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The recent introduction of the right to oncological oblivion in some European states raises critical issues. While designed to protect cancer survivors from discrimination, this right may compromise occupational health surveillance for workers exposed to carcinogenic hazards. This commentary raises questions for future policy and research.
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To investigate the effects of multisensory-integrated virtual reality (VR) training on gait adaptability and its regulatory mechanisms on the somatomotor network (SMN) in patients with stroke. In this randomized controlled trial, 68 patients with stroke were allocated to a VR group (multisensory-integrated VR training) or a control group (conventional rehabilitation). Both groups received 30-minute sessions, 5 days/week for 4 weeks. The primary outcome was gait adaptability assessed by the Dynamic Gait Index (DGI). Secondary outcomes included the Timed Up and Go Test (TUGT), Berg Balance Scale (BBS), and Fugl-Meyer Assessment for Lower Extremity (FMA-LE). Functional near-infrared spectroscopy (fNIRS) measured resting-state functional connectivity within the SMN and task-evoked activation during stepping and obstacle crossing. The VR group showed significantly greater improvements than the control group in DGI total score (P = 0.010), TUGT (P = 0.005), and BBS (P < 0.001 ). fNIRS analysis revealed that the VR group exhibited significantly greater increases in task-evoked activation in the right posterior parietal cortex (PPC) and supplementary motor area (SMA) during stepping (P = 0.029 and P = 0.032, respectively), and in the right SMA during unaffected-limb obstacle crossing (P = 0.048). Resting-state functional connectivity analysis showed significantly enhanced connections within the SMN, including left SMA-right PPC and right PPC-left dorsolateral prefrontal cortex (DLPFC) (both P < 0.05). Correlation analyses revealed that increased right SMA activation during obstacle crossing was positively correlated with TUGT improvement (r = 0.590, P = 0.001), while enhanced right PPC-left DLPFC connectivity was positively correlated with DGI improvement (r = 0.403, P = 0.041). Multisensory-integrated VR training was associated with improvements in gait adaptability and balance in patients with stroke. The underlying mechanisms may involve enhanced activation in the SMA and PPC, along with changes in functional connectivity within the SMN and between the SMN and cognitive control networks. However, given that the significant improvements in DGI, TUGT, and BBS were not sustained under the most conservative assumptions about missing data, these findings should be considered preliminary and warrant confirmation in studies with lower attrition rates. Chinese Clinical Trial Registry, ChiCTR2500111919 (retrospectively registered). Registered 7 November 2025. Available from https//www.chictr.org.cn (registration number ChiCTR2500111919). Protocol The full trial protocol is available from the corresponding author upon reasonable request.
Schizophrenia spectrum disorders (SSD) feature deficits in movement intention, predictive mechanisms, and agency. While prior work characterised BOLD amplitude during movement preparation and temporal dynamics across the entire movement period, it remains unknown whether preparatory neural (BOLD) response timing and duration are selectively impaired in SSD. We analysed fMRI data from 20 SSD patients and 20 healthy controls during active and passive hand movements with video feedback (own vs. other hand). Preparatory and executory BOLD responses were modelled separately using the canonical HRF and its temporal (TD) and dispersion (DD) derivatives to evaluate timing and duration. Patients with SSD showed pronounced preparatory abnormalities under own-hand feedback, including delayed responses in right supplementary motor area during active movement preparation. Passive- and active-specific timing was reversed (earlier/later) in the left (caudate, middle temporal gyrus, superior parietal gyrus) and right (postcentral gyrus, right precentral gyrus, anterior cingulate cortex). Response duration showed reduced/reversed modulation (shorter/longer) in the right supplementary motor area, bilateral supramarginal gyrus, left inferior parietal cortex, and bilateral middle temporal gyrus. Earlier response timing in right precentral gyrus during active own-hand were negatively correlated with delusions of being controlled and formal thought disorder. No group differences emerged during execution.
Reward brain circuitry dysfunction is a hypothesized mechanism of bipolar disorder and alcohol use disorder co-occurrence (BD + AUD) that remains largely untested. This neuroimaging study represents the first investigation of functional connectivity in BD + AUD. Following a two-by-two factorial design (N = 90), individuals with BD + AUD (n = 22), AUD alone (n = 20), BD alone (n = 23), and healthy control participants (n = 25) were administered a fMRI alcohol-cue reactivity paradigm. Generalized psychophysiological interaction (PPI) modeling (p < 0.001; p-FDR < 0.05) was performed for regions of interest, including the right dorsal anterior insula, inferior frontal gyrus, and bilateral amygdala and dorsal striatum (i.e., caudate body). Extracted beta weights were explored for bivariate associations with key behavioral correlates (AUD age of onset, alcohol craving and dependence severity, abstinence duration, and impulsivity) (p < 0.05). BD + AUD individuals exhibited cue-modulated hyperconnectivity between the left dorsal striatum and right posterior cingulate cortex (p-FDR = 0.045) versus the AUD and BD groups, who both exhibited hypoconnectivity between these regions versus healthy participants. Additionally, there were main effects of AUD and BD (p-FDR ≤ 0.040) on cue-modulated functional connectivity of the right dAI (↓ middle frontal gyrus [MFG]) and left amygdala (↑ right superior temporal gyrus, anterior cingulate cortex, and MFG), respectively. Select functional connectivity data were associated with trait characteristics of AUD in BD + AUD (r ≥±0.50, p ≤ 0.026) but not AUD. A distinct pattern of cortico-striato-limbic functional connectivity and brain-behavior relationships was found to characterize BD + AUD with implications for treatment development. Namely, leveraging neuromodulation techniques that can effectively normalize the identified circuitry disruptions could represent a novel path for treatment advances in BD + AUD.
The right of patients to decline information about their health, prognosis, and available treatment options is a salient principle in both domestic law and international declarations and conventions. This right may be considered either unnegotiable or subject to certain terms and conditions. While respecting this right may seem straightforward, doing so in clinical practice can be challenging. This article uses a realistic hypothetical scenario to examine the epistemic, moral, and practical challenges that can arise, particularly with patients nearing the end of life. These challenges include how and when to honor the right and its potential conflict with moral values such as self-determination, authenticity, and avoiding harm to oneself and others. The end of life exacerbates these issues because of the irretrievability of decisions and the successive reduction of possible courses of action, as well as potentially changing preferences. These potential conflicts of values deserve further attention and must be considered when deciding whether to honor a patient's wish not to know.
Neuroimaging studies in familial high-risk (FHR) individuals are vital for identifying vulnerability markers independent of overt illness. However, research on purely non-prodromal FHR cohorts using comparative multimodal approaches remains limited. This study addresses this gap through multimodal MRI analysis-including cortical morphometry, white matter microstructure, tractography, and functional connectivity-in non-prodromal FHR for psychosis (FHR-P, n = 18), bipolar disorder (FHR-BD, n = 19), and healthy controls (HC, n = 25). FHR-BD showed increased right inferior parietal surface area and right middle temporal volume compared to HC. Conversely, FHR-P exhibited reduced right superior frontal cortical thickness compared to FHR-BD and decreased left pallidum volume compared to HC. White matter analysis revealed significantly lower fractional anisotropy in FHR-P compared to both FHR-BD and HC. FHR-BD showed higher axial diffusivity than HC in the forceps minor, uncinate fasciculus, and right-fronto-occipital fasciculus. No significant differences were found in network-based statistics or graph theoretical measures. These findings reveal shared and distinct neurobiological alterations in non-prodromal FHR-P and FHR-BD, suggesting that grey and white matter disruptions constitute endophenotypes even without clinical symptoms. The lack of network-level findings may reflect the modest sample size, requiring further investigation in larger cohorts.
Narrative generation requires the integration of linguistic, social, and conceptual knowledge to transform internal representations into coherent discourse. Few studies have examined how the distinct stages of comprehension and production are supported by the brain. In this fMRI study, 27 participants viewed a nine-panel cartoon, planned a story, and then orally produced it during scanning. Story comprehension elicited greater activation than fixation within the default mode network (DMN), including medial prefrontal cortex, posterior cingulate cortex, and precuneus, as well as the right insula, regions implicated in situation model construction, emotional inference, and mental simulation. Story production engaged a broader bilateral network encompassing hippocampus, basal ganglia, right temporoparietal junction (TPJ), and left anterior temporal lobe (ATL), reflecting additional demands on lexical selection, memory retrieval, and social-cognitive processes. Exploratory regression analyses revealed that higher lexical diversity (Maas) was associated with reduced activation in the right inferior frontal gyrus during comprehension and increased activation in the precuneus. Regression analysis also showed that a measure of social cognition (TASIT) was associated with cerebellar activation, supporting its emerging role in mentalizing and social prediction. These findings demonstrate that narrative generation relies on dynamic interactions among DMN, language, and cerebellar systems, with comprehension and production sharing a common representational foundation but diverging in their linguistic, memory, and social-cognitive demands. Regression results highlight potential neural mechanisms linking individual differences in lexical and social processing to narrative performance.
Chronic low back pain (CLBP) is a prevalent condition with unclear pathophysiology and substantial socioeconomic burden. Cerebral blood flow (CBF) alterations have been implicated in CLBP, yet previous arterial spin labeling (ASL) studies using single post-labeling delay (PLD) have yielded inconsistent results. In this study, multi-PLD ASL was combined with machine learning to characterize CBF alterations in CLBP and to explore their classification feasibility. Seventy-eight patients with CLBP and seventy-eight age- and sex-matched healthy controls underwent multi-PLD ASL scanning. Voxel-wise comparisons of normalized CBF were performed, followed by correlation analyses with clinical measures. Radiomics features extracted from brain regions showing significant CBF differences were used to construct machine learning classification models via a rigorous nested cross-validation and LASSO feature selection framework. Compared with healthy controls, patients with CLBP exhibited significant hyperperfusion in the right lingual gyrus and right thalamus. CBF values in the right lingual gyrus were positively correlated with Oswestry Disability Index scores, while thalamic CBF was positively correlated with pain intensity. Among the evaluated models, the XGBoost classifier achieved the best performance, with an area under the curve of 0.842 (95% CI: 0.774-0.901). These findings indicate that region-specific CBF alterations are closely associated with pain severity and functional impairment in CLBP. Machine learning analysis of CBF radiomic features shows potential discriminative performance in identifying patients with CLBP.
Phakomatoses, also known as neurocutaneous syndromes are rare disorders characterized by multisystem involvement with variable neurological manifestations in children, including intracranial vascular malformations. Cavernous malformations may present with acute haemorrhage and stroke-like symptoms. Diagnostic difficulty arises when radiologic findings suggest a benign lesion, yet histopathology reveals discordant malignant pathology. An 8-year-old female presented with sudden-onset left hemiparesis and recurrent seizures. Physical examination revealed multiple cutaneous naevi, raising suspicion of a syndromic association. Brain magnetic resonance imaging demonstrated a well-circumscribed right parietal intra-axial lesion with a "popcorn" appearance and hypointense susceptibility blooming, highly suggestive of a cavernous malformation. Cranial computed tomography scan subsequently showed an associated large intracerebral haematoma. The patient underwent right parietal craniotomy with haematoma evacuation and excision of the lesion. The immediate postoperative course was initially satisfactory with neurological improvement. Histopathological examination of the excised specimen, however, revealed a malignant neoplasm, establishing a significant radiologic-histologic discordance which fundamentally altered the diagnostic interpretation. The patient had a relapse of symptoms two months after surgery, with repeat neuroimaging showing multicentric tumour recurrence, necessitating referral for adjuvant neuro-oncologic management. This case illustrates a rare diagnostic pitfall and challenge in paediatric neurosurgery, where a malignant intracranial tumour mimicked a cavernous malformation in the context of cutaneous stigmata. The report emphasizes the limitations of neuroimaging alone and underscores the importance of careful clinicoradiologic correlation, histopathological confirmation, and multidisciplinary evaluation when managing presumed vascular lesions in children, particularly in resource-limited settings.
High bone mineral density (BMD) is common and sometimes an incidental finding. The causes are numerous. Among them, none has previously been attributed to total body irradiation (TBI). We present the case of a 56-year-old female patient with a history of T-lymphoblastic lymphoma at age 33 who was treated with allogeneic hematopoietic stem cell transplantation following a conditioning regimen including a single-fraction 10 Gray TBI. This patient was in complete remission but experienced several transplant-related late effects. She presented to the rheumatology outpatient clinic with chronic mechanical low back pain and a history of early menopause. Bone assessment by densitometry revealed high bone mineral density with a lumbar spine L2-L4 T-score of +6.3 standard deviation (SD) (1.939 g/cm²), right femoral neck T-score of +7.2 SD (1.849 g/cm²), right total femur T-score of +4 SD (1.484 g/cm²), distal radioulnar T-score of +0.7 SD (0.495 g/cm²). Imaging revealed sclerotic lesions in the vertebrae, femoral cortices and pelvis. An etiological workup excluded other causes such as fluorosis, mastocytosis, renal osteodystrophy, hypoparathyroidism/pseudohypoparathyroidism and myelofibrosis. Bone growth factors and resorption markers were normal. Genetic sequencing showed no significant abnormalities. Based on this comprehensive evaluation, TBI was identified as a possible contributing factor to the occurrence of high BMD. The patient was managed with analgesics and regular follow-up. This case highlights the importance of a systematic etiologic approach to high bone mineral density and underscores the need for future scientific research to better understand this phenomenon for which the pathological relationship with radiation exposure remains unknown.
The role of dominant frequency (DF)-guided ablation after pulmonary vein isolation (PVI) in persistent atrial fibrillation (AF) remains uncertain. We evaluated the clinical and mechanistic impact of DF mapping in a multicenter randomized study. In this multicenter, prospective study, 103 patients were enrolled. Patients with high-DF sites (≥ 7 Hz) were randomized 1:1 to PVI plus DF ablation (DF group, n = 32) or PVI alone (PVI group, n = 32). Patients without high-DF sites (< 7 Hz, n = 39) underwent PVI only (non-DF group; exploratory cohort). The primary endpoint was freedom from documented AF recurrence without antiarrhythmic drugs (AADs) at 12 months. AF-free survival off AADs was 81.3% in the DF group versus 68.9% in the PVI group (p = 0.228) at 12 months. Arrhythmia-free survival with or without AADs was 78.1% versus 65.6% (p = 0.263). The non-DF group showed the most favorable outcomes (83.3%, p = 0.065 vs PVI group). No adverse events were associated with DF mapping or ablation. Multivariate analysis identified right atrial (RA) low-voltage area extent (HR 1.031, 95% CI 1.005-1.058, p = 0.018) and LA diameter (HR 0.899, 95% CI 0.816-0.991, p = 0.032) as independent predictors of recurrence. In this multicenter randomized trial, adjunctive DF-guided ablation following PVI did not result in a statistically significant improvement in arrhythmia-free survival compared with PVI alone. However, the absence of high-DF sites was associated with favorable outcomes, and RA low-voltage burden emerged as an independent predictor of recurrence, supporting the potential mechanistic value of DF mapping and highlighting the prognostic importance of right atrial structural remodeling. UMIN000042543.
Primary cardiac tumors are extremely rare in fetal life, with rhabdomyomas being the most frequently encountered. In contrast, fetal cardiac myxomas are exceptionally uncommon, and reports of diagnosis during the first trimester are exceedingly rare. We report a fetal right atrial myxoma diagnosed at 12 weeks' gestation. Fetal echocardiography revealed a hyperechoic, pedunculated mass originating from the right atrial wall. Serial follow-up demonstrated rapid tumor growth, with increasing pericardial effusion and reversed A-wave flow in the ductus venosus by 14 weeks' gestation, indicating early and severe hemodynamic compromise. After detailed parental counseling regarding the poor prognosis, the pregnancy was electively terminated. Postmortem examination revealed a gelatinous intracardiac mass, and histopathological analysis confirmed the diagnosis of cardiac myxoma, showing stellate cells embedded in a myxoid stroma. To our knowledge, this represents the earliest gestational age at which a fetal cardiac myxoma has been diagnosed and histopathologically confirmed. This case highlights that fetal cardiac myxomas, although histologically benign, may demonstrate rapid progression and lead to significant hemodynamic deterioration even in the first trimester, underscoring the importance of early fetal echocardiographic evaluation and timely parental counseling.
Policy Points A quarter of a century since bioethicist Edmund Pellegrino warned about the commodification of health and health care, the problem has significantly worsened. Commodification of health and health care objectifies and dehumanizes people and undermines core concepts of holistic person-centered health, much less core human rights, including fulfillment of human potential and comprehensive health care. Multilevel sustained strategies and multisector coalitions are required to decommodify and humanize health and health care based on mental models, national and state policies, practices, resource flow, power dynamics, and relationships and connections. Edmund Pellegrino warned about the growing commodification of health and health care in the United States. After twenty-five years, it is worth revisiting Pellegrino's critique and examining this critique in the current era. We conducted a targeted review of the literature to revisit the state of commodification in health and health care as defined by Pellegrino, examined its relationship to dehumanization, and explored prospects for addressing commodification. The commodification of health and health care substantially worsened in the US, characterized by increased health care corporatization and consolidation, biomedical lobbying, and unaffordable costs. Commodification and dehumanization reinforce each other, undermining rights to health and health care, the provision of holistic person-centered health, and the fulfillment of human potential. Decommodifying and humanizing health and health care requires a paradigm shift towards whole-person definitions of health; the acknowledgement of human relationships as a foundation; the recognition of health as a social good; and the need for society and healthcare to partner to optimize health, including providing health care to all. This paradigm shift will require collective, cross-sectoral advocacy and mobilization not only by diverse health care professional organizations but also by organizations outside health care that are committed to improving health for all.
Internalizing disorders have been linked to alterations in default mode network (DMN) resting-state functional connectivity (RSFC). Given the increased risk of internalizing disorders in offspring of parents with a history of internalizing disorders, this study examined associations between parental depression and anxiety severity and adolescent DMN RSFC. Participants were 116 parent-adolescent dyads with youth between ages of 11-17 years. Structured diagnostic interviews and self-report questionnaires were completed by parents and adolescents to assess history and severity of internalizing disorders. Adolescents completed resting-state functional magnetic resonance imaging to determine the RSFC between regions of the DMN including the medial prefrontal cortex (mPFC), posterior cingulate cortex (PCC), and bilateral lateral parietal cortices (LPC). Analyses examined region-of-interest (ROI) to ROI RSFC, with bivariate correlations and linear regressions used to assess whether child age, sex, child internalizing symptoms, and parental internalizing symptoms were associated with child RSFC alterations. After controlling for child age, sex, internalizing symptoms, and in-scanner motion, increased parental depressive severity was associated with increased child RSFC between the PCC and right LPC. Child internalizing symptoms were also linked to decreased RSFC between the right LPC and the mPFC. This study is limited by its modest sample size relative to effect sizes for functional connectivity-phenotype associations, cross-sectional design, and a relatively homogeneous sample in terms of ethnicity, socioeconomic status, and parental sex. Results suggest that, among youth with a parental history of depression or anxiety, increased severity of parental depression is associated with altered offspring DMN RSFC.
The clinical trajectory of pulmonary vascular disease (PVD) is governed by the functional and molecular integration of the right ventricle (RV) and pulmonary vasculature-the cardiopulmonary unit. Right ventricular-pulmonary arterial (RV-PA) coupling (Ees/Ea) is the principal determinant of survival. This review synthesizes contemporary pathophysiology and therapeutics through the lens of RV-PA coupling, reflecting the recognition of active heart-lung crosstalk. Advancing beyond traditional reviews, this article (1) formalizes a phenotype-guided treatment algorithm based on coupling derangement, (2) integrates emerging concepts of molecular crosstalk mediated by extracellular vesicles, and (3) positions sotatercept as a "coupling drug" targeting both components of the cardiopulmonary unit. We detail maladaptive pathways-including metabolic reprogramming, inflammation, fibrosis, and sex hormone signaling-that degrade RV contractility (Ees) under chronic pressure overload. The pharmacotherapeutic landscape is critically evaluated: from established vasodilators that indirectly support the RV by reducing afterload (Ea) to transformative disease-modifying agents like sotatercept that reverse vascular remodeling and the emerging frontier of direct RV-targeted therapies. We argue that the future of PVD management lies in a precision-based strategy using deep phenotyping to classify patients by dominant coupling derangements and matching them with mechanism-based therapies. The paradigm must shift beyond symptomatic vasodilation toward regimens explicitly designed to restore the physiological balance of the cardiopulmonary unit, carefully distinguishing between validated standards of care and investigational approaches.
This operative video report demonstrates two cases of endoscopic fenestration for enlarging symptomatic thalamic cysts causing obstructive hydrocephalus. A literature review of 29 cases (1987-2026)1-17 reveals hydrocephalus present in the majority of cases. Common presentations include headache, gait disturbance, and cognitive changes. The first case involves a 62-year-old female with progressive proprioceptive deficits and imbalance due to a 2.5 cm right thalamic cyst protruding into the third ventricle. The second case involves a 59-year-old female presenting with altered mental status and headaches from an enlarging right thalamic cyst. In both cases, a frontal transcortical endoscopic approach was utilized to fenestrate the cysts into the lateral and third ventricles in combination with an endoscopic third ventriculostomy. To ensure precise access, two separate trajectories were employed: one providing a straight-line path to the cyst wall and another to the floor of the third ventricle. Fenestration was achieved using blunt dissection and Fogarty balloon dilation, followed by further enlargement with alligator clamps. Postoperatively, both patients experienced complete resolution of symptoms and mass effect. These cases illustrate that while benign thalamic neuroepithelial cysts are rarely symptomatic10, they can be effectively treated with endoscopic fenestration. While treatment approaches in the literature vary, endoscopic or microsurgical fenestration remains the most common intervention. This technique, utilizing a high-resolution rigid endoscope coupled with stereotactic navigation and preoperative trajectory planning, allows for safe and effective treatment of these deep cystic lesions.
Treating primary back pain in horses can be challenging and often necessitates a multimodal approach. Whole-body vibration therapy (WBV) has been used in both horses and humans to alleviate pain and strengthen muscles. A recent study showed worsening back pain following a 30-minute session of WBV; however, the immediate effects of WBV were not evaluated. The purpose of this study was to assess the immediate effects of whole-body vibration therapy on horses with back pain after a single session of WBV. The objective of the current study was to determine the immediate effects on mechanical nociceptive thresholds (MNTs) after a single treatment of WBV in horses with thoracolumbar pain. Eight horses with thoracolumbar pain and pathology were enrolled. Horses underwent WBV for a single 30-minute session (frequency of 40Hz, amplitude of 0.8mm, acceleration of 4.9m/s2, vertical vibration). MNTs were measured approximately 2 cms to the left and right of midline at the thoracic spine (T13, T18), lumbar spine (L3, L6), and sacrum (S2) before WBV, immediately following WBV, and 24 hours later. Mean MNTs were on average 0.2 times higher immediately following WBV with no significant difference from baseline (P = 0.98). Mean MNTs were on average two times lower than baseline 24 hours after WBV (P < 0.0001). Mean MNTs decreased regardless of back pathology, initial pain or location of MNTs. The immediate effects of WBV therapy in horses with thoracolumbar pain may result in minimal improvement in pain and may exacerbate pain when used short-term. Short-term use of WBV should be used with caution in horses with thoracolumbar pain.
A generalization of the classical concordance correlation coefficient (CCC) is considered under a three-level design where multiple raters rate every subject over time, and each rater is rating every subject multiple times at each measuring time point. The ratings can be discrete or continuous. A methodology is developed for the interval estimation of the CCC based on a suitable linearization of the model along with an adaptation of the fiducial inference approach. The resulting confidence intervals have satisfactory coverage probabilities and shorter expected widths compared to the interval based on Fisher's Z-transformation, even under moderate sample sizes. Two real applications available in the literature are discussed. The first application is based on a clinical trial to determine if various treatments are more effective than a placebo for treating knee pain associated with osteoarthritis. The CCC was used to assess agreement among the manual measurements of the joint space widths on plain radiographs by two raters, and the computer-generated measurements of digitalized radiographs. The second example is on a corticospinal tractography and the CCC was once again applied in order to evaluate the agreement between a well-trained technologist and a neuroradiologist regarding the measurements of fiber number in both the right and left corticospinal tracts. Other relevant applications of our general approach are highlighted in many areas including artificial intelligence.