Integrative COVID-19 biological network inference with probabilistic core decomposition.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for millions of deaths around the world. To help contribute to the understanding of crucial knowledge and to further generate new hypotheses relevant to SARS-CoV-2 and human protein interactions, we make use of the information abundant Biomine probabilistic database and extend the experimentally identified SARS-CoV-2-human protein-protein interaction (PPI) network in silico. We generate an extended network by integrating information from the Biomine database, the PPI network and other experimentally validated results. To generate novel hypotheses, we focus on the high-connectivity sub-communities that overlap most with the integrated experimentally validated results in the extended network. Therefore, we propose a new data analysis pipeline that can efficiently compute core decomposition on the extended network and identify dense subgraphs. We then evaluate the identified dense subgraph and the generated hypotheses in three contexts: literature validation for uncovered virus targeting genes and proteins, gene function enrichment analysis on subgraphs and literature support on drug repurposing for identified tissues and diseases related to COVID-19. The major types of the generated hypotheses are proteins with their encoding genes and we rank them by sorting their connections to the integrated experimentally validated nodes. In addition, we compile a comprehensive list of novel genes, and proteins potentially related to COVID-19, as well as novel diseases which might be comorbidities. Together with the generated hypotheses, our results provide novel knowledge relevant to COVID-19 for further validation.

Scalable probabilistic truss decomposition using central limit theorem and H-index.

Truss decomposition is a popular notion of hierarchical dense substructures in graphs. In a nutshell, k-truss is the largest subgraph in which every edge is contained in at least k triangles. Truss decomposition aims to compute k-trusses for each possible value of k. There are many works that study truss decomposition in deterministic graphs. However, in probabilistic graphs, truss decomposition is significantly more challenging and has received much less attention; state-of-the-art approaches do not scale well to large probabilistic graphs. Finding the tail probabilities of the number of triangles that contain each edge is a critical challenge of those approaches. This is achieved using dynamic programming which has quadratic run-time and thus not scalable to real large networks which, quite commonly, can have edges contained in many triangles (in the millions). To address this challenge, we employ a special version of the Central Limit Theorem (CLT) to obtain the tail probabilities efficiently. Based on our CLT approach we propose a peeling algorithm for truss decomposition that scales to large probabilistic graphs and offers significant improvement over state-of-the-art. We also design a second method which progressively tightens the estimate of the truss value of each edge and is based on h-index computation. In contrast to our CLT-based approach, our h-index algorithm (1) is progressive by allowing the user to see near-results along the way, (2) does not sacrifice the exactness of final result, and (3) achieves all these while processing only one edge and its immediate neighbors at a time, thus resulting in smaller memory footprint. We perform extensive experiments to show the scalability of both of our proposed algorithms.

Comparison of clinicopathologic variables in coexistence cancers of the endometrium and ovary: A review of 55 cases in an academic center in Iran.

BACKGROUND: The coexistence primary cancers of the endometrium and ovary are relatively uncommon. The purpose of this study was to characterize patients diagnosed primary synchronous endometrial and ovarian cancer (SEOC), endometrial cancer (EC) with ovarian metastasis, and ovarian cancer (OC) with endometrial metastasis and compare clinicopathologic variables and prognosis. MATERIALS AND METHODS: All the patients with diagnosis of both endometrium and OC, who hospitalized between 2002 and 2012 in an academic center affiliated to Tehran University of Medical Sciences, were evaluated with respect to different clinicopathologic variables, follow-up times, and outcomes. RESULTS: Fifty-five patients had been diagnosed with both endometrium and OC. 17, 26, and 12 patients were diagnosed as SEOC, EC, and OC, respectively. The frequency of abnormal uterine bleeding was significantly lower in OC (16.7%) compared to others (58.8% in SEOC and 53.8% in EC). However, the abdominal/pelvic pain was significantly higher in OC (50%) compared to others (35.3% in SEOC and 34.6% in EC) (P < 0.05). Complex atypical hyperplasia (87.5%), endometriosis (88.8%), and endometrioid carcinoma (54.5%) was observed most in SEOC group. The duration of follow-up time was between 3 and 171 months with a mean of 16 months. There was no death in SEOC who followed. Survivals of patients between three group were statistically significant (P = 0.032). CONCLUSION: Our results showed that overall survival (OS) and progression-free survival (PFS) of SEOC patients is better than those with EC and OC (P = 0.032).

Hysteroscopy in patients with repeated implantation failure improves the outcome of assisted reproductive technology in fresh and frozen cycles.

AIM: Repeated implantation failure (RIF) is still a problem for many patients and their physicians. Some interventions have been practiced to overcome the problem; one is uterine cavity assessment before assisted reproductive technology (ART) cycles. This study aimed to evaluate the effect of hysteroscopy in women experiencing recurrent implantation failure with apparently normal uterine cavity before assisted reproductive techniques. MATERIAL AND METHODS: This was a cohort study with historical controls conducted in a university hospital. A total of 353 women with RIF undergoing ART with normal hysterosalpingography and transvaginal ultrasound were evaluated. The intervention group underwent hysteroscopy with a rigid, 30°, 4-mm hysteroscope in the menstrual cycle just before ART; in the control group hysteroscopy was not performed. Basal characteristics, stimulation parameters and pregnancy rates were compared between the two groups. RESULTS: Chemical pregnancy occurred in 58.5% of women in the hysteroscopy group versus 34.1% of control women (odds ratio [OR]: 2.7; 95% confidence interval [CI]: 1.7-4.2; P < 0.001). Clinical pregnancy occurred in 50.7% and 30.3% of women in the hysteroscopy and control groups, respectively (OR: 2.4; 95%CI: 1.5-3.7; P < 0.001). Delivery rate was 35.5% in hysteroscopy women and 21.1% in control women (OR: 1.9; 95%CI: 1.2-3.1; P = 0.008). The results of hysteroscopy were normal in 103 women (72.5%), and they revealed inflammation in 22 (15.5%), polyp in 16 (11.3%) and Asherman syndrome in one patient (0.7%). CONCLUSIONS: Hysteroscopy in the menstrual cycle before ovarian stimulation in fresh cycles and before endometrial preparation in frozen thawed cycles in women experiencing recurrent implantation failure with apparently normal uterine cavity significantly increases the pregnancy rates in fresh and frozen cycles, respectively.

Chemical priming for spinal cord injury: a review of the literature part II-potential therapeutics.

INTRODUCTION: Spinal cord injury is a complex cascade of reactions secondary to the initial mechanical trauma that puts into action the innate properties of the injured cells, the circulatory, inflammatory, and chemical status around them, into a non-permissive and destructive environment for neuronal function and regeneration. Priming means putting a cell, in a state of "arousal" towards better function. Priming can be mechanical as trauma is known to enhance activity in cells. MATERIALS AND METHODS: A comprehensive review of the literature was performed to better understand the possible chemical primers used for spinal cord injuries. CONCLUSIONS: Taken together, many studies have shown various promising results using the substances outlined herein for treating SCI.

Chemical priming for spinal cord injury: a review of the literature. Part I-factors involved.

INTRODUCTION: There are significant differences between the propensity of neural regeneration between the central and peripheral nervous systems. MATERIALS AND METHODS: Following a review of the literature, we describe the role of growth factors, guiding factors, and neurite outgrowth inhibitors in the physiology and development of the nervous system as well as the pathophysiology of the spinal cord. We also detail their therapeutic role as well as those of other chemical substances that have recently been found to modify regrowth following cord injury. CONCLUSIONS: Multiple factors appear to have promising futures for the possibility of improving spinal cord injury following injury.

Estradiol supplementation during the luteal phase in poor responder patients undergoing in vitro fertilization: a randomized clinical trial.

PURPOSE: This study was designed to evaluate the effects of adding Estradiol (E2) supplementation to progesterone (P) on improvement of pregnancy outcomes in poor responder patients who underwent in vitro fertilization (IVF). METHODS: In a prospective randomized clinical trial, 118 poor responder patients, older than 38 years without contraindications of estradiol consumption from Infertility clinic of a university hospital were randomly divided (by computerized software) into two groups. Control group (59 patients) received only P and intervention group (59 patients) received P and E2 (4 mg/d). Supplementation was done with 4 mg E2 in the luteal phase. Fertilization rate, implantation rate, biochemical and clinical pregnancy rates, abortion rate, ongoing pregnancy, multiple pregnancy and ectopic pregnancy rates were documented for those who completed the study protocol in each group (per protocol analysis) and compared between groups. RESULT: Fifty five patients in control group and 53 patients in intervention group successfully completed the study protocol. Treatment outcomes were not significantly different between two groups. CONCLUSION: For poor responder women who underwent IVF, addition of E2 to P supplementation could not significantly improve pregnancy outcomes.

COVID19 Prevention & Care; A Cancer Specific Guideline.

On March 11th 2020, the coronavirus outbreak was declared a pandemic by the WHO. One of the groups that is considered high risk in this pandemic are cancer patients as they are treated with a variety of immune system suppressor treatment modalities and this puts them in a great risk for infectious disease (including COVID-19). Therefore, cancer patients require higher level measures for preventing and treating infectious diseases. furthermore, cancer patients may bear additional risk due to the restriction of access to the routine diagnostic and therapeutic services during such epidemic. Since most of the attention of health systems is towards patients affected with COVID-19, the need for structured and unified approaches to COVID-19 prevention and care specific to cancer patients and cancer centers is felt more than ever. This article provides the recommendations and possible actions that should be considered by patients, their caregivers and families, physician, nurses, managers and staff of medical centers involved in cancer diagnosis and treatment. We pursued two major goals in our recommendations: first, limiting the exposure of cancer patients to medical environments and second, modifying the treatment modalities in a manner that reduces the probability of myelosuppression such as delaying elective diagnostic and therapeutic services, shortening the treatment course, or prolonging the interval between treatment courses.

Effect of eradication of Helicobacter pylori on platelet recovery in patients with chronic idiopathic thrombocytopenic purpura: a controlled trial.

Several recent studies have suggested that an association exists between Helicobacter pylori (HP) eradication and improvement in platelet count in a significant proportion of patients with idiopathic thrombocytopenic purpura (ITP). In this controlled study, we prospectively examined adult patients with chronic ITP for HP infection, and assessed the effect of HP eradication on platelet count. One hundred forty-two consecutive Iranian patients with chronic ITP were assessed. Those who met the criteria and had platelet counts >30 x 10(9)/L within the medication-free screening month were enrolled (n = 129; 66 females; mean age, 29.2 +/- 7.0 years). HP-positive patients received a 2-week course of triple HP eradication therapy (i.e., amoxicillin, clarithromycin, and omeprazole) and were followed for 48 weeks. An ITP response was defined as a platelet count of >100 x 10(9)/L 24 weeks after treatment, together with an increase in the platelet count >30 x 10(9)/L over the baseline value. HP infection was detected in 79 (61%) patients. HP-positive patients were significantly older than HP-negative subjects (P = 0.018). HP eradication was successful in 87% (62/71) of those who completed the eradication therapy. Whereas 48% (30/62) of HP-eradicated patients showed an ITP response, no HP-negative patient had an ITP response. The ITP response persisted for 48 weeks in 93% (28/30) of the responders. The ITP responders had a shorter disease duration than the nonresponders (P = 0.002). The management of mild-to-moderate chronic ITP in Iranian patients, especially those with a recent onset of disease, should include an investigation for and eradication of infection with HP.

Diagnostic performance of 64-channel multislice computed tomography in assessment of significant coronary artery disease in symptomatic subjects.

The recent development of 64-channel multislice computed tomography (MSCT) has resulted in noninvasive coronary artery imaging improvement. This study was conducted to determine the accuracy of 64-slice MSCT in a relatively unselected group of 143 patients with presentations suggestive of coronary artery disease, including those with unstable angina pectoris, who underwent both coronary computed tomographic angiography and invasive coronary angiography. No arrhythmia was considered an exclusion criterion except for atrial fibrillation or frequent extrasystoles. In patients with fast heart rates, a beta blocker was administered orally. Data were obtained using electrocardiography gated 64-slice MSCT. Computed tomographic angiography and invasive coronary angiography findings of each coronary segment were compared to determine the sensitivity, specificity, positive predictive value, and negative predictive value of MSCT in the detection of their normalcy or insignificant (<50% diameter decrease) stenosis versus significant (>or=50% diameter decrease) stenosis or total occlusion. In per-patient assessment, the calculated sensitivity, specificity, positive predictive value, and negative predictive value of MSCT were 96%, 67%, 91%, and 83%, respectively. These values in per-artery evaluation were 94%, 94%, 87%, and 97%, and corresponding values in per-segment analysis were 92%, 97%, 77%, and 99%, respectively. In conclusion, computed tomographic angiography has high diagnostic performance in the assessment of significant coronary artery disease in most patients in a daily routine practice, including those presenting with unstable angina pectoris symptoms.

Finite element analysis of post dental implant fixation in drilled mandible sites.

BACKGROUND: Implant loosening may occur after dental implant placement as a result of the mechanical conditions created around the implant. In this research, the effect of bone drilling conditions on the magnitude of stress created in newly-formed bone around the implant, after placement, was investigated using FEA analysis. METHOD: The simulations performed in this study were based on the three-dimensional (3D) shape of the created cavities, extracted from the drilled cortical bone of the jaws. With this aim, a dental implant model was placed in the jaw and a shell of the 3D bone cavity remained as a newly-formed cortical bone after implant placement. Then, a load was exerted on the implant model and the value of stress created on the newly-formed bone was obtained. Overall, eight combined models were used in all the eight drilling and loading simulations. The examined variables were rotational speed of drill bit, its feed rate and head angle. Also, an animal test was performed to investigate the accuracy of the simulation results. RESULTS: The results of this study showed that the amount of principal stress was the least (16.7MPa) for a newly-formed cortical bone whose cavity was created under drilling condition at the same head angle and feed rate of the drill bit with a rotational speed of 400rpm. The same results were obtained for the head angle and feed rate of a drill bit of 70° and 1.5mm/s, respectively. CONCLUSIONS: Drilling conditions have effect on the stress created in a newly-formed cortical bone after dental implant loading.

Analysis of DNA gyrA Gene Mutation in Clinical and Environmental Ciprofloxacin-Resistant Isolates of Non-Tuberculous Mycobacteria Using Molecular Methods.

BACKGROUND: During the past several years, nontuberculous mycobacteria (NTM) have been reported as some of the most important agents of infection in immunocompromised patients. OBJECTIVES: The aim of this study was to evaluate the ciprofloxacin susceptibility of clinical and environmental NTM species isolated from Isfahan province, Iran, using the agar dilution method, and to perform an analysis of gyrA gene-related ciprofloxacin resistance. MATERIALS AND METHODS: A total of 41 clinical and environmental isolates of NTM were identified by conventional and multiplex PCR techniques. The isolates were separated out of water, blood, abscess, and bronchial samples. The susceptibility of the isolates to 1 µg/mL, 2 µg/mL and 4 µg/mL of ciprofloxacin concentrations was determined by the agar dilution method according to CLSI guidelines. A 120-bp area of the gyrA gene was amplified, and PCR-SSCP templates were defined using polyacrylamide gel electrophoresis. The 120-bp of gyrA amplicons with different PCR-SSCP patterns were sequenced. RESULTS: The frequency of the identified isolates was as follows: Mycobacterium fortuitum, 27 cases; M. gordonae, 10 cases; M. smegmatis, one case; M. conceptionense, one case; and M. abscessus, two cases. All isolates except for M. abscessus were sensitive to all three concentrations of ciprofloxacin. The PCR-SSCP pattern of the gyrA gene of resistant M. abscessus isolates showed four different bands. The gyrA sequencing of resistant M. abscessus isolates showed 12 alterations in nucleotides compared to the M. abscessus ATCC 19977 resistant strain; however, the amino acid sequences were similar. CONCLUSIONS: This study demonstrated the specificity and sensitivity of the PCR-SSCP method for finding mutations in the gyrA gene. Due to the sensitivity of most isolates to ciprofloxacin, this antibiotic should be considered an appropriate drug for the treatment of related diseases.

The role of Doppler indices in predicting intra ventricular hemorrhage and perinatal mortality in fetal growth restriction.

OBJECTIVES: The aim of this study is to determine whether Doppler indices predict intra-ventricular hemorrhage and perinatal mortality in fetal growth restricted pregnancies (FGR). MATERIAL AND METHODS: In this cohort study, 43 FGR fetuses underwent multi-vessel Doppler ultrasounds weekly or twice weekly after admission. Blood gases of the umbilical cord were analyzed immediately after delivery. Ultrasonography of the neonatal brain was performed after birth. Intra ventricular hemorrhage (IVH) and perinatal mortality were studied as outcomes. RESULTS: The median gestational age at the diagnosis of fetal growth restriction was 31 weeks, and the median age at delivery was 33.4 weeks. Seven cases had IVH. The chance of IVH was about five times greater in cases of absent/reversed umbilical diastolic flow (AREDF). The predicting factors for IVH were gestational age at delivery, birth weight, and acidosis. Nine neonates died in the neonatal period. AREDF, the Resistance Index of middle cranial artery (MCA/RI) and umbilical artery (UA), and absent/reversed "a" waves in ductus venosus (DV) were the Doppler indices predicting perinatal mortality. The other prognostic factors for perinatal mortality were gestational age at diagnosis and delivery, final amniotic fluid, Apgar score, and acidosis. CONCLUSION: Doppler indices, such as AREDF, can be predictors of IVH or perinatal death, and an absent or reversed "a" wave in the ductus venosus and the hypoxic index can be significant predictors of death in fetuses with fetal growth restriction. However, other important factors for IVH were gestational age at delivery and birth weight. The most important factors predicting perinatal mortality were gestational age, birth weight, acidosis, low AF, and low Apgar score.

Predictive value of the level of vitamin D in follicular fluid on the outcome of assisted reproductive technology.

OBJECTIVE: To assess the correlation between the levels of vitamin D in follicular fluid and serum, and to determine whether the level of 25-hydroxyvitamin D (25OH-D) in follicular fluid of infertile women undergoing assisted reproductive technology (ART) is associated with the outcome. STUDY DESIGN: Eighty-two infertile women undergoing ART at an academic tertiary care centre were recruited for a prospective cohort study. Levels of 25OH-D in follicular fluid and serum were measured. Standardized regimens for pituitary downregulation and controlled ovarian hyperstimulation were employed. Patient and cycle parameters, and clinical pregnancy (defined as evidence of intra-uterine gestation sac plus heart rate on ultrasound) were determined. RESULTS: A significant correlation was found between the levels of vitamin D in follicular fluid and serum (r=0.767, p=0.001). The overall rates of chemical, clinical and ongoing pregnancy were 35.5% (n=29), 29.3% (n=24) and 23.2% (n=19), respectively. No significant difference was found in these pregnancy rates between the tertiles of 25OH-D level in follicular fluid (p=0.959, 0.995 and 0.604, respectively). The median serum level of vitamin D was 8.13 (range 5.37-13.62)ng/ml in the clinically pregnant group and 8.29 (range 5.93-21.23)ng/ml in the non-pregnant group (p=0.235). Interestingly, the median level of vitamin D in follicular fluid was 9.19 (range 5.25-19.51)ng/ml in the clinically pregnant group and 10.34 (range 5.89-29.69)ng/ml in the non-pregnant group (p=0.433). The fertilization rate decreased significantly and the implantation rate increased (not significantly) with increasing tertiles of 25OH-D level in follicular fluid. CONCLUSIONS: The level of 25OH-D in follicular fluid is reflective of body stores of vitamin D. Most subjects in this study were deficient in vitamin D, but this study found that vitamin D deficiency does not play a pivotal role in the outcome of ART.

Apical right ventricular dysfunction in patients with pulmonary hypertension demonstrated with magnetic resonance.

OBJECTIVE: To evaluate segmental right ventricular (RV) dysfunction in pulmonary hypertension (PH) using cardiac magnetic resonance (CMR). DESIGN: Cross-sectional analysis in a retrospective cohort of consecutive adult patients. SETTING: Mount Sinai Hospital in New York. PATIENTS: 192 patients with known or suspected PH undergoing right heart catheterisation and CMR. PH was defined as mean pulmonary artery pressure ≥ 25 mm Hg. Abnormal RV ejection fraction (RVEF) was defined as <50%. Patients were classified into: group 1 (no PH, normal RVEF; n = 40), group 2 (PH, normal RVEF; n = 41) or group 3 (PH, abnormal RVEF; n=111). INTERVENTIONS: CMR and right heart catheterisation within a 2-week interval. Main outcome measures On cine CMR images, the stack of RV short-axis views was divided into two equal halves. Basal and apical RVEF were calculated using Simpson's method, and a ratio of basal-to-apical RVEF (RVEF(ratio)) was derived. RESULTS: Basal RVEF did not differ between groups 1 and 2 (63 ± 8% vs 64 ± 8%; p = 1); however, patients in group 2 had significantly lower apical RVEF (46 ± 13% vs 58 ± 10%; p<0.01) and higher RVEF(ratio) (median 1.4 vs 1.1; p<0.01). Both apical and basal RVEF were reduced in group 3 compared with groups 1 and 2 (p<0.01), and the RVEF(ratio) increased with increasing PH severity (p<0.01 for trend). An apical RVEF <50% was more sensitive than global RV dysfunction for the detection of PH. CONCLUSIONS: Apical dysfunction appears to occur before global RVEF decreases in chronic PH, potentially constituting an early and sensitive marker of RV dysfunction in this setting.

Diagnostic value of coronary artery calcium scoring in low-intermediate risk patients evaluated in the emergency department for acute coronary syndrome.

Early and accurate triage of patients with possible ischemic chest pain remains challenging in the emergency department because current risk stratification techniques have significant cost and limited availability. The aim of this study was to determine the diagnostic value of the coronary artery calcium score (CACS) for the detection of obstructive coronary artery disease (CAD) in low- to intermediate-risk patients evaluated in the emergency department for suspected acute coronary syndromes. A total of 225 patients presenting to the emergency department with acute chest pain and Thrombolysis In Myocardial Infarction (TIMI) scores <4 who underwent non-contrast- and contrast-enhanced coronary computed tomographic angiography were included. CACS was calculated from the noncontrast scan using the Agatston method. The prevalence of obstructive CAD (defined from the contrast scan as ≥ 50% maximal reduction in luminal diameter in any segment) was 9% and increased significantly with higher scores (p <0.01 for trend). CACS of 0 were observed in 133 patients (59%), of whom only 2 (1.5%) had obstructive CAD. The diagnostic accuracy of CACS to detect obstructive CAD was good, with an area under the receiver-operating characteristic curve of 0.88 and a negative predictive value of 99% for a CACS of 0. In a multivariate model, CACS was independently associated with obstructive CAD (odds ratio 7.01, p = 0.02) and provided additional diagnostic value over traditional CAD risk factors. In conclusion, CACS appears to be an effective initial tool for risk stratification of low- to intermediate-risk patients with possible acute coronary syndromes, on the basis of its high negative predictive value and additive diagnostic value.

N-acetylcysteine does not prevent contrast-induced nephropathy after cardiac catheterization in patients with diabetes mellitus and chronic kidney disease: a randomized clinical trial.

BACKGROUND: Patients with diabetes mellitus (DM) and chronic kidney disease (CKD) constitute to be a high-risk population for the development of contrast-induced nephropathy (CIN), in which the incidence of CIN is estimated to be as high as 50%. We performed this trial to assess the efficacy of N-acetylcysteine (NAC) in the prevention of this complication. METHODS: In a prospective, double-blind, placebo controlled, randomized clinical trial, we studied 90 patients undergoing elective diagnostic coronary angiography with DM and CKD (serum creatinine > or = 1.5 mg/dL for men and > or = 1.4 mg/dL for women). The patients were randomly assigned to receive either oral NAC (600 mg BID, starting 24 h before the procedure) or placebo, in adjunct to hydration. Serum creatinine was measured prior to and 48 h after coronary angiography. The primary end-point was the occurrence of CIN, defined as an increase in serum creatinine > or = 0.5 mg/dL (44.2 micromol/L) or > or = 25% above baseline at 48 h after exposure to contrast medium. RESULTS: Complete data on the outcomes were available on 87 patients, 45 of whom had received NAC. There were no significant differences between the NAC and placebo groups in baseline characteristics, amount of hydration, or type and volume of contrast used, except in gender (male/female, 20/25 and 34/11, respectively; P = 0.005) and the use of statins (62.2% and 37.8%, respectively; P = 0.034). CIN occurred in 5 out of 45 (11.1%) patients in the NAC group and 6 out of 42 (14.3%) patients in the placebo group (P = 0.656). CONCLUSION: There was no detectable benefit for the prophylactic administration of oral NAC over an aggressive hydration protocol in patients with DM and CKD. TRIAL REGISTRATION: NCT00808795.