Comparison of efficacy of daily and alternate day maintenance treatment of GERD with Vonoprazan 10-mg using Gastroesophageal Reflux Disease Symptom Assessment Scale.

Objectives: To compare efficacy of 10-mg of vonoprazan daily & on alternate days by Gastroesophageal Reflux Disease Symptom Assessment Scale (GSAS). Method: This prospective interventional cohort was done at Department of Medicine/Gastroenterology Dow Medical College, Karachi, Pakistan during the period August 2022 & January 2023. Potential participants fulfilling inclusion and exclusion criteria were asked to fill out GSAS questionnaires after their written consent. Patients were allocated in to two groups using random tables. Group-A was given Tab Vonoprazan 10-mg daily for two weeks. Group-B was given Tab Vonoprazan 10-mg on alternate day. GSAS was scored by totaling scores across symptoms and then they are divided by the total number of non-missing symptom scores. Both groups were assessed week-0 & week-2. Results: Only 90 proformas that were completely filled were included, Group-A had 30 males and 15 females while Group-B had 29 males and 16 females. No significant difference in score was found in GSAS score at week-0 except that in item 'gurgling' while at week two there was no significant difference between any of the items. Total GSAS score were significantly lower at Week-2 than at week-0 (p = <.001). Conclusions: Vonoprazan of 10-mg on alternate day is equally effective as 10-mg daily in maintenance of GERD patients at two weeks.

Medical Students' Perceptions at Dow University of Health Sciences using Dundee Ready Education Environment Measure Inventory.

Objectives: To assess medical students' perceptions regarding learning, teachers, academics, atmosphere at campus and social self-perceptions at Dow University of Health Sciences using Dundee Ready Education Environment Measure (DREEM) Inventory. Method: This cross-sectional observational study was conducted from March 1st, 2022 to September 30th, 2022. All medical students at Dow University of Health Sciences were offered to participate. All students were given the choice to respond to DREEM questionnaire via online Form or printed copy anonymously. The DREEM Inventory measures five domains of students' perceptions of a given institution. Comparison of responses between different years and institution was carried out by χ2 test. Means scores were compared by Student's t-test and ANOVA, p-value of ≤.05 was taken as significant. Results: Total of 1054 out of 1750 (60.23%) students submitted fully completed forms and were included, out of these 632 (60.0%) belonged to Dow Medical College & 422 (40.0%) belonged to Dow International Medical College. The mean ±SD of total score of DREEM by DMC students was 100.07 ±31.46 and that of DIMC was 100.52 ±32.73. According to DREEM Global scoring both colleges scores fell into category of "many problems". Analysis according to domains showed that maximum score was given to 2nd domain of their "perception regarding teachers" and minimum score was allocated to 5th domain regarding "social self-perceptions". Conclusion: Overall Students perceived environment at DUHS as "many problems" category. This needs to be investigated for betterment of Educational Environment (EE) at campus.

Phytochemical characterization and phospholipase A2 inhibitory effect of Vitex negundo L. root extracts.

ETHNOPHARMACOLOGICAL RELEVANCE: Snake bites are a critical health issue in many parts of the world particularly in Asian countries lacking efficient health facilities in rural areas. Cobra is the most common snake type in Asia and is responsible for a large number of mortalities particularly in rural areas. Plants are usually considered the most effective and easy-to-approach treatment for snake bites in rural areas of various countries. Vitex negundo L. is an important medicinal plant traditionally used to treat snake bite envenomation in many countries of Asia. AIM OF THE STUDY: From literature survey of plants traditionally used in the treatment of snake bites in Asian countries including India, Pakistan and Sri Lanka, roots of V. negundo were selected for the present study. Anti-snake venom potential of its roots was assessed through various in vitro assays targeting the phospholipase A2 enzyme. MATERIALS AND METHODS: V. negundo roots were sequentially extracted in different organic solvents to get fractions and in methanol to get total extract. The extracts were evaluated for phospholipase A2 (PLA2) inhibitory potential through inhibition of venom-induced hemolysis, ADP-induced platelet aggregation, PLA2-induced fatty acid hydrolysis and anticoagulant effect of cobra venom. Antioxidant power was determined using DPPH and superoxide radical scavenging assays. GC-MS and HPLC analysis was performed for the total methanol extract. RESULTS: Strong PLA2 inhibitory effect was observed for all the extracts. The ethyl acetate, acetone and methanol fractions significantly inhibited toxic effects of cobra venom under in vitro conditions. Radical scavenging potential of these fractions was also significantly high as compared to non-polar fractions in both DPPH and superoxide scavenging assays. Phytochemical analysis indicated high phenolic and flavonoid contents in these fractions. GC-MS and HPLC analysis of total methanol extract confirmed the presence of bis(2-ethylhexyl) phthalate, phenol, o-Guaiacol, palmitic acid-methyl ester, methyl stearate, quercetin and kaempferol in the plant. CONCLUSION: The study concluded that the roots of V. negundo, particularly their polar extracts, have strong PLA2 inhibitory effect against cobra venom confirming their traditional use to manage snake bites. The roots of this plant can be further studied for isolation of plant-based antisera.

Cryoanesthesia with ethyl chloride spray versus 5% lidocaine gel in alleviating oral local anesthetic injection pain for buccal anaesthesia: A randomized clinical (controlled) trial.

Background: Numbing the area of oral mucosa with cold application prior to administration of regional anesthesia has been widely used by various dentists in alleviating pain caused by needle prick. Cryoanesthesia using Endo-ice as topical anesthesia has been studied as a replacement to prevail the fallibility of topical anaesthetics. This study aimed to evaluate and compare effectiveness of ethyl chloride spray with 5% lidocaine gel in alleviating buccal anesthesia injection pain. Methods: Total of 90 outpatients were randomly divided into 3 groups as follows: Group 1 - cryotherapy with ethyl chloride at the anesthetic site preceding before administration of local anesthesia; Group 2 - topical application of 5% LIDOCAINE GEL preceding before administration of local anesthesia; and group 3 - control that did not receive any topical agent preceding before administration of local anesthesia. Visual analogue scale (VAS) was used to document pain immediately after injection prick. Results: About comparison of pain scores, significant difference was found between group 1 (ethyl chloride) and group 2 (topical lidocaine) patients (P=0.001). For group 1, about 15 (50%) patients suffered from mild pain, followed by 14 (46.67%) patients suffering from moderate pain. However, majority of the 21 (70%) patients in group 2 suffered from moderate pain. All the patients in group 3 suffered from severe pain. Conclusion: Importance of alleviating fear of needle injection phobia amongst patients is of paramount importance. Ethyl chloride was found to be more effective than topical lidocaine in alleviating needle injection pain before administration of local anesthetic injection.

Correlation of HbA1c with Serum Iron & Transferrin Saturation in Non-Diabetic Patients with Iron Deficiency.

Objective: To determine correlation of HbA1c with serum iron and transferrin saturation in non-diabetic patients with iron deficiency. Methods: This cross-sectional comparative study was conducted at Dr Ruth KM Pfau Civil Hospital Karachi from 15th September 2021 to 14th March 2022, on non-diabetic patients based on fasting blood sugar (FBS) of <100 mg/dl. Patients were divided into two groups. Group one included patients having iron deficiency anemia (ID), whereas group two included same number of age and sex matched healthy subjects taken as controls, without ID. Blood sample was taken for HbA1c, CBC, serum iron and total iron binding capacity. Transferrin saturation (TSAT) was calculated. Comparison of quantitative variables with ID and non-ID group was done by Student's t-test. Correlation of HbA1c with iron &TSAT was done in both groups using Kendal tau-b test, as data was not normally distributed. Results: Out of 230 patients, 83 (36.1%) were males while 147(63.9%) were females. Mean age of patients was 43.7±13.28 years. Mean HbA1c level was significantly high in ID group (5.89±0.43) as compared to non-ID group (5.52±0.50) with a p-value <.001. The HbA1c levels correlated negatively with hemoglobin, serum iron levels and transferrin saturation with a p-value <.001. Conclusion: Low serum Iron and TSAT was related to elevation in HbA1c value. Iron deficiency needs to be corrected before HbA1c interpretation.

Liver and Renal Injury with Remdesivir Treatment in SARS-CoV-2 Patients.

Objective: To determine the effect of Remdesivir on liver enzymes and renal functions in SARS-CoV-2 patients. Methods: This prospective cohort study was conducted at Dr. Ruth KM Pfau, Civil Hospital Karachi between 1st December 2021 to 31st January, 2022. All patients of severe SARS-CoV-2 infection who received Inj. Remdesivir for five days as per protocol of SARS-CoV-2 management were included. Biodata of selected patients including age, gender, diabetic, hypertensive status was recorded. Patients Liver Function Tests and Serum Creatinine were performed on days 0, 3, 5, 7 and 14. Result: This study included 85 patients, out of which 55 (64.7%) were males and 30 (35.3%) were females. Out of 85 patients, Remdesivir was stopped in 3 (3.5%) patients. Among these three patients Remdesivir was stopped in one patient on day three because of decrease in CrCl to <30 ml/min. His CrCl improved after stopping Remdesivir. In the remaining two patients, Remdesivir was stopped due to increase in ALT to greater than 10 times from normal values on day three. Similarly, in these two patients the ALT improved after stopping Remdesivir. Conclusion: Only three patients developed adverse effects resulting in stopping of Remdesivir, however these were reversible on stopping the drug. Therefore, Remdesivir is a relatively safe drug and well tolerated in SARS-CoV-2 patients.

Diagnostic and prognostic role of cancer stem cell biomarkers in oral squamous cell carcinoma; A Systematic Review.

Objectives: To evaluate the role of cancer stem cell biomarkers in diagnosis and prognosis of OSCC patients. METHODS: The search strategy was entered into PubMed NLM, EBSCO CINAHL, EBSCO Dentistry & Oral Sciences Source, Wiley Cochrane Library, and Scopus. The full text eligible studies (n=7) were assessed for their quality using the JBI Critical Appraisal Checklist to evaluates the methodological quality of the studies based on possibility of bias in its design, conduct, and analysis. Selected studies were further analysed based on different parameters such as publication year, sample size, and outcomes. RESULTS: A total of 432 studies were identified through the search strategy. A total of 306 records were removed before screening either because of duplication or marked ineligible by the automation tools. The screened records were 126 out of which 104 were removed as they were not conducted on OSCC. Twenty-two reports were sought for retrieval, however, we could not find the full text of 3 studies and12 studies were excluded because the biomarkers were not associated with cancer stem cells. The most common cancer stem cell biomarkers associated with OSCC were MCT1,VEGF-A, GD15, HIF1 α, Ki67, Hsp 70, Cyclin D1, and CD44. CONCLUSIONS: Various stem cell biomarkers have been found to have diagnostic and prognostic role in oral squamous cell carcinoma such as Cyclin D1, VEGF-A, GD15, and CD44. They can be used to predict the overall survival rate, local progression-free survival rate, and distant metastasis-free survival rate in Head and Neck cancer patients.

Validation and exploratory factor analysis of Urdu Version of Chronic Liver Disease Questionnaire.

Objective: To present and validate psychometric properties of Urdu version CLDQ, yet another objective was to do exploratory factorial analysis (EFA) of CLDQ Urdu version. Methods: This Cross-sectional Analytical Study was conducted at Dr. Ruth K.M. Pfau Civil Hospital Karachi during the period Nov. 15, 2021 to Jan. 30, 2022. CLDQ Urdu questionnaire was self-administered by the patients. The questionnaire consisted of 29 items and responses were recorded on 7-point Likert type scale. Reliability testing was done by Cronbach's α, test value of >0.7 is taken as reliable. Exploratory factor analysis (EFA) was conducted with principal component analysis with varimax rotation. Adequacies for conduction of EFA depended on Kaiser-Meyer-Olkin (KMO) value of ≥0.5 and Bartlett's Test of Sphericity (BTS) of ≤0.05. Mean CLDQ Urdu scores were also compared with Child Class using ANOVA and post-hoc analysis was done. Results: A total of 320 patients were selected after informed consent. All conditions for adequate EFA were met (Cronbach's α =.949; KMO = .846; BTS ≤.001). Mean CLDQ Urdu score was 156.74 in male and 133.27 in female (p<.001). Child Class-A had best quality of life with score of 186.63 ±6.91 and Child Class-C had the worst with scores of 109.78 ±21.33. EFA resulted in reduction of domains to 4 (Muscular Symptoms, Emotional Symptoms, Abdominal Symptoms & Somnolence) & reduced the number of items from 29 to 11. Conclusion: Urdu CLDQ version is validated in our settings. EFA resulted in reductions in number of domains and items. CLDQ Urdu showed that quality of life decreases significantly with Child Class.

Mechanistic insights on the possible protective role of polyphenols extracted from Tamarix aphylla aerial parts against sodium arsenite-induced hepatotoxicity in rats.

Arsenic exposure is associated with the induction of hepatotoxicity. Current study was aimed to investigate the hepato-protective ability of polyphenolic components of Tamarix aphylla (TA) ethanolic extract against sodium arsenite (SA)-induced liver injury of rats. Significantly higher quantities of phenolic (318.7±2.5 mgg-1GAE) and flavonoid (250.69 ±3.3 mgg-1QE) contents were present. Inhibitory concentration (IC50) exhibited an excellent potential for antioxidant (IC50= 25.99 µg/mL) assay. High performance liquid chromatography (HPLC) confirmed the existence of myercetin (10.40ppm), sinapic acid (2.131ppm), kaempferol (0.486ppm), caffeic acid (5.094 ppm). Forty-two rats were divided into 7 groups. Group 1 received normal saline (2 mL/kg/day, orally for 21 days), Group 2 received SA (10mg/kg/day for 21 days), and Group 3 received SA alone for 7 days (10mg/kg) and continues with silymarine for 21 days (25mg/kg orally). Group 4, 5, 6 received SA alone for 7 days and continue with TA extract up to 21 days (125mg/kg, 250mg/kg, and 500mg/kg orally) respectively, and Group 7 received TA extract (500mg/kg) for 21 days. SA was administered to all treated groups for 21 days. Treatment with polyphenolic ethanolic extract of TA restored the hepatic indices and oxidative markers in a dose-dependent manner. The upregulation in tumor necrosis factor-α, interleukin-6, and cyclooxygenase-2 upon SA treatment suggesting inflammation was normalized by the treatment of rats. Above mentioned biochemical findings were supported well with histopathological screening. Present findings suggest that TA polyphenolic ethanolic extract could mitigate the oxidative stress and inflammation induced by SA in liver tissue.

Assessment of SARS-CoV-2 vaccination status in SARS-COV-2 infected patients admitted in Dr Ruth K.M. Pfau, Civil Hospital Karachi.

Objectives: To determine the frequency of vaccination status in patients with SARS-CoV-2 infection. Methods: This case-control study was conducted at Dr Ruth KM Pfau Civil Hospital Karachi, Pakistan between September 2021 to October 2021. All patients who had positive PCR on nasopharyngeal swab for SARS-CoV-2 infection were included. Information regarding vaccination status and brand of vaccination administered and duration between the last dose of vaccine and positive PCR was noted. The disease status of patients was classified on admission into severe and non-severe disease. Results: Study included 143 patients, out of which 58 (40.6%) were males and 85 (59.4%) were females. Majority of our patients (78.3%) were unvaccinated. Frequency of Severe SARS-CoV-2 Infection in fully vaccinated patients was less than in unvaccinated patients. The odds of developing severe COVID infection in unvaccinated patients versus vaccinated was 8.55 times higher (OR = 6.23, 95% CI 2.58-28.35). Proportion of vaccinated females was less as compared to males. Significant differences were found in severity between hypertension (p<.001), diabetes (<.001) and age (p<.001). Conclusion: The frequency of SARS-CoV-2 infection was greater in unvaccinated patients. The odds of developing severe COVID infection in unvaccinated patients versus vaccinated was 8.55 times higher.

Compliance to donning and doffing of personal protective equipment among dental healthcare practitioners during the coronavirus pandemic: a quality improvement plan, do, study and act (PDSA) Initiative.

INTRODUCTION: With the emergence of SARS-Cov-2, the Centers for Disease Control and Prevention (CDC) defined mandatory guidelines for donning and doffing personal protective equipment (PPE) among dental healthcare professionals. The study's objective was to improve the compliance of the donning and doffing protocols for PPE among dental practitioners by the Plan, Do, Study, and Act (PDSA) cycle. MATERIALS AND METHODS: A quasi-experimental study was conducted on a sample of dental healthcare professionals using the non-probability purposive technique. In the first planning stage, compliance with CDC-approved donning and doffing was assessed on the clinical premises. In the second stage, an educational session was arranged with all the healthcare professionals to explain stepwise guidelines of donning and doffing to improve the quality of donning and doffing compliance. In the third stage, improvement in the quality outcome was then assessed after the session. Data were normally distributed. Qualitative variables for all the steps of donning and doffing are reported as frequency and percentages. Pareto charts were made to assess the non-compliance rate for donning and doffing protocols among dental healthcare professionals. RESULTS: There was an improvement of 44.55% in the hand hygiene practices before wearing the PPE after the second step of the PDSA cycle. A percentage improvement of 7.4% was recorded for removing jewellery, wearing the gown and wearing a surgical cap. No improvement was seen in securing the mask/ respirator ties, washing hands after wearing the respirator, placing the goggles or face shield practices. CONCLUSIONS: PDSA cycle improved the overall compliance to PPE donning and doffing practices. Most of the protocols were followed by the dental healthcare professionals; however, some of them remained the same or worsened due to ease in SARS-CoV 2 restrictions.

Transcriptomic analysis reveals the key role of histone deacetylation via mediating different phytohormone signalings in fiber initiation of cotton.

BACKGROUND: Histone deacetylation is one of the most important epigenetic modifications and plays diverse roles in plant development. However, the detailed functions and mechanisms of histone deacetylation in fiber development of cotton are still unclear. HDAC inhibitors (HDACi) have been commonly used to study the molecular mechanism underlying histone deacetylation or to facilitate disease therapy in humans through hindering the histone deacetylase catalytic activity. Trichostatin A (TSA)-the most widely used HDACi has been extensively employed to determine the role of histone deacetylation on different developmental stages of plants. RESULTS: Through in vitro culture of ovules, we observed that exogenous application of TSA was able to inhibit the fiber initiation development. Subsequently, we performed a transcriptomic analysis to reveal the underlying mechanisms. The data showed that TSA treatment resulted in 4209 differentially expressed genes, which were mostly enriched in plant hormone signal transduction, phenylpropanoid biosynthesis, photosynthesis, and carbon metabolism pathways. The phytohormone signal transduction pathways harbor the most differentially expressed genes. Deeper studies showed that some genes promoting auxin, Gibberellic Acid (GA) signaling were down-regulated, while some genes facilitating Abscisic Acid (ABA) and inhibiting Jasmonic Acid (JA) signaling were up-regulated after the TSA treatments. Further analysis of plant hormone contents proved that TSA significantly promoted the accumulation of ABA, JA and GA3. CONCLUSIONS: Collectively, histone deacetylation can regulate some key genes involved in different phytohormone pathways, and consequently promoting the auxin, GA, and JA signaling, whereas repressing the ABA synthesis and signaling to improve the fiber cell initiation. Moreover, the genes associated with energy metabolism, phenylpropanoid, and glutathione metabolism were also regulated by histone deacetylation. The above results provided novel clues to illuminate the underlying mechanisms of epigenetic modifications as well as related different phytohormones in fiber cell differentiation, which is also very valuable for the molecular breeding of higher quality cotton.

Assessment of frailty in cirrhosis using bedside measures and its correlation with Child-Turcotte-Pugh, MELD & MELD-Na Scores.

Objectives: To assess frailty in cirrhotic by calculating Liver Frailty Index (LFI) using bedside clinical tests and correlate it with Child-Turcotte-Pugh (CTP), MELD, MELD Na, Fib- 4 and Transient Elastography (TE) scores. Methods: This cross-sectional observational comparative study was carried out in Dr Ruth KM Pfau Civil Hospital, Karachi from August 2020 to September 2021. Patients were subjected to three performance-based testing including dominant hand grip strength (HGS), Chair to Stand (CTS) Time & Three Position Balance (TPB). LFI was calculated using the online LFI calculator, available at http://liverfrailtyindex.ucsf.edu and classified as 'Robust' if LFI <3.2, 'Prefrail' LFI between 3.2 and 4.4, and 'Frail' as LFI ≥4.5. Correlation of frailty with MELD, MELD-Na and CTP Scores was done. Means of MELD & MELD-Na Scores and CTP scores were calculated in all 3 classes of frailty using one way ANOVA. A p-value of ≤.05 was taken as significant. Results: Out of 118 patients, 62 (52.5%) were males. Mean MELD score was 11.4 ±3.3, MELD-Na was 15.97 ±8.54, CTP 8.25 ±2.21, Fib-4 was 2.79 ±1.034 and TE score was 18.20 ±9.17. Mean LFI was 3.87 ±1.07; mean HGS was 18.12 ±4.68; mean of CTS was 9.62 ±3.55. LFI Class distribution in our cohort showed Robust were 36 (30.5%), Prefrail 34 (28.8%) and Frail were 48 (40.8%). Correlation of all these variables with LFI showed significant correlation with LFI, but highest correlation coefficient was seen with MELD-Na. Conclusion: Significant correlation between frailty score in cirrhotic with cirrhosis severity scores highlights the need for frequently assessing LFI in all cirrhotic at regular follow up visits.

Physical Activity, Dietary Habits and Factors Associated with Depression Among Medical Students of Sindh, Pakistan, During the COVID-19 Pandemic.

Objective: To find out the association of physical activity, dietary habits and factors associated with depression among medical students of Sindh, Pakistan, during the coronavirus disease 2019 (COVID-19) pandemic. Methods: An online cross-sectional study was conducted between June and August, 2020, on medical students from three medical institutions of Sindh, Pakistan. The study comprised three structured questionnaires related to demographic details, physical activity, dietary and sleep habits, COVID-19 pandemic-associated factors and patient health questionnaire, PHQ-9. A total of 864 students completed the questionnaires and participated in the study. The data was analysed on SPSS version 23. Results: Our study showed that 244 (28.2%) medical students had mild depression, 192 (22.2%) had moderate depression, 80 (9.3%) had moderately severe depression and 80 (9.3%) had severe depression during the COVID-19 pandemic. Out of 864 students, 268 (31%) had no depression. Socioeconomic status, body mass index (BMI), chronic disease/comorbidity, addiction and non-medical prescription drug use were found to be statistically significant predictors of depression among medical students. On multilogistic regression analysis, physical activity, social media/app use and sleeping habits during COVID-19 were associated with depression (p-value < 0.05). Conclusion: The COVID-19 pandemic adversely affected physical activity and sleeping habits in association with depression among medical students. Promoting healthy eating habits, adequate physical activity, and a healthy lifestyle, particularly among students during lockdowns, is a critical component of coping with mental stress and depression. The findings of this study will aid in future research and campaign design in preparation for future pandemics and lockdowns.

Comparison of Vonoprazan and Amoxicillin Dual Therapy with Standard Triple Therapy with Proton Pump Inhibitor for Helicobacter Pylori eradication: A Randomized Control Trial.

Objectives: To compare the efficacy of Vonoprazan based dual treatment versus PPI based treatment for the eradication of Helicobacter pylori infection. Methods: A randomized controlled trial was conducted in Department of Medicine/Gastroenterology Ruth KM Pfau Civil Hospital, DMC during the period of 22 June to 21 September 2021. Sample size was calculated as 96 in each Group. All patients of age 18-75 years with Helicobacter Pylori Infection were inducted and randomly allocated to two groups. Group-A: were given Capsule Amoxicillin 1 gm; Tablet Clarithromycin 500 mg; Capsule Omeprazole 20 mg all medications were given twice daily for two weeks. Group-B were given Capsule Amoxicillin 1 gm; Tablet Vonoprazan 20 mg (Vonozon©, m/s Getz Pharma, Pakistan) twice daily for two weeks. Confirmation of Hp eradication was done by stool Hp antigen test four weeks after completion of treatment. Nine and four patients were lost to follow-up in Group-A & B respectively. Analysis was conducted on 87 patients in Group-A and 92 patients in Group-B. Results: Out of eighty-seven patients in Group-A and ninety-two patients in Group-B, 73 (83.9%) patients in Group-A and 86 (93.5%) patients in Group-B had negative H pylori result respectively after treatment (p = .042). Significantly higher frequencies of adverse events were observed in Group-A as compared to Group-B in nausea/vomiting (p = .035) and bloating (p = .045). Conclusion: VA-dual provides an acceptable eradication rate with fewer adverse events.

Inhibition of LSD1 Attenuates Oral Cancer Development and Promotes Therapeutic Efficacy of Immune Checkpoint Blockade and YAP/TAZ Inhibition.

Lysine-specific demethylase 1 (LSD1) is a histone demethylase that contributes to the etiology of oral squamous cell carcinoma (OSCC) in part by promoting cancer stem cell phenotypes. The molecular signals regulated by LSD1, or acting with LSD1, are poorly understood, particularly in the development of OSSC. In this study, we show that conditional deletion of the Lsd1 gene or pharmacologic inhibition of LSD1 in the tongue epithelium leads to reduced development of OSCC following exposure to the tobacco carcinogen 4NQO. LSD1 inhibition attenuated proliferation and clonogenic survival and showed an additive effect when combined with the YAP inhibitor Verteporfin. Interestingly, LSD1 inhibition upregulated the expression of PD-L1, leading to immune checkpoint inhibitor therapy responses. IMPLICATIONS: Collectively, our studies reveal a critical role for LSD1 in OSCC development and identification of tumor growth targeting strategies that can be combined with LSD1 inhibition for improved therapeutic application.

RNA-Seq with a novel glabrous-ZM24fl reveals some key lncRNAs and the associated targets in fiber initiation of cotton.

BACKGROUND: Cotton fiber is an important natural resource for textile industry and an excellent model for cell biology study. Application of glabrous mutant cotton and high-throughput sequencing facilitates the identification of key genes and pathways for fiber development and cell differentiation and elongation. LncRNA is a type of ncRNA with more than 200 nt in length and functions in the ways of chromatin modification, transcriptional and post-transcriptional modification, and so on. However, the detailed lncRNA and associated mechanisms for fiber initiation are still unclear in cotton. RESULTS: In this study, we used a novel glabrous mutant ZM24fl, which is endowed with higher somatic embryogenesis, and functions as an ideal receptor for cotton genetic transformation. Combined with the high-throughput sequencing, fatty acid pathway and some transcription factors such as MYB, ERF and bHLH families were identified the important roles in fiber initiation; furthermore, 3,288 lncRNAs were identified, and some differentially expressed lncRNAs were also analyzed. From the comparisons of ZM24_0 DPA vs ZM24_-2 DPA and fl_0 DPA vs ZM24_0 DPA, one common lncRNA MSTRG 2723.1 was found that function upstream of fatty acid metabolism, MBY25-mediating pathway, and pectin metabolism to regulate fiber initiation. In addition, other lncRNAs MSTRG 3390.1, MSTRG 48719.1, and MSTRG 31176.1 were also showed potential important roles in fiber development; and the co-expression analysis between lncRNAs and targets showed the distinct models of different lncRNAs and complicated interaction between lncRNAs in fiber development of cotton. CONCLUSIONS: From the above results, a key lncRNA MSTRG 2723.1 was identified that might mediate some key genes transcription of fatty acid metabolism, MYB25-mediating pathway, and pectin metabolism to regulate fiber initiation of ZM24 cultivar. Co-expression analysis implied that some other important lncRNAs (e.g., MSTRG 3390.1, MSTRG 48719.1, and MSTRG 31176.1) were also showed the different regulatory model and interaction between them, which proposes some valuable clues for the lncRNAs associated mechanisms in fiber development.

Are we missing varices by implementing Baveno-VI recommendation of not screening patients with Compensated Advanced Chronic Liver Disease?

OBJECTIVES: This study aimed to validate Baveno-VI recommendations for variceal screening in cACLD in our region and proposed our own cutoff values. METHODS: Prospective cross-sectional study was conducted on cACLD patients from August 2020 till April 2021. Patients segregated into Group-A, having Liver stiffness measurement (LSM) of ≥ 20 kPa and platelet of ≤ 150 × 109 cells/L; and Group-B having LSM of < 20 kPa and PLT of > 150 × 109 cells/L. Gastroscopic findings were segregated into three categories, VNT, Varices Not Needing Treatment (VNNT) and No Varix (NV). ROC plots were generated for LSM and Platelet for VNT for sensitivity, specificity, Negative and Positive Predictive Values were calculated. RESULTS: A total of 134 patients of cACLD were included. Group-A had 72 (53.7%) patients and Group-B had 62 (46.3%) patients. Group-A had 6 (8.3%) NV; 18 (25.0%) VNNT and 48 (66.7%) VNT. Group-B had 26 (41.9%) NV, 24 (38.7%) VNNT and 12 (19.4%) VNT. The sensitivity of 66.7%, specificity of 80.6% and NPV of 67.56% was obtained. Thus 19.4% VNT were missed on following Baveno VI recommendations. ROC in our study suggested cutoff value of 11.5 kPa with sensitivity of 100% and 1-sepcifity pf 78% (AUROC = 0.865; p < .001) of LSM below which screening gastroscopy could be avoided. The positive and negative predicted values for 84.85% and 100% respectively. Cut off value of platelet count for VNNT came out to be ≥ 97.5 × 109 cells/L with AUROC 0.891 (p < .001), having sensitivity of 100 % and 1-specificity of 83.3%. CONCLUSIONS: Substantial number of VNT in cACLD patients are missed by following Baveno-VI recommendations and these needs to be revised on regional basis.

Updated role of ABA in seed maturation, dormancy, and germination.

Background: Seed is vital for plant survival and dispersion, however, its development and germination are influenced by various internal and external factors. Abscisic acid (ABA) is one of the most important phytohormones that influence seed development and germination. Until now, impressive progresses in ABA metabolism and signaling pathways during seed development and germination have been achieved. At the molecular level, ABA biosynthesis, degradation, and signaling genes were identified to play important roles in seed development and germination. Additionally, the crosstalk between ABA and other hormones such as gibberellins (GA), ethylene (ET), Brassinolide (BR), and auxin also play critical roles. Although these studies explored some actions and mechanisms by which ABA-related factors regulate seed morphogenesis, dormancy, and germination, the complete network of ABA in seed traits is still unclear. Aim of review: Presently, seed faces challenges in survival and viability. Due to the vital positive roles in dormancy induction and maintenance, as well as a vibrant negative role in the seed germination of ABA, there is a need to understand the mechanisms of various ABA regulators that are involved in seed dormancy and germination with the updated knowledge and draw a better network for the underlying mechanisms of the ABA, which would advance the understanding and artificial modification of the seed vigor and longevity regulation. Key scientific concept of review: Here, we review functions and mechanisms of ABA in different seed development stages and seed germination, discuss the current progresses especially on the crosstalk between ABA and other hormones and signaling molecules, address novel points and key challenges (e.g., exploring more regulators, more cofactors involved in the crosstalk between ABA and other phytohormones, and visualization of active ABA in the plant), and outline future perspectives for ABA regulating seed associated traits.

Dynamic roles and intricate mechanisms of ethylene in epidermal hair development in Arabidopsis and cotton.

Ethylene affects many aspects of plant growth and development, including root hairs and trichomes growth in Arabidopsis, as well as fiber development in cotton, though the underlying mechanism is unclear. In this article, we update the research progress associated with the main genes in ethylene biosynthesis and signaling pathway, and we propose a clear ethylene pathway based on genome-wide identification of homologues in cotton. Expression pattern analysis using transcriptome data revealed that some candidate genes may contribute to cotton fiber development through the ethylene pathway. Moreover, we systematically summarized the effects of ethylene on the development of epidermal hair and the underlying regulatory mechanisms in Arabidopsis. Based on the knowledge of ethylene-promoted cell differentiation, elongation, and development in different tissues or plants, we advised a possible regulatory network for cotton fiber development with ethylene as the hub. Importantly, we emphasized the roles of ethylene as an important node in regulating cotton vegetative growth, and stress resistance, and suggested utilizing multiple methods to subtly modify ethylene synthesis or signaling in a tissue or spatiotemporal-specific manner to clarify its exact effect on architecture, adaptability of the plant, and fiber development, paving the way for basic research and genetic improvement of the cotton crop.