Miracle-dz/UniFAR-FTUs huggingface dataset:
De-epithelialized Gingival Graft versus Subepithelial Connective Tissue Graft in the Treatment of Multiple Adjacent Gingival Recessions Using the Tunnel Technique: 1-year results of a randomized clinical trial.

AIM To compare the clinical efficacy and postoperative morbidity of de-epithelialized gingival graft (DGG) with subepithelial connective tissue graft (SCTG) on treatment of multiple adjacent gingival recessions (MAGRs) with tunnel technique (TUN) and to evaluate histological characteristics of the palatal grafts. METHODS Twenty-seven patients with MAGRs affecting at least 2 adjacent teeth were treated with either DGG+TUN or SCTG+TUN. Recession depth(RD) and width(RW), probing depth(PD), clinical attachment level(CAL), keratinized tissue height(KTH), gingival thickness(GT), and complete and mean root coverage(CRC, MRC) were evaluated at 6 and 12 months postoperatively. Multilevel analysis was performed to identify patient- and tooth/site-related predictors for the 12-month MRC outcomes. Postoperative patient morbidity and histological characteristics of palatal graft samples obtained during harvesting were investigated. RESULTS At the 12-month follow-up, MRC was 91.72±16.59% and 84.72±19.72% in DGG+TUN and SCTG+TUN groups (P=0.001). Multilevel regression analysis identified RD, KTH, and GT as variables associated with MRC. No significant difference between the groups was observed regarding postoperative patient morbidity parameters. Cellularity was found significantly higher in the SCTG samples compared to the DGG samples (P<0.05). CONCLUSIONS Although DGG+TUN presented higher MRC and CRC compared to SCTG+TUN in the treatment of MAGRs, treatment method was not a significant predictive factor for the amount of MRC outcomes while RD, KTH, and GT were significant predictive factors. CLINICAL RELEVANCE Scientific rationale for study: Limited information is available about the effects of connective tissue grafts (CTGs) obtained by different harvesting techniques on root coverage outcomes as well as patient's postoperative morbidity and aesthetic evaluation in the treatment of MAGRs using the tunnel technique (TUN). On the other hand, patient- and tooth/site-related prognostic indicators may have a critical role in obtaining the treatment outcomes. PRINCIPAL FINDINGS DGG combined with TUN showed higher mean root coverage (MRC) and complete root coverage (CRC) compared to SCTG in the treatment of MAGRs. Nevertheless, tooth/site related prognostic factors could impact root coverage outcomes regardless of CTG harvesting technique. Both procedures showed similar outcomes in terms of patient's postoperative morbidity and aesthetic evaluation at the 1-year follow-up. PRACTICAL IMPLICATIONS DGG could be a predictable and safe option as an autologous palatal graft when combined with TUN for the treatment of MAGRs. Baseline defect and gingival anatomical characteristics should be considered when appraising the therapeutic prognosis of MAGRs.
Chitin‐lipid interactions and the potential relationship between Demodex and SARS‐CoV‐2

Already from the early days of the COVID‐19 pandemic, regulatory agencies have attempted to ascertain the possible routes of SARS‐CoV‐2 viral transmission. It is hypothesized that the lipid bilayer that surrounds the SARS‐CoV‐2 improves its ability to remain stable on sebum‐rich skin and serves as another possible route of contracting the virus. One possible aspect of these observations that has yet to be explored in detail is what role arthropods that have been associated with human skin infestation, such as Demodecidae or Pyemotidae species, play in viral transmission. It seems likely that arthropod‐coronavirus interactions may take place through the molecular attraction forces between the chitin found on the exoskeleton of mites commonly found on human skin and the lipids present on the viral envelope of the SARS‐CoV‐2. We believe this may mean that arthropods are currently an overlooked cofactor in viral infection which may have some important biomedical implications for both prevention and treatment.
Neutrophil-to-Lymphocyte Ratio, derived Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio and Lymphocyte-to-Monocyte Ratio as risk factors in critically ill COVID-19 patients, a single centered study.

Background A lot remains anonymous about the characteristics and laboratory findings that may evaluate poor outcomes in patients with Coronavirus disease 2019.The aim of this study was to determine the relationship of change in the peripheral blood factors of Neutrophil-to-Lymphocyte Ratio, derived-Neutrophil-to-Lymphocyte Ratio, Lymphocyte-to-Monocyte Ratio, and Platelet-to-Lymphocyte Ratio in hospitalized patients with COVID-19 and its severity. Methods Cross-sectional analytical study was performed at Department of Haematology in Pak Emirates Military Hospital affiliated with Army Medical College, Rawalpindi, Pakistan from March-July 2020. We included 735 patients confirmed by real-time reverse transcriptase polymerase-chain-reaction test for subacute respiratory syndrome corona virus-2 of all ages, irrespective of gender and were classified in groups of severe and non-severe groups. Results Data of blood and baseline characteristics were compared in between the two groups and found to be significant (p-value <0.001). The median age was 46.3 years, and 82 cases were only females. Receiver operator curve demonstrated larger area under the curve of NLR, d-NLR, and PLR and showed them as independent diagnostic biomarkers which were significantly associated with the severity of illness. Binary logistic regression performed in the form of forest plot also showed these factors were significantly linked with the severity (p-value <0.001). Conclusion NLR, d-NLR, and PLR along with pre-existing co morbidities can be used as an independent biomarker for the poor clinical outcome of COVID-19 illness.
Reduced Gene Dosage of Histone H4 Prevents CENP-A Mislocalization and Chromosomal Instability in Saccharomyces cerevisiae.

Mislocalization of the centromeric histone H3 variant (Cse4 in budding yeast, CID in flies, CENP-A in humans) to non-centromeric regions contributes to chromosomal instability (CIN) in yeast, fly, and human cells. Overexpression and mislocalization of CENP-A has been observed in cancers, however, the mechanisms that facilitate the mislocalization of overexpressed CENP-A have not been fully explored. Defects in proteolysis of overexpressed Cse4 (GALCSE4) leads to its mislocalization and synthetic dosage lethality (SDL) in mutants for E3 ubiquitin ligases (Psh1, Slx5, SCFMet30, SCFCdc4), Doa1, Hir2, and Cdc7. In contrast, defects in sumoylation of overexpressed cse4K215/216/A/R prevent its mislocalization and do not cause SDL in a psh1Δ strain. Here, we used a genome-wide screen to identify factors that facilitate the mislocalization of overexpressed Cse4 by characterizing suppressors of the psh1Δ GALCSE4 SDL. Deletions of histone H4 alleles (HHF1 or HHF2), which were among the most prominent suppressors, also suppress slx5Δ, cdc4-1, doa1Δ, hir2Δ, and cdc7-4 GALCSE4 SDL. Reduced dosage of H4 leads to defects in sumoylation and reduced mislocalization of overexpressed Cse4, which contributes to suppression of CIN when Cse4 is overexpressed. We determined that the hhf1-20, cse4-102, and cse4-111 mutants, which are defective in the Cse4-H4 interaction, also exhibit reduced sumoylation of Cse4 and do not display psh1Δ GALCSE4 SDL. In summary, we have identified genes that contribute to the mislocalization of overexpressed Cse4 and defined a role for the gene dosage of H4 in facilitating Cse4 sumoylation and mislocalization to non-centromeric regions, leading to CIN when Cse4 is overexpressed.
Management of Aortic Stenosis: A Systematic Review of Clinical Practice Guidelines and Recommendations.

AIMS Multiple guidelines exist for the management of aortic stenosis (AS). We systematically reviewed current guidelines and recommendations, developed by national or international medical organizations, on management of AS to aid clinical decision making. METHODS AND RESULTS Publications in MEDLINE and EMBASE between June 1st, 2010 and January 15th, 2021 were identified. Additionally, the International Guideline Library, National Guideline Clearinghouse, National Library for Health Guidelines Finder, Canadian Medical Association Clinical Practice Guidelines Infobase, and websites of relevant organizations were searched. Two reviewers independently screened titles and abstracts. Two reviewers assessed rigor of guideline development and extracted the recommendations.Of the 7 guidelines and recommendations retrieved, 5 showed considerable rigor of development. Those rigorously developed, agreed on the definition of severe AS and diverse hemodynamic phenotypes, indications and contraindications for intervention in symptomatic severe AS, surveillance intervals in asymptomatic severe AS, and the importance of multidisciplinary teams (MDT) and shared decision-making.Discrepancies exist in age and surgical risk cut-offs for recommending surgical (SAVR) vs. transcatheter aortic valve implantation (TAVI), the use of biomarkers and complementary multimodality imaging for decision-making in asymptomatic patients and surveillance intervals for non-severe AS. CONCLUSIONS Contemporary guidelines for aortic stenosis management agree on the importance of MDT involvement and shared decision-making for individualized treatment and unanimously indicate valve replacement in severe, symptomatic AS. Discrepancies exist in thresholds for age and procedural risk used in choosing between SAVR and TAVI, role of biomarkers and complementary imaging modalities to define AS severity and risk of progression in asymptomatic patients.
FDA Approval Summary: Fam-Trastuzumab Deruxtecan-Nxki for the Treatment of Unresectable or Metastatic HER2-Positive Breast Cancer

On December 20, 2019, the FDA granted accelerated approval to fam-trastuzumab deruxtecan-nxki [DS-8201a; T-DXd; tradename ENHERTU (Daiichi Sankyo)] for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2–based regimens in the metastatic setting. Approval was based on data from study DS8201-A-U201 (DESTINY-Breast01) with supportive safety data from study DS8201-A-J101. The primary efficacy endpoint in DESTINY-Breast01 was overall response rate (ORR) based on confirmed responses by blinded independent central review (ICR) using RECIST v1.1 in all participants who were assigned to receive the recommended dose of 5.4 mg/kg while secondary endpoints included duration of response (DoR). The confirmed ORR based on ICR in these 184 patients was 60.3% [95% confidence interval (CI): 52.9–67.4] and the median DoR was 14.8 months (95% CI: 13.8–16.9). Interstitial lung disease, including pneumonitis, was experienced in patients treated with T-DXd and can be severe, life threatening, or fatal. In addition, neutropenia and left ventricular dysfunction were included as Warnings and Precautions in labeling. Other important common adverse reactions were nausea, fatigue, vomiting, alopecia, constipation, decreased appetite, anemia, diarrhea, and thrombocytopenia. Overall, the totality of efficacy and safety data supported the accelerated approval of T-DXd for the intended indication.
eLearning in Physical Therapy: Lessons Learned From Transitioning a Professional Education Program to Full eLearning During the COVID-19 Pandemic

Abstract Objective The objectives of this cross-sectional qualitative study were to explore the perspectives of students enrolled in one physical therapist undergraduate education program in Australia about their experience with transitioning to full eLearning and student recommendations to improve the learning experience during the COVID-19 pandemic. Methods Seven focus groups with 28 undergraduate physical therapist students were conducted following the transitioning to full eLearning as a result of strict physical distancing measures. Focus group questions explored the students’ experiences of the transition from face-to-face to full eLearning approach and the students’ recommendations for improving future eLearning experiences. Data were analyzed using inductive thematic analysis. Results The 3 themes identified were: (1) students presenting heightened negative feelings such as anxiety, stress, and reduced motivation to study; (2) students continuing to value the face-to-face learning, as it provided social support and facilitated feedback from peers and tutors; (3) student recommendations for eLearning included having online lectures and supplementary videos but face-to-face practical classes and developing healthy learning habits such as scheduled times for studying, exercise, and other activities that regulate stress. Conclusions The transition to a full eLearning approach in an undergraduate physical therapist education program during the COVID-19 pandemic revealed that students had heightened negative emotions due to the pandemic. Students valued face-to-face practical classes to learn and receive social support from peers and tutors. Student recommendations to future eLearning suggested changes to curriculum development geared toward a greater blended approach to learning. Blended learning may include using online lectures instead of face-to-face lectures and online resources to supplement student learning of practical skills. Impact As higher education moves toward a more blended approach, lessons learned from this study can help educators design future physical therapist education programs. The findings can also assist programs in delivering a full eLearning approach as the COVID-19 pandemic continues.
Zinc oxide nanoparticles mediated substantial physiological and molecular changes in tomato

There has long been debate about how nanoproducts meet agricultural requirements. This study aimed to investigate tomato responses to the long-time foliar application of zinc oxide nanoparticles (ZnO-NP; 0 and 3 mgl-1) or bulk type (BZnO). Both ZnO-NP and BZnO treatments, especially the nanoform, were significantly capable of improving growth, biomass, and yield. The ZnO-NP treatment upregulated the expression of the R2R3MYB transcription factor by 2.6 folds. The BZnO and ZnO-NP treatments transcriptionally up-regulated WRKY1 gene by 2.5 and 6.4 folds, respectively. The bHLH gene was also upregulated in response to BZnO (2.3-fold) or ZnO-NP (4.7-fold). Moreover, the ZnO-NP application made a contribution to upregulation in the EREB gene whereas the bulk compound did not make a significant change. Upregulation in the HsfA1a gene also resulted from the ZnO-NP (2.8-fold) or BZnO (1.6-fold) supplementation. The MKK2 and CAT genes displayed a similar upregulation trend in response to the supplements by an average of 3-folds. While the application of ZnO-NP slightly down-regulated the histone deacetylases (HDA3) gene by 1.9-fold, indicating epigenetic modification. The supplements, especially the nano-product, enhanced concentrations of K, Fe, and Zn in both leaves and fruits. The concentrations of Chla, Chlb, and carotenoids were increased in response to the BZnO or ZnO-NP treatments. Likewise, BZnO or ZnO-NP mediated an increase in activity of nitrate reductase and proline content in leaves. These treatments increased soluble phenols and phenylalanine ammonia-lyase activity. With a similar trend, the BZnO or ZnO-NP application improved the activities of catalase and peroxidase enzymes. The reinforcement in metaxylem and secondary tissues resulted from the applied supplements. This study provides comprehensive comparative evidence on how ZnO-NPs may remodel the chromatin ultrastructure and transcription program, and confer stress tolerance in crops. This study also underlines the necessity of providing integrated transcriptome and proteome data in future studies.
Antenatal corticosteroids for impending late preterm (34-36+6 weeks) deliveries—A systematic review and meta-analysis of RCTs

Background Administration of antenatal corticosteroids (ANC) for impending preterm delivery beyond 34 weeks of gestation continues to be a controversial issue despite various guidelines for obstetricians and gynaecologists. Objective To compare outcomes following exposure to ANC for infants born between 34–36+6 weeks’ gestation. Methods A systematic review of randomised controlled trials (RCT) reporting neonatal outcomes after ANC exposure between 34–36+6 weeks’ gestation using Cochrane methodology. Databases including PubMed, Embase, Emcare, Cochrane Central library and Google Scholar were searched in May 2020. Primary outcomes: (1) Need for respiratory support (Mechanical ventilation, CPAP, high flow) or oxygen (2) Hypoglycemia. Secondary outcomes included respiratory distress syndrome (RDS), transient tachypnoea of newborn (TTN), need for neonatal resuscitation at birth [only in the delivery room immediately after birth (not in neonatal intensive care unit (NICU)], admission to NICU, mortality and developmental follow up. Level of evidence (LOE) was summarised by GRADE guidelines. Main results Seven RCTs (N = 4144) with low to high risk of bias were included. Only one RCT was from high income countries, Meta-analysis (random-effects model) showed (1) reduced need for respiratory support [5 RCTs (N = 3844); RR = 0.68 (0.47–0.98), p = 0.04; I2 = 55%; LOE: Moderate] and (2) higher risk of neonatal hypoglycaemia [4 RCTs (N = 3604); RR = 1.61(1.38–1.87), p<0.00001; I2 = 0%; LOE: High] after ANC exposure. Neonates exposed to ANC had reduced need for resuscitation at birth. The incidence of RDS, TTN and surfactant therapy did not differ significantly. None of the included studies reported long-term developmental follow up. Conclusions Moderate quality evidence indicates that ANC exposure reduced need for respiratory support, and increased the risk of hypoglycaemia in late preterm neonates. Large definitive trials with adequate follow up for neurodevelopmental outcomes are required to assess benefits and risks of ANC in this population.
MYH1 is a candidate gene for recurrent rhabdomyolysis in humans

Rhabdomyolysis is a serious medical condition characterized by muscle injury, and there are recognized genetic causes especially in recurrent forms. The majority of these cases, however, remain unexplained. Here, we describe a patient with recurrent rhabdomyolysis in whom extensive clinical testing failed to identify a likely etiology. Whole‐exome sequencing revealed a novel missense variant in MYH1, which encodes a major adult muscle fiber protein. Structural biology analysis revealed that the mutated residue is extremely well conserved and is located in the actin binding cleft. Furthermore, immediately adjacent mutations in that cleft in other myosins are pathogenic in humans. Our results are consistent with the finding that MYH1 is mutated in rhabdomyolysis in horses and suggest that this gene should be investigated in cases with recurrent rhabdomyolysis.
Risk factors for progression of appendiceal neuroendocrine tumours: low‐stage tumours <5 mm appear to be overwhelmingly indolent and may merit a separate designation

Appendiceal well‐differentiated neuroendocrine tumours (NETs) are usually incidental and clinically benign. Several studies have reported different risk factors for nodal metastasis. The aim of this study was to investigate our appendiceal NETs (App‐NETs) to determine the factors associated with malignant behaviour.
The impact of splinting mobile mandibular incisors on Oral Health-Related Quality of Life - Preliminary observations from a randomized clinical trial.

AIM To compare the Oral Health-Related Quality of Life (OHRQoL) of patients with mobile mandibular incisors before and after full-mouth disinfection (FMD) with and without splinting. MATERIAL AND METHODS 34 periodontitis patients with ≥1 mobile mandibular incisor (degree II/III) were randomly allocated to the test- or control-group. All patients received FMD and the test-group additional splinting of teeth 33-43. OHRQoL was assessed before (BL) and three months after FMD (RE) using the Oral Health Impact Profile (OHIP)-14. Data were compared within and between the groups (Wilcoxon-test/Mann-Whitney-U-test). RESULTS 28 patients (13 test-group/15 control-group) were re-evaluated. FMD led to a reduction of the mean probing pocket depth (PPD; in mm) (test-group: BL-PPD 3.89±1.03, RE-PPD 2.82±0.53; control-group: BL-PPD 3.58±0.66, RE-PPD 2.77±0.59; each p≤0.001), the mean clinical attachment level (CAL; in mm) (test-group: BL-CAL 5.22±1.38, RE-CAL 4.79±0.85; control-group: BL-CAL 4.58±1.10, RE-CAL 4.41±0.96; each p≤0.05), and the mean OHIP-14 summary scores (test-group: BL-OHIP 21.7±11.06, RE-OHIP 9.9±8.96, p=0.0046; control-group: BL-OHIP 16.8±8.27, RE-OHIP 11.7±8.55; p=0.0217). The reduction of the OHIP-G14 scores was considerably higher in the test-group but statistically not significant (p=0.080). CONCLUSIONS The results show a positive impact of non-surgical periodontal treatment on OHRQoL and a possible tendency for further improvement by splinting mobile mandibular incisors.
Associations of Plasma Glucagon Levels with Estimated Glomerular Filtration Rate, Albuminuria and Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus

Background Type 2 diabetes mellitus (T2DM) is characterized by elevated fasting glucagon and impaired suppression of postprandial glucagon secretion, which may participate in diabetic complications. Therefore, we investigated the associations of plasma glucagon with estimated glomerular filtration rate (eGFR), albuminuria and diabetic kidney disease (DKD) in T2DM patients. Methods Fasting glucagon and postchallenge glucagon (assessed by area under the glucagon curve [AUCgla]) levels were determined during oral glucose tolerance tests. Patients with an eGFR <60 mL/min/1.73 m2 and/or a urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g who presented with diabetic retinopathy were identified as having DKD. Results Of the 2,436 recruited patients, fasting glucagon was correlated with eGFR and UACR (r=–0.112 and r=0.157, respectively; P<0.001), and AUCgla was also correlated with eGFR and UACR (r=–0.267 and r=0.234, respectively; P<0.001). Moreover, 31.7% (n=771) presented with DKD; the prevalence of DKD was 27.3%, 27.6%, 32.5%, and 39.2% in the first (Q1), second (Q2), third (Q3), and fourth quartile (Q4) of fasting glucagon, respectively; and the corresponding prevalence for AUCgla was 25.9%, 22.7%, 33.7%, and 44.4%, respectively. Furthermore, after adjusting for other clinical covariates, the adjusted odds ratios (ORs; 95% confidence intervals) for DKD in Q2, Q3, and Q4 versus Q1 of fasting glucagon were 0.946 (0.697 to 1.284), 1.209 (0.895 to 1.634), and 1.521 (1.129 to 2.049), respectively; the corresponding ORs of AUCgla were 0.825 (0.611 to 1.114), 1.323 (0.989 to 1.769), and 2.066 (1.546 to 2.760), respectively. Additionally, when we restricted our analysis in patients with glycosylated hemoglobin <7.0% (n=471), we found fasting glucagon and AUCgla were still independently associated with DKD. Conclusion Both increased fasting and postchallenge glucagon levels were independently associated with DKD in T2DM patients.