Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer.

We report a comprehensive analysis of 412 muscle-invasive bladder cancers characterized by multiple TCGA analytical platforms. Fifty-eight genes were significantly mutated, and the overall mutational load was associated with APOBEC-signature mutagenesis. Clustering by mutation signature identified a high-mutation subset with 75% 5-year survival. mRNA expression clustering refined prior clustering analyses and identified a poor-survival "neuronal" subtype in which the majority of tumors lacked small cell or neuroendocrine histology. Clustering by mRNA, long non-coding RNA (lncRNA), and miRNA expression converged to identify subsets with differential epithelial-mesenchymal transition status, carcinoma in situ scores, histologic features, and survival. Our analyses identified 5 expression subtypes that may stratify response to different treatments.

Prediction of cerebral aneurysm rupture risk by machine learning algorithms: a systematic review and meta-analysis of 18,670 participants.

It is possible to identify unruptured intracranial aneurysms (UIA) using machine learning (ML) algorithms, which can be a life-saving strategy, especially in high-risk populations. To better understand the importance and effectiveness of ML algorithms in practice, a systematic review and meta-analysis were conducted to predict cerebral aneurysm rupture risk. PubMed, Scopus, Web of Science, and Embase were searched without restrictions until March 20, 2023. Eligibility criteria included studies that used ML approaches in patients with cerebral aneurysms confirmed by DSA, CTA, or MRI. Out of 35 studies included, 33 were cohort, and 11 used digital subtraction angiography (DSA) as their reference imaging modality. Middle cerebral artery (MCA) and anterior cerebral artery (ACA) were the commonest locations of aneurysmal vascular involvement-51% and 40%, respectively. The aneurysm morphology was saccular in 48% of studies. Ten of 37 studies (27%) used deep learning techniques such as CNNs and ANNs. Meta-analysis was performed on 17 studies: sensitivity of 0.83 (95% confidence interval (CI), 0.77-0.88); specificity of 0.83 (95% CI, 0.75-0.88); positive DLR of 4.81 (95% CI, 3.29-7.02) and the negative DLR of 0.20 (95% CI, 0.14-0.29); a diagnostic score of 3.17 (95% CI, 2.55-3.78); odds ratio of 23.69 (95% CI, 12.75-44.01). ML algorithms can effectively predict the risk of rupture in cerebral aneurysms with good levels of accuracy, sensitivity, and specificity. However, further research is needed to enhance their diagnostic performance in predicting the rupture status of IA.

Efficacy and safety of topical JAK inhibitors in the treatment of atopic dermatitis in paediatrics and adults: A systematic review.

Atopic dermatitis (AD) is the most common skin inflammatory disease. Dysregulation of innate and adaptive immune systems plays a major role in the pathophysiology of AD. JAKi (Janus Kinase Inhibitors) reduce the production of pro-inflammatory cytokines and represent a promising novel treatment for AD. To assess and summarize the overall efficacy and safety of topial JAKi in the treatment of AD in adults and pediatrics, a broad search was performed on Ovid Medline, Ovid Embase, Cochrane Library, Web of Sciences, Scopus, CINAHL and Google Scholar until 14 June 2022. After screening, 19 studies remained for the final review. The current systematic review was conducted according to PRISMA, and the protocol was registered in PROSPERO (ID #CRD42022303321). Topical delgocitinib, tofacitinib, ruxolitinib, cerdulatinib and ifidancitinib are effective in treating AD and significantly improve EASI, IGA, pruritus-NRS score and some other indexes in adults. Moreover, topical delgocitinib was observed to have a great efficacy in the treatment of AD in paediatrics. All topical JAKi showed minimal risk of mild-to-moderate adverse effects. Available topical JAKi are effective and safe modalities in treating AD. Nevertheless, further studies with longer duration and head-to-head comparative trials are necessary to find the best option with the least adverse effects.

Association of meal-specific protein intake and cardiometabolic risk factors: a cross-sectional study.

We aimed to investigate the association of main meals' specific protein intake with cardiometabolic risk factors, including general and abdominal obesity, serum lipid profile, and blood pressure (BP). This cross-sectional study was conducted on 850 subjects aged 20-59 years. Dietary intakes were assessed by completing three 24-h recalls, and the protein intake of each meal was extracted. Anthropometric measures, lipid profile, fasting blood sugar and BP were measured. Multivariate logistic regression controlling for age, physical activity, sex, marital status, smoking status, BMI and energy intake was applied to obtain OR and CI. The mean age was 42 years, and the mean BMI of the participants was 27·2. The mean protein intake for breakfast, lunch and dinner was 12·5, 22·2 and 18·7 g/d, respectively. After adjustment for confounders, higher protein intake was not associated with any of the cardiometabolic risk factors, including LDL-cholesterol, HDL-cholesterol, total cholesterol (TC), TAG, body weight, BP and fasting plasma glucose, in any of the three main meals consumed within a day. Adherence to a higher protein intake at each meal was not associated with cardiometabolic risk factors in Iranian adults. Further prospective studies are needed to justify our findings.

Post-discharge health assessment in survivors of coronavirus disease: a time-point analysis of a prospective cohort study.

PURPOSE:  The objective of this study was to quantitatively evaluate psychological and quality of life-related complications at three months following discharge in hospitalized coronavirus disease 2019 (COVID-19) patients during the pandemic in Iran. METHODS: In this time-point analysis of prospective cohort study data, adult patients hospitalized with symptoms suggestive of COVID-19 were enrolled. Patients were stratified in analyses based on severity. The primary outcomes consisted of psychological problems and pulmonary function tests (PFTs) in the three months following discharge, with Health-related quality of life (HRQoL) as the secondary outcome. Exploratory predictors were determined for both primary and secondary outcomes. RESULTS: 283 out of 900 (30%) eligible patients were accessible for the follow-up assessment and included in the study. The mean age was 53.65 ± 13.43 years, with 68% experiencing a severe disease course. At the time of the final follow-up, participants still reported persistent symptoms, among which fatigue, shortness of breath, and cough were the most common. Based on the regression-adjusted analysis, lower levels of forced expiratory volume in one second (FEV1) to forced vital capacity (FVC) ratio was associated with higher levels of depression (standardized ß = - 0.161 (SE = 0.042), P = 0.017) and stress levels (standardized ß =- 0.110 (SE = 0.047), P = 0.015). Furthermore, higher levels of anti-SARS-CoV-2 immunoglobulin-M (IgM) were associated with significantly lower levels of depression (standardized ß = - 0.139 (SE = 0.135), P = 0.031). CONCLUSIONS: There is an association between lung damage during COVID-19 and the reduction of pulmonary function for up to three months from acute infection in hospitalized patients. Varying degrees of anxiety, depression, stress, and low HRQoL frequently occur in patients with COVID-19. More severe lung damage and lower COVID-19 antibodies were associated with lower levels of psychological health.

A Systematic Review of Histopathologic Surveys on Mucocutaneous Biopsies in Patients Developed COVID-19 Vaccine-Related Dermatologic Manifestations.

ABSTRACT: Coronavirus 2 is an infectious agent primarily identified as the cause of a pandemic viral pneumonia. With the mass vaccination against this virus, one of the health issues is the safety of currently available vaccines considering their adverse reactions. This systematic review was conducted to assess and summarize all reported data on histopathologic findings associated with mucocutaneous reactions that developed after COVID-19 vaccination for a better pathophysiology interpretation and clinical management of these reactions. A systematic search was performed in PubMed, Web of Science, and Scopus databases as well as Google Scholar engine for relevant English articles published till July 1, 2022. This review includes 131 studies with a total number of 287 cases. Eruptions that underwent a biopsy were mostly described as erythematous maculopapular, papulosquamous, vasculitis-like, lichenoid, or urticarial lesions. Histopathology revealed spongiosis, interstitial, and perivascular lymphohistiocytic infiltration, erythrocyte extravasation, parakeratosis, endothelial inflammation, and the like. Findings were highly consistent with morbilliform erythema, psoriasiform dermatosis, leukocytoclastic vasculitis, and lichenoid or urticarial drug reactions. The majority of these reactions had a mild nature and were primarily observed in patients with underlying health conditions. Microscopic evaluation was also consistent with transient inflammatory changes, and features like neutrophilic infiltrates, subcorneal pustules, and vasculopathy were less frequently reported than what seen in COVID infection. Therefore, dermatologic reactions developing after vaccination in the general population should not hinder a complete vaccination.

A systematic review of the comparison between needling (RF-needling, meso-needling, and micro-needling) and ablative fractional lasers (CO2, erbium YAG) in the treatment of atrophic and hypertrophic scars.

The aim of this study is to compare needling (RF-needling, meso-needling, micro-needling) and ablative fractional lasers (CO2, erbium-YAG) in the treatment of atrophic and hypertrophic scars in a systematic review. The database was searched, and 10 articles were selected that were relevant in terms of content, topic, and purpose and met the inclusion criteria. Of all the articles reviewed in this study, there were 2 randomized split-face trials (20%), 1 controlled nonrandomized trial (10%), 1 controlled randomized phase III clinical trial (10%), 1 prospective trial (10%), 1 prospective nonrandomized open-label trial (10%), and 1 randomized comparative trial (10%), with the type of study not reported in 3 articles. We used Endnote X8 to review the articles and extract data. After review, the studies were analyzed and categorized. No statistically significant difference was found between the two methods, laser and micro-needling, in the treatment of atrophic and hypertrophic scars in 60% of the articles studied, and both showed significant improvement (70% or more improvement to complete response). Significant improvement was noted in 20% of the studies reviewed for the laser and micro-needling treatment methods. The results of this study show that needling and ablative fractional lasers are tolerable and safe procedures with no significant difference in the treatment of skin scars in sixty percent of the studies.

A Proteomic Survey of the Cystic Fibrosis Transmembrane Conductance Regulator Surfaceome.

The aim of this review article is to collate recent contributions of proteomic studies to cystic fibrosis transmembrane conductance regulator (CFTR) biology. We summarize advances from these studies and create an accessible resource for future CFTR proteomic efforts. We focus our attention on the CFTR interaction network at the cell surface, thus generating a CFTR 'surfaceome'. We review the main findings about CFTR interactions and highlight several functional categories amongst these that could lead to the discovery of potential biomarkers and drug targets for CF.

Prevalence of Gestational Diabetes in Iran: A Systematic Review and Meta-analysis.

Background: Pregnant women who have gestational diabetes mellitus (GDM) are more prone to adverse pregnancy outcomes. We estimated the prevalence of GDM in Iran. Methods: Web of Science, Scopus, PubMed, Google Scholar, and Persian databases (SID, Magiran, Irandoc, and) were searched using the MeSH and non-MeSH terms in abstract, title, or keywords of articles until June 2021, with no limitation in time. Random effects models were applied to summarize the GDM prevalence in Iran. The obtained data were quantitatively analyzed to determine an effect size for each paper. The pooled effect size was introduced as prevalence and 95% confidence interval. Sensitivity analyses and subgroup analyses were done to determine heterogeneity. Publication bias was assessed by the classic fail-safe N and Egger test. Results: A total of 53 papers were considered for meta-analysis, involving 56,521 Iranians. The total GDM prevalence in Iran was 7.6% (95% CI, 6.1%-9.4%). Conclusion: This meta-analysis was the newest to estimate the GDM prevalence among Iranian women. Our results suggest a high prevalence of GDM in Iran, showing that Iran might have many GDM patients.

A comparative review on mucocutaneous reactions caused by Covid-19 infection versus Covid-19 vaccination.

The prevalence and severity of mucocutaneous manifestations in Covid-19 infection are generally higher than those reported in Covid vaccines. Therefore, comparing the mucocutaneous reactions of the Covid-19 infection and vaccination is necessary to enhance our knowledge about such reactions and guide us to evaluate the risk of infection or vaccination. A thorough literature search was conducted on PubMed, Google Scholar, and EBSCO (LISTA), and 2069 articles were downloaded. After screening, 11 studies remained for the final review. The literature review revealed that the prevalence and severity of postvaccine mucocutaneous adverse reactions have been less common compared to Covid-19 infection. Postvaccine adverse reactions primarily occurred after the first dose administration and such reactions were manageable with antihistamines and corticosteroids administration. This comparative analysis highlights the frequency and potential severity of mucocutaneous reactions due to Covid-19 infection and Covid-19 vaccination. It also affirmed that potentially critical (serious) mucocutaneous reactions are more likely to occur in Covid-19 infection compared to Covid vaccination. Moreover, postvaccine reactions predominantly happened after the first dose and were reported to be non-life-threatening, self-manageable and with a lower incidence of potentially critical events. It was also concluded that the incidence of mucocutaneous reactions decreased in the following doses. Hence, given the low rate of such reactions following Covid-19 vaccination, vaccines have a lower risk of mucocutaneous reactions occurrence than Covid-19 infection. Further, due to the limited number of studies, we recommend that large-scale trials evaluate such reactions comparing various types of Covid-19 vaccines in healthy individuals and those with autoimmune skin disorders.

A systematic review of the efficacy and safety of topical cyclosporine in dermatology.

Cyclosporine-A (Cyc-A) was initially prescribed as systemic therapy for patients receiving solid organ transplants or in patients with graft versus host disease (GVHD). Topical Cyc-A is an ideal form of cyclosporine in the treatment of mucocutaneous disorders as it causes fewer systemic side effects and has more stable results than steroids; however, poor absorption through the skin makes the development of new formulations necessary to improve skin permeability. The aim of this study was to evaluate the efficacy and safety of topical Cyc-A in different dermatological conditions. A thorough systematic review was performed on PubMed/Medline, Embase, Scopus, and Web of Science databases as well as Google Scholar, and relevant studies from 2000 until January 3, 2022, were selected. The study was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA). Topical Cyc-A was observed to be an effective medication in the treatment of oral lichen planus, psoriasis, burning mouth syndrome, Pyoderma Gangrenosum, and Zoon's balanitis. Adverse side effects such as dysphagia, burning sensation, lips swelling, and gastrointestinal upset were reported following Cyc-A mouthwash use, whereas mild erythema, dryness, and fissuring of the skin were observed following the Cyc-A lipogel application. Topical Cyc-A was found to be a good alternative to traditional treatment regimens for immune-mediated mucocutaneous conditions. Cyc-A can be considered as a safe and efficient option in cases of long-term treatment as it does not have the same adverse effects of long-term steroids.

Comparative Efficacy of 3 Adjuvant Medications Used in Combination with Intrathecal Bupivacaine for Caesarian Section Anesthesia: A Randomized, Double-Blind Clinical Trial.

Background: A number of different medications are used in combination with intrathecal bupivacaine for cesarean section anesthesia, but their relative efficacy has not been well established. Objective: To study the relative efficacy of adding either intrathecal fentanyl, intrathecal sufentanil, or intravenous acetaminophen-morphine-fentanyl to intrathecal bupivacaine spinal anesthesia for pain control in elective cesarean section operations. Methods: In this randomized, double-blinded, controlled trial, 105 pregnant women eligible for cesarean section received 10 mg intrathecal bupivacaine (0.5%) in combination with 2 µg intrathecal sufentanil (group 1), 10 µg intrathecal fentanyl (group 2), and an intravenous cocktail of 1 g acetaminophen, 5 mg morphine, and 100 µg fentanyl (group 3). Patients were assessed for analgesia, time to block, and adverse effects. Results: The 3 groups were similar in terms of the time to onset of sensory block and the duration of both sensory and motor block. Groups 1 and 3 differed significantly in the time to peak sensory block, whereas group 1 differed significantly from groups 2 and 3 in the time to peak motor block. The sensory block level reached T4 in most patients. Significant differences in pain (visual analog scale) were demonstrated between groups 1 and 3 at 5 minutes after spinal injection, between groups 1 and 2 at the end of the surgery and upon arrival to the recovery room, and between all groups in the recovery room. Conclusions: When used in addition to 10 mg intrathecal bupivacaine, an intravenous cocktail of 1 g acetaminophen-5 mg morphine-100 µg fentanyl was as efficient as either 10 µg intrathecal fentanyl or 2 µg intrathecal sufentanil in terms of sensory and motor block duration and produced a higher dermatomal level of sensory block. However, intrathecal sufentanil provided better anesthesia quality (less time to onset of motor block and peak sensory-motor block) and better pain control. (Curr Ther Res Clin Exp. 2023; 84:XXX-XXX).

Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma.

BACKGROUND: Papillary renal-cell carcinoma, which accounts for 15 to 20% of renal-cell carcinomas, is a heterogeneous disease that consists of various types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal-cell carcinoma, and no effective forms of therapy for advanced disease exist. METHODS: We performed comprehensive molecular characterization of 161 primary papillary renal-cell carcinomas, using whole-exome sequencing, copy-number analysis, messenger RNA and microRNA sequencing, DNA-methylation analysis, and proteomic analysis. RESULTS: Type 1 and type 2 papillary renal-cell carcinomas were shown to be different types of renal cancer characterized by specific genetic alterations, with type 2 further classified into three individual subgroups on the basis of molecular differences associated with patient survival. Type 1 tumors were associated with MET alterations, whereas type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2-antioxidant response element (ARE) pathway. A CpG island methylator phenotype (CIMP) was observed in a distinct subgroup of type 2 papillary renal-cell carcinomas that was characterized by poor survival and mutation of the gene encoding fumarate hydratase (FH). CONCLUSIONS: Type 1 and type 2 papillary renal-cell carcinomas were shown to be clinically and biologically distinct. Alterations in the MET pathway were associated with type 1, and activation of the NRF2-ARE pathway was associated with type 2; CDKN2A loss and CIMP in type 2 conveyed a poor prognosis. Furthermore, type 2 papillary renal-cell carcinoma consisted of at least three subtypes based on molecular and phenotypic features. (Funded by the National Institutes of Health.).

Effect of different oxidative stress degrees generated by hydrogen peroxide on motility and DNA fragmentation of zebrafish (Danio rerio) spermatozoa.

An increase in reactive oxygen species (ROS) or decrease in antioxidant barriers can provoke lipid peroxidation of the membranes or DNA damage of the spermatozoa. The aim of this work is to study the effect of the different degrees of oxidative stress generated by H2 O2 incubation on total motility, kinetics, and DNA fragmentation of zebrafish (Danio rerio) spermatozoa. For this process, experimental groups were incubated in 50 µM (Low; L) and 200 µM (High; H) H2 O2 , respectively, for 20 min at 4ºC. Sperm motility parameters were obtained with a computer-assisted sperm analysis (CASA) system. Sperm DNA fragmentation (SDF) was assessed using the sperm chromatin dispersion test. Both low and high H2 O2 concentration groups showed lower motility than control groups. Progressive motility of spermatozoa incubated in the H group dropped rapidly in comparison with other groups. Regarding SDF, the control and L groups had significantly lower values than the H group (25.0% and 31.6% vs. 48.1% fragmented sperm for C, L, and H groups, respectively; p < 0.05). Sperm motility, mostly progressive motility, decreased as H2 O2 concentration increased, mainly when time after sperm activation increased. SDF increased as the H2 O2 concentration increased. However, measurements of the halo area did not agree with the subjective SDF rate.

Effect of Melatonin on the Outcome of Assisted Reproductive Technique Cycles in Women with Diminished Ovarian Reserve: A Double-Blinded Randomized Clinical Trial.

Diminished ovarian reserve (DOR) significantly decreases the success rate of the assisted reproductive technique (ART). In this study, we assessed the effect of melatonin on the ART outcomes in women with DOR. A double-blinded, randomized, clinical trial was performed on 80 women with DOR as a pilot study in Shiraz, between 2014 and 2015. DOR was defined as the presence of 2 of the following 3 criteria: 1) anti-Müllerian hormone ≤1, 2) follicle-stimulating hormone ≥10, and 3) bilateral antral follicle count ≤6. The women received 3 mg/d melatonin or a placebo since the fifth day of one cycle prior to gonadotropin stimulation and continued the treatment up to the time of ovum pickup. The ART outcomes were compared between the groups using SPSS software. Finally, there were 32 women in the case and 34 in the placebo groups. The mean age and basal ovarian reserve test were the same between the groups. The serum estradiol level on the triggering day was significantly higher in the case group (P=0.005). The mean number of MII oocytes was higher in the case group, but the difference did not reach statistical significance. Number of the patients who had mature MII oocytes (P=0.014), top-quality embryos with grade 1 (P=0.049), and embryos with grades 1 and 2 (P=0.014) was higher among the women who received melatonin. However, the other ART outcomes were not different between the groups. The serum estradiol level was higher and more women with DOR had good-quality oocytes and embryos after receiving melatonin; however, no other outcome was different between the case and control groups. Trial Registration Number: IRCT2014041417264N1.

BioBloom tools: fast, accurate and memory-efficient host species sequence screening using bloom filters.

Large datasets can be screened for sequences from a specific organism, quickly and with low memory requirements, by a data structure that supports time- and memory-efficient set membership queries. Bloom filters offer such queries but require that false positives be controlled. We present BioBloom Tools, a Bloom filter-based sequence-screening tool that is faster than BWA, Bowtie 2 (popular alignment algorithms) and FACS (a membership query algorithm). It delivers accuracies comparable with these tools, controls false positives and has low memory requirements. Availability and implementaion: www.bcgsc.ca/platform/bioinfo/software/biobloomtools.

Autologous adipose tissue injection in the treatment of alopecia: A mini-review.

BACKGROUND: Alopecia may decrease patients' quality of life and self-confidence by limiting their social life. Therefore, the main goal of the treatment is to limit or halt the progression of inflammation, scarring, and hair loss. The promising effect of fat injection on hair regrowth, limited adverse effects, and subsiding inflammation can be proof of its efficacy and safety in treating alopecia. AIMS: This review sought to assess the role of autologous fat tissue injection in scarring and non-scarring alopecia. METHODS: Accordingly, a thorough search was performed on the Web of Science, Scopus, and PubMed/Medline databases, as well as the Google Scholar search engine, for studies published from inception until September 1st, 2023, using the related keywords. RESULTS: Autologous fat grafting (AFG) is a novel and potentially effective modality for treating alopecia, particularly primary and secondary cicatricial alopecia. AFG can be an effective semi-invasive option for treating refractory lichen planopilaris because it induces angiogenesis, which supports hair regrowth. In addition to cicatricial alopecia, AFG held promise for treating non-scarring alopecia, including androgenic alopecia and alopecia areata. The adipose-derived regenerative cells (ADRCs) in adipose tissue (AT) secrete different growth factors, further supporting hair regeneration. Moreover, different anti-inflammatory and anti-oxidative agents are known in AT, preventing further damage to hair follicles. CONCLUSIONS: AFG can significantly control inflammatory processes, improve signs and symptoms, and increase hair density and diameter.

The role of microRNAs in acrylamide toxicity.

The chemical compound known as Acrylamide (AA) is employed in different industries worldwide and is also found in thermal-processed food. AA has been acting as a reproductive toxicant, carcinogen, and neurotoxic in various animals, which may promote several toxic impacts in animal and human species. Up to now, various studies have focused on the harmful mechanisms and intervention actions of AA. However, the underlying mechanisms that AA and its toxic effects can exert have remained uncertain. MicroRNAs (miRNAs) are a class of short, non-coding RNAs that are able to act as epigenetic regulators. These molecules can regulate a wide range of cellular and molecular processes. In this regard, it has been shown that different chemical agents can dysregulate miRNAs. To determine the possible AA targets along with mechanisms of its toxicity, it is helpful to study the alteration in the profiles of miRNA regulation following AA intake. The current research aimed to evaluate the miRNAs' mediatory roles upon the AA's toxic potentials. This review study discussed the AA, which is made within the food matrix, the way it is consumed, and the potential impacts of AA on miRNAs and its association with different cancer types and degenerative diseases. The findings of this review paper indicated that AA might be capable of altering miRNA signatures in different tissues and exerting its carcinogen effects.