Miracle-dz/UniFAR-FTUs huggingface dataset:
Influence of the loading protocol and platform-switching in two-implant bar-retained overdentures: 3-year results from a randomized controlled equivalence clinical trial.

OBJECTIVES To test the null hypothesis that vertical peri-implant bone level alterations (ΔIBL) are equivalent in immediately (IL), and 3-month post-placement (DL) loaded implants in mandibular implant overdentures (IODs) on two implants. MATERIALS AND METHODS Thirty-two patients receiving two interforaminal implants, one with a platform-switched, and one with a platform-matching abutment, were randomly assigned to the IL or DL group (allocation ratio 1:1). All implants were primarily splinted with chairside customized bars, converting the existing removable complete dentures to IODs. Standardized radiographs were recorded. The influence of the loading protocol (IL vs. DL), implant platform (platform switched vs. platform matching), implant site (43 vs. 33), participant age (≤ 65 vs. > 65 years), and definition of baseline (implant placement vs. implant loading), were analyzed, applying linear regression analyses (α=0.05). The equivalence range was [-0.4; 0.4]. RESULTS Three participants of the IL group were lost during follow-up. The overall mean ΔIBL was -0.96 +/- 0.89 mm. The ΔIBL was equivalent in terms of the implant platform and implant site, but not in terms of participant age (in favor of more elderly participants) and the loading protocol. A significantly smaller ΔIBL was observed in the IL when the baseline was considered to be implant placement (p=0.017), but not when it was considered to be implant loading (p=0.084). CONCLUSION Immediate loading of primary splinted implants, in two-implant bar-retained overdentures, seems beneficial relative to loading three months post-placement, with respect to ΔIBL. The ΔIBL were equivalent in terms of platform-switching.
Cellular senescence limits translational readthrough

ABSTRACT The origin and evolution of cancer cells is considered to be mainly fueled by DNA mutations. Although translation errors could also expand the cellular proteome, their role in cancer biology remains poorly understood. Tumor suppressors called caretakers block cancer initiation and progression by preventing DNA mutations and/or stimulating DNA repair. If translational errors contribute to tumorigenesis, then caretaker genes should prevent such errors in normal cells in response to oncogenic stimuli. Here, we show that the process of cellular senescence induced by oncogenes, tumor suppressors or chemotherapeutic drugs is associated with a reduction in translational readthrough (TR) measured using reporters containing termination codons withing the context of both normal translation termination or programmed TR. Senescence reduced both basal TR and TR stimulated by aminoglycosides. Mechanistically, the reduction of TR during senescence is controlled by the RB tumor suppressor pathway. Cells that escape from cellular senescence either induced by oncogenes or chemotherapy have an increased TR. Also, breast cancer cells that escape from therapy-induced senescence express high levels of AGO1x, a TR isoform of AGO1 linked to breast cancer progression. We propose that senescence and the RB pathway reduce TR limiting proteome diversity and the expression of TR proteins required for cancer cell proliferation.
Adult Day Program Directors’ Experiences Managing the COVID-19 Pandemic

Abstract Adult day programs (ADPs) provide community-based supervised recreational services to older adults living with chronic conditions and their caregivers. Most ADPs continued operating during the pandemic, tasking directors with the responsibility of managing the complexities of the coronavirus disease (COVID-19) pandemic. This study explored how ADP directors managed and experienced the COVID-19 pandemic. Semi-structured interviews were conducted with 18 ADP directors from a large health care region in Ontario. Thematic analysis resulted in four themes that detailed how participants: 1) responded to the pandemic with adapted services; 2) navigated the pandemic responses within systems and organizations, and with each other, clients, and caregivers; 3) felt personally during the pandemic; and 4) gained new insights on their clients and the importance of ADPs in the health care system due to the pandemic. Findings highlight pre-existing and emerging gaps and opportunities within ADP service provision for clients and caregivers, as well as service providers and directors.
Natural History of Facioscapulohumeral Dystrophy in Children

Background and Objectives Data on the natural history of facioscapulohumeral dystrophy (FSHD) in childhood are limited and critical for improved patient care and clinical trial readiness. Our objective was to describe the disease course of FSHD in children. Methods We performed a nationwide, single-center, prospective cohort study of FSHD in childhood assessing muscle functioning, imaging, and quality of life over 2 years of follow-up. Results We included 20 children with genetically confirmed FSHD who were 2 to 17 years of age. Overall, symptoms were slowly progressive, and the mean FSHD clinical score increased from 2.1 to 2.8 (p = 0.003). The rate of progression was highly variable. At baseline, 16 of 20 symptomatic children had facial weakness; after 2 years, facial weakness was observed in 19 of 20 children. Muscle strength did not change between baseline and follow-up. The most frequently and most severely affected muscles were the trapezius and deltoid. The functional exercise capacity, measured with the 6-minute walk test, improved. Systemic features were infrequent and nonprogressive. Weakness-associated complications such as lumbar hyperlordosis and dysarthria were common, and their prevalence increased during follow-up. Pain and fatigue were frequent complaints in children, and their prevalence also increased during follow-up. Muscle ultrasonography revealed a progressive increase in echogenicity. Discussion FSHD in childhood has a slowly progressive but variable course over 2 years of follow-up. The most promising outcome measures to detect progression were the FSHD clinical score and muscle ultrasonography. Despite this disease progression, an improvement on functional capacity may still occur as the child grows up. Pain, fatigue, and a decreased quality of life were common symptoms and need to be addressed in the management of childhood FSHD. Our data can be used to counsel patients and as baseline measures for treatment trials in childhood FSHD.
Donor age and sex have limited effects on the mechanical and microstructural properties of human connective tissues

Connective tissues, such as tendons, ligaments, and capsules, play a large role in locomotion and joint stability and are often subjected to traumatic injuries and degeneration. The purpose of this study was to evaluate if the mechanical and microstructural properties of connective tissues correlate with the age and sex of the human donor. Dissected samples were prepared for mechanical testing, consisting of 10 cycles of preconditioning, a stress‐relaxation ramp and hold, and a quasi‐static ramp to failure. During the testing protocol, the microstructural organization of tissues was analyzed using quantitative polarized light imaging. A linear mixed model was used to assess whether tissue type, donor age, or donor sex were significantly associated with mechanical and microstructural tissue properties. Tissue type had a significant effect on all parameters, while donor age and sex did not. Groupings by tissue type (i.e., tendon vs. ligament vs. capsule) were evident for microstructural data, with tendons having a tighter grouping and ligaments having a larger spread of values. The interaction of tissue type and age yielded a significant effect for linear modulus only (p = 0.007), with the palmaris tendon appearing to have the largest contribution to this effect. There were no significant interaction effects between sex and tissue type or donor age. Donor age appears to affect linear modulus in some, but not all, tissue types. Otherwise, age and sex do not have significant effects on the mechanical and microstructural properties of the range of connective tissues that were analyzed in this study.
Transanal rectopexy for external rectal prolapse

Purpose The surgical management of patients with full-thickness rectal prolapse (FTRP) continues to remain a challenge in the laparoscopic era. This study retrospectively assesses a cohort of patients undergoing a transanal suture sacro rectopexy supported by sclerosant injection into the presacral space under ultrasound guidance. Methods Patients with FTRP underwent a sutured transrectal presacral fixation of 2/3 of the circumference of the rectum from the third sacral vertebra to the sacrococcygeal junction through a side-viewing operating proctoscope. The procedure was supplemented by ultrasound-guided injection into the retrorectal space of a 2 mL solution of sodium tetradecyl sulfate/polidocanol mixed with air. Patients were functionally assessed before and 6 months after surgery with the Agachan constipation score and the Pescatori incontinence score. Results There were 36 adult patients (26 males; the range of age, 23–92 years). The mean operative time was 27 minutes (range, 23–50 minutes) with no recorded perioperative morbidity. The median follow-up was 66 months (range, 48–84 months) with 1 (2.8%) recurrence presenting 18 months after surgery. There were 19 patients (52.8%) who presented with incontinence before surgery with 17 out of 19 (89.5%) reporting improvement in their Pescatori score (P<0.001). No patient had worsening incontinence and there were no de novo incontinence cases. Constipation scores improved in 23 out of 36 patients (63.9%) with a mean score reduction difference of 7.91 (P=0.001). Conclusion Transanal sutured sacral rectopexy with supplemental presacral sclerosant injection is safe and effective in the management of FTRP with sustained improvement in bowel function.
Higher Self-Esteem Associated With Less Symptoms of Anxiety and Depression Among Young Adults After the Loss of a Parent to Cancer—A Longitudinal Study

Objective: The purpose of the study was to examine associations between self-esteem and symptoms of anxiety and depression among young adults who lost a parent to cancer. Methods: Older adolescents and young adults, aged 16 to 28 years, who had lost their parent to cancer and had accepted an invitation to join a support group, completed a questionnaire 5 to 8 months after the loss and a similar questionnaire about 10 months later (follow-up). Of a total of 77 young adults who participated in the study, 56 completed both questionnaires. Self-esteem was measured with the Rosenberg Self-Esteem Scale. Symptoms of anxiety and depression were measured with the Hospital Anxiety and Depression Scale. Univariate and multiple linear regression models were used to analyze the associations. Result: Self-esteem was significantly associated with symptoms of anxiety and depression at baseline and at follow-up. Conclusion: This study reveals that self-esteem is a valuable explanatory variable, and that it is associated with both symptoms of anxiety and depression in bereavement. This new knowledge could be used to guide future support to parentally bereaved young adults.
Anti‐diabetic drugs and sarcopenia: emerging links, mechanistic insights, and clinical implications

Sarcopenia, characterized by loss of skeletal muscle mass, quality, and strength, has become a common hallmark of ageing and many chronic diseases. Diabetes mellitus patients have a higher prevalence of sarcopenia, which greatly aggravates the metabolic disturbance and compromises treatment response. Preclinical and clinical studies have shown differential impacts of anti‐diabetic drugs on skeletal muscle mass, strength, and performance, highlighting the importance of rational therapeutic regimen from the perspective of sarcopenia risk. In this review, we provide an update on the regulation of muscle mass and quality by major anti‐diabetic drugs, focusing primarily on emerging data from clinical studies. We also discuss the underlying mechanisms and clinical implications for optimal selection of anti‐diabetic drugs to reduce the risk of sarcopenia. In view of the lifelong use of anti‐diabetic drugs, we propose that a better understanding of the sarcopenia risk and interventional strategies is worthy of attention in future studies.
The lectin pathway does not contribute to glomerular injury in the nephrotoxic nephritis model

Rapidly progressive crescentic glomerulonephritis occurs in number systemic and primary glomerular diseases, including anti‐glomerular basement membrane disease, anti‐neutrophil cytoplasmic antibody vasculitis and lupus nephritis. Our understanding of pathogenic mechanisms comes from animal models of disease such as the nephrotoxic nephritis model. The lectin pathway of complement activation has been shown to play a key role in several models of inflammation including renal ischaemia reperfusion. However, the lectin pathway is not required for crescentic glomerulonephritis in the anti‐myeloperoxidase model of anti‐neutrophil cytoplasmic antibody vasculitis. The aim of the current study was to explore the role of the lectin pathway in the nephrotoxic nephritis model, which is another model of crescentic glomerulonephritis.
Effect of Levetiracetam Use Duration on Overall Survival of Isocitrate Dehydrogenase Wild-Type Glioblastoma in Adults

Background and Objectives The association between levetiracetam and survival with isocitrate dehydrogenase (IDH) wild-type glioblastomas is controversial. We investigated whether the duration of levetiracetam use during the standard chemoradiation protocol affects overall survival (OS) of patients with IDH wild-type glioblastoma. Methods In this observational single-institution cohort study (2010–2018), inclusion criteria were (1) age ≥18 years; (2) newly diagnosed supratentorial tumor; (3) histomolecular diagnosis of IDH wild-type glioblastoma; and (4) standard chemoradiation protocol. To assess the survival benefit of levetiracetam use during the standard chemoradiation protocol (whole duration, part time, and never subgroups), a Cox proportional hazard model was constructed. We performed a case-matched analysis (1:1) between patients with levetiracetam use during the whole duration of the standard chemoradiation protocol and patients with levetiracetam use part time or never according to the following criteria: sex, age, epileptic seizures at diagnosis, Radiation Therapy Oncology Group recursive partitioning analysis (RTOG-RPA) class, tumor location, preoperative volume, extent of resection, and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status. Patients with unavailable O6-methylguanine-DNA methyltransferase promoter methylation status (48.5%) were excluded. Results A total of 460 patients were included. The median OS was longer in the 116 patients with levetiracetam use during the whole duration of the standard chemoradiation protocol (21.0 months; 95% confidence interval [CI] 17.2–24.0) than in the 126 patients with part-time levetiracetam use (16.8 months; 95% CI 12.4–19.0) and in the 218 patients who never received levetiracetam (16.0 months; 95% CI 15.5–19.4; p = 0.027). Levetiracetam use during the whole duration of the standard chemoradiation protocol (adjusted hazard ratio [aHR] 0.69; 95% CI 0.52–0.93; p = 0.014), MGMT promoter methylation (aHR 0.53; 95% CI 0.39–0.71; p < 0.001), and gross total tumor resection (aHR 0.57; 95% CI 0.44–0.74; p < 0.001) were independent predictors of longer OS. After case matching (n = 54 per group), a longer OS was found for levetiracetam use during the whole duration of the standard chemoradiation protocol (hazard ratio 0.63; 95% CI 0.42–0.94; p = 0.023). Discussion Levetiracetam use during the whole standard chemoradiation protocol possibly improves OS of patients with IDH wild-type glioblastoma. It should be considered in the antitumor strategy of future multicentric trials. Classification of Evidence This study provides Class III evidence that in individuals with IDH wild-type glioblastoma, levetiracetam use throughout the duration of standard chemotherapy is associated with longer median OS.
Expression of Senescence and Apoptosis Biomarkers in Synchronous Bilateral Breast Cancer: A Case Report

Background: Synchronous bilateral breast cancer (SBBC) provides a special condition where two independent breast tumors are exposed to cancer pharmacotherapy within a uniform pharmacokinetic milieu. Both senescence and apoptosis are established responses to therapy; however, they have potentially variable contributions to the overall outcome of treatment, which are yet to be determined. Methods: In this report, we describe the clinicopathological picture of two SBBC cases that received standard anticancer treatment and assess their expression profile of several molecular hallmarks of senescence and apoptosis. Results: Our analysis identified that synchronous tumors have variable expression profiles of both senescence- and apoptosis-associated biomarkers, despite comparable pathological responses to neoadjuvant chemotherapy and current survival rates. Conclusions: Our results highlight the variable expression of senescence- and apoptosis-associated markers in breast tumors (despite the shared somatic genetic background) and invites a large-scale assessment of both senescence and apoptosis in breast cancer tissue in vivo and their contribution to the pathological response and overall survival.
Neural stem/precursor cells dynamically change their epigenetic landscape to differentially respond to BMP signaling for fate switching during brain development

In this study, Katada et al. investigated NPC fate regulation and, using multiple genome-wide analyses, they demonstrate that Smads, transcription factors that act downstream from BMP signaling, target dramatically different genomic regions in neurogenic and gliogenic NPCs. Their results show the regulation of NPC property change mediated by the interplay between cell-extrinsic cues and -intrinsic epigenetic programs during cortical development.
Risk of Bleeding after Transcatheter Aortic Valve Replacement: impact of Preoperative Antithrombotic Regimens

Introduction Bleeding after transcatheter aortic valve replacement (TAVR) has a negative impact on the outcome of the procedure. Risk factors for bleeding vary widely in the literature, and the impact of preoperative antithrombotic agents has not been fully established. The objectives of our study were to assess bleeding after TAVR as defined by the Valve Academic Research Consortium-2 (VARC-2), identify its risk factors, and correlate with antithrombotic treatment in addition to its effect on procedural mortality. Methods The study included 374 patients who underwent TAVR from 2009 to 2018. We grouped the patients into four groups according to the VARC-2 definition of bleeding. Group 1 included patients without bleeding (n=265), group 2 with minor bleeding (n=22), group 3 with major bleeding (n=61), and group 4 with life-threatening bleeding (n=26). The median age was 78 (25th-75th percentiles: 71-82), and 226 (60.4%) were male. The median EuroSCORE was 3.4 (2-6.3), and there was no difference among groups (P=0.886). The TAVR approach was transfemoral (90.9%), transapical (5.6%), and trans-subclavian (1.9%). Results: Predictors of bleeding were stroke (OR: 2.465; P=0.024) and kidney failure (OR: 2.060; P=0.046). Preoperative single and dual antiplatelet therapy did not increase the risk of bleeding (P=0.163 and 0.1, respectively). Thirty-day mortality occurred in 14 patients (3.7%), and was significantly higher in patients with life-threatening bleeding (n=8 [30.8%]; P<0.001). Conclusion: Bleeding after TAVR is common and can be predicted based on preprocedural comorbidities. Preprocedural antithrombotic therapy did not affect bleeding after TAVR in our population.
Malignancies and Biosensors: A Focus on Oral Cancer Detection through Salivary Biomarkers

Oral cancer is among the deadliest types of malignancy due to the late stage at which it is usually diagnosed, leaving the patient with an average five-year survival rate of less than 50%. The booming field of biosensing and point of care diagnostics can, in this regard, play a major role in the early detection of oral cancer. Saliva is gaining interest as an alternative biofluid for non-invasive diagnostics, and many salivary biomarkers of oral cancer have been proposed. While these findings are promising for the application of salivaomics tools in routine practice, studies on larger cohorts are still needed for clinical validation. This review aims to summarize the most recent development in the field of biosensing related to the detection of salivary biomarkers commonly associated with oral cancer. An introduction to oral cancer diagnosis, prognosis and treatment is given to define the clinical problem clearly, then saliva as an alternative biofluid is presented, along with its advantages, disadvantages, and collection procedures. Finally, a brief paragraph on the most promising salivary biomarkers introduces the sensing technologies commonly exploited to detect oral cancer markers in saliva. Hence this review provides a comprehensive overview of both the clinical and technological advantages and challenges associated with oral cancer detection through salivary biomarkers.
Comparison of Kit-Based Metabolomics with Other Methodologies in a Large Cohort, towards Establishing Reference Values

Metabolic profiling is an omics approach that can be used to observe phenotypic changes, making it particularly attractive for biomarker discovery. Although several candidate metabolites biomarkers for disease expression have been identified in recent clinical studies, the reference values of healthy subjects have not been established. In particular, the accuracy of concentrations measured by mass spectrometry (MS) is unclear. Therefore, comprehensive metabolic profiling in large-scale cohorts by MS to create a database with reference ranges is essential for evaluating the quality of the discovered biomarkers. In this study, we tested 8700 plasma samples by commercial kit-based metabolomics and separated them into two groups of 6159 and 2541 analyses based on the different ultra-high-performance tandem mass spectrometry (UHPLC-MS/MS) systems. We evaluated the quality of the quantified values of the detected metabolites from the reference materials in the group of 2541 compared with the quantified values from other platforms, such as nuclear magnetic resonance (NMR), supercritical fluid chromatography tandem mass spectrometry (SFC-MS/MS) and UHPLC-Fourier transform mass spectrometry (FTMS). The values of the amino acids were highly correlated with the NMR results, and lipid species such as phosphatidylcholines and ceramides showed good correlation, while the values of triglycerides and cholesterol esters correlated less to the lipidomics analyses performed using SFC-MS/MS and UHPLC-FTMS. The evaluation of the quantified values by MS-based techniques is essential for metabolic profiling in a large-scale cohort.