Immune cell dysregulation and lymphopenia characterize COVID-19 pathology in moderate to severe disease. While underlying inflammatory factors have been extensively studied, homeostatic and mucosal migratory signatures remain largely unexplored as causative factors. In this study we evaluated the association of circulating IL-6, soluble mucosal addressin cell adhesion molecule (sMAdCAM) and IL-15 with cellular dysfunction characterizing mild and hypoxemic stages of COVID-19. A cohort of SARS-CoV-2 infected individuals (n=125) at various stages of disease progression together with healthy controls (n=16) were recruited from COVID Care Centres (CCCs) across Mumbai, India. Multiparametric flow cytometry was used to perform in-depth immune subset characterization and to measure plasma IL-6 levels. sMAdCAM, IL-15 levels were quantified using ELISA. Distinct depletion profiles, with relative sparing of CD8 effector memory and CD4+ regulatory T cells were observed in hypoxemic disease within the lymphocyte compartment. An apparent increase in the frequency of intermediate monocytes characterized both mild as well as hypoxemic disease. IL-6 levels inversely correlated with those of sMAdCAM and both markers showed converse associations with observed lympho-depletion suggesting opposing roles in pathogenesis. Interestingly, IL-15, a key cytokine involved in lymphocyte activation and homeostasis, was detected in symptomatic individuals but not in healthy controls or asymptomatic cases. Further, negative association of plasma IL-15 with depleted T, B and NK subsets suggested a compensatory production of this cytokine in response to the profound lymphopenia. Finally, higher levels of plasma IL-15 and IL-6, but not sMAdCAM, were associated with longer duration of hospitalization.

Purpose: Literature mining portrays major role of ADAM17 in cancer and inflammation, but due to its structural similarity of the catalytic site to that of the MMPs, it is a challenging task to design a candidate drug for targeting ADAM17. Herein, we have exploited the analogues of some existing inhibitors, with an aim at discovering a potent inhibitor, which might be repurposed as a drug against ADAM17 inflicted cancer progression. Methods: STRINGS database provided us with the ADAM17 mediated protein-protein interaction network. Gene ontology analysis was performed using WebGestalt to obtain the interacting proteins in biological processes, along with their role in signalling pathway and the gene-disease associations. The analogues were screened using the PubChem database. Molecular docking and MD-simulation studies were performed to obtain the dynamic properties of the protein-inhibitor complex. Furthermore, the pharmacodynamic properties of the compounds ascertained their inhibitory and drug-likeliness properties. Results: Our analysis provided sufficient evidence in considering ADAM17 as an eminent regulator of various cancer signalling pathways, which can be considered as a predominant marker in cancer patients. Upon screening of the existing analogues, we delineated our choice into two specific compounds (I6 and I9, analogues of IK862), possessing the lowest binding energy (-9.1 Kcal/mol), stable MD-simulation studies and superior pharmacodynamic properties. Conclusion: The present information paves the avenue to persuade further in-vitro and in-vivo research to provide the efficacy of inhibiting ADAM17 with small molecular compounds (I6 and I9) in the treatment of various malignancies.

Background and Purpose: The transient receptor potential vanilloid 1 (TRPV1) ion channels enhance cytotoxic immune response and may have therapeutic potential in cancer treatment. Hence, we here determined how activation of TRPV1 alters immune response of tumor-bearing mice. Experimental Approach: Three different metastatic subset of 4T1 breast carcinoma cells were used to induce tumors in Balb-c mice. Mix leukocyte cultures (MLCs) using spleens and draining lymph nodes were prepared and stimulated with various challenges. Effects of four different TRPV1 agonists, antagonist (AMG9810) and Gambogic Amide (GA), a TrkA agonist that sensitizes TRPV1, on secreted levels of cytokines were determined. Results: MLCs of tumor-bearing mice secreted markedly higher levels of IL-6 and lower levels of IFN-γ compared to control mice. We observed differential effects of TRPV1 agonists, antagonist and GA in control and mice bearing different subset of metastatic cells. TRPV1 and TrkA agonists increased IFN–γ and IL-17 secretion in control mice while they markedly increased IL-6 secretion and suppressed IFN–γ secretion in tumor-bearing mice. Unexpectedly, AMG9810 acted as an inverse agonist and did not antagonize the effects of TRPV1 agonists and GA did not sensitize TRPV1 channels. Conclusions: Our results demonstrate constitutive activity of TRPV1 in immune cells, suggesting cross activation. Excessive chronic activation of TRPV1 in immune cells in the presence of metastatic breast carcinoma may have detrimental effects. Unexpected findings further document that a drug can have multiple intrinsic activities and depending on surrounding factors can act on the same receptor as an agonist, antagonist or inverse agonist.

The potential of azasteroids as novel drug candidates has prompted numerous studies towards the syntheses of heterosteroidal skeletons. Preparation of novel azasteroidal compounds and the modification of substituents on their steroidal skeletons might provide excellent congeners with useful biological properties. We present herein, a computational investigations on the Diels-Alder/(3 + 2) tandem sequential cycloaddition reaction of 21 distinctive derivatives of furylcinnamate with phenyl azides. First, we performed the computational study on the originally reported reaction of ester-substituted furylcinnamate derivatives 1a and 1b with phenyl azide (3) under the experimental conditions. We extended the scope of this tandem cycloaddition reactions by studying several variants of 1a, 1b and 1c and their reactivity towards 3. In all instances of tandem reactions considered in this study, the Diels-Alder cycloaddition step is the rate determining step (rds). Electron withdrawing-substituted 1a, 1b, and 1c decreases the rds whiles electron donating substituents substantially increase the rds. The parent reaction (1a) selectively proceeds via transition states T5Exa to give tandem adduct 5Exa, the experimentally observed tandem product. In the case of 1b and 1c, the reaction is competitively favored via T4Ex and T5Ex to give corresponding 4Ex and 5Ex (the experimentally observed tandem adducts). The various substituents studied demonstrate that the tandem adduct obtained is highly dependent on the substituents on the Diels-Alder intermediate. Whereas electron withdrawing groups substantially decrease the rds, the direct opposite is true for electron donating groups. A plot of electrophilicity indices and chemical hardness against activation energies gives a good correlation.

Objectives: To study the association between the mastoid process length (MPL) and surgery success when treating chronic otitis media (COM). Postoperative hearing results and the effect of eustachian tube density and performing mastoidectomy were also explored. Settings: Tertiary referral hospital Participants: We included 127 patients who underwent tympanoplasty with or without intact canal wall mastoidectomy. Main outcome measures: MPL was measured on preoperative computed tomography (CT) scans. The primary outcome of this study is whether MPL is correlated with the success of tympanoplasty at 1 year after surgery. The secondary outcome is the correlation of MPL and the postoperative hearing outcomes. Our analysis used ABG as a binary outcome with cutoff > 10 dB and Gap cposure as a binary outcome with cutoff >= 0 dB. Results: Longer MPL was reversly associated with reperforation of the tympanic membrane at 1 year after surgery in patients who received tympanoplasty without mastoidectomy (odds ratio = 0.89 with 95% confidential interval: 0.79~0.99). The success rate of tympanoplasty with canal wall up mastoidectomy was higher than that of tympanoplasty alone in patients with COM. There was no significant association of MPL with postoperative ABG (odds raio = 1.0) or postoperative gap closure (odds ratio = 1.03). Conclusions: A longer MPL was associated with a favorable surgical outcome when performing tympanoplasty without mastoidectomy. Performing ICWM in addition to tympanoplasty was associated with an improved success rate.

Abstract: Objective: Investigate the relationship between the mastoid pneumatization and the paranasal sinus volumes in patients with unilateral chronic otitis media (COM) and make a contribution to understanding of COM etiopathogenesis. Methods:101 patients were divided into two groups: group 1, COM with isolated tympanic membrane perforation, consists of 51 patients and group 2, COM with cholesteatoma/retraction pocket, consists of 50 patients. Mastoid and sinus volumes were evaluated on preoperative temporal bone High-Resolution Computed Tomography (HRCT). Results: Sphenoid sinus volumes were significantly lower at the diseased side (p< 0.05), while there is no statistically difference in the maxillary and frontal sinus volumes. Also, the sphenoid sinus volumes significantly lower at the side of the ear with sclerotic mastoid than others (p<0.001). Conclusions: Long-standing childhood COM might restrict to pneumatization of the same sided sphenoid sinus considering the delayed development of the sphenoid sinus compared with other sinuses.

Colorectal carcinoma (CRC) is extremely rare among pediatrics, particularly before puberty. It usually begins with nonspecific signs and symptoms, so the index of suspicion is low, consequently, the diagnosis may be delayed. Reports in the literature indicate that poor prognostic factors are more common in children than in adults, resulting in a worse outcome. Our objective is to report clinical profile, treatment and prognosis of CRC in children and adolescents admitted in our institution, and to perform a systematic review of reports in the bibliography.

For two commutative idempotents Π1 and Π2, Π1+Π2−Π1Π2 is clearly idempotent. By studying the characterisation of two idempotents generated from factorizations of idempotent operator, we give a necessary and sufficient condition for when there is no another idempotent operator Π3 which has the same range with Π1Π2 such that Π1+ Π2− Π3is idempotent

Winter dormancy (WD) is the most crucial strategy for plants as they must cope with potentially deadly environments. In recent decades, this process in economically important perennial eudicots has been extensively studied due to changing climates. However, in evergreen monocots without chilling requirements, dormancy processes are so far a mystery. We compared the WD process in closely related evergreen and deciduous iris species across critical developmental stages. Both species exhibit a peculiar “shallow WD” with distinct durations, and could easily resume growth under warm conditions. Combining results from the multipronged approach, SVP/DAM or FUL/AP1 from MADS-box was associated with dormancy- or growth-related module, respectively, and coexpressed with important pathways. Also, gene expression patterns and physiological changes highlighted potential ABA and JA antagonism in coordinating growth and stress responses, while differences in carbohydrate metabolism and reactive oxygen species scavenging contributed to species-specific “shallow WD” durations. Moreover, a detailed analysis of MIKCC MADS-box in irises revealed common features in eudicots and possible new roles for members in perennial monocots during “shallow WD.” In essence, our results not only provide a portrait of a peculiar WD process in perennial monocots but also offer new insights into the regulatory mechanism underlying WD in plants.

Several Hermite-Hadamard and Fejér type inequalities are obtained for the recently introduced new class of (h,g;m)-convex functions. This class unifies a certain range of convexity, thus allowing the generalizations of know results.

Background This study aimed to evaluate the relationship between dominant frequencies (DFs)/rotors and low-voltage areas (LVAs) using the Advisor HD grid (HDG) after pulmonary vein isolation (PVI) in non-paroxysmal atrial fibrillation (AF). Methods A total of 73 non-paroxysmal AF patients were prospectively investigated. After pulmonary vein isolation (PVI), an online real-time phase mapping system was used to detect the location of rotors with critical non-passively activated ratios (%NPs) of≧50% in each LA segment, and high-DFs of ≧7Hz were simultaneously mapped. After recovering sinus rhythm, LVAs (<0.5mV) were mapped using the HDG. Results Sixty-eight of 73 (93.2%) AF patients had minimum to mild LVAs (<10%) regardless of an enlarged LAD and LA volume (45±6.1mm and 142±30ml). There were no significant differences in the max and mean DF values and %NPs between the patients with and without recurrent AF/AT (atrial tachycardia). However, LVAs were significantly greater in the patients with AF/AT than in those without (6.4±8.0% vs. 2.5±2.6% P=0.003). Furthermore, the number of high-DF sites overlapping with LVAs was significantly greater in the patients with AF/AT than in those without (0.5±0.8 vs. 0.2±0.7, P=0.019). The AF/AT freedom off anti-arrhythmic drugs after the PVI was significantly lower in the patients with high-DFs sites overlapping with LVAs than in those without during 11.6±0.8 months of follow-up (35.7% vs. 69.5%, p=0.021). Conclusions High-DF sites overlapping with LVAs detected accurately by the HDG, regardless of whether a minimum to mild extent, might be more selective targets after a PVI in non-paroxysmal AF patients.

Abstract Background. The evaluation of long-term inflammatory response and function in postoperative patients with aortic valve replacement (AVR) deserves special analysis because it is important to try to prevent reoperation and improve durability and functionality of the prostheses. Methods In this study we included a cohort of patients with aortic valve damage treated by AVR with mechanical prosthesis, bioprosthesis and we included a control group. Results. We found that IL-4 and OPN levels were higher in patients with mechanical vs. biological prostheses (p = 0.01 and p = 0.04 respectively), OPG levels were decreased (p = 0.01), women had lower levels of ET-1 and IL-6, (p = 0.02) (p = 0.04) respectively. Patients older than 60 years had decreased levels of IL-1ß p <0.001) and a higher concentration of IL-4 p < 0.05). IL-1ß, OPG and TNFα were higher in patients with less than 5 years of evolution versus more than 10 years (p = 0.004, p = 0.02 and p = 0.03 respectively). Factors such as age, gender, prosthetic, and elevated IL-1B and ET-1 levels are associated with valve dysfunction prosthetic. These results indicate that the inflammatory involvement present prior to valve replacement may be perpetuated by various factors in the long term. Conclusions The findings provide us with the opportunity to effectively treat patients with AVR in the postoperative period, which could prolong the functionality of the bioprostheses.

BACKGROUND: Nasal nitric oxide (nNO) a noninvasive indicator for eosinophilic airway inflammation, has not been adequately studied in different types of rhinitis. The aim of this study was to compare nNO levels between allergic (AR) and non-allergic rhinitis (NAR). METHODS: Patients were included based on their chronic nasal symptoms. Total nasal symptoms score (TNSS) were evaluated. nNO was measured transnasally with a flow of 5ml/s from the nostril with an NO analyzer (NIOX MINO; Aerocrine, Sweden). Results were evaluated as parts per billion (ppb). RESULTS: 443 patients (277 F/166 M) - 337 with AR (76%) and 106 with NAR (24%) - were assessed. Patients with AR had significantly higher TNSS, more severe disease, and longer duration of disease compared to NAR group. Allergic rhinitics had significantly higher nNO levels than NAR (370 ppb vs 290 ppb) (p=0.001). Likewise, significant differences were observed in female gender, in patients with BMI≥25 kg/m² and those without sinusitis between the two groups. When nNO were further evaluated in comorbid asthma, patients with AR wo/asthma had the highest TNSS and had significantly higher nNO level (p<0.001). NAR+A group, with the longest duration of rhinitis, was significantly older and had the lowest nNO level (p<0.001). CONCLUSIONS: This study showed that nNO levels were significantly higher in AR patients than NAR. Although there is no recommended standard threshold for nNO, this study confirmed the utility of nNO in differentiating AR and NAR in addition to its known fast and non-invasive advantages.

Product retention in the hollow fibers is a common issue in ATF-based cell culture system. In this study, the effects of four major process factors on product (therapeutic antibody/recombinant protein) retention were investigated using Chinese hamster ovary cell. Hollow fibers made of polysulfone presented a product retention rate from 15% ± 8% to 43% ± 18% higher than those made of polyether sulfone varying with specific processes. Higher harvest flowrate and ATF exchange rate increased product retention by 13% ± 10% and up to 31% ± 13%, respectively. Hollow fibers with larger pore sizes (0.65 μm) appeared to have increased product retention by 38% ± 7% compared with smaller ones (0.2 μm) in this study. Further investigation revealed that the effects of pore size on retention could be correlated to the particle size distribution in the cell culture broth. A hollow fiber with a larger pore size (>0.5 μm) may reduce protein retention when small particles (approximately 0.01-0.2 μm in diameter) are dominant in the culture. However, if majority of the particles are larger than 0.2 μm in diameter, hollow fiber with smaller pore sizes (0.2 μm) could be a solution to reducing product retention. Alternatively, process optimization may modulate particle size distribution towards reduced production retention with selected ATF hollow fibers. This study for the first time highlights the importance of matching proper pore sizes of hollow fibers with the cell culture particles distribution and offers methods to reducing product retention and ATF column clogging in perfusion cell cultures.

This pilot project explored knowledge, attitudes and practices related to contraception in Alexandria, Egypt using questionnaire assisted interviews. The goal of the study was to test and validate the survey instrument for a larger scale study. Methods: Participants were women randomly selected at outpatient clinics at Alexandria University Hospitals in September and October 2020. The inclusion criteria were to be 18 years or older female and to be able to give consent. The recruitment goal for this pilot study was 100 participants. The consented participants were interviewed using a questionnaire survey about demographics, socio-structural and contraceptive use. The questionnaire was tested before the interviews using a focus group of 11 randomly selected volunteer women who attended the Obstetrics and Gynecology Department at the University of Alexandria in Egypt. Results: The age of study participants ranged from 18–60 with a mean of 34 years. Almost all participants had previously heard of various contraceptive methods and 75% used them before. The majority of the participants did not know about emergency contraception and believed that there was nothing to be done to prevent pregnancy after an unprotected sexual encounter. Most respondents had a favorable attitude toward family planning, and their main sources of information about the topic were family and friends. Conclusions: Preliminary findings show that most women knew about contraception methods, though not many of them heard of emergency contraception. Because of the patriarchal nature of Egyptian society, sexual health and family planning education should target the whole population.

Introduction: Lymphoepithelioma-like carcinoma of the bladder (LELC-B) is a rare variant of bladder tumors and until today only 145 cases are reported in the literature. It has a worse prognosis and survival rates in comparison with papillary muscle invasive tumors. However, general treatment options including radical cystectomy, chemotherapy and radiotherapy; discovery of the programmed death cell ligand-1 (PDL-1) expression for LELC-B recently, may lead a novel immunohistochemical diagnostic method and PDL-1 immunostaining may increase detection of this variant. Case Presentation: A 72-year-old male patient with lower urinary tract symptoms is diagnosed as bladder tumor with imaging modalities. After transurethral resection of this bladder tumor, immunopathological diagnose was muscle invasive bladder tumor predominantly lymphepithelioma like carcinoma of the bladder. PDL-1 immunostaining was also highly positive(>%50). Discussion/Conclusion: Lymphoepithelioma-like cancer of bladder is an undifferantiated aggressive rare variant of bladder cancers. Its identifiability may increase with detection of PDL-1 expression. In the future, that might pave a road to targeted immunotherapies as an alternative for selected patients.

Objective During the course of COVID-19 disease, respiratory acidosis, respiratory alkalosis, metabolic acidosis and metabolic alkalosis may occur. This study aims to determine the acid-base imbalance by interpreting the blood gas of the patients with COVID-19 pre-diagnosis admitted to the emergency department. Method The study was planned retrospectively. Blood gas samples of all patients pre-diagnosed with COVID-19 were taken at first admission to the emergency department and analysed in the laboratory. According to clinical, radiological and microbiological evaluation, the patients were divided into two groups as COVID-19 (+) (n=171) and control group [(COVID-19 (-)] (n=129). Data analysis was conducted using SPSS version 19.0. p<0.05 was accepted for the level of statistical significance. Results In the control group, normal blood gas levels were observed more frequently than in the COVID-19 (+) group (p <0.05). Ionized calcium and potassium levels in blood gas were found to be lower in the COVID-19 (+) group than in the control group (p <0.05). Conclusion It is extremely important to take blood gas samples from the patients with COVID-19 pre-diagnosis in terms of guiding the treatment to be conducted in the emergency department.

Skin is the largest organ and outer enclosure of the integumentary system that protects human body from pathogens. Among various cancers in the world, skin cancer is one of the most commonly diagnosed cancer which can be either melanoma or non-melanoma. Melanoma cancers are very fatal compared with non-melanoma cancers but the chances of survival rate are high when diagnosed and treated earlier. The main aim of this work is to analyze and investigate the performance of Non-Subsampled Bendlet Transform (NSBT) on various classifiers for detecting melanoma from dermoscopic images. NSBT is a multiscale and multidirectional transform based on second order shearlet system which precisely classifies the curvature over other directional representation systems. Here two-phase classification is employed using k-Nearest Neighbour (kNN), Naive Bayes (NB), Decision Trees (DT) and Support Vector Machines (SVM). The first phase classification is used to classify the images from PH2 database into normal and abnormal images and the second phase classification classifies the abnormal images into benign and malignant. Experimental result shows the improvement in classification accuracy, sensitivity and specificity compared with the state of art methods.

Convexity with respect to Caputo factional derivative is introduced and applied in general nonlinear programming problems. The KKT conditions are developed and proved the sufficient optimality conditions. Several consequences of the new findings are discussed. Many counterexamples are presented to justify the present investigation.

In this paper, we prove some results on the existence and space-time decay properties of higher order derivatives in time and space variables of global strong solutions of the Cauchy problem for the Navier-Stokes equations in weighed L^\infty(\mathbb R^d,|x|^\gamma{\rm dx})\cap L^\infty(\mathbb R^d,|x|^\beta{\rm dx}) spaces. The estimate for the decay rate is optimal in the sense that it coincides with the decay rate of a solution to the heat equation.

Background: To describe current practice in terms of perioperative management routines used by otolaryngologists who practice obstructive sleep apnea (OSA) surgical management. Methods: The study comprises an international, web-based, cross-sectional survey. The authors surveyed otolaryngologists and maxillofacial surgeons who practice OSA surgical management worldwide, using an in-house designed survey tool. We developed a new measure called “experience” (years x patients per year) and found no correlations with specific recommendations. Results: The response rate was 62%, with 81% reporting no postoperative oxygen and 83% no use of postoperative positive airway pressure (PAP) support. Regarding hospitalization stays, for palatal surgeries, 43 (88% ) of respondents discharge patients under 24 hours postoperatively, while in multi-level surgeries, 14% discharge patients after 4-7 days of hospitalization. Only 59% of respondents reported using opioids for pain management, 82% administered prophylactic antibiotics, and 86% said they routinely prescribed steroids. In investigating the different correlations and various postoperative management decisions, we did not find any significant differences among groups with few exceptions: (1) a positive correlation between prescribing prophylactic antibiotics (Pv=0.043) and recommending postoperative oxygen support (Pv=0.01) among physicians who prescribe pre-operative steroids, and (2) for physicians who recommend postoperative oxygen support, a positive correlation between recommending postoperative PAP support (Pv=0.03) and intensive care unit or intermediate unit monitoring (Pv=0.02). Conclusion: This survey study elucidated the heterogeneity of pre-operative and postoperative management tools for surgical patients suffering from OSA who undergo surgical intervention. Keywords: Obstructive Sleep Apnea; postoperative management; postoperative monitoring; antibiotic; steroids

Objective: To evaluate efficacy and safety of platelet rich plasma (PRP) for stress urinary incontinence (SUI) treatment. Design: Prospective observational pilot study. Setting: Tertiary referral urogynecology unit in Greece. Sample: Adult women with urodynamically confirmed SUI. Methods: Twenty women met the inclusion criteria and attended follow-ups. All participants underwent 2 PRP injections into the lower one-third of the anterior vaginal wall at 4-6 week intervals. At baseline they underwent urodynamic studies, a 1-hr pad test and completed the ICIQ-FLUTS and KHQ questionnaires. At follow up visits (1,3 and 6 months) patients underwent the 1hr-pad test and completed the KHQ, ICIQ-FLUTS and PGI-I. Primary outcome was to evaluate post-treatment SUI. Secondary outcomes included assessment of patient reported questionnaires, assessment of urine loss (1hr-pad test) and the level of discomfort during injections (VAS score). Statistical analysis was performed before PRP and 1,3 and 6 months after the last treatment. Results: A significant improvement of SUI symptoms was observed 3 months after treatment with a further improvement at 6 months. A mean reduction of 50.2% of urine loss was observed in the 1hr-pad test. At 6-month follow-up 80.0% of women reported to be at least improved. No adverse effects were observed. Conclusions: PRP injections were both effective and safe in the short term and could be offered as an alternative outpatient procedure for the treatment of SUI. However, these encouraging findings warrant further investigation with randomized controlled trials. Funding: No funding to declare. Keywords: PRP; Stress urinary incontinence; Minimally invasive treatment, Female Incontinec

Objective To determine the relationship between local microenvironment and cervical cancer (CC). Discovering differential florae and metabolites associating with CC. Design Observational study. Participants 10 LSIL patients, 10 HSIL patients, 10 CC patients and 10 healthy controls were enrolled in our study. Methods We performed 16S rDNA sequencing and metabolomic analysis in the cervicovaginal fluid to reveal the differential florae and metabolites during cervical carcinogenesis. Results Carcinogenesis was associated with alterations in microbiome diversity, individual taxa, and functions. Bacterial diversity was increased and the composition was changed by the influence of cervical cancer carcinogensis. Lactobacillus was significantly reduced in LSIL and CC patients. On the contrary, the relative abundance of Prevotella was significantly elevated in LSIL patients. Lipids were significantly declined in LSIL and HSIL patients compared to HC participants, and significantly elevated in CC compared to LSIL and HSIL patients. Pathway enrichment analysis found phenylalanine, tyrosine and tryptophan biosynthesis pathway was crucial in cervical carcinogenesis. Conclusions These results showed that microbic and metabolomic profiling are capable of distinguishing CC from precancer and highlighted potential biomarkers for the early detection of cervical dysplasia. These differential microorganisms and metabolites expected to become a potential tool to assist in the diagnosis of cervical cancer. Funding We would like to thank Development & Demonstration Program of Wuxi (N20192004), Key Research & Development Program of Jiangsu Province (BE2015617), The 5th Phase of “Project 333” of Jiangsu (BRA2019024) and Innovation and Entrepreneurship Training Program for College Students in Jiangsu Province (KYCX19_1182) for their support.

In this work, we study the multiplicity results for parametric fractional equations involving the square root of the Laplacian $A_{1/2}$ in a smooth bounded domain $\Omega \subset \mathbb{R}^n (n\geq 2)$ and with zero Dirichlet boundary conditions. In fact, using a consequence of the local minimum theorem due to Bonanno we look into the existence one solution under algebraic conditions on the nonlinear term, and then by employing two critical point theorems, one due to due Averna and Bonanno, and another one due to Bonanno we guarantee the existence of two and three solutions for the problem $A_{1/2}u=\lambda f(u)$ in $\Omega$ with boundary condition $u=0$ on $\partial\Omega$.