Effect of combination of Beta Glucan and Lactobacillus rhamnosus HerizI on white blood cell counts and serum levels of IL-4 and IL-12 in women with breast cancer undergoing chemotherapy: A randomized double-blind placebo-controlled clinical trial.

BACKGROUND: Aim of this study was the isolation of native probiotic and determine the effect of combination of Beta Glucan and Lactobacillus rhamnosus Heriz I on White Blood Cell Counts and serum levels of IL-4and IL-12 in breast cancer women receiving Chemotherapy. METHODS: This study was randomized double-blind placebo-controlled clinical trial in 30 women with breast cancer. Women in the intervention group received two 10-mg capsules of soluble 1-3,1-6, D-beta glucan and one capsule of Lactobacillus rhamnosus strain Heriz I (2 × 107 CFU) daily and placebo group received placebo during 21days, interval between two courses of chemotherapy. White blood cells, neuthrophil, lymphocyte and monocyte counts, serum levels of IL-4 and IL-12 were measured before and after the study. RESULTS: We isolated Lactobacillus rhamnosus Heriz I from conventional yogurt of Heriz region and registered in NCBI GeneBank. After administration, in both groups white blood cells counts decreased. At the end of study, serum level of IL-4 was decreased in combination group compared to placebo (P = 0.005). Also, serum level of IL-12 in combination group increased non-significantly (P = 0.066). CONCLUSION: The findings suggest that combination of Beta Glucan and Lactobacillus rhamnosus Heriz I may be useful as immunomodulary supplements in chemotherapy patients however further studies were needed.

Comparison of global decolonization efficacy with mupirocin nasal drop and chlorhexidine mouthwash in acute leukemia patients: randomized clinical trial.

PURPOSE: Neutropenic fever remains a major complication in acute leukemia. Decolonization is assumed as a promising intervention for eradicating causative agents of infection. METHODS: In this randomized clinical trial, 96 patients with acute leukemia were assigned randomly to mupirocin nasal drop 2% (n = 32), chlorhexidine mouthwash 0.2% (n = 33), and control group (n = 31). In control group, patients did not receive any medication for decolonization. All patients received treatment for 5 days (2 days prior to chemotherapy until 3 days after chemotherapy). Pharynx and nasal swabs were taken prior to the intervention and at the end of decolonization period in all groups. Antibiotic susceptibility testing was performed by the disc diffusion method in order to identify bacterial isolates. RESULTS: Bacterial recovery of both nasal and pharynx swabs was observed after global decolonization with mupirocin nasal drop. Decolonization with mupirocin significantly eradicated Coagulase-negative staphylococci (CONS) in both nasal and pharynx swabs (p-value = 0.000). Moreover, mupirocin decreased Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) species. Chlorhexidine mouthwash significantly eradicated CONS in pharynx swabs (p-value = 0.000). In addition, both decolonization strategies decreased both antibiotic use and frequency of fever in leukemic patients. CONCLUSION: Global decolonization with mupirocin nasal drop not only eradicates both nasal and pharynx microorganisms, but also reduces antibiotic requirement and frequency of fever in patients with acute leukemia. The protocol of the present study was approved on December 2016 (registry number: IRCT20160310026998N6).

Sperm chromatin structure assay (SCSA®) and flow cytometry-assisted TUNEL assay provide a concordant assessment of sperm DNA fragmentation as a function of age in a large cohort of approximately 10,000 patients.

BACKGROUND: Sperm DNA integrity is increasingly seen as a critical characteristic determining reproductive success, both in natural reproduction and in assisted reproductive technologies (ART). Despite this awareness, sperm DNA and nuclear integrity tests are still not part of routine examinations for either infertile men or fertile men wishing to assess their reproductive capacity. This is not due to the unavailability of DNA and sperm nuclear integrity tests. On the contrary, several relevant but distinct tests are available and have been used in many clinical trials, which has led to conflicting results and confusion. The reasons for this are mainly the lack of standardization between different clinics and between the tests themselves. In addition, the small number of samples analyzed in these trials has often weakened the value of the analyses performed. In the present work, we used a large cohort of semen samples, covering a wide age range, which were simultaneously evaluated for sperm DNA fragmentation (SDF) using two of the most frequently used SDF assays, namely the TUNEL assay and the sperm chromatin structure assay (SCSA®). At the same time, as standard seminal parameters (sperm motility, sperm morphology, sperm count) were available for these samples, correlations between age, SDF and conventional seminal parameters were analyzed. RESULTS: We show that the SCSA® and TUNEL assessments of SDF produce concordant data. However, the SDF assessed by TUNEL is systematically lower than that assessed by SCSA®. Regardless of the test used, the SDF increases steadily during aging, while the HDS parameter (High DNA stainability assessed via SCSA®) remains unchanged. In the cohort analyzed, conventional sperm parameters do not seem to discriminate with aging. Only sperm volume and motility were significantly lower in the oldest age group analyzed [50-59 years of age]. CONCLUSIONS: In the large cohort analyzed, SDF is an age-dependent parameter, increasing linearly with aging. The SCSA® assessment of SDF and the flow cytometry-assisted TUNEL assessment are well correlated, although TUNEL is less sensitive than SCSA®. This difference in sensitivity should be taken into account in the final assessment of the true level of fragmentation of the sperm nucleus of a given sample. The classical sperm parameters (motility, morphology, sperm count) do not change dramatically with age, making them inadequate to assess the fertility potential of an individual.

RéSUMé: CONTEXTE: l'intégrité de l'ADN des spermatozoïdes est de plus en plus considérée comme une caractéristique essentielle déterminant le succès de la reproduction, tant dans la reproduction naturelle que dans les techniques de reproduction assistée (AMP). Malgré cette prise de conscience, les tests d'intégrité nucléaire des spermatozoïdes ne font toujours pas partie des examens de routine pour les hommes infertiles ou fertiles souhaitant évaluer leur capacité de reproduction. Cette situation n'est pas due à l'indisponibilité des tests. Au contraire, plusieurs tests pertinents mais distincts sont disponibles et ont été utilisés dans de nombreux essais cliniques, ce qui a donné lieu à des résultats contradictoires et à une certaine confusion. Les raisons en sont principalement le manque de normalisation entre les différentes cliniques et entre les tests eux-mêmes. En outre, le petit nombre d'échantillons analysés dans ces essais a souvent affaibli la valeur des analyses effectuées. Dans le présent travail, nous avons utilisé une vaste cohorte d'échantillons, couvrant une large tranche d'âge, évalués simultanément pour la fragmentation de l'ADN des spermatozoïdes à l'aide de deux des tests les plus fréquemment utilisés, à savoir le test TUNEL et le test de la structure de la chromatine des spermatozoïdes (SCSA®). Parallèlement, comme les paramètres séminaux standard (motilité, morphologie, numération) étaient disponibles pour ces échantillons, les corrélations entre l'âge, le niveau de fragmentation et les paramètres séminaux conventionnels ont été analysées. RéSULTATS: Nous montrons que les évaluations SCSA® et TUNEL produisent des données concordantes. Cependant, le SDF évalué par TUNEL est systématiquement plus faible que celui évalué par SCSA®. Quel que soit le test utilisé, la fragmentation augmente régulièrement au cours du vieillissement, alors que le paramètre HDS (« High DNA stainability¼ évalué par le test SCSA®) reste inchangé. Dans la cohorte analysée, les paramètres spermatiques conventionnels ne semblent pas varier avec le vieillissement. Seuls le volume et la mobilité des spermatozoïdes étaient significativement plus faibles dans le groupe d'âge le plus élevé analysé [50­59 ans]. CONCLUSIONS: Dans la grande cohorte analysée, la fragmentation de l'ADN spermatique est un paramètre dépendant de l'âge, augmentant linéairement avec le vieillissement. L'évaluation du SDF par SCSA® et l'évaluation via le test TUNEL assistée par cytométrie de flux sont bien corrélées, bien que le TUNEL soit moins sensible que le SCSA®. Cette différence de sensibilité doit être prise en compte dans l'évaluation finale du niveau réel de fragmentation du noyau des spermatozoïdes d'un échantillon donné. Les paramètres classiques du sperme (motilité, morphologie, nombre de spermatozoïdes) ne changent pas de façon spectaculaire avec l'âge, ce qui les rend inadéquats pour évaluer le potentiel de fertilité d'un individu.

Integrative Bioinformatics Analysis of The Cell Division Cycle and Ribosomal Pathways in The Rat Varicocele: Implications for Drug Discovery.

OBJECTIVE: Varicocele is a common cause of male infertility, affecting a substantial proportion of infertile men. Recent studies have employed transcriptomic analysis to identify candidate genes that may be implicated in the pathogenesis of this condition. Accordingly, this study sought to leverage rat gene expression profiling, along with protein-protein interaction networks, to identify key regulatory genes, related pathways, and potentially effective drugs for the treatment of varicocele. MATERIALS AND METHODS: In this in-silico study, differentially expressed genes (DEGs) from the testicular tissue of 3 rats were screened using the edgeR package in R software and the results were compared to 3 rats in the control group. Data was obtained from GSE139447. Setting a -11 and P<0.05 as cutoff points for statistical significance, up and down-regulated genes were identified. Based on Cytoscape plugins, protein-protein interaction (PPI) networks were drawn, and hub genes were highlighted. ShinyGO was used for pathway enrichment. Finally, effective drugs were identified from the drug database. RESULTS: Among the 1277 DEGs in this study, 677 genes were up-regulated while 600 genes were down-regulated in rats with varicocele compared to the control group. Using protein-protein interaction networks, we identified the top five up-regulated genes and the top five down-regulated genes. Enrichment analysis showed that the up-regulated genes were associated with the cell division cycle pathway, while the down-regulated genes were linked to the ribosome pathway. Notably, our findings suggested that dexamethasone may be a promising therapeutic option for individuals with varicocele. CONCLUSION: The current investigation indicates that in varicocele the cell division cycle pathway is up-regulated while the ribosome pathway is down-regulated compared to controls. Based on these findings, dexamethasone could be considered a future candidate drug for the treatment of individuals with varicocele.

High-dose vitamin D supplementation is related to an improvement in serum alkaline phosphatase in COVID-19 patients; a randomized double-blinded clinical trial.

BACKGROUND: The benefits and harms of vitamin D supplementation in the treatment of COVID-19 have not yet been fully documented. In this study, we aimed to evaluate the effects of high-dose vitamin D supplementation on liver function tests in COVID-19. METHOD: This double-blinded randomized clinical trial was conducted on 140 hospitalized patients aged > 30 years. Patients were randomly allocated to receive either intervention group (n = 70 receiving 50,000 IU of vitamin D capsules orally as a single dose and then 10,000 IU syrup daily from the second day of admission for 30 days) and the control group (n = 70 receiving 1000 IU vitamin D syrup orally per day). Liver function tests (LFT), including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and Lactate Dehydrogenase (LDH) were evaluated at baseline and at the end of the intervention. Decision tree analysis was performed to identify the predictors for change in liver enzymes. RESULTS: Among COVID-19 patients, a significant decrease was observed in serum level of ALP between intervention and placebo groups (p = 0.04). In addition, decision tree analysis revealed that GGT, temperature, serum magnesium level at baseline and gender were the most important predictors of ALT changes in COVID-19 patients. CONCLUSION: High-dose vitamin D supplementation improved ALP markers among COVID-19 patients. More randomized controlled trials with longer follow-up times will be required.

The effect of low dietary inflammatory index score formula on inflammatory, metabolic, and clinical outcomes in critically ill traumatic brain injury patients: A single-blind randomized controlled pilot study.

In traumatic brain injury (TBI) patients, a complex cascade of inflammatory responses are frequently observed following trauma. Numerous dietary agents have long been found to have potential in modulating inflammatory responses. This pilot study, designed an enteral formula with low inflammatory properties based on the dietary inflammatory index (DII®) and evaluated its effect on inflammatory and metabolic factors in critically ill TBI patients. This single-blind randomized controlled pilot study was conducted at the Neurosurgical ICU of Shahid Kamyab Hospital (Mashhad, Iran). A total of 20 TBI patients were randomly assigned to receive either low-DII score or standard formula at the intensive care unit (ICU). The primary outcomes of the study included clinical status, inflammatory biomarkers, APACHE II, SAPS II, SOFA, and NUTRIC scores. The trial groups did not differ significantly in baseline values. Following 14 days of intervention, there was a statistically significant decrease in the APACHE II, SAPS II, and NUTRIC scores and a significant increase in the GCS score in the low-DII score formula group compared to the standard formula group. Over 2 weeks, high sensitivity C-reactive protein (hs-CRP) values of -2.73 (95% CI: -3.67, -1.79) mg/dL in the low-DII score formula group versus 0.65 (95% CI: -0.29, 1.58) mg/dL in controls were obtained. Moreover, the length of hospital stay was longer for the standard formula group than for the low-DII score formula group. The low-DII score formula improves inflammatory factors (serum hs-CRP) and metabolic biomarkers (LDL-c and FBS). Furthermore, clinical outcomes, including the length of hospital stay and disease severity, appear to be enhanced.

Subtype distribution of lymphomas in northwestern Iran: a retrospective analysis of 659 cases according to World Health Organization classification.

BACKGROUND: The distribution of lymphoma subtypes differs strikingly by geographic variations. However, there is limited information on this research in northern Iran. This study aims to evaluate the incidence, subtype, age, sex, and extranodal distribution of lymphomas diagnosed according to the latest WHO classification in a large referral center in northwest Iran. METHODS: In a retrospective study, the medical records of all patients with a diagnosis of lymphoma made between 2018 and 2021 were retrieved from the pathology archive of Imam Reza Medical Center, Tabriz. Lymphoma diagnosis was also made based on the appreciation of morphologic and immunophenotypic features and genetic characteristics in the context of clinical presentation. RESULTS: This study includes a total of 659 patients with lymphoma diagnosed from 2018 to 2021. The number of lymphoma patients were increased each year, with 51 (7.7%), 96 (14.6%), 244 (40.7%), and 268 (40.7%) reported from 2018 to 2021, respectively. 59% of the patients were men. The participants' mean age was 50.5 ± 19.8 years, while the mean age at diagnosis was 49.3 ± 19.6 years. 2.1% were precursor lymphoid neoplasm, 61.6% were mature B cell neoplasm, 8.8% were mature T cell neoplasm, and 27.5% were Hodgkin lymphoma. The most prevalent subtype of mature B-cell lymphoma was DLBCL (55.1%), followed by SLL (18.7%). Extranodal involvement was seen in 40.5% of all cases. CONCLUSION: The subtype distribution of lymphomas in northwest Iran is reported and compared with studies all over the world and inside Iran.

Comparing efficacy and safety of P013, a proposed pertuzumab biosimilar, with the reference product in HER2-positive breast cancer patients: a randomized, phase III, equivalency clinical trial.

BACKGROUND: Breast cancer is the most frequently diagnosed cancer and the leading reason for cancer-related death among women. Neoadjuvant treatment with dual-HER2 (human epidermal growth factor receptor 2) blockade has shown promising effects in this regard. The present study aimed to compare the efficacy and safety of a proposed pertuzumab biosimilar with the reference pertuzumab. METHODS: This randomized, phase III, multicenter, equivalency clinical trial was conducted on chemotherapy-naive women with HER2-positive breast cancer. Patients were randomly assigned (1:1) to receive six cycles of either P013 (CinnaGen, Iran) or the originator product (Perjeta, Roche, Switzerland) along with trastuzumab, carboplatin, and docetaxel every 3 weeks. Patients were stratified by cancer type (operable, locally advanced, inflammatory) and hormone receptor status. The primary endpoint was breast pathologic complete response (bpCR). Secondary endpoints included comparisons of total pCR, overall response rate (ORR), breast-conserving surgery (BCS), safety, and immunogenicity. RESULTS: Two hundred fourteen patients were randomized to treatment groups. bpCR rate in the per-protocol population was 67.62% in the P013 and 71.57% in the reference drug groups. Based on bpCR, P013 was equivalent to the reference pertuzumab with a mean difference of - 0.04 (95% CI: - 0.16, 0.09). Secondary endpoints were also comparable between the two groups. CONCLUSIONS: The proposed biosimilar P013 was equivalent to the reference product in terms of efficacy. The safety of both medications was also comparable.

Responsible enzymes for metabolizing vitamin D in patients with acute leukemia and the relationship with treatment outcomes: a case-control study.

Anti-cancer properties of vitamin D have been reported in studies. The aim of this study was to evaluate the expression of some key enzymes involved in vitamin D metabolism and the serum levels of related proteins. Fifty-four patients with acute myeloid leukemia (AML) and 55 eligible individuals were studied as the control group. The expression of VDR, CYP27B1, and CYP24A1 genes was measured. Serum levels of related proteins were quantified. The association between the studied variables and treatment outcomes: duration of fever and neutropenia, length of hospital stay, achievement of complete remission and overall survival has been investigated. Expression of CYP24A1 gene and serum levels of CYP27B1 and CYP24A1 proteins were significantly higher in the patient group. CYP24A1 gene expression, its blood concentrations and serum levels of CYP27B1 were significantly higher in the AML group. Vitamin D status and key enzymes did not show a strong change in AML patients neither did associate with treatment outcomes except CYP24A1.

Plant PhysioSpace: a robust tool to compare stress response across plant species.

Generalization of transcriptomics results can be achieved by comparison across experiments. This generalization is based on integration of interrelated transcriptomics studies into a compendium. Such a focus on the bigger picture enables both characterizations of the fate of an organism and distinction between generic and specific responses. Numerous methods for analyzing transcriptomics datasets exist. Yet, most of these methods focus on gene-wise dimension reduction to obtain marker genes and gene sets for, for example, pathway analysis. Relying only on isolated biological modules might result in missing important confounders and relevant contexts. We developed a method called Plant PhysioSpace, which enables researchers to compute experimental conditions across species and platforms without a priori reducing the reference information to specific gene sets. Plant PhysioSpace extracts physiologically relevant signatures from a reference dataset (i.e. a collection of public datasets) by integrating and transforming heterogeneous reference gene expression data into a set of physiology-specific patterns. New experimental data can be mapped to these patterns, resulting in similarity scores between the acquired data and the extracted compendium. Because of its robustness against platform bias and noise, Plant PhysioSpace can function as an inter-species or cross-platform similarity measure. We have demonstrated its success in translating stress responses between different species and platforms, including single-cell technologies. We have also implemented two R packages, one software and one data package, and a Shiny web application to facilitate access to our method and precomputed models.

Rosai-Dorfman disease presenting with solitary liver mass without lymphadenopathy: A case report.

Rosai-Dorfman disease (RDD), as a lymphoproliferative disorder with unknown etiology, is commonly identified with systemic clinical manifestations in various organs. In this case study, RDD occurrence was reported with an exceedingly liver mass.

Evaluation of iron overload by cardiac and liver T2* in ß-thalassemia: Correlation with serum ferritin, heart function and liver enzymes.

Introduction: In this study, we aimed to assess the relationship of cardiac and hepatic T2* magnetic resonance imaging (MRI) values as a gold standard for detecting iron overload with serum ferritin level, heart function, and liver enzymes as alternative diagnostic methods. Methods: A total 58 patients with beta-thalassemia major who were all transfusion dependent were evaluated for the study. T2* MRI of heart and liver, echocardiography, serum ferritin level, and liver enzymes measurement were performed. The relationship between T2* MRI findings and other assessments were examined. Cardiac and hepatic T2* findings were categorized as normal, mild, moderate, and severe iron overload. Results: 22% and 11% of the patients were suffering from severe iron overload in heart and liver, respectively. The echocardiographic findings were not significantly different among different iron load categories in heart or liver. ALT level was significantly higher in patient with severe iron overload than those with normal iron load in heart (P =0.005). Also, AST level was significantly lower in normal iron load group than mild, moderate, and severe iron load groups in liver (P <0.05). The serum ferritin level was significantly inversely correlated with cardiac T2* values (r = -0.34, P =0.035) and hepatic T2* values (r = -0.52, P =0.001). Conclusion: Cardiac and hepatic T2* MRI indicated significant correlation with serum ferritin level.

Effect of gut microbiota modulation on feeding tolerance of enterally fed critically ill adult patients: a systematic review.

PURPOSE: The objective of this systematic review was to evaluate the effect of pre-, pro-, and synbiotics on feeding tolerance of enterally fed critically ill adult patients. METHODS: MEDLINE, Science Direct, Web of Knowledge, and the Cochrane Central Register of Controlled Trials were searched up to November 2019. English language randomized controlled trials reporting the effect of pre, pro or synbiotics on the feeding tolerance of enterally fed critically ill adult patients were included. RESULTS: Overall, 15 papers were selected for review. Among six studies reporting the energy intake, only two studies showed significantly higher energy intake in the prebiotic-receiving groups. Among four RCTs reporting frequency or time to achieve the target calorie, only one found a significant effect of probiotics to reduce the time to achieve a target dose of calorie. About the prevalence or duration of diarrhea, 7 out of 12 RCTs reported a beneficial effect. All but one study found no beneficial effects for gut microbiota manipulation on clinical endpoints including length of stay (LOS) in hospital and intensive care unit (ICU). CONCLUSION: It should be noticed that the heterogeneity in study designs, product format, and ICU patient populations makes it difficult to draw any general conclusion. Overall, it seems that pre, pro, or synbiotics have no significant beneficial effect on feeding tolerance and clinical endpoints in critically ill adults, but they may reduce the prevalence or duration of diarrhea.

Downregulation of fatty acid oxidation by involvement of HIF-1α and PPARγ in human gastric adenocarcinoma and related clinical significance.

Lipid metabolism rewiring in gastric adenocarcinoma (GA) pathogenesis is still not clearly elucidated. This study aimed to describe the role of lipid catabolism in GA patient outcomes and possible therapeutic targets by analyzing the effect of hypoxia-inducible factor-1α (HIF-1α) on fatty acid oxidation (FAO). AGS cell line was cultured in normoxic and hypoxic conditions, and FAO-related genes were analyzed by real-time-PCR and Western-blot. The study group comprised 108 newly diagnosed GA patients and 152 control cases. Serum concentrations of medium and long-chain acyl-CoA dehydrogenases (MCAD and LCAD) proteins were measured using ELISA, and local expression of HIF-1α, carnitine palmitoyl transferase 1 (CPT1A) and peroxisome proliferator-activated receptor γ (PPARγ) was evaluated by immunohistochemistry. In addition, gene expression of PPARγ, CPT1A, LCAD, and MCAD was assessed by real-time-PCR. In vitro findings indicate HIF-1α upregulation and FAO-related genes and proteins reduction in the hypoxic culture of AGS cells. GA patients had significantly lower circulating levels of LCAD compared to controls. Higher protein expression of HIF-1α and downregulated CPT1A and PPARγ were observed in GA tissues versus controls. Gene expression of CPT1A, PPARγ, LCAD, and MCAD were repressed in GA tissues compared to controls. Moreover, reduced expression of CPT1A, PPARγ, and MCAD were correlated with HIF-1α upregulation in GA. Poor patient outcome was associated with lower PPARγ and LCAD expression in GA. HIF-1α upregulation in human GA patients and AGS cells was paralleled by downregulation of lipid catabolism genes potentially via reduced PPARγ-mediated FAO. This metabolic adaptation to hypoxic condition may play a role in GA pathogenesis and might have clinical and therapeutic value in GA patients.

Methodological challenges in translational drug response modeling in cancer: A systematic analysis with FORESEE.

Translational models directly relating drug response specific processes that can be observed in vitro to their in vivo role in cancer patients constitute a crucial part of the development of personalized medication. Unfortunately, current studies often focus on the optimization of isolated model characteristics instead of examining the overall modeling workflow and the interplay of the individual model components. Moreover, they are often limited to specific data sets only. Therefore, they are often confined by the irreproducibility of the results and the non-transferability of the approaches into other contexts. In this study, we present a thorough investigation of translational models and their ability to predict the drug responses of cancer patients originating from diverse data sets using the R-package FORESEE. By systematically scanning the modeling space for optimal combinations of different model settings, we can determine models of extremely high predictivity and work out a few modeling guidelines that promote simplicity. Yet, we identify noise within the data, sample size effects, and drug unspecificity as factors that deteriorate the models' robustness. Moreover, we show that cell line models of high accuracy do not necessarily excel in predicting drug response processes in patients. We therefore hope to motivate future research to consider in vivo aspects more carefully to ultimately generate deeper insights into applicable precision medicine.

Challenges, consequences, and lessons for way-outs to emergencies at hospitals: a systematic review study.

BACKGROUND: Emergency Department (ED) overcrowding adversely affects patients' health, accessibility, and quality of healthcare systems for communities. Several studies have addressed this issue. This study aimed to conduct a systematic review study concerning challenges, lessons and way outs of clinical emergencies at hospitals. METHODS: Original research articles on crowding of emergencies at hospitals published from 1st January 2007, and 1st August 2018 were utilized. Relevant studies from the PubMed and EMBASE databases were assessed using suitable keywords. Two reviewers independently screened the titles, abstracts and the methodological validity of the records using data extraction format before their inclusion in the final review. Discussions with the senior faculty member were used to resolve any disagreements among the reviewers during the assessment phase. RESULTS: Out of the total 117 articles in the final record, we excluded 11 of them because of poor quality. Thus, this systematic review synthesized the reports of 106 original articles. Overall 14, 55 and 29 of the reviewed refer to causes, effects, and solutions of ED crowding, respectively. The review also included four articles on both causes and effects and another four on causes and solutions. Multiple individual patients and healthcare system related challenges, experiences and responses to crowding and its consequences are comprehensively synthesized. CONCLUSION: ED overcrowding is a multi-facet issue which affects by patient-related factors and emergency service delivery. Crowding of the EDs adversely affected individual patients, healthcare delivery systems and communities. The identified issues concern organizational managers, leadership, and operational level actions to reduce crowding and improve emergency healthcare outcomes efficiently.

Outcomes of Crowding in Emergency Departments; a Systematic Review.

INTRODUCTION: Emergency Department (ED) crowding is a global public health phenomenon affecting access and quality of care. In this study, we seek to conduct a systematic review concerning the challenges and outcomes of ED crowding. METHODS: This systematic review utilized original research articles published from 1st January 2007, to 1st January 2019. Relevant articles from the PubMed (MEDLINE), EMBASE, and Google scholar databases were extracted using predesigned keywords. Following the PRISMA guidelines, two reviewers independently evaluated the quality of the studies using Critical Appraisal Skills Programme for cohort studies and qualitative studies, and Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument for studies. RESULTS: Out of the total of 73 articles in the final record, we excluded 15 of them because of poor quality. This systematic review synthesized the reports of 58 original articles. The outcomes of multiple individual patients and healthcare-related challenges are comprehensively assessed. CONCLUSIONS: ED crowding affects individual patients, healthcare systems and communities at large. The negative influences of crowding on healthcare service delivery result in delayed service delivery, poor quality care, and inefficiency; all negatively affecting the emergency patients' healthcare outcomes, in turn.

FORESEE: a tool for the systematic comparison of translational drug response modeling pipelines.

SUMMARY: Translational models that utilize omics data generated in in vitro studies to predict the drug efficacy of anti-cancer compounds in patients are highly distinct, which complicates the benchmarking process for new computational approaches. In reaction to this, we introduce the uniFied translatiOnal dRug rESponsE prEdiction platform FORESEE, an open-source R-package. FORESEE not only provides a uniform data format for public cell line and patient datasets, but also establishes a standardized environment for drug response prediction pipelines, incorporating various state-of-the-art pre-processing methods, model training algorithms and validation techniques. The modular implementation of individual elements of the pipeline facilitates a straightforward development of combinatorial models, which can be used to re-evaluate and improve already existing pipelines as well as to develop new ones. AVAILABILITY AND IMPLEMENTATION: FORESEE is licensed under GNU General Public License v3.0 and available at https://github.com/JRC-COMBINE/FORESEE and https://doi.org/10.17605/OSF.IO/RF6QK, and provides vignettes for documentation and application both online and in the Supplementary Files 2 and 3. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Risk factors for paclitaxel-induced peripheral neuropathy in patients with breast cancer.

BACKGROUND: Paclitaxel induced peripheral neuropathy (PIPN) is a major debilitating side effect of paclitaxel in patients with breast cancer with no fully known mechanisms. The aim of the study was to find out the possible risk factors for PIPN. METHODS: Eligible patients with node positive breast cancer undergoing chemotherapy with paclitaxel were assessed. They belonged to an initial randomized controlled trial in which the effectiveness of omega-3 fatty acids in preventing and reducing severity of PIPN was evaluated (protocol ID: NCT01049295). Reduced total neuropathy score (r-TNS) was used for measuring PIPN. All analyses were performed adjusting for intervention effect. The association between age, BMI, BSA, pathological grade, molecular biomarkers and PIPN was evaluated. RESULTS: Fifty-seven patients with breast cancer were investigated. Age was significantly associated with risk of PIPN (RR:1.50, P value = .024). Body mass index and BSA had significant association with severity of PIPN (B:1.28, P = .025; and B: 3.88, P = .010 respectively). Also, BSA showed a significant association with the risk of PIPN (RR: 2.28, P = .035; B: 3.88, P = .035). Incidence and severity of PIPN were much more pronounced in progesterone receptor positive (PR+) patients (RR:1.88, P = .015 and B:1.54, P = .012). Multivariate analysis showed that age and the status of PR+ were independent risk factor for incidence and the status of PR+ was the only independent risk factor for severity of PIPN. CONCLUSION: Age, BSA and the status of PR+, should be considered as the risk factors for PIPN before commencement of chemotherapy with paclitaxel in patients with breast cancer. Older patients, those with greater BSA and PR+ patients may need closer follow up and more medical attention due to greater incidence and severity of PIPN.