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Since the start of the COVID-19 outbreak, the race for testing new platforms designed to confer immunity against SARS-CoV-2, has been rampant and unprecedented, leading to conditional emergency authorization of various vaccines. Despite progress on early multidrug therapy for COVID-19 patients, the current mandate is to immunize the world population as quickly as possible. The lack of thorough testing in animals prior to clinical trials, and authorization based on safety data generated during trials that lasted less than 3.5 months, raise questions regarding vaccine safety. The recently identified role of SARS-CoV-2 Spike glycoprotein for inducing endothelial damage characteristic of COVID-19, even in absence of infection, is extremely relevant given that most of the authorized vaccines induce endogenous production of Spike. Given the high rate of occurrence of adverse effects that have been reported to date, as well as the potential for vaccine-driven disease enhancement, Th2-immunopathology, autoimmunity, and immune evasion, there is a need for a better understanding of the benefits and risks of mass vaccination, particularly in groups excluded from clinical trials. Despite calls for caution, the risks of SARS-CoV-2 vaccination have been minimized or ignored by health organizations and government authorities. As for any investigational biomedical program, data safety monitoring boards (DSMB) and event adjudication committees (EAC), should be enacting risk mitigation. If DSMBs and EACs do not do so, we will call for a pause in mass vaccination. If DSMBs and EACs do not exist, then vaccination should be halted immediately, in particular for demographic groups at highest risk of vaccine-associated death or serious adverse effects, during such time as it takes to assemble these boards and commence critical and independent assessments. We urge for pluralistic dialogue in the context of health policies, emphasizing critical questions that require urgent answers, particularly if we wish to avoid a global erosion of public confidence in science and public health. 

Juncheng Wei

and 8 more

Objective: To compare the diagnostic efficiency of fluorescence colposcope with dye TMTP1-PEG4-ICG versus conventional colposcope with acetic acid and Lugol’s iodine in identifying cervical precancerous lesions. Design and setting: Randomized controlled trial conducted at Colposcopy Center. Population: Women with abnormal cervical cancer screening results including cytology and/or HPV test. Methods: All participants were randomized to fluorescence colposcope group or conventional colposcope group. Patients of fluorescence colposcope group were applied dye TMTP1-PEG4-ICG to the cervix uteri. Patients of conventional colposcope group routinely administrated acetic acid and Lugol’s iodine to stain the cervix uteri. Main outcome measures: The colposcopists gave colposcope assessment impressions according to the cervical staining reactions and fluorescence signal-to-background ratio (SBR) calculation results. The diagnostic efficiency of fluorescence colposcope and conventional colposcope was calculated on a per-patient and per-site basis. Results: 195 women were successfully completed the study protocol and were randomized to fluorescence colposcope group (n=97) and conventional colposcope group (n=98). The accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of fluorescence colposcope on a per-patient basis were 61.9%, 66.7%, 61.0%, 23.8%, 90.9%, respectively. The above data corresponded to 73.9%, 69.6%, 74.2%, 15.5%, and 97.3% on a per-site basis in fluorescence colposcope group. In the conventional colposcope group, the above diagnostic indicators corresponded to 59.2%, 54.2%, 60.8%, 31.0%, 80.4%, respectively. Conclusions: The fluorescence colposcope with dye TMTP1-PEG4-ICG was comparable to the conventional colposcope with acetic acid and Lugol’s iodine, and exhibited better accuracy, sensitivity and excellent NPV on the basis of per cervical sites.

Udoka Okaro

and 2 more

Biofilm communities cause many infectious diseases. Biofilms are diverse microbial species found either attached to a surface or aggregated into an extracellular matrix. Bacteria form biofilms as a default mode of growth or as a response mechanism to environmental conditions like stress. As such, biofilm strains are increasingly virulent causing a wide variety of chronic persistent diseases, are typically antibiotic-resistant and known to improve host mortality rate. Most biofilms contain polysaccharides, proteins, extracellular DNA (eDNA), RNA, and water. Determining and quantifying the major components of a biofilm may indicate an appropriate treatment for biofilm eradication. Burkholderia pseudomallei is a Gram-negative, motile bacillus typically found in surface water and/or soil in endemic regions. It is the etiologic agent of melioidosis and is capable of forming both surface adherent and air-liquid interface biofilms (pellicle) in broth cultures. This study evaluates the components of established biofilms using B. pseudomallei and Burkholderia thailandensis, a closely related nonpathogenic species. Using assays, fluorescent dyes and microscopy, we quantified the major components of biofilms produced by five genetically related B. pseudomallei strains and compared them to B. thailandensis E264. Our data show that biofilm produced by the B. pseudomallei 1026b derivatives and B. thailandensis E264 significantly differ. The molecular composition of the surface adherent biofilm is similar to the molecular composition of the air-liquid pellicle. Finally, the eDNA quantity biofilm produced by JW270 which bears a CPS I deletion, is significantly increased in comparison to 1026 and Bp82 biofilm.

JUYOUNG LEE

and 3 more

Objective: To analyze the proportion of backup ventilation during neurally adjusted ventilatory assist (NAVA) in preterm infants at different gestational ages and to analyze the trends in backup ventilation in relation to clinical deteriorations. Methods: A prospective observational study was conducted in 18 preterm infants born at a median (range) 27+4 (23+4–34+4) weeks of gestation with a median (range) birth weight of 1,100 (460–2,820) g, who received respiratory support with either invasive or noninvasive NAVA. Data on ventilator settings and respiratory variables were collected daily; the mean values of each 24-hour recording were computed for each respiratory variable. For clinical deterioration, ventilator data were reviewed at 6-hour intervals for 30 hours prior to the event. Results: A total of 354 ventilator days were included: 269 and 85 days during invasive and noninvasive NAVA, respectively. The time on backup ventilation (%/min) significantly decreased, and the neural respiratory rate increased with increasing postmenstrual age during both invasive and noninvasive NAVA. The median time on backup ventilation was less than 15%/min, and the median neural respiratory rate was more than 45 breaths/min for infants above 26+0 weeks of gestation during invasive NAVA. The relative backup ventilation significantly increased prior to the episode of clinical deterioration. Conclusion: The proportion of backup ventilation during NAVA showed how the control of breathing matured with increasing gestational age. Even the most immature infants triggered most of their breaths by their own respiratory effort. An acute increase in the proportion of backup ventilation anticipated clinical deterioration.

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Colum Keohane

and 6 more

Abstract Objective To determine whether the introduction of a one-stop see and treat clinic offering early reflux ablation for Venous Leg Ulcer (VLU) patients in July 2016 has affected rates of unplanned inpatient admissions due to venous ulceration. Design Review of inpatient admission data and analysis of related costs. Materials The Hospital Inpatient Enquiry collects data from acute public hospitals in Ireland on admissions and discharges, coded by diagnosis and acuity. This was the primary source of all data relating to admissions and length of stay. Costs were calculated from data published by the Health Service Executive in Ireland on average costs per inpatient stay for given diagnosis codes. Methods Data were collected on admission rates, length of stay, overall bed day usage, and costs across a four-year period; the two years since the introduction of the rapid access clinic, and the two years immediately prior as a control. Results 218 patients admitted with VLUs accounted for a total of 2,529 inpatient bed-days, with 4.5(2-6) unplanned admissions, and a median hospital stay of 7(4-13) days per month. Median unplanned admissions per month decreased from 6(2.5-8.5) in the control period, to 3.5(2-5) after introduction of the clinic p=.040. Bed-day usage was significantly reduced from median 62.5(27-92.5), to 36.5(21-44) bed-days per month (p=.035), though length of stay remained unchanged (p=.57). Cost of unplanned inpatient admissions fell from median \euro33,336.25(\euro14,401.26-\euro49,337.65) per month to \euro19,468.37(\euro11,200.98-\euro22,401.96) (p=.03). Conclusions Admissions for inpatient management of VLUs have fallen after beginning aggressive endovenous treatment of venous reflux in a dedicated one-stop see-and-treat clinic for these patients. As a result, bed-day usage has also fallen, leading to cost savings.

Mohammed Al-Sadawi

and 7 more

Abstract: Background: This meta-analysis assessed the relationship between Obstructive Sleep Apnea (OSA) and echocardiographic parameters of diastolic dysfunction (DD), which are used in the assessment of Heart Failure with Preserved Ejection Fraction (HFpEF). Methods: We searched the databases including Ovid MEDLINE, Ovid Embase Scopus, Web of Science, Google Scholar, and EBSCO CINAHL from inception up to December 26th, 2020. The search was not restricted to time, publication status or language. Comparisons were made between patients with OSA, diagnosed in-laboratory polysomnography (PSG) or home sleep apnea testing (HSAT), and patients without OSA in relation to established markers of diastolic dysfunction. Results: Primary search identified 2512 studies. A total of 18 studies including 2509 participants were included. The two groups were free of conventional cardiovascular risk factors. Significant structural changes were observed between the two groups. Patients with OSA exhibited greater LAVI (3.94 CI [0.8, 7.07]; p=0.000) and left ventricular mass index (11.10 CI [2.56,19.65]; p=0.000) as compared to control group. The presence of OSA was also associated with more prolonged DT (10.44 ms CI [0.71,20.16]; p=0.04), IVRT (7.85 ms CI[4.48, 11.22]; p=0.000), and lower E/A ratio (-0.62 CI [-1,-0.24]; p=0.001) suggestive of early DD. The E/e’ ratio (0.94 CI[0.44, 1.45]; p=0.000) was increased. Conclusion: An association between OSA and echocardiographic parameters of DD was detected that was independent of conventional cardiovascular risk factors. OSA may be independently associated with DD perhaps due to higher LV mass. Investigating the role of CPAP therapy in reversing or ameliorating diastolic dysfunction is recommended.

Gunter Sturm

and 38 more

Background: There is controversy whether taking β-blockers or ACE inhibitors (ACEI) is a risk factor for more severe systemic insect sting reactions (SSR) and whether it increases the number or severity of adverse events (AE) during venom immunotherapy (VIT). Methods: In this open, prospective, observational, multicenter trial, we recruited patients with a history of a SSR and indication for VIT. The primary objective of this study was to evaluate whether patients taking β-blockers or ACEI show more systemic AE during VIT compared to patients without such treatment. Results: In total, 1,425 patients were enrolled and VIT was performed in 1,342 patients. Of all patients included, 388 (27.2%) took antihypertensive (AHT) drugs (10.4% took β-blockers, 11.9% ACEI, 5.0% β-blockers and ACEI). Only 5.6% of patients under AHT treatment experienced systemic AE during VIT as compared with 7.4% of patients without these drugs (OR: 0.74, 95% CI: 0.43–1.22, p=0.25). The severity of the initial sting reaction was not affected by the intake of β-blockers or ACEI (OR: 1.14, 95% CI: 0.89–1.46, p=0.29). In total, 210 (17.7%) patients were re-stung during VIT and 191 (91.0%) tolerated the sting without systemic symptoms. Of the 19 patients with VIT treatment failure, 4 took β-blockers, none an ACEI. Conclusions: This trial provides robust evidence that taking β-blockers or ACEI does neither increase the frequency of systemic AE during VIT nor aggravate SSR. Moreover, results suggest that these drugs do not impair effectiveness of VIT. (Funded by Medical University of Graz, Austria; Clinicaltrials.gov number, NCT04269629)

Nazanin Kermani

and 12 more

Background. Patients with severe asthma may have a greater risk of dying from COVID-19 disease. Angiotensin converting enzyme-2 (ACE2) and the enzyme proteases, transmembrane protease serine 2 (TMPRSS2) and FURIN, are needed for viral attachment and invasion into host cells. Methods. We examined microarray mRNA expression of ACE2, TMPRSS2 and FURIN in sputum, bronchial brushing and bronchial biopsies of the European U-BIOPRED cohort. Clinical parameters and molecular phenotypes, including asthma severity, sputum inflammatory cells, lung functions, oral corticosteroid (OCS) use, and transcriptomic-associated clusters, were examined in relation to gene expression levels. Results. ACE2 levels were significantly increased in sputum of severe asthma compared to mild-moderate asthma. In multivariate analyses, sputum ACE2 levels were positively associated with OCS use and male gender. Sputum FURIN levels were significantly related to neutrophils (%) and the presence of severe asthma. In bronchial brushing samples, TMPRSS2 levels were positively associated with male gender and body mass index, whereas FURIN levels with male gender and blood neutrophils. In bronchial biopsies, TMPRSS2 levels were positively related to blood neutrophils. The neutrophilic molecular phenotype characterised by high inflammasome activation expressed significantly higher FURIN levels in sputum than the eosinophilic Type 2-high or the pauci-granulocytic oxidative phosphorylation phenotypes. Conclusion. Levels of ACE2 and FURIN may differ by clinical or molecular phenotypes of asthma. Sputum FURIN expression levels were strongly associated with neutrophilic inflammation and with inflammasome activation. This might indicate the potential for a greater morbidity and mortality outcome from SARS-CoV-2 infection in neutrophilic severe asthma.

Mehmet Pehlivaoğlu

and 5 more

Aim: This study evaluated the effect of intracavitary levobupivacaine infusion diluted with locally applied isotonic solution for pain control in cystoscopy. Methods: Included in this study are 100 patients who had previously undergone transurethral tumor resection for bladder tumor and were followed up by cystoscopy. The patients were randomized into five groups (n = 20). In the first, second, third, and fourth groups, 4, 6, 8, and 10 mL of levobupivacaine HCl (5.0 mg/mL) were mixed with 26, 24, 22, and 20 mL of isotonic solution, respectively. Hence, the total mixture was 30 mL for each group. The fifth group was the control group. In this group, the standard method commonly used in most clinics was utilized. That is, a gel containing Cathejell-2% lidocaine (25 mg lidocaine) was applied. Cystoscopic interventions were performed with a 17.5 Fr rigid cystoscope and 0°, 30°, and 70° lens. During cystoscopy and 30 min later, the pain status of patients was assessed using the Visual Analogue Scale (VAS), and patient satisfaction was questioned. Results: The mean VAS score during and after the cystoscopy procedure was significantly lower in the levobupivacaine groups compared to the lidocaine group. In addition, patient satisfaction in the levobupivacaine groups was significantly higher than in the lidocaine group. No drug-related side-effects were observed in all groups. Conclusion: Thus, levobupivacaine is a more effective drug than lidocaine alone to control pain during cystoscopy. The use of levobupivacaine is recommended to prevent possible complications of general anesthesia by eliminating the need for the aforementioned as well as its cost-saving advantage.

Yanhui Dong

and 4 more

Groundwater age is often used to estimate groundwater recharge through a simplified analytical approach. This estimated recharge is thought to be representative of the mean recharge between the point of entry and the sampling point. However, given the complexity in actual recharge, whether the mean recharge is reasonable is still unclear. This study examined the validity of the method to estimate long-term average groundwater recharge and the possibility of obtaining reasonable spatial recharge pattern. We first validated our model in producing reasonable age distributions using a constant flux boundary condition. We then generated different flow fields and age patterns by using various spatially-varying flux boundary conditions with different magnitudes and wavelengths. Groundwater recharge was estimated and analyzed afterwards using the method at the spatial scale. We illustrated the main findings with a field example in the end. Our results suggest that we can estimate long-term average groundwater recharge with 10% error in many parts of an aquifer. The size of these areas decreases with the increase in both the amplitude and the wavelength. The chance of obtaining a reasonable groundwater recharge is higher if an age sample is collected from the middle of an aquifer and at downstream areas. Our study also indicates that the method can also be used to estimate local groundwater recharge if age samples are collected close to the water table. However, care must be taken to determine groundwater age regardless of conditions.

Xinyi Guan

and 4 more

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