BACKGROUND: Grade 1/2 PanNETs are mostly managed similarly, typically without any adjunct treatment with the belief that their overall metastasis rate is low. In oncology literature, Ki67-index of 10% is increasingly being used as the cutoff in stratifying patients to different protocols, although there are no systematic pathology-based studies supporting this approach.
METHODS: Ki67-index was correlated with clinicopathologic parameters in 190 resected PanNETs. A validation cohort (n = 145) was separately analyzed.
RESULTS: In initial cohort, maximally selected rank statistics method revealed 12% to be the discriminatory cutoff (close to 10% rule of thumb). G2b cases had liver/distant metastasis rate of almost threefold higher than that of G2a and showed significantly higher frequency of all histopathologic signs of aggressiveness (tumor size, perineural/vascular invasion, infiltrative growth pattern, lymph node metastasis). In validation cohort, these figures were as striking. When all cases were analyzed together, compared with G1, the G2b category had nine times higher liver/distant metastasis rate (6.1 vs. 58.5%; p < 0.001) and three times higher lymph node metastasis rate (20.5 vs. 65.1%; p < 0.001).
CONCLUSIONS: G2b PanNETs act very similar to G3, supporting management protocols that regard them as potential therapy candidates. Concerning local management, metastatic behavior in G2b cases indicate they may not be as amenable for conservative approaches, such as watchful waiting or enucleation. This substaging should be considered into diagnostic guidelines, and clinical trials need to be devised to determine the more appropriate management protocols for G2b (10% to ≤ 20%) group, which shows liver/distant metastasis in more than half of the cases, which at minimum warrants closer follow-up.

Insomnia, as a difficulty in initiating and maintaining sleep, coupled with cardiovascular diseases (CVDs) increase the risk of aggravate daytime symptoms, mortality, and morbidity. Cognitive behavioral therapy (CBT) is thought to have a significant impact on insomnia treatment, but in patients with CVDs, there is a paucity of data. To provide a comprehensive appraisal on the impact of CBT on the treatment of insomnia in patients with CVDs. We searched Ovid, Scopus, Web of science, and Cochrane central, to randomized controlled trials (RCTs) from inception till November 2022. Outcomes of interest were insomnia severity index (ISI), Pittsburgh Sleep Quality Index (PSQI), sleep efficiency (SE), Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS), and sleep disorders questionnaire (SDQ). Pooled data were analyzed using mean difference (MD) with its 95% confidence interval (CI) in a random effect model using STATA 17 for Mac. Nine RCTs comprising 365 patients were included in the analysis. CBT significantly reduced scores of ISI (MD =  - 3.22, 95%  CI - 4.46 to - 1.98, p < 0.001), PSQI (MD =  - 2.33, 95%  CI - 3.23 to - 1.44, p < 0.001), DBAS (MD =  - 0.94, 95%  CI - 1.3 to - 0.58, p < 0.001), SDQ (MD =  - 0.38, 95%  CI - 0.56 to - 0.2, p < 0.001). Also, it increased the score of SE (MD = 6.65, 95% CI 2.54 to 10.77, p < 0.001). However, there was no difference in terms of ESS. CBT is an easy and feasible intervention with clinically significant improvement in insomnia symptoms. Further large-volume studies are needed to assess sustained efficacy.

BACKGROUND: Oral diseases are a major global public health problem, impacting the quality of life of those affected. While consensus exists on the importance of high-quality, evidence-informed guidelines to inform practice and public health decisions in medicine, appropriate methodologies and standards are not commonly adhered to among producers of oral health guidelines. This study aimed to systematically identify organizations that develop evidence-informed guidelines in oral health globally and survey the methodological process followed to formulate recommendations.
METHODS: We searched numerous electronic databases, guideline repositories, and websites of guideline developers, scientific societies, and international organizations (January 2012-October 2023) to identify organizations that develop guidelines addressing any oral health topic and that explicitly declare the inclusion of research evidence in their development. Pairs of reviewers independently evaluated potentially eligible organizations according to predefined selection criteria and extracted data about the organization\'s characteristics, key features of their guidelines, and the process followed when formulating formal recommendations. Descriptive statistics were used to analyze and summarize data.
RESULTS: We included 46 organizations that developed evidence-informed guidelines in oral health. The organizations were mainly professional associations and scientific societies (67%), followed by governmental organizations (28%). In total, organizations produced 55 different guideline document types, most of them containing recommendations for clinical practice (77%). Panels were primarily composed of healthcare professionals (87%), followed by research methodologists (40%), policymakers (24%), and patient partners (18%). Most (60%) of the guidelines reported their funding source, but only one out of three (33%) included a conflict of interest (COI) policy management. The methodology used in the 55 guideline document types varied across the organizations, but only 19 (35%) contained formal recommendations. Half (51%) of the guideline documents referred to a methodology handbook, 46% suggested a structured approach or system for rating the certainty of the evidence and the strength of recommendations, and 37% mentioned using a framework to move from evidence to decisions, with the GRADE-EtD being the most widely used (27%).
CONCLUSIONS: Our findings underscore the need for alignment and standardization of both terminology and methodologies used in oral health guidelines with current international standards to formulate trustworthy recommendations.

This study describes a novel method for grading pathological sections of gliomas. Our own integrated hyperspectral imaging system was employed to characterize 270 bands of cancerous tissue samples from microarray slides of gliomas. These samples were then classified according to the guidelines developed by the World Health Organization, which define the subtypes and grades of diffuse gliomas. We explored a hyperspectral feature extraction model called SMLMER-ResNet using microscopic hyperspectral images of brain gliomas of different malignancy grades. The model combines the channel attention mechanism and multi-scale image features to automatically learn the pathological organization of gliomas and obtain hierarchical feature representations, effectively removing the interference of redundant information. It also completes multi-modal, multi-scale spatial-spectral feature extraction to improve the automatic classification of glioma subtypes. The proposed classification method demonstrated high average classification accuracy (>97.3%) and a Kappa coefficient (0.954), indicating its effectiveness in improving the automatic classification of hyperspectral gliomas. The method is readily applicable in a wide range of clinical settings, offering valuable assistance in alleviating the workload of clinical pathologists. Furthermore, the study contributes to the development of more personalized and refined treatment plans, as well as subsequent follow-up and treatment adjustment, by providing physicians with insights into the underlying pathological organization of gliomas.

BACKGROUND: Although physical activity (PA) is associated with significant health benefits, only a small percentage of adolescents meet recommended PA levels. This systematic review with meta-analysis explored the modifiable determinants of adolescents\' device-based PA and/or sedentary behaviour (SB), evaluated in previous interventions and examined the associations between PA/SB and these determinants in settings.
METHODS: A search was conducted on five electronic databases, including papers published from January 2010 to July 2023. Randomized Controlled Trials (RCTs) or Controlled Trials (CTs) measuring adolescents\' device-based PA/SB and their modifiable determinants at least at two time points: pre- and post-intervention were considered eligible. PA/SB and determinants were the main outcomes. Modifiable determinants were classified after data extraction adopting the social-ecological perspective. Robust Bayesian meta-analyses (RoBMA) were performed per each study setting. Outcomes identified in only one study were presented narratively. The risk of bias for each study and the certainty of the evidence for each meta-analysis were evaluated. The publication bias was also checked.
UNASSIGNED: CRD42021282874.
RESULTS: Fourteen RCTs (eight in school, three in school and family, and one in the family setting) and one CT (in the school setting) were included. Fifty-four modifiable determinants were identified and were combined into 33 broader determinants (21 individual-psychological, four individual-behavioural, seven interpersonal, and one institutional). RoBMAs revealed none or negligible pooled intervention effects on PA/SB or determinants in all settings. The certainty of the evidence of the impact of interventions on outcomes ranged from very low to low. Narratively, intervention effects in favour of the experimental group were detected in school setting for the determinants: knowledge of the environment for practicing PA, d = 1.84, 95%CI (1.48, 2.20), behaviour change techniques, d = 0.90, 95%CI (0.09, 1.70), choice provided, d = 0.70, 95%CI (0.36, 1.03), but no corresponding effects on PA or SB were found.
CONCLUSIONS: Weak to minimal evidence regarding the associations between the identified modifiable determinants and adolescents\' device-based PA/SB in settings were found, probably due to intervention ineffectiveness. Well-designed and well-implemented multicomponent interventions should further explore the variety of modifiable determinants of adolescents\' PA/SB, including policy and environmental variables.

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OBJECTIVE: To describe the methodology used by the Reassessment Campaign on Veterinary Resuscitation (RECOVER) to re-evaluate the scientific evidence relevant to CPR in small and large animals, to newborn resuscitation, and to first aid and to formulate the respective consensus-based clinical guidelines.
METHODS: This report describes the evidence-to-guidelines process employed by RECOVER that is based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach and includes Information Specialist-driven systematic literature search, evidence evaluation conducted by more than 200 veterinary professionals, and provision of clinical guidelines in the domains of Preparedness and Prevention, Basic Life Support, Advanced Life Support, Post-cardiac Arrest Care, Newborn Resuscitation, First Aid, and Large Animal CPR.
METHODS: Transdisciplinary, international collaboration in academia, referral practice, and general practice.
RESULTS: For this update to the RECOVER 2012 CPR guidelines, we answered 135 Population, Intervention, Comparator, and Outcome (PICO) questions with the help of a team of Domain Chairs, Information Specialists, and more than 200 Evidence Evaluators. Most primary contributors were veterinary specialists or veterinary technician specialists. The RECOVER 2024 Guidelines represent the first veterinary application of the GRADE approach to clinical guideline development. We employed an iterative process that follows a predefined sequence of steps designed to reduce bias of Evidence Evaluators and to increase the repeatability of the quality of evidence assessments and ultimately the treatment recommendations. The process also allowed numerous important knowledge gaps to emerge that form the foundation for prioritizing research efforts in veterinary resuscitation science.
CONCLUSIONS: Large collaborative, volunteer-based development of evidence- and consensus-based clinical guidelines is challenging and complex but feasible. The experience gained will help refine the process for future veterinary guidelines initiatives.

Oncobiosis has emerged as a key contributor to the development, and modulator of the treatment efficacy of cancer. Hereby, we review the modalities through which the oncobiome can support the progression of tumors, and the emerging therapeutic opportunities they present. The review highlights the inherent challenges and limitations faced in sampling and accurately characterizing oncobiome. Additionally, the review underscores the critical need for the standardization of microbial analysis techniques and the consistent reporting of microbiome data. We provide a suggested metadata set that should accompany microbiome datasets from oncological settings so that studies remain comparable and decipherable.

UNASSIGNED: Autism is a neurodevelopmental condition that is increasing in prevalence worldwide. There has been an exponential increase in autism-related research since 2010, when the first Singapore Clinical Practice Guidelines (CPG) on autism was published. Understanding of autism has since evolved to adopt a lifespan approach beyond that of a childhood condition. The aim of this CPG was to provide an updated set of recommendations for children and adolescents to aid clinical practice for professionals.
UNASSIGNED: A multidisciplinary workgroup that comprised representatives from various sectors worked on this CPG. Clinical questions were organised into 10 different sections, each with its own subgroup of members. Seventeen existing international guidelines were evaluated using the Appraisal of Guidelines for REsearch & Evaluation II (AGREE-II) framework, of which 4 met criteria to act as references. Literature review across multiple databases was conducted between January 2011 to 2023; Grading of Recommendations, Assessment, Development and Evaluation (GRADE-like) methodology was used to synthesise evidence. Recommendation statements were derived, following Delphi-style consensus surveys among the workgroup. The draft guidelines underwent external review and public consultation before being formalised.
UNASSIGNED: Recommendation and good practice statements pertaining to care of children and adolescents on the autism spectrum across 10 different sections were developed. Evidence matrices complement these recommendations and detail relevant evidence behind each recommendation statement.
UNASSIGNED: It is intended for these guidelines to promote effective management and healthcare services for children and adolescents on the autism spectrum, by reinforcing good and evidence-based clinical practice within our national context.

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