Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity: The STEP 3 Randomized Clinical Trial.

Importance: Weight loss improves cardiometabolic risk factors in people with overweight or obesity. Intensive lifestyle intervention and pharmacotherapy are the most effective noninvasive weight loss approaches. Objective: To compare the effects of once-weekly subcutaneous semaglutide, 2.4 mg vs placebo for weight management as an adjunct to intensive behavioral therapy with initial low-calorie diet in adults with overweight or obesity. Design, Setting, and Participants: Randomized, double-blind, parallel-group, 68-week, phase 3a study (STEP 3) conducted at 41 sites in the US from August 2018 to April 2020 in adults without diabetes (N = 611) and with either overweight (body mass index ≥27) plus at least 1 comorbidity or obesity (body mass index ≥30). Interventions: Participants were randomized (2:1) to semaglutide, 2.4 mg (n = 407) or placebo (n = 204), both combined with a low-calorie diet for the first 8 weeks and intensive behavioral therapy (ie, 30 counseling visits) during 68 weeks. Main Outcomes and Measures: The co-primary end points were percentage change in body weight and the loss of 5% or more of baseline weight by week 68. Confirmatory secondary end points included losses of at least 10% or 15% of baseline weight. Results: Of 611 randomized participants (495 women [81.0%], mean age 46 years [SD, 13], body weight 105.8 kg [SD, 22.9], and body mass index 38.0 [SD, 6.7]), 567 (92.8%) completed the trial, and 505 (82.7%) were receiving treatment at trial end. At week 68, the estimated mean body weight change from baseline was -16.0% for semaglutide vs -5.7% for placebo (difference, -10.3 percentage points [95% CI, -12.0 to -8.6]; P < .001). More participants treated with semaglutide vs placebo lost at least 5% of baseline body weight (86.6% vs 47.6%, respectively; P < .001). A higher proportion of participants in the semaglutide vs placebo group achieved weight losses of at least 10% or 15% (75.3% vs 27.0% and 55.8% vs 13.2%, respectively; P < .001). Gastrointestinal adverse events were more frequent with semaglutide (82.8%) vs placebo (63.2%). Treatment was discontinued owing to these events in 3.4% of semaglutide participants vs 0% of placebo participants. Conclusions and Relevance: Among adults with overweight or obesity, once-weekly subcutaneous semaglutide compared with placebo, used as an adjunct to intensive behavioral therapy and initial low-calorie diet, resulted in significantly greater weight loss during 68 weeks. Further research is needed to assess the durability of these findings. Trial Registration: ClinicalTrials.gov Identifier: NCT03611582.

A randomized prospective study of the immediate outcomes of the use of a hydro-jet dissector and an ultrasonic surgical aspirator for laparoscopic liver resection.

BACKGROUND: No prospective randomized trials comparing transection techniques for the liver parenchyma transection during laparoscopic liver resection have been performed. The aim of the study was to compare the immediate outcomes of hydro-jet dissection with ultrasonic surgical aspirator in laparoscopic liver parenchyma transection in a prospective randomized single-center study. METHODS: Consecutive patients with liver benign and malignant tumors presenting to a single center from May 2017 to May 2020 were enrolled in the study. The primary endpoint was the intraoperative estimated blood loss. The secondary endpoints included duration of parenchymal transection, morbidity, and overall hospital stay. RESULTS: A total of 68 patients were enrolled in the study, with 34 patients in each group. There were no differences between groups in the difficulty of resection (according to IWATE criteria and IMM score) and other basic surgical parameters. No differences were found in all primary and secondary endpoints except the expenditure. The cost of equipment was significantly higher in the group of ultrasonic aspirator. CONCLUSION: Despite the wider use of the ultrasonic aspirator in laparoscopic liver surgery, hydro-jet and ultrasonic surgical aspirators have shown similar efficacy and safety for transection of the liver parenchyma during laparoscopic resection.

Combining E-PASS model and disease specific risk factors to predict severe morbidity after liver and bile duct resection for perihilar cholangiocarcinoma.

BACKGROUND: Estimation of physiologic ability and surgical stress system (E-PASS) has been shown to be effective in predicting morbidity after surgery for perihilar cholangiocarcinoma (PHCC). Nevertheless, E-PASS does not include an assessment of the disease specific risk factors. The aim of the study was to estimate the combined impact of E-PASS and specific preoperative factors on major morbidity for PHCC patients. METHODS: A retrospective analysis of a prospectively collected data was performed. Severe morbidity according to complication comprehensive index was defined as ≥40 points. A value of comprehensive risk score (CRS) ≥1 was taken as critical. RESULTS: Multivariate analysis of perioperative data from 122 patients revealed significant impact of five factors (CRS ≥1, future liver remnant volume <50%, T4 stage, moderate and severe cholangitis, INR) on the risk of severe morbidity after resection. The AUC for the combination of these factors was classified as good predictive value (0.810, 95% CI 0.729-0.891) and poor predictive value (0.673, 95% CI 0.573-0.773) for CRS alone (p = 0.040). CONCLUSION: A combination of E-PASS with disease specific risk factors is a reliable predictive model for major morbidity for patients undergoing radical surgery for PHCC.

Measuring semantic similarity of clinical trial outcomes using deep pre-trained language representations.

BACKGROUND: Outcomes are variables monitored during a clinical trial to assess the impact of an intervention on humans' health.Automatic assessment of semantic similarity of trial outcomes is required for a number of tasks, such as detection of outcome switching (unjustified changes of pre-defined outcomes of a trial) and implementation of Core Outcome Sets (minimal sets of outcomes that should be reported in a particular medical domain). OBJECTIVE: We aimed at building an algorithm for assessing semantic similarity of pairs of primary and reported outcomes.We focused on approaches that do not require manually curated domain-specific resources such as ontologies and thesauri. METHODS: We tested several approaches, including single measures of similarity (based on strings, stems and lemmas, paths and distances in an ontology, and vector representations of phrases), classifiers using a combination of single measures as features, and a deep learning approach that consists in fine-tuning pre-trained deep language representations.We tested language models provided by BERT (trained on general-domain texts), BioBERT and SciBERT (trained on biomedical and scientific texts, respectively).We explored the possibility of improving the results by taking into account the variants for referring to an outcome (e.g.the use of a measurement tool name instead on the outcome name; the use of abbreviations).We release an open corpus with annotation for similarity of pairs of outcomes. RESULTS: Classifiers using a combination of single measures as features outperformed the single measures, while deep learning algorithms using BioBERT and SciBERT models outperformed the classifiers.BioBERT reached the best F-measure of 89.75%.The addition of variants of outcomes did not improve the results for the best-performing single measures nor for the classifiers, but it improved the performance of deep learning algorithms: BioBERT achieved an F-measure of93.38%. CONCLUSIONS: Deep learning approaches using pre-trained language representations outperformed other approaches for similarity assessment of trial outcomes, without relying on any manually curated domain-specific resources (ontologies and other lexical resources). Addition of variants of outcomes further improved the performance of deep learning algorithms.

Comprehensive Approach to Open Access Publishing: Platforms and Tools.

The Open Access Initiative is gaining momentum due to the worldwide availability of advanced digital tools, online publishing platforms, and systems for tracking academic contributions. Several declarations and initiatives, including Plan S, have already laid a foundation for moving away from subscription to full and immediate open-access publishing. The global initiatives imply targeting journals satisfying the upgraded quality and visibility criteria. To meet these criteria, a comprehensive approach to Open Access is recommended. This article overviews the essential components of the comprehensive approach, increasing transparency, adherence to ethical standards, and diversification of evaluation metrics. With the increasing volume of quality open-access journals, their indexing with free databases and search engines is becoming increasingly important. The Directory of Open Access Journals and PubMed Central currently free searches of open-access sources. These services, however, cannot fully satisfy the increasing demands of the users, and attempts are underway to upgrade the indexing and archiving of open-access sources in China, Japan, Korea, Russia, and elsewhere. The wide use of identifiers is essential for transparency of scholarly communications. Peer reviewers are now offered credits from Publons. These credits are transferrable to their Open Researcher and Contributor iDs. Various social media channels are increasingly used by scholars to comment on articles. All these comments are tracked by related metric systems, such as Altmetrics. Combined with traditional citation evaluations, the alternative metrics can help timely identify and promote publications influencing education, research, and practice.

Updated Editorial Guidance for Quality and Reliability of Research Output.

Over the past few years, updated editorial policy statements of several associations have provided a platform for improving the quality of scientific research and publishing. The updates have particularly pointed to the need for following research reporting standards, authorship and contributorship regulations, implementing digital tools for the identification and crediting academic contributors, and moving towards optimal ethical open-access models. This article overviews some of the recent editorial policy statements of global editorial associations and reflects on the role of the regional counterparts in advancing scholarly publishing. One of the globally promoted documents is the Recommendations of the International Committee of Medical Journal Editors (ICMJE). Its latest versions contain statements on proper research reporting, reviewing, editing, and publishing. Points on ethical target journals and 'predatory' sources are also available. This year, in a move to update its editorial policy, the Committee on Publication Ethics (COPE) released the Core Practices, comprehensively reflecting on the major issues in publication ethics. Updated joint statements of medical writers associations are also available to implement transparent policy on contributorship in sponsor-supported research projects and related reports. Several suggestions are put forward to improve global editorial statements on online profiling, crediting, and referencing. It is also highlighted that knowledge and implementation of updated editorial guidance is essential for editors' good standing.

Predatory Publishing Is a Threat to Non-Mainstream Science.

This article highlights the issue of wasteful publishing practices that primarily affect non-mainstream science countries and rapidly growing academic disciplines. Numerous start-up open access publishers with soft or nonexistent quality checks and huge commercial interests have created a global crisis in the publishing market. Their publishing practices have been thoroughly examined, leading to the blacklisting of many journals by Jeffrey Beall. However, it appears that some subscription journals are also falling short of adhering to the international recommendations of global editorial associations. Unethical editing agencies that promote their services in non-mainstream science countries create more problems for inexperienced authors. It is suggested to regularly monitor the quality of already indexed journals and upgrade criteria of covering new sources by the Emerging Sources Citation Index (Web of Science), Scopus, and specialist bibliographic databases. Regional awareness campaigns to inform stakeholders of science communication about the importance of ethical writing, transparency of editing services, and permanent archiving can be also helpful for eradicating unethical publishing practices.

Statement on Publication Ethics for Editors and Publishers.

The digitization and related developments in journal editing and publishing necessitate increasing the awareness of all stakeholders of science communication in the emerging global problems and possible solutions. Journal editors and publishers are frequently encountered with the fast-growing problems of authorship, conflicts of interest, peer review, research misconduct, unethical citations, and inappropriate journal impact metrics. While the number of erroneous and unethical research papers and wasteful, or 'predatory', journals is increasing exponentially, responsible editors are urged to 'clean' the literature by correcting or retracting related articles. Indexers are advised to implement measures for accepting truly influential and ethical journals and delisting sources with predatory publishing practices. Updating knowledge and skills of authors, editors and publishers, developing and endorsing recommendations of global editorial associations, and (re)drafting journal instructions can be viewed as potential tools for improving ethics of academic journals. The aim of this Statement is to increase awareness of all stakeholders of science communication of the emerging ethical issues in journal editing and publishing and initiate a campaign of upgrading and enforcing related journal instructions.

The Pressure to Publish More and the Scope of Predatory Publishing Activities.

This article overviews unethical publishing practices in connection with the pressure to publish more. Both open-access and subscription publishing models can be abused by 'predatory' authors, editors, and publishing outlets. Relevant examples of 'prolific' scholars are viewed through the prism of the violation of ethical authorship in established journals and indiscriminately boosting publication records elsewhere. The instances of ethical transgressions by brokering editorial agencies and agents, operating predominantly in non-Anglophone countries, are presented to raise awareness of predatory activities. The scheme of predatory publishing activities is presented, and several measures are proposed to tackle the issue of predatory publishing. The awareness campaigns by professional societies, consultations with information facilitators, implementation of the criteria of best target journals, and crediting of scholars with use of integrative citation metrics, such as the h-index, are believed to make a difference.

Efficacy and safety of once weekly semaglutide 2·4 mg for weight management in a predominantly east Asian population with overweight or obesity (STEP 7): a double-blind, multicentre, randomised controlled trial.

BACKGROUND: Data on the benefits of the once weekly GLP-1 receptor agonist semaglutide 2·4 mg for weight management in people from east Asia are insufficient. The objective of this study was to determine the efficacy and safety of once weekly semaglutide 2·4 mg versus placebo for weight management in a predominantly east Asian adult population. METHODS: This randomised phase 3a, double-blind multicentre controlled trial (STEP 7) recruited participants from 23 hospitals and trial centres in China, Hong Kong, Brazil, and South Korea. Adults with overweight or obesity, with or without type 2 diabetes, were randomly assigned (2:1) to receive a subcutaneous injection of either semaglutide 2·4 mg or placebo once a week for 44 weeks, plus a diet and physical activity intervention. Randomisation was done in blocks of six with an interactive web response system and was stratified by diagnosis of type 2 diabetes. Participants, investigators, and the trial sponsor were masked to treatment allocation until after database lock. Primary endpoints were percentage change in mean bodyweight and proportion of participants having reached a weight reduction of at least 5% of bodyweight from baseline to week 44. Safety was assessed in all participants who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT04251156, and is now complete. FINDINGS: From Dec 8, 2020, to Aug 23, 2022, 448 participants were screened, of whom 375 were randomly assigned to either the semaglutide 2·4 mg group (n=249) or the placebo group (n=126). Estimated mean percentage change in bodyweight from baseline to week 44 was -12·1% (SE 0·5) with semaglutide 2·4 mg versus -3·6% (0·7) with placebo (estimated treatment difference -8·5 percentage points [95% CI -10·2 to -6·8]; p<0·0001). At week 44, the proportion of participants who lost 5% or more of their bodyweight was higher in the semaglutide 2·4 mg group than in the placebo group (203/238 [85%] vs 36/116 [31%]); odds ratio 13·1 (95% CI 7·4-23·1; p<0·0001). Adverse events were reported by 231 (93%) of 249 participants in the semaglutide 2·4 mg group and 108 (86%) of 126 participants in the placebo group, the most common of which were gastrointestinal disorders (168/249, 67% vs 45/126, 36%). INTERPRETATION: The results of this study support the use of semaglutide 2·4 mg for weight management in people of east Asian ethnicity with overweight or obesity and with or without type 2 diabetes. FUNDING: Novo Nordisk. TRANSLATIONS: For the Mandarin, Portuguese and South Korean translations of the abstract see Supplementary Materials section.

Reporting guidelines used varying methodology to develop recommendations.

BACKGROUND AND OBJECTIVES: We investigated the developing methods of reporting guidelines in the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) Network's database. METHODS: In October 2018, we screened all records and excluded those not describing reporting guidelines from further investigation. Twelve researchers performed duplicate data extraction on bibliometrics, scope, development methods, presentation, and dissemination of all publications. Descriptive statistics were used to summarize the findings. RESULTS: Of the 405 screened records, 262 described a reporting guidelines development. The number of reporting guidelines increased over the past 3 decades, from 5 in the 1990s and 63 in the 2000s to 157 in the 2010s. Development groups included 2-151 people. Literature appraisal was performed during the development of 56% of the reporting guidelines; 33% used surveys to gather external opinion on items to report; and 42% piloted or sought external feedback on their recommendations. Examples of good reporting for all reporting items were presented in 30% of the reporting guidelines. Eighteen percent of the reviewed publications included some level of spin. CONCLUSION: Reporting guidelines have been developed with varying methodology. Reporting guideline developers should use existing guidance and take an evidence-based approach, rather than base their recommendations on expert opinion of limited groups of individuals.

Computational Literature-based Discovery for Natural Products Research: Current State and Future Prospects.

Literature-based discovery (LBD) mines existing literature in order to generate new hypotheses by finding links between previously disconnected pieces of knowledge. Although automated LBD systems are becoming widespread and indispensable in a wide variety of knowledge domains, little has been done to introduce LBD to the field of natural products research. Despite growing knowledge in the natural product domain, most of the accumulated information is found in detached data pools. LBD can facilitate better contextualization and exploitation of this wealth of data, for example by formulating new hypotheses for natural product research, especially in the context of drug discovery and development. Moreover, automated LBD systems promise to accelerate the currently tedious and expensive process of lead identification, optimization, and development. Focusing on natural product research, we briefly reflect the development of automated LBD and summarize its methods and principal data sources. In a thorough review of published use cases of LBD in the biomedical domain, we highlight the immense potential of this data mining approach for natural product research, especially in context with drug discovery or repurposing, mode of action, as well as drug or substance interactions. Most of the 91 natural product-related discoveries in our sample of reported use cases of LBD were addressed at a computer science audience. Therefore, it is the wider goal of this review to introduce automated LBD to researchers who work with natural products and to facilitate the dialogue between this community and the developers of automated LBD systems.

Viscoelasticity of periodontal ligament: an analytical model.

BACKGROUND: Understanding of viscoelastic behaviour of a periodontal membrane under physiological conditions is important for many orthodontic problems. A new analytic model of a nearly incompressible viscoelastic periodontal ligament is suggested, employing symmetrical paraboloids to describe its internal and external surfaces. METHODS: In the model, a tooth root is assumed to be a rigid body, with perfect bonding between its external surface and an internal surface of the ligament. An assumption of almost incompressible material is used to formulate kinematic relationships for a periodontal ligament; a viscoelastic constitutive equation with a fractional exponential kernel is suggested for its description. RESULTS: Translational and rotational equations of motion are derived for ligament's points and special cases of translational displacements of the tooth root are analysed. Material parameters of the fractional viscoelastic function are assessed on the basis of experimental data for response of the periodontal ligament to tooth translation. A character of distribution of hydrostatic stresses in the ligament caused by vertical and horizontal translations of the tooth root is defined. CONCLUSIONS: The proposed model allows generalization of the known analytical models of the viscoelastic periodontal ligament by introduction of instantaneous and relaxed elastic moduli, as well as the fractional parameter. The latter makes it possible to take into account different behaviours of the periodontal tissue under short- and long-term loads. The obtained results can be used to determine loads required for orthodontic tooth movements corresponding to optimal stresses, as well as to simulate bone remodelling on the basis of changes in stresses and strains in the periodontal ligament caused by such movements.