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Background: Mirror hand is a rare congenital anomaly. Most of these cases are sporadic and associated with defective sonic hedgehog during embryogenesis. In this report, we present the case of a child with this rare congenital anomaly and its management., Case Presentation: A 2.5-year-old Asian female child presented with left-sided Al Qattan type 1A ulnar dimelia with restriction of wrist and elbow range of motion. Radiological examination revealed duplication of ulna with polydactyly. Management of mirror hand is a great surgical challenge, so preoperative planning and staged management is essential for the functional outcome of this condition. We successfully achieved fine and gross motor skills of the hand with acceptable cosmetic results at 2 years of follow-up., Conclusion: It is crucial to remember that early intervention, ideally between 18 and 24 months of age, is key for optimal functional outcomes. Meticulous preoperative planning and surgical technique are essential. Long-term follow-up and parental counseling about the need for supervised physical therapy are important for managing secondary deformities. Additionally, digital subtraction angiography should be performed to rule out any associated neurovascular malformations., Competing Interests: Declarations. Ethics approval and consent to participate: Ethical approval is not required for individual case reports, where the patient and their family consent is obtained and anonymity is maintained. Informed consent: Written informed consent was obtained from the patient’s legal guardian for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Consent for publication: Written informed consent was obtained from the patient's legal guardian for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Competing interests: No competing interests from any of the authors., (© 2024. The Author(s).)

The study aimed to estimate the genetic parameters and predict the genotypic values of postharvest physiological deterioration and root characteristics in cassava (Manihot esculentaCrantz) using restricted maximum likelihood (REML) and the best linear unbiased prediction (BLUP). A total of 76 cassava accessions were evaluated over two growing seasons. The evaluated traits included postharvest physiological deterioration response (PPD), root length (RL), root diameter (RD), root weight (RW), dry matter content (DMC), total starch content (TS) and total sugar content (TSU). All the traits had a higher phenotypic variance component than genetic or environmental variance, with genotypic variance making up a larger portion of the total phenotypic variance. Heritability estimates ranged from low to high, with high heritability values being recorded for dry matter content, PPD, and root diameter. The study discovered high genotypic coefficients of variation (CVg) for PPD, root weight and diameter, indicating strong genotypic variability beneficial for selection. As larger genetic effects than non-genetic effects lead to increased selection gains, the highest CVr values for dry matter content and PPD suggest the biggest probability of selection gain. Postharvest Physiological deterioration (PPD) had the highest genetic advance, indicating significant gain in the following generation. Thirty eight genotypes were selected as the most promising based on BLUP index, promoting improvement and genetic gain in several traits. The genotypes selected can be included in cassava breeding programs for PPD tolerance and other tuber traits., Competing Interests: Declarations Conflict of interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Charcot arthropathy is a myriad of osseous degenerative changes that can affect theoretically any joint of the body. The pathophysiology of this condition is based on microtrauma, leading to the deterioration of articular nerves. The most common cause in the upper extremity is syringomyelia., Case Report: A 64-year-old male patient presented with painless right wrist swelling and deformity. His radiographs showed degenerative changes in radiocarpal and intercarpal joints. Magnetic resonance imaging of the brain and cervical spine demonstrated Type II Chiari malformation and syringomyelia, and neurological evaluation revealed myelopathy., Conclusion: Charcot arthropathy of the wrist, an exceedingly rare condition, is a diagnosis of exclusion. The common causes of arthritis of the wrist such as Rheumatoid arthritis and tuberculosis must be ruled out. When a patient presents with wrist Charcot arthropathy thorough neurological examination must be done. Diabetes mellitus, tabes dorsalis, and leprosy are the other frequently cited causes that must be looked for., Competing Interests: Conflict of Interest: Nil, (Copyright: © Indian Orthopaedic Research Group.)

Wastewater management has become necessary in this industrialized era to meet the water needs of the world. Wastewater is one of the major crises in depletion of the environment. Photocatalysis is considered as the best way to remove pollutants. Therefore, in this study, pure and g-C 3 N 4 -SnWO 4 nanocomposites were produced employing hydrothermal route. Prepared composites were studied by various techniques. SnWO 4 band gap were altered by introduction of g-C 3 N 4 . The morphology was uniformly developed by the addition of g-C 3 N 4 to the SnWO 4 . Evans Blue dye was employed as model pollutant. The photocatalytic action was improved by adding g-C 3 N 4 , which formed a heterojunction with SnWO 4 . The calculated rate constant was 0.000878, 0.0068, 0.01 and 0.0122 min -1 for EB, SnWO 4 -EB, 0.1 g g-C 3 N 4 -SnWO 4 -EB and 0.2 g g-C 3 N 4 -SnWO 4 -EB. The rate constant increased for 0.2 g g-C 3 N 4 -SnWO 4 photocatalyst. A heterojunction appeared between g-C 3 N 4 and SnWO 4 facilitated SnWO 4 for better e - /h + pair's separation and a lower recombination rate, which increased photocatalytic action of product. 0.2 g of g-C 3 N 4 -SnWO 4 is a promising candidate for future wastewater degradation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Fast radio bursts (FRBs) are millisecond-duration events detected from beyond the Milky Way. FRB emission characteristics favour highly magnetized neutron stars, or magnetars, as the sources 1 , as evidenced by FRB-like bursts from a galactic magnetar 2,3 , and the star-forming nature of FRB host galaxies 4,5 . However, the processes that produce FRB sources remain unknown 6 . Although galactic magnetars are often linked to core-collapse supernovae (CCSNe) 7 , it is uncertain what determines which supernovae result in magnetars. The galactic environments of FRB sources can be used to investigate their progenitors. Here, we present the stellar population properties of 30 FRB host galaxies discovered by the Deep Synoptic Array (DSA-110). Our analysis shows a marked deficit of low-mass FRB hosts compared with the occurrence of star formation in the Universe, implying that FRBs are a biased tracer of star formation, preferentially selecting massive star-forming galaxies. This bias may be driven by galaxy metallicity, which is positively correlated with stellar mass 8 . Metal-rich environments may favour the formation of magnetar progenitors through stellar mergers 9,10 , as higher-metallicity stars are less compact and more likely to fill their Roche lobes, leading to unstable mass transfer. Although massive stars do not have convective interiors to generate strong magnetic fields by dynamo 11 , merger remnants are thought to have the requisite internal magnetic-field strengths to result in magnetars 11,12 . The preferential occurrence of FRBs in massive star-forming galaxies suggests that a core-collapse supernova of merger remnants preferentially forms magnetars., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Atypical intradermal smooth muscle neoplasm, also commonly termed cutaneous leiomyosarcoma, is a soft tissue tumor with a low risk of aggressive behavior. These lesions arise in the dermis with possible superficial subcutaneous extension, demonstrate cytologic atypia, and often show mitotic activity., Methods: A retrospective review of patient demographics, tumor characteristics, and treatment methods was conducted in a consecutive series of patients presenting to MD Anderson Cancer Center (MDACC) from 2002 to 2021 (n = 95). All pathology was reviewed by MDACC pathologists and determined to be atypical intradermal smooth muscle neoplasm., Results: Median age at diagnosis was 58 years (range 22-86), and 74% were male. Ninety-five percent (n = 90) of patients identified as White, non-Hispanic. Most tumors were slow-growing, solitary, and painless nodules. Tumors were in the lower extremities (44.2%), followed by the upper extremity (28.4%), trunk (22.1%), and head and neck (5.2%). All patients (n = 44, 46.3%) who had a punch/incisional biopsy for diagnostic purposes had a subsequent tumor excision. Unplanned excision or excisional biopsy was performed on the remaining 46 (48%) patients. Of this subset, 41 of the 46 aforementioned patients (89%) had positive margins and underwent re-excision. Final pathology in 25/38 (66%) re-excision specimens was negative for residual tumor despite an initial positive margin. Two patients in the cohort had local recurrence 2 and 3 years after initial surgery. Both patients had positive margins, underwent excision of the recurrent tumor, and remain free of disease. After median follow-up of 6.9 years (range 1 day-18 years), 5-year recurrence-free survival was 96% and overall survival (OS) of the entire cohort was 78%., Conclusion: In this study of consecutive patients presenting with atypical intradermal smooth muscle neoplasm, we found good OS and local control after definitive surgical excision with negative margins, including excisional biopsy with close margins. Atypical intradermal smooth muscle neoplasm is unlikely to metastasize and has an excellent prognosis. Guidelines to determine optimal surveillance strategies for these patients should be revisited., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Transcranial Doppler (TCD) is a non-invasive, bedside tool that allows for real-time monitoring of the patient's hemodynamic status following mechanical thrombectomy (MT). This systematic review and meta-analysis aims to evaluate the predictive value of TCD parameters following successful MT (Thrombolysis in Cerebral Infarction 2b-3)., Methods: In July 2024, we searched PubMed, Embase, and Scopus, to identify observational studies in which TCD parameters were measured within 48 hours of MT. Using random-effects models, we compared four TCD parameters (mean flow velocity (MFV), MFV index, pulsatility index (PI), and peak systolic velocity (PSV) among groups with vs without hemorrhagic transformation (HT) and favorable vs poor functional recovery (modified Rankin Scale 0-2 vs 3-6)., Results: Eleven studies comprising 1432 patients (59% male; mean age range: 63-73 years) were included. The MFV and MFV index were higher in patients with HT (Hedges' g=0.42 and 0.54, P=0.015 and 0.005, respectively). Patients with MFV index ≥1.3 showed a higher risk of all HT (RR 1.97; 95% confidence interval (CI) 1.28 to 3.03, P=0.002), symptomatic HT (RR 4.68; 95% CI 1.49 to 14.65, P=0.008), and poor functional status at 90 days (RR 1.65; 95% CI 1.27 to 2.14, P=0.029), respectively. There was no difference in mean PSV (P=0.1) and PI (P=0.3) among groups with and without HT., Conclusion: This study underscores the prognostic value of the MFV index in predicting HT, symptomatic HT, and poor functional recovery after successful MT in the anterior circulation. Large-scale, multi-center studies are necessary to confirm these findings and to validate the MFV index as a reliable predictor for improving post-thrombectomy care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Major depressive disorder (MDD) often goes undiagnosed due to the absence of clear biomarkers. We sought to identify voice biomarkers for MDD and separate biomarkers indicative of MDD predisposition from biomarkers reflecting current depressive symptoms. Using a two-stage meta-analytic design to remove confounds, we tested the association between features representing vocal pitch and MDD in a multisite case-control cohort study of Chinese women with recurrent depression. Sixteen features were replicated in an independent cohort, with absolute association coefficients (beta values) from the combined analysis ranging from 0.24 to 1.07, indicating moderate to large effects. The statistical significance of these associations remained robust, with P-values ranging from 7.2 × 10 -6 to 6.8 × 10 -58 . Eleven features were significantly associated with current depressive symptoms. Using genotype data, we found that this association was driven in part by a genetic correlation with MDD. Significant voice features, reflecting a slower pitch change and a lower pitch, achieved an AUC-ROC of 0.90 (sensitivity of 0.85 and specificity of 0.81) in MDD classification. Our results return vocal features to a more central position in clinical and research work on MDD., Competing Interests: Disclosures: No conflict of interest.

Objective: Among patients with diabetes living in the U.S. with newly detected mild or moderate nonproliferative diabetic retinopathy (NPDR) without diabetic macular edema (DME), we aimed to characterize determinants for receiving standards of care and progression to vision-threatening diabetic retinopathy (VTDR) (severe NPDR, proliferative diabetic retinopathy, DME)., Research Design and Methods: Electronic health records of patients newly detected with NPDR without DME between 2015 and 2023 were analyzed with use of the Epic Cosmos research platform. We characterized the adjusted associations of urban versus rural residence, race and ethnicity (Hispanic, non-Hispanic [NH] White, NH Black, other), and glycemic control (HbA1c <7.0%, 7.0%-8.9%, ≥9%, unavailable) separately with guideline-recommended care (two of three: ophthalmology visit, primary care visit, and measurement of HbA1c, blood pressure, and LDL cholesterol) in the 2 years after diagnosis and with progression to VTDR., Results: Average (SD) age for the analytic sample (n = 102,919) was 63 (13.5) years, and 51% were female, 59% NH White, and 7% rural residents. Only 40% received guideline-recommended care, and 14% progressed to VTDR (median follow-up 35 months [interquartile range 18-63]). Urban residence was associated with receiving standards of care in both years (risk ratio 1.08 [95% CI 1.05-1.12]) and progression to VTDR (hazard ratio 1.07 [95% CI 0.99-1.15]). Racial and ethnic minority individulas were more likely to progress to VTDR. Individuals with poor or unknown glycemic control were less likely to receive standards of care and more likely to progress to VTDR., Conclusions: Understanding the management and progression of newly detected NPDR will require disentangling the independent and interdependent contributions of geography, race and ethnicity, and glycemia., (© 2024 by the American Diabetes Association.)

Competing Interests: The authors state that there is no competing/conflict of interest.

Quasi-periodic eruptions (QPEs) are luminous bursts of soft X-rays from the nuclei of galaxies, repeating on timescales of hours to weeks 1-5 . The mechanism behind these rare systems is uncertain, but most theories involve accretion disks around supermassive black holes (SMBHs) undergoing instabilities 6-8 or interacting with a stellar object in a close orbit 9-11 . It has been suggested that this disk could be created when the SMBH disrupts a passing star 8,11 , implying that many QPEs should be preceded by observable tidal disruption events (TDEs). Two known QPE sources show long-term decays in quiescent luminosity consistent with TDEs 4,12 and two observed TDEs have exhibited X-ray flares consistent with individual eruptions 13,14 . TDEs and QPEs also occur preferentially in similar galaxies 15 . However, no confirmed repeating QPEs have been associated with a spectroscopically confirmed TDE or an optical TDE observed at peak brightness. Here we report the detection of nine X-ray QPEs with a mean recurrence time of approximately 48 h from AT2019qiz, a nearby and extensively studied optically selected TDE 16 . We detect and model the X-ray, ultraviolet (UV) and optical emission from the accretion disk and show that an orbiting body colliding with this disk provides a plausible explanation for the QPEs., (© 2024. The Author(s).)

Light intensity is a critical environmental factor influencing plant growth and development. To survive high light conditions, plants have evolved various protective mechanisms, including non-photochemical quenching (NPQ). However, NPQ can limit effective photosynthetic yield when transitioning to low light conditions. This phenomenon is underexplored in cassava (Manihot esculenta ), a starchy storage root crop known for its high biological efficiency and climate resilience. To address this knowledge gap, we assessed the photoprotective abilities and growth responses of six cassava varieties under natural environmental light conditions (control) and intermittent high light (IHL) conditions by adding 900μmolm-2 s-1 using full-spectrum LED lights, on top of the natural ambient daylight. Our results demonstrated a significant impact of light treatment on aboveground biomass, total crop biomass, chlorophyll a and b content, photosynthetic rate, and NPQ values during transitions from low to high light and vice versa. Notably, cassava variety 'Sree Suvarna' exhibited the highest yield under both control and IHL conditions. These findings suggest that screening cassava varieties for their ability to postpone photoinhibition and recover quickly from photoinhibition may enhance photosynthetic performance. Such strategies have important implications for improving the efficiency and resilience of cassava crops, ultimately contributing to sustainable agricultural productivity.

Type 2 diabetes mellitus (T2DM) is a complex disease that can lead to a variety of life-threatening secondary health conditions. Current treatment strategies primarily revolve around tight glucose control that is difficult to achieve and often turns out to be dangerous due to possible hypoglycemic events. Numerous long-term studies have demonstrated that complex pathways, including low-grade inflammation due to fluctuating glucose levels, are involved in the progression of the disease and the development of secondary health conditions. Growing clinical evidence supports the effectiveness of using multiple medications, possibly in combination with insulin, to effectively manage T2DM. On the other hand, despite the huge, largely untapped potential therapeutic benefit of 'polyphenols', there remains a general skepticism of the practice. However, for any evidence-based clinical intervention, the balance of benefits and risks takes center stage and is governed by biopharmaceutics principles. In this article, we outline the current clinical perspectives on pharmaceutical drug combinations, rationale for early initiation of insulin, and the advantages of novel dosage forms to meet the pathophysiological changes of T2DM, emphasizing the need for further clinical studies to substantiate these approaches. We also make the case for traditional medicines and their combinations with pharmaceutical drugs and outline the inherent challenges in doing so, while also providing recommendations for future research and clinical practice. Significance Statement Type 2 diabetes is associated with life-threatening secondary health conditions that are often difficult to treat. This review provides an in-depth account of preventing/delaying secondary health conditions through combination therapies and emphasizes the role of effective delivery strategies in realizing the translation of such combinations. We will build the case for the importance of polyphenols in diabetes, determine the reasons for skepticism, and potential combinations with pharmaceutical drugs., (Copyright © 2024 American Society for Pharmacology and Experimental Therapeutics.)

Tenosynovial giant cell tumor (TGCT) is a rare, locally invasive soft tissue tumor arising from the synovium of joints, bursa and tendon sheaths and is associated with the overexpression of the colony-stimulating factor 1 (CSF-1) gene. Pimicotinib is an orally available, highly selective and potent small molecule CSF-1 receptor (CSF-1R) inhibitor with robust efficacy and safety profile in patients with TGCT and is under development in multiple diseases. In an open-label Phase I study in patients with TGCT not amenable to surgery, pimicotinib showed superior efficacy and safety. In this article, we elucidate the rationale and study design of the multi-region Phase III MANEUVER trial (NCT05804045), which is designed to assess the efficacy and safety of pimicotinib in patients with TGCT not amenable to surgical resection in Asia, North America and Europe.

Aims and Objective: Proximal femur replacement (PFR) is most commonly performed after a large resection of the proximal femur to remove tumor and is known to have high complication rates and worse function than a primary total hip replacement (THA). Many surgeons feel that current billing practices fail to adequately differentiate this procedure from a THA. This study aims to examine patients undergoing a primary THA or oncologic PFR and compare the relative economic impact and complication rates between cohorts., Materials & Methods: Patient data was queried using a national database, identifying non-pediatric patients who underwent a primary THA or oncologic PFR. Exclusionary criteria were implemented, resulting in two cohorts, each with 380 patients matched in a 1:1 manner controlling for age, gender, and Charlson Comorbidity Index. Utilizing 2022 billing data, oncologic PFRs generated an average of 41.03 RVUs and primary THAs generated 19.60 RVUs. Total hospital cost was used to generate a cost:RVU ratio for each cohort. Key systemic and joint complication rates were additionally compared between cohorts., Results: The oncologic PFR cohort had significantly higher 90-day rates of anemia, deep vein thrombosis, and prosthetic dislocation compared to the primary THA cohort. The 90-day median hospital cost for oncologic PFR was $28,562.21 with a cost:RVU ratio of $696:1. The corresponding median hospital cost for primary THA was $9667.72, with a cost:RVU ratio of $493:1., Conclusion: Hospitals incur more cost per RVU for an oncologic PFR than a primary THA. Relative to primary THA, reimbursement for oncologic PFR is under-evaluated., Competing Interests: None., (© 2024 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Objective: We evaluated survival outcomes by primary tumor site in synovial sarcoma (SS) patients with localized and metastatic disease at diagnosis., Methods: We conducted a retrospective review of 504 SS patients diagnosed from 1974 to 2020. Kaplan-Meier method, log-rank test, and Cox-proportional hazards regression were used., Results: Among 504 patients, 401 (79.6%) presented with localized disease, and 103 (20.4%) with metastases. For patients with localized disease, (1) 5-year OS by tumor site was as follows: 80% (95% CI, 67%-89%) for head/neck, 30% (95% CI, 18%-42%) for intrathoracic, 51% (95% CI, 35%-65%) for abdomen/pelvis, 71% (95% CI, 62%-79%) for proximal-extremity, and 83% (71%, 91%) for distal-extremity. (2) On multivariable analysis, tumor site (compared with proximal-extremity: intrathoracic tumors [HR: 1.95; 95% CI, 1.22-3.16]; hand/foot [HR: 0.52; 95% CI, 0.28-0.97]), tumor size (compared with <5 cm, 5-10 cm [HR: 1.80; 95% CI, 1.14-2.85]; ≥10 cm [HR: 4.37; 95% CI, 2.69-7.11]), and use of neo/adjuvant radiation (HR: 0.54; 95% CI, 0.37-0.79) remained significantly associated with OS. For patients with metastatic disease, (1) 5-year OS was 12% (95% CI, 6%-21%) and (2) the only factor that remained significantly associated with OS on multivariable analysis was surgical resection for the primary tumor (HR: 0.14; 95% CI, 0.08-0.26)., Conclusions: The primary tumor location plays a significant role in predicting outcomes for patients with localized SS. Even though patients present with metastatic disease, surgical resection of the primary tumor improves their survival. These findings are critical for patient counseling and designing a personalized treatment plan that reflects the corresponding outcomes., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: To assess the placental biometry, placental biomarkers and uterine artery Doppler in each trimester of pregnancy for prediction of early-onset fetal growth restriction (EO FGR)., Methods: In this prospective cohort study placental biometry; biomarkers PAPP-A, sFLT-1, and PlGF along with the uterine artery blood flow evaluation was done serially at 11-14, 20-24 and 28-32 weeks of gestation. The above parameters were compared between women with early onset FGR and controls., Results: Out of 1008 fully followed cases, the small for gestational age fetuses were 227/1008 (22.5 %), and EO FGR were 84/1008(8.3 %).The placental length, volume, and PlGF levels were significantly lower, whereas the uterine artery PI(Ut PI) was significantly higher at all time points among cases. The sFLT-1 level showed a significant increase among cases, whereas it decreased among controls from the first to the second trimester. The detection rate using PV/UtA PI was 60 % in the first trimester and 66.7 % in the second trimester at 30 % FPR., Conclusion: The PV/Ut PI in first and the second trimester was a good marker for the prediction of pregnancies at increased risk of developing EO FGR., Competing Interests: Declaration of competing interest We are submitting the article titled " Placental biophysical model for prediction of early onset fetal growth restriction in first and second trimester of pregnancy” to your journal to be considered for publication. The article is not under consideration in any other journal. All authors are active participants, there is no conflict of interest among authors., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Speech-based automatic depression detection systems have been extensively explored over the past few years. Typically, each speaker is assigned a single label (Depressive or Non-depressive), and most approaches formulate depression detection as a speech classification task without explicitly considering the non-uniformly distributed depression pattern within segments, leading to low generalizability and robustness across different scenarios. However, depression corpora do not provide fine-grained labels (at the phoneme or word level) which makes the dynamic depression pattern in speech segments harder to track using conventional frameworks. To address this, we propose a novel framework, Speechformer-CTC, to model non-uniformly distributed depression characteristics within segments using a Connectionist Temporal Classification (CTC) objective function without the necessity of input-output alignment. Two novel CTC-label generation policies, namely the Expectation-One-Hot and the HuBERT policies, are proposed and incorporated in objectives on various granularities. Additionally, experiments using Automatic Speech Recognition (ASR) features are conducted to demonstrate the compatibility of the proposed method with content-based features. Our results show that the performance of depression detection, in terms of Macro F1-score, is improved on both DAIC-WOZ (English) and CONVERGE (Mandarin) datasets. On the DAIC-WOZ dataset, the system with HuBERT ASR features and a CTC objective optimized using HuBERT policy for label generation achieves 83.15% F1-score, which is close to state-of-the-art without the need for phoneme-level transcription or data augmentation. On the CONVERGE dataset, using Whisper features with the HuBERT policy improves the F1-score by 9.82% on CONVERGE1 (in-domain test set) and 18.47% on CONVERGE2 (out-of-domain test set). These findings show that depression detection can benefit from modeling non-uniformly distributed depression patterns and the proposed framework can be potentially used to determine significant depressive regions in speech utterances.

Introduction: The traditional medicinal system of India, Ayurveda, has mentioned Cordia Dichotoma as a potential treatment for various ailments. In the current research, the extracts of Cordia Dichotoma was examined to evaluate their antidepressant potential., Materials and Methods: Here, green leaves of Cordia Dichotoma were used to prepare chloroform, ethanol, and aqueous extracts (referred to as CdCe, CdEe, and CdAe respectively). The research focused on investigating the antidepressant effects of these extracts using behavioral models in experimental animals. Additionally, locomotor activity was assessed as part of the evaluation process., Results: Immobility time was reduced with CdEe Cordia Dichotoma rFST & mTST when at 200 mg/kg and 400 mg/kg body weight. The CdAe showed reduction in immobility time in the repeated rFST) at 400 mg/kg, while in the mTST, significant effects were observed at 200 and 400 mg/kg. Regarding the chloroform extract, it only exhibited a significant reduction in immobility time in the modified Tail Suspension Test (mTST) at a low dose of 200 mg/kg. However, no noticeable change in motor dysfunction was observed with CCl4 and aqueous extracts at doses of 200 and 400 mg/kg. It is worth noting that the chloroform extract (CdCe) did lead to a significant decrease in locomotor activity at the same dosage level. Taken together, these findings suggest that extracts obtained from Cordia Dichotoma leaves may possess antidepressant properties.

Monkeypox (Mpox) has emerged as a significant threat to the global population. Initially identified in a rural area of Africa in 1970, after the eradication of smallpox, it spread rapidly across various African nations. The ongoing evolution of the monkeypox virus (MPXV), which causes Mpox, and its potential for cross-species transmission led to a global outbreak in 2022. Despite the control measures during the outbreak, Mpox cases continue in several African nations, posing a persistent public health threat. Global surveillance is crucial to eradicating MPXV from human populations and preventing its resurgence. Factors contributing to MPXV's increased transmissibility and immune evasion include its mutation rate, adaptability, and genetic evolution. Therefore, understanding the epidemiology and virology of Mpox is essential for developing effective prevention and control strategies. This study explores the history of human Mpox, the complexity of MPXV, how it replicates, and drug-resistant mutations. It will also stress how important it is to study how the circadian clock affects virus replication in infectious diseases in order to effectively fight this new public health threat. Understanding these aspects is crucial for developing effective strategies against Mpox as well as addressing the challenges posed by genetic mutations and resistance. The compiled information in this review underscores the critical need for continued research and monitoring to tackle the evolving dynamics of Mpox and its broader impact on global health., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Mani et al.)

The resurgence of monkeypox (Mpox), an orthopoxvirus infection closely related to smallpox, presents a significant global health challenge. This study presents a comprehensive overview of Mpox, focusing on its clinical manifestations, diagnostic strategies, and testing methodologies. A thorough review of the literature and available data on Mpox, emphasizing diagnostic assays, clinical indicators, and laboratory testing, constitutes the core of this analysis. The study involves insights from Mpox patients and healthcare professionals engaged in its diagnosis and management. Contextualizing the research within the global spread of Mpox addresses the complexities associated with the diagnosis of the disease. The findings illuminate diverse Mpox diagnostic techniques, encompassing viral culture, immunological methods, serology, quantitative polymerase chain reaction (qPCR), electron microscopy, and advanced technologies such as artificial intelligence (AI) and the GeneXpert system. qPCR is highlighted as the benchmark for MPXV detection and quantification. These diagnostic advancements have significantly enhanced the precision and efficiency of Mpox diagnosis, facilitating prompt identification and treatment of infected individuals. The study underscores the critical importance of accurate and timely diagnosis, proper handling and transportation of clinical specimens, and the imperative for point-of-care (POC) testing to control the global spread of Mpox., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Arunagiri et al.)

Next generation electrical grid considered as Smart Grid has completely embarked a journey in the present electricity era. This creates a dominant need of machine learning approaches for security aspects at the larger scale for the electrical grid. The need of connectivity and complete communication in the system uses a large amount of data where the involvement of machine learning models with proper frameworks are required. This massive amount of data can be handled by various process of machine learning models by selecting appropriate set of consumers to respond in accordance with demand response modelling, learning the different attributes of the consumers, dynamic pricing schemes, various load forecasting and also data acquisition process with more cost effectiveness. In connected to this process, considering complex smart grid security and privacy based methods becomes a major aspect and there can be potential cyber threats for the consumers and also utility data. The security concerns related to machine learning model exhibits a key factor based on different machine learning algorithms used and needed for the energy application at a future perspective. This work exhibits as a detailed analysis with machine learning models which are considered as cyber physical system model with smart grid. This work also gives a clear understanding towards the potential advantages, limitations of the algorithms in a security aspect and outlines future direction in this very important area and fast-growing approach., Competing Interests: The authors have no conflict of interest., (© 2024 The Authors. Published by Elsevier Ltd.)

Background: Rhabdomyosarcomas are the most common soft tissue sarcoma in children, and pediatric alveolar rhabdomyosarcoma (ARMS) prognosis has improved based on cooperative studies. However, in adults, ARMS is significantly rarer, has poorer outcomes, and currently lacks optimal treatment strategies. Objective: This study aimed to evaluate the clinical outcome of an adult ARMS population with different front-line systemic chemotherapies and determine if any chemotherapy regimen is associated with improved survival. Materials and methods: This is a retrospective study of histologically confirmed fusion-positive ARMS patients over 18 years of age, who were treated at MD Anderson Cancer Center (MDACC) from 2004 to 2021 and received systemic chemotherapy. Descriptive clinical statistics were performed, including staging, front-line chemotherapy, multimodal therapy usage, response rates, and survival analyses. Results: 49 ARMS patients who received upfront chemotherapy were identified. Locoregional treatments included radiotherapy (RT) alone (29%, n = 14), surgery alone (10%, n = 5), or both (45%, n = 22). Median overall survival (OS) for the entire cohort was 3.6 years, and the overall response rate to systemic therapy was 89%. No chemotherapy regimen showed OS benefit, specifically analyzing the pediatric-based vincristine, actinomycin-D, cyclophosphamide (VAC) or adult-based vincristine, doxorubicin, ifosfamide (VDI) regimens, even when controlled for other clinical risk factors. Conclusion: In this single-center contemporary series, adult ARMS patient outcomes remain poor. There was no statistically significant OS difference in patients who did or did not receive adult or pediatric based ARMS regimens, although a high overall response rate to chemotherapy was seen across the entire cohort. Based on these observations, further randomized prospective studies are necessary to delineate which frontline chemotherapy regimen is most beneficial in this rare adult cancer., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background and Purpose: Chronic inflammation plays a pivotal role in the development of Type 2 diabetes mellitus (T2DM). Previous studies have shown that haem oxygenase-1 (HO-1) plays a proinflammatory role during metabolic stress, suggesting that HO-1 inhibition could be an effective strategy to treat T2DM. However, the application of HO-1 inhibitors is restricted due to solubility-limited bioavailability. In this study, we encapsulated the HO-1 inhibitor, zinc protoporphyrin IX (ZnPP), within nanoparticles and investigated their role in regulating glucose homeostasis and chronic inflammation during obesity., Experimental Approach: We delivered DMSO-dissolved ZnPP (DMSO-ZnPP) and ZnPP-laden nanoparticles (Nano-ZnPP) to diet-induced obese male mice for 6 weeks. Glucose and insulin tolerance tests were carried out, liver and adipose tissue gene expression profiles analysed, and systemic inflammation analysed using flow cytometry., Key Results: Nanoparticles significantly increased the delivery efficiency of ZnPP in both cells and mice. In mice with diet-induced obesity, inhibition of HO-1 by Nano-ZnPP significantly decreased adiposity, increased insulin sensitivity, and improved glucose tolerance. Moreover, Nano-ZnPP treatment attenuated both local and systemic inflammatory levels during obesity. Mechanistically, Nano-ZnPP significantly attenuated glucagon, TNF, and fatty acid synthesis signalling pathways in the liver. In white adipose tissue, the oxidative phosphorylation signalling pathway was enhanced and the inflammation signalling pathway diminished by Nano-ZnPP. Our results show that Nano-ZnPP has better effects on the improvement of glucose homeostasis and attenuation of chronic inflammation, than those of DMSO-dissolved ZnPP., Conclusions and Implications: These findings indicate that ZnPP-laden nanoparticles are potential therapeutic agents for treating T2DM., (© 2024 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Migraine affects up to 20 percent of the global population and ranks as the second leading cause of disability worldwide. In parallel, ischemic stroke stands as the second leading cause of mortality and the third leading cause of disability worldwide. This review aims to elucidate the intricate relationship between migraine and stroke, highlighting the role of genetic, vascular, and hormonal factors. Epidemiological evidence shows a positive association between migraine, particularly with aura, and ischemic stroke (IS), though the link to hemorrhagic stroke (HS) remains inconclusive. The shared pathophysiology between migraine and stroke includes cortical spreading depression, endothelial dysfunction, and genetic predispositions, such as mutations linked to conditions like CADASIL and MELAS. Genetic studies indicate that common loci may predispose individuals to both migraine and stroke, while biomarkers such as endothelial microparticles and inflammatory cytokines offer insights into the underlying mechanisms. Additionally, hormonal influences, particularly fluctuations in estrogen levels, significantly impact migraine pathogenesis and stroke risk, highlighting the need for tailored interventions for women. The presence of a patent foramen ovale (PFO) in migraineurs further complicates their risk profile, with device closure showing promise in reducing stroke occurrence. Furthermore, white matter lesions (WMLs) are frequently observed in migraine patients, suggesting potential cognitive and stroke risks. This review hopes to summarize the links between migraine and its associated conditions and ischemic stroke, recognizing the profound implications for clinical management strategies for both disorders. Understanding the complex relationship between migraine and ischemic stroke holds the key to navigating treatment options and preventive interventions to enhance overall patient outcomes., 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., (Copyright © 2024 Ravi, Osouli Meinagh and Bavarsad Shahripour.)

Skin cancer is a terrifying disorder that affects all individuals. Due to the significant increase in the rate of melanoma skin cancer, early detection of skin cancer is now more critical than ever before. Malignant melanoma is one of the most serious forms of skin cancer, and it is caused by abnormal melanocyte cell growth. In recent years, skin cancer predictive categorization has become more accurate and predictive due to multiple deep learning algorithms. Malignant melanoma is diagnosed using the Recurrent Convolution Neural Network-Long Short-Term Memory (RCNN-LSTM), which is one of the deep learning classification approaches. Using the International Skin Image Collection and the RCNN-LSTM, the data are categorized and analyzed to gain a better understanding of skin cancer. The method begins with data preprocessing, which prepares the dataset for classification. Additionally, the RCNN is employed to extract the features that are vital to the prediction process. The LSTM is accountable for the final step, classification. There are further factors to examine, such as the precision of 94.60%, the sensitivity of 95.67%, and the F1-score of 95.13%. Other benefits of the suggested study include shorter prediction durations of 95.314, 122.530, and 131.205 s and lower model loss of 0.25%, 0.19%, and 0.15% for input sizes 10, 15, and 20, respectively. Three datasets had a reduced categorization error of 5.11% and an accuracy of 95.42%. In comparison to previous approaches, the work discussed here produces superior outcomes. RESEARCH HIGHLIGHTS: Recurrent convolutional neural network (RCNN) deep learning approach for optimizing time prediction and error classification in early melanoma detection. It extracts a high number of specific features from the skin disease image, making the classification process easier and more accurate. To reduce classification errors in accurately detecting melanoma, context dependency is considered in this work. By accounting for context dependency, the deprivation state is avoided, preventing performance degradation in the model. To minimize melanoma detection model loss, a skin disease image augmentation or regularization process is performed in this work. This strategy improves the accuracy of the model when applied to fresh, previously unobserved data., (© 2024 Wiley Periodicals LLC.)

One-third of systemic lupus erythematosus (SLE) patients experience various degrees of ocular manifestations, with immunosuppressants recommended as a treatment option. Targeted immune suppression via oral administration is challenging due to the harsh gastrointestinal tract environment combined with complex physiological barriers. Here, we report the efficacy of orally administered cyclosporine (CsA)-laden polymer nanoparticles decorated with the ligand - Gambogic Acid (P2Ns-GA-CsA) in sustained lymph node delivery. This is the first report demonstrating the CD71 specificity of P2Ns-GA-CsA in the CD71 knockout mouse model and the influence of spacer length in achieving target tissue bioavailability in a lupus mouse model. P2Ns-GA-CsA effectively regulates T-cell chemotaxis by PD-L1 at a 50 % lower dose compared to conventional CsA in a mouse model exhibiting lupus-associated corneal inflammation. Collectively, these results suggest the possibility for further development of P2Ns-GA to target a diverse range of lymphatic disorders., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: R.G. M.A. and M.N.V.R.K. are inventors on patent applications related to the technology described in the manuscript (owned and managed by Texas A&M University, exclusively licensed to Peroral Biosciences, Inc.,). M.N.V.R.K. is a non-paid scientific advisory board member of Peroral Biosciences, Inc., and M.A. is a shareholder of Peroral Biosciences, Inc.

This study delves into mitigating ground motion induced by underground blasts on superstructures. A parametric analysis is conducted to assess the performance of base isolated structures under different blast scenarios. The analysis is conducted using Newmark's time step integration method, and the absolute acceleration of the structure and displacement of the isolator bearing are calculated to evaluate the response. Results demonstrate the significant effectiveness of base isolation in reducing blast-induced vibrations. The parameters of the base isolator, including damping ratio and time period, are systematically varied to understand their impact on the response. Key findings include the significant influence of the ground medium on both fixed base and base isolated superstructures, with soil-rock interface locations reducing floor acceleration under various blast load intensities. The N-Z bearing system is shown to effectively reduce the dynamic response in both rock and soil media. This study recommends specific combinations of ground medium and site location for optimal protection against blast threats. Ultimately, this study facilitates a better understanding of the dynamic interaction between underground blasts and superstructures, paving the way for more effective blast-resistant structural designs., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

People with Parkinson's disease (PWP) face critical challenges, including lack of access to neurological care, inadequate measurement and communication of motor symptoms, and suboptimal medication management and compliance. We have developed QDG-Care: a comprehensive connected care platform for Parkinson's disease (PD) that delivers validated, quantitative metrics of all motor signs in PD in real time, monitors the effects of adjusting therapy and medication adherence and is accessible in the electronic health record. In this article, we describe the design and engineering of all components of QDG-Care, including the development and utility of the QDG Mobility and Tremor Severity Scores. We present the preliminary results and insights from an at-home trial using QDG-Care. QDG technology has enormous potential to improve access to, equity of, and quality of care for PWP, and improve compliance with complex time-critical medication regimens. It will enable rapid "Go-NoGo" decisions for new therapeutics by providing high-resolution data that require fewer participants at lower cost and allow more diverse recruitment., (© 2024. The Author(s).)

Objective: To compare radiographic measurements of lateral tibial slope (LTS), medial TS (MTS), and coronal TS (CTS) in MRI-defined intact, injured, and mucoid-degenerated native ACL knees and determine inter-reader reliability., Materials and Methods: Patient records from 2 years at tertiary care hospitals were reviewed for individuals aged 18-100 undergoing 3-Tesla knee MRI and radiographs. Two randomly selected cohorts, control, and pathologic ACLs on MRI with 86 patients each, were age, gender, and BMI-matched. A fellowship-trained musculoskeletal radiologist reevaluated curated images, characterizing ACL status. Two trained medical students independently collected clinical data and measured slopes on blinded radiographs. ICC, Cohen's kappa, and case-control matching were performed using SPSS statistical package, with ICC and ANOVA used for comparisons., Results: Among 172 patients with 172 MRIs and radiographs, there were 86 controls and 86 ACL lesions. There were 108/172 (62.79%) males and 64/172 (37.21%) females. ICCs were 0.966 for MTS, 0.975 for LTS, and 0.978 for CTS. Mucoid degeneration patients had a higher BMI and were older than control (p < .05) or completely torn (p < .001) ACL patients. There was no difference in TS between normal and pathologic ACLs; however, LTS-MTS differences were larger with partial tears (2.5 ± 4.9) than normal ACLs by 4.5° (± 1.2, p < .001), complete tears by 4.5° (± 1.3, p < .001), and mucoid degeneration by 4.9° (± 1.5, p = .001)., Conclusion: Various TS measurements are reliable. LTS-MTS differences are associated with different ACL lesions compared to normal ACLs., (© 2024. The Author(s), under exclusive licence to International Skeletal Society (ISS).)

Neurological complications, both acute and chronic, are reported commonly in COVID-19 affected individuals. In this context, the understanding of pathogenesis of SARS-CoV-2 in specific cells of central nervous system (CNS) origin is relevant. The present study explores infection biology of a clinical isolate of SARS-CoV-2 in human cell lines of neural origin such as the glioblastoma (U87-MG), neuroblastoma (SHSY5Y) and microglia (C20). Despite showing clear evidence of infection by immunofluorescence with an anti-spike protein antibody, all the three neural cell lines were observed to be highly restrictive to the replication of the infecting virus. While the U87-MG glioblastoma cells demonstrated no cytopathic effects and a low viral titre with no signs of replication, the SHSY5Y neuroblastoma cells exhibited cytopathic effects with bleb formation but no evidence of viable virus. The C20 microglial cells showed neither signs of cytopathic effects nor viable virus. Ultrastructural studies demonstrated intracellular virions in infected neural cells. The presence of lipid droplets in infected SHSY5Y cells suggested an impact on host cell metabolism. The decrease in viral RNA levels over time in all the neural cell lines suggested restricted viral replication. In conclusion, this study highlights the limited susceptibility of neural cells to SARS-CoV-2 infection. This reduced permissibility of neural cell lines to SARS-CoV-2 may point to their inherent lower expression of receptors that support viral entry in addition to the intracellular factors that potently inhibit viral replication. The study findings prompt further investigation into the mechanisms of SARS-CoV-2 infection of neural cells., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The study aimed to achieve the following objectives: (1) to perform the fusion of thermal and visible tongue images with various fusion rules of discrete wavelet transform (DWT) to classify diabetes and normal subjects; (2) to obtain the statistical features in the required region of interest from the tongue image before and after fusion; (3) to distinguish the healthy and diabetes using fused tongue images based on deep and machine learning algorithms. The study participants comprised of 80 normal subjects and age- and sex-matched 80 diabetes patients. The biochemical tests such as fasting glucose, postprandial, Hba1c are taken for all the participants. The visible and thermal tongue images are acquired using digital single lens reference camera and thermal infrared cameras, respectively. The digital and thermal tongue images are fused based on the wavelet transform method. Then Gray level co-occurrence matrix features are extracted individually from the visible, thermal, and fused tongue images. The machine learning classifiers and deep learning networks such as VGG16 and ResNet50 was used to classify the normal and diabetes mellitus. Image quality metrics are implemented to compare the classifiers' performance before and after fusion. Support vector machine outperformed the machine learning classifiers, well after fusion with an accuracy of 88.12% compared to before the fusion process (Thermal-84.37%; Visible-63.1%). VGG16 produced the classification accuracy of 94.37% after fusion and attained 90.62% and 85% before fusion of individual thermal and visible tongue images, respectively. Therefore, this study results indicates that fused tongue images might be used as a non-contact elemental tool for pre-screening type II diabetes mellitus., (© 2024. The Author(s).)

Background: Electronic health records (EHRs) are live, digital patient records that provide a thorough overview of a person's complete health data. Electronic health records (EHRs) provide better healthcare decisions and evidence-based patient treatment and track patients' clinical development. The EHR offers a new range of opportunities for analyzing and contrasting exam findings and other data, creating a proper information management mechanism to boost effectiveness, quick resolutions, and identifications., Aim: The aim of this studywas to implement an interoperable EHR system to improve the quality of care through the decision support system for the identification of lung cancer in its early stages., Objective: The main objective of the proposed system was to develop an Android application for maintaining an EHR system and decision support system using deep learning for the early detection of diseases. The second objective was to study the early stages of lung disease to predict/detect it using a decision support system., Methods: To extract the EHR data of patients, an android application was developed. The android application helped in accumulating the data of each patient. The accumulated data were used to create a decision support system for the early prediction of lung cancer. To train, test, and validate the prediction of lung cancer, a few samples from the ready dataset and a few data from patients were collected. The valid data collection from patients included an age range of 40 to 70, and both male and female patients. In the process of experimentation, a total of 316 images were considered. The testing was done by considering the data set into 80:20 partitions. For the evaluation purpose, a manual classification was done for 3 different diseases, such as large cell carcinoma, adenocarcinoma, and squamous cell carcinoma diseases in lung cancer detection., Results: The first model was tested for interoperability constraints of EHR with data collection and updations. When it comes to the disease detection system, lung cancer was predicted for large cell carcinoma, adenocarcinoma, and squamous cell carcinoma type by considering 80:20 training and testing ratios. Among the considered 336 images, the prediction of large cell carcinoma was less compared to adenocarcinoma and squamous cell carcinoma. The analysis also showed that large cell carcinoma occurred majorly in males due to smoking and was found as breast cancer in females., Conclusion: As the challenges are increasing daily in healthcare industries, a secure, interoperable EHR could help patients and doctors access patient data efficiently and effectively using an Android application. Therefore, a decision support system using a deep learning model was attempted and successfully used for disease detection. Early disease detection for lung cancer was evaluated, and the model achieved an accuracy of 93%. In future work, the integration of EHR data can be performed to detect various diseases early., Competing Interests: The authors declare no conflict of interest, financial or otherwise., (© 2024 The Author(s). Published by Bentham Open.)

Dehydroepiandrosterone sulphate (DHEAS), the biochemical indicator of adrenarche and pubarche, is of paramount importance in the evaluation of puberty-related disorders. The reference range of DHEAS should be ethnicity, age, sex, pubarche and Tanner stage specific. Anthropometry, puberty assessment and hormonal parameters were estimated using electrochemiluminescence assay. Bone age was estimated using the BoneXpert software. Of 2191 healthy Indian children aged 5-18 y screened at Chandigarh, 1919 were included in the final analysis (994 boys). The median DHEAS levels at pubarche stage P2 were 82.10 (55.0-129.0) g/dl in girls and 132.50 (95.12-205.50) g/dl in boys. By ROC analysis, the level of DHEAS at pubarche was 63.7 g/dl (sensitivity 72.6%, specificity 64.4%) in girls and 82.2 g/dl (sensitivity 81.8%, specificity 68.8%) in boys. The median age at adrenarche was 9.5 y in both sexes. On multivariate regression analysis; bone age, body mass index (BMI), gonadal steroids, and insulin-like growth factor-1 (IGF-1) significantly correlated with serum DHEAS levels in either sex., (© 2023. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Speech signals are valuable biomarkers for assessing an individual's mental health, including identifying Major Depressive Disorder (MDD) automatically. A frequently used approach in this regard is to employ features related to speaker identity, such as speaker-embeddings. However, over-reliance on speaker identity features in mental health screening systems can compromise patient privacy. Moreover, some aspects of speaker identity may not be relevant for depression detection and could serve as a bias factor that hampers system performance. To overcome these limitations, we propose disentangling speaker-identity information from depression-related information. Specifically, we present four distinct disentanglement methods to achieve this - adversarial speaker identification (SID)-loss maximization (ADV), SID-loss equalization with variance (LEV), SID-loss equalization using Cross-Entropy (LECE) and SID-loss equalization using KL divergence (LEKLD). Our experiments, which incorporated diverse input features and model architectures, have yielded improved F1 scores for MDD detection and voice-privacy attributes, as quantified by Gain in Voice Distinctiveness G V   D and De-Identification Scores (DeID). On the DAIC-WOZ dataset (English), LECE using ComparE16 features results in the best F1-Scores of 80% which represents the audio-only SOTA depression detection F1-Score along with a G V   D of -1.1 dB and a DeID of 85%. On the EATD dataset (Mandarin), ADV using raw-audio signal achieves an F1-Score of 72.38% surpassing multi-modal SOTA along with a G V   D of -0.89 dB dB and a DeID of 51.21%. By reducing the dependence on speaker-identity-related features, our method offers a promising direction for speech-based depression detection that preserves patient privacy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Opioids are commonly prescribed to address intense, ongoing pain associated with cancer, as well as long-lasting noncancer-related pain when alternative methods have proven ineffective. Individuals who exhibit both chronic pain and misuse of opioids face a significant danger of experiencing adverse health outcomes and the potential loss of life related to opioid use. Thus, there is a current movement to prescribe naloxone to those considered high-risk for opioid overdose. Naloxone has been explored as an antidote to reverse acute respiratory depression. Conversely, naloxone can give rise to other problems, including hypertension and cardiac arrhythmias. Thus, the importance of nanotechnology-enabled drug delivery strategies and their role in mitigating naloxone side-effects are significant. In this review, we explore the latest advancements in nanotechnology-enabled naloxone and alternative methods for addressing the opioid crisis through the utilization of non-opioid natural alternatives for chronic pain management., Competing Interests: The authors declare the following competing financial interest(s): M.A. and M.N.V.R.K. are inventors on patent applications related to the technology described in the manuscript licensed to Peroral Biosciences, Inc. M.N.V.R.K. is a non-paid scientific advisory board member of Peroral Biosciences, Inc., and M.A. is a shareholder of Peroral Biosciences, Inc., (© 2024 American Chemical Society.)

Receptor-mediated polyester drug delivery systems have tremendous potential for improving the clinical performance of existing pharmaceutical drugs. Despite significant progress made in this area, it remains unclear how and to what extent the polyester nanoparticle surface topography would affect the in vitro , ex vivo and in vivo performance of a drug, and if there exists a correlation between in vitro and in vivo , as well as healthy versus pathophysiological states. Herein, we report a systematic investigation of the interactions between ligands and receptors as a function of the linker length, two-carbon (2C) versus four-carbon (4C). The in vitro , ex vivo and in vivo in healthy models validate the hypothesis that 4C has better reach and binding to the receptors. The results indicate that 4C offered better performance over 2C in vivo in improving the oral bioavailability of insulin (INS) by 1.1-fold (3.5-fold compared to unfunctionalized nanoparticles) in a healthy rat model. Similar observations were made in pathophysiological models; however, the effects were less prominent compared to those in healthy models. Throughout, ligand decorated nanoparticles outperformed unfunctionalized nanoparticles. Finally, a semimechanistic pharmacokinetic and pharmacodynamic (PKPD) model was developed using the experimental data sets to quantitatively evaluate the effect of P2Ns-GA on oral bioavailability and efficacy of insulin. The study presents a sophisticated oral delivery system for INS or hydrophilic therapeutic cargo, highlighting the significant impact on bioavailability that minor adjustments to the surface chemistry can have.

The genetic influence on human vocal pitch in tonal and non-tonal languages remains largely unknown. In tonal languages, such as Mandarin Chinese, pitch changes differentiate word meanings, whereas in non-tonal languages, such as Icelandic, pitch is used to convey intonation. We addressed this question by searching for genetic associations with interindividual variation in median pitch in a Chinese major depression case-control cohort and compared our results with a genome-wide association study from Iceland. The same genetic variant, rs11046212-T in an intron of the ABCC9 gene, was one of the most strongly associated loci with median pitch in both samples. Our meta-analysis revealed four genome-wide significant hits, including two novel associations. The discovery of genetic variants influencing vocal pitch across both tonal and non-tonal languages suggests the possibility of a common genetic contribution to the human vocal system shared in two distinct populations with languages that differ in tonality (Icelandic and Mandarin)., (© 2024. The Author(s).)

Acute encephalitis syndrome (AES) in children poses a significant public health challenge in India. This study aims to explore the utility of host inflammatory mediators and neurofilament (NfL) levels in distinguishing etiologies, assessing disease severity, and predicting outcomes in AES. We assessed 12 mediators in serum (n = 58) and 11 in cerebrospinal fluid (CSF) (n = 42) from 62 children with AES due to scrub typhus, viral etiologies, and COVID-associated multisystem inflammatory syndrome (MIS-C) in Southern India. Additionally, NfL levels in serum (n = 20) and CSF (n = 18) were examined. Clinical data, including Glasgow coma scale (GCS) and Liverpool outcome scores, were recorded. Examining serum and CSF markers in the three AES etiology groups revealed notable distinctions, with scrub typhus differing significantly from viral and MIS-C causes. Viral causes had elevated serum CCL11 and CCL2 compared with scrub typhus, while MIS-C cases showed higher HGF levels than scrub typhus. However, CSF analysis showed a distinct pattern with the scrub typhus group exhibiting elevated levels of IL-1RA, IL-1β, and TNF compared with MIS-C, and lower CCL2 levels compared with the viral group. Modeling the characteristic features, we identified that age ≥3 years with serum CCL11 < 180 pg/mL effectively distinguished scrub typhus from other AES causes. Elevated serum CCL11, HGF, and IL-6:IL-10 ratio were associated with poor outcomes (p = 0.038, 0.005, 0.02). Positive CSF and serum NfL correlation, and negative GCS and serum NfL correlation were observed. Median NfL levels were higher in children with abnormal admission GCS and poor outcomes. Measuring immune mediators and brain injury markers in AES provides valuable diagnostic insights, with the potential to facilitate rapid diagnosis and prognosis. The correlation between CSF and serum NfL, along with distinctive serum cytokine profiles across various etiologies, indicates the adequacy of blood samples alone for assessment and monitoring. The association of elevated levels of CCL11, HGF, and an increased IL-6:IL-10 ratio with adverse outcomes suggests promising avenues for therapeutic exploration, warranting further investigation., (© 2024 Wiley Periodicals LLC.)

Background: Undifferentiated pleomorphic sarcomas (UPSs) are amongst the most common subtypes of soft-tissue sarcomas. Few real-world data on the use of immune checkpoint blockade (ICB) in UPS patients and other high-grade pleomorphic STS patients are available., Purpose: The purpose of our study is to describe the efficacy and toxicity of ICB in patients with advanced UPSs and other high-grade pleomorphic sarcomas treated at our institution., Methods: This is a retrospective, observational study of all patients with metastatic high-grade pleomorphic sarcomas treated with FDA-approved ICB at MD Anderson Cancer Center between 1 January 2015 and 1 January 2023. Patients included in trials for which results are not yet published were excluded., Results: Thirty-six patients with advanced/metastatic pleomorphic sarcomas were included. The median age was 52 years. A total of 26 patients (72%) had UPSs and 10 patients (28%) had other high-grade pleomorphic sarcomas. The median follow-up time was 8.8 months. The median PFS was 2.9 months. The 3-month PFS and 6-month PFS were 46% and 32%, respectively. The median OS was 12.9 months. The 12-month OS and 24-month OS were 53% and 29%, respectively. The best response, previous RT, and type of ICB treatment were significantly and independently associated with shorter PFS ( p = 0.0012, p = 0.0019 and p = 0.036, respectively). No new safety signal was identified, and the toxicity was overall manageable with no toxic deaths and only four patients (11%) stopping treatment due to toxicity., Conclusions: Real-world retrospective data are consistent with the published literature, with a promising 6-month PFS of 32%. Partial or stable responders to ICB treatment have significantly improved PFS compared to progressors.

Objective: The study aimed to compare ZOOMit diffusion-weighted imaging (DWI) MRI with conventional DWI MRI for visualizing small bones in the foot, soft tissue abscesses, and osteomyelitis., Materials and Methods: The cohort consisted of a consecutive series of patients with potential foot and ankle infections referred for MR imaging. Patients were imaged using both conventional and ZOOMit DWI in the same setting. Blinded reads were then conducted in separate settings and independent of known clinical diagnosis by two expert radiologists. The results from the reads were compared statistically using paired t-tests and with biopsy specimen analysis, both anatomopathological and microbiological., Results: There was improvement in fat suppression using ZOOMit sequence compared to conventional DWI (p = .001) with no significant difference in motion artifacts (p = .278). ZOOMit had a higher rate of concordance with pathology findings for osteomyelitis (72%, 31/43 cases) compared with conventional DWI (60%, 26/43 cases). ZOOMit also identified 46 additional small bones of the foot and ankle (405/596, 68.0%) than conventional DWI (359/596, 60.2%). Conventional DWI however exhibited a more negative contrast-to-noise ratio (CNR) than ZOOMit (p = 0.001)., Conclusion: ZOOMit DWI improves distal extremity proton diffusion assessment and helps visualize more bones in the foot, with less image distortion and improved fat saturation at the expense of reduced CNR. This makes it a viable option for assessing lower extremity infections., Clinical Relevance Statement: This study highlights the novel utilization of ZOOMit diffusion-weighted imaging (DWI) for the assessment of lower extremity lesions compared to conventional DWI., Key Points: • Distal extremity diffusion-weighted imaging (DWI) is often limited. • ZOOMit DWI displayed improved fat suppression with less motion artifacts and better visualization of the lower extremity bones than conventional DWI. • ZOOMit shows decreased contrast-to-noise ratio than conventional DWI., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Cassava (Manihot esculenta Crantz), an important tropical crop, is affected by extreme climatic events, including rising CO2 levels. We evaluated the short-term effect of elevated CO2 concentration (ECO2 ) (600, 800 and 1000ppm) on the photosynthetic efficiency of 14 cassava genotypes. ECO2 significantly altered gaseous exchange parameters (net photosynthetic rate (P n ), stomatal conductance (g s ), intercellular CO2 (C i ) and transpiration (E )) in cassava leaves. There were significant but varying interactive effects between ECO2 and varieties on these physiological characteristics. ECO2 at 600 and 800ppm increased the P n rate in the range of 13-24% in comparison to 400ppm (ambient CO2 ), followed by acclimation at the highest concentration of 1000ppm. A similar trend was observed in g s and E . Conversely, C i increased significantly and linearly across increasing CO2 concentration. Along with C i , a steady increase in water use efficiency [WUEintrinsic (P n /g s ) and WUEinstantaneous (P n /E )] across various CO2 concentrations corresponded with the central role of restricted stomatal activity, a common response under ECO2 . Furthermore, P n had a significant quadratic relationship with the ECO2 (R 2 =0.489) and a significant and linear relationship with C i (R 2 =0.227). Relative humidity and vapour pressure deficit during the time of measurements remained at 70-85% and ~0.9-1.31kPa, respectively, at 26±2°C leaf temperature. Notably, not a single variety exhibited constant performance for any of the parameters across CO2 concentrations. Our results indicate that the potential photosynthesis can be increased up to 800ppm cassava varieties with high sink capacity can be cultivated under protected cultivation to attain higher productivity.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. nab -Sirolimus is approved in the United States for the treatment of metastatic or locally advanced malignant perivascular epithelioid cell tumor (PEComa) on the basis of the primary analysis results of the phase II Advanced Malignant Perivascular Epithelioid Cell Tumors (AMPECT) trial (ClinicalTrials.gov identifier: NCT02494570). Results from the primary analysis were previously published; however, the median duration of response (mDOR) had not been reached at that time. Here, 3 years after the primary analysis, we report final efficacy and safety data (data cutoff: April 29, 2022). At study completion, the confirmed overall response rate (by independent radiologist review using RECIST v1.1) was 38.7% (95% CI, 21.8 to 57.8), with an additional converted confirmed complete response (n = 2). Median progression-free survival remained the same at 10.6 months (95% CI, 5.5 to 41.2). The mDOR was reached at 39.7 months (95% CI, 6.5 to not reached [NR]), and the median overall survival at completion was 53.1 months (95% CI, 22.2 to NR). The most common treatment-related adverse events (TRAEs) were stomatitis (82.4%) and fatigue and rash (each 61.8%). No new or unexpected adverse events occurred, and no grade ≥4 TRAEs were reported. These results highlight the long-term clinical benefit of nab- sirolimus in patients with advanced malignant PEComa, with a DOR of >3 years.

Objective: The vast majority of gastrointestinal stromal tumors (GISTs) are driven by activating mutations in KIT , PDGFRA , or components of the succinate dehydrogenase (SDH) complex ( SDHA , SDHB , SDHC , and SDHD genes). A small fraction of GISTs lack alterations in KIT , PDGFRA , and SDH . We aimed to further characterize the clinical and genomic characteristics of these so-called "triple-negative" GISTs. Methods: We extracted clinical and genomic data from patients seen at MD Anderson Cancer Center with a diagnosis of GIST and available clinical next generation sequencing data to identify "triple-negative" patients. Results: Of the 20 patients identified, 11 (55.0%) had gastric, 8 (40.0%) had small intestinal, and 1 (5.0%) had rectal primary sites. In total, 18 patients (90.0%) eventually developed recurrent or metastatic disease, and 8 of these presented with de novo metastatic disease. For the 13 patients with evaluable response to imatinib (e.g., neoadjuvant treatment or for recurrent/metastatic disease), the median PFS with imatinib was 4.4 months (range 0.5-191.8 months). Outcomes varied widely, as some patients rapidly developed progressive disease while others had more indolent disease. Regarding potential genomic drivers, four patients were found to have alterations in the RAS/RAF/MAPK pathway: two with a BRAF V600E mutation and two with NF1 loss-of-function (LOF) mutations (one deletion and one splice site mutation). In addition, we identified two with TP53 LOF mutations, one with NTRK3 fusion ( ETV6-NTRK3 ), one with PTEN deletion, one with FGFR1 gain-of-function (GOF) mutation (K654E), one with CHEK2 LOF mutation (T367fs*), one with Aurora kinase A fusion ( AURKA-CSTF1 ), and one with FANCA deletion. Patients had better responses with molecularly targeted therapies than with imatinib. Conclusions: Triple-negative GISTs comprise a diverse cohort with different driver mutations. Compared to KIT / PDGFRA -mutant GIST, limited benefit was observed with imatinib in triple-negative GIST. In depth molecular profiling can be helpful in identifying driver mutations and guiding therapy.

Introduction: Migraine is a prevalent and disabling primary headache disorder worldwide, causing significant years lost due to disability (YLD) and impacting various aspects of everyday life. Despite its high prevalence and substantial burden, there is a lack of comprehensive data on clinical patterns and management trends, in places like Tamil Nadu, India. This study aims and also fill gaps by investigating and analyzing the clinical characteristics, treatment patterns, and illness burden among patients with episodic migraine (EM) and chronic migraine (CM) in the state of Tamil Nadu., Study: This cross-sectional retrospective study was conducted at the Department of Neurology, Madras Medical College, Chennai, over a three-month period starting from January 2024 to March 2024. The study included migraine patients aged 18 years and above who met the International Classification of Headache Disorders (ICHD)-3 criteria and took treatment at the department. Data were collected using patient interviews, medical records, and counseling sessions and using a pre-designed questionnaire. Patient demographics, clinical characteristics, symptom prevalence, prescription patterns, and illness burden were analyzed accordingly. The Migraine Disability Assessment (MIDAS) questionnaire was used to measure the burden of illness., Results: The analysis involved 400 migraine patients, 92.5% of them having EM and 7.5% of them having CM. The mean age of patients was 37.5 years, with a predominance of females (73.5%). Patients with CM had having significantly higher average number of headache days per month when compared to those with EM. Tension-type headache (TTH) and medication-overuse headache (MOH) were more prevalent in those CM patients. Trigger factors include lack of sleep, bright light exposure, and stress. Comorbidities such as diabetes mellitus, obesity, and depression were significantly higher in CM patients. Acute treatment included NSAIDs and Triptans, while preventive therapy was more commonly used in CM patients. The mean MIDAS score was significantly higher in CM patients, which indicates greater disability., Conclusion: The study provides valuable insights into the clinical characteristics, treatment patterns, and burden of illness among migraine patients in Tamil Nadu, India. Significant differences were observed between EM and CM patients, which highlights the need for comprehensive management strategies. Preventive therapy, lifestyle modifications, and comprehensive assessment of disability are all important in addressing the variable needs of migraine patients and also reducing the burden of illness. Further research is necessary to explore additional factors influencing migraine outcomes in this population., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Irfan et al.)

Introduction: The utility of ablation index (AI) to guide ventricular tachycardia (VT) ablation in patients with structural heart disease is unknown. The aim of this study was to assess procedural characteristics and clinical outcomes achieved using AI-guided strategy (target value 550) or conventional non-AI-guided parameters in patients undergoing scar-related VT ablation., Methods: Consecutive patients (n = 103) undergoing initial VT ablation at a single center from 2017 to 2022 were evaluated. Patient groups were 1:1 propensity-matched for baseline characteristics. Single lesion characteristics for all 4707 lesions in the matched cohort (n = 74) were analyzed. The impact of ablation characteristics was assessed by linear regression and clinical outcomes were evaluated by Cox proportional hazard model., Results: After propensity-matching, baseline characteristics were well-balanced between AI (n = 37) and non-AI (n = 37) groups. Lesion sets were similar (scar homogenization [41% vs. 27%; p = .34], scar dechanneling [19% vs. 8%; p = .18], core isolation [5% vs. 11%; p = .4], linear and elimination late potentials/local abnormal ventricular activities [35% vs. 44%; p = .48], epicardial mapping/ablation [11% vs. 14%; p = .73]). AI-guided strategy had 21% lower procedure duration (-47.27 min, 95% confidence interval [CI] [-81.613, -12.928]; p = .008), 49% lower radiofrequency time per lesion (-13.707 s, 95% CI [-17.86, -9.555]; p < .001), 21% lower volume of fluid administered (1664 cc [1127, 2209] vs. 2126 cc [1750, 2593]; p = .005). Total radiofrequency duration (-339 s [-24%], 95%CI [-776, 62]; p = .09) and steam pops (-155.6%, 95% CI [19.8%, -330.9%]; p = .08) were nonsignificantly lower in the AI group. Acute procedural success (95% vs. 89%; p = .7) and VT recurrence (0.97, 95% CI [0.42-2.2]; p = .93) were similar for both groups. Lesion analysis (n = 4707) demonstrated a plateau in the magnitude of impedance drops once reaching an AI of 550-600., Conclusion: In this pilot study, an AI-guided ablation strategy for scar-related VT resulted in shorter procedure time and average radiofrequency time per lesion with similar acute procedural and intermediate-term clinical outcomes to a non-AI-guided approach utilizing traditional ablation parameters., (© 2024 Wiley Periodicals LLC.)

Based on the demonstrated clinical activity of immune-checkpoint blockade (ICB) in advanced dedifferentiated liposarcoma (DDLPS) and undifferentiated pleomorphic sarcoma (UPS), we conducted a randomized, non-comparative phase 2 trial ( NCT03307616 ) of neoadjuvant nivolumab or nivolumab/ipilimumab in patients with resectable retroperitoneal DDLPS (n = 17) and extremity/truncal UPS (+ concurrent nivolumab/radiation therapy; n = 10). The primary end point of pathologic response (percent hyalinization) was a median of 8.8% in DDLPS and 89% in UPS. Secondary end points were the changes in immune infiltrate, radiographic response, 12- and 24-month relapse-free survival and overall survival. Lower densities of regulatory T cells before treatment were associated with a major pathologic response (hyalinization > 30%). Tumor infiltration by B cells was increased following neoadjuvant treatment and was associated with overall survival in DDLPS. B cell infiltration was associated with higher densities of regulatory T cells before treatment, which was lost upon ICB treatment. Our data demonstrate that neoadjuvant ICB is associated with complex immune changes within the tumor microenvironment in DDLPS and UPS and that neoadjuvant ICB with concurrent radiotherapy has significant efficacy in UPS., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Importance: Angiosarcoma is an aggressive vascular malignant neoplasm presenting either as a primary or secondary cancer, often arising after radiotherapy or in the context of preexisting lymphedema. Comprehensive data describing its incidence and presentation patterns are needed., Objective: To describe the incidence, presenting characteristics, and change over time of angiosarcoma in the US., Design, Setting, and Participants: This retrospective cross-sectional study used data from the US Cancer Statistics (USCS) National Program of Cancer Registries-Surveillance, Epidemiology, and End Results Combined Database, which captures more than 99% of newly diagnosed cancers in the US. The study included all 19 289 patients in the US with a new diagnosis of angiosarcoma between 2001 and 2020 captured in the USCS database. Statistical analysis was performed from June to September 2023., Main Outcomes and Measures: Incidence of angiosarcoma, demographics of patients with angiosarcoma, and extent of disease at presentation., Results: The study included 19 289 patients (median age, 71 years [IQR, 59-80 years]; 10 506 women [54.5%]) with a new diagnosis of angiosarcoma. The US incidence of angiosarcoma doubled between 2001 (657 cases) and 2019 (1312 cases), reflecting both an increase in the adjusted incidence rate of 1.6% per year (P = .001), to 3.3 cases per 1 000 000 person-years (95% CI, 3.1-3.5 cases per 1 000 000 person-years), and an increase in the population at risk. In 2020, the reported incidence rate (3.0 cases per 1 000 000 person-years) and cases of angiosarcoma (n = 1159) were modestly lower than in 2019. Overall, 72.3% of cases of angiosarcoma (n = 13 955) were cutaneous, subcutaneous, or breast angiosarcomas; 24.4% were visceral (n = 4701); and 3.3% were located in unknown or rare primary sites (n = 633). Secondary breast and chest wall angiosarcomas among women represented the largest contribution to increasing incidence. Among breast angiosarcomas, 99.2% (2684 of 2705) were in women and 71.9% (1944 of 2705) were secondary. A total of 80.4% of chest wall or thorax cases among women (1861 of 2316) were secondary vs 26.5% among men (112 of 422), and 63.9% of upper extremity cases among women (205 of 321) were secondary vs 26.8% (56 of 209) among men (P = .001). Rates of secondary angiosarcoma in the abdomen and lower extremities were similar between men and women. The incidence rate of visceral angiosarcoma was also found to be increasing (1.5% per year; P = .001)., Conclusions and Relevance: This cross-sectional study describes angiosarcoma presentation patterns and incidence rates in the US over a 20-year period and shows that the number of cases in men and women increased, with the greatest increase among women with secondary angiosarcoma of the chest, breast, and upper extremity. These data increase awareness of a rare but highly morbid disease and highlight the need for improved early detection of angiosarcoma among patients at high risk, such as women with a history of breast cancer.