Clinical practice guideline and expert consensus recommendations for rehabilitation among children with cancer: A systematic review.

Increased attention to the rehabilitation needs of children with cancer is vital to enhance health, quality-of-life, and productivity outcomes. Among adults with cancer, rehabilitation recommendations are frequently incorporated into guidelines, but the extent to which recommendations exist for children is unknown. Reports included in this systematic review are guideline or expert consensus reports containing recommendations related to rehabilitation referral, evaluation, and/or intervention for individuals diagnosed with cancer during childhood (younger than 18 years). Eligible reports were published in English from January 2000 to August 2022. Through database searches, 42,982 records were identified; 62 records were identified through citation and website searching. Twenty-eight reports were included in the review: 18 guidelines and 10 expert consensus reports. Rehabilitation recommendations were identified in disease-specific (e.g., acute lymphoblastic leukemia), impairment-specific (e.g., fatigue, neurocognition, pain), adolescent and young adult, and long-term follow-up reports. Example recommendations included physical activity and energy-conservation techniques to address fatigue, referral to physical therapy for chronic pain management, ongoing psychosocial surveillance, and referral to speech-language pathology for those with hearing loss. High-level evidence supported rehabilitation recommendations for long-term follow-up care, fatigue, and psychosocial/mental health screening. Few intervention recommendations were included in guideline and consensus reports. In this developing field, it is critical to include pediatric oncology rehabilitation providers in guideline and consensus development initiatives. This review enhances the availability and clarity of rehabilitation-relevant guidelines that can help prevent and mitigate cancer-related disability among children by supporting access to rehabilitation services.

Older adult participation in cancer clinical trials: A systematic review of barriers and interventions.

Cancer is a disease of aging and, as the world's population ages, the number of older persons with cancer is increasing and will make up a growing share of the oncology population in virtually every country. Despite this, older patients remain vastly underrepresented in research that sets the standards for cancer treatments. Consequently, most of what we know about cancer therapeutics is based on clinical trials conducted in younger, healthier patients, and effective strategies to improve clinical trial participation of older adults with cancer remain sparse. For this systematic review, the authors evaluated published studies regarding barriers to participation and interventions to improve participation of older adults in cancer trials. The quality of the available evidence was low and, despite a literature describing multifaceted barriers, only one intervention study aimed to increase enrollment of older adults in trials. The findings starkly amplify the paucity of evidence-based, effective strategies to improve participation of this underrepresented population in cancer trials. Within these limitations, the authors provide their opinion on how the current cancer research infrastructure must be modified to accommodate the needs of older patients. Several underused solutions are offered to expand clinical trials to include older adults with cancer. However, as currently constructed, these recommendations alone will not solve the evidence gap in geriatric oncology, and efforts are needed to meet older and frail adults where they are by expanding clinical trials designed specifically for this population and leveraging real-world data.

Cardio-oncology care in the era of the coronavirus disease 2019 (COVID-19) pandemic: An International Cardio-Oncology Society (ICOS) statement.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has given rise to a pandemic of unprecedented proportions in the modern era because of its highly contagious nature and impact on human health and society: coronavirus disease 2019 (COVID-19). Patients with cardiovascular (CV) risk factors and established CV disease (CVD) are among those initially identified at the highest risk for serious complications, including death. Subsequent studies have pointed out that patients with cancer are also at high risk for a critical disease course. Therefore, the most vulnerable patients are seemingly those with both cancer and CVD, and a careful, unified approach in the evaluation and management of this patient population is especially needed in times of the COVID-19 pandemic. This review provides an overview of the unique implications of the viral outbreak for the field of cardio-oncology and outlines key modifications in the approach to this ever-increasing patient population. These modifications include a shift toward greater utilization of cardiac biomarkers and a more focused CV imaging approach in the broader context of modifications to typical practice pathways. The goal of this strategic adjustment is to minimize the risk of SARS-CoV-2 infection (or other future viral outbreaks) while not becoming negligent of CVD and its important impact on the overall outcomes of patients who are being treated for cancer.

The role of variable retrieval in effective learning.

Current research on memory indicates that learning is most effective when it involves spaced retrieval practice of study materials. Here, we investigated whether the benefits of both retrieval practice and spacing can be further boosted when variability is introduced across practice sessions. Across six experiments, participants learned translations of foreign vocabulary, with foreign words embedded in contextual sentences hinting at the meaning of these words. These sentences were then either kept constant or varied from one learning cycle to another. Whenever repeated practice took the form of retrieval from long-term memory with contextual sentences serving as cues (with or without feedback after retrieval attempts), variable sentences led to better learning of the meanings of the embedded foreign words than constant sentences. The benefits of variable retrieval were observed both immediately after study and after a 24-h delay, and they were larger when retrieval practice was spaced rather than massed. However, these benefits were not appreciated by the learners who judged learning to be more effective with constant rather than variable cues. This metacognitive illusion, misaligning the effectiveness of learning and its appraisal by learners, was confirmed in the seventh experiment which focused on learning lecture content. Thus, while spaced retrieval practice employing variable cues clearly produces robust benefits for memory performance, such benefits may be severely underappreciated by the learners.

A leadership-level culture cycle intervention changes teachers' culturally inclusive beliefs and practices.

Despite an abundance of support for culturally inclusive learning environments, there is little consensus regarding how to change educational contexts to effectively and sustainably foster cultural inclusion. To address this gap, we report findings from a research-practice partnership that leveraged the Culture Cycle Framework (CCF) to expand educators' praxis to include both independent and interdependent models of self. Most U.S. schools validate independent cultural models (i.e., those that prioritize individuality, uniqueness, and personal agency) and overlook interdependent models (i.e., those that prioritize connectedness, relationality, and collective well-being), which are more common among students from marginalized racial and socioeconomic backgrounds. Using a quasi-experimental longitudinal design, we trained school leadership to integrate ideas about cultural inclusion (i.e., validating the importance of both independent and interdependent cultural models) into school-wide flagship practices. We assessed downstream indicators of culture change by surveying teachers and students across the district and found that a) leadership-level training enhanced school-wide beliefs about cultural inclusion, b) teachers' endorsement of culturally inclusive beliefs predicted their use of culturally inclusive practices, and c) teachers' use of culturally inclusive practices predicted enhanced psychosocial and academic outcomes among students. This research represents a comprehensive culture change effort using the CCF and illustrates a means of fostering inclusion-focused educational culture change and assessing downstream consequences of culture change initiatives.

Cell line authentication: a necessity for reproducible biomedical research.

Immortalized or continuous cell lines are invaluable tools in basic and preclinical research. However, the widespread use of misidentified cell lines is a serious threat to scientific reproducibility. Based on the experiences of mandatory cell line authentication at the International Journal of Cancer (IJC), we provide an overview of the issues pertinent to misidentified cell lines and discuss available solutions. We also summarize the lessons learned, revealing that at least 5% of the human cell lines used in manuscripts considered for peer review are misidentified. About 4% of the considered manuscripts are rejected for severe cell line problems, and most are subsequently published in other journals. In order to diminish such malpractice and its consequences for the scientific record, we postulate that strict multi-layered quality control is essential. Besides journals and publishers, we encourage scientists, research institutions, and funders to take action on the matter and revise their respective policies. Hence, we provide concrete recommendations on introducing regular authentication schemes and staff training, and discuss future steps for enhancing good cell culture practices.

Follow the trail: Using insights from the growth of palliative care to propose a roadmap for cancer rehabilitation.

Despite research explicating the benefits of cancer rehabilitation interventions to optimize physical, social, emotional, and vocational functioning, many reports document low rates of referral to and uptake of rehabilitation in oncology. Cancer rehabilitation clinicians, researchers, and policy makers could learn from the multidisciplinary specialty of palliative care, which has benefited from a growth strategy and has garnered national recognition as an important and necessary aspect of oncology care. The purpose of this article is to explore the actions that have increased the uptake and integration of palliative care to yield insights and multimodal strategies for the development and growth of cancer rehabilitation. After examining the history of palliative care and its growth, the authors highlight 5 key strategies that may benefit the field of cancer rehabilitation: 1) stimulating the science in specific gap areas; 2) creating clinical practice guidelines; 3) building clinical capacity; 4) ascertaining and responding to public opinion; and 5) advocating for public policy change. Coordinated and simultaneous advances on these 5 strategies may catalyze the growth, utilization, and effectiveness of patient screening, timely referrals, and delivery of appropriate cancer rehabilitation care that reduces disability and improves quality of life for cancer survivors who need these services.

Equitably improving outcomes for cancer survivors and supporting caregivers: A blueprint for care delivery, research, education, and policy.

Cancer care delivery is being shaped by growing numbers of cancer survivors coupled with provider shortages, rising costs of primary treatment and follow-up care, significant survivorship health disparities, increased reliance on informal caregivers, and the transition to value-based care. These factors create a compelling need to provide coordinated, comprehensive, personalized care for cancer survivors in ways that meet survivors' and caregivers' unique needs while minimizing the impact of provider shortages and controlling costs for health care systems, survivors, and families. The authors reviewed research identifying and addressing the needs of cancer survivors and caregivers and used this synthesis to create a set of critical priorities for care delivery, research, education, and policy to equitably improve survivor outcomes and support caregivers. Efforts are needed in 3 priority areas: 1) implementing routine assessment of survivors' needs and functioning and caregivers' needs; 2) facilitating personalized, tailored, information and referrals from diagnosis onward for both survivors and caregivers, shifting services from point of care to point of need wherever possible; and 3) disseminating and supporting the implementation of new care methods and interventions.

Implementing personalized pathways for cancer follow-up care in the United States: Proceedings from an American Cancer Society-American Society of Clinical Oncology summit.

A new approach to cancer follow-up care is necessary to meet the needs of cancer survivors while dealing with increasing volume and provider shortages, knowledge gaps, and costs to both health care systems and patients. An approach that triages patients to personalized follow-up care pathways, depending on the type(s) and level(s) of resources needed for patients' long-term care, is in use in the United Kingdom and other countries and has been shown to meet patients' needs, more efficiently use the health care system, and reduce costs. Recognizing that testing and implementing a similar personalized approach to cancer follow-up care in the United States will require a multipronged strategy, the American Cancer Society and the American Society of Clinical Oncology convened a summit in January 2018 to identify the needed steps to move this work from concept to implementation. The summit identified 4 key strategies going forward: 1) developing a candidate model (or models) of care delivery; 2) building the case for implementation by conducting studies modeling the effects of personalized pathways of follow-up care on patient outcomes, workforce and health care resources, and utilization and costs; 3) creating consensus-based guidelines to guide the delivery of personalized care pathways; and 4) identifying and filling research gaps to develop and implement needed care changes. While these national strategies are pursued, oncology and primary care providers can lay the groundwork for implementation by assessing their patients' risk of recurrence and the chronic and late effects of cancer as well as other health care needs and resources available for care and by considering triaging patients accordingly, referring patients to appropriate specialized survivorship clinics as these are developed, helping to support patients who are capable of self-managing their health, setting expectations with patients from diagnosis onward for the need for follow-up in primary care and/or a survivorship clinic, and improving coordination of care between oncology and primary care.

Experiment aversion does not appear to generalize.

Over the past decade, governments and organizations around the world have established behavioral insights teams advocating for randomized experiments. However, recent findings by M. N. Meyer et al., Proc. Natl. Acad. Sci. U.S.A. 116, 10723-10728 (2019) and P. R. Heck, C. F. Chabris, D. J. Watts, M. N. Meyer, Proc. Natl. Acad. Sci. U.S.A. 117, 18948-18950 (2020) suggest that people often rate randomized experiments as less appropriate than the policies they contain even when approving the implementation of either policy untested and when none of the individual policies is clearly superior. The authors warn that this could cause policymakers to avoid running large-scale field experiments or being transparent about running them and might contribute to an adverse heterogeneity bias in terms of who is participating in experiments. In one direct and six conceptual preregistered replications (total N = 5,200) of the previously published larger-effect studies, using the same main dependent variable but with variations in scenario wordings, recruitment platforms, and countries, and the addition of further measures to assess people's views, we test the generalizability and robustness of these findings. Together, we find that the original results do not appear to generalize. That is, our triangulation reveals insufficient evidence to conclude that people exhibit a common pattern of behavior that would be consistent with relative experiment aversion, thereby supporting recent findings by R. Mislavsky, B. Dietvorst, U. Simonsohn, Mark. Sci. 39, 1092-1104 (2020). Thus, policymakers may not need to be concerned about employing evidence-based practices more so than about universally implementing policies.

An astonishing regularity in student learning rate.

Leveraging a scientific infrastructure for exploring how students learn, we have developed cognitive and statistical models of skill acquisition and used them to understand fundamental similarities and differences across learners. Our primary question was why do some students learn faster than others? Or, do they? We model data from student performance on groups of tasks that assess the same skill component and that provide follow-up instruction on student errors. Our models estimate, for both students and skills, initial correctness and learning rate, that is, the increase in correctness after each practice opportunity. We applied our models to 1.3 million observations across 27 datasets of student interactions with online practice systems in the context of elementary to college courses in math, science, and language. Despite the availability of up-front verbal instruction, like lectures and readings, students demonstrate modest initial prepractice performance, at about 65% accuracy. Despite being in the same course, students' initial performance varies substantially from about 55% correct for those in the lower half to 75% for those in the upper half. In contrast, and much to our surprise, we found students to be astonishingly similar in estimated learning rate, typically increasing by about 0.1 log odds or 2.5% in accuracy per opportunity. These findings pose a challenge for theories of learning to explain the odd combination of large variation in student initial performance and striking regularity in student learning rate.

American Society for Microbiology evidence-based laboratory medicine practice guidelines to reduce blood culture contamination rates: a systematic review and meta-analysis.

SUMMARYBlood cultures (BCs) are one of the critical tests used to detect bloodstream infections. BC results are not 100% specific. Interpretation of BC results is often complicated by detecting microbial contamination rather than true infection. False positives due to blood culture contamination (BCC) vary from 1% to as high as >10% of all BC results. False-positive BC results may result in patients undergoing unnecessary antimicrobial treatments, increased healthcare costs, and delay in detecting the true cause of infection or other non-infectious illness. Previous guidelines from the Clinical and Laboratory Standards Institute, College of American Pathologists, and others, based on expert opinion and surveys, promoted a limit of ≤3% as acceptable for BCC rates. However, the data supporting such recommendations are controversial. A previous systematic review of BCC examined three practices for reducing BCC rates (venipuncture, phlebotomy teams, and pre-packaged kits). Subsequently, numerous studies on different practices including using diversion devices, disinfectants, and education/training to lower BCC have been published. The goal of the current guideline is to identify beneficial intervention strategies to reduce BCC rates, including devices, practices, and education/training by providers in collaboration with the laboratory. We performed a systematic review of the literature between 2017 and 2022 using numerous databases. Of the 11,319 unique records identified, 311 articles were sought for full-text review, of which 177 were reviewed; 126 of the full-text articles were excluded based on pre-defined inclusion and exclusion criteria. Data were extracted from a total of 49 articles included in the final analysis. An evidenced-based committee's expert panel reviewed all the references as mentioned in Data Collection and determined if the articles met the inclusion criteria. Data from extractions were captured within an extraction template in the US Agency for Healthcare Research and Quality's Systematic Review Data Repository (https://srdr.ahrq.gov/). BCC rates were captured as the number of events (contaminated samples) per arm (standard practice versus improvement practice). Modified versions of the National Heart, Lung, and Blood Institute Study Quality Assessment Tools were used for risk of bias assessment (https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools). We used Grading of Recommendations, Assessment, Development and Evaluations to assess strength of evidence. There are several interventions that resulted in significant reduction in BCC rates: chlorhexidine as a disinfectant for skin preparation, using a diversion device prior to drawing BCs, using sterile technique practices, using a phlebotomy team to obtain BCs, and education/training programs. While there were no substantial differences between methods of decreasing BCC, our results indicate that the method of implementation can determine the success or failure of the intervention. Our evidence-based systematic review and meta-analysis support several interventions to effectively reduce BCC by approximately 40%-60%. However, devices alone without an education/training component and buy-in from key stakeholders to implement various interventions would not be as effective in reducing BCC rates.

Pre-supplementary Motor Cortex Mediates Learning Transfer from Perceptual to Motor Timing.

When we intensively train a timing skill, such as learning to play the piano, we not only produce brain changes associated with task-specific learning but also improve our performance in other temporal behaviors that depend on these tuned neural resources. Since the neural basis of time learning and generalization is still unknown, we measured the changes in neural activity associated with the transfer of learning from perceptual to motor timing in a large sample of subjects (n = 65; 39 women). We found that intense training in an interval discrimination task increased the acuity of time perception in a group of subjects that also exhibited learning transfer, expressed as a reduction in inter-tap interval variability during an internally driven periodic motor task. In addition, we found subjects with no learning and/or generalization effects. Notably, functional imaging showed an increase in pre-supplementary motor area and caudate-putamen activity between the post- and pre-training sessions of the tapping task. This increase was specific to the subjects that generalized their timing acuity from the perceptual to the motor context. These results emphasize the central role of the cortico-basal ganglia circuit in the generalization of timing abilities between tasks.

Implementation of Obesity Science Into Clinical Practice: A Scientific Statement From the American Heart Association.

Obesity is a recognized public health epidemic with a prevalence that continues to increase dramatically in nearly all populations, impeding progress in reducing incidence rates of cardiovascular disease. Over the past decade, obesity science has evolved to improve knowledge of its multifactorial causes, identifying important biological causes and sociological determinants of obesity. Treatments for obesity have also continued to develop, with more evidence-based programs for lifestyle modification, new pharmacotherapies, and robust data to support bariatric surgery. Despite these advancements, there continues to be a substantial gap between the scientific evidence and the implementation of research into clinical practice for effective obesity management. Addressing barriers to obesity science implementation requires adopting feasible methodologies and targeting multiple levels (eg, clinician, community, system, policy) to facilitate the delivery of obesity-targeted therapies and maximize the effectiveness of guideline-driven care to at-need patient populations. This scientific statement (1) describes strategies shown to be effective or promising for enhancing translation and clinical application of obesity-based research; (2) identifies key gaps in the implementation of obesity science into clinical practice; and (3) provides guidance and resources for health care professionals, health care systems, and other stakeholders to promote broader implementation and uptake of obesity science for improved population-level obesity management. In addition, advances in implementation science that hold promise to bridge the know-do gap in obesity prevention and treatment are discussed. Last, this scientific statement highlights implications for health research policy and future research to improve patient care models and optimize the delivery and sustainability of equitable obesity-related care.

Thirty Years of Neuroscientific Investigation of Placebo and Nocebo: The Interesting, the Good, and the Bad.

Over the past 30 years there has been a surge of research on the placebo effect using a neuroscientific approach. The interesting aspects of this effort are related to the identification of several biological mechanisms of both the placebo and nocebo effects, the latter of which is defined as a negative placebo effect. Some important translational implications have emerged both in the setting of clinical trials and in routine medical practice. One of the principal contributions of neuroscience has been to draw the attention of the scientific and medical communities to the important role of psychobiological factors in therapeutic outcomes, be they drug related or not. Indeed, many biological mechanisms triggered by placebos and nocebos resemble those modulated by drugs, suggesting a possible interaction between psychological factors and drug action. Unfortunately, this new knowledge regarding placebos has the potential of being dangerously exploited by pseudoscience.

Effect of Brain-Gut Behavioral Treatments on Abdominal Pain in Irritable Bowel Syndrome: Systematic Review and Network Meta-Analysis.

BACKGROUND & AIMS: Some brain-gut behavioral treatments (BGBTs) are beneficial for global symptoms in irritable bowel syndrome (IBS). United States management guidelines suggest their use in patients with persistent abdominal pain, but their specific effect on this symptom has not been assessed systematically. METHODS: We searched the literature through December 16, 2023, for randomized controlled trials (RCTs) assessing efficacy of BGBTs for adults with IBS, compared with each other or a control intervention. Trials provided an assessment of abdominal pain resolution or improvement at treatment completion. We extracted data as intention-to-treat analyses, assuming dropouts to be treatment failures and reporting pooled relative risks (RRs) of abdominal pain not improving with 95% confidence intervals (CIs), ranking therapies according to the P score. RESULTS: We identified 42 eligible randomized controlled trials comprising 5220 participants. After treatment completion, the BGBTs with the largest numbers of trials and patients recruited demonstrating efficacy for abdominal pain, specifically, included self-guided/minimal contact cognitive behavioral therapy (CBT) (RR, 0.71; 95% CI, 0.54-0.95; P score, 0.58), face-to-face multicomponent behavioral therapy (RR, 0.72; 95% CI, 0.54-0.97; P score, 0.56), and face-to-face gut-directed hypnotherapy (RR, 0.77; 95% CI, 0.61-0.96; P score, 0.49). Among trials recruiting only patients with refractory global IBS symptoms, group CBT was more efficacious than routine care for abdominal pain, but no other significant differences were detected. No trials were low risk of bias across all domains, and there was evidence of funnel plot asymmetry. CONCLUSIONS: Several BGBTs, including self-guided/minimal contact CBT, face-to-face multicomponent behavioral therapy, and face-to-face gut-directed hypnotherapy may be efficacious for abdominal pain in IBS, although none was superior to another.

Respiratory Isolation for Tuberculosis: A Historical Perspective.

Although tuberculosis is an ancient disease, recognition of its airborne route of transmission, with implications for respiratory isolation, is only relatively recent. Since the time of Hippocrates, the dogma among health practitioners was that the disease was hereditary or that it could be contracted by inhaling "miasma", or corrupted air. Consequently, isolation of patients was not routine practice, and, in fact, patients with scrofula (morbus regius, or "king's evil) sought to be cured by the "royal touch" throughout the middle ages. The sanatorium, which emerged in the mid-19th century, initially served as a place of healing, where patients could receive the appropriate diet, rest therapy, graduated exercise, and abundant fresh air. Major scientific breakthroughs, including Robert Koch's 1882 discovery of the tubercle bacillus as the disease's etiological agent and early 20th century experimental evidence that the organism could be transmitted via expectorated droplet nuclei, helped to reinforce the important public health role of sanatoria and tuberculosis hospitals in preventing disease transmission through isolation. The advent of highly efficacious and oral antitubercular regimens in the mid-20th century and the concurrent declining incidence of the disease contributed to the closure of tuberculosis sanatoria and hospitals in the US and western Europe. Over the past several decades, tuberculosis treatment in the US has been conducted in the outpatient setting under the supervision of local public health departments. Patients receiving treatment are required to remain in respiratory isolation in the home until they are deemed noninfectious based on multiple sputum samples. This historical review demonstrates that despite changing medical knowledge, drug therapies, and social conditions over time, the role of isolation remains an important topic of debate in the treatment of patients with pulmonary tuberculosis.

Emerging role of artificial intelligence in diagnosis, classification and clinical management of glioma.

Glioma represents a dominant primary intracranial malignancy in the central nervous system. Artificial intelligence that mainly includes machine learning, and deep learning computational approaches, presents a unique opportunity to enhance clinical management of glioma through improving tumor segmentation, diagnosis, differentiation, grading, treatment, prediction of clinical outcomes (prognosis, and recurrence), molecular features, clinical classification, characterization of the tumor microenvironment, and drug discovery. A growing body of recent studies apply artificial intelligence-based models to disparate data sources of glioma, covering imaging modalities, digital pathology, high-throughput multi-omics data (especially emerging single-cell RNA sequencing and spatial transcriptome), etc. While these early findings are promising, future studies are required to normalize artificial intelligence-based models to improve the generalizability and interpretability of the results. Despite prominent issues, targeted clinical application of artificial intelligence approaches in glioma will facilitate the development of precision medicine of this field. If these challenges can be overcome, artificial intelligence has the potential to profoundly change the way patients with or at risk of glioma are provided with more rational care.

Neuroanatomical Disposition, Natural Development, and Training-Induced Plasticity of the Human Auditory System from Childhood to Adulthood: A 12-Year Study in Musicians and Nonmusicians.

Auditory perception is fundamental to human development and communication. However, no long-term studies have been performed on the plasticity of the auditory system as a function of musical training from childhood to adulthood. The long-term interplay between developmental and training-induced neuroplasticity of auditory processing is still unknown. We present results from AMseL (Audio and Neuroplasticity of Musical Learning), the first longitudinal study on the development of the human auditory system from primary school age until late adolescence. This 12-year project combined neurologic and behavioral methods including structural magnetic resonance imaging (MRI), magnetoencephalography (MEG), and auditory tests. A cohort of 112 typically developing participants (51 male, 61 female), classified as "musicians" (n = 66) and "nonmusicians" (n = 46), was tested at five measurement timepoints. We found substantial, stable differences in the morphology of auditory cortex (AC) between musicians and nonmusicians even at the earliest ages, suggesting that musical aptitude is manifested in macroscopic neuroanatomical characteristics. Maturational plasticity led to a continuous increase in white matter myelination and systematic changes of the auditory evoked P1-N1-P2 complex (decreasing latencies, synchronization effects between hemispheres, and amplitude changes) regardless of musical expertise. Musicians showed substantial training-related changes at the neurofunctional level, in particular more synchronized P1 responses and bilaterally larger P2 amplitudes. Musical training had a positive influence on elementary auditory perception (frequency, tone duration, onset ramp) and pattern recognition (rhythm, subjective pitch). The observed interplay between "nature" (stable biological dispositions and natural maturation) and "nurture" (learning-induced plasticity) is integrated into a novel neurodevelopmental model of the human auditory system.Significance Statement We present results from AMseL (Audio and Neuroplasticity of Musical Learning), a 12-year longitudinal study on the development of the human auditory system from childhood to adulthood that combined structural magnetic resonance imaging (MRI), magnetoencephalography (MEG), and auditory discrimination and pattern recognition tests. A total of 66 musicians and 46 nonmusicians were tested at five timepoints. Substantial, stable differences in the morphology of auditory cortex (AC) were found between the two groups even at the earliest ages, suggesting that musical aptitude is manifested in macroscopic neuroanatomical characteristics. We also observed neuroplastic and perceptual changes with age and musical practice. This interplay between "nature" (stable biological dispositions and natural maturation) and "nurture" (learning-induced plasticity) is integrated into a novel neurodevelopmental model of the human auditory system.

Translating mesenchymal stem cell and their exosome research into GMP compliant advanced therapy products: Promises, problems and prospects.

Mesenchymal stem cells (MSCs) are one of the few stem cell types used in clinical practice as therapeutic agents for immunomodulation and ischemic tissue repair, due to their unique paracrine capacity, multiple differentiation potential, active components in exosomes, and effective mitochondria donation. At present, MSCs derived from tissues such as bone marrow and umbilical cord are widely applied in preclinical and clinical studies. Nevertheless, there remain challenges to the maintenance of consistently good quality MSCs derived from different donors or tissues, directly impacting their application as advanced therapy products. In this review, we discuss the promises, problems, and prospects associated with translation of MSC research into a pharmaceutical product. We review the hurdles encountered in translation of MSCs and MSC-exosomes from the research bench to an advanced therapy product compliant with good manufacturing practice (GMP). These difficulties include how to set up GMP-compliant protocols, what factors affect raw material selection, cell expansion to product formulation, establishment of quality control (QC) parameters, and quality assurance to comply with GMP standards. To avoid human error and reduce the risk of contamination, an automatic, closed system that allows real-time monitoring of QC should be considered. We also highlight potential advantages of pluripotent stem cells as an alternative source for MSC and exosomes generation and manufacture.