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1.
J Contemp Dent Pract ; 25(4): 320-325, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38956845

ABSTRACT

AIM: The aim of the present research was to assess the mesiodistal angulation of the maxillary anterior teeth utilizing Image J computer software, a Profile projector, and a Custom-made jig. MATERIALS AND METHODS: A total of 34 subjects (17 males and 17 females) were chosen from a group of 18-30 years old with bilateral Angle Class I molars and canine relationships. One manual approach (Custom-made jig) and two digital methods (J computer software, a Profile projector) were used to record the mesiodistal angulation in incisal view. The individuals had alginate impressions made, and a facebow was used to capture the maxilla's spatial relationship with the cranium. The articulated cast with the help of mounting ring moved to the specially customized jig, then the angulations was measured in the incisal view after the casts were placed in a semi-adjustable articulator. Data were recorded and statistically analyzed. RESULTS: The mesiodistal angulation in the incisal view via three methods between the 17 males and 17 females has statistically significant different. Although the mesiodistal angulation for maxillary lateral incisor and canine did not show any statistically significant difference, the maximum and minimum values obtained were always greater in males in comparison with the females. This indicates that the positions of six maxillary anterior teeth in the males resulted in the creation of upward sweep of incisal edges of central and lateral incisors which was also referred to as "smiling line" producing masculine surface anatomy more squared and vigorous while feminine surface anatomy being more rounded, soft, and pleasant. There was no statistically significant difference between the right and left sides, indicating bilateral arch symmetry and the symmetrical place of the right teeth compared with the left side's corresponding teeth. CONCLUSION: On conclusion, according to the current study's findings, all three approaches can measure the mesiodistal angulations of maxillary anterior teeth in incisal view with clinically acceptable accuracy. The digital methods, which included using the Image J computer software and the profile projector, achieved more accurate results than the manual method. CLINICAL SIGNIFICANCE: The outcomes of this study's mesiodistal angulations can be used as a reference for placing teeth in both fully and partially edentulous conditions. This study contributes to a better understanding of the importance of achieving the ideal occlusion in the Indian population by placing the maxillary anterior teeth at the proper mesiodistal angulation. How to cite this article: Shadaksharappa SH, Lahiri B, Kamath AG, et al. Evaluation of Mesiodistal Angulation of Maxillary Anterior Teeth in Incisal View Using Manual and Digital Methods: An In Vivo Study. J Contemp Dent Pract 2024;25(4):320-325.


Subject(s)
Incisor , Maxilla , Humans , Male , Female , Maxilla/anatomy & histology , Adolescent , Incisor/anatomy & histology , Young Adult , Adult , Software , Image Processing, Computer-Assisted/methods , Cuspid/anatomy & histology
2.
Curr Diabetes Rev ; 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38956912

ABSTRACT

INTRODUCTION/OBJECTIVES: Recently, there has been a notable increase in interest in various forms of vegetarianism, which may be due to the growing prevalence of health issues, such as Type 2 Diabetes Mellitus (T2DM). Adhering to a vegan diet may have positive health outcomes. As a result, we conducted a review article to gather data from previous research studies on the effects of a vegan diet on different aspects of managing patients with T2DM. METHODS: We searched the PubMed website for research studies on how a vegan diet affects the outcomes of patients with T2DM. The research studies were categorized according to the type of data collected, such as prevalence, incidence, body weight, insulin resistance, glycemic control, and lipid profile. RESULTS: It was found that following a vegetarian diet can significantly reduce the risk of mortality from heart disease. Additionally, studies have demonstrated that a vegetarian diet is linked to several improvements in T2DM. However, long-term weight loss plans and managing T2DM is a comprehensive intervention that includes caloric restriction, exercise, and behavioral modification. CONCLUSION: Incorporating a vegan diet can be a valuable factor to consider in managing T2DM, as it can offer numerous benefits, such as increased insulin sensitivity, weight loss, and reduced blood sugar levels. It helps to reduce cholesterol levels, LDL, and triglyceride levels, which are all risk factors associated with T2DM. By reducing these risk factors, the vegan diet can improve the overall health of T2DM patients.

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3.
BMC Med Res Methodol ; 24(1): 82, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38580928

ABSTRACT

BACKGROUND: This retrospective analysis aimed to comprehensively review the design and regulatory aspects of bioequivalence trials submitted to the Saudi Food and Drug Authority (SFDA) since 2017. METHODS: This was a retrospective, comprehensive analysis study. The Data extracted from the SFDA bioequivalence assessment reports were analyzed for reviewing the overall design and regulatory aspects of the successful bioequivalence trials, exploring the impact of the coefficient of variation of within-subject variability (CVw) on some design aspects, and providing an in-depth assessment of bioequivalence trial submissions that were deemed insufficient in demonstrating bioequivalence. RESULTS: A total of 590 bioequivalence trials were included of which 521 demonstrated bioequivalence (440 single active pharmaceutical ingredients [APIs] and 81 fixed combinations). Most of the successful trials were for cardiovascular drugs (84 out of 521 [16.1%]), and the 2 × 2 crossover design was used in 455 (87.3%) trials. The sample size tended to increase with the increase in the CVw in trials of single APIs. Biopharmaceutics Classification System Class II and IV drugs accounted for the majority of highly variable drugs (58 out of 82 [70.7%]) in the study. Most of the 51 rejected trials were rejected due to concerns related to the study center (n = 21 [41.2%]). CONCLUSION: This comprehensive analysis provides valuable insights into the regulatory and design aspects of bioequivalence trials and can inform future research and assist in identifying opportunities for improvement in conducting bioequivalence trials in Saudi Arabia.


Subject(s)
Drugs, Generic , Humans , Therapeutic Equivalency , Drugs, Generic/therapeutic use , Saudi Arabia , Retrospective Studies , Sample Size
4.
Nat Protoc ; 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38565959

ABSTRACT

Methods for analyzing the full complement of a biomolecule type, e.g., proteomics or metabolomics, generate large amounts of complex data. The software tools used to analyze omics data have reshaped the landscape of modern biology and become an essential component of biomedical research. These tools are themselves quite complex and often require the installation of other supporting software, libraries and/or databases. A researcher may also be using multiple different tools that require different versions of the same supporting materials. The increasing dependence of biomedical scientists on these powerful tools creates a need for easier installation and greater usability. Packaging and containerization are different approaches to satisfy this need by delivering omics tools already wrapped in additional software that makes the tools easier to install and use. In this systematic review, we describe and compare the features of prominent packaging and containerization platforms. We outline the challenges, advantages and limitations of each approach and some of the most widely used platforms from the perspectives of users, software developers and system administrators. We also propose principles to make the distribution of omics software more sustainable and robust to increase the reproducibility of biomedical and life science research.

5.
ACS Bio Med Chem Au ; 4(1): 37-52, 2024 Feb 21.
Article in English | MEDLINE | ID: mdl-38404747

ABSTRACT

The tragic COVID-19 pandemic, which has seen a total of 655 million cases worldwide and a death toll of over 6.6 million seems finally tailing off. Even so, new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to arise, the severity of which cannot be predicted in advance. This is concerning for the maintenance and stability of public health, since immune evasion and increased transmissibility may arise. Therefore, it is crucial to continue monitoring antibody responses to SARS-CoV-2 in the general population. As a complement to polymerase chain reaction tests, multiplex immunoassays are elegant tools that use individual protein or peptide antigens simultaneously to provide a high level of sensitivity and specificity. To further improve these aspects of SARS-CoV-2 antibody detection, as well as accuracy, we have developed an advanced serological peptide-based multiplex assay using antigen-fused peptide epitopes derived from both the spike and the nucleocapsid proteins. The significance of the epitopes selected for antibody detection has been verified by in silico molecular docking simulations between the peptide epitopes and reported SARS-CoV-2 antibodies. Peptides can be more easily and quickly modified and synthesized than full length proteins and can, therefore, be used in a more cost-effective manner. Three different fusion-epitope peptides (FEPs) were synthesized and tested by enzyme-linked immunosorbent assay (ELISA). A total of 145 blood serum samples were used, compromising 110 COVID-19 serum samples from COVID-19 patients and 35 negative control serum samples taken from COVID-19-free individuals before the outbreak. Interestingly, our data demonstrate that the sensitivity, specificity, and accuracy of the results for the FEP antigens are higher than for single peptide epitopes or mixtures of single peptide epitopes. Our FEP concept can be applied to different multiplex immunoassays testing not only for SARS-CoV-2 but also for various other pathogens. A significantly improved peptide-based serological assay may support the development of commercial point-of-care tests, such as lateral-flow-assays.

6.
Sci Rep ; 13(1): 16779, 2023 Oct 05.
Article in English | MEDLINE | ID: mdl-37798359

ABSTRACT

Every year manufacturers of household appliances improve their devices, trying to make everyday life easier for users. New smart devices have many useful features, but not all users can easily cope with the complexity of the devices. One of the main tasks of household appliance manufacturers is to ensure the convenience of using appliances, taking into account the increasing complexity. Therefore, any manufacturer supplies equipment with a short but useful instruction manual. Practice shows that no printed user manual can compare with a demonstration of the device operation by a professional consultant. Instructions for home appliances using augmented reality technology will allow users to get the necessary detailed information about the device in a short period of time. As part of this work, the task of developing an artificial intelligence-based module is being solved. This module consists of developed classification, matching, and tracking submodules that can provide simple and fast visual instructions to users of household appliances in real time. The identification of household appliances is performed with more than 0.9 accuracy, and the tracking inside an unidentified object using the camera of a mobile device is processed with the success score of about 0.68 and frames per second (FPS) about 7. Mobile applications based on the proposed intelligent modules for Android and iOS were developed.

7.
bioRxiv ; 2023 Aug 07.
Article in English | MEDLINE | ID: mdl-37609176

ABSTRACT

Data-driven computational analysis is becoming increasingly important in biomedical research, as the amount of data being generated continues to grow. However, the lack of practices of sharing research outputs, such as data, source code and methods, affects transparency and reproducibility of studies, which are critical to the advancement of science. Many published studies are not reproducible due to insufficient documentation, code, and data being shared. We conducted a comprehensive analysis of 453 manuscripts published between 2016-2021 and found that 50.1% of them fail to share the analytical code. Even among those that did disclose their code, a vast majority failed to offer additional research outputs, such as data. Furthermore, only one in ten papers organized their code in a structured and reproducible manner. We discovered a significant association between the presence of code availability statements and increased code availability (p=2.71×10-9). Additionally, a greater proportion of studies conducting secondary analyses were inclined to share their code compared to those conducting primary analyses (p=1.15*10-07). In light of our findings, we propose raising awareness of code sharing practices and taking immediate steps to enhance code availability to improve reproducibility in biomedical research. By increasing transparency and reproducibility, we can promote scientific rigor, encourage collaboration, and accelerate scientific discoveries. We must prioritize open science practices, including sharing code, data, and other research products, to ensure that biomedical research can be replicated and built upon by others in the scientific community.

8.
Sci Rep ; 13(1): 11619, 2023 07 18.
Article in English | MEDLINE | ID: mdl-37464006

ABSTRACT

The examination of seated occupants' ride comfort under whole-body vibration is a complex topic that involves multiple factors. Whole-body vibration refers to the mechanical vibration that is transmitted to the entire body through a supporting surface, such as a vehicle seat, when traveling on rough or uneven surfaces. There are several methods to assess ride comfort under whole-body vibration, such as subjective assessments, objective measurements, and mathematical models. Subjective assessments involve asking participants to rate their perceived level of discomfort or satisfaction during the vibration exposure, typically using a numerical scale or questionnaire. Objective measurements include accelerometers or vibration meters that record the actual physical vibrations transmitted to the body during the exposure. Mathematical models use various physiological and biomechanical parameters to predict the level of discomfort based on the vibration data. The examination of seated occupants ride comfort under whole-body vibration has been of great interest for many years. In this paper, a multi-body biomechanical model of a seated occupant with a backrest is proposed to perform ride comfort analysis. The novelty of the present model is that it represents complete passenger by including thighs, legs, and foot which were neglected in the past research. A multi-objective firefly algorithm is developed to evaluate the biomechanical parameters (mass, stiffness and damping) of the proposed model. Based on the optimized parameters, segmental transmissibilities are calculated and compared with experimental readings. The proposed model is then combined with a 7-dofs commercial car model to perform a ride comfort study. The ISO 2631-1:1997 ride comfort standards are used to compare the simulated segmental accelerations. Additionally, the influence of biomechanical parameters on most critical organs is analyzed to improve ride comfort. The outcomes of the analysis reveal that seated occupants perceive maximum vibration in the 3-6 Hz frequency range. To improve seated occupants' ride comfort, automotive designers must concentrate on the pelvis region. The adopted methodology and outcomes are helpful to evaluate protective measures in automobile industries. Furthermore, these procedures may be used to reduce the musculoskeletal disorders in seated occupants.


Subject(s)
Automobiles , Vibration , Humans , Sitting Position , Physical Therapy Modalities , Travel , Biomechanical Phenomena
9.
Brief Bioinform ; 24(4)2023 07 20.
Article in English | MEDLINE | ID: mdl-37291798

ABSTRACT

The ability to identify and track T-cell receptor (TCR) sequences from patient samples is becoming central to the field of cancer research and immunotherapy. Tracking genetically engineered T cells expressing TCRs that target specific tumor antigens is important to determine the persistence of these cells and quantify tumor responses. The available high-throughput method to profile TCR repertoires is generally referred to as TCR sequencing (TCR-Seq). However, the available TCR-Seq data are limited compared with RNA sequencing (RNA-Seq). In this paper, we have benchmarked the ability of RNA-Seq-based methods to profile TCR repertoires by examining 19 bulk RNA-Seq samples across 4 cancer cohorts including both T-cell-rich and T-cell-poor tissue types. We have performed a comprehensive evaluation of the existing RNA-Seq-based repertoire profiling methods using targeted TCR-Seq as the gold standard. We also highlighted scenarios under which the RNA-Seq approach is suitable and can provide comparable accuracy to the TCR-Seq approach. Our results show that RNA-Seq-based methods are able to effectively capture the clonotypes and estimate the diversity of TCR repertoires, as well as provide relative frequencies of clonotypes in T-cell-rich tissues and low-diversity repertoires. However, RNA-Seq-based TCR profiling methods have limited power in T-cell-poor tissues, especially in highly diverse repertoires of T-cell-poor tissues. The results of our benchmarking provide an additional appealing argument to incorporate RNA-Seq into the immune repertoire screening of cancer patients as it offers broader knowledge into the transcriptomic changes that exceed the limited information provided by TCR-Seq.


Subject(s)
Benchmarking , Neoplasms , Humans , Receptors, Antigen, T-Cell/genetics , T-Lymphocytes , Neoplasms/genetics , Sequence Analysis, RNA
10.
Ann Med Surg (Lond) ; 85(5): 2097-2101, 2023 May.
Article in English | MEDLINE | ID: mdl-37228937

ABSTRACT

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have been implemented in treating diabetic patients for the past 10 years. Euglycemic diabetic ketoacidosis (euDKA) can be a life-threatening complication in diabetic patients. The authors report a severe euDKA with lactic acidosis in a type 2 diabetes mellitus (T2DM) patient. This report highlights the importance of the early detection and treatment of EuDKA to avoid complications. Case presentation: Forty-four-year-old female with T2DM had multiple visits to the emergency department with recurrent diarrhoea and vomiting. On her third visit, she presented with shortness of breath and tachypnoea, found to have severe metabolic acidosis with euglycemia. She was admitted to ICU with euDKA secondary to SGLT2i and was managed accordingly. Clinical discussion: The association between SGLT2i and euDKA in T2DM is controversial. SGLT2i leads to euDKA by stimulating lipolysis and ketogenesis in the setting of volume depletion, carbohydrate deficiency, and upregulation of counter-regulatory stress hormones. EuDKA can be life-threatening, especially if not diagnosed and managed properly. The treatment protocol is similar to hyperglycaemic diabetic ketoacidosis. Our case has been reported in line with the CARE criteria.34. Conclusion: SGLT2i benefits in diabetic patients outweigh the risks. Clinicians are advised to counsel diabetic patients maintained on SGLT2 and educate them regarding holding the medication in the setting of acute illness, volume depletion, decreased oral intake, and surgery. In addition, there should be a high index of suspicion for patients presenting with metabolic acidosis in the background of SGLT2i use to provide early diagnosis and management.

11.
Adv Mater ; 35(19): e2210665, 2023 May.
Article in English | MEDLINE | ID: mdl-36808776

ABSTRACT

An experimental investigation and the optical modeling of the structural coloration produced from total internal reflection interference within 3D microstructures are described. Ray-tracing simulations coupled with color visualization and spectral analysis techniques are used to model, examine, and rationalize the iridescence generated for a range of microgeometries, including hemicylinders and truncated hemispheres, under varying illumination conditions. An approach to deconstruct the observed iridescence and complex far-field spectral features into its elementary components and systematically link them to ray trajectories that emanate from the illuminated microstructures is demonstrated. The results are compared with experiments, wherein microstructures are fabricated with methods such as chemical etching, multiphoton lithography, and grayscale lithography. Microstructure arrays patterned on surfaces with varying orientation and size lead to unique color-traveling optical effects and highlight opportunities for how total internal reflection interference can be used to create customizable reflective iridescence. The findings herein provide a robust conceptual framework for rationalizing this multibounce interference mechanism and establish approaches for characterizing and tailoring the optical and iridescent properties of microstructured surfaces.

12.
Front Public Health ; 10: 955458, 2022.
Article in English | MEDLINE | ID: mdl-36238245

ABSTRACT

Introduction: The human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (HIV/AIDS) are worldwide public health issues. Since Saudi Arabia is growing more accessible to the outside world, it is critical to analyze the general population's knowledge of HIV/AIDS transmission modes and attitudes toward HIV/AIDS infected people, and the level of HIV/AIDS awareness. Therefore, this study aimed to assess the knowledge of HIV/AIDS transmission modes and attitudes toward HIV/AIDS infected people, as well as the level of HIV/AIDS awareness among the general population in the Kingdom of Saudi Arabia. Methods: The current online community-based cross-sectional descriptive study was conducted among the general population of the Kingdom of Saudi Arabia using a self-administrated electronic questionnaire between October 2017 and February 2018. A score <3 was considered a negative response. In contrast, scores of 3 and 4 were considered positive responses. The sum score of each outcome was evaluated according to Bloom's cutoff point. The scores for knowledge and attitude were transformed into mean percentage scores by dividing the sum scores obtained by the respondents by the number of items multiplied by 100. Consequently, the overall mean percentage of scores for each category of knowledge and attitude at 60% and above was considered a good level, whereas <60% was deemed a poor level. Results: A total of 2,081 subjects residing in the Kingdom of Saudi Arabia participated in this survey. The mean score of the participant's responses to knowledge items on HIV/AIDS transmission modes was 84.2 ± 15.8%. The mean score of the participant's responses to attitude items toward HIV/AIDS infected people was 50.1 ± 49.9%. The mean score of the participant's responses to attitude items toward the level of HIV/AIDS awareness in Saudi Arabia was 55.7 ± 3.6%. Many socio-demographic variables were significantly associated with mean scores of knowledge of HIV/AIDS transmission modes, mean scores of attitude toward HIV/AIDS infected people, and mean scores of attitude toward the level of HIV/AIDS awareness (P-value ≤ 0.05). The Spearman rank correlation explained significant negative linear correlations between knowledge of HIV/AIDS transmission modes-attitudes toward HIV/AIDS infected people and knowledge of HIV/AIDS transmission modes-attitudes toward the level of HIV/AIDS awareness of r = -0.040 and r = -0.070, respectively (P-value ≤ 0.05). Otherwise, there was a positive linear correlation between attitudes toward HIV/AIDS infected people-attitudes toward the level of HIV/AIDS awareness (r = 0.080, P-value = 0.072). Conclusions: The study showed that a high percentage of the respondents had good knowledge of HIV/AIDS transmission modes. However, a low rate of the study respondents had positive attitudes toward HIV/AIDS infected people and the level of HIV/AIDS awareness among the general population in Saudi Arabia. Therefore, there is a dire need for advocacy campaigns and policies to help reduce HIV stigmatization levels.


Subject(s)
Acquired Immunodeficiency Syndrome , HIV Infections , Cross-Sectional Studies , Health Knowledge, Attitudes, Practice , Humans , Saudi Arabia
13.
Curr Oncol ; 29(10): 7558-7568, 2022 10 10.
Article in English | MEDLINE | ID: mdl-36290872

ABSTRACT

The clinical behaviors, prognosis, and appropriate treatments of papillary tumors of the pineal region (PTPR) are not fully defined due to the rarity of these tumors. At diagnosis, PTPR may present with clinical symptoms, including headache with obstructive hydrocephalus, diplopia, vomiting, and lethargy, as well as neurological signs, including Argyll Robertson pupils and Parinaud's syndrome due to compression of the dorsal midbrain, specifically the periaqueductal region with horizontal nystagmus. Radiological assessment of pineal region lesions is challenging, with a wide range of potential differential diagnoses. PTPR typically presents as a heterogeneous, well-circumscribed mass in the pineal region, which might contain cystic areas, calcifications, hemorrhages, or protein accumulations. Here, we report three female pediatric patients with PTPR treated in King Fahad Medical City (KFMC) in Saudi Arabia. Histological and immunohistochemical diagnosis was confirmed by analysis of genome-wide DNA methylation profiles. This case series expands on the available reports on the clinical presentations of PTPR and provides important information on the responses to different treatment modalities.


Subject(s)
Brain Neoplasms , Pineal Gland , Pinealoma , Humans , Female , Child , Pinealoma/diagnostic imaging , Pinealoma/therapy , Brain Neoplasms/diagnosis , Pineal Gland/diagnostic imaging , Pineal Gland/metabolism , Pineal Gland/pathology
14.
Cureus ; 14(7): e27087, 2022 Jul.
Article in English | MEDLINE | ID: mdl-36000129

ABSTRACT

BACKGROUND: Pulmonary embolism (PE) is a common acute life-threatening cardiovascular disorder. It is the third most common cause of hospital-related death and early detection and management of PE are crucial. The study aimed to evaluate the association between vital signs and laboratory investigations with PE. METHODS: This is a retrospective, hospital records-based, observational study, conducted among patients who were admitted to the emergency department of King Saud Medical City in Riyadh, Saudi Arabia with a suspected diagnosis of PE during the period of March 2021 to March 2022. Data were collected by searching patients' files and recording demographic data, and information about the clinical presentation, workup, and outcome. Data were entered and analyzed using SPSS version 26 (IBM, Armonk, NY), utilizing Chi-square statistics to test differences between groups, and logistic regression analyses to identify predictors of PE. RESULTS: The study included 92 patients, with a preponderance of females (70.7%), and those aged 40-60 years (51.1%). Diabetes mellitus (44.6%), and hypertension (30.4%) were the most common comorbidities among others, while shortness of breath (SOB) (83.7%), and chest pain (44.6%) were among the most commonly reported symptoms. A majority of patients had tachycardia (64.1%), while about half had low oxygen saturation (51.5%), and nearly one-third had tachypnea (29.3%), which was more predominant among those not diagnosed with PE. Logistic regression analysis revealed that SOB, respiratory rate, and oxygen saturation were the only significant predictors of PE. CONCLUSION: Although being an integral part of the initial assessment in the hospital, measuring the vital signs is not always reflective of the likelihood of PE, and they should not be the only metric relied upon to make decisions about treatment approaches in patients with PE. Physicians should ensure the employment of evidence-based clinical prediction rules and guidelines when diagnosing and managing PE.

16.
Guillaume Butler-Laporte; Gundula Povysil; Jack A Kosmicki; Elizabeth T Cirulli; Theodore Drivas; Simone Furini; Chadi Saad; Axel Schmidt; Pawel Olszewski; Urszula Korotko; Mathieu Quinodoz; Elifnaz Celik; Kousik Kundu; Klaudia Walter; Junghyung Jung; Amy D Stockwell; Laura G Sloofman; Daniel M Jordan; Ryan C Thompson; Diane Del Valle Del Valle; Nicole Simons Simons; Esther Cheng Cheng; Robert Sebra Sebra; Eric E Schadt; Seunghee Schulze-Kim Shulze-Kim; Sacha Gnjatic Gnjatic; Miriam Merad Merad; Joseph D Buxbaum; Noam D Beckmann; Alexander W Charney; Bartlomiej Przychodzen; Timothy Chang; Tess D Pottinger; Ning Shang; Fabian Brand; Francesca Fava; Francesca Mari; Karolina Chwialkowska; Magdalena Niemira; Szymon Pula; J Kenneth Baillie; Alex Stuckey; Antonio Salas; Xabier Bello; Jacobo Pardo-Seco; Alberto Gomez-Carballa; Irene Rivero-Calle; Federico Martinon-Torres; Andrea Ganna; Konrad J Karczewski; Kumar Veerapen; Mathieu Bourgey; Guillaume Bourque; Robert JM Eveleigh; Vincenzo Forgetta; David Morrison; David Langlais; Mark Lathrop; Vincent Mooser; Tomoko Nakanishi; Robert Frithiof; Michael Hultstrom; Miklos Lipcsey; Yanara Marincevic-Zuniga; Jessica Nordlund; Kelly M Schiabor Barrett; William Lee; Alexandre Bolze; Simon White; Stephen Riffle; Francisco Tanudjaja; Efren Sandoval; Iva Neveux; Shaun Dabe; Nicolas Casadei; Susanne Motameny; Manal Alaamery; Salam Massadeh; Nora Aljawini; Mansour S Almutairi; Yaseen M Arab; Saleh A Alqahtan; Fawz S Al Harthi; Amal Almutairi; Fatima Alqubaishi; Sarah Alotaibi; Albandari Binowayn; Ebtehal A Alsolm; Hadeel El Bardisy; Mohammad Fawzy; - COVID-19 Host Genetics Initiative; - DeCOI Host Genetics Group; - GEN-COVID Multicenter Study (Italy); - Mount Sinai Clinical Intelligence Center; - GEN-COVID consortium (Spain); - GenOMICC Consortium; - Japan COVID-19 Task Force; - Regeneron Genetics Center; Daniel H Geschwind; Stephanie Arteaga; Alexis Stephens; Manish J Butte; Paul C Boutros; Takafumi N Yamaguchi; Shu Tao; Stefan Eng; Timothy Sanders; Paul J Tung; Michael E Broudy; Yu Pan; Alfredo Gonzalez; Nikhil Chavan; Ruth Johnson; Bogdan Pasaniuc; Brian Yaspan; Sandra Smieszek; Carlo Rivolta; Stephanie Bibert; Pierre-Yves Bochud; Maciej Dabrowski; Pawel Zawadzki; Mateusz Sypniewski; Elzbieta Kaja; Pajaree Chariyavilaskul; Voraphoj Nilaratanakul; Nattiya Hirankarn; Vorasuk Shotelersuk; Monnat Pongpanich; Chureerat Phokaew; Wanna Chetruengchai; Katsuhi Tokunaga; Masaya Sugiyama; Yosuke Kawai; Takanori Hasegawa; Tatsuhiko Naito; Ho Namkoong; Ryuya Edahiro; Akinori Kimura; Seishi Ogawa; Takanori Kanai; Koichi Fukunaga; Yukinori Okada; Seiya Imoto; Satoru Miyano; Serghei Mangul; Malak S Abedalthagafi; Hugo Zeberg; Joseph J Grzymski; Nicole L Washington; Stephan Ossowski; Kerstin U Ludwig; Eva C Schulte; Olaf Riess; Marcin Moniuszko; Miroslaw Kwasniewski; Hamdi Mbarek; Said I Ismail; Anurag Verma; David B Goldstein; Krzysztof Kiryluk; Alessandra Renieri; Manuel AR Ferreira; J Brent Richards.
Preprint in English | medRxiv | ID: ppmedrxiv-22273040

ABSTRACT

Host genetics is a key determinant of COVID-19 outcomes. Previously, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75-10.05, p=5.41x10-7). This association was consistent across sexes. These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights. Author SummaryCOVID-19 clinical outcomes vary immensely, but a patients genetic make-up is an important determinant of how they will fare against the virus. While many genetic variants commonly found in the populations were previously found to be contributing to more severe disease by the COVID-19 Host Genetics Initiative, it isnt clear if more rare variants found in less individuals could also play a role. This is important because genetic variants with the largest impact on COVID-19 severity are expected to be rarely found in the population, and these rare variants require different technologies to be studies (usually whole-exome or whole-genome sequencing). Here, we combined sequencing results from 21 cohorts across 12 countries to perform a rare variant association study. In an analysis comprising 5,085 participants with severe COVID-19 and 571,737 controls, we found that the gene for toll-like receptor 7 (TLR7) on chromosome X was an important determinant of severe COVID-19. Importantly, despite being found on a sex chromosome, this observation was consistent across both sexes.

17.
J Epidemiol Glob Health ; 12(1): 85-91, 2022 03.
Article in English | MEDLINE | ID: mdl-34978705

ABSTRACT

BACKGROUND: Disease severity among patients infected with SARS-CoV-2 varies remarkably. Preliminary studies reported that the ABO blood group system confers differential viral susceptibility and disease severity caused by SARS-CoV-2. Thus, differences in ABO blood group phenotypes may partly explain the observed heterogeneity in COVID-19 severity patterns, and could help identify individuals at increased risk. Herein, we explored the association between ABO blood group phenotypes and COVID-19 susceptibility and severity in a Saudi Arabian cohort. METHODS: In this retrospective cohort study, we performed ABO typing on a total of 373 Saudi patients infected with SARS-CoV-2 and conducted association analysis between ABO blood group phenotype and COVID-19 infection severity. We then performed gender-stratified analysis by dividing the participating patients into two groups by gender, and classified them according to age. RESULTS: The frequencies of blood group phenotypes A, B, AB and O were 27.3, 23.6, 5.4 and 43.7%, respectively. We found that blood group phenotype O was associated with a lower risk of testing positive for COVID-19 infection (OR 0.76 95% CI 0.62-0.95, p = 0.0113), while blood group phenotype B was associated with higher odds of testing positive (OR 1.51 95% CI 1.17-1.93, p = 0.0009). However, blood group phenotype B was associated with increased risk in the mild and moderate group but not the severe COVID-19 infection group. Blood group phenotype O was protective in all severity groups. CONCLUSION: Our findings provide evidence that blood group phenotype B is a risk for COVID-19 disease while blood group phenotype O is protective from COVID-19 infection. However, further studies are necessary to validate these associations in a larger sample size and among individuals of different ethnic groups.


Subject(s)
ABO Blood-Group System , COVID-19 , ABO Blood-Group System/genetics , COVID-19/epidemiology , Humans , Phenotype , Retrospective Studies , SARS-CoV-2 , Saudi Arabia/epidemiology , Severity of Illness Index
18.
Clin Immunol ; 234: 108911, 2022 01.
Article in English | MEDLINE | ID: mdl-34929414

ABSTRACT

BACKGROUND: Natural killer (NK) cells play an essential role against viruses. NK cells express killer cell immunoglobulin-like receptors (KIRs) which regulate their activity and function. The polymorphisms in KIR haplotypes confer differential viral susceptibility and disease severity caused by infections. We investigated the association between KIR genes and COVID-19 disease severity. METHODS: 424 COVID-19 positive patients were divided according to their disease severity into mild, moderate and severe. KIR genes were genotyped using next generation sequencing (NGS). Association between KIR genes and COVID-19 disease severity was conducted and significant correlations were reported. RESULTS: In the COVID-19 patients, KIR Bx genotype was more common than AA genotype. The Bx genotype was found more frequently in patients with mild disease, while in severe disease the AA genotype was more common than the Bx genotype. The KIR2DS4 gene carried the highest risk for severe COVID-19 infection (OR 8.48, pc= 0.0084) followed by KIR3DL1 (OR 7.61, pc= 0.0192). CONCLUSIONS: Our findings suggest that KIR2DS4 and KIR3DL1 genes carry risk for severe COVID-19 disease.


Subject(s)
COVID-19/genetics , Genetic Predisposition to Disease/genetics , Polymorphism, Genetic/genetics , Receptors, KIR/genetics , Adult , COVID-19/metabolism , Female , Gene Frequency/genetics , Genotype , Humans , Killer Cells, Natural/metabolism , Male , Middle Aged , SARS-CoV-2/pathogenicity
20.
ArXiv ; 2021 Apr 28.
Article in English | MEDLINE | ID: mdl-33948451

ABSTRACT

More than any other infectious disease epidemic, the COVID-19 pandemic has been characterized by the generation of large volumes of viral genomic data at an incredible pace due to recent advances in high-throughput sequencing technologies, the rapid global spread of SARS-CoV-2, and its persistent threat to public health. However, distinguishing the most epidemiologically relevant information encoded in these vast amounts of data requires substantial effort across the research and public health communities. Studies of SARS-CoV-2 genomes have been critical in tracking the spread of variants and understanding its epidemic dynamics, and may prove crucial for controlling future epidemics and alleviating significant public health burdens. Together, genomic data and bioinformatics methods enable broad-scale investigations of the spread of SARS-CoV-2 at the local, national, and global scales and allow researchers the ability to efficiently track the emergence of novel variants, reconstruct epidemic dynamics, and provide important insights into drug and vaccine development and disease control. Here, we discuss the tremendous opportunities that genomics offers to unlock the effective use of SARS-CoV-2 genomic data for efficient public health surveillance and guiding timely responses to COVID-19.

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