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Abstract Limitations in chronic pain therapies necessitate novel interventions that are effective, accessible, and safe. Brain–computer interfaces (BCIs) provide a promising modality for targeting neuropathology underlying chronic pain by converting recorded neural activity into perceivable outputs. Recent evidence suggests that increased frontal theta power (4–7 Hz) reflects pain relief from chronic and acute pain. Further studies have suggested that vibrotactile stimulation decreases pain intensity in experimental and clinical models. This longitudinal, non-randomized, open-label pilot study's objective was to reinforce frontal theta activity in six patients with chronic upper extremity pain using a novel vibrotactile neurofeedback BCI system. Patients increased their BCI performance, reflecting thought-driven control of neurofeedback, and showed a significant decrease in pain severity (1.29 ± 0.25 MAD, p = 0.03, q = 0.05) and pain interference (1.79 ± 1.10 MAD p = 0.03, q = 0.05) scores without any adverse events. Pain relief significantly correlated with frontal theta modulation. These findings highlight the potential of BCI-mediated cortico-sensory coupling of frontal theta with vibrotactile stimulation for alleviating chronic pain.

Flooding is Pakistan's most common natural hazard, and it is exacerbated by increased rainfall and urbanization. Khyber Pakhtunkhwa (KPK), Pakistan flood-prone zones were determined by superimposing six flood parameters in an ArcGIS environment: elevation, slope, rainfall accumulation, land cover, soil geometry, and gap/buffer from water channel. Cellular automata based on artificial neural network (CA-ANN) along QGIS plugin module of Land Use Change Simulations (MOLUSCE) was used for predicting year 2050 land use, with a kappa value of 0.83. The results indicated that of the 75775 km2 land area covered by this research region, 3.37% (2553.62 km2) falls in extremely high risk, 18.44% (13972.91 km2) falls in high risk, 11.26% (8532.27 km2) falls in moderate risk, 0.51% (386.45 km2) falls in low risk, and just 66.42% (50329.76 km2) falls in very low risk areas. In KPK, like in any other place, a multi-criteria flood risk-vulnerability assessment is consequently necessary for preparation and post-hazard planning. Without a doubt, the outcomes reported here are crucial for flood risk assessments and hazard management decision-making. Key words: natural disasters; floods; remote sensing; geographic information system, multi-criteria evaluation; weighted overlay.

Abstract. Introduction:. There is a need to identify objective cortical electrophysiological correlates for pain relief that could potentially contribute to a better pain management. However, the field of developing brain biomarkers for pain relief is still largely underexplored. Objectives:. The objective of this study was to investigate cortical electrophysiological correlates associated with relief from chronic pain. Those features of pain relief could serve as potential targets for novel therapeutic interventions to treat pain. Methods:. In 12 patients with chronic pain in the upper or lower extremity undergoing a clinically indicated nerve block procedure, brain activity was recorded by means of electroencephalogram before and 30 minutes after the nerve block procedure. To determine the specific cortical electrophysiological correlates of relief from chronic pain, 12 healthy participants undergoing cold-pressor test to induce experimental acute pain were used as a control group. The data were analyzed to characterize power spectral density patterns of pain relief and identify their source generators at cortical level. Results:. Chronic pain relief was associated with significant delta, theta, and alpha power increase at the frontal area. However, only midfrontal theta power increase showed significant positive correlation with magnitude of reduction in pain intensity. The sources of theta power rebound were located in the left dorsolateral prefrontal cortex (DLPFC) and midline frontal cortex. Furthermore, theta power increase in the midline frontal cortex was significantly higher with chronic vs acute pain relief. Conclusion:. These findings may provide basis for targeting chronic pain relief via modulation of the midline frontal theta oscillations.

Advanced glycation end-products (AGEs) induce the production of reactive oxygen species (ROS) and extra cellular matrix (ECM) degradation via suppression of neuropilin-1 (NRP-1) and interaction with AGE-receptors (RAGE). This study aimed to reveal whether modulation of NRP-1 by rosuvastatin (RT) prevents AGE-induced renal injury via targeting RAGE/matrix metalloproteinase-2 (MMP-2) signaling in diabetic rats. Treatment with RT ameliorated the altered level of markers of glycemic control, renal injury, cholesterol, triglyceride (TG) and hepatic HMG-CoA reductase activity; the level of circulatory carboxymethyl-lysine (CML) and the accumulation of fluorogenic-AGEs in renal tissue was reduced; the expression of renal NRP-1, a checkpoint target, was stimulated; the transcription of RAGE, NFκB-2, TGF-β1 and MMP-2 was suppressed; the circulatory carbonyl content (CC) and paraoxonase-1 (PON-1) activity was ameliorated, and renal histopathological features were attenuated as evidenced by improved glomerular appearance, Bowman’s space and abundant podocytes in kidneys. In conclusion, RT exhibited the potential to counteract diabetes and AGE-induced renal pathologies via stimulation of NRP-1, suppression of RAGE, and of genes responsible for ECM disintegration (MMP-2) and the inflammatory response (NFκB-2).

Background: Osteomalacia represents a risk factor for hip fracture (HF), which is one of the most common and costly injuries in elderly. Objectives: This study was performed to determine the frequency of histopathologic and laboratory osteomalacia in elderly patients with HF. Patients and Methods: Totally, 87 patients with HF, admitted to Imam Khomeini hospital, Tehran, Iran, from 2005 to 2006, were studied. Laboratory investigations included serum calcium, phosphorus, alkaline phosphatase (ALP), albumin and 25-hydroxy vitamin D3 [25 (OH) D3]. Open biopsy from ipsilateral iliac crest was performed during the same surgery. Results: The average age was 78.06 ± 8.4 years. Bone biopsy showed osteomalacia in eight patients (9.2%), hypocalcaemia in 42.5%, hypophosphatemia in 17.2%, hypoalbuminemia in 66.6% and 25 (OH) D3 deficiencies in 66.6%. Concomitant hypophosphatemia and hypovitaminosis [25 (OH) D3 < 10 ng/mL] was detected in 13 patients (14.6%). An increased level of serum ALP was found in 52.8%. Five (38.5%) patients had only laboratory osteomalacia, when histopathological findings were negative. Conclusions: Elderly patients with femoral neck or intertrochanteric fractures may have osteomalacia, as a treatable cause for osteopenia, and laboratory tests may not be precise criteria for diagnosis in HF patients.

Nicolau syndrome is a rare drug reaction due to intramuscular injection administration that can lead to limb loss or even death. A 3.8- year-old Iranian boy received an intramuscular injection of Benzathine Penicillin. Immediately after injection the child developed lower limb pain and livedoid discolouration and was referred to our department. The patient was diagnosed to develop Nicolau syndrome and fasciotomy carried out due to compartment syndrome. Pharmacologic therapy with Heparin, Cefazolin and Methylprednisolone was initiated. On 18th day, he was discharged, although he was not able to move. Finally, after 6 months of care at home, physiotherapy and Electromyography (EMG) at regular intervals, the child was gradually able to move and his claudication improved.

Oncolytic virotherapy (OVT) aims to disrupt the tumor microenvironment and provide a unique therapeutic approach against solid tumors. Herpes simplex virus type-1 (HSV-1) has shown strong promise for treating various solid tumors and has been approved to treat melanoma and glioma in human patients. Previously, we reported the generation of an engineered HSV-1 vaccine strain VC2, which has shown exceptional promise as an oncolytic and immunotherapeutic virus. In the present work, we engineered VC2 to constitutively express the murine granulocyte-macrophage colony-stimulating factor (GM-CSF) gene inserted in place of HSV-1 Glycoprotein C (gC). We tested the efficacy of VC2-GMCSF for its ability to generate antitumor response in the 4T1 stage four metastatic breast cancer mouse model. GM-CSF expression enhanced VC2 viral replication and infectious virus production. Tumors formed after 7 days of engraftment in the mammary fat pad of Balb/CJ mice were treated by injecting ~5 × 10 4 plaque forming units (PFU) of VC2/VC2-GMCSF once. Intratumor treatment did not appreciably reduce average primary tumor sizes. However, metastatic foci were significantly reduced in mice lungs treated with VC2-GMCSF compared to VC2 or mock treatment. VC2-GMCSF intratumoral treatment induced a stronger intratumor T cell infiltration but not an increased cytotoxic activity. A significant T cell infiltration was observed in the metastatic areas in VC2-GMCSF treated animals, which was associated with reduced pro-tumor marker PDL1 and VEGF gene expression. These results show that constitutive expression of GM-CSF enhanced the overall efficacy of VC2 for OVT. VC2-GMCSF holds promise as oncolytic and immunotherapeutic virotherapy for breast and other cancers., (© 2025 Wiley Periodicals LLC.)

Background: Parkinson disease (PD) and cardiovascular diseases (CVD) present significant health burdens, particularly among older adults. Patients with PD have an elevated risk of CVD-related mortality. Analyzing mortality trends in this population may help guide focused interventions., Methods: Mortality data were extracted from the CDC WONDER database, using ICD-10 code G20 for PD and I00-I99 for CVD. Age-adjusted mortality rates (AAMR) per 100,000 were calculated and trends were examined across variables including gender, year, race, and urbanization, place of death, region, and state. Annual percentage change (APC) with 95% confidence intervals (CI) was computed using Joinpoint regression., Results: A total of 138 151 CVD-related deaths were reported among individuals with PD. The AAMR decreased from 23.5 in 1999 to 12.7 in 2020, with a notable decline between 1999 and 2014 (APC: -5.13; 95% CI, -5.44 to -4.86), followed by a modest increase from 2014 to 2020 (APC: 1.37; 95% CI, 0.16-3.05). Males exhibited higher AAMRs compared to females (Male AAMR: 22.6 vs. Female AAMR: 10.4). Non-Hispanic (NH) Whites had the highest AAMR (16.1), followed by Hispanics (11.2), NH Asians (10.2), and NH Blacks (9.7). Nonmetropolitan areas showed a higher AAMR (16.3) compared to metropolitan areas (14.9). State-level analysis indicated Nebraska with the highest AAMR (21.4), while Georgia recorded the lowest (9.9)., Conclusions: CVD-related mortality in PD patients has declined overall, though rates rose slightly from 2014 to 2020. Gender, racial, and geographic disparities highlight the need for targeted strategies to reduce cardiovascular risks in this population., (© 2025 The Author(s). Clinical Cardiology published by Wiley Periodicals, LLC.)

Background: Stroke remains the second leading cause of death worldwide, with a 20 % risk of recurrence within 5 years. Preventing secondary stroke events is crucial for patient management. Kraft et al. highlighted the potential of telemedicine in secondary prevention, but noted the need for further research. Our study incorporates recent trials to provide an updated analysis of telemedical strategies in stroke prevention., Methods: We reviewed and analyzed RCTs and observational studies from PubMed, Cochrane, Google Scholar, and Clinicaltrials.gov (May 19, 2016 - March 20, 2024) comparing telephone-based follow-up to standard care in stroke patients. The meta-analysis focused on SBP changes within 12 months. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies, sourced from PubMed, Cochrane, Google Scholar, and ClinicalTrials.gov (May 19, 2016 - March 20, 2024). We compared telephone-based follow-up to standard care in stroke patients, and the primary outcome was systolic blood pressure (SBP) changes within 12 months., Results: Our systematic review included data from 21,904 patients. The meta-analysis focused on studies with comparable systolic blood pressure (SBP) data. It involved 3,501 individuals in the control group and 3,485 in the experimental group. The analysis revealed a significant reduction in SBP with telemedicine strategies for secondary stroke prevention, with a p-value of 0.003. Additionally, a systemic review of the included studies demonstrated that these strategies improved medication adherence, lifestyle habits, and physical performance, positively correlating with better health outcomes and reduced mortality risk., Conclusion: With the inclusion of recent clinical trials, our updated systematic review and meta-analysis concludes that telemedicine supports secondary prevention in cerebrovascular diseases, particularly blood pressure control. While telemedicine may have a role in reducing recurrent stroke risk, we believe further studies with longer follow-up periods are needed to validate the role of telemedical strategies in reducing recurrence rates., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest and no financial interests related to the material of this manuscript. Funding No financial support was received for this study., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aims: Atrial Fibrillation (AF) is one of the most strongly associated risk factors for stroke. Our study aims to analyze changes in mortality from 1999 to 2020 in patients with AF and stroke., Methods: Using the Centre for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC-WONDER), we retrospectively analyzed annual age-adjusted mortality rates (AAMR) per million from 1999 to 2020 in stroke patients with AF. Temporal trends were analyzed, and Annual Percentage Change (APC) was calculated using the JoinPoint regression model across variations in demographics (sex, race) and regional subgroups., Results: Around 490 000 deaths were reported between 1999 and 2020 from stroke and AF across the 25-85+ age group. AAMR initially decreased until 2008 (APC = -0.9), followed by an increase till 2020 (APC = 1.1). Women had a higher AAMR than men throughout the years. Non-Hispanic white patients had a marginally higher AAMR than all other races and ethnicities. The highest AAMR was observed in the western region. States like Vermont, Oregon, Washington, Alaska, Minnesota, and West Virginia were in the top 90th percentile, while Nevada, Louisiana, Florida, New York, New Mexico, and Arizona were in the bottom 10th percentile. Nonmetropolitan areas had consistently higher AAMRs throughout the 2 decades., Conclusion: An overall rise in mortality has been observed in stroke and AF patients, with a greater surge in 2019. The need for healthcare policy changes, especially in areas with high mortality and awareness of healthier lifestyle factors, can be an essential preventative measure to help mitigate growing mortality rates., (© 2024 The Author(s). Clinical Cardiology published by Wiley Periodicals LLC.)

Developing molecular spin technologies requires microscopic knowledge of their spin-dynamics. Calculation of phonon modes, phonon scattering and spin-phonon coupling for a dysprosocenium single-molecule magnet (SMM) give simulations of spin-dynamics that agree with experiment. They show that low-energy phonon scattering is a significant contribution to the high-performance of dysprosocenium SMMs.

Introduction: Clinical trials are essential to the advancement of clinical therapies that improve the outcomes of people with cancer. However, enrollment in clinical trials remains a challenge. The Clinical Trial Navigator [CTN] Program was designed to address the current gap in the cancer care journey by assisting with the clinical trials search process., Methods: Between March 2019 and July 2024, applicants of the CTN program included people with cancer, their family members, and/or their care team. Applicants entered the CTN program through a REDCap ® survey that collected the patient's medical history. A final curated list of potential clinical trials was provided to the applicant. Metrics of success included clinical trial referral and enrollment, and we examined the factors that impacted these outcomes., Results: A total of 445 people with cancer applied to the CTN program during the study. Of the 262 patients with referral and enrollment information, a trial referral occurred in 27.5% [n = 72]. Of the 72 patients who were referred to a clinical trial, 13 [18.1%] were enrolled, 9 [12.5%] are pending enrollment, and 50 [69.4%] were not enrolled. We identified a potential trial for 88% of applicants, with a median of one potential trial per patient. Physicians were highly involved as applicants., Interpretation: The CTN program is successful in searching for clinical trials for people with cancer. Ongoing implementation into other Canadian sites, assessments of patient-reported outcomes, website and social media campaigns, and research into the factors that impact referral and enrollment are underway.

Racial and ethnic disparities have long been studied in the delivery of healthcare. One such avenue is acute pediatric appendicitis, which continues to be an area of significant and continual research. Because of its routine clinical presentation and standardized management, acute pediatric appendicitis serves as an appropriate proxy for studying discrepancies in healthcare. Our review therefore aims to comprehensively highlight the various dimensions of its clinical management subject to disparities, their collective clinical impact, and future recommendations to mitigate it., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Khan, Dar, Nabi, Ali, Humayun and Riaz.)

Establishing cause-effect relationships from observational data often relies on untestable assumptions. It is crucial to know whether, and to what extent, the conclusions drawn from non-experimental studies are robust to potential unmeasured confounding. In this paper, we focus on the average causal effect (ACE) as our target of inference. We generalize the sensitivity analysis approach developed by Robins et al., Franks et al., and Zhou and Yao. We use semiparametric theory to derive the non-parametric efficient influence function of the ACE, for fixed sensitivity parameters. We use this influence function to construct a one-step, split sample, truncated estimator of the ACE. Our estimator depends on semiparametric models for the distribution of the observed data; importantly, these models do not impose any restrictions on the values of sensitivity analysis parameters. We establish sufficient conditions ensuring that our estimator has $\sqrt{n}$ asymptotics. We use our methodology to evaluate the causal effect of smoking during pregnancy on birth weight. We also evaluate the performance of estimation procedure in a simulation study., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Biometric Society.)

Competing Interests: The authors disclose no conflict of interest.