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Amal Mohammed Sindi, Khalid Aljohani Department of Oral Diagnostic Sciences, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi ArabiaCorrespondence: Amal Mohammed Sindi, Department of Oral Diagnostic Sciences, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia, Email amsindi@kau.edu.saPurpose: Diagnosing oral and maxillofacial lesions is a multi-step, multidisciplinary process. If a clinical diagnosis is achievable, then a histopathological diagnosis is indicated to support and confirm the diagnosis. Histopathological examination of tissue biopsies is therefore an essential part of the diagnosis and/or treatment plan. The purpose of this study was to investigate the agreement between the clinical and histopathological diagnoses of oral and maxillofacial lesions and the patient, lesion, and healthcare provider factors that may affect this agreement.Patients and Methods: This was an observational, cross-sectional study of all patients who had been referred to the Oral Pathology Central Laboratory at the Faculty of Dentistry and University Dental Hospital at King Abdulaziz University in Jeddah, Saudi Arabia, between 2018 and 2022 for diagnosis of oral and maxillofacial lesions. Data extracted included information about the referring dental provider such as their clinical experience (number of years), specialty, certification, and education. Agreement between the clinical and histopathological diagnoses was evaluated, and logistic regression was used to assess provider characteristics associated with the accuracy of diagnosis.Results: The clinical and pathological diagnoses were concordant in 44.1% (n=378) of cases, and concordance was highest for odontogenic tumors (72.7%, n=24), significantly higher than for inflammatory lesions (37.3%, n=111). The anatomical locations with the highest diagnostic accuracy were the ventral surface of the tongue (71.4%, n=5), followed by the lips (52.6%, n=20). Patient age and sex and the dentist’s years of experience were not associated with diagnostic agreement (p=0.2, p=0.9, and p=0.08, respectively). However, concordant diagnoses were significantly associated with the dentist’s rank (p=0.02) and specialty (p=0.01). Clinical diagnoses made by oral surgeons at the time of biopsy were 1.6-times more likely (p=0.01) to agree with the pathological diagnosis compared with those made by other specialties when controlling for education, certification, and years of experience.Conclusion: These data are a reminder that a clinical diagnosis alone is not sufficient to secure the final diagnosis and to plan treatment. Histopathological examination remains essential for most oral and maxillofacial lesions.Keywords: dentist, oral diseases, clinical diagnosis, biopsy, histopathological diagnosis

Khaled S Allemailem,1 Ahmad Almatroudi,1 Arshad Husain Rahmani,1 Faris Alrumaihi,1 Arwa Essa Alradhi,2 Amal M Alsubaiyel,3 Mohammad Algahtani,4 Rand Mohammad Almousa,5 Ali Mahzari,6 Abdulmajeed AA Sindi,7 Gasim Dobie,8 Amjad Ali Khan9 1Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi Arabia; 2General Administration for Infectious Disease Control, Ministry of Health, Riyadh 12382, Saudi Arabia; 3Department of Pharmaceutics, College of Pharmacy, Qassim University, Buraydah 51452, Saudi Arabia; 4Department of Laboratory & Blood Bank, Security Forces Hospital, Mecca 21955, Saudi Arabia; 5Department of Education, General Directorate of Education, Qassim 52361, Saudi Arabia; 6Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Al-Baha University, Al-Baha 65527, Saudi Arabia; 7Department of Basic Medical Sciences, Faculty of Applied Medical Sciences, Al-Baha University, Al-Baha 65527, Saudi Arabia; 8Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Jazan University, Gizan 82911, Saudi Arabia; 9Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi ArabiaCorrespondence: Amjad Ali Khan, Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, P.O. Box 6666, Buraydah, 51452, Saudi Arabia, Email akhan@qu.edu.saAbstract: The genome editing approach by clustered regularly interspaced short palindromic repeats (CRISPR)/associated protein 9 (CRISPR/Cas9) is a revolutionary advancement in genetic engineering. Owing to its simple design and powerful genome-editing capability, it offers a promising strategy for the treatment of different infectious, metabolic, and genetic diseases. The crystal structure of Streptococcus pyogenes Cas9 (SpCas9) in complex with sgRNA and its target DNA at 2.5 Å resolution reveals a groove accommodating sgRNA:DNA heteroduplex within a bilobate architecture with target recognition (REC) and nuclease (NUC) domains. The presence of a PAM is significantly required for target recognition, R-loop formation, and strand scission. Recently, the spatiotemporal control of CRISPR/Cas9 genome editing has been considerably improved by genetic, chemical, and physical regulatory strategies. The use of genetic modifiers anti-CRISPR proteins, cell-specific promoters, and histone acetyl transferases has uplifted the application of CRISPR/Cas9 as a future-generation genome editing tool. In addition, interventions by chemical control, small-molecule activators, oligonucleotide conjugates and bioresponsive delivery carriers have improved its application in other areas of biological fields. Furthermore, the intermediation of physical control by using heat-, light-, magnetism-, and ultrasound-responsive elements attached to this molecular tool has revolutionized genome editing further. These strategies significantly reduce CRISPR/Cas9’s undesirable off-target effects. However, other undesirable effects still offer some challenges for comprehensive clinical translation using this genome-editing approach. In this review, we summarize recent advances in CRISPR/Cas9 structure, mechanistic action, and the role of small-molecule activators, inhibitors, promoters, and physical approaches. Finally, off-target measurement approaches, challenges, future prospects, and clinical applications are discussed.Keywords: CRISPR/Cas9, sgRNA, genome editing, off-target effects, spatiotemporal control, clinical translation

One of the risk components that are most vulnerable to earthquake disasters is children. Klaten Regency is one of the areas frequently shaken by earthquakes. Therefore, this study aims to measure students' adaptive capacity and resilience to earthquakes in the Klaten Regency. Respondents in this study were students of SMP M 8 Wedi, MTs M 10 Wedi, and SMP M 21gantiwarno, Klaten Regency. The adaptive capacity of students is measured based on institutional memory, innovative learning, and connectedness. In contrast, students' resilience level is measured based on emotion regulation, control over problems, optimism, empathy, self-efficacy, ability to analyze issues, and achievement. Data were collected using a questionnaire and processed using descriptive statistics. The level of adaptive capacity and resilience of the student community to natural disasters has different characteristics due to the influence of several factors such as the location of the school in a disaster-prone area, the integration of disaster material into learning, experience in disaster emergency response conditions, school policies on disaster mitigation and family or community factors environment. The best level of adaptive capacity is found in SMP Muhammadiyah 8 Wedi with 62.90%, and MTs Muhammadiyah 10 Wedi has a poor level of adaptive capacity with 44.32%. Moreover, based on gender characteristics, the level of adaptive capacity of male students is better than female students, with the lowest percentage being female at MTs Muhammadiyah 10 Wedi. The highest level of student resilience is found at MTs Muhammadiyah 10 Wedi at 61.36%, while SMP Muhammadiyah 21 Gantiwarno is classified as poor at 33.33%. Based on gender characteristics, the highest level of resilience is female at MTs Muhammadiyah 10 Wedi, with 91.67%.

The Library and Archives Service of South Labuhanbatu Regency is an agency implementing local government affairs in the field of libraries and archives. The purpose of this research is to find out the various efforts of the South Labuhanbatu Regency Library and Archives Service in implementing work programs that are in line with the SDGs. This study uses data collection techniques through observation, interviews, and documentation. In this study, researchers used a data validity test through data triangulation. The data analysis used refers to the Miles and Huberman model. In this study there were 4 people as informants, consisting of librarians at the Library and Archives Service of South Labuhanbatu Regency. Based on the research that has been carried out, it can be concluded that the Library and Archives Service of Labuhanbatu Selatan Regency has an important role in supporting the SDGs, especially in pillars 1 and 4, namely poverty alleviation and delivery of quality education. The results of this research can be used by libraries to develop information services that support the SDGs.

The aim of this research is to make it easier for teachers to implement fitness tests for Indonesian students in the East Kalimantan region, as well as to produce an application for the Indonesian Student Fitness Test to support the grand design of national sports in East Kalimantan. To find out the effectiveness of this application as a medium for implementing fitness tests for Indonesian students. In this research, the development media used is the procedural development model, because this model is descriptive, namely a procedure that outlines the steps that must be followed in producing a product. The validation score results from media experts on the product as a whole aspect are "Very Good" with a percentage of 86% and PJOK Teachers are "Very Good" with a percentage of 91%. The final product in this research is a website-based Indonesian fitness test application to make it easier for students to carry out fitness tests independently.

The purpose of this study was determine public awareness of mental health services as well as effective community counseling strategies to improve mental health literacy. The research method used a cross-sectional surveycross-sectional survey. The research used was conducted on 339 respondents with an age range of 13-50 years. The sampling was done by non-probability sampling technique. Data were collected using a community awareness instrument for mental health services. The instrument for detecting has high reliability with a Cronbach's Alpha value of 0.726. Data collection implements an internet-based survey through the account Sobat Konseling and processes it online. Descriptive analysis was used to calculate the presentation of data. The results showed that a total of 240 (70.79%) respondents consider mental health important, and 323 respondents said they care about their own health, 108 respondents (31.86%) can identify the health symptoms they are experiencing. Individuals who have high literacy about health tend to have good self-care. It is known from to the results of this study, 256 respondents (75.5%) read information about mental health and 185 respondents (57.52%) understood the symptoms of mental health disorders. Some were able to identify symptoms of mental disorders in themselves. However, it is necessary to increase mental health literacy in order to achieve a healthy mentality.

Abdulelah Sameer Sindi,1 Rashmi Mittal,2,3 Khurshid Mattoo,3,4 Anchal Deep,3,5 Shafait Ullah Khateeb,1 Youssef Abdullah Algarni,1 Suheel Manzoor Baba,1,6 Areej M Hakami7 1Department of Restorative Dental Sciences, College of Dentistry, King Khalid University, Abha, 61421, Kingdom of Saudi Arabia; 2Department of Prosthodontics, S. R. Aggarwal Dental Clinic, Badaut, Uttar Pradesh, 250611, India; 3Department of Prosthodontics, Subharti Dental College and Hospital, Swami Vivekananda Subharti University, Uttar Pradesh, 250005, India; 4Department of Prosthetic Dental Sciences, College of Dentistry, Jazan University, Jazan, 45142, Kingdom of Saudi Arabia; 5Department of Prosthodontics, IDEAS Dental College, Madhya Pradesh Medical Science University, Madhya Pradesh, 482003, India; 6Department of Restorative Dentistry, Subharti Dental College and Hospital, Swami Vivekananda Subharti University, Uttar Pradesh, 250005, India; 7Department of Prosthodontics, College of Dentistry, Jazan University, Jazan, 45142, Kingdom of Saudi ArabiaCorrespondence: Khurshid Mattoo, Department of Prosthetic Dental Sciences, College of Dentistry, Jazan University, Jazan, 45142, Kingdom of Saudi Arabia, Tel +966595086078, Fax +960173295000, Email drkamattoo@rediffmail.comBackground: Patients health education by healthcare workers has been affected by pandemic guidelines. This study aimed to evaluate the influence of an audio-mediated intervention for patient health education (PHE) on treatment compliance and treatment satisfaction among patients seeking prosthodontic treatment during the Covid pandemic.Methods: A total of 666 patients (aged 40– 70 years) who fulfilled the study criteria were treated for denture-associated disease. PHE for 5 different categories was performed using an educational audio (MP3) in the experimental group (Group E), and traditional methods (oral/verbal) in the control group (Group C). Patient/clinician satisfaction with the PHE program was evaluated with a pre-validated questionnaire, whereas treatment compliance and satisfaction were evaluated using a denture hygiene index (DHI) and a visual analog scale (VAS). Differences between qualitative variables were determined using the chi-square test, whereas continuous variables were assessed using an unpaired t-test. Differences were considered to be statistically significant at p ≤ 0.05.Results: Patient satisfaction with PHE was significantly higher and differed in the Group E for two parameters: education method (80%), educational material (94%). For all parameters of procedural education, patient/clinician satisfaction was significantly higher for Group E [method (93%), material (85%), patient preparation (89%), personalized education (84%), program (93%)]. From three different ratings of disease education, 70% in Group E rated education as “effective” as compared to 41% in the Group C. Effectiveness of post treatment, education measured through DHI, revealed a lower hygiene score in Group E (m = 1.18) as compared to Group C (m = 2.92), with differences being significant. For treatment satisfaction, patients in Group E rated higher for speech (m = 8.21), ease of chewing (m = 7.36), and general satisfaction (m = 7.9).Conclusion: This study concluded that using audio as a means of imparting PHE positively influences the treatment compliance and satisfaction among outpatients and overcomes the drawback of wearing mask during the pandemic.Keywords: patient education, prosthodontics, treatment satisfaction, denture hygiene, multimedia, patient compliance

Abstract Background Among individuals experiencing homelessness, the prevalence of alcohol use disorder is extremely high. Alcohol-related harms are compounded by the use of non-beverage alcohol (NBA; e.g. rubbing alcohol, cooking wine). The dangers of NBA consumption pose significant risks to the individual and to others when consumed in large quantities and when mixed with other substances. The objectives of this paper are to describe the alcohol consumption patterns of individuals experiencing homelessness, identify substance use patterns, psychological stressors, and related harms associated with NBA consumption, and compare NBA consumers to non-NBA consumers in relation to their use of services and perceived barriers to care. Methods Using a cross-sectional survey, 150 individuals experiencing homelessness were recruited from Edmonton’s inner city and adjoining areas. Frequency, quantity, and volume of alcohol consumption were used to assess patterns of alcohol use in the last 6 months. Descriptive statistics and bivariate analyses were used to compare participants reporting NBA consumption and non-NBA consumption (p ≤ 0.05). Results The majority of participants were male (71.3%) and self-identified as Indigenous (74.0%). Overall, 24% (n = 36) reported NBA consumption within the last six months. NBA consumers were older than non-NBA consumers (p = 0.005), reported different perceived living stability (p = 0.022), and had higher psychological distress (p = 0.038). The majority of NBA consumers reported not receiving harm reduction services while also not needing such services (n = 18, 51.4%), which differed from non-NBA consumers (p = 0.003). Structural barriers (e.g. availability, location, cost) were most frequently reported as reasons for unmet harm reduction (60.9%) and hospital care (58.3%) needs, while barriers to skills training (58.5%) and counselling services (53.6%) were mostly motivational (e.g. personal beliefs). Conclusions Within such an already marginalized population experiencing homelessness, individuals who consume NBA represent a vulnerable subpopulation who require adapted and distinct health and social services to stabilize and recover. Current harm reduction services are not prepared to effectively assist this group of individuals, and specific treatment programs are rare. Managed alcohol programs are a feasible approach but must be tailored to the specific needs of those who consume NBA, which is especially important for Indigenous people. More comprehensive assessments of NBA consumption are needed for program development and policy recommendations.

Khaled Hosny,1– 3 Hani Asfour,4 Waleed Rizg,1– 3 Nabil A Alhakamy,1– 3 Amal Sindi,5 Hala Alkhalidi,6 Walaa Abualsunun,1 Rana Bakhaidar,1 Alshaimaa M Almehmady,1 Sara Akeel,5 Sarah Ali,5 Adel Alghaith,7 Sultan Alshehri,7 Rasha Khallaf8 1Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; 2Center of Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 3Advanced Drug Delivery Research Group, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 4Department of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 5Oral diagnostic sciences department, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia; 6Department of Clinical pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; 7Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; 8Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62511, EgyptCorrespondence: Khaled HosnyDepartment of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi ArabiaTel +966 561682377Email elswaify2000@yahoo.com; kmhomar@kau.edu.saIntroduction: Natural oil-based nanoemulsions (NEs) have been widely investigated in many diseases that affect the oral cavity. NEs are delivery systems that enhance the solubility of lipid therapeutics and improve their delivery to target sites; they are known as self-nanoemulsifying drug delivery systems (SNEDDSs). The current investigation’s aim was to produce an oregano essential oil-based nanoemulsion (OEO-SNEDD) that would have antibacterial and antifungal effects against oral microbiota and improve oral health.Methods: Several OEO-SNEDDSs were developed using different percentages of OEO (10%, 14%, and 18%), percentages of a surfactant mixture Pluracare L64:Lauroglycol FCC (18%, 32%, and 36%), Smix ratios (1:2, 1:1, and 2:1), and hydrophilic-lipophilic balances (HLBs) of the surfactant mixture (8, 10, and 12) using the Box‒Behnken design. The optimized concentration of excipients was determined using a pseudoternary phase diagram to obtain the NEs. The formulations were evaluated for their droplet size, stability index, and antibacterial and antifungal activities.Results: The NEs had a droplet size of 150 to 500 nm and stability index of 47% to 95%, and the produced formulation reached antibacterial and antifungal inhibition zones of up to 19 and 17 mm, respectively. The Box‒Behnken design was adopted to get the optimum formulation, which was 18% OEO, 36% Smix, 10.29 HLB of Smix, and a 1.25:1 Smix ratio. The optimized formulation had a lower ulcer index compared with various other formulations evaluated in rats.Conclusion: This study illustrated that OEO-SNEDDSs can provide good protection against oral microbial infections.Keywords: oregano essential oil, nanoemulsion, Box‒Behnken design, ulcer index, required HLB, carvacrol, thymol, stability index

The Covid-19 pandemic has hit the whole world, including Indonesia. This has an impact on various activities, one of which is the learning process, so the process must be done virtually. Therefore, learning alternatives are needed so that students feel interested in learning using the Connected Mathematics Project (CMP) model. This study aims to describe the learning interest of students using LKPD with the CMP model during the Covid-19 pandemic. This research is a descriptive qualitative research. The subjects of this study were students of junior high school class VIII as many as 22 students who were randomly selected in one school. The instrument used in this study was a learning interest questionnaire which was distributed via distributed google form which contained 19 questions as a reference to determine student’s learning interest using the LKPD with the CMP model. The data analysis technique used is qualitative analysis. The results of the study showed that there was a positive impact on students' learning interest, seen from the average percentage of the indicator was 80.09% with a good category. Then for each indicator there are two indicators with very good categories, and four indicators with good criteria. Based on the results of this study, it can be concluded that students have a good interest in learning using LKPD with the CMP model.

Nada A Alhindi, Amal M Sindi, Nada O Binmadi, Wael Y Elias Oral Diagnostic Science Department, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia Background: Oral and maxillofacial lesions (OMFL) comprise a broad spectrum of benign and malignant lesions that affect the oral cavity. However, few epidemiological studies have evaluated oral cavity lesions, and very few have focused on oral soft tissue pathology. The purpose of this study was to identify the prevalence and distribution of OMFL that had been diagnosed histologically at the Oral Pathology Laboratory, Faculty of Dentistry, King Abdulaziz University. Materials and methods: A retrospective study was conducted to assess the distribution of OMFL among the oral cavity biopsies submitted to the Oral Pathology Laboratory during the period from 1996 to 2016. Information on sex, age, location of the lesion, and histopathologic diagnosis was analyzed. Results: A total of 1,218 cases were examined. Among these, reactive/adaptive lesions were the most common type (n=245; 20.1%) and cystic lesions were the second most common (n=214; 17.6%), followed by inflammatory lesions (n=152; 12.5%) and epithelial pathology (n=115; 9.4%). Conclusion: The results of the present study provide valuable information on the prevalence of OMFL in Jeddah, Saudi Arabia. Reactive conditions were the most frequently diagnosed pathologies. Most oral and maxillofacial biopsies were soft tissue lesions, benign in nature, and inflammatory in origin. Further studies are necessary to provide more information on head and neck diseases in the general population to develop better future oral health policies. Keywords: oral and maxillofacial pathology, Saudi Arabia, Jeddah, oral lesions

UNLABELLED: Coccidioidomycosis, also known as Valley fever, is a disease caused by the fungal pathogen Coccidioides. Unfortunately, patients are often misdiagnosed with bacterial pneumonia, leading to inappropriate antibiotic treatment. The soil Bacillus subtilis-like species exhibits antagonistic properties against Coccidioides in vitro; however, the antagonistic capabilities of host microbiota against Coccidioides are unexplored. We sought to examine the potential of the tracheal and intestinal microbiomes to inhibit the growth of Coccidioides in vitro. We hypothesized that an uninterrupted lawn of microbiota obtained from antibiotic-free mice would inhibit the growth of Coccidioides, while partial in vitro depletion through antibiotic disk diffusion assays would allow a niche for fungal growth. We observed that the microbiota grown on 2×GYE (GYE) and Columbia colistin and nalidixic acid with 5% sheeps blood agar inhibited the growth of Coccidioides, but microbiota grown on chocolate agar did not. Partial depletion of the microbiota through antibiotic disk diffusion revealed diminished inhibition and comparable growth of Coccidioides to controls. To characterize the bacteria grown and identify potential candidates contributing to the inhibition of Coccidioides, 16S rRNA sequencing was performed on tracheal and intestinal agar cultures and murine lung extracts. We found that the host bacteria likely responsible for this inhibition primarily included Lactobacillus and Staphylococcus. The results of this study demonstrate the potential of the host microbiota to inhibit the growth of Coccidioides in vitro and suggest that an altered microbiome through antibiotic treatment could negatively impact effective fungal clearance and allow a niche for fungal growth in vivo. IMPORTANCE: Coccidioidomycosis is caused by a fungal pathogen that invades the host lungs, causing respiratory distress. In 2019, 20,003 cases of Valley fever were reported to the CDC. However, this number likely vastly underrepresents the true number of Valley fever cases, as many go undetected due to poor testing strategies and a lack of diagnostic models. Valley fever is also often misdiagnosed as bacterial pneumonia, resulting in 60%-80% of patients being treated with antibiotics prior to an accurate diagnosis. Misdiagnosis contributes to a growing problem of antibiotic resistance and antibiotic-induced microbiome dysbiosis; the implications for disease outcomes are currently unknown. About 5%-10% of symptomatic Valley fever patients develop chronic pulmonary disease. Valley fever causes a significant financial burden and a reduced quality of life. Little is known regarding what factors contribute to the development of chronic infections and treatments for the disease are limited.

King Abdulaziz University provides its educational services to over 180 thousand students. The number of vehicles entering and existing the university’s reached 350 thousand vehicles per day; Based on that, the transportation network within and around the campus experiences high vehicles delay. The first step to deal with the issue is by developing a conceptual travel demand modelling framework, which set the map for developing the travel demand models. This research presents a conceptual travel demand modelling framework, which is divided into four stages: define the evaluation time period (short, mid, long time span), establish a data collection program, prioritize transportation issues at campus, and model the transportation issues and propose solutions. The university has various departments. Each one contributes to the transportation movement by one way or the other. The framework incorporates these departments in the modelling framework with the aid of technology with the aim of relieving the pressure on the university’s transportation network in a timely manner and with minimum cost. Implementation of this modelling framework showed that management strategies supported with specialized transportation studies will accomplish that aim, while in the same time, it will ensure a sustainable transportation system, and improve the quality of life.

Background: Homeless individuals with mental illness are challenging to recruit and retain in longitudinal research studies. The present study uses information from the Vancouver site of a Canadian multi-city longitudinal randomized controlled trial on housing first interventions for homeless individuals. We were able to recruit 500 participants and retain large number of homeless individuals with mental illness; 92% of the participants completed the 6-month follow up interview, 84% the 24-month follow up, while 80% completed all follow-up visits of the study. Purpose: In this article, we describe the strategies and practices that we considered as critical for successful recruitment and retention or participants in the study. Methods: We discuss issues pertaining to research staff hiring and training, involvement of peers, relationship building with research participants, and the use of technology and social media, and managing challenging situations in the context of recruitment and retention of marginalized individuals. Conclusions: Recruitment and retention of homeless participant with mental illness in longitudinal studies is feasible. It requires flexible, unconventional and culturally competent strategies. Longitudinal research projects with vulnerable and hidden populations may benefit from extensive outreach work and collaborative approaches that are based on attitudes of mutual respect, contextual knowledge and trust. Keywords: Housing first intervention, Homelessness, Mental illness, Recruitment, Retention, Longitudinal study

Abstract Alzheimer’s disease (AD) is a progressive neurodegenerative condition marked by cognitive deterioration and changes in behavior. Acetylcholinesterase (AChE), which hydrolyzes acetylcholine, is a key drug target for treating AD. This research aimed to identify new AChE inhibitors using the IMPPAT database. We used known drugs as a basis to search for similar chemicals in the IMPPAT database and created a library of 127 plant-based compounds. Initial screening of these compounds was performed using molecular docking, followed by an analysis of their drug-likeness and ADMET properties. Compounds with favorable properties underwent density functional theory (DFT) calculations to assess their electronic properties such as HOMO-LUMO gap, electron density, and molecular orbital distribution. These descriptors provided insights into each compound’s reactivity, stability, and binding potential with AChE. Promising candidates were further evaluated through molecular dynamics (MD) simulations over 100 ns and MMPBSA analysis for the last 30 ns. Two compounds, Biflavanone (IMPHY013027) with a binding free energy of − 130.394 kcal/mol and Calomelanol J (IMPHY007737) with − 107.908 kcal/mol, demonstrated strong binding affinities compared to the reference molecule HOR, which has a binding free energy of − 105.132 kcal/mol. These compounds exhibited promising drug-ability profiles in both molecular docking and MD simulations, indicating their potential as novel AChE inhibitors for AD treatment. However, further experimental validation is necessary to verify their effectiveness and safety.

Colombia posee gran diversidad de plantas medicinales, pero pocas han sido objeto de investigación. En este trabajo se evaluó la actividad antiproliferativa de aceites esenciales obtenidos por hidrodestilación asistida por microondas. Se analizaron 15 muestras de 11 especies en ensayos del MTT en células cancerosas MCF-7, HeLa y HepG-2 y se incluyeron células normales humanas (HEK293) y de animales (Vero y BF16F10) para evaluar selectividad. La composición química de muestras activas se determinó por cromatografía de gases acoplada a espectrometría de masas (GC-MS). Aceites esenciales de cuatro especies mostraron actividad antiproliferativa (CI50: 50 μg/mL) en células HeLa y/o MCF-7, en el siguiente rango (índice de selectividad en paréntesis): Piper cumanense H.B.K. (4,7) > Piper subflavum var. espejuelanum C.DC (3,9) > Salvia officinalis L. (3,6) > Piper eriopodom (Miq.) C. DC. (3,1). Ninguna muestra fue activa en células HepG-2. El análisis por CG-MS identificó β-cariofileno, α-copaeno, β-pineno, α-pineno y linalol como componentes mayoritarios. Los aceites esenciales activos pueden ser punto de partida para desarrollo de medicamentos herbales para cuidado paliativo del cáncer.

Blood coagulation is a vital physiological process involving a complex network of biochemical reactions, which converge to form a blood clot that repairs vascular injury. This process unfolds in three phases: initiation, amplification, and propagation, ultimately leading to thrombin formation. Coagulation begins when tissue factor (TF) is exposed on an injured vessel's wall. The first step is when activated factor VII (VIIa) in the plasma binds to TF, forming complex TF:VIIa, which activates factor X. Activated factor X (Xa) is necessary for coagulation, so the regulation of its activation is crucial. Tissue Factor Pathway Inhibitor (TFPI) is a critical regulator of the initiation phase as it inhibits the activation of factor X. While previous studies have proposed two pathways-direct and indirect binding-for TFPI's inhibitory role, the specific biochemical reactions and their rates remain ambiguous. Many existing mathematical models only assume an indirect pathway, which may be less effective under physiological flow conditions. In this study, we revisit datasets from two experiments focused on activated factor X formation in the presence of TFPI. We employ an adaptive Metropolis method for parameter estimation to reinvestigate a previously proposed biochemical scheme and corresponding rates for both inhibition pathways. Our findings show that both pathways are essential to replicate the static experimental results. Previous studies have suggested that flow itself makes a significant contribution to the inhibition of factor X activation. We added flow to this model with our estimated parameters to determine the contribution of the two inhibition pathways under these conditions. We found that direct binding of TFPI is necessary for inhibition under flow. The indirect pathway has a weaker inhibitory effect due to removal of solution phase inhibitory complexes by flow.

Background: In healthy individuals, plasma levels of clotting proteins naturally vary within a range of 50% to 150% of their mean values. We do not know how these variations modify thrombin generation. Objectives: To assess the impact of protein level variations on simulated thrombin generation in normal and factor (F)VIII-, FIX-, or FXI-deficient blood. Methods: We used a mathematical model of flow-mediated coagulation to simulate thrombin generation with all possible combinations of clotting protein variations within the normal range and for various tissue factor levels. We selected, analyzed, and ranked combinations that enhanced thrombin generation compared with baseline. Results: Protein variations most strongly affected thrombin generation at intermediate tissue factor levels. Low tissue factor levels prevented coagulation initiation, while high tissue factor levels always triggered thrombin generation. At intermediate levels, we identified protein variations that substantially modified thrombin generation. Low-normal FV shortened lag times and increased thrombin generation, whereas high-normal FV lengthened lag times and reduced thrombin generation. With severe FVIII and FIX deficiencies, low-normal tissue factor pathway inhibitor α and antithrombin amplified the effect of low-normal FV. For moderate FVIII and FIX deficiencies, high-normal tissue factor pathway inhibitor α and antithrombin enhanced the impact of high-normal FV in reducing thrombin production. In normal and FXI-deficient blood, high-normal FVIII and FIX significantly boosted thrombin generation. Conclusion: Our mathematical model predicted how variations in clotting protein levels, within the normal range, could contribute to the variability of bleeding phenotypes observed with clotting factor deficiencies. Our study generated experimentally testable hypotheses that could aid in developing new therapies toward normal hemostasis.

Antecedentes: Conocer la tendencia de productos de plantas a causar toxicidad en humanos es parte de la investigación orientada al descubrimiento de un medicamento natural. Las pruebas en animales son relativamente costosas, de bajo rendimiento, asociadas a sufrimiento del animal y diferencias relativas a la especie hacen difícil inferir efectos en humanos. Las pruebas en célula viva son recomendadas. Objetivo: Estudiar la tendencia a toxicidad de aceites esenciales (AE) de plantas de Colombia usando un ensayo basado en célula. Método: Los AE de 18 especies distintas de plantas fueron estudiados. Se usó el ensayo del MTT en seis líneas celulares de humano y animal derivadas de tejido normal y canceroso, las cuales se trataron antes y después de la proliferación. Los AE se organizaron en el orden de una agrupación jerárquica con base en los valores de CC50 y la sumatoria de la jerarquía ponderada en el panel de células (ΣJPi ) se usó como indicador de similitud. Cuanto mayor fue el valor de ΣJPi menor fue la tendencia a toxicidad. Resultados: Los AE con valores de CC50 > 200 µg/mL en al menos cinco condiciones experimentales presentaron valores de ΣJPi > 6,0 sugiriendo baja tendencia a toxicidad y fueron en orden descendente (ΣJPi en paréntesis): Calycolpus moritzianus (O.Berg) Burret (9,7) < Psidium sartorianum (O. Berg) Nied. (8,9) < Wedelia calycina (6,5) < Lippia micromera Schauer (6,2) ≈ Piper haltonii . (6,2). AE con valores de CC50 < 100 µg/mL en cuatro o más condiciones experimentales presentaron valores ΣJPi < 4.0 sugiriendo alta tendencia a toxicidad y fueron en orden ascendente: Tagetes caracasana Kunth (2,7 – 2,8) > Chromolaena odorata (L.) R.M.King & H.Rob. (3,0) > Ageratina aff. popayanensis (Hieron.) R.M.King & H.Rob. (3,1) > Lantana colombiana López-Pal.(3,3) >Turnera disffusa. (3,4). AE de Tagetes caracasana presentó actividad antiproliferante (CI50: 42,2 y 47,9 µg/mL) sobre células humanas de cáncer de cérvix. Conclusión: El abordaje metodológico permitió identificar AE con baja y alta tendencia a toxicidad. Los resultados podrían tener valor para predecir actividad in vivo y priorizar muestras para futuras investigaciones.

RNA-sequencing (RNA-seq) is a gold-standard method to profile genome-wide changes in gene expression. RNA-seq uses high-throughput sequencing technology to quantify the amount of RNA in a biological sample. With the increasing popularity of RNA-seq, many variations on the protocol have been proposed to extract unique and relevant information from biological samples. 3' Tag-Seq (also called TagSeq, 3' Tag-RNA-Seq, and Quant-Seq 3' mRNA-Seq) is one RNA-seq variation where the 3' end of the transcript is selected and amplified to yield one copy of cDNA from each transcript in the biological sample. We present a simple, easy-to-use, and publicly available computational workflow to analyze 3' Tag-Seq data. The workflow begins by trimming sequence adapters from raw FASTQ files. The trimmed sequence reads are checked for quality using FastQC and aligned to the reference genome, and then read counts are obtained using STAR. Differential gene expression analysis is performed using DESeq2, based on differential analysis of gene count data. The outputs of this workflow are MA plots, tables of differentially expressed genes, and UpSet plots. This protocol is intended for users specifically interested in analyzing 3' Tag-Seq data, and thus normalizations based on transcript length are not performed within the workflow. Future updates to this workflow could include custom analyses based on the gene counts table as well as data visualization enhancements. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol: Running the 3' Tag-Seq workflow Support Protocol: Generating genome indices.

In response to the COVID-19 pandemic, many higher educational institutions moved their courses on-line in hopes of slowing disease spread. The advent of multiple highly-effective vaccines offers the promise of a return to "normal" in-person operations, but it is not clear if-or for how long-campuses should employ non-pharmaceutical interventions such as requiring masks or capping the size of in-person courses. In this study, we develop and fine-tune a model of COVID-19 spread to UC Merced's student and faculty population. We perform a global sensitivity analysis to consider how both pharmaceutical and non-pharmaceutical interventions impact disease spread. Our work reveals that vaccines alone may not be sufficient to eradicate disease dynamics and that significant contact with an infectious surrounding community will maintain infections on-campus. Our work provides a foundation for higher-education planning allowing campuses to balance the benefits of in-person instruction with the ability to quarantine/isolate infectious individuals.

Genetic regulatory networks (GRNs) regulate the flow of genetic information from the genome to expressed messenger RNAs (mRNAs) and thus are critical to controlling the phenotypic characteristics of cells. Numerous methods exist for profiling mRNA transcript levels and identifying protein-DNA binding interactions at the genome-wide scale. These enable researchers to determine the structure and output of transcriptional regulatory networks, but uncovering the complete structure and regulatory logic of GRNs remains a challenge. The field of GRN inference aims to meet this challenge using computational modeling to derive the structure and logic of GRNs from experimental data and to encode this knowledge in Boolean networks, Bayesian networks, ordinary differential equation (ODE) models, or other modeling frameworks. However, most existing models do not incorporate dynamic transcriptional data since it has historically been less widely available in comparison to "static" transcriptional data. We report the development of an evolutionary algorithm-based ODE modeling approach (named EA) that integrates kinetic transcription data and the theory of attractor matching to infer GRN architecture and regulatory logic. Our method outperformed six leading GRN inference methods, none of which incorporate kinetic transcriptional data, in predicting regulatory connections among TFs when applied to a small-scale engineered synthetic GRN in Saccharomyces cerevisiae. Moreover, we demonstrate the potential of our method to predict unknown transcriptional profiles that would be produced upon genetic perturbation of the GRN governing a two-state cellular phenotypic switch in Candida albicans. We established an iterative refinement strategy to facilitate candidate selection for experimentation; the experimental results in turn provide validation or improvement for the model. In this way, our GRN inference approach can expedite the development of a sophisticated mathematical model that can accurately describe the structure and dynamics of the in vivo GRN.

La finalidad de los diseños óptimos es determinar las condiciones experimentales adecuadas de tal forma que se pueda garantizar inferencias estadísticas lo más precisas posibles en términos de mínima varianza. Esta teoría presupone el conocimiento de la función que relaciona las variables explicativas con la variable respuesta, en esta situación, por lo general, se obtienen diseños con tantos puntos de soporte como parámetros tiene el modelo propuesto. Dado que los diseños con $p-$puntos de soporte asumen que la función del modelo es conocida, éstos pueden llegar a ser no tan óptimos en algunas situaciones prácticas, debido a que no permiten probar la bondad de ajuste del modelo asumido [1]. En este artículo se presenta una generalización de la metodología propuesta en [2] para aumentar el número de puntos en el criterio D-optimalidad. Se encuentra una expresión para la varianza de la respuesta predicha en términos de una constante de ponderación delta, la cual permitirá determinar los puntos a adicionar al diseño D-óptimo. Se propone una estrategia para la elección de la constante delta. Finalmente se proporciona un diseño seudo-óptimo con p + s puntos de experimentación. MSC: 62K05

IntroductionChronic hepatitis B virus (HBV) infection is an increasing cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected individuals. HIV-positive patients are commonly co-infected with HBV due to shared routes of transmission.ObjectivesOur aim was to determine the risk factors, prevalence, genotypes, and mutations of the Surface S gene of HBV, and occult hepatitis B infection (OBI) among patients infected with HIV in a northeastern Colombian city.MethodsA cross-sectional study was conducted with 275 HIV-positive patients attending an outpatient clinic in Bucaramanga, Colombia during 2009-2010. Blood samples were collected and screened for serological markers of HBV (anti-HBs, anti-HBc and HBsAg) through ELISA assay. Regardless of their serological profile, all samples were tested for the HBV S gene by nested-PCR and HBV genotypes were determined by phylogenetic inference. Clinical records were used to examine demographic, clinical, virological, immunological and antiretroviral therapy (ART) variables of HIV infection.ResultsParticipants were on average 37±11 years old and 65.1% male. The prevalence of HIV-HBV coinfection was 12% (95%CI 8.4-16.4) of which 3.3% had active HBV infection and 8.7% OBI. The prevalence of HIV-HBV coinfection was associated with AIDS stage and ART treatment. Sequence analysis identified genotype F, subgenotype F3 in 93.8% of patients and genotype A in 6.2% of patients. A C149R mutation, which may have resulted from failure in HBsAg detection, was found in one patient with OBI.ConclusionsThe present study found a high prevalence of HIV-HBV coinfection with an incidence of OBI 2.6-fold higher compared to active HBV infection. These findings suggest including HBV DNA testing to detect OBI in addition to screening for HBV serological markers in HIV patients.

Menu engineering (ME) is a step-by-step process wich is designed to help management in evaluating the current and future menu pricing, menu composition and to set decisions about price and menu. The main objectives of ME are tomake the next menu more profitable and to attract of guest’s attention. It has two critical aspect, that are contribution margin/CM (related to profit) and menu mix/MM (related to an item popularity rate amoing other item). The combination of CM and MM wll result in an item classification (star, plowhorse, question and dog), so that management can design the decision alternatives related to menu item.From the ME application for four months, Bengawan Solo Restaurant has 10 star item menu, 13 qustion items, 2 plowhorse items and 9 dog items. In this case, selling technique performed by waiters and waitresses also influence the ME result. The menegement concerns about the physical presentation and kitchen location. The quality handling should not only be conducted physically, but also pay more attention to halal aspect and food safety or HACCP (hazard analysis and certical control point), in order to produce high quality product that are safe to be consumed.