Genetic variants of dectin-1 and their antifungal immunity impact in hematologic malignancies: A comprehensive systematic review.

BACKGROUND: Fungal infections pose a significant threat to individuals with hematologic malignancies due to compromised immune systems. Dectin-1, a pivotal pattern recognition receptor, plays a central role in antifungal immune responses. Understanding its genetic variants' impact is crucial for advancing personalized therapeutic approaches. METHODS: Employing systematic review methods, studies were meticulously selected and assessed for relevance. Data extraction encompassed Dectin-1 genetic variants, antifungal immune responses, and disease outcomes. RESULTS: Findings unveiled a complex relationship between Dectin-1 genetic variants and antifungal immunity in hematologic malignancies. Variable associations emerged, influencing susceptibility to fungal infections and disease prognosis. Moreover, implications for treatment outcomes were explored, suggesting potential avenues for tailored interventions. CONCLUSIONS: This systematic review underscores the need for further investigation into the precise influence of Dectin-1 genetic variants on antifungal immunity and disease progression in hematologic malignancies. Insights gained could pave the way for personalized therapeutic strategies, optimizing infection prevention and malignancy management. By delving into the intricate connections between genetic nuances, immune responses, and clinical trajectories, this review contributes to the ongoing discourse surrounding hematologic malignancies, fungal infections, and their multifaceted interplay.

Intervention Bundle for Optimization of Procedural Sedation for Newborns Undergoing Magnetic Resonance Imaging: A Single-Center Quality Improvement Project in Qatar.

Introduction: Magnetic resonance imaging (MRI) is a common procedure in tertiary care neonatal intensive care units (NICUs). MRIs aid in detailing structural anatomy and are increasingly utilized for prognostication. Keeping babies calm and motion-free in the MRI suite is challenging, and various approaches have been adopted to obtain the best image quality. We share our experience of intervention bundle for procedural sedation with the novel use of buccal midazolam in our NICU for babies undergoing MRI. Methods: This single-center quality improvement project comprised two epochs. Epoch 1 from April 2018 to December 2020 provided baseline data regarding sedation use and helped identify causes for suboptimal images and the adverse event rate. Following the implementation of an interventional bundle comprising specific midazolam dose recommendations tailored to background risk factors and streamlining the procedural sedation process, similar comparative data were collected in epoch 2 (May 2021 to December 2022) after a washout period. Results: Of 424 patients, 238 and 108 had MRI done under either procedural sedation protocol or feed and wrap technique in epoch 1 and 2, respectively. After excluding babies whose MRIs were performed under sedative infusions, 30 (13%) babies had adverse events in epoch 1, while only 8 (7%) events occurred in epoch 2. There was also a 37% improvement in the documentation of procedural sedation between the two epochs. Conclusion: Procedural sedation with buccal midazolam under neonatologist supervision is safe, efficient, and effective in babies undergoing MRI in this single-center study. More extensive studies may be warranted to assess the suitability of this sedation modality for broader use.

Importance of lumbar instability in the study of associations between muscle morphology, pain, and disability in chronic low back pain.

OBJECTIVE: The purpose of this study was to (1) evaluate the relationship between lumbar extensor muscle morphology, with pain and disability in patients with chronic low back pain (CLBP) and (2) compare these relationships in subgroup of CLBP with and without lumbar structural segmental instability. DESIGN AND METHODS: This cross-sectional study included 183 patients with CLBP. Standing lateral lumbar flexion/extension radiographs were used to assess lumbar structural segmental instability. Lumbar multifidus (MF), erector spinae (ES), and psoas major (PM) morphology were determined from axial magnetic resonance imaging. Associations between lumbar muscle morphologies and patient pain and disability were evaluated in two groups with and without lumbar instability. RESULTS: Patients' disability was negatively associated with PM total cross-sectional area (beta = -22.82, 95%CI = -37.05 to -8.59) and functional cross-sectional area (beta = -23.45, 95%CI = -37.81 to -9.09). MF morphology was negatively associated with disability in the lumbar instability group. Pain intensity was only associated to PM total cross-sectional area (Beta = -3.33, 95%CI = -6.43 to -2.24) and functional cross-sectional area (Beta = -3.22, 95%CI = -6.40 to -0.05) only in the lumbar instability group. CONCLUSION: PM atrophy was associated with greater disability and pain in CLBP, but MF atrophy was associated with greater disability in CLBP patients with lumbar structural segmental instability.

For a proper use of frequentist inferential statistics in public health.

As widely noted in the literature and by international bodies such as the American Statistical Association, severe misinterpretations of P-values, confidence intervals, and statistical significance are sadly common in public health. This scenario poses serious risks concerning terminal decisions such as the approval or rejection of therapies. Cognitive distortions about statistics likely stem from poor teaching in schools and universities, overly simplified interpretations, and - as we suggest - the reckless use of calculation software with predefined standardized procedures. In light of this, we present a framework to recalibrate the role of frequentist-inferential statistics within clinical and epidemiological research. In particular, we stress that statistics is only a set of rules and numbers that make sense only when properly placed within a well-defined scientific context beforehand. Practical examples are discussed for educational purposes. Alongside this, we propose some tools to better evaluate statistical outcomes, such as multiple compatibility or surprisal intervals or tuples of various point hypotheses. Lastly, we emphasize that every conclusion must be informed by different kinds of scientific evidence (e.g., biochemical, clinical, statistical, etc.) and must be based on a careful examination of costs, risks, and benefits.

Protocol of a prospective multicenter study on comorbidity impact on multiple sclerosis and antibody-mediated diseases of the central nervous system (COMMIT).

Comorbidities in patients with multiple sclerosis (MS) and antibody-mediated diseases of the central nervous system (CNS) including neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein (MOG)-antibody-associated disease (MOGAD) are common and may influence the course of their neurological disease. Comorbidity may contribute to neuronal injury and therefore limit recovery from attacks, accelerate disease progression, and increase disability. This study aims to explore the impact of comorbidity, particularly vascular comorbidity, and related risk factors on clinical and paraclinical parameters of MS, NMOSD and MOGAD. We propose COMMIT, a prospective multicenter study with longitudinal follow-up of patients with MS, NMOSD, and MOGAD, with or without comorbidities, as well as healthy subjects as controls. Subjects will be stratified by age, sex and ethnicity. In consecutive samples we will analyze levels of inflammation and neurodegeneration markers in both fluid and cellular compartments of the peripheral blood and cerebrospinal fluid (CSF) using multiple state-of-the-art technologies, including untargeted proteomics and targeted ultrasensitive ELISA assays and quantitative reverse transcription polymerase chain reaction (RT-qPCR) as well as high-dimensional single-cell technologies i.e., mass cytometry and single-cell RNA sequencing. Algorithm-based data analyses will be used to unravel the relationship between these markers, optical coherence tomography (OCT) and magnetic resonance imaging (MRI), and clinical outcomes including frequency and severity of relapses, long-term disability, and quality of life. The goal is to evaluate the impact of comorbidities on MS, NMOSD, and MOGAD which may lead to development of treatment approaches to improve outcomes of inflammatory demyelinating diseases of the CNS.

Co-production of high-concentration fermentable sugar and lignin-based bio-adhesive from corncob residue via an enhanced enzymatic hydrolysis.

Xylose plants (produce xylose from corncob through dilute acid treatment) generate a large amount of corncob residue (CCR), most of which are burned and lacked of valorization. Herein, to address this issue, CCR was directly used as starting material for high-solid loading enzymatic hydrolysis via a simple strategy by combining PFI homogenization (for sufficient mixing) with batch-feeding. A maximum glucose concentration of 187.1 g/L was achieved after the saccharification with a solid loading of 25 wt% and enzyme dosage of 10 FPU/g-CCR. Furthermore, the residue of enzymatic hydrolysis (REH) was directly used as a bio-adhesive for plywood production with both high dry (1.7 MPa) and wet (1.1 MPa) surface bonding strength (higher than the standard (0.7 MPa)), and the excellent adhesion was due to the interfacial crosslinking between the REH adhesive (containing lignin, free glucose, and nanosized fibers) and cell wall of woods. Compared with traditional reported adhesives, the REH bio-adhesive has advantages of formaldehyde-free, good moisture resistance, green process, relatively low cost and easy realization. This study presents a simple and effective strategy for better utilization of CCR, which also provides beneficial reference for the valorization of other kinds of lignocellulosic biomass.

Whole genome sequencing identifies a homozygous splicing variant in TDRKH segregating with non-obstructive azoospermia in an Iranian family.

Non-obstructive azoospermia (NOA) resulting from primary spermatogenic failure represents one of the most severe forms of male infertility, largely because therapeutic options are very limited. Beyond their diagnostic value, genetic tests for NOA also hold prognostic potential. Specifically, genetic diagnosis enables the establishment of genotype-testicular phenotype correlations, which, in some cases, provide a negative predictive value for testicular sperm extraction (TESE), thereby preventing unnecessary surgical procedures. In this study, we employed whole-genome sequencing (WGS) to investigate two generations of an Iranian family with NOA and identified a homozygous splicing variant in TDRKH (NM_001083965.2: c.562-2A>T). TDRKH encodes a conserved mitochondrial membrane-anchored factor essential for piRNA biogenesis in germ cells. In Tdrkh knockout mice, de-repression of retrotransposons in germ cells leads to spermatogenic arrest and male infertility. Previously, our team reported TDRKH involvement in human NOA cases through the investigation of a North African cohort. This current study marks the second report of TDRKH's role in NOA and human male infertility, underscoring the significance of the piRNA pathway in spermatogenesis. Furthermore, across both studies, we demonstrated that men carrying TDRKH variants, similar to knockout mice, exhibit complete spermatogenic arrest, correlating with failed testicular sperm retrieval.

Voice Disorders in Patients with Fibromyalgia: Case Series and Review of the Literature.

OBJECTIVE: To investigate the prevalence of phonatory disorders and their impact on quality of life in a cohort of patients with fibromyalgia (FMS), and to review the literature. STUDY DESIGN: Prospective cohort study. METHODS: All adult patients presenting to the rheumatology clinic at a tertiary referral center between January 2024 and April 2024 and diagnosed with FMS were prospectively recruited. The primary outcome measure used to screen for dysphonia was the Voice Handicap Index-10 (VHI-10). All patients were also asked to fill the Fibromyalgia Rapid Screening Tool (FiRST) and the short form of the McGill pain questionnaire (SF-MPQ). RESULTS: A total of 70 female patients were included, divided equally into a study and control group (n = 35). The mean FiRST score and the mean SF-MPQ score were significantly higher in the study group compared to the control group (6.20 ± 1.05 vs 1.26 ± 1.65) and (26.14 ± 13.16 vs 2.6 ± 4.23), respectively. There was a statistically significant difference in the mean VHI-10 score between the study group and the control group (8.51 ± 7.66 vs 0.74 ± 0.98; P < 0.001). More than one third of patients in the study group had a VHI-10 score above 11 (37.1%) compared to none in the control group (P < 0.001). There was a strong positive correlation between the VHI-10 score and the FiRST and SF-MPQ scores (r = 0.612; P < 0.001 and r = 0.794; P < 0.001, respectively). CONCLUSION: The findings suggest that two out five patients with FMS have vocal complaints that impact their quality of life. Healthcare providers need to recognize these phonatory disorders, that are often masked by other systemic manifestations of the disease.

Symptomatic intracerebral hemorrhage in proximal and distal medium middle cerebral artery occlusion patients treated with mechanical thrombectomy.

BACKGROUND: Acute ischemic stroke (AIS) caused by distal medium vessel occlusions (DMVOs) represents a significant proportion of overall stroke cases. While intravenous thrombolysis (IVT) has been a primary treatment, advancements in endovascular procedures have led to increased use of mechanical thrombectomy (MT) in DMVO stroke patients. However, symptomatic intracerebral hemorrhage (sICH) remains a critical complication of AIS, particularly after undergoing intervention. This study aims to identify factors associated with sICH in DMVO stroke patients undergoing MT. METHODS: This retrospective analysis utilized data from the Multicenter Analysis of Distal Medium Vessel Occlusions: Effect of Mechanical Thrombectomy (MAD-MT) registry, involving 37 centers across North America, Asia, and Europe. Middle cerebral artery (MCA) DMVO stroke patients were included. The primary outcome measured was sICH, as defined per the Heidelberg Bleeding Classification. Univariable and multivariable logistic regression were used to identify factors independently associated with sICH. RESULTS: Among 1708 DMVO stroke patients, 148 (8.7%) developed sICH. Factors associated with sICH in DMVO patients treated with MT included older age (adjusted odds ratio (aOR) 1.01, 95% confidence interval (95% CI) 1.00 to 1.03, P=0.048), distal occlusion site (M3, M4) compared with medium occlusions (M2) (aOR 1.71, 95% CI 1.07 to 2.74, P=0.026), prior use of antiplatelet drugs (aOR 2.06, 95% CI 1.41 to 2.99, P<0.001), lower Alberta Stroke Program Early CT Scores (ASPECTS) (aOR 0.75, 95% CI 0.66 to 0.84, P<0.001), higher preoperative blood glucose level (aOR 1.00, 95% CI 1.00 to 1.01, P=0.012), number of passes (aOR 1.27, 95% CI 1.15 to 1.39, P<0.001), and successful recanalization (Thrombolysis In Cerebral Infarction (TICI) 2b-3) (aOR 0.43, 95% CI 0.28 to 0.66, P<0.001). CONCLUSION: This study provides novel insight into factors associated with sICH in patients undergoing MT for DMVO, emphasizing the importance of age, distal occlusion site, prior use of antiplatelet drugs, lower ASPECTS, higher preoperative blood glucose level, and procedural factors such as the number of passes and successful recanalization. Pending confirmation, consideration of these factors may improve personalized treatment strategies.

The safety and efficacy of adipose tissue-derived exosomes in treating mild to moderate plaque psoriasis: A clinical study.

AIM: This study evaluates the safety and efficacy of autologous adipose-derived mesenchymal stem cell-derived exosomes as a treatment for Psoriasis, a chronic immune-related skin and joint disorder, compared to current treatments like topicals, phototherapy, and systemic. MATERIALS AND METHODS: The study isolated exosomes from Mesenchymal Stem Cells(MSCs) of healthy adipose tissue using ultracentrifugation. 12 patients with plaque psoriasis were divided into three groups and given single doses of exosomes. Tissue samples were collected pre- and post-treatment and examined for inflammatory(TNFα, IL23, IL17, IFNγ, CD3) and anti-inflammatory (FOXP3, IL10) markers. The severity of the lesion was also evaluated. KEY FINDINGS: In this study, it was found that erythema and induration (P < 0.05) decreased significantly in patients receiving 200 µg. Still, this reduction in scaling was not significant, the thickness was significantly reduced in patients receiving 100 and 200 µg doses (P < 0.05). H&E evaluation showed that the decreasing trend in these patients was not significant (P > 0.05). IHC evaluation in patients receiving doses of 100 and 200 µg showed a decrease in the presence of IL17 (P < 0.05, <0.001) & CD3(P < 0.001, <0.05) and a considerable increase in FOXP3(P ≤ 0.001), in the tissue samples of the patients. Examining the expression of inflammatory factors also shows that dose 200 µg decreased the expression of IL17(P > 0.05), IFNγ(P > 0.05), IL23(P < 0.05), & TNFα(P ≤ 0.05) and increased the expression of the anti-inflammatory factor IL10(P < 0.05). SIGNIFICANCE: The study indicates that a 200 µg dose is optimal for patients, but a larger patient population is needed for more reliable results. Additionally, higher doses or multiple injections with specific intervals can increase confidence.

Consanguineous marriage among familial multiple sclerosis subjects: A national registry-based study.

Background: The rising prevalence of familial multiple sclerosis (MS) in Iran has spurred interest in the potential impact of parental consanguinity on the risk of developing the disease. This study aims to aggregate current knowledge on parental consanguinity and its possible effect on MS risk, particularly among familial MS patients from various regions and ethnicities in Iran. The objective is to enhance the understanding of MS genetics and encourage further research in this field. Materials and methods: A cross-sectional study was conducted on clinically definite familial MS (FMS) patients registered in the nationwide MS registry of Iran (NMSRI). Data were extracted and supplemented with structured telephone follow-ups to gather detailed histories of MS in relatives and the familial relationships of the patients' parents. A family penetration score was proposed. Descriptive statistics and inferential statistical tests were used to analyze the data at a significance level of 0.05, adhering to ethical guidelines. Results: Out of 19,911 individuals registered in the NMSRI, 2307 FMS patients across 13 provinces were included in the final analysis. Among these, 385 (19.3 %) reported parental consanguinity, with 283 (14.2 %) having parents who were cousins and 102 (5.1 %) having parents who were distant relatives. The data showed no significant association between parental kinship and variables such as MS phenotype, number of affected relatives with MS, hospitalization rates, and expanded disability status scale score. Similarly, MS severity did not differ based on parental consanguinity (P-value >0.05). While the rate of consanguineous marriage was higher among patients with an onset age less than 18 years, there was no statistically significant difference in disease onset age based on parental consanguinity status. Conclusion: Our study highlights the complexity of factors influencing MS development, including genetic and environmental components. These results highlight the need for further research to achieve a more comprehensive understanding of MS etiology.

The relationship between demographic factors and known risk factors with breast cancer in women aged 30-69.

Background: Breast cancer is one of the most important causes of cancer deaths in women. The present study was conducted to determine the relationship between demographic factors and known risk factors with breast cancer in women aged 30-69. Method: This case-control study was conducted with two matched and unmatched control groups. Three hundred fifty women aged 30-69 with breast cancer, 350 age-matched women without cancer, and 350 not age-matched women were included in the study. Controls were selected from the records of women whose breast cancer screening results were normal. Study subjects were evaluated regarding the risk factors for breast cancer. The data collection tool was a checklist including the risk factors investigated in the integrated health system. The collected data were analyzed utilizing SPSS22 software at a significance level of less than 0.05. Results: The average age in the case group was 46.63±11.77 years and 49.61±8.39 in the unmatched control group. The average age of marriage in the case group was 21.54±4.31, and the average age of women at first pregnancy in the case group was 24.06±3.39 years. In the case group, 163 people (46.57%) lived in the city, 221 people (63.14%) were over 40 years old, and 337 people (96.28%) were married. In multivariate analysis, the variable 'age of marriage' 0.821 (0.691-0.976) and 'age of first pregnancy' 1.213 (1.020-1.443) showed a significant relationship with breast cancer which were observed as predictors of breast cancer in comparison to the unmatched control group (P-value <0.05). Conclusion: The age of the first pregnancy and the type of delivery were observed as predictors of breast cancer. Therefore, by performing breast cancer screening in women who are exposed to these risk factors, early diagnosis of the disease and increasing the speed of their treatment can be significantly helped.

Design, synthesis, in vitro, and in silico anti-α-glucosidase assays of N-phenylacetamide-1,2,3-triazole-indole-2-carboxamide derivatives as new anti-diabetic agents.

In this work, a novel series of N-phenylacetamide-1,2,3-triazole-indole-2-carboxamide derivatives 5a-n were designed by consideration of the potent α-glucosidase inhibitors containing indole and carboxamide-1,2,3-triazole-N-phenylacetamide moieties. These compounds were synthesized by click reaction and evaluated against yeast α-glucosidase. All the newly title compounds demonstrated superior potency when compared with acarbose as a standard inhibitor. Particularly, compound 5k possessed the best inhibitory activity against α-glucosidase with around a 28-fold improvement in the inhibition effect in comparison standard inhibitor. This compound showed a competitive type of inhibition in the kinetics. The molecular docking and dynamics demonstrated that compound 5k with a favorable binding energy well occupied the active site of α-glucosidase.

Switching from injectable to other Disease Modifying Therapies may improve sexual dysfunction in people with Multiple Sclerosis.

BACKGROUND: Multiple Sclerosis (MS) a central nervous system autoimmune disorder, mainly affecting young adults and more prevalent among women, can lead to sexual dysfunction (SD) among both males and females with MS. Female sexual dysfunction can be defined as dyspareunia, a lack of sexual desire, disorders in the arousal and orgasm phases, and sexual pain disorders. The purpose of this study is to investigate the changes in sexual function among females with MS whose treatment was switched from first-line injectable medications to other agents after a six-month duration. And assess the changes in all three domains of SD. METHODS: In this longitudinal study females diagnosed with MS, aged between 18 and 50 years old, and were candidates for switching their treatment from interferon beta-1a (intra-muscular and subcutaneous), and Glatiramer Acetate (GA), to Fingolimod, Dimethyl Fumarate (DMF), or Natalizumab (NTZ) due to patients' convenience and tolerability and adverse events were included. "Multiple Sclerosis Intimacy and Sexuality Questionnaire-19" was used to evaluate the SD changes before and six months after the new treatment initiation. Statistical analysis was conducted using SPSS V.24 software. Histograms and the Shapiro-Wilk test were used to assess the normality of the variables; due to the non-normal distribution of quantitative variables (except for age), the Wilcoxon signed-rank test was used to compare the scores, before and six months after the medication change. The level of significance was considered less than 0.05. RESULTS: Out of 107 female participants (average age: 35.09 ± 5.61), The mean of overall MSISQ-19 scores, before and six months after the medication change were not significant (p-value = 0.091). However, considering the subdomains, the medication changes only affected the tertiary subdomain of MSISQ-19 (p-value = 0.017). Still, the scores of other subdomains did not change significantly (p-value = 0.761 for primary SD and 0.479 for secondary SD). Also, there wasn't any significant difference between EDSS before and after the medication change (p-value = 0.461). CONCLUSIONS: To our knowledge, this was the first study, assessing the effect of MS medication change on the improvement of SD among patients. According to the results of the presented cross-sectional study, we found that during a six-month period, the tertiary subdomain of MSISQ-19 symptoms improved significantly, while the changes in other SD domains were not significant.

Molecular docking studies, DFT, and ADMET calculations of some flavonoids and their characteristic structural features involved in inhibition of pro-inflammatory enzymes.

Inflammation is an immune system response triggered by pathogens, damaged cells, or stimuli. Some regulatory enzymes, such as phosphodiesterase, hyaluronidase, collagenase, and lipoxygenase, play an essential role in the inflammatory process. Polyphenolic compounds, such as flavonoids, are active suppressors of inflammatory cytokines, modulators of transcription factors, and inflammation-related pathways. A set of flavonoid structures was screened and docked against inflammation pathway enzymes. Amentoflavone has been shown to cause interactions with phosphodiesterase enzymes, while Bilobetin and Silibinin demonstrated an increase in binding energy with collagenase enzymes. The retrieved compounds from the docking study were subjected to DFT theory. The results showed that the LUMO orbital is located on the flavonoid part. The thermochemical parameters indicated that Silibinin is more stable than other compounds. The ADMET profile predicted that Silibinin can be used orally among the compounds. Silibinin can be introduced as a promising anti-inflammatory agent demonstrating phosphodiesterase and collagenase inhibitory properties.

Exploring the virome: An integral part of human health and disease.

The human microbiome is a complex network of microorganisms that includes viruses, bacteria, and fungi. The gut virome is an essential component of the immune system, which is responsible for regulating the growth and responses of the host's immune system. The virome maintains a crucial role in the development of numerous diseases, including inflammatory bowel disease (IBD), Crohn's disease, and neurodegenerative disorders. The human virome has emerged as a promising biomarker and therapeutic target. This comprehensive review summarizes the present understanding of the virome and its implications in matters of health and disease, with a focus on the Human Microbiome Project.

Waterpipe tobacco smoking and multiple sclerosis: a systematic review and meta-analysis.

BACKGROUND: Multiple sclerosis (MS), as an autoimmune disease of the central nervous system (CNS), has a significant burden among people worldwide. Tobacco smoking is one of the most prevalent habits of patients with different diseases including those with MS and among the methods of use, waterpipe tobacco smoking is gaining popularity. Herein, we aimed to systematically evaluate the association between waterpipe smoking and MS. METHODS: Relevant studies were identified to be included in this systematic review and meta-analysis through a systematic search in PubMed, Scopus, Web of Science, and Embase. Studies were screened by title/abstract and then by their full text. Extraction of data was performed for relevant studies. Odds ratios (OR) and their 95% confidence intervals (CIs) of the association between waterpipe smoking and MS were used to pool the results observed in each study. RESULTS: After the screening, a total of five studies were included in our systematic review, comprised of 3087 individuals, among which there were 1135 cases with MS. Random-effect meta-analysis revealed that ever-smoking waterpipe had a significant association with MS (OR 1.73, 95% CI 1.38-2.17, p-value <0.0001). Similarly, past waterpipe smoking was significantly higher in those with MS, compared with controls (OR 2.17, 95% CI 1.61-2.92, p-value < 0.0001). Based on the reported results, smoking both tobacco and waterpipe had an additive association with MS. Finally, no association was found between the Expanded Disability Status Scale (EDSS) and waterpipe smoking. CONCLUSION: Waterpipe as one of the common ways of tobacco smoking becoming popular has an association with MS and even the use of waterpipe for a certain period in the lifetime has a significant correlation with MS. Further large-scale studies are needed to confirm these findings. These results could help clinicians in risk-stratifying the patients and to provide better care for the MS population.

FnR: R package for computing inbreeding and numerator relationship coefficients.

BACKGROUND: Inbreeding and relationship coefficients are essential for conservation and breeding programs. Whether dealing with a small conserved population or a large commercial population, monitoring the inbreeding rate and designing mating plans that minimize the inbreeding rate and maximize the effective population size is important. Free, open-source, and efficient software may greatly contribute to conservation and breeding programs and help students and researchers. Efficient methods exist for calculating inbreeding coefficients. Therefore, an efficient way of calculating the numerator relationship coefficients is via the inbreeding coefficients. i.e., the relationship coefficient between parents is twice the inbreeding coefficient of their progeny. A dummy progeny is introduced where no progeny exists for a pair of individuals. Calculating inbreeding coefficients is very fast, and finding whether a pair of individuals has a progeny and picking one from multiple progenies is computationally more demanding. Therefore, the R package introduces a dummy progeny for any pair of individuals whose relationship coefficient is of interest, whether they have a progeny or not. RESULTS: Runtime and peak memory usage were benchmarked for calculating relationship coefficients between two sets of 250 and 800 animals (200,000 dummy progenies) from a pedigree of 2,721,252 animals. The program performed efficiently (200,000 relationship coefficients, which involved calculating 2,721,252 + 200,000 inbreeding coefficients) within 3:45 (mm:ss). Providing the inbreeding coefficients (for real animals), the runtime was reduced to 1:08. Furthermore, providing the diagonal elements of D in A = TDT ' (d), the runtime was reduced to 54s. All the analyses were performed on a machine with a total memory size of 1 GB. CONCLUSIONS: The R package FnR is free and open-source software with implications in conservation and breeding programs. It proved to be time and memory efficient for large populations and many dummy progenies. Calculation of inbreeding coefficients can be resumed for new animals in the pedigree. Thus, saving the latest inbreeding coefficient estimates is recommended. Calculation of d coefficients (from scratch) was very fast, and there was limited value in storing those for future use.