Update on Treatments for Parkinson's Disease Motor Fluctuations - An International Parkinson and Movement Disorder Society Evidence-Based Medicine Review.

Objective: To update evidence-based medicine recommendations for treating motor fluctuations of Parkinson's disease (PD).

Background: The International Parkinson and Movement Disorder Society (MDS) Evidence Based Medicine in Movement Disorders Committee recommendations for the treatments of PD were first published in 2002 and regularly updated. The current review uses a new methodology, including the Cochrane Risk of Bias tool and a modified version of GRADE (Grading of Recommendations, Assessment, Development, and Evaluations).

Copy Number Variation and Haplotype Analysis of 17q21.31 Reveals Increased Risk Associated with Progressive Supranuclear Palsy and Gene Expression Changes in Neuronal Cells.

Background: The 17q21.31 region with various structural forms characterized by the H1/H2 haplotypes and three large copy number variations (CNVs) represents the strongest risk locus in progressive supranuclear palsy (PSP).

Objective: To investigate the association between CNVs and structural forms on 17q.

Catheter Ablation of Atrial Fibrillation in Patients With Psoriasis: A Multicenter Study.

Background: Psoriasis is linked to an increased risk of atrial fibrillation (AF). However, data on the electrophysiological substrate and outcomes of AF ablation in patients with psoriasis are lacking.

Methods: We conducted a retrospective, multicenter study involving 48 patients with psoriasis (median age, 66 years [56-72]; 79% male) and paroxysmal (n=25.

DAGIP: alleviating cell-free DNA sequencing biases with optimal transport.

Cell-free DNA (cfDNA) is a rich source of biomarkers for various pathophysiological conditions. Preanalytical variables, such as the library preparation protocol or sequencing platform, are major confounders of cfDNA analysis. We present DAGIP, a novel data correction method that builds on optimal transport theory and deep learning, which explicitly corrects for the effect of such preanalytical variables and can infer technical biases.

Contexts, affective and physical states and their variations during physical activity in older adults: an intensive longitudinal study with sensor-triggered event-based ecological momentary assessments.

Background: To design effective tailored interventions to promote physical activity (PA) among older adults, insights are needed into the contexts in which older adults engage in PA and their affective and physical experiences. Sensor-triggered event-based ecological momentary assessment (EMA) is an innovative method for capturing real-life contexts, as well as affective and physical states, during or immediately after specific events, such as PA. This study aimed to (1) describe the physical and social contexts, and the affective and physical states during PA among older adults, (2) evaluate how these constructs fluctuate during PA episodes, and (3) describe affective states during PA according to the context.

School staff experiences on involvement in a co-creation process: a Health CASCADE scoping review and thematic synthesis.

Background: Implementing public health interventions in schools requires active involvement of multiple stakeholders and adaptation of interventions to fit local contexts, to account for successful design, implementation, and consequently effectiveness of these interventions. Active collaboration, preferably in a co-creation process, with school staff is needed to enhance the implementation of school-based public health interventions. However, involving them in research through a co-creation process is challenging due to competing demands on their time.

Modulating tumor immunity using advanced microbiome therapeutics producing an indole metabolite.

The gut microbiome has emerged as a key player in modulating immune responses against cancer, suggesting that microbial interventions can enhance treatment outcomes. Indole metabolites produced by probiotic bacteria activate the aryl hydrocarbon receptor (AhR), a transcription factor important for immune cell regulation. Cancer patients with high plasma concentrations of these metabolites have shown improved survival.

Uncovering the genetic architecture of inherited retinal disease in a consanguineous Iranian cohort.

An integrated approach combining whole exome sequencing (WES) and autozygosity mapping was used to molecularly diagnose inherited retinal disease (IRD) in 192 unrelated Iranian families, 76.1% of which originate from a consanguineous background. Data analysis was performed using an in-house pipeline to detect single-nucleotide variants (SNVs), small insertions and deletions, copy number variants (CNVs) and runs of homozygosity (ROHs).

Machine learning-based spatial characterization of tumor-immune microenvironment in the EORTC 10994/BIG 1-00 early breast cancer trial.

Breast cancer (BC) represents a heterogeneous ecosystem and elucidation of tumor microenvironment components remains essential. Our study aimed to depict the composition and prognostic correlates of immune infiltrate in early BC, at a multiplex and spatial resolution. Pretreatment tumor biopsies from patients enrolled in the EORTC 10994/BIG 1-00 randomized phase III neoadjuvant trial (NCT00017095) were used; the CNN11 classifier for H&E-based digital TILs (dTILs) quantification and multiplex immunofluorescence were applied, coupled with machine learning (ML)-based spatial features.

Echinacoside reduces intracellular c-di-GMP levels and potentiates tobramycin activity against Pseudomonas aeruginosa biofilm aggregates.

Cyclic diguanylate (c-di-GMP) is a central biofilm regulator in Pseudomonas aeruginosa, where increased intracellular levels promote biofilm formation and antibiotic tolerance. Targeting the c-di-GMP network may be a promising anti-biofilm approach, but most strategies studied so far aimed at eliminating surface-attached biofilms, while in vivo P. aeruginosa biofilms often occur as suspended aggregates.

Nano-confined controllable crystallization in supramolecular polymeric membranes for ultra-selective desalination.

Innovations in self-assembly and aggregate engineering have led to membranes that better balance water permeability with salt rejection, overcoming traditional trade-offs. Here we demonstrate a strategy that uses multivalent H-bond interactions at the nano-confined space to manipulate controllable and organized crystallization. Specifically, we design amphiphilic oligomers featuring hydrophobic segments with strongly polar end-capped motifs.

NURR1 Deficiency Is Associated to Altered Microglial Phenotype in Male Mice.

The transcription factor NUclear Receptor Related 1 (NURR1) regulates the development and maintenance of midbrain dopaminergic (mDA) neurons, which control voluntary movement, motivation, and reward. NURR1 also plays anti-inflammatory functions in microglia, protecting mDA neurons from inflammation-induced death. It remains to be determined to what extent NURR1 exerts its function in microglia.

Age-related differences across the adult lifespan: a comparison of six field assessments of physical function.

Background: Age-related declines in physical capabilities often result from decreased lower-limb muscle strength and power, which are measurable through field tests. Various tests can detect functional declines in older adults, but their responsiveness to age-related differences is less understood in those without substantial impairments. Therefore, this study evaluated and compared the ability of field tests to detect age-related changes in physical and muscle function across adulthood.

Guidance on the production of EuGMS guidelines.

The European Geriatric Medicine Society (EuGMS) will publish clinical guidelines grounded in evidence-based knowledge pertaining to identification, prevention, diagnosis and management of conditions that are relevant to older people. The primary goal is to produce relevant recommendations that address areas not currently covered by organ-based clinical guidelines, thereby mitigating uncertainty and enhancing the quality of care for older patients, in particular those with multimorbidity and frailty. This document, approved by the Academic Board and the Executive Board of the EuGMS, informs on the creation and organization of the Guideline Committee, the procedures to develop clinical guidelines, methodological aspects and ethical issues related to their production and dissemination.

Trabecular bone score to assess bone microarchitecture in end-stage renal disease patients.

Rationale: This study evaluates TBS for estimating bone microarchitecture in ESRD patients using HR-pQCT as the reference technique.

Main Results: TBS correlates significantly with vBMD and bone microarchitecture, unlike aBMD.

Significance: TBS may complement bone health assessment in ESRD patients by offering additional information alongside aBMD.

Evaluation of enzyme activity predictions for variants of unknown significance in Arylsulfatase A.

Continued advances in variant effect prediction are necessary to demonstrate the ability of machine learning methods to accurately determine the clinical impact of variants of unknown significance (VUS). Towards this goal, the ARSA Critical Assessment of Genome Interpretation (CAGI) challenge was designed to characterize progress by utilizing 219 experimentally assayed missense VUS in the Arylsulfatase A (ARSA) gene to assess the performance of community-submitted predictions of variant functional effects. The challenge involved 15 teams, and evaluated additional predictions from established and recently released models.

SUCCOR 10 years: a decade's perspective on radical hysterectomy outcomes in cervical cancer.

Objective: Interest in long-term outcomes of radical hysterectomy for cervical cancer has increased, especially after the LACC trial findings, which showed worse outcomes for minimally invasive surgery. However, limited information is available on 10-year oncological outcomes, particularly, recurrence and survival. The primary objective of this study was to analyze the 10-year oncological outcomes of patients with International Federation of Gynecology and Obstetrics 2009 stage IB1 cervical cancer treated with radical hysterectomy performed via minimally invasive or open approaches.

2024 John J Bonica Award Lecture: Less is More.

'Less is More' reflects the idea of Ludwig Mies van der Rohe, who only retained the essentials in his designs. This principle is also applicable in different areas of pain medicine.Several pioneers have worked hard to introduce the multidisciplinary approach to obtain the most appropriate treatment for the patient.

Holistic approaches in systemic lupus erythematosus: do physicians avoid addressing difficult-to-treat but highly relevant symptoms?

Despite advancements in the management of systemic lupus erythematosus (SLE), patients experience poor health-related quality of life (hrQoL) and premature death due to disease severity and treatment side effects. Achieving remission offers substantial benefits, including improved hrQoL and reduced mortality, yet the complexity of SLE, with its diverse underlying immune mechanisms and clinical manifestations, hampers progress. Involvement of the central nervous system with symptoms like fatigue, pain and brain fog often goes unaddressed due to limited evidence-based guidance and measurement tools.

Society for Immunotherapy of Cancer (SITC) consensus statement on essential biomarkers for immunotherapy clinical protocols.

Immunotherapy of cancer is now an essential pillar of treatment for patients with many individual tumor types. Novel immune targets and technical advances are driving a rapid exploration of new treatment strategies incorporating immune agents in cancer clinical practice. Immunotherapies perturb a complex system of interactions among genomically unstable tumor cells, diverse cells within the tumor microenvironment including the systemic adaptive and innate immune cells.

Self-assembling peptide IEIK13 for intra-operative hemostasis in cranial neurosurgery: clinical trial on efficacy and safety.

Objective: This paper describes the results of the first-in-human prospective clinical trial of a hemostatic hydrogel of the self-assembling peptide IEIK13 for hemostasis in intracranial surgery. Both safety and efficacy of IEIK13 for intraoperative hemostasis of oozing bleeding were evaluated in this multicenter trial.

Methods: A total of 80 participants underwent a surgical intervention, during which 203 intradural bleeding sites were treated with IEIK13.

Performance of the EQ-5D-5L with skin irritation and self-confidence bolt-on items in patients with urticaria.

Objectives: This study aimed to validate the EQ-5D-5L with the addition of skin irritation and self-confidence bolt-on items in Chinese patients with urticaria.

Methods: The skin irritation and self-confidence bolt-on items were translated into Simplified Chinese and cognitively debriefed. A cross-sectional survey was subsequently conducted among patients diagnosed with urticaria in Guangdong Province, China.

Colon Cancer Screening, Surveillance, and Treatment: Novel AI driving strategies in the management of colon lesions.

Colonoscopy, a crucial procedure for detecting and removing colorectal polyps, has seen transformative advancements through the integration of Artificial Intelligence (AI), specifically in Computer-Aided Detection (CADe) and Diagnosis (CADx). These tools enhance real-time detection and characterization of lesions, potentially reducing human error, and standardizing the quality of colonoscopy across endoscopists. CADe has proven effective in increasing adenoma detection rate, potentially reducing long-term colorectal cancer incidence.