution. Results and Conclusions: We used simulated whole-genome methylation data and in silico mixtures of real data to compare existing deconvolution tools with two new models developed here. We found that adapting an existing model CelFiE to incorporate methylation haplotype information improved deconvolution accuracy by ~30% over other tools, including the original CelFiE. In addition to overall higher accuracy, our new tool CelFiE Integrated Single-molecule Haplotypes (or CelFiE-ISH) outperformed others in detecting rare cell types present at 0.1% and below. Detection of rare cell types is important for the analysis of circulating DNA, which we demonstrate using a patient-derived plasma sequencing dataset.Finally,we show that marker selection strategy has a strong effect on deconvolution accuracy, concluding that haplotype-aware deconvolution can take advantage of markers tailored for that purpose.

17.
medrxiv; 2023.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2023.08.05.23293566

ABSTRACT

Introduction: Non-pharmacologic interventions (NPIs), such as universal masking, implemented during the SARS-CoV-2 pandemic have reduced respiratory infections among children. This study focuses on evaluating the impact of NPIs on Mycoplasma pneumoniae infections in children, analyzing data from two hospitals in Arkansas, and examining age-related differences and coinfections with other viruses. Methods: The study was approved by the Institutional Review Board and included patients aged [≤]18 years with upper respiratory tract symptoms. Data from the FilmArray(R) Respiratory Panel (FARP) were collected and divided into pre-NPI and NPI periods for analysis. Total test positivity rate and interval change in the positivity rate were evaluated. Statistical differences were determined by Chi-square ({chi}-independence) analysis. Results: A total of 68,949 tests were performed with a statistical increase in testing during the NPI period. The overall test positivity rate for M. pneumoniae decreased by 74% (0.86% to 0.03%) during the NPI period, and the preschool age group had the highest number of positive tests in the pre- and NPI periods (Pre-NPI: n=40, NPI: n=12 positive tests, p=<0.001). The reduction in M. pneumoniae infections was consistent across age groups. Coinfections with other respiratory viruses, particularly human rhinovirus/enterovirus, were observed at much lower levels. Conclusions: NPIs effectively reduced M. pneumoniae in pediatric patients in Arkansas, and coinfections with specific viruses still occurred, albeit at lower levels during the SARS-CoV-2 pandemic. As NPIs are relaxed and the pandemic ends, we expect M. pneumoniae infections to return to pre-pandemic levels within the next 1-2 years.


Subject(s)
Pneumonia, Mycoplasma , Pneumonia , Respiratory Tract Infections
18.
medrxiv; 2023.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2023.08.01.23293500

ABSTRACT

PurposeTo analyze the prevalence of lower urinary tract symptoms (LUTS) in patients who survived moderate and severe forms of COVID-19 and the risk factors for LUTS six months after hospital discharge. Materials and MethodsIn this prospective cohort study, patients were evaluated six months after being hospitalized due to COVID-19. LUTS were assessed using the International Prostate Symptom Score. General health was assessed through the Hospital Anxiety and Depression Scale and the EQ5D-L5 scale, which evaluates mobility, ability to perform daily activities, pain and discomfort and completed a self-perception health evaluation. ResultsOf 255 participants, 54.1% were men and the median age was 57.3 [44.3 - 66.6] years. Pre-existing comorbidities included diabetes (35.7%), hypertension (54.5%), obesity (30.2%) and physical inactivity (65.5%). 124 (48.6%) had a hospital stay >15 days, 181 (71.0%) were admitted to an ICU and 124 (48.6%) needed mechanical ventilation. Median IPSS score was 6 [3-11] and did not differ between men and women. Moderate to severe LUTS affected 108 (42.4%) patients (40.6% men and 44.4% women; p=0.610). Nocturia (58.4%) and frequency (45.9%) were the most prevalent symptoms and urgency was the only symptom that affected men (29.0%) and women (44.4%) differently (p=0.013). LUTS significantly impacted the quality of life of 60 (23.5%) patients with women more severely affected (p=0.004). Preexisting diabetes, hypertension and self-perception of worse general health were associated with LUTS. ConclusionsLUTS are highly prevalent and bothersome six months after hospitalization due to COVID-19. Assessment of LUTS may help ensure appropriate diagnosis and treatment in these patients.


Subject(s)
Nocturia , COVID-19 , Pain , Diabetes Mellitus , Obesity , Hypertension , Anxiety Disorders , Lower Urinary Tract Symptoms
19.
preprints.org; 2023.
Preprint in English | PREPRINT-PREPRINTS.ORG | ID: ppzbmed-10.20944.preprints202307.1790.v1

ABSTRACT

Despite successful vaccination efforts, the emergence of new SARS-CoV-2 variants poses ongoing challenges to control COVID-19. Understanding humoral responses concerning SARS-CoV-2 infections and their impact is crucial for developing future vaccines that are effective worldwide. Here, we identified 41 immunodominant linear IgG B-cell epitopes in its Spike glycoprotein with a SPOT synthesis peptide array probed with a pool of serum from hospitalized COVID-19 patients. Bioinformatics showed a restricted set of epitopes unique to SARS-CoV-2 compared to other coronavirus family members. Potential crosstalk was also detected with Dengue virus (DENV), confirmed by screening individuals infected with DENV before the COVID-19 pandemic in a commercial ELISA assay for anti-SARS-CoV-2 antibodies. Higher reactivity indices were often measured in individuals with a pre-pandemic dengue infection than those with COVID-19. A high-resolution evaluation of antibody reactivity against peptides representing epitopes in the spike protein identified ten sequences in the NTD, RBD, and S2 domains. Functionally, antibody-dependent enhancement (ADE) in SARS-CoV-2 infection of monocytes was observed with pre-pandemic dengue-positive sera. A significant increase in viral load was measured compared to controls, with no detectable neutralization or considerable cell death, suggesting its role in viral entry. This study highlights the importance of identifying the epitopes generated during the humoral response to a pathogenic infection to understand the potential interplay of previous and future conditions on disease. Vaccine development and optimization strategies should be mindful of the potential for A.D.E. that could differ geographically due to endemic biological risks.


Subject(s)
Severe Acute Respiratory Syndrome , COVID-19
20.
medrxiv; 2023.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2023.07.06.23292300

ABSTRACT

Analysis of incident, longitudinal RNA viral loads in saliva and nasal swabs and culturable viral titers in nasal swabs collected twice-daily by a tricenarian male infected with SARS-CoV-2 revealed the ratio between viral load and viral titer can be five orders of magnitude higher during early infection than late infection.


Subject(s)
Infections
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