Miracle-dz/UniFAR-FTUs huggingface dataset:
Accuracy of CBCT-based root canal length predetermination using new endodontic planning software compared to measurements performed with an electronic apex locator ex vivo.

OBJECTIVE To evaluate the accuracy of the new endodontic planning software (3D Endo Dentsply Sirona) based on cone beam computed tomography (CBCT) to predetermine root canal lengths compared with measurements performed with an electronic apex locator (Raypex 6; VDW) ex vivo. MATERIALS AND METHODS CBCT scans of forty extracted human maxillary (n = 20) and mandibular (n = 20) molars were taken, and root canal lengths were predetermined with the 3D Endo software using the apical foramen (AF) and the adjoining cusp as references. Root canal lengths were determined with the Raypex 6 using the same references. To evaluate the accuracy, absolute differences between both methods and the actual root canal length (gold standard) were calculated and statistically analyzed. RESULTS Differences between lengths measured with the 3D Endo and the Raypex 6 compared with the gold standard showed no significant differences (P = 0.879). Mean differences were 0.37 mm versus 0.35 mm in the maxillary molars, and 0.30 mm versus 0.31 mm in the mandibular molars. A total of 75.8% (3D Endo) and 79.1% (Raypex 6) of all measurements were within the limits of ± 0.5 mm. Both methods showed a tendency to result in short measurements (P < 0.001). CONCLUSIONS Within the limitations of this study, the 3D Endo software enables an accurate three-dimensional (3D) predetermination of root canal lengths.
Metformin hydrochloride and wound healing: from nanoformulation to pharmacological evaluation

Abstract Niosomes as drug delivery systems have the ability to decrease drugs' side effects and increase their therapeutic effectiveness. Metformin HCl is an oral antihyperglycemic agent belonging to biguanides. It is the most commonly chosen drug as a startup therapy for patients newly diagnosed with type 2 diabetes. This study aims to encapsulate metformin HCl inside niosomes to be used as a transdermal formulation helping to prolong its antidiabetic effect and investigate its ability to enhance wound healing in diabetic patients. Thin film hydration method was used to prepare metformin HCl niosomes using different proportions of Span 60, Span 40, Tween 80, and cholesterol. All formulations were characterized using transmission electron microscope, zeta potential, and vesicle size. In vitro release studies, stability studies and in vivo evaluation were conducted on selected niosomal formulations. The results of entrapment efficiency ranged from 13% to 32%. Vesicle sizes were determined in nano-range. The in vitro release profile of metformin HCl from niosomes occurred in two consecutive phases. Biological evaluation on diabetic rats revealed that metformin HCl niosomal gel given every 2 days showed a better sustained antidiabetic effect than oral doses given daily. It also showed an improvement in wound healing for diabetic rats given metformin formulations compared to nontreated ones.
Boost Symbolic Execution Using Dynamic State Merging and Forking

Symbolic execution has achieved wide application in software testing and analysis. However, path explosion remains the bottleneck limiting scalability of most symbolic execution engines in practice. One of the promising solutions to address this issue is to merge explored states and decrease number of paths. Nevertheless, state merging leads to increase in complexity of path predicates at the same time, especially in the situation where variables with concrete values are turned symbolic and chances of concretely executing some statements are dissipated. As a result, calculating expressions and constraints becomes much more timeconsuming and thus, the performance of symbolic execution is weakened in contrast. To resolve the problem, we propose a merge-fork framework enabling states under exploration to switch automatically between merging mode and forking mode. First, active state forking is introduced to enable forking a state into multiple ones as if a certain merging action taken before were eliminated. Second, we perform dynamic mergefork analysis to cut source code into pieces and continuously evaluate efficiency of different merging strategies for each piece. Our approach dynamically combines paths under exploration to maximize opportunities for concrete execution and ease the burden on underlying solvers. We implement the framework on the foundation of the symbolic execution engine KLEE, and conduct experiments on GNU Coreutils code using our prototype to present the effect of our proposition. Experiments show up to 30% speedup and 80% decrease in queries compared to existing works.
Profiling mycobacterial communities in pulmonary nontuberculous mycobacterial disease

The diagnosis of pulmonary non-tuberculous mycobacterial disease (pNTM) is dependent on the isolation of NTM in culture, which is prone to overgrowth and contamination and may not capture the diversity of mycobacteria present, including rare or unidentified species. This study aimed to develop a culture independent method of detecting and identifying mycobacteria from sputum samples using partial sequencing of the hsp65 gene. DNA was extracted from sputum samples from subjects with pNTM and disease controls. Multiplexed partial sequencing of the hsp65 gene was performed using the Illumina MiSeq and custom primers. A reference database of hsp65 sequences was created for taxonomy assignment. Sequencing results were obtained from 42 subjects (31 cases, 11 controls). Mycobacterial sequences were identified in all subjects. In 90.5% of samples more than one species was found (median 5.5). The species isolated in culture was detected by sequencing in 81% of subjects and was the most abundant species in 62%. The sequencing of NTM from clinical samples reveals a far greater diversity than conventional culture and suggests NTM are present as communities rather than a single species. NTM were found to be present even in the absence of isolation in culture or clinical disease.
Postoperative pain after glide path preparation using manual, reciprocating and continuous rotary instruments: a randomized clinical trial

AIM To compare the incidence, intensity and prediction of postoperative pain after glide path preparation with manual, continuous rotary and a novel reciprocating glide path instrument. METHODOLOGY The study included 240 patients, who were treated by four specialists according to a planned treatment protocol. Following access cavity preparation and prior to glide path preparation, the subjects were randomly assigned to one of the three groups according to the glide path instrument by choosing a sealed envelope containing the group name: R-Pilot (VDW, Munich, Germany), ProGlider (Dentsply Sirona, Ballaigues, Switzerland) and stainless steel K-files (Dentsply Sirona; n = 80). Following glide path preparation, the teeth underwent standardized single visit root canal treatment procedures. The root canals were chemomechanically prepared using the ProTaper Next rotary system (Dentsply Sirona) under copious irrigation with 5.25% NaOCl. Final irrigation was performed with 17% EDTA and distilled water. Root fillings were placed using an epoxy resin sealer and gutta-percha with a cold lateral compaction technique. After coronal restorations were placed, the patients were discharged with a questionnaire about the incidence and intensity of pain at 6, 12, 18, 24, 48 and 72 h postoperatively. The data were analysed using chi-square, anova and Tukey tests and logistic regression analysis. RESULTS The presence of preoperative pain (OR ranged between 3.5 and 14.3) and the glide path preparation techniques (OR between 2.2 and 4.1) were associated with significant effects on the incidence of postoperative pain when comparing manual versus engine-driven glide path preparation (P < 0.05). Patients in the R-Pilot (Mean VAS ranged between 1.57-0.21) and ProGlider (1.97-0.28) groups reported significantly less postoperative pain scores than those in the manual group (2.82-1.32; P < 0.05). There was no significant difference between R-Pilot and ProGlider groups regarding the postoperative pain scores (P > 0.05). CONCLUSION Preparation of glide paths with rotating or reciprocating NiTi instruments was associated with less postoperative pain levels and incidence compared to manual glide path preparation with no significant difference between rotating and reciprocating instruments. Preoperative pain was the most significant predictor for the occurrence of postoperative pain.
DNA methylation-based age prediction and telomere length in white blood cells and cumulus cells of infertile women with normal or poor response to ovarian stimulation

An algorithm assessing the methylation levels of 353 informative CpG sites in the human genome permits accurate prediction of the chronologic age of a subject. Interestingly, when there is discrepancy between the predicted age and chronologic age (age acceleration or “AgeAccel”), patients are at risk for morbidity and mortality. Identification of infertile patients at risk for accelerated reproductive senescence may permit preventative action. This study aimed to assess the accuracy of the “epigenetic clock” concept in reproductive age women undergoing fertility treatment by applying the age prediction algorithm in peripheral (white blood cells [WBCs]) and follicular somatic cells (cumulus cells [CCs]), and to identify whether women with premature reproductive aging (diminished ovarian reserve) were at risk of AgeAccel in their age prediction. Results indicated that the epigenetic algorithm accurately predicts age when applied to WBCs but not to CCs. The age prediction of CCs was substantially younger than chronologic age regardless of the patient’s age or response to stimulation. In addition, telomeres of CCs were significantly longer than that of WBCs. Our findings suggest that CCs do not demonstrate changes in methylome-predicted age or telomere-length in association with increasing female age or ovarian response to stimulation.
Next Generation Sequencing Analysis in Early Onset Dementia Patients

Background: Early onset dementias (EOD) are rare neurodegenerative dementias that present before 65 years. Genetic factors have a substantially higher pathogenetic contribution in EOD patients than in late onset dementia. Objective: To identify known and/or novel rare variants in major candidate genes associated to EOD by high-throughput sequencing. Common-risk variants of apolipoprotein E (APOE) and prion protein (PRNP) genes were also assessed. Methods: We studied 22 EOD patients recruited in Memory Clinics, in the context of studies investigating genetic forms of dementia. Two methodological approaches were applied for the target-Next Generation Sequencing (NGS) analysis of these patients. In addition, we performed progranulin plasma dosage, C9Orf72 hexanucleotide repeat expansion analysis, and APOE genotyping. Results: We detected three rare known pathogenic mutations in the GRN and PSEN2 genes and eleven unknown-impact mutations in the GRN, VCP, MAPT, FUS, TREM2, and NOTCH3 genes. Six patients were carriers of only common risk variants (APOE and PRNP), and one did not show any risk mutation/variant. Overall, 69% (n = 9) of our early onset Alzheimer’s disease (EAOD) patients, compared with 34% (n = 13) of sporadic late onset Alzheimer’s disease (LOAD) patients and 27% (n = 73) of non-affected controls (ADNI, whole genome data), were carriers of at least two rare/common risk variants in the analyzed candidate genes panel, excluding the full penetrant mutations. Conclusion: This study suggests that EOD patients without full penetrant mutations are characterized by higher probability to carry polygenic risk alleles that patients with LOAD forms. This finding is in line with recently reported evidence, thus suggesting that the genetic risk factors identified in LOAD might modulate the risk also in EOAD.
Spatial shifts in frame-based Gamma Knife radiosurgery: A case for cone beam CT imaging as quality assurance using the Gamma Knife® Icon™.

Background Cone beam CT (CBCT) imaging has been integrated into the most recent version of the Leksell Gamma Knife for the primary purpose to facilitate fractionated therapy. Case description This case study presents three patients where the CBCT system of the Gamma Knife Icon discovered potentially clinically significant frame shifts. In each case, patients were imaged with volumetric MR prior to stereotactic frame placement. Immediately following frame placement, diagnostic stereotactic CT imaging was acquired with a stereotactic indicator box attached to the frame. Following treatment planning and immediately before radiosurgery, a CBCT was acquired using the on-board imaging functionality of the Gamma Knife Icon, which provides a registration of the patient's anatomy to stereotactic space independent of that provided by the stereotactic frame/fiducials. Co-registration of the CT and CBCT provides an estimate of the difference between these two estimates of stereotactic coordinates. The vector magnitudes of the differences measured at the center of stereotactic space were 0.93mm, 2.64mm and 2.18 mm for Case 1, Case 2 and Case 3 respectively. Conclusions Use of the CBCT functionality of the Gamma Knife Icon to verify the consistency of frame placement can prevent clinically significant targeting errors due to frame slippage or frame adapter mounting errors, and allows any required adjustments to be made without interrupting the overall treatment workflow.
Enhancing cofactor recycling in the bioconversion of racemic alcohols to chiral amines with alcohol dehydrogenase and amine dehydrogenase by coupling cells and cell‐free system

Alcohol dehydrogenase (ADH) and amine dehydrogenase (AmDH)‐catalyzed one‐pot cascade conversion of an alcohol to an amine provides a simple preparation of chiral amines. To enhance the cofactor recycling in this reaction, we report a new concept of coupling whole‐cells with the cell‐free system to enable separated intracellular and extracellular cofactor regeneration and recycling. This was demonstrated by the respective biotransformation of racemic 4‐phenyl‐2‐butanol 1a and 1‐phenyl‐2‐propanol 1b to (R)‐4‐phenylbutan‐2‐amine 3a and (R)‐1‐phenylpropan‐2‐amine 3b. Escherichia coli cells expressing S‐enantioselective CpsADH, R‐enantioselective PfODH, and NADH oxidase (NOX) was developed to oxidize racemic alcohols 1a–b to ketones 2a–b with full conversion via intracellular NAD+ recycling. AmDH and glucose dehydrogenase (GDH) were used to convert ketones 2a–b to amines (R)‐3a–b with 89–94% conversion and 891–943 times recycling of NADH. Combining the cells and enzymes for the cascade transformation of racemic alcohols 1a–b gave 70% and 48% conversion to the amines (R)‐3a and (R)‐3b in 99% ee, with a total turnover number (TTN) of 350 and 240 for NADH recycling, respectively. Improved results were obtained by using the E. coli cells with immobilized AmDH and GDH: (R)‐3a was produced in 99% ee with 71–84% conversion and a TTN of 1410‐1260 for NADH recycling, the highest value so far for the ADH–AmDH‐catalyzed cascade conversion of alcohols to amines. The concept might be generally applicable to this type of reactions.
Mortality in people with dementia, delirium, and unspecified cognitive impairment in the general hospital: prospective cohort study of 6,724 patients with 2 years follow-up

Purpose Cognitive impairment is common in older people admitted to hospital, but the outcomes are generally poorly understood, and previous research has shown inconsistent associations with mortality depending on the type of cognitive impairment examined and duration of follow-up. This study examines mortality in older people with any cognitive impairment during acute hospital admission. Patients and methods Prospective cohort of 6,724 people aged ≥65 years with a structured cognitive assessment on acute admission were included in this study. Cognitive spectrum disorder (CSD) was defined as delirium alone, known dementia alone, delirium superimposed on known dementia, or unspecified cognitive impairment. Mortality associated with different types of CSD was examined using a non-proportional hazards model with 2-year follow-up. Results On admission, 35.4% of patients had CSD, of which 52.6% died within 2 years. After adjustment for demographics and comorbidity, delirium alone was associated with increased mortality in the 6 months post-admission (HR =1.45, 95% CI 1.28–1.65) and again after 1 year (HR =1.44, 95% CI 1.17–1.77). Patients with known dementia (alone or with superimposed delirium) had increased mortality only after 3 months from admission (HR =1.85, 95% CI 1.56–2.18 and HR =1.80, 95% CI 1.52–2.14) compared with patients with unspecified cognitive impairment after 6 months (HR =1.55, 95% CI 1.21–1.99). Similar but partially attenuated associations were seen after adjustment for functional ability. Conclusion Mortality post-admission is high in older people with CSD. Immediate risk is highest in those with delirium, while dementia or unspecified cognitive impairment is associated with medium- to long-term risk. These findings suggest that individuals without dementia who develop delirium are more seriously ill (have required a larger acute insult in order to precipitate delirium) than those with pre-existing brain pathology (dementia). Further research to explain the mortality patterns observed is required in order to translate the findings into clinical care.
Oral health-related quality of life among male subjects with oral submucous fibrosis in a tertiary care hospital

Background: Oral submucous fibrosis is very common in Asia. It has many deleterious effects on individual's oral functions. Thus, there is a need to assess the effect of oral submucous fibrosis on quality of life. Objective: To assess the oral health-related quality of life (OHRQoL) in male subjects with oral submucous fibrosis. Methods: Two hundred and thirty male subjects in the age range of 20–40 years were recruited in the cross-sectional, two-group comparative study. Of 230 male subjects, 115 were oral submucous fibrosis subjects who were included in the study group and 115 healthy subjects formed the control group. English version of the oral health impact profile-14 (OHIP-14) was used to assess the OHRQoL. Wilcoxon signed-rank, Kruskal–Wallis, and Bonferroni tests were applied, and the P = 0.05 was considered as level of significance. Results: The mean and median OHIP-14 scores were 19.10 ± 0.66 and 18.00 in the study group and 3.98 ± 3.80 and 3.00 in the control group subjects, respectively (P < 0.001). Mean score of all the seven domains of OHIP-14 was significantly more in oral submucous fibrosis subjects (P < 0.001). All the oral submucous fibrosis subjects had one or more negative effects on OHRQoL compared to 64.34% of healthy subjects. Stage-4 of the oral submucous fibrosis had maximum effect on quality of life compared to other stages (P < 0.001). Conclusions: The quality of life among males is severely affected by oral submucous fibrosis, and Stage-4 of oral submucous fibrosis has maximum effect on the quality of life.
Patient-Reported Outcomes Over 5 Years After Whole- or Partial-Breast Radiotherapy: Longitudinal Analysis of the IMPORT LOW (CRUK/06/003) Phase III Randomized Controlled Trial

Purpose IMPORT LOW demonstrated noninferiority of partial-breast and reduced-dose radiotherapy versus whole-breast radiotherapy for local relapse and similar or reduced toxicity at 5 years. Comprehensive patient-reported outcome measures collected at serial time points are now reported. Patients and Methods IMPORT LOW recruited women with low-risk breast cancer after breast-conserving surgery. Patients were randomly assigned to 40 Gy whole-breast radiotherapy (control), 36 Gy whole-breast and 40 Gy partial-breast radiotherapy (reduced-dose), or 40 Gy partial-breast radiotherapy only (partial-breast) in 15 fractions. European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires Core 30 and Breast Cancer–Specific Module, Body Image Scale, protocol-specific items, and the Hospital Anxiety and Depression Scale were administered at baseline, 6 months, and 1, 2, and 5 years. Patterns of moderate/marked adverse effects (AEs) were assessed using longitudinal regression models, and baseline predictors were investigated. Results A total of 41 of 71 centers participated in the patient-reported outcome measures substudy; 1,265 (95%) of 1,333 patients consented, and 557 (58%) of 962 reported no moderate/marked AEs at 5 years. Breast appearance change was most prevalent and persisted over time (approximately 20% at each time point). Prevalence of breast hardness, pain, oversensitivity, edema, and skin changes reduced over time (P < .001 for each), whereas breast shrinkage increased (P < .001). Analysis by treatment group showed average number of AEs per person was lower in partial-breast (incidence rate ratio, 0.77; 95% CI, 0.71 to 0.84; P < .001) and reduced-dose (incidence rate ratio, 0.83; 95% CI, 0.76 to 0.90; P < .001) versus whole-breast group and decreased over time in all groups. Younger age, larger breast size/surgical deficit, lymph node positivity, and higher levels of anxiety/depression were baseline predictors of subsequent AE reporting. Conclusion Most AEs reduced over time, with fewer AEs in the partial-breast and reduced-dose groups. Baseline predictors for AE reporting were identified. These findings will facilitate informed discussion and shared decision making for future patients receiving moderately hypofractionated breast radiotherapy.
Olfactomedin 4 marks a subset of neutrophils in mice

Neutrophils are the most abundant immune cell of the innate immune system and participate in essential immune functions. Heterogeneity within neutrophils has been documented, but it is difficult to distinguish if these are altered activation states of a single population or separate subpopulations of neutrophils determined at the time of differentiation. Several groups have identified a subset of human neutrophils that express olfactomedin 4 (OLFM4) and increased OLFM4+ neutrophils during sepsis is correlated with worse outcome, suggesting these neutrophils or the OLFM4 they secrete may be pathogenic. We tested if mice could be used as a model to study OLFM4+ neutrophils. We found the OLFM4 expressing subset of neutrophils is conserved in mice. Depending on the strain, 7–35% of murine neutrophils express OLFM4 and expression is determined early in neutrophil differentiation. OLFM4+ neutrophils phagocytose and transmigrate with similar efficiency as OLFM4− neutrophils. Here we show that within neutrophil extracellular traps (NETs) OLFM4+ and OLFM4− neutrophils undergo NETosis and OLFM4 colocalizes. Finally, we generated an OLFM4 null mouse and show that these mice are protected from death when challenged with sepsis, providing further evidence that the OLFM4 expressing subpopulation of neutrophils, or the OLFM4 they secrete, may be pathogenic during overwhelming infection.