Miracle-dz/UniFAR-FTUs huggingface dataset:
The Lrat−/− Rat: CRISPR/Cas9 Construction and Phenotyping of a New Animal Model for Retinitis Pigmentosa

Purpose: We developed and phenotyped a pigmented knockout rat model for lecithin retinol acyltransferase (LRAT) using CRISPR/Cas9. The introduced mutation (c.12delA) is based on a patient group harboring a homologous homozygous frameshift mutation in the LRAT gene (c.12delC), causing a dysfunctional visual (retinoid) cycle. Methods: The introduced mutation was confirmed by DNA and RNA sequencing. The expression of Lrat was determined on both the RNA and protein level in wildtype and knockout animals using RT-PCR and immunohistochemistry. The retinal structure and function, as well as the visual behavior of the Lrat−/− and control rats, were characterized using scanning laser ophthalmoscopy (SLO), optical coherence tomography (OCT), electroretinography (ERG) and vision-based behavioral assays. Results: Wildtype animals had high Lrat mRNA expression in multiple tissues, including the eye and liver. In contrast, hardly any expression was detected in Lrat−/− animals. LRAT protein was abundantly present in wildtype animals and absent in Lrat−/− animals. Lrat−/− animals showed progressively reduced ERG potentials compared to wildtype controls from two weeks of age onwards. Vison-based behavioral assays confirmed reduced vision. Structural abnormalities, such as overall retinal thinning, were observed in Lrat−/− animals. The retinal thickness in knockout rats was decreased to roughly 80% by four months of age. No functional or structural differences were observed between wildtype and heterozygote animals. Conclusions: Our Lrat−/− rat is a new animal model for retinal dystrophy, especially for the LRAT-subtype of early-onset retinal dystrophies. This model has advantages over the existing mouse models and the RCS rat strain and can be used for translational studies of retinal dystrophies.
Studies on behavior of suspension of silica nanoparticle in aqueous polyacrylamide solution for application in enhanced oil recovery

ABSTRACT The use of nanoparticle/polymer suspension for high-temperature and high-saline reservoir was investigated by measuring rheological properties and characterizing the interaction between polymer and nanoparticle. Polyacrylamide (PAM) and silica nanoparticle were used in this study. The result indicates that silica/PAM suspension have higher viscosity and viscosity retention was improved in the presence of salt and at high temperature as compared to simple PAM solution. Improved performance was attributed to the formation of complex macromolecular structure. PAM gets adsorbed on the surface of silica due to hydrogen bonding and the silica particle act as physical cross-linker between polymeric chains, resulting in improvement of viscosity.
Comparison of Two Types of Pit and Fissure Sealants in Reducing the Incidence of Dental Caries Using a Split-Mouth Design

Objectives To evaluate the effectiveness of two pit and fissure sealants (PFS) in reducing the incidence of dental caries in schoolchildren. Material and Methods A randomized split-mouth experimental design was used in a sample of 140 subjects assigned to two groups. The sealants used were Clinpro©3M and BeautiSealant©Shofu placed in first permanent molars (FPMs). Each sealant was compared to molars in the controls to determine effectiveness over a period of 6 months. The study had a 12.9% loss to follow-up. No statistically significant differences (p>0.05) were observed for sex, age, baseline dmft, or type of sealants. Nonparametric tests were used for statistical analysis. Results Average dmft index at baseline was 4.10±3.16. Lower incidence of caries was observed in FPMs with pit and fissure sealants (p<0.01), regardless of the type used. When sealants remained intact there was a lower caries incidence compared to sealants partially or completely missing – but differences were only significant for FPM 16. Caries incidence was higher for BeautiSealant sealed teeth than for Clinpro’s, but only statistically significant in FPMs 16, 36 and 46 (p< 0.05). Caries incidence was higher in those cases with a higher baseline dmft but it only reached statistical significance in FPMs 26 and 36. Relative risks for dental caries were lower in sealed teeth (p<0.01). Conclusions Pit and fissures sealants are an effective preventive treatment to reduce caries during a 6-month follow-up in schoolchildren 6 to 8 years of age, regardless of the type of sealant used. The sealant brand that showed greater effectiveness in terms of prevention and retention was Clinpro©3M.
β-LAPachone is renoprotective in streptozotocin-induced diabetic mice via regulating the PI3K/Akt/mTOR signaling pathway

Objective(s): β-LAPachone (B-LAP) is a natural product with established anti-inflammatory properties. In this study, we investigated the protective potential of B-LAP against diabetic nephropathy in streptozotocin (STZ) induced diabetic mice. Materials and Methods: Diabetes induction in mice was carried out by a single intraperitoneal injection of STZ. 2.5 mg/kg/day and 5 mg/kg/day doses of B-LAP were administered orally for twelve weeks and renal histoarchitecture, caspase-3, tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), glutathione peroxidase (GPX), as well as urinary nephrin and neutrophil gelatinase-associated lipocalin (NGAL) were evaluated. Additionally, kidney levels of PI3K, phosphorylated (p)-Akt, p-mTOR, p-CREB, and SIRT1 were assessed in the present investigation. Results: 5 mg/kg B-LAP significantly decreased urinary excretions of nephrin and NGAL. It also mitigated renal TNF-α and MDA levels and simultaneously improved GPX activities. 5 mg/kg B-LAP improved renal function in diabetic mice as indicated by elevated values of creatinine clearance. While B-LAP elevated renal levels of SIRT1, it alleviated PI3K, p-Akt, p-mTOR, and p-CREB levels in the kidneys of diabetic mice. Conclusion: Collectively, these findings suggest B-LAP as a potential renoprotective agent in STZ-induced diabetic mice probably via modulating the PI3K/Akt/mTOR pathway.
Inherited Retinal Diseases Due to RPE65 Variants: From Genetic Diagnostic Management to Therapy

Inherited retinal diseases (IRDs) are a heterogeneous group of conditions that include retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) and early-onset severe retinal dystrophy (EO[S]RD), which differ in severity and age of onset. IRDs are caused by mutations in >250 genes. Variants in the RPE65 gene account for 0.6–6% of RP and 3–16% of LCA/EORD cases. Voretigene neparvovec is a gene therapy approved for the treatment of patients with an autosomal recessive retinal dystrophy due to confirmed biallelic RPE65 variants (RPE65-IRDs). Therefore, the accurate molecular diagnosis of RPE65-IRDs is crucial to identify ‘actionable’ genotypes—i.e., genotypes that may benefit from the treatment—and is an integral part of patient management. To date, hundreds of RPE65 variants have been identified, some of which are classified as pathogenic or likely pathogenic, while the significance of others is yet to be established. In this review, we provide an overview of the genetic diagnostic workup needed to select patients that could be eligible for voretigene neparvovec treatment. Careful clinical characterization of patients by multidisciplinary teams of experts, combined with the availability of next-generation sequencing approaches, can accelerate patients’ access to available therapeutic options.
Understanding Uncontrolled Eating after Bariatric Surgery: The Role of Excessive Skin and Body Image Shame

Excess skin and disordered eating behaviors are referred to as some of the major negative consequences of bariatric surgery as well as body image shame. This study sought to explore how discomfort with excessive skin, body image shame, psychological distress, eating-related psychopathology, and negative urgency interact to understand uncontrolled eating among woman submitted to bariatric surgery. A cross-sectional sample of 137 women was evaluated postoperatively through self-report questionnaires assessing discomfort with excess skin, body image shame, eating-related psychopathology, negative urgency, and uncontrolled eating in a hospital center in the north of Portugal. Pearson correlations and Structural Equation Modeling (SEM) were performed. Body image shame mediated the relationship between discomfort with excess skin and eating-related psychopathology. In turn, the relationship between eating-related psychopathology and uncontrolled eating was mediated by negative urgency. This study highlights the impact of excess skin and body image shame on eating behavior post-bariatric-surgery. Considering the proven impact of uncontrolled eating on weight-loss results post-surgery, understanding the mechanisms underlying this problem is highly important. Our findings provide helpful insight for multidisciplinary teams committed to providing care to bariatric patients struggling with body image and eating difficulties.
Citric Acid-Mediated Abiotic Stress Tolerance in Plants

Several recent studies have shown that citric acid/citrate (CA) can confer abiotic stress tolerance to plants. Exogenous CA application leads to improved growth and yield in crop plants under various abiotic stress conditions. Improved physiological outcomes are associated with higher photosynthetic rates, reduced reactive oxygen species, and better osmoregulation. Application of CA also induces antioxidant defense systems, promotes increased chlorophyll content, and affects secondary metabolism to limit plant growth restrictions under stress. In particular, CA has a major impact on relieving heavy metal stress by promoting precipitation, chelation, and sequestration of metal ions. This review summarizes the mechanisms that mediate CA-regulated changes in plants, primarily CA’s involvement in the control of physiological and molecular processes in plants under abiotic stress conditions. We also review genetic engineering strategies for CA-mediated abiotic stress tolerance. Finally, we propose a model to explain how CA’s position in complex metabolic networks involving the biosynthesis of phytohormones, amino acids, signaling molecules, and other secondary metabolites could explain some of its abiotic stress-ameliorating properties. This review summarizes our current understanding of CA-mediated abiotic stress tolerance and highlights areas where additional research is needed.
COVID-19 Vaccine–Related Discussion on Twitter: Topic Modeling and Sentiment Analysis

Background Vaccination is a cornerstone of the prevention of communicable infectious diseases; however, vaccines have traditionally met with public fear and hesitancy, and COVID-19 vaccines are no exception. Social media use has been demonstrated to play a role in the low acceptance of vaccines. Objective The aim of this study is to identify the topics and sentiments in the public COVID-19 vaccine–related discussion on social media and discern the salient changes in topics and sentiments over time to better understand the public perceptions, concerns, and emotions that may influence the achievement of herd immunity goals. Methods Tweets were downloaded from a large-scale COVID-19 Twitter chatter data set from March 11, 2020, the day the World Health Organization declared COVID-19 a pandemic, to January 31, 2021. We used R software to clean the tweets and retain tweets that contained the keywords vaccination, vaccinations, vaccine, vaccines, immunization, vaccinate, and vaccinated. The final data set included in the analysis consisted of 1,499,421 unique tweets from 583,499 different users. We used R to perform latent Dirichlet allocation for topic modeling as well as sentiment and emotion analysis using the National Research Council of Canada Emotion Lexicon. Results Topic modeling of tweets related to COVID-19 vaccines yielded 16 topics, which were grouped into 5 overarching themes. Opinions about vaccination (227,840/1,499,421 tweets, 15.2%) was the most tweeted topic and remained a highly discussed topic during the majority of the period of our examination. Vaccine progress around the world became the most discussed topic around August 11, 2020, when Russia approved the world’s first COVID-19 vaccine. With the advancement of vaccine administration, the topic of instruction on getting vaccines gradually became more salient and became the most discussed topic after the first week of January 2021. Weekly mean sentiment scores showed that despite fluctuations, the sentiment was increasingly positive in general. Emotion analysis further showed that trust was the most predominant emotion, followed by anticipation, fear, sadness, etc. The trust emotion reached its peak on November 9, 2020, when Pfizer announced that its vaccine is 90% effective. Conclusions Public COVID-19 vaccine–related discussion on Twitter was largely driven by major events about COVID-19 vaccines and mirrored the active news topics in mainstream media. The discussion also demonstrated a global perspective. The increasingly positive sentiment around COVID-19 vaccines and the dominant emotion of trust shown in the social media discussion may imply higher acceptance of COVID-19 vaccines compared with previous vaccines.
Cytological analysis of tracheal wash and bronchoalveolar lavage fluid in health and respiratory disease in dromedary camels

Background Tracheal wash (TW) and bronchoalveolar lavage (BAL) have proven to be useful tools for the identification of disease-associated changes in the respiratory tract in human and different animal species. In the dromedary camel, little is known about cytological analysis of TW and BAL in health and disease. The aim of the present study was to evaluate the cytological composition of TW and BAL in health and respiratory disease in dromedary camels. Methods TW and BAL samples were collected from dromedary camels and cytological analysis was performed by microscopic examination of prepared smears. Camels with clinical respiratory disease (n = 18) were compared with apparently healthy (control) camels (n = 9). Results In the apparently healthy camels, differential cytological analysis of TW samples identified macrophages and neutrophils as the main cell populations with lesser proportions of lymphocytes and epithelial cells and very rare abundance of eosinophils and mast cells. In the TW of camels with respiratory disease, neutrophils were the most abundant cells followed by macrophages and lymphocytes. In the BAL of healthy camels, macrophages represented the main cell type followed by lymphocytes and neutrophils. In respiratory-diseased camels, BAL samples contained higher percentages of neutrophils with reduced percentages of macrophages and lymphocytes in comparison to camels from the control group. Collectively, the results of the current study revealed higher abundance of neutrophils in the TW and BAL from dromedary camels than many other veterinary species. The cytological patterns of TW and BAL from camels with respiratory diseases were characterized by increased proportion of neutrophils and decreased proportion of macrophages in comparison to healthy camels. The proportion of lymphocytes was also decreased in TW samples from diseased camels.
The Sensitivity and Specificity of White Blood Cells and Nitrite in Dipstick Urinalysis in Association With Urine Culture in Detecting Infection in Adults From October 2016 to October 2019 at King Abdulaziz Medical City

Background Urinary tract infection (UTI) is one of the most common clinical presentations that exhaust the patients and confuse physicians. Some of the risk factors that contribute to UTIs are age, female gender, and diabetes. Urinalysis is used to detect abnormalities in the urine, such as the presence of leukocytes, blood, and nitrite. However, urinalysis accuracy depends on the patient and the analyzer. On the other hand, urine culture is considered gold standard for diagnosing UTI. For that, the aim of this study is to determine the sensitivity of white blood cells (WBC) and nitrite in dipstick urinalysis in detecting UTI. Methods A cross-sectional study was conducted at King Abdulaziz Medical City on adult patients aged 19-65 years who underwent dipstick urinalysis and culture at the same visit from October 2016 to October 2019. The data were collected from the medical records from all the departments by using a data collection sheet through Best Care system. The sample was selected conveniently, and it was determined to be 359 patients with a confidence interval of 95%. Data were analyzed using IBM SPSS version 20 (IBM Corp., Armonk, NY, USA). Chi-square test was used to analyze the association between the outcome and the results of the dipstick urinalysis and urine culture. P-value lower than 0.05 was considered significant. Results Three hundred and fifty-nine patients were included into the study with a majority of females (81.1%) with a mean age of 47.5 years. Two hundred and fifty-two patients were culture positive, WBC sensitivity and specificity were 62.7% and 100%, and nitrite sensitivity and specificity were 20.6% and 93.5%, respectively. Ninety-nine diabetic patients were culture positive; for diabetic patients, WBC sensitivity and specificity were 65.7% and 100% and nitrite sensitivity and specificity were 18.2% and 97.6%, respectively, while for non-diabetic patients, WBC sensitivity and specificity were 60.85% and 100% and nitrite sensitivity and specificity were 22.2% and 90.8%, respectively. Conclusion Our study showed that results of WBC are more sensitive and specific than those of nitrite in comparison to the gold standard (urine culture). Diabetics and non-diabetics have slightly different results. According to our results it is difficult to depend on the dipstick urinalysis without culture. More studies are recommended in this field.
Thismia sitimeriamiae (Thismiaceae), an extraordinary new species from Terengganu, Peninsular Malaysia

Abstract We describe an extraordinary new species in the genus Thismia from the Terengganu State of Malaysia in the Malay Peninsula. The new species, which we name Thismia sitimeriamiae, is distinct from all other Thismia species known to science, most notably in its unique mitre configuration formed by the inner tepals and its floral surface morphology characterised by conspicuous orange trichomes. We discuss our findings in the context of underestimated species diversity in the genus Thismia and implications for their conservation. We recommend assigning T. sitimeriamiae the conservation status as Critically Endangered (CR) according to IUCN criteria.
Content analysis of the official curriculum of undergraduate degree in Iran's medical sciences universities from the perspective of social health: A qualitative study

BACKGROUND: Social health is considered as an important part of good health both individually and socially. The purpose of this study was to examine the content of the official medical sciences curriculum in undergraduate degrees from a social health perspective. MATERIALS AND METHODS: This qualitative content analysis study was conducted in 2019 at the Isfahan University of Medical Sciences using a deductive approach based on Hsieh and Shannon's directed content analysis. For this purpose, official curricula in the fields of Public Health, Occupational Health, Environmental Health, Nursing, Midwifery, Nutrition Sciences, and Health Services Management were analyzed using MAXQDA 12. RESULTS: The results showed that a total of 136 codes related to the components of social health were identified in the topics of undergraduate medical sciences majors. Most to least relevant topics belonged to the fields of Public Health (61 codes), Midwifery (22 codes), Nursing (16 codes), Occupational Health (12 codes), Environmental Health and Nutrition Sciences (each 10 codes), and Health Services Management (5 codes), respectively. Among the components of social health, only the component related to access to insurance and health services was mentioned in all seven disciplines. However, the components of poverty and inequality were only included in three disciplines (Public Health, Nursing, Midwifery). CONCLUSION: Regarding insufficient focus on social health in curricula, revision of educational curricula is suggested from the perspective of social health, particularly in areas such as poverty and inequality, unemployment, population, violence, and gender discrimination.
Impact of Sodium–Glucose Co-Transporter 2 Inhibitors on Cardiac Protection

Sodium–glucose co-transporter 2 (SGLT2) inhibitors have been approved as a new class of anti-diabetic drugs for type 2 diabetes mellitus (T2DM). The SGLT2 inhibitors reduce glucose reabsorption through renal systems, thus improving glycemic control in all stages of diabetes mellitus, independent of insulin. This class of drugs has the advantages of no clinically relevant hypoglycemia and working in synergy when combined with currently available anti-diabetic drugs. While improving sugar level control in these patients, SGLT2 inhibitors also have the advantages of blood-pressure improvement and bodyweight reduction, with potential cardiac and renal protection. In randomized control trials for patients with diabetes, SGLT2 inhibitors not only improved cardiovascular and renal outcomes, but also hospitalization for heart failure, with this effect extending to those without diabetes mellitus. Recently, dynamic communication between autophagy and the innate immune system with Beclin 1-TLR9-SIRT3 complexes in response to SGLT2 inhibitors that may serve as a potential treatment strategy for heart failure was discovered. In this review, the background molecular pathways leading to the clinical benefits are examined in this new class of anti-diabetic drugs, the SGLT2 inhibitors.
Impaired Set-Shifting from Dorsal Stream Disconnection: Insights from a European Series of Right Parietal Lower-Grade Glioma Resection

Simple Summary Awake surgery with cognitive monitoring has increasingly been implemented to preserve brain networks and functionality. More recently, not only surgery in the left but also in the right hemisphere, i.c. , the parietal lobe, was associated with potential risk for deficits in cognitive functions, such as cognitive flexibility. We describe an explorative pilot study in an international consortium within clinical care as usual. Careful interpretation of our findings indicates that disconnection of the lateral part of the dorsal stream correlated with impaired set-shifting. More importantly, it illustrates the need for international collaboration on neuropsychological tests and methodologies to improve our understanding of white matter networks at risk during awake surgery. Abstract Awake surgery with cognitive monitoring has increasingly been implemented to preserve brain networks and functionality. More recently, not only surgery in the left but also in the right hemisphere, i.c. , the parietal lobe, was associated with potential risk for deficits in cognitive functions, such as cognitive flexibility. In this explorative pilot study, we compare cognitive performance more than three months after surgery with baseline measurements and explore the association between cognitive decline and subcortical tracts that may have been severed during surgery in the right hemisphere. Twenty-two patients who underwent surgery for a right parietal low-grade glioma were assessed pre- and postoperatively using the Trail Making Test and the Stroop task to administer set-shifting abilities and inhibition. Volume measurements and lesion–symptom mapping analyses were performed on postoperative MRI scans. Careful interpretation of the results shows a change in TMT performance and not on the Stroop Task when the lateral part of the arcuate fasciculus is damaged, indicating that disconnection of the lateral part of the dorsal stream might be correlated specifically with impaired set-shifting and not with inhibition. More importantly, this study underlines the need for international concertation to allow larger studies to increase power and perform more detailed analyses.