bluuebunny/crossref_metadata_2025_split huggingface dataset:
METHA-NeP: effectiveness and safety of methadone for neuropathic pain: a controlled randomized trial
Authors: Pentiado Júnior Jorge Alberto Martins , Barbosa Marcell Maduro , Kubota Gabriel Taricani , Martins Pedro Nascimento , Moreira Larissa Iulle , Fernandes Ana Mércia , da Silva Valquíria Aparecida , Júnior Jefferson Rosi , Yeng Lin Tchia , Teixeira Manoel Jacobsen , Ciampi de Andrade Daniel 
Published: October 2024

Abstract
In this randomized, double-blind, parallel placebo-controlled clinical trial, we evaluated the efficacy of methadone as an add-on therapy for people with chronic neuropathic pain (NP). Eighty-six patients were randomly assigned to receive methadone or placebo for 8 weeks. The primary outcome was the proportion of participants achieving at least 30% pain relief from baseline using a 100-mm pain Visual Analogue Scale. Secondary outcomes included global impression of change, NP symptoms, sleep quality, quality of life, pain interference in daily activities, and mood. A larger number of responders were found in the methadone (68%), compared to the placebo (33%) arm; risk difference 33.6%; 95% confidence interval 13.0%-54.3%; P = 0.003; number needed to treat = 3.0. Methadone reduced pain intensity (P < 0.001), burning (P = 0.023), pressing (P = 0.005), and paroxysmal dimensions (P = 0.006) of NP. Methadone also improved sleep (P < 0.001) and increased the patient's global impression of improvement (P = 0.002). Methadone did not significantly impact quality of life, pain interference, or mood. Treatment-emergent adverse events occurred in all methadone- and in 73% of placebo-treated patients (P < 0.001). No serious adverse events or deaths occurred. Discontinuation due to adverse events was reported in 2 participants in the methadone and none in the placebo arm. Methadone use as an add-on to an optimized treatment for NP with first- and/or second-line drugs provided superior analgesia, improved sleep, and enhanced global impression of change, without being associated with significant serious adverse effects that would raise safety concerns.
Brain predicted age in chronic pelvic pain: a study by the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network
Authors: Leech Kristan A. , Kettlety Sarah A. , Mack Wendy J. , Kreder Karl J. , Schrepf Andrew , Kutch Jason J. 
Published: October 2024

Abstract
The effect of chronic pain on brain-predicted age is unclear. We performed secondary analyses of a large cross-sectional and 3-year longitudinal data set from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network to test the hypothesis that chronic pelvic pain accelerates brain aging and brain aging rate. Brain-predicted ages of 492 chronic pelvic pain patients and 72 controls were determined from T1-weighted MRI scans and used to calculate the brain-predicted age gap estimation (brainAGE; brain-predicted − chronological age). Separate regression models determined whether the presence of chronic pelvic pain could explain brainAGE and brain aging rate when accounting for covariates. We performed secondary analyses to understand whether brainAGE was associated with factors that subtype chronic pelvic pain patients (inflammation, widespread pain, and psychological comorbidities). We found a significant association between chronic pelvic pain and brainAGE that differed by sex. Women with chronic pelvic pain had higher brainAGE than female controls, whereas men with chronic pelvic pain exhibited lower brainAGE than male controls on average—however, the effect was not statistically significant in men or women when considered independently. Secondary analyses demonstrated preliminary evidence of an association between inflammatory load and brainAGE. Further studies of brainAGE and inflammatory load are warranted.
Harmonizing neuropathic pain research: outcomes of the London consensus meeting on peripheral tissue studies
Authors: Villa Sara , Aasvang Eske K. , Attal Nadine , Baron Ralf , Bourinet Emmanuel , Calvo Margarita , Finnerup Nanna B. , Galosi Eleonora , Hockley James R.F. , Karlsson Pall , Kemp Harriet , Körner Jannis , Kutafina Ekaterina , Lampert Angelika , Mürk Margarita , Nochi Zahra , Price Theodore J. , Rice Andrew S.C. , Sommer Claudia , Taba Pille , Themistocleous Andreas C. , Treede Rolf-Detlef , Truini Andrea , Üçeyler Nurcan , Bennett David L. , Schmid Annina B. , Denk Franziska 
Published: October 2024

Abstract
Neuropathic pain remains difficult to treat, with drug development hampered by an incomplete understanding of the pathogenesis of the condition, as well as a lack of biomarkers. The problem is compounded by the scarcity of relevant human peripheral tissues, including skin, nerves, and dorsal root ganglia. Efforts to obtain such samples are accelerating, increasing the need for standardisation across laboratories. In this white paper, we report on a consensus meeting attended by neuropathic pain experts, designed to accelerate protocol alignment and harmonization of studies involving relevant peripheral tissues. The meeting was held in London in March 2024 and attended by 28 networking partners, including industry and patient representatives. We achieved consensus on minimal recommended phenotyping, harmonised wet laboratory protocols, statistical design, reporting, and data sharing. Here, we also share a variety of relevant standard operating procedures as supplementary protocols. We envision that our recommendations will help unify human tissue research in the field and accelerate our understanding of how abnormal interactions between sensory neurons and their local peripheral environment contribute towards neuropathic pain.
Glial-modulating agents for the treatment of pain: a systematic review
Authors: Gilron Ian , Xiao Maggie Z. X. , Carley Meg , Salter Michael W. , Hutchinson Mark R. , Moulin Dwight E. , Moore R. Andrew , Ross-White Amanda 
Published: October 2024

Abstract
Preclinical research supports a critical role for nervous system glia in pain pathophysiology. This systematic review of human trials of potential glia-modulating drugs for the prevention or treatment of pain followed a predefined search strategy and protocol registration. We searched for English language, randomized, double-blind trials comparing putative glia-modulating drugs to placebo or other comparators. The primary outcomes included validated participant-reported measures of pain intensity or relief and, in studies of opioid administration, measures of opioid consumption and/or opioid-related adverse effects. Twenty-six trials (2132 participants) of glial modulators (12 minocycline, 11 pentoxifylline, and 3 ibudilast) were included. Because of clinical heterogeneity related to study drug, participant population, outcome measures, and trial design, no meta-analysis was possible. Only 6 trials reported a positive effect of the treatment (pentoxifylline—4 trials; minocycline—2 trials), whereas 11 trials reported mixed results and 9 trials reported no effect. This review does not provide convincing evidence of efficacy of current pharmacological targets of nervous system glial function for pain treatment or prevention. However, in light of ample preclinical evidence of the importance of neuroimmune signalling and glial functions in pain pathophysiology, continued strategic human research is anticipated to identify (1) drugs with maximal activity as selectively targeted glial modulators, (2) the necessary timing and duration of pharmacological glial modulation needed for pain prevention or treatment for specific injuries or pain conditions, and (3) the best design of future clinical trials of glial-targeted drugs for pain treatment and/or prevention.
Spondylolysis in Adolescent Athletes: A Descriptive Study of 533 Patients
Authors: Moeller James L. 
Published: October 2024

Objective:
The objective of this descriptive study was to evaluate spondylolysis in adolescent athletes, including age at time of injury, sport associated with injury, examination findings, site of injury, studies used for diagnosis, treatments, duration of treatment, and outcomes.

Design:
This was a retrospective chart review of patients who presented with a diagnosis of spondylolysis over a 17-year period.

Setting:
Community primary care sports medicine practice.

Patients:
All patients between 10 and 20 years of age diagnosed with spondylolysis.

Interventions:
There was no set intervention protocol. A variety of interventions and combination of interventions were used and determined by the treating physician on a case-by-case basis.

Main Outcome Measures:
Clearance for return to sport activity.

Results:
Males comprised 317 of the 533 patients. Soccer, gymnastics/cheer, football, and basketball were the most common sports associated with spondylolysis. Bilateral injuries were most common. L5 was the most common level for injury. Bracing and formal physical therapy as treatments were associated with longer duration of care. Most patients were treated successfully with nonoperative treatment. Recurrence of injury was rare.

Conclusions:
Spondylolysis is a common cause of back pain in adolescent athletes. Males are more likely to experience these injuries and are older at presentation compared than females. Spondylosis may be encountered in many sports. Nonoperative treatment leads to successful outcomes in most patients.
Development of Interprofessional Competencies Through the Process of Collaborative Clinical Reasoning
Authors: Hart Stephanie , Lysaght Christine , Wedge Ryan 
Published: October 2024

Purpose:
Effective interprofessional (IP) collaboration is essential for managing complex patient cases. Collaborative clinical reasoning (CCR) is an approach where IP teams collectively analyze and address complex clinical cases, facilitating a shared understanding of patient management. While simulation and case-based learning are established methods for fostering IP collaboration, the process by which students develop a shared mental model for patient management after a simulated home visit and how this approach promotes the development of IP competencies is unknown. Understanding this process is critical for advancing IP competences that are fundamental to case management practice. The purpose of this study was to explore students’ perceptions of the CCR processes used to develop an integrated care plan following a simulated home visit.

Primary Practice Settings:
Home care and community-based practice settings

Methodology and Sample:
A qualitative descriptive approach was employed to explore PT and nursing student teams’ perceptions of the CCR processes used to develop an integrated care plan following a simulated home visit. Written responses to five reflection questions were analyzed using conventional content analysis among n = 87 physical therapy and nursing students.

Results:
There were three overarching themes: clarifying roles; developing a mutual approach; embracing shared values. Students’ perceptions reflected skills needed to develop IP competencies including CCR. More research is needed to explore how student teams resolve disputes and use interdisciplinary knowledge in the process of CCR.

Implications for Case Management Practice:
Findings highlight the importance of IP collaboration in clinical case management, emphasizing the need for case managers to facilitate clear role clarification, mutual approaches, and shared values among IP teams to enhance integrated care planning and improve patient outcomes. These insights can inform training and development programs for case managers on IP teams, promoting the adoption of CCR in practice.
Learning by the Visualization of a Nurse-Led Critical Care Outreach Service Using the Functional Resonance Analysis Method
Authors: op ‘t Hoog Sabine Adriana Johanna Josepha , van Mersbergen-de Bruin Mariëlle , Damen Nikki Laurina Mathilda , Chaboyer Wendy , Weggelaar-Jansen Anne Marie , Eskes Anne M. , Vloet Lilian Christina Maria , Vermeulen Hester 
Published: October 2024

Objectives
Quality improvements (QIs) in dynamic and complex health care contexts require resilience and take variability into account in quality improvement. The Functional Resonance Analysis Method (FRAM) helps us understand resilience and gain insight into (un)desirable variability in the complex system of daily practice. We explored how using FRAM in the Deming cycle of a QI project can help professionals and researchers learn from, reflect upon, and improve complex processes. We used FRAM in a Dutch hospital to study a QI: Critical Care Outreach Service (CCOS).

Methods
The aim was to use FRAM before and after implementation to create a FRAM model and reflect to health care professionals the mismatch between Work As Imagined (WAI) and Work As Done (WAD). The WAI FRAM model was co-created with professionals before the implementation of CCOS. We used descriptions of tasks and processes for ICU nurses and verified them in 30-minute semistructured interviews (N = 2). WAD was created by input of semistructured interviews with key professionals in CCOS (N = 21) and 3 nonparticipant observations of trained CCOS nurses. We validated WAD in 2 dialogue sessions with key professionals (N = 11). Data collection continued until saturation.

Results
Juxtaposing the WAI and WAD models showed that WAD contained additional functions and highlighted unexpectedly complex functions. Reflecting on the application of FRAM with health care professionals revealed opportunities and challenges, especially time investment.

Conclusions
FRAM helps professionals outline processes and tasks (WAI), learn from, and reflect upon their daily practice (WAD). FRAM models help professionals identify variability proactively to improve practices that enhance resilient performance.
Prospective Study of Contamination Spread Produced During Open Surgical vs Conventional Percutaneous vs Novel Percutaneous Tracheostomy During COVID-19 Era in a Pig Model
Authors: Ishii Shun , Amundson Julia R , Agos Andrew S , Tokarczyk Arthur , Torre Reynaldo , Kuchta Kristine , Ujiki Michael B , Greenberg Steven B 
Published: October 2024

BACKGROUND:
Because of concerns about provider contamination during tracheostomy procedures in a pandemic such as COVID-19, it is essential to objectively evaluate aerosol generation in all tracheostomy approaches, including newly developed tracheostomy procedures. We performed open surgical tracheostomy (OST), conventional percutaneous tracheostomy (CPT), and novel percutaneous tracheostomy (NPT), a modification of CPT designed to reduce contamination spread, in pig models and then compared the degree of contamination with providers using Glo Germ (Glo Germ).

STUDY DESIGN:
Six Yorkshire pigs were used for data collection. Either OST, CPT, or NPT was performed on the pigs by the same team including a surgeon, anesthesiologist, and respiratory therapist. A mixture of Glo Germ and water was administered via an atomizer into the oral cavity to the tracheal bifurcation before each procedure, and additionally dispersed via an aersolizer in the trachea and lungs through the endotracheal tube before and throughout the procedure. Before and immediately after each procedure, prespecified body parts of the providers were photographed and 2 independent examiners blindly evaluated the photographs to determine degree of Glo Germ contamination using a 3-point Likert scale.

RESULTS:
Total contamination among provider team average score (minimum 0, maximum 2), was significantly lower for OST than CPT (0.29 ± 0.59 vs 0.63 ± 0.65; p < 0.01) or NPT (0.29 ± 0.59 vs 0.59 ± 0.66; p < 0.01). No significant difference was seen in overall contamination of any provider between CPT and NPT (0.63 ± 0.65 vs 0.59 ± 0.66; p = 0.92).

CONCLUSIONS:
Our results suggest that OST causes significantly less aerosol contamination to providers than either CPT or NPT.
Inducing representational change in the hippocampus through real-time neurofeedback
Authors: Peng Kailong , Wammes Jeffrey D. , Nguyen Alex , Iordan Coraline Rinn , Norman Kenneth A. , Turk-Browne Nicholas B. 
Published: October 2024

When you perceive or remember something, other related things come to mind, affecting how these competing items are subsequently perceived and remembered. Such behavioural consequences are believed to result from changes in the overlap of neural representations of these items, especially in the hippocampus. According to multiple theories, hippocampal overlap should increase (integration) when there is high coactivation between cortical representations. However, prior studies used indirect proxies for coactivation by manipulating stimulus similarity or task demands. Here, we induce coactivation in visual cortex more directly using closed-loop neurofeedback from real-time functional magnetic resonance imaging (fMRI). While viewing one object, participants were rewarded for activating the representation of another object as strongly as possible. Across multiple real-time fMRI sessions, participants succeeded in using this neurofeedback to increase coactivation. Compared with a baseline of untrained objects, this protocol led to memory integration in behaviour and the brain: the trained objects became harder for participants to discriminate behaviourally in a categorical perception task and harder to discriminate neurally from patterns of fMRI activity in their hippocampus as a result of losing unique features. These findings demonstrate that neurofeedback can be used to alter and combine memories.
This article is part of the theme issue ‘Neurofeedback: new territories and neurocognitive mechanisms of endogenous neuromodulation’.
Effects of fMRI neurofeedback of right inferior frontal cortex on inhibitory brain activation in children with ADHD
Authors: Lukito Steve , Lam Sheut-Ling , Criaud Marion , Westwood Samuel , Kowalczyk Olivia S. , Curran Sarah , Barrett Nadia , Abbott Christopher , Liang Holan , Simonoff Emily , Barker Gareth J. , Giampietro Vincent , Rubia Katya 
Published: October 2024

We aimed to replicate previous effects of functional magnetic resonance imaging neurofeedback (fMRI-NF) in right inferior frontal cortex (rIFC) on IFC activation during a Stop Task in a larger group of boys with attention-deficit/hyperactivity disorder (ADHD). The present double-blind, randomized controlled trial tested the effects of 15 runs of active versus sham fMRI-NF of rIFC on performance and activation associated with successful and failed inhibition versus Go trials during a tracking Stop task in 88 boys with ADHD (44 active; 44 sham), controlling for age and medication status. No significant group-by-time interaction effects were observed for performance or brain activation during the successful stop trials, and post hoc analysis showed very low numbers of active fMRI-NF learners. Nevertheless, during error monitoring, there was a significant group-by-time interaction effect on post-error reaction time slowing and in left IFC activation, which were both increased after active compared to sham fMRI-NF. The findings are in line with our previous observation of left IFC upregulation after fMRI-NF of rIFC relative to active fMRI-NF of parahippocampal gyrus. This highlights the potentially wider regional effects that fMRI-NF of a particular self-control target region has on other self-regulatory regions in ADHD.
This article is part of the theme issue ‘Neurofeedback: new territories and neurocognitive mechanisms of endogenous neuromodulation’.
Transcriptional profiling reveals a previously unknown population of Cdkn2a-positive tumor-associated macrophages in aggressive brain cancer
Authors: Melo dos Santos Letícya Simone , Kich Grun Lucas , Nathali Scholl Juliete , Barbé-Tuana Florencia María , Demaria Marco 
Published: October 2024

AbstractMicroglia, the resident immune cells of the Central Nervous System (CNS), play crucial roles in homeostasis, immune responses, and the modulation of neuronal functions. In brain tumors, microglia are difficult to distinguish from infiltrating macrophages and are collectively called Tumor-Associated Macrophages (TAMs). While these cells exhibit plasticity, support tumor growth, and suppress antitumor immune responses, their identity and function remain largely unknown. Cellular senescence, a state of growth arrest associated with the upregulation of the cell cycle inhibitor p16INK4A(Cdkn2a), can both suppress and promote tumor progression via the secretion of inflammatory and tissue remodeling factors, collectively known as Senescence-Associated Secretory Phenotype (SASP). By leveraging existing single-cell RNA sequencing (scRNA-seq) data of murine brain tumors, we identified a population of Cdkn2a-positive TAMs involved in immune regulation and neurogenesis, characterized by high expression of Emb and Cd93, which we named MECC (Microglia-like, and Emb-, CD93- and Cdkn2a-positive) cells. In humans, these cells were more prevalent in recurrent glioblastoma and associated with poorer prognosis. Comparative analysis of brain samples from patients with neurodegeneration and healthy older individuals revealed the specificity of MECCs for brain tumors. These findings suggest that MECCs are a unique and distinct cell population associated with aggressive brain tumors, which could potentially serve as targets for novel treatments.
Clinical Recognition of Frontotemporal Dementia with Right Temporal Predominance; Consensus Recommendations of the International Working Group
Authors: Ulugut Hulya , Younes Kyan , Montembeault Maxime , Bertoux Maxime , Irish Muireann , Kumfor Fiona , Fumagalli Giorgio G. , Samanci Bedia , Illán-Gala Ignacio , Thompson Jennifer C. , Santillo Alexander F , Englund Elisabet , Waldö Maria Landqvist , Riedl Lina , Van den Stock Jan , Vandenbulcke Mathieu , Vandenberghe Rik , Laforce Robert Jr , Ducharme Simon , Pressman Peter S. , Caramelli Paulo , de Souza Leonardo Cruz , Takada Leonel T. , Gurvit Hakan , Diehl-Schmid Janine , Galimberti Daniela , Pasquier Florence , Weintraub Sandra , Miller Bruce L. , Sturm Virginia E. , Whitwell Jennifer L. , Boeve Bradley , Rohrer Jonathan D. , Piguet Olivier , Gorno-Tempini Maria Luisa , Josephs Keith A. , Snowden Julie , Rowe James B. , Warren Jason D. , Rankin Katherine P. , Pijnenburg Yolande A.L. ,   International rtvFTD working group
Published: October 2024

AbstractAccurate diagnosis of frontotemporal dementia (FTD) with right anterior temporal lobe (RATL) predominance remains challenging due to lack of clinical characterization, and standardized terminology. The recent research of the International Working Group (IWG) identified common symptoms but also unveiled broad terminologies lacking precision and operationalization, with risk of misdiagnoses, inappropriate referrals and poor clinical management. Based on the published evidence (91267 articles screened) and expert opinion (105 FTD specialists across 52 centers), the IWG delineates three primary domains of impairment causing behavioral, memory and language problems: (i) multimodal knowledge of non-verbal information including people, living beings, landmarks, flavors/odors, sounds, bodily sensations, emotions and social cues; (ii) socioemotional behavior encompassing emotion expression, social response and motivation; and (iii) prioritization for focus on specific interests, hedonic valuation and personal preferences. This study establishes a consensus on clinical profile, phenotypic nomenclature, and future directions to enhance diagnostic precision and therapeutic interventions.