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Ersoy Kocabicak,1–3 Yasin Temel,1,2 Anke Höllig,4 Björn Falkenburger,5 Sonny KH Tan2,4 1Department of Neurosurgery, Maastricht University Medical Centre, 2Department of Neuroscience, Maastricht University, Maastricht, the Netherlands; 3Department of Neurosurgery, Ondokuz Mayis University, Samsun, Turkey; 4Department of Neurosurgery, 5Department of Neurology, RWTH Aachen University, Aachen, Germany Abstract: Deep brain stimulation (DBS) has become a well-accepted therapy to treat movement disorders, including Parkinson’s disease, essential tremor, and dystonia. Long-term follow-up studies have demonstrated sustained improvement in motor symptoms and quality of life. DBS offers the opportunity to selectively modulate the targeted brain regions and related networks. Moreover, stimulation can be adjusted according to individual patients’ demands, and stimulation is reversible. This has led to the introduction of DBS as a treatment for further neurological and psychiatric disorders and many clinical studies investigating the efficacy of stimulating various brain regions in order to alleviate severe neurological or psychiatric disorders including epilepsy, major depression, and obsessive–compulsive disorder. In this review, we provide an overview of accepted and experimental indications for DBS therapy and the corresponding anatomical targets. Keywords: deep brain stimulation, movement disorders, neurological disorders, psychiatric disorders, Parkinson’s disease

Autologous hematopoietic cell transplantation (AHCT) is a commonly used treatment in multiple myeloma (MM). However, real-world global demographic and outcome data are scarce. We collected data on baseline characteristics and outcomes from 61 725 patients with newly diagnosed MM who underwent upfront AHCT between 2013 and 2017 from nine national/international registries. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), relapse incidence (RI) and non-relapse mortality (NRM). Median OS amounted to 90.2 months (95% CI 88.2-93.6) and median PFS 36.5 months (95% CI 36.1-37.0). At 24 months, cumulative RI was 33% (95% CI 32.5%-33.4%) and NRM was 2.5% (95% CI 2.3%-2.6%). In the multivariate analysis, superior outcomes were associated with younger age, IgG subtype, complete hematological response at auto-HCT, Karnofsky score of 100%, international staging scoring (ISS) stage 1, HCT-comorbidity index (CI) 0, standard cytogenetic risk, auto-HCT in recent years, and use of lenalidomide maintenance. There were differences in the baseline characteristics and outcomes between registries. While the NRM was 1%-3% at 12 months worldwide, the OS at 36 months was 69%-84%, RI at 12 months was 12%-24% and PFS at 36 months was 43%-63%. The variability in these outcomes is attributable to differences in patient and disease characteristics as well as the use of maintenance and macroeconomic factors. In conclusion, worldwide data indicate that AHCT in MM is a safe and effective therapy with an NRM of 1%-3% with considerable regional differences in OS, PFS, RI, and patient characteristics. Maintenance treatment post-AHCT had a beneficial effect on OS., (© 2024 The Author(s). American Journal of Hematology published by Wiley Periodicals LLC.)

Background: Influenza A results in significant morbidity and mortality. VIR-2482, an engineered human monoclonal antibody with extended half-life, targets a highly conserved epitope on the stem region of influenza A hemagglutinin and may protect against seasonal and pandemic influenza., Methods: This double-blind, randomized, placebo-controlled, phase 2 study examined the safety and efficacy of VIR-2482 for seasonal influenza A illness prevention in unvaccinated healthy adults. Participants (N = 2977) were randomized 1:1:1 to receive VIR-2482 450 mg, VIR-2482 1200 mg, or placebo via intramuscular injection. Primary and secondary efficacy endpoints were the proportions of participants with reverse transcriptase-polymerase chain reaction-confirmed influenza A infection and either protocol-defined influenza-like illness (ILI) and Centers for Disease Control and Prevention-defined ILI or World Health Organization-defined ILI, respectively., Results: VIR-2482 450 mg and 1200 mg prophylaxis did not reduce the risk of protocol-defined ILI with reverse transcriptase-polymerase chain reaction-confirmed influenza A versus placebo (relative risk reduction, 3.8% [95% confidence interval (CI), -67.3 to 44.6] and 15.9% [95% CI, -49.3 to 52.3], respectively). At the 1200-mg dose, the relative risk reductions in influenza A illness were 57.2% (95% CI: -2.5 to 82.2) using Centers for Disease Control and Prevention ILI and 44.1% (95% CI: -50.5 to 79.3) using World Health Organization ILI definitions, respectively. Serum VIR-2482 levels were similar regardless of influenza status; variants with reduced VIR-2482 susceptibility were not detected. Local injection site reactions were mild and similar across groups., Conclusions: VIR-2482 1200 mg intramuscular was well tolerated but did not significantly prevent protocol-defined ILI. Secondary endpoint analyses suggest this dose may have reduced influenza A illness. Trial registration: ClinicalTrials.gov identifier, NCT05567783., Competing Interests: Potential conflicts of interest. S. K. T., D. C., D. P., M. L. A., K. B., W. W. Y., and P. S. P. are employees of Vir Biotechnology, Inc and report stock ownership in Vir Biotechnology, Inc. C. M. H. is a former employee and shareholder of Vir Biotechnology, Inc. and is a coauthor on select Vir Biotechnology, Inc. patents. J. M. and M. D. have nothing to disclose. C. F. reports receiving grant support from Vir Biotechnology, Inc. for conduct of the clinical trial. F. G. H. has received consulting fees from The University of Alabama and Krog Associates; served as a nonpaid consultant to Vir Biotechnology, Inc. and other companies involved in developing influenza therapeutics or vaccines, including Appili, Arcturus, Eradivir, Gilead, GSK, Janssen/JNJ, Fujifilm, Merck, Ridgeback, Roche/Genentech, Sanofi Pasteur, and Via Nova; is a trustee of the International Society for Influenza and other Respiratory Viruses; and has participated on a data safety monitoring board or advisory board for Imperial College London, University of Oxford, and Enanta. Cidara, Enanta, Shionogi, and Versatope have made charitable donations for Dr. Hayden's consulting time, and both Shionogi and Roche have provided meeting travel support. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Quality of life (QOL) is an important clinical endpoint in paediatric chronic conditions. How parent-proxy reports differ from child self-reported QOL in patients with anorectal malformation (ARM) and Hirschsprung's disease (HD) has not been well examined to date. This study evaluates agreement between parent-proxy and child-reported QOL scores in ARM and HD patients compared to healthy controls., Methods: We recruited ARM and HD patients aged 5-17 years and their parents at four tertiary referral centres between December 2020 to February 2023 who had corrective surgery done >12 months prior. Healthy controls were age-matched and gender-matched. They completed the Pediatric Quality of Life Inventory™ (PedsQL™) Generic Core Scales and General Well-Being (GWB) Scale. The questionnaires were administered in parallel parent-proxy-report and child self-report formats. Appropriate statistical analysis was performed with p < 0.05 significance. Data are reported as median (interquartile range). Ethical approval was obtained., Results: There were 65 ARM, 54 HD and 83 controls. There were no significant differences between parent-reported scores and child-reported scores overall in the Total, Psychosocial Health and Physical Health components of Core Scales for ARM, HD and controls. However, parent-reported scores were significantly higher than child-reported scores overall in ARM, HD and controls in the GWB Scale., Conclusion: Our findings show that parent-rated and child-rated overall QOL was similar in Core Scales for ARM, HD, and controls. However, parents overestimated child's overall GWB for ARM, HD and controls. This highlights the importance of capturing the perspectives of both parents and children to inform strategies to improve patient care., Level of Evidence: Level III., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Down syndrome (DS) is a common abnormality associated with anorectal malformation (ARM) and Hirschsprung's disease (HD). However, quality of life (QOL) in ARM and HD patients with DS is under-researched. This study compares parent-reported QOL and bowel function in ARM and HD patients with DS to those without., Methods: Between December 2020 to February 2023, parents of ARM and HD patients with and without DS aged 3-17 years who had undergone surgery > 12 months prior at four tertiary referral centers were recruited. We used the Pediatric Quality of Life Inventory™ (PedsQL™) Generic Core Scales, General Well-Being (GWB) Scale and Family Impact (FI) Module questionnaires, and the Rintala bowel function score (BFS)., Results: There were 101 ARM, 9 (8.9%) of whom had DS; and 87 HD, of whom 6 (6.9%) had DS. Parent-reported Core scores in ARM and HD with DS were comparable to those without DS. However, ARM and HD with DS had worse scores in the FI Module and bowel function than those without DS., Conclusion: Although parent-reported QOL in ARM and HD with DS is similar to those without DS, family impact and BFS are worse. Our findings are limited by small sample size in proportion of DS patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Clear cell renal cell carcinoma (ccRCC), the most common type of kidney cancer, is largely incurable in the metastatic setting. ccRCC is characterized by excessive lipid accumulation that protects cells from stress and promotes tumor growth, suggesting that the underlying regulators of lipid storage could represent potential therapeutic targets. Here, we evaluated the regulatory roles of GPR1 and CMKLR1, two G protein-coupled receptors of the protumorigenic adipokine chemerin that is involved in ccRCC lipid metabolism. Both genetic and pharmacologic suppression of either receptor suppressed lipid formation and induced multiple forms of cell death, including apoptosis, ferroptosis, and autophagy, thereby significantly impeding ccRCC growth in cell lines and patient-derived xenograft models. Comprehensive lipidomic and transcriptomic profiling of receptor competent and depleted cells revealed overlapping and unique signaling of the receptors granting control over triglyceride synthesis, ceramide production, and fatty acid saturation and class production. Mechanistically, both receptors enforced suppression of adipose triglyceride lipase, but each receptor also demonstrated distinct functions, such as the unique ability of CMKLR1 to control lipid uptake through regulation of sterol regulatory element-binding protein 1c and the CD36 scavenger receptor. Treating patient-derived xenograft models with the CMKLR1-targeting small molecule 2-(α-naphthoyl) ethyltrimethylammonium iodide (α-NETA) led to a dramatic reduction in tumor growth, lipid storage, and clear-cell morphology. Together, these findings provide mechanistic insights into lipid regulation in ccRCC and identify a targetable axis at the core of the histologic definition of this tumor that could be exploited therapeutically. Significance: Extracellular control of lipid accumulation via G protein receptor-mediated cell signaling is a metabolic vulnerability in clear cell renal cell carcinoma, which depends on lipid storage to avoid oxidative toxicity., (©2024 American Association for Cancer Research.)

Abortive transcript (AT) is a 2-19 nt long non-coding RNA that is produced in the abortive initiation stage. Abortive initiation was found to be closely related to RNA polymerase through in vitro experiments. Therefore, the distribution of AT length and the scale of abortive initiation are correlated to the promoter, discriminator, and transcription initiation sequence, and can be affected by transcription elongation factors. AT plays an important role in the occurrence and development of various diseases. Here we summarize the discovery of AT, the factors responsible for AT formation, the detection methods and biological functions of AT, to provide new clues for finding potential targets in the early diagnosis and treatment of cancers., Competing Interests: Conflict-of-interest statement: All authors have no conflicts of interest to declare., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Purpose: Children with anorectal malformation (ARM) and Hirschsprung's disease (HD) often experience bowel symptoms into adulthood, despite definitive surgery. This study evaluates the quality of life (QOL) and bowel functional outcome of children treated for ARM and HD in comparison to healthy controls., Methods: Between December 2020 and February 2023, we recruited patients with ARM and HD aged 3-17 years at four tertiary referral centres, who had primary corrective surgery done >12 months prior. Healthy controls were age-matched and sex-matched. All participants completed the Pediatric Quality of Life Inventory Generic Core Scales 4.0, General Well-Being (GWB) Scale 3.0 and Family Impact (FI) Module 2.0 Questionnaires. Bowel Function Score (BFS) Questionnaires were also administered. We also performed subgroup analysis according to age categories. Appropriate statistical analysis was performed with p<0.05 significance. Ethical approval was obtained., Results: There were 306 participants: 101 ARM, 87 HD, 118 controls. Patients with ARM and HD had significantly worse Core and FI Scores compared with controls overall and in all age categories. In the GWB Scale, only ARM and HD adolescents (13-17 years) had worse scores than controls. ARM and HD had significantly worse BFSs compared with controls overall and in all age categories. There was significant positive correlation between BFS and Core Scores, GWB Scores and FI Scores., Conclusion: Patients with ARM and HD had worse QOL than controls. Lower GWB Scores in adolescents suggests targeted interventions are necessary. Bowel function influences QOL, indicating the need for continuous support into adulthood., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The Malaysian healthcare system is under strain due to an aging population, the rising prevalence of chronic diseases, and heavy workloads among physicians. As costs and requirements continue to rise, telemedicine is critical for bridging gaps in supply and demand. However, there are limited studies on telemedicine adoption among Malaysian physicians. Furthermore, the existing literature on telemedicine adoption does not contain a comprehensive framework that integrates the multidimensional social influence, and technological, clinical, and individual factors., Objective: This research investigates the adoption of telemedicine among Malaysian physicians. It draws from the Technology Acceptance Model (TAM) and Kelman's Social Influence Theory., Methods: A survey was conducted among 230 participants in hospitals located in Kuala Lumpur and Selangor. The data were analyzed using Partial Least Squares Structural Equation Modeling (PLS-SEM)., Results: The study identified crucial factors influencing telemedicine adoption, including informational influences, rewards, perceived ease of use, and usefulness. Meanwhile, the Importance-performance Map Analysis (IPMA) identified perceived ease of use as the most important factor for physicians, but the highest performance was patient's records., Conclusions: The proposed integrated model enhances the understanding of telemedicine adoption and highlights the differential effects of individual, technological, clinical, and multidimensional social influence factors from the physicians' perspective. The findings can guide future studies and influence implementation strategies for telemedicine promotion in the Malaysian healthcare context. Hospitals should prioritize user-friendly technology and information provision, while telemedicine providers should enhance the accessibility of patient records to facilitate telemedicine adoption. Policymakers should consider supporting training programs that will boost physicians' confidence in effectively utilizing telemedicine., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Purpose: Although fewer than 5% of high-grade gliomas (HGG) are BRAF-V600E mutated, these tumors are notable as BRAF-targeted therapy shows efficacy for some populations. The purpose of this study was to evaluate response to the combination of encorafenib with binimetinib in adults with recurrent BRAF-V600-mutated HGG., Patients and Methods: In this phase 2, open-label, Adult Brain Tumor Consortium (ABTC) trial (NCT03973918), encorafenib and binimetinib were administered at their FDA-approved doses continuously in 28-day cycles. Eligible patients were required to have HGG or glioblastoma with a BRAF-V600E alteration that was recurrent following at least one line of therapy, including radiotherapy., Results: Five patients enrolled between January 2020 and administrative termination in November 2021 (due to closure of the ABTC). Enrolled patients received treatment for 2 to 40 months; currently one patient remains on treatment. Centrally determined radiographic response rate was 60%, with one complete response and two partial responses. Methylation profiling revealed that all tumors cluster most closely with anaplastic pleomorphic xanthoastrocytoma (PXA). Transcriptional profile for MAPK-response signature was similar across all tumors at baseline and did not correlate with response in this small population. Circulating tumor DNA measured in plasma samples before treatment, during response, and upon progression showed feasibility of detection for the BRAF-V600E alteration. No new safety signal was detected., Conclusions: Encorafenib and binimetinib exhibit positive tumor responses in patients with recurrent BRAF-V600E mutant HGG in this small series, warranting therapeutic consideration. Although toxicity remains a concern for BRAF-targeted therapies, no new safety signal was observed in these patients., (©2024 American Association for Cancer Research.)

Purpose: Patients with anorectal malformation (ARM) and Hirschsprung's disease (HD) live with long-term impact of these diseases even into adulthood. We aimed to explore the physical, social and emotional impact of these diseases in adolescents and young adults to develop best practices for transition care., Methods: We conducted one-on-one in-depth interviews with ARM and HD patients aged  ≥ 11 years who had undergone surgery at four tertiary referral centers. All interviews were audio-recorded and transcribed verbatim. We analyzed transcripts for recurring themes, and data were collected until data saturation was reached. Three researchers independently coded the transcripts for major themes using thematic analysis approach., Results: We interviewed 16 participants (11 males) between October 2022 and April 2023. Ages ranged from 11 to 26 years. Five major themes emerged: (1) personal impact (subthemes: physical, emotional and mental health, social, school), (2) impact on family, (3) perceptions of their future (subthemes: relationships, career, state of health), (4) sources of support (subthemes: family, peers, partner), and (5) transition care (subthemes: concerns, expectations). Only females expressed concerns regarding future fertility., Conclusion: This study highlights the evolving problems faced by adolescents and young adults with ARM and HD, especially gender-specific concerns. Our findings can inform efforts to provide individualized care., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The de novo design of small molecule-binding proteins has seen exciting recent progress; however, high-affinity binding and tunable specificity typically require laborious screening and optimization after computational design. We developed a computational procedure to design a protein that recognizes a common pharmacophore in a series of poly(ADP-ribose) polymerase-1 inhibitors. One of three designed proteins bound different inhibitors with affinities ranging from <5 nM to low micromolar. X-ray crystal structures confirmed the accuracy of the designed protein-drug interactions. Molecular dynamics simulations informed the role of water in binding. Binding free energy calculations performed directly on the designed models were in excellent agreement with the experimentally measured affinities. We conclude that de novo design of high-affinity small molecule-binding proteins with tuned interaction energies is feasible entirely from computation.

Introduction: Haemophilia is one of the commonest inherited bleeding disorders which may lead to long term disabilities if not treated properly. Our aim of study is to understand the clinical characteristic, treatment and complications of adult haemophilia patients in our centre., Materials and Methods: A retrospective cross-sectional review of all adult haemophilia A (HA) or haemophilia B (HB) patients who received treatment in Hospital Pulau Pinang from January 2021 to December 2022 was conducted. Data was retrieved from patients' medical records., Results: A total of 75 haemophilia patients (64 HA and 11 HB) were included in this study with median age of 37 years (range 19 70). 42 of them had severe haemophilia (50% of HA, 91% of HB). All HB and 93.8% of severe HA patients were on prophylaxis. Six severe and one mild HA patients developed inhibitor with four of them currently on non-factor prophylaxis. 24 patients (32%) had prior hepatitis C infection and all of them have been successfully treated. The mean annual bleeding rate for severe haemophilia patients were 1.77 (SD ±3.6). Target joints were observed in 9.3% of patients with ankle joint (71.4%) being the most affected joint. More than one quarter (26.7%) of our patients have comorbidities with majority of them having hypertension (17/20), followed by diabetes mellitus (5/20) and ischemic heart disease (5/20)., Conclusion: Our study showed that a significant number of adult patients with haemophilia have comorbidities. Apart from optimising factor replacement therapy, future planning should include improvement in screening, risk modification and prevention of cardiovascular disease.

Background: B56ε is a regulatory subunit of the serine/threonine protein phosphatase 2A, which is abnormally expressed in tumors and regulates various tumor cell functions. At present, the application of B56ε in pan-cancer lacks a comprehensive analysis, and its role and mechanism in hepatocellular carcinoma (HCC) are still unclear., Aim: To analyze B56ε in pan-cancer, and explore its role and mechanism in HCC., Methods: The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Profiling Interactive Analysis, and Tumor Immune Estimation Resource databases were used to analyze B56ε expression, prognostic mutations, somatic copy number alterations, and tumor immune characteristics in 33 tumors. The relationships between B56ε expression levels and drug sensitivity, immunotherapy, immune checkpoints, and human leukocyte antigen (HLA)-related genes were further analyzed. Gene Set Enrichment Analysis (GSEA) was performed to reveal the role of B56ε in HCC. The Cell Counting Kit-8, plate cloning, wound healing, and transwell assays were conducted to assess the effects of B56ε interference on the malignant behavior of HCC cells., Results: In most tumors, B56ε expression was upregulated, and high B56ε expression was a risk factor for adrenocortical cancer, HCC, pancreatic adenocarcinoma, and pheochromocytoma and paraganglioma (all P < 0.05). B56ε expression levels were correlated with a variety of immune cells, such as T helper 17 cells, B cells, and macrophages. There was a positive correlation between B56ε expression levels with immune checkpoint genes and HLA-related genes (all P < 0.05). The expression of B56ε was negatively correlated with the sensitivity of most chemotherapy drugs, but a small number showed a positive correlation (all P < 0.05). GSEA analysis showed that B56ε expression was related to the cancer pathway, p53 downstream pathway, and interleukin-mediated signaling in HCC. Knockdown of B56ε expression in HCC cells inhibited the proliferation, migration, and invasion capacity of tumor cells., Conclusion: B56ε is associated with the microenvironment, immune evasion, and immune cell infiltration of multiple tumors. B56ε plays an important role in HCC progression, supporting it as a prognostic marker and potential therapeutic target for HCC., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Rain Classroom was one of the most popular online learning platforms in Chinese higher education during the pandemic. However, there is little research on user intention under the guidance of technology acceptance and unified theory (UTAUT)., Objective: This research aims to determine factors influencing students' behavioural intention to use Rain Classroom., Methods: In this cross-sectional and correlational investigation, 1138 medical students from five medical universities in Guangxi Province, China, made up the sample. This study added self-efficacy (SE), motivation (MO), stress (ST), and anxiety (AN) to the UTAUT framework. This study modified the framework by excluding actual usage variables and focusing only on intention determinants. SPSS-26 and AMOS-26 were used to analyze the data. The structural equation modelling technique was chosen to confirm the hypotheses., Results: Except for facilitating conditions (FC), all proposed factors, including performance expectancy (PE), effort expectancy (EE), social influence (SI), self-efficacy (SE), motivation (MO), anxiety (AN), and stress (ST), had a significant effect on students' behavioural intentions to use Rain Classroom., Conclusions: The research revealed that the proposed model, which was based on the UTAUT, is excellent at identifying the variables that influence students' behavioural intentions in the Rain Classroom. Higher education institutions can plan and implement productive classrooms., (© 2024. The Author(s).)

This study assessed the corrosion resistance, intracutaneous reactivity, acute systemic toxicity, and in situ tissue effect of the implantation of porous NiTi fabricated by metal injection molding in animal models. For the intracutaneous reactivity study, five intracutaneous injections were administered per site with and without the tested extract in polar and nonpolar solutions. The extract was also delivered via intravenous and intraperitoneal routes for acute systemic toxicity. TiAl6 V4 (control) and porous NiTi were implanted in rabbit femora for a period of 13 weeks to evaluate the in situ tissue response. Corrosion was evaluated through open and cyclic polarization in PBS, while biocompatibility was investigated by assessing the general conditions, skin irritation score (edema and erythema), and histopathology. No active dissolution or hysteresis loop was observed in the corrosion study. None of the animals exhibited death, moribundity, impending death, severe pain, self-mutilation, or overgrooming. No edema was observed at injection sites. Only the positive control showed an erythematous reaction at 24, 48, and 72 h observations ( p < 0.001). Porous NiTi showed a low in situ biological response for inflammation, neovascularization, and fibrosis in comparison to the control implant ( p = 0.247, 0.005, and 0.011, respectively). Porous NiTi also demonstrated high pitting corrosion resistance while causing no acute hypersensitivity or acute systemic toxicity. The study concludes that porous NiTi implants were unlikely to cause local sensitization, acute systemic toxicity, or chronic inflammatory reactions in an animal model. Porous NiTi also exhibited osseointegration equivalent to Ti6AI4 V of known biocompatibility.

Purpose of Review: The purpose of this review is to summarize the latest evidence on the prevention and progression of diabetic kidney disease (DKD), as well as novel pharmacological interventions from preclinical and early clinical studies with promising findings in the reduction of this condition's burden., Recent Findings: We will cover the latest evidence on the reduction of proteinuria and kidney function decline in DKD achieved through established renin-angiotensin-aldosterone system (RAAS) system blockade and the more recent addition of SGLT2i, nonsteroidal mineralocorticoid receptor antagonists (MRAs) and GLP1-RA, that combined will most likely integrate the mainstay for current DKD treatment. We also highlight evidence from new mechanisms of action in DKD, including other haemodynamic anti-inflammatory and antifibrotic interventions, oxidative stress modulators and cell identity and epigenetic targets., Summary: Renal specific outcome trials have become more popular and are increasing the available armamentarium to diminish the progression of renal decline in patients at greater risk of end-stage kidney disease (ESKD) such as diabetic individuals. A combined pharmaceutical approach based on available rigorous studies should include RAAS blockade, SGLT2 inhibitors, nonsteroidal MRA and expectedly GLP1-RA on a personalized based-intervention. New specific trials designed to address renal outcomes will be needed for innovative therapies to conclude on their potential benefits in DKD., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: The aim of this systematic review was to evaluate the survival and complication rates of resin composite laminate veneers., Methods: Randomized controlled trials and cohort studies with a minimum 2-year follow-up assessing survival and complication rates of resin composite laminate veneers on permanent dentition from 1998 to May 2022. Literature searches were conducted in MEDLINE (PubMed), Scopus, and the Cochrane Central Register of Controlled Trials electronic databases. References cited in the related reviews and included full-text articles were also hand-searched to further identify potentially relevant studies., Results: A total of 827 articles were identified. Twenty-two studies were considered for full-text review after the title and abstract screening stage. After exclusion, 7 studies (3 randomized controlled trials and 4 cohort studies) were included in the systematic review. Three published scales were adopted for the quality and risk of bias assessment. At the survival rate threshold, the overall heterogeneity (I 2 ) for randomized controlled trials was 50.5% (P = .108). The overall pooled survival rate of the randomized controlled trials was 88% (95% CI: 81%-94%), with the mean follow-up time ranging from 24 to 97 months. Surface roughness, color mismatch, and marginal discoloration were the most reported complications., Conclusion: Resin composite laminate veneers demonstrated moderately high survival rates for the entire sample and the direct laminate veneer group demonstrated higher survival rates than the indirect approach. Most of the complications were regarded as clinically acceptable with or without reintervention., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: This study investigates the factors associated with the elderly's intention to use OGS. Building on the Technology Acceptance Model, we propose several elderly-specific and functional-ageing constructs related to the perceived ease of use and usefulness of OGS., Methods: The questionnaire was distributed physically and digitally to non-OGS users aged above 60, living in the Klang Valley, Malaysia, using a non-probability sampling approach. A total of 302 data were analysed using PLS structural equation modelling., Results: The findings indicate that perceived ease of use, functional ability, life-course events, and digital literacy are associated with the elderly's perception of OGS's usefulness, while life-course events, digital literacy, technology anxiety, and facilitating conditions are associated with the perceived ease of use., Conclusion: This study contributes to the OGS literature by addressing ageing complexities with OGS adoption among the elderly population, thereby offering insights for marketers and the government to tailor services and provide relevant support., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Global climate change and rapid urbanization, mainly driven by anthropogenic activities, lead to urban flood vulnerability and uncertainty in sustainable stormwater management. This study projected the temporal and spatial variation in urban flood susceptibility during the period 2020-2050 on the basis of shared socioeconomic pathways (SSPs). A case study in Guangdong-Hong Kong-Macao Greater Bay Area (GBA) was conducted for verifying the feasibility and applicability of this approach. GBA is predicted to encounter the increase in extreme precipitation with high intensity and frequency, along with rapid expansion of constructed areas, resulting in exacerbating of urban flood susceptibility. The areas with medium and high flood susceptibility will be expected to increase continuously from 2020 to 2050, by 9.5 %, 12.0 %, and 14.4 % under SSP1-2.6, SSP2-4.5, and SSP5-8.5 scenarios, respectively. In terms of the assessment of spatial-temporal flooding pattern, the areas with high flood susceptibility are overlapped with that in the populated urban center in GBA, surrounding the existing risk areas, which is consistent with the tendency of construction land expansion. The approach in the present study will provide comprehensive insights into the reliable and accurate assessment of urban flooding susceptibility in response to climate change and urbanization., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Accumulation of filamentous aggregates of tau protein in the brain is a pathological hallmark of Alzheimer's disease (AD) and many other neurodegenerative tauopathies. The filaments adopt disease-specific cross-β amyloid conformations that self-propagate and are implicated in neuronal loss. Development of molecular diagnostics and therapeutics is of critical importance. However, mechanisms of small molecule binding to the amyloid core is poorly understood. We used cryo-electron microscopy to determine a 2.7 Å structure of AD patient-derived tau paired-helical filaments bound to the PET ligand GTP-1. The compound is bound stoichiometrically at a single site along an exposed cleft of each protofilament in a stacked arrangement matching the fibril symmetry. Multiscale modeling reveals pi-pi aromatic interactions that pair favorably with the small molecule-protein contacts, supporting high specificity and affinity for the AD tau conformation. This binding mode offers critical insight into designing compounds to target different amyloid folds found across neurodegenerative diseases., (© 2023. The Author(s).)

This study aims to investigate the souvenir-person-place bonding for sustaining cultural heritage. Previous studies acknowledge souvenirs could represent a place; however, how people perceive souvenirs as representative of the place still needs to be studied. This study comprehends the traditional craft by identifying the dimensions of place-based craft souvenirs and exploring the connections between souvenirs, craft, and place. A qualitative approach was employed. In-depth interviews, participant and non-participant observations were conducted in Jinan, China, a long-history city with many traditional crafts. Thirty documents were imported into ATLAS.ti software for analysis. The 'place-based craft souvenir', 'evaluation of souvenir', 'place meaning', and 'satisfaction' emerged as the four main themes of 'souvenir-person-place bonding'. These 'souvenir-people-place' bonding motivate individuals' understanding of traditional craft and place, contributing to the sustainability of the traditional craft., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Climate change has led to the increased intensity and frequency of extreme meteorological events, threatening the drainage capacity in urban catchments and densely built-up cities. To alleviate urban flooding disasters, strategies coupled with green and grey infrastructure have been proposed to support urban stormwater management. However, most strategies rely largely on diachronic rainfall data and ignore long-term climate change impacts. This study described a novel framework to assess and to identify the optimal solution in response to uncertainties following climate change. The assessment framework consists of three components: (1) assess and process climate data to generate long-term time series of meteorological parameters under different climate conditions; (2) optimise the design of Grey-Green infrastructure systems to establish the optimal design solutions; and (3) perform a multi-criteria assessment of economic and hydrological performance to support decision-making. A case study in Guangzhou, China was carried out to demonstrate the usability and application processes of the framework. The results of the case study illustrated that the optimised Grey-Green infrastructure could save life cycle costs and reduce total outflow (56-66%), peak flow (22-85%), and TSS (more than 60%) compared to the fully centralised grey infrastructure system, indicating its high superior in economic competitiveness and hydrological performance under climate uncertainties. In terms of spatial configuration, the contribution of green infrastructure appeared not as critical as the adoption of decentralisation of the drainage networks. Furthermore, under extreme drought scenarios, the decentralised infrastructure system exhibited an exceptionally high degree of removal performance for non-point source pollutants., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Backgrounds and Aims: We investigated associations between hepatitis B virus (HBV) genome-length haplotype number (HN) at baseline in subjects with HBeAg-positive chronic hepatitis B (CHB), and the likelihood of achieving functional cure during direct-acting antiviral therapy METHOD: We analysed 86 HBeAg-positive baseline samples from patients with HBV genotypes A and D who were enrolled in a Phase II trial of tenofovir disoproxil fumarate (TDF) to determine if HN was a biomarker of HBsAg loss during therapy. Findings were validated using baseline samples from 181 patients with HBV genotypes A and D from an independent clinical trial utilising TDF or tenofovir alafenamide therapy in HBeAg-positive CHB., Results: In the HBeAg-positive test cohort, patients with genotypes A or D and ≤2 haplotypes had a minimum of 21-fold higher likelihood of achieving HBsAg loss on TDF. Baseline HN (p < 0.0001) was a stronger predictor of HBsAg loss on therapy than HBsAg titre (p = 0.03), HBeAg titre (p = 0.0002), or the presence of HBV basal core promoter (A1762T, p = 0.0379 and G1764A, p = 0.0176) or G1896A precore mutations (p = 0.0218). This finding was validated in the independent validation cohort. HN was statistically higher in patients with HBV genotypes B or C infection compared to genotypes A and D., Conclusion: Baseline HN ≤2 predicts which patients with HBV genotypes A or D will more likely progress to functional cure on current direct-acting antiviral therapy, with greater accuracy than current biomarkers including baseline HBsAg and HBeAg titre., (© 2022 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)