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Aim: To evaluate the changes in periodontal parameters (reduction in probing pocket depth [PPD], gain in clinical attachment level [CAL] and reduction in full-mouth bleeding on probing [BoP]) after subgingival instrumentation of periodontal pockets at different time points in systemically healthy patients suffering from periodontitis., Materials and Methods: Four databases were searched for RCTs that carried out subgingival instrumentation in periodontal pockets and evaluated PPD at a minimum of two consecutive time points other than baseline. The analysis was conducted for both all pocket depths and stratified for initially shallow (4-5 mm) and deep (≥6 mm) pockets and data were extracted for various time points, 1-2, 3-4 and 5-6 months. Weighted mean effects (WMEs) were calculated with 95% confidence interval (CI) and predictive intervals were calculated., Results: Twenty-nine RCTs were identified, and all of them were included in the meta-analysis. The results showed that for both shallow and deep pockets there was a small though clinically meaningful change between 1- to 2-month and 3- to 4-month time points and between these and 5-6 months., Conclusions: In systemically healthy patients, the greater part of reduction in PPD and gain in CAL occurs within the first 1-2 months after subgingival instrumentation. However, additional benefits in terms of pocket depth reduction occur beyond these early time points., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Two-dimensional semiconductors, such as transition metal dichalcogenides, have demonstrated tremendous promise for the development of highly tunable quantum devices. Realizing this potential requires low-resistance electrical contacts that perform well at low temperatures and low densities where quantum properties are relevant. Here we present a new device architecture for two-dimensional semiconductors that utilizes a charge-transfer layer to achieve large hole doping in the contact region, and implement this technique to measure the magnetotransport properties of high-purity monolayer WSe 2 . We measure a record-high hole mobility of 80,000 cm 2  V -1  s -1 and access channel carrier densities as low as 1.6 × 10 11  cm -2 , an order of magnitude lower than previously achievable. Our ability to realize transparent contact to high-mobility devices at low density enables transport measurements of correlation-driven quantum phases including the observation of a low-temperature metal-insulator transition in a density and temperature regime where Wigner crystal formation is expected and the observation of the fractional quantum Hall effect under large magnetic fields. The charge-transfer contact scheme enables the discovery and manipulation of new quantum phenomena in two-dimensional semiconductors and their heterostructures., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Despite high rates of success for dental implants, implant failure due to several causes may require explantation. In the present retrospective study, implants removed between 2000 and 2022 have been registered and the cause of removal has been established. All implants were removed by a single operator (PPM) in the department of Oral Surgery of the George Eastman Dental Hospital in Rome, Italy. Characteristics of removed implants such as implant surface, morphology (bone versus tissue level implants), type of restoration (fixed versus removable), in the case of fixed restorations, mode of retention (cement versus screw-retained), location of the implant (maxillary versus mandibular arch) were recorded. Furthermore, patient-level characteristics were also recorded (systemic health conditions and medications taken, smoking habits and previous history of periodontitis). In total, 381 implants in 381 patients were removed in the 20-year time-span. The most frequent cause of removal was peri-implantitis (82.4% of implants), followed by implant malposition and loss of osteointegration. The survival time was not affected by the cause of removal, while bone level implants had a longer survival time versus tissue level implants. Maxillary implants had a higher prevalence of peri-implantitis compared to mandibular implants.

Objectives: This study aimed to describe characteristics and outcomes associated with difficult airway response team (DART) encounters in the emergency department (ED)., Methods: We performed a descriptive analysis of a prospective, single-center database of DART encounters in the ED from April 1, 2016 to March 31, 2021 cross-referenced with retrospective chart review. Adult ED patients ≥18 years old for whom a DART was activated were eligible. We prospectively collected activation characteristics, intubation indications, operator characteristics, and intubation methods used for DART encounters. Retrospective chart review was conducted to obtain patient demographics and outcome variables. Descriptive analyses were computed for all outcomes., Results: We analyzed 89 DART encounters. No intubation attempts were made prior to DART activation in 52 cases (58.4%). The most common indications for intubation were angioedema ( n  = 17, 19.1%) or other airway obstruction ( n  = 15, 16.9%). A definitive airway was established by anesthesiology ( n  = 46, 51.7%), emergency medicine ( n  = 25, 28.1%), trauma surgery ( n  = 9, 10.1%), and ENT ( n  = 5, 5.6%). The most common method of intubation used to establish a definitive airway was video laryngoscopy with a bougie or D-blade ( n  = 29, 32.6%) followed by flexible fiberoptic intubation ( n  = 19, 21.3%). A surgical airway was required in eight encounters (cricothyrotomy [ n  = 4, 4.5%]; tracheostomy [ n  = 4, 4.5%]). Cases were managed in the ED ( n  = 73, 82%), operating room (OR) ( n  = 10, 11.2%), and intensive care unit (ICU) ( n  = 1, 1.1%). All patients requiring intubation had an endotracheal or surgical airway established., Conclusion: Our findings provide important insights regarding ED DART utilization and have implications when considering institution of a DART in the ED., Competing Interests: Rosemarie Fernandez reports grant funding from the Defense Health Agency and the National Science Foundation. Nicholas G. Maldonado, Meredith Thompson, Caroline Srihari, Liam Holtzman, Jonathan Liu, Rolando Otero, and Muhammad Abdul Baker Chowdhury have no conflicts of interest to report., (© 2024 The Authors. Journal of the American College of Emergency Physicians Open published by Wiley Periodicals LLC on behalf of American College of Emergency Physicians.)

Purpose: To assess the implant failure rate and clinical and radiographic outcomes of implants affected by peri-implantitis that received surgical treatment., Materials and Methods: A systematic search was conducted of three databases (PubMed, Embase and Cochrane Library) to identify studies that examined implant failure and biological outcomes after surgical peri-implantitis treatment, including ≥ 10 patients and reporting on a follow-up period of at least 12 months. Data and risk of bias were assessed qualitatively and quantitively. Surgical modalities were subdivided into reconstructive, non-reconstructive and combined. Meta-analyses were performed for implant failure, marginal bone level and probing pocket depth at 12 and 36 months with the respective subset of available data for each time and endpoint., Results: A total of 45 studies with 3,463 treated implants were included in the quantitative evaluation. Meta-analyses revealed low implant failure rates of 1.2% (95% confidence interval 0.4%, -2.1%) and 4.2% (95% confidence interval 1.0%, -8.8%) at 12 and 36 months, respectively. No significant difference between the subgroups was observed at 12 months. At 36 months, reconstructive modalities showed a significantly lower implant failure rate (1.0%; 95% confidence interval 0.0%, 5.0%; P = 0.04, χ2(1) = 4.1) compared to non-reconstructive modalities (8.0%; 95% confidence interval 2.0%, 18.0%). The mean probing pocket depth was 3.71 mm (95% confidence interval 3.48, 3.94 mm) at 12 months and 3.63 mm (95% confidence interval 3.02, 4.24 mm) at 36 months. The mean marginal bone loss was 3.31 mm (95% confidence interval 2.89, 3.74 mm) at 12 months and 2.38 mm (95% confidence interval 1.01, 3.74 mm) at 36 months. No significant differences between the modalities were observed for bleeding on probing after either of these time points. Cumulative interventions during supportive therapy were reported in 9% of the studies., Conclusion: Surgical treatment of peri-implantitis results in a low implant failure rate in the short and medium term. No differences were noted between the different interventions with regard to failure rate. Surrogate therapeutic endpoints were improved after treatment, without significant differences between the different modalities. Therapeutic success and/or disease resolution and cumulative interventions during supportive therapy are seldom reported in the literature, but limited long-term outcomes are documented consistently.

The Notch pathway is an evolutionarily preserved signaling pathway involved in a variety of vital cell functions. Additionally, it is one of the key regulators of inflammation, and controls the differentiation and function of different cells. Moreover, it was found to be involved in skeletal development and bone remodeling process. This review provides an overview of the involvement of the Notch signaling pathway in the pathogenesis of alveolar bone resorption in different forms of pathological conditions such as apical periodontitis, periodontal disease, and peri-implantitis. In vitro and in vivo evidence have confirmed the involvement of Notch signaling in alveolar bone homeostasis. Nonetheless, Notch signaling system, along with complex network of different biomolecules are involved in pathological process of bone resorption in apical periodontitis, periodontitis, and peri-implantitis. In this regard, there is a substantial interest to control the activity of this pathway in the treatment of disorders associated with its dysregulation. This review provides knowledge on Notch signaling and outlines its functions in alveolar bone homeostasis and alveolar bone resorption. Further investigations are needed to determine whether inhibition of the Notch signaling pathways might be beneficial and safe as a novel approach in the treatment of these pathological conditions., Competing Interests: None., (© 2023 The Authors.)

Two-dimensional transition-metal dichalcogenides (TMDs) have attracted tremendous interest due to the unusual electronic and optoelectronic properties of isolated monolayers and the ability to assemble diverse monolayers into complex heterostructures. To understand the intrinsic properties of TMDs and fully realize their potential in applications and fundamental studies, high-purity materials are required. Here, we describe the synthesis of TMD crystals using a two-step flux growth method that eliminates a major potential source of contamination. Detailed characterization of TMDs grown by this two-step method reveals charged and isovalent defects with densities an order of magnitude lower than those in TMDs grown by a single-step flux technique. For WSe 2 , we show that increasing the Se/W ratio during growth reduces point defect density, with crystals grown at 100:1 ratio achieving charged and isovalent defect densities below 10 10 and 10 11 cm -2 , respectively. Initial temperature-dependent electrical transport measurements of monolayer WSe 2 yield room-temperature hole mobility above 840 cm 2 /(V s) and low-temperature disorder-limited mobility above 44,000 cm 2 /(V s). Electrical transport measurements of graphene-WSe 2 heterostructures fabricated from the two-step flux grown WSe 2 also show superior performance: higher graphene mobility, lower charged impurity density, and well-resolved integer quantum Hall states. Finally, we demonstrate that the two-step flux technique can be used to synthesize other TMDs with similar defect densities, including semiconducting 2H-MoSe 2 and 2H-MoTe 2 and semimetallic T d -WTe 2 and 1T'-MoTe 2 .

Aim: The present multi-centre randomized clinical trial with 12 months of follow-up aimed at studying the added effect of sub-marginal instrumentation before surgical treatment of peri-implantitis., Materials and Methods: Forty-two patients diagnosed with peri-implantitis were recruited. After a behavioural intervention phase including oral hygiene instructions, patients were randomized to either receiving supra- and sub-marginal instrumentation on their affected implants (control group: 21 patients and 29 implants) or only supra-marginal instrumentation (test group: 21 patients and 24 implants), before undergoing surgery. Changes in the deepest probing pocket depth (PPD) with respect to baseline and a composite outcome of treatment success (no implant loss, no bone loss > 0.5 mm, no bleeding or suppuration on probing [BoP/SoP], and PPD ≤ 5 mm) at the 12-month examination were regarded as the primary outcomes of the trial., Results: At the 12-month examination, changes in the deepest PPD with respect to baseline amounted to -2.96 mm in the control group and to -3.11 mm in the test one (MD = -0.16; SE = 0.56; p = .769), while 21.4% of the implants in the control group and 33.3% in the test group presented treatment success (OR = 1.83; SE = 1.15; p = .338). With the exception of a longer non-surgical treatment duration in the control group (differences in  = -14.29 min; SE = 2.91; p < .001), no other secondary (e.g., soft-tissue recession, keratinized mucosa height, and bone level changes, as well as BoP, SoP, profuse bleeding and implant loss rates) or exploratory (i.e., early wound healing, aesthetics, surgical and total treatment duration, surgery difficulty, intra-operative bleeding, and adverse events) outcome demonstrated statistically significant differences between groups., Conclusions: The present multi-centre randomized clinical trial did not demonstrate an added effect of performing sub-marginal instrumentation 6 weeks before the surgical treatment of peri-implantitis. Larger clinical trials are however needed to confirm the present findings (Clinicaltrials.gov: NCT03620331)., (© 2022 The Authors. Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

With new advances in infectious disease, antifouling surfaces, and environmental microbiology research comes the need to understand and control the accumulation and attachment of bacterial cells on a surface. Thus, we employ intrinsic phase-shift reflectometric interference spectroscopic measurements of silicon diffraction gratings to non-destructively observe the interactions between bacterial cells and abiotic, microstructured surfaces in a label-free and real-time manner. We conclude that the combination of specific material characteristics ( i.e. , substrate surface charge and topology) and characteristics of the bacterial cells ( i.e. , motility, cell charge, biofilm formation, and physiology) drive bacteria to adhere to a particular surface, often leading to a biofilm formation. Such knowledge can be exploited to predict antibiotic efficacy and biofilm formation, and enhance surface-based biosensor development, as well as the design of anti-biofouling strategies.

Background: The use of CGP in guiding treatment decisions in aNSCLC with acquired resistance to ALK TKIs is questionable., Methods: We prospectively assessed the impact of CGP on the decision-making process in ALK-rearranged aNSCLC patients following progression on 2 nd /3 rd -generation ALK TKIs. Physician's choice of the most recommended next-line systemic treatment (NLST) was captured before and after receival of CGP results; the percentage of cases in which the NLST recommendation has changed was assessed along with the CGP turnaround time (TAT). Patients were divided into groups: patients in whom the NLST was initiated after (group 1) and before (group 2) receival of the CGP results. Time-to-treatment discontinuation (TTD) and overall survival (OS) with NLST were compared between the groups., Results: In 20 eligible patients (median [m]age 63 years [range, 40-89], females 75%, adenocarcinoma 100%, failure of alectinib 90%, FoundationOne Liquid CDx 80%), CGP has altered NLST recommendation in 30% of cases. CGP findings were as follows: ALK mutations 30% (l1171X 10%, G1202R, L1196M, G1269A, G1202R+l1171N+E1210K 5% each), CDKN2A/B mutation/loss 10%, c-met amplification 5%. CGP mTAT was 2.9 weeks [IQR, 2.4-4.4]. mTTD was 11.3 months (95% CI, 2.1-not reached [NR]) and 5.4 months (95% CI, 2.0-NR) in groups 1 and 2, respectively (p-0.34). mOS was 13.2 months (95% CI, 2.9-NR) and 13.0 months (95% CI, 6.0-NR) in groups 1 and 2, respectively (p-0.86)., Conclusion: CGP has a significant impact on the decision-making process in ALK-rearranged aNSCLC following progression on 2 nd /3 rd -generation ALK TKIs., Competing Interests: Author TS was employed by the company Statistical Consulting Unit. Disclosure (all outside of the submitted work): AR reported personal fees from Roche, Astra Zeneca, Merck Sharpe & Dohme, Novartis, Takeda, Elli Lilly, support for attending meetings from Bristol Myers Squibb, Roche, Boehringer Ingelheim. AO reported advisory fees from Merck Sharpe & Dohme, Bristol Myers Squibb, Roche, Astra Zeneca, Novartis, Boehringer Ingelheim. Damien Urban reported personal and consulting fees from Roche, Merck Sharpe & Dohme, Takeda, Astra Zeneca, Rhenium Oncotest, Bristol Myers Squibb. MM reported consulting fees from Boehringer Ingelheim, Roche, Astra Zeneca, MSD, BMS, Abbvie, Takeda, Pomicell. AZ reported grants from Bristol Myers Squibb, personal fees from Roche, Merck Sharpe & Dohme, Bristol Myers Squibb, Astra Zeneca, Takeda. JB reported grants and personal fees from Merck Sharpe & Dohme, Bristol Myers Squibb, Astra Zeneca, Roche, Abbvie, Takeda, OncoHost, ImmuneAI, Bayer, Novartis. AA reported research funding from Bristol Myers Squibb, personal and consulting fees from Bristol Myers Squibb, Roche, Pfizer, Astra Zeneca, Takeda, Novartis. NP reported research funding from Bristol-Myers Squibb, Eli Lilly, Foundation Medicine, Gaurdant360, Merk, MSD, Novartis, NovellusDx, Pfizer, Roche, Takeda, IP: Volatile Organic Compounds For Detecting Cell Dysplasia And Genetic Alterations Associated With Lung Cancer, WO2012023138; Breath Analysis of Pulmonary Nodules, US20130150261 A1; Apparatus for treating a target site of a body, WO/2015/059646 - all outside of the submitted work. ED reported grants from Astra Zeneca, Boehringer Ingelheim, personal fees from Boehringer Ingelheim, Roche, Astra Zeneca, Pfizer, Merck Sharpe & Dohme, Bristol Myers Squibb, Novartis, Takeda, Sanofi, Merck Serono, Medison Pharma, Janssen Israel- all outside of the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Raphael, Onn, Holtzman, Dudnik, Urban, Kian, Cohen, Moskovitz, Zer, Bar, Rabinovich, Grynberg, Oedegaard, Agbarya, Peled, Shochat and Dudnik.)

Introduction: Both pembrolizumab (P) as a monotherapy or in combination with platinum-based chemotherapy (PCT) represent standard first-line treatment options for advanced non-small cell lung cancer (aNSCLC) with PD-L1 tumor proportion score (TPS)≥50%. No predictive biomarkers exist to guide treatment decisions., Methods: 423 consecutive patients with EGFR/ALK/ROS1-wild-type PD-L1 TPS≥50% aNSCLC receiving P (n = 302) or PCT (n = 121) as a first-line treatment were identified in the electronic databases of 5 Israeli cancer centers. Overall survival (OS, months [mo]) was assessed in correlation with blood biomarkers (BB: NLR, dNLR, PLR, SII, LIPI, ALI); a predictive score was developed., Results: In the propensity score matching analysis (n = 236; 118 patients in each group matched for age, sex and ECOG PS), mOS was 17.2mo (95% CI, 13.2-36.5) and 21.3mo (95% CI, 14.8-NR) in groups P and PCT, respectively (P = .44). In group P, NLR, dNLR, PLR, LIPI, and ALI significantly correlated with OS in uni- and multivariate COX regression analyses (P < .05), whereas in group PCT, none of the BB demonstrated a significant correlation. A predictive score was developed (each parameter receiving one point): age≥65, female sex, never-smoking status, adenocarcinoma histology, dNLR≥3. In patients with predictive score 3-5, OS was significantly longer with PCT as compared to P: mOS NR (95% CI, 15.3-NR) and 8.7mo (95% CI, 5.8-13.7) (P = .0005), while OS didn't differ significantly in patients with predictive score 0-2 (P = .61)., Conclusion: With the limitations of the retrospective analysis, the proposed dNLR-based score appears to predict OS with P and PCT., (Copyright © 2021 Elsevier Inc. All rights reserved.)