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Tetranuclear [2 × 2] square-grid-like Ln III clusters have been synthesized by reacting LnCl 3 ·6H 2 O salts with bis[α-hydroxy( p -bromophenyl)methyl]phosphinic acid [R 2 PO 2 H, where R = CH(OH)PhBr] and pivalic acid. Single-crystal X-ray diffraction studies show the formation of [Me 4 N] 2 [Ln 4 (μ 2 -η 1 :η 1 -PO 2 R 2 ) 8 (η 2 -CO 2 Bu t ) 4 (μ 4 -CO 3 )] [Ln = Er ( 1 ), Dy ( 2 ), and Tb ( 3 )]. Direct-current studies reveal significant ferromagnetic interactions between Dy III in 2 and Tb III in 3 and an antiferromagnetic interaction between Er III in 1 . Dynamic magnetic susceptibility measurements confirm a single-molecule magnet (SMM) behavior in both 0 and 1200 Oe applied magnetic fields for 2 . Complexes 2 and 3 show single molecular toroic (SMT) behavior with a mixed magnetic moment.

Aim & objective: Combinatorial delivery of Doxorubicin (DOX) and Baicalein (BAC) has a potential to improve breast cancer treatment by mitigating the cardiotoxicity induced by DOX. The nanoformulation has been optimized and subjected to pharmacokinetic studies using LC-MS/MS. Materials & methods: Nanoformulation bearing DOX and BAC was optimized using quality by design approach and method validation was done following USFDA guidelines. Results: The particle size, PDI and zeta potential of developed nanoformulation were 162.56 ± 2.21 nm, 0.102 ± 0.03 and -16.5 ± 1.21 mV, respectively. DOX-BAC-SNEDDs had a higher AUC 0-t values of 6128.84 ± 68.71 and 5896.62 ± 99.31 ng/mL/h as compared with DOX-BAC suspension. Conclusion: These findings hold promise for advancing breast cancer treatment and facilitating therapeutic drug monitoring.

Background: Disease remission or low disease activity are key treatment targets for patients with systemic lupus erythematosus (SLE). Pivotal trials of belimumab were conducted before the introduction of these targets. In this study, we aimed to pool data across trials to assess attainment of remission and low disease activity in a large, racially and culturally diverse patient population with SLE., Methods: In this integrated post-hoc analysis, we pooled data from five phase 3 trials of belimumab (BLISS-76 [NCT00410384], BLISS-52 [NCT00424476], BLISS-NEA [NCT01345253], BLISS-SC [NCT01484496], and EMBRACE [NCT01632241]), in patients with active, autoantibody-positive SLE. Patients were randomly assigned to receive belimumab (10 mg/kg per month intravenously or 200 mg per week subcutaneously) or placebo, plus standard therapy. The proportion of patients with Definitions of Remission in SLE (DORIS) remission and lupus low disease activity state (LLDAS) were analysed every 4 weeks from week 4 to week 52 for belimumab versus placebo, using modified Poisson regression adjusted for trial variance, in all patients and in subgroups per baseline SLE Disease Activity Index-2000 score (<10 or ≥10); anti-double stranded DNA positivity (yes or no); low complement 3 (C3) or C4 levels (yes or no); anti-dsDNA positivity or low C3 or C4 levels (yes and no); prednisone-equivalent dose (≤7·5 mg per day or >7·5 mg per day); antimalarial use (yes or no); and by race (Black African ancestry or African American, Asian, Indigenous American, or White)., Findings: Data for 3086 patients (1869 in the belimumab group and 1217 in the placebo group) were analysed. 2913 (94%) of 3086 patients were women and 173 (6%) were men, and the median age was 36 years (IQR 28-45). The proportion of patients with DORIS remission was significantly higher in the belimumab group than the placebo group at weeks 28, 48, and 52 (week 52: 148 [8%] of 1869 participants vs 68 [6%] of 1217 participants; risk ratio 1·51 [95% CI 1·15-1·99]; p=0·0055). The proportion of patients who attained LLDAS was higher in the belimumab group than the placebo group at weeks 8, 24, 32-52 (week 52: 322 [17%] of 1869 participants vs 125 [10%] of 1217 participants; 1·74 [1·44-2·12]; p<0·0001). A higher proportion of patients had DORIS remission at week 52 in the belimumab group than the placebo group among all baseline subgroups denoting high disease activity, with the exception of those on a prednisone-equivalent dose higher than 7·5 mg per day in whom there was no difference for DORIS remission with belimumab versus placebo. The proportion of patients with LLDAS was significantly higher among patients in the belimuab group than those who received placebo from week 44 in all baseline subgroups denoting high disease activity or earlier in some subgroups, and the differences were maintained at week 52., Interpretation: In adults with active SLE, belimumab plus standard therapy yielded greater benefit than placebo plus standard therapy in attaining DORIS remission (for which low rates were attained in both groups) and LLDAS, with differences observed as early as week 28 for DORIS remission and week 8 for LLDAS., Funding: Swedish Rheumatism Association, King Gustaf V's 80-year Foundation, Swedish Society of Medicine, Nyckelfonden, Professor Nanna Svartz Foundation, Ulla and Roland Gustafsson Foundation, Region Stockholm, and the Karolinska Institutet., Competing Interests: Declaration of interests IP reports grants and speaker honoraria from Amgen, AstraZeneca, Aurinia, BMS, Eli Lilly, Gilead, GSK, Janssen, Novartis, Otsuka, and Roche. MZ reports speaker honoraria from Eli Lilly, AstraZeneca, and GSK. AA has received consulting fees from AbbVie, Amgen, AstraZeneca, Aurinia, BMS, Celgene, Eli Lilly, Idorsia, Janssen, Genentech, GSK, Mallinckrodt, Pfizer, and UCB. RvV reports grants from Pfizer and Roche; consulting fees from AbbVie, AstraZeneca, Biogen, Biotest, BMS, Galapagos, Gilead, Janssen, Pfizer, Sanofi, Servier, UCB, and Vielabio; and speaker honoraria from AbbVie, Galapagos, GSK, Janssen, Pfizer, UCB, and Roche. MN reports grants from Janssen Pharmaceuticals; and consulting fees and speaker honoraria from AstraZeneca, Boehringer Ingelheim, GSK, and Janssen Pharmaceuticals. RAL, CH, MK, HAQ, and DC are employees of GSK and hold stocks and shares in the company. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Competing Interests: Conflicts of interest None to declare.

Aim & Objective: This study evaluates the potential of combining paclitaxel (PTX) and bortezomib (BTZ) for breast cancer therapy. Materials & Methods: The nanoformulation was optimized via Box-Behnken Design (BBD), with method validation adhering to US-FDA guidelines. Results: Multiple reaction monitoring transitions for PTX, BTZ and internal standard were m/z 855.80→286.60, 366.80→226.00 and 179.80→110.00, respectively. Elution done on C18 Luna column with 0.1% FA in MeOH:10 mM ammonium acetate. The size of nanoformulation was 133.9 ± 1.97 nm, PDI 0.19 ± 0.01 and zeta potential -19.20 ± 1.36 mV. Pharmacokinetics showed higher C max for PTX-BTZ-NE (313.75 ± 10.71 ng/ml PTX, 11.92 ± 0.53 ng/ml BTZ) versus free PTX-BTZ (104 ± 13.06 ng/ml PTX, 1.9 ± 0.08 ng/ml BTZ). Conclusion: Future findings will contribute to the treatment of breast cancer using PTX and BTZ.

Chronic kidney disease-induced secondary hyperparathyroidism (CKD-SHPT) heightens fracture risk through impaired mineral homeostasis and elevated levels of uremic toxins (UTs), which in turn enhance bone remodeling. Etelcalcetide (Etel), a calcium-sensing receptor (CaSR) agonist, suppresses parathyroid hormone (PTH) in hyperparathyroidism to reduce excessive bone resorption, leading to increased bone mass. However, Etel's effect on bone quality, chemical composition, and strength is not well understood. To address these gaps, we established a CKD-SHPT rat model and administered Etel at a human-equivalent dose concurrently with disease induction. The effects on bone and mineral homeostasis were compared with a CKD-SHPT (vehicle-treated group) and a control group (rats without SHPT). Compared with vehicle-treated CKD-SHPT rats, Etel treatment improved renal function, reduced circulating UT levels, improved mineral homeostasis parameters, decreased PTH levels, and prevented mineralization defects. The upregulation of mineralization-promoting genes by Etel in CKD-SHPT rats might explain its ability to prevent mineralization defects. Etel preserved both trabecular and cortical bones with attendant suppression of osteoclast function, besides increasing mineralization. Etel maintained the number of viable osteocytes to the control level, which could also contribute to its beneficial effects on bone. CKD-SHPT rats displayed increased carbonate substitution of matrix and mineral, decreased crystallinity, mineral-to-matrix ratio, and collagen maturity, and these changes were mitigated by Etel. Further, Etel treatment prevented CKD-SHPT-induced deterioration in bone strength and mechanical behavior. Based on these findings, we conclude that in CKD-SHPT rats, Etel has multiscale beneficial effects on bone that involve remodeling suppression, mineralization gene upregulation, and preservation of osteocytes., Competing Interests: Declaration of competing interest There is no known conflict of interest related to this research work and no competing financial interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Societal guidelines support atrial fibrillation (AF) treatment during surgical aortic valve replacement (SAVR). Recently, many patients with AF at low to intermediate risk are managed by transcatheter aortic valve replacement (TAVR). Therefore, we evaluated longitudinal outcomes in these populations., Methods: The United States Centers for Medicare and Medicaid Services inpatient claims database was evaluated for all beneficiaries with AF undergoing TAVR or SAVR with/without AF treatment (2018-2020). Treatment of AF included concomitant left atrial appendage obliteration, with/without surgical ablation, or endovascular appendage occlusion and/or catheter ablation at any time. Diagnosis-related group and International Classification of Diseases, 10th Revision, codes defined procedures with doubly robust risk adjustment across each group., Results: A total of 24,902 patients were evaluated (17,453 TAVR; 7,449 SAVR). Of patients undergoing SAVR, 3176 (42.6%) underwent AF treatment (SAVR+AF). Only 656 TAVR patients (4.5%) received AF treatment. Comparing well-balanced SAVR+AF vs SAVR vs TAVR, there were no differences in the in-hospital incidence of renal failure, bleeding, or stroke, but increased pacemaker requirement (odds ratio [OR], 3.45; P < .0001) and vascular injury (OR, 9.09; P < .0001) were noted in TAVR and higher hospital mortality (OR, 4.02; P < .0001) in SAVR+AF. SAVR+AF was associated with lower readmission for stroke compared with SAVR alone (hazard ratio [HR], 0.87; P = .029) and TAVR (HR, 0.68; P < .0001) and with improved survival vs TAVR (HR, 0.79; P = .019)., Conclusions: In Medicare beneficiaries with AF requiring aortic valve replacement, SAVR+AF was associated with improved longitudinal survival and freedom from stroke compared with TAVR. SAVR+AF treatment should be considered first-line therapy for patients with AF requiring aortic valve replacement., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Anaplasma phagocytophilum is an intracellular tick-transmitted bacterial pathogen that infects neutrophils in mammals and causes granulocytic anaplasmosis. In this study, we investigated the molecular chaperones ClpB and DnaK from A. phagocytophilum. In Escherichia coli, ClpB cooperates with DnaK and its co-chaperones DnaJ and GrpE in ATP-dependent reactivation of aggregated proteins. Since ClpB is not produced in metazoans, it is a promising target for developing antimicrobial therapies, which generates interest in studies on that chaperone's role in pathogenic bacteria. We found that ClpB and DnaK are transcriptionally upregulated in A. phagocytophilum 3-5 days after infection of human HL-60 and tick ISE6 cells, which suggests an essential role of the chaperones in supporting the pathogen's intracellular life cycle. Multiple sequence alignments show that A. phagocytophilum ClpB and DnaK contain all structural domains that were identified in their previously studied orthologs from other bacteria. Both A. phagocytophilum ClpB and DnaK display ATPase activity, which is consistent with their participation in the ATP-dependent protein disaggregation system. However, despite a significant sequence similarity between the chaperones from A. phagocytophilum and those from E. coli, the former were not as effective as their E. coli orthologs during reactivation of aggregated proteins in vitro and in supporting the survival of E. coli cells under heat stress. We conclude that the A. phagocytophilum chaperones might have evolved with distinct biochemical properties to maintain the integrity of pathogenic proteins under unique stress conditions of an intracellular environment of host cells., Competing Interests: Declarations of 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Nitroimidazoles comprise a class of broad-spectrum anti-microbial drugs with efficacy against parasites, mycobacteria, and anaerobic Gram-positive and Gram-negative bacteria. Among these drugs, metronidazole (MTZ) is commonly used with other antibiotics to prevent infection in open fractures. However, the effect of MTZ on bone remains understudied. In this paper, we evaluated six nitroimidazole drugs for their impact on osteoblast differentiation and identified MTZ as having the highest osteogenic effect. MTZ enhanced bone regeneration at the femur osteotomy site in osteopenic ovariectomized (OVX) rats at the human equivalent dose. Moreover, in OVX rats, MTZ significantly improved bone mass and strength and improved microarchitecture compared to the vehicle-treated rats, which was likely achieved by an osteogenic mechanism attributed to the stimulation of the Wnt pathway in osteoblasts. To mitigate the reported neurological and genotoxic effects of MTZ, we designed an injectable sustained-release in situ gel formulation of the drug that improved fracture healing efficacy by 3.5-fold compared to oral administration. This enhanced potency was achieved through a significant increase in the circulating half-life and bioavailability of MTZ. We conclude that MTZ exhibits osteogenic effects, further accentuated by our sustained-release delivery system, which holds promise for enhancing bone regeneration in open fractures.

Background: Despite prospective randomized evidence supporting concomitant treatment of atrial fibrillation (AF) during mitral valve (MV) surgery, variation in surgical management of AF remains. We assessed longitudinal outcomes after surgical treatment of persistent or paroxysmal AF during MV surgery in Medicare beneficiaries., Methods: All Medicare beneficiaries with a diagnosis of AF undergoing MV surgery (2018-2020) were evaluated. Patients were stratified by no AF treatment, left atrial appendage obliteration (LAAO) alone, or surgical ablation and LAAO (SA+LAAO). Doubly robust risk adjustment and subgroup analysis by persistent or paroxysmal AF were performed., Results: A total of 7517 patients with preoperative AF underwent MV surgery (32.1% no AF treatment, 23.1% LAAO alone, 44.7% SA+LAAO). After doubly robust risk adjustment, AF treatment with SA+LAAO or LAAO alone were associated with lower 3-year readmission for stroke or bleeding. However, SA+LAAO was associated with reduced 3-year mortality and readmission for AF or heart failure compared with no AF treatment or LAAO alone. Compared with no AF treatment or LAAO alone, SA+LAAO was associated with lower composite end point of stroke (hazard ratio, 0.75) or death (hazard ratio, 0.83) at 3 years. Subgroup analysis identified similar longitudinal benefits of SA+LAAO in patients with persistent or paroxysmal AF., Conclusions: In Medicare beneficiaries with AF undergoing MV surgery, SA+LAAO was associated with improved longitudinal outcomes compared with LAAO alone or no AF treatment in patients with paroxysmal or persistent AF. These contemporary real-world data further clarify the benefit of SA+LAAO during MV surgery across all types of AF., Competing Interests: Disclosures J. Scott Rankin reports financial support was provided by AtriCure Inc. The other authors have no conflicts of interest to disclose., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Phytosomes (phytophospholipid complex) are dosage forms that have recently been introduced to increase the stability and therapeutic effect of herbal medicine. Currently, bioactive herbs and the phytochemicals they contain are considered to be the best remedies for chronic diseases. One promising approach to increase the efficacy of plant-based therapies is to improve the stability and bioavailability of their bio-active ingredients. Phytosomes employ phospholipids as their active ingredients, and use their amphiphilic properties to solubilize and protect herbal extracts. The unique properties of phospholipids in drug delivery and their use in herbal medicines to improve bioavailability results in significantly enhanced health benefits. The introduction of phytosome nanotechnology can alter and revolutionize the current state of drug delivery. The goal of this review is to explain the application of phytosomes, their future prospects in drug delivery, and their advantages over conventional formulations. Please cite this article as: Chauhan D, Yadav PK, Sultana N, Agarwal A, Verma S, Chourasia MK, Gayen JR. Advancements in nanotechnology for the delivery of phytochemicals. J Integr Med. 2024; 22(4): 385-398., (Copyright © 2024 Shanghai Yueyang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine. Published by Elsevier B.V. All rights reserved.)

We report a 5-year-old girl with transient complete atrioventricular (AV) block following surgical closure of a symptomatic conoventricular ventricular septal defect (VSD) which recovered on post-operative day 9. She later presented with exertional dizziness and fatigue. While congenital cardiac defect repairs are occasionally complicated by complete heart block, this patient was found to have intra-Hisian Wenckebach which is rare in the pediatric population and can be very difficult to discern from surface electrocardiograms and by Holter monitoring. Mechanisms of post-surgical AV block, including intra-Hisian Wenckebach, are not well characterized in the pediatric population., (© 2023 The Authors. Pacing and Clinical Electrophysiology published by Wiley Periodicals LLC.)

Synthesis of nonameric cationic clusters [Dy 9 (acac) 16 (μ 3 -OH) 8 (μ 4 -OH) 2 ]OH·6H 2 O ( 1 ), [Dy 8 Tb (acac) 16 (μ 3 -OH) 8 (μ 4 -OH) 2 ]OH·2H 2 O ( 2 ), and [Gd 9 (acac) 16 (μ 3 -OH) 8 (μ 4 -OH) 2 ]OH·6H 2 O ( 3 ) (acac = acetylacetonate) is reported. The emission spectrum of 1 shows Dy(III) ion characteristic bands assignable to the 4 F 9/2 → 6 H J ( J = 15/2 to 9/2) transitions. Emission due to both Dy(III) and Tb(III) ions is observed for 2 in the visible range, with Tb(III) specific bands appearing due to the 5 D 4 → 7 F J ( J = 6, 4, and 3) transitions. Cluster 3 exhibits a significant magnetocaloric effect (MCE), with -Δ S m values increasing with decrease in temperature and increase in field, reaching -Δ S m max = 20.98 J kg -1 K -1 at 2 K and 9 T. Isotropic magnetic coupling constants ( J s ) in 3 derived from density functional theory (DFT) calculations reveal that the exchange interactions are antiferromagnetic and weak. Compound 3 possesses S = 7/2 ground state arising from the central Gd(III) ion along with several nested excited states due to competing antiferromagnetic interactions that yield reasonably large MCE values. Utilizing computed exchange coupling interactions, we have performed ab initio CASSCF/RASSI-SO/POL&#95;ANISO calculations on antiferromagnetic 1 and 2 to estimate the exchange interactions using the Lines model. For 2 , Dy(III)···Tb(III) exchange interactions were extracted for the first time and were found to be weakly antiferromagnetically coupled.

Five different millets (foxtail, little, barnyard, kodo and browntop) with and without sprouting were subjected to flaking. Phytic acid and phenolic content tends to decrease significantly, whereas antioxidant activity increased up to 77.32% on flaking of millets. A significant decrease in peak and final viscosity was observed in millet flakes. A-type diffraction pattern was predominant for unsprouted millets whereas the flaked millets showed V-type crystallinity. The protein digestibility significantly increased up to 37.77% in flakes made from sprouted millets. The mineral bioavailability upon flaking of millets increased, especially Ca (88.22% for little), Fe (43.04% for barnyard) and Zn (61.77% for kodo), which is attributed to the reduction in phytic acid. Flaking, however, led to an increase in rapidly and slowly digestible starch with a corresponding decrease in resistant starch. Among the unsprouted and sprouted millet flakes, foxtail received the highest sensory scores for overall acceptability., Competing Interests: Declaration of competing interest The authors state that they have no personal relationships or conflicting financial interests that could have appeared to have an impact on the work discussed in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Enterobacter cloacae cardiac implantable electronic device infections are rare but can be associated with significant morbidity and mortality. We report an 11-year-old female with Enterobacter cloacae infection of a dual-chamber transvenous pacemaker pocket. The report is supplemented by a comprehensive review of the literature on Enterobacter cloacae cardiac implantable electronic device infections., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Immunogenic cell death (ICD) is a form of cell death by which cancer treatments can induce a clinically relevant antitumor immune response in a broad range of cancers. In multiple myeloma (MM), the proteasome inhibitor bortezomib is an ICD inducer and creates durable therapeutic responses in patients. However, eventual relapse and resistance to bortezomib appear inevitable. Here, by integrating patient transcriptomic data with an analysis of calreticulin (CRT) protein interactors, we found that GABA type A receptor-associated protein (GABARAP) is a key player whose loss prevented tumor cell death from being perceived as immunogenic after bortezomib treatment. GABARAP is located on chromosome 17p, which is commonly deleted in patients with high risk MM. GABARAP deletion impaired the exposure of the eat-me signal CRT on the surface of dying MM cells in vitro and in vivo, thus reducing tumor cell phagocytosis by dendritic cells and the subsequent antitumor T-cell response. Low GABARAP was independently associated with shorter survival in patients with MM and reduced tumor immune infiltration. Mechanistically, we found that GABARAP deletion blocked ICD signaling by decreasing autophagy and altering Golgi apparatus morphology, with consequent defects in the downstream vesicular transport of CRT. Conversely, upregulating autophagy using rapamycin restored Golgi morphology, CRT exposure, and ICD signaling in GABARAPKO cells undergoing bortezomib treatment. Therefore, coupling an ICD inducer, such as bortezomib, with an autophagy inducer, such as rapamycin, may improve patient outcomes in MM, in which low GABARAP in the form of del(17p) is common and leads to worse outcomes., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Bisphenols (BP), including BPA and "BPA-free" structural analogs, are commonly used plasticizers that are present in many plastics and are known endocrine disrupting chemicals. Prenatal exposure to BPA has been associated with negative neurodevelopmental and behavioral outcomes in children and in rodent models. Prenatal BPA exposure has also been shown to impair postnatal maternal care provisioning, which can also affect offspring neurodevelopment and behavior. However, there is limited knowledge regarding the biological effects of prenatal exposure to bisphenols other than BPA and the interplay between prenatal bisphenol exposure and postnatal maternal care on adult behavior. The purpose of the current study was to determine the interactive impact of prenatal bisphenol exposure and postnatal maternal care on neurodevelopment and behavior in rats. Our findings suggest that the effects of prenatal bisphenol exposure on eye-opening, adult attentional set shifting and anxiety-like behavior in the open field are dependent on maternal care in the first five days of life. Interestingly, maternal care might also attenuate the effects of prenatal bisphenol exposure on eye opening and adult attentional set shifting. Finally, transcriptomic profiles in male and female medial prefrontal cortex and amygdala suggest that the interactive effects of prenatal bisphenol exposure and postnatal maternal care converge on estrogen receptor signaling and are involved in biological processes related to gene expression and protein translation and synthesis. Overall, these findings indicate that postnatal maternal care plays a critical role in the expression of the effects of prenatal bisphenol exposure on neurodevelopment and adult behavior. Understanding the underlying biological mechanisms involved might allow us to identify potential avenues to mitigate the adverse effects of prenatal bisphenol exposure and improve health and well-being in human populations., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lauby et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Vestibular schwannomas (VS) are the most common tumor of the skull base with available treatment options that carry a risk of iatrogenic injury to the facial nerve, which can significantly impact patients' quality of life. As facial nerve outcomes remain challenging to prognosticate, we endeavored to utilize machine learning to decipher predictive factors relevant to facial nerve outcomes following microsurgical resection of VS. A database of patient-, tumor- and surgery-specific features was constructed via retrospective chart review of 242 consecutive patients who underwent microsurgical resection of VS over a 7-year study period. This database was then used to train non-linear supervised machine learning classifiers to predict facial nerve preservation, defined as House-Brackmann (HB) I vs. facial nerve injury, defined as HB II-VI, as determined at 6-month outpatient follow-up. A random forest algorithm demonstrated 90.5% accuracy, 90% sensitivity and 90% specificity in facial nerve injury prognostication. A random variable (rv) was generated by randomly sampling a Gaussian distribution and used as a benchmark to compare the predictiveness of other features. This analysis revealed age, body mass index (BMI), case length and the tumor dimension representing tumor growth towards the brainstem as prognosticators of facial nerve injury. When validated via prospective assessment of facial nerve injury risk, this model demonstrated 84% accuracy. Here, we describe the development of a machine learning algorithm to predict the likelihood of facial nerve injury following microsurgical resection of VS. In addition to serving as a clinically applicable tool, this highlights the potential of machine learning to reveal non-linear relationships between variables which may have clinical value in prognostication of outcomes for high-risk surgical procedures., (© 2024. The Author(s).)

Background and Objectives: Neural tube defects (NTDs) are an important cause of global morbidity worldwide. Well-planned global neurosurgery and public health efforts can aid vulnerable communities, but there is a need to elucidate the global burden of NTDs and identify regions without available data to better target interventions., Methods: A scoping review to quantify worldwide NTD prevalence using the PubMed/Medline and birth defects surveillance registries was conducted. Data published after January 1, 1990, encompassing prevalence values of at least the 2 most prevalent NTDs-spina bifida and encephalocele-were abstracted. Average NTD prevalence rates were aggregated by World Health Organization (WHO) region and World Bank classification, and differences were determined using the analysis of variance test. Differences in availability of nationally representative data by WHO region and World Bank classification were determined using χ2 tests., Results: This review captured 140 studies from a total of 93 of 194 WHO member countries. The percentage of countries within a geographic region with available NTD prevalence data was highest in the Eastern Mediterranean (EMR) (85.7%) and lowest in Africa (AFR) (31.3%). The NTD prevalence range was 0.9-269.6 per 10 000 births. Statistically significant differences in reported NTD prevalence rates existed by WHO Region (P = .00027) and World Bank income level of study country (P = .00193). Forty countries (43%) had conducted national-level studies assessing NTD prevalence. There was a statistically significant difference in the availability of nationally representative prevalence data depending on the WHO region (P = .0081) and World Bank classification of study country (P = .0017)., Conclusion: There is a gap in availability of NTD prevalence data worldwide, with many WHO member states lacking national-level NTD prevalence estimates. These findings highlight the need for greater NTD surveillance efforts to identify the countries with the greatest need for targeted global intervention., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Sesame (Sesamum indicum L.) is a globally cultivated oilseed crop renowned for its historical significance and widespread growth in tropical and subtropical regions. With notable nutritional and medicinal attributes, sesame has shown promising effects in combating malnutrition cancer, diabetes, and other diseases like cardiovascular problems. However, sesame production faces significant challenges from environmental threats such as charcoal rot, drought, salinity, and waterlogging stress, resulting in economic losses for farmers. The scarcity of information on stress-resistance genes and pathways exacerbates these challenges. Despite its immense importance, there is currently no platform available to provide comprehensive information on sesame, which significantly hinders the mining of various stress-associated genes and the molecular breeding of sesame. To address this gap, here a free, web-accessible, and user-friendly genomic web resource (SesameGWR, http://backlin.cabgrid.res.in/sesameGWR/) has been developed This platform provides key insights into differentially expressed genes, transcription factors, miRNAs, and molecular markers like simple sequence repeats, single nucleotide polymorphisms, and insertions and deletions associated with both biotic and abiotic stresses.. The functional genomics information and annotations embedded in this web resource were predicted through RNA-seq data analysis. Considering the impact of climate change and the nutritional and medicinal importance of sesame, this study is of utmost importance in understanding stress responses. SesameGWR will serve as a valuable tool for developing climate-resilient sesame varieties, thereby enhancing the productivity of this ancient oilseed crop., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Lower institutional volume has been associated with inferior pediatric cardiac surgery outcomes. This study explored the variation in mortality rates among low-, mid-, and high-volume hospitals performing pediatric cardiac surgery in the United States., Methods: The Kids' Inpatient Database was explored for the years 2016 and 2019. Hospitals performing only off-bypass coarctation and ventricular septal defect repair were omitted. The hospitals were divided into 3 groups by their annual case volume. Multivariable logistic regression models were fit to obtain risk-adjusted in-hospital mortality rates., Results: A total of 25,749 operations performed by 235 hospitals were included in the study. The risk-adjusted mortality rate for the entire sample was 1.9%. There were 140 hospitals in the low-volume group, 64 hospitals in the mid-volume group, and 31 in the high-volume group. All groups had low-mortality (mortality <1.9%) and high-mortality (mortality >1.9%) hospitals. Among low-volume hospitals, 53% were low-mortality (n = 74) and 47% were high-mortality (n = 66) hospitals. Among mid-volume hospitals, 58% were low-mortality (n = 37) and 42% were high-mortality (n = 27) hospitals. Among high-volume hospitals, 68% were low-mortality (n = 21) and 32% were high-mortality (n = 10) hospitals. There was no statistically significant difference in risk-adjusted in-hospital mortality when comparing low-, mid-, and high-volume centers for 7 Society of Thoracic Surgeons benchmark procedures., Conclusions: This national, real-world, risk-adjusted volume outcome analysis highlights that volume alone may not be the sole arbiter to predict quality of pediatric cardiac surgery outcomes. Using case volume alone as a surrogate for quality may unfairly asperse high-performing, low-volume programs., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The use of marijuana, derived from the Cannabis plant, has a lengthy history dating back thousands of years. With the recent legalization of marijuana in many US states, concerns about its health effects have grown. Despite traditional beliefs in its cardioprotective properties, there is a rising incidence of marijuana-induced pericarditis. This article presents a case that highlights the potential connection between marijuana use and cardiac complications. We herein present a case of a 30-year-old male with habitual marijuana use coming in with pericarditis., Case: A 30-year-old male, a habitual marijuana user, presented to the emergency department with recurrent chest pain and shortness of breath. Notably, similar episodes were resolved when he abstained from marijuana. Diagnostic findings upon admission included elevated inflammatory markers, EKG showing diffuse ST segment elevations and PR depressions, echocardiographic evidence of pericardial effusion and EKG consistent with pericarditis. After excluding other causes, marijuana was identified as the likely trigger for his cardiac symptoms., Decision Making: NSAIDS and colchicine were started at therapeutic doses for the patient. Cardiology and Cardiothoracic Surgery were consulted. No drainage was planned as patient was clinically stable and improved with medical management alone., Conclusion: The emerging link between marijuana use and pericarditis presents a unique clinical challenge. Comprehensive population-based studies are needed to understand the cardiovascular implications of marijuana use and to develop appropriate management guidelines. Clinicians should approach marijuana use cautiously, considering potential cardiovascular risks, and remain vigilant for pericarditis as a potential consequence of marijuana use during patient evaluations., Competing Interests: Conflict of interest: The authors have no conflicts of interest to declare. All co-authors have seen and agree with the contents of the manuscript and there is no financial interest to report. We certify that the submission is original work and is not under review at any other publication., (© 2024 Greater Baltimore Medical Center.)

Background: Societal guidelines support concomitant management of atrial fibrillation (AF) in patients undergoing cardiac surgery. To assess real-world adoption and outcomes, this study evaluated Medicare beneficiaries with AF who underwent isolated coronary artery bypass grafting (CABG) with surgical ablation (SA) or left atrial appendage obliteration (LAAO) or both procedures in combination (SA + LAAO)., Methods: The US Centers for Medicare & Medicaid Services inpatient claims database identified all patients with AF who underwent isolated CABG from 2018 to 2020. Diagnosis-related group and International Classification of Diseases-10th revision procedure codes defined covariates for doubly robust risk adjustment., Results: A total of 19,524 patients with preoperative AF who underwent isolated CABG were stratified by SA + LAAO (3475 patients; 17.8%), LAAO only (4541 patients; 23.3%), or no AF treatment (11,508 patients; 58.9%). After doubly robust risk adjustment, longitudinal analysis highlighted that concomitant AF treatment with SA + LAAO (hazard ratio [HR], 0.74; P = .049) or LAAO alone (HR, 0.75; P = . 031) was associated with a significant reduction in readmission for stroke at 3 years compared with no AF treatment. Furthermore, SA + LAAO (HR, 0.86; P = .016) but not LAAO alone (HR, 0.97; P = .573) was associated with improved survival compared with no AF treatment. Finally, SA + LAAO was associated with a superior composite outcome of freedom from stroke or death at 3 years compared with LAAO alone (HR, 0.86;, P = .033) or no AF treatment (HR, 0.81; P = .001)., Conclusions: In Medicare beneficiaries with AF who underwent isolated CABG, concomitant AF treatment was associated with reduced 3-year readmission for stroke. SA + LAAO was associated with superior reduction in stroke or death at 3 years compared with LAAO alone or no AF treatment., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: Recent approval of transcatheter aortic valve replacement (TAVR) in patients at low surgical risk has resulted in a rapid real-world expansion of TAVR in patients not otherwise examined in recent low-risk trials. We sought to evaluate the outcomes of surgical aortic valve replacement (SAVR) versus TAVR in low-risk Medicare beneficiaries., Methods: Using the US Centers for Medicare and Medicaid Services claims database, we evaluated all beneficiaries undergoing isolated SAVR (n = 33,210) or TAVR (n = 77,885) (2018-2020). International Classification of Diseases 10th revision codes were used to define variables and frailty was defined by the validated Kim index. Doubly robust risk adjustment was performed with inverse probability weighting and multilevel regression models, as well as competing-risk time to event analysis. A low-risk cohort was identified to simulate recent low-risk trials., Results: A total of 15,749 low-risk patients (8144 SAVR and 7605 TAVR) were identified. Comparison was performed with doubly robust risk adjustment accounting for all factors. TAVR was associated with lower perioperative stroke (odds ratio, 0.62; P < .001) and hospital mortality (odds ratio, 0.16; P < .001) compared with SAVR. However, risk-adjusted longitudinal analysis demonstrated TAVR was associated with higher late risk of stroke (hazard ratio, 1.65; P < .001), readmission for valve reintervention (hazard ratio, 1.88; P < .001), and all-cause mortality (hazard ratio, 1.54; P < .001) compared with SAVR., Conclusions: Among low-risk Medicare beneficiaries younger than age 75 years undergoing isolated AVR, SAVR was associated with higher index morbidity and mortality but improved 3-year risk-adjusted stroke, valve reintervention, and survival compared with TAVR., Competing Interests: Conflict of Interest Statement Dr Rankin serves as a consultant to Atricure. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2024 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Introduction: Novel injectables possess applications in both local and systemic therapeutics delivery. The advancement in utilized materials for the construction of complex injectables has tremendously upgraded their safety and efficacy., Areas Covered: This review focuses on various strategies to produce novel injectables, including oily dispersions, in situ forming implants, injectable suspensions, microspheres, liposomes, and antibody-drug conjugates. We herein present a detailed description of complex injectable technologies and their related drug formulations permitted for clinical use by the United States Food and Drug Administration (USFDA). The excipients used, their purpose and the challenges faced during manufacturing such formulations have been critically discussed., Expert Opinion: Novel injectables can deliver therapeutic agents in a controlled way at the desired site. However, several challenges persist with respect to their genericization. Astronomical costs incurred by innovator companies during product development, complexity of the product itself, supply limitations with respect to raw materials, intricate manufacturing processes, patent evergreening, product life-cycle extensions, relatively few and protracted generic approvals contribute to the exorbitant prices and access crunch. Moreover, regulatory guidance are grossly underdeveloped and significant efforts have to be directed toward development of effective characterization techniques.

KCNT1 mutations are associated with childhood epilepsy, developmental delay, and vascular malformations. We report a child with a likely pathogenic KCNT1 mutation (c.1885A>C, p.Lys629Glu) with recurrent pulmonary haemorrhage due to aortopulmonary collaterals successfully managed with coil embolisation followed by right upper lobectomy.

Objective: Race plays a salient role in access to surgical care. However, few investigations have assessed the impact of race within surgical populations after care has been delivered. The objective of this study was to employ an exact matching protocol to a homogenous population of spine surgery patients in order to isolate the relationships between race and short-term postoperative outcomes., Methods: In total, 4263 consecutive patients who underwent single-level, posterior-only lumbar fusion at a single multihospital academic medical center were retrospectively enrolled. Of these patients, 3406 patients self-identified as White and 857 patients self-identified as non-White. Outcomes were initially compared across all patients via logistic regression. Subsequently, White patients and non-White patients were exactly matched on the basis of key demographic and health characteristics (1520 matched patients). Outcome disparities were evaluated between the exact-matched cohorts. Primary outcomes were readmissions, emergency department (ED) visits, reoperations, mortality, intraoperative complications, and discharge disposition., Results: Before matching, non-White patients were less likely to be discharged home and more likely to be readmitted, evaluated in the ED, and undergo reoperation. After matching, non-White patients experienced higher rates of nonhome discharge, readmissions, and ED visits. Non-White patients did not have more surgical complications either before or after matching., Conclusions: Between otherwise similar cohorts of spinal fusion cases, non-White patients experienced unfavorable discharge disposition and higher risk of multiple adverse postoperative outcomes. However, these findings were not accounted for by differences in surgical complications, suggesting that structural factors underlie the observed disparities.

Background and Objectives: Race has implications for access to medical care. However, the impact of race, after access to care has been attained, remains poorly understood. The objective of this study was to isolate the relationship between race and short-term outcomes across patients undergoing a single, common neurosurgical procedure., Methods: In this retrospective cohort study, 3988 consecutive patients undergoing single-level, posterior-only open lumbar fusion at a single, multihospital, academic medical center were enrolled over a 6-year period. Among them, 3406 patients self-identified as White, and 582 patients self-identified as Black. Outcome disparities between all White patients vs all Black patients were estimated using logistic regression. Subsequently, coarsened exact matching controlled for outcome-mitigating factors; White and Black patients were exact-matched 1:1 on key demographic and health characteristics (matched n = 1018). Primary outcomes included 30-day and 90-day hospital readmissions, emergency department (ED) visits, reoperations, mortality, discharge disposition, and intraoperative complication., Results: Before matching, Black patients experienced increased rate of nonhome discharge, readmissions, ED visits, and reoperations (all P < .001). After exact matching, Black patients were less likely to be discharged to home (odds ratio [OR] 2.68, P < .001) and had higher risk of 30-day and 90-day readmissions (OR 2.24, P < .001; OR 1.91, P < .001; respectively) and ED visits (OR 1.79, P = .017; OR 2.09, P < .001). Black patients did not experience greater risk of intraoperative complication (unintentional durotomy)., Conclusion: Between otherwise homogenous spinal fusion cohorts, Black patients experienced unfavorable short-term outcomes. These disparities were not explained by differences in intraoperative complications. Further investigation must characterize and mitigate institutional and societal factors that contribute to outcome disparities., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

The NACHT-, leucine-rich-repeat-, and pyrin domain-containing protein 3 (NLRP3) is a critical intracellular inflammasome sensor and an important clinical target against inflammation-driven human diseases. Recent studies have elucidated its transition from a closed cage to an activated disk-like inflammasome, but the intermediate activation mechanism remains elusive. Here we report the cryo-electron microscopy structure of NLRP3, which forms an open octamer and undergoes a ~ 90° hinge rotation at the NACHT domain. Mutations on open octamer's interfaces reduce IL-1β signaling, highlighting its essential role in NLRP3 activation/inflammasome assembly. The centrosomal NIMA-related kinase 7 (NEK7) disrupts large NLRP3 oligomers and forms NEK7/NLRP3 monomers/dimers which is a critical step preceding the assembly of the disk-like inflammasome. These data demonstrate an oligomeric cooperative activation of NLRP3 and provide insight into its inflammasome assembly mechanism., (© 2024. The Author(s).)

Aim: A newer LC-MS/MS method was developed and validated for the simultaneous quantification of raloxifene (RL) and cladrin (CL). Methodology: Both drugs were resolved in RP-18 (4.6 × 50 mm, 5 μ) Xbridge Shield column using acetonitrile and 0.1% aqueous solution of formic acid (FA) (70:30% v/v) as mobile phase by using biological matrices in female Sprague-Dawley rats using-MS/MS. Results: The developed method was found to be linear over the concentration ranges of 1-600 ng/ml, and lower limit of quantification was 1 ng/ml for RL and CL, respectively. Pharmacokinetic results of RL+CL showed C max  = 4.23 ± 0.61, 26.97 ± 1.14 ng/ml, at T max (h) 5.5 ± 1.00 and 3.5 ± 1.00, respectively. Conclusion: Pharmacokinetic study results will be useful in the future for the combined delivery of RL and CL for osteoporosis treatment.

Objective: Augmented reality (AR) is an emerging technology that may accelerate skill acquisition and improve accuracy of thoracolumbar pedicle screw placements. We aimed to quantify the relative assistance of AR compared with freehand (FH) pedicle screw accuracy across different surgical experience levels., Methods: A spine fellowship-trained and board-certified attending neurosurgeon, postgraduate year 4 neurosurgery resident, and second-year medical student placed 32 FH and 32 AR-assisted thoracolumbar pedicle screws in 3 cadavers. A cableless, voice-activated AR system was paired with a headset. Accuracy was assessed using χ 2 analysis and the Gertzbein-Robbins scale. Angular error, distance error, and time per pedicle screw were collected and compared., Results: The attending neurosurgeon had 91.6% (11/12) clinically acceptable (Gertzbein-Robbins scale A or B) insertion in both FH and AR groups; the resident neurosurgeon had 100% (9/9) FH and AR in both cases; the medical student had 72.3% (8/11) FH accuracy and 81.8% (9/11) AR accuracy. The medical student displayed significantly lower ideal (Gertzbein-Robbins scale A) FH accuracy compared with the resident neurosurgeon (P = 0.017) and attending neurosurgeon (P = 0.005), but no difference when using AR. FH screw placement was faster by both the attending neurosurgeon (median 46 seconds vs. 94.5 seconds, P = 0.0047) and the neurosurgery resident neurosurgeon (median 144 seconds vs. 140 seconds, P = 0.05). Total clinically acceptable AR and FH accuracy was 90.6% (29/32) and 87.5% (28/32), respectively (P = 0.69)., Conclusions: AR screw placement allowed an inexperienced medical student to double their accuracy in 1 training session. With subsequent iterations, this promising technology could serve as an important tool for surgical training., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Drought and heat frequently co-occur during crop growth leading to devastating yield loss. The knowledge of the genetic loci governing component traits of yield under combined drought and heat stress is essential for enhancing the climate resilience. The present study employed a mapping population of 180 recombinant inbred lines (RILs) derived from a cross between GW322 and KAUZ to identify quantitative trait loci (QTLs) governing the component traits of yield under heat and combined stress conditions. Phenotypic evaluation was conducted across two consecutive crop seasons (2021-2022 and 2022-2023) under late sown irrigation (LSIR) and late sown restricted irrigation (LSRI) conditions at the Indian Council of Agricultural Research Institute-Indian Agricultural Research Institute (ICAR-IARI), New Delhi. Various physiological and agronomic traits of importance were measured. Genotyping was carried out with 35K SNP Axiom breeder's genotyping array. The linkage map spanned a length of 6769.45 cM, ranging from 2.28 cM/marker in 1A to 14.21 cM/marker in 5D. A total of 35 QTLs were identified across 14 chromosomes with 6B containing the highest (seven) number of QTLs. Out of 35 QTLs, 16 were major QTLs explaining the phenotypic variance greater than 10%. The study identified eight stable QTLs along with two hotspots on chromosomes 6B and 5B. Five QTLs associated with traits thousand-grain weight (TGW), normalized difference vegetation index (NDVI), and plant height (PH) were successfully validated. Candidate genes encoding antioxidant enzymes, transcription factors, and growth-related proteins were identified in the QTL regions. In silico expression analysis highlighted higher expression of transcripts TraesCS2D02G021000.1, TraesCS2D02G031000, TraesCS6A02G247900, and TraesCS6B02G421700 under stress conditions. These findings contribute to a deeper understanding of the genetic architecture underlying combined heat and drought tolerance in wheat, providing valuable insights for wheat improvement strategies under changing climatic conditions., 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 Manjunath, Krishna, Devate, Sunilkumar, Patil, Chauhan, Singh, Kumar, Jain, Singh and Singh.)

Background and Objectives: Smartphone activity data recorded through high-fidelity accelerometry can provide accurate postoperative assessments of patient mobility. The "big data" available through smartphones allows for advanced analyses, yielding insight into patient well-being. This study compared rate of change in functional activity data between lumbar fusion (LF) and lumbar decompression (LD) patients to determine preoperative and postoperative course differences., Methods: Twenty-three LF and 18 LD patients were retrospectively included. Activity data (steps per day) recorded in Apple Health, encompassing over 70 000 perioperative data points, was classified into 6 temporal epochs representing distinct functional states, including acute preoperative decline, immediate postoperative recovery, and postoperative decline. The daily rate of change of each patient's step counts was calculated for each perioperative epoch., Results: Patients undergoing LF demonstrated steeper preoperative declines than LD patients based on the first derivative of step count data (P = .045). In the surgical recovery phase, LF patients had slower recoveries (P = .041), and LF patients experienced steeper postoperative secondary declines than LD patients did (P = .010). The rate of change of steps per day demonstrated varying perioperative trajectories that were not explained by differences in age, comorbidities, or levels operated., Conclusion: Patients undergoing LF and LD have distinct perioperative activity profiles characterized by the rate of change in the patient daily steps. Daily steps and their rate of change is thus a valuable metric in phenotyping patients and understanding their postsurgical outcomes. Prospective studies are needed to expand upon these data and establish causal links between preoperative patient mobility, patient characteristics, and postoperative functional outcomes., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Background: Several studies have been conducted on 4-H chromene compounds because of their intriguing pharmacological and biological properties. Various new natural compounds having a chromene foundation have been reported over the past 20 years., Objective: In the present study, we reported the acute oral toxicity, antioxidant activity, and molecular docking study of the most active 4H-chromene derivative2-(4-Bromo-phenoxy)-N-[6-chloro-4-(4- chlorophenyl)-3-cyano-4H-chromen-2-yl]-acetamide (A9)., Method: The acute oral toxicity was carried out as per OECD 423 guidelines. For investigating the antioxidant activity, various biochemical parameters in colon tissue like SOD, CAT, MDA, PC and GSH and also enzyme levels, such as ALT, AST, ALP, and LDH, were measured in this experiment., Results: Acute oral toxicity study indicated that the A9 ligand was found to be safer in animals. Additionally, the A9 ligand had significant antioxidant properties at various doses and was not found to be harmful to the liver. Due to its stronger binding energy and the appropriate interactions that induce inhibition, the A9 ligand's antioxidant function was also validated by additional molecular docking research., Conclusion: This compound can be exploited as a lead molecule in further research., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)