Gender differences in cardiovascular outcomes of kidney transplant recipients: A retrospective cohort study.

The purpose of this study was to investigate gender differences in cardiovascular outcomes of kidney transplant recipients (KTRs). Here, a retrospective cohort study was conducted, and data from the National Health Insurance Research Database in Taiwan were used. In total, 2904 patients who had end-stage renal disease (ERSD) and received kidney transplantation (KT) were identified by propensity score matching (PSM) and were enrolled from 1997 to 2012, with follow-up ending in 2013. Besides, major adverse cardiovascular events (MACEs) were defined as a composite of all-cause mortality, nonfatal myocardial infarction, and nonfatal strokes. Apart from that, hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated by Cox regression, while the Bayesian network model was constructed to assess the importance of risk factors for MACEs. Furthermore, the original cohort was a sensitivity analysis. Women had a lower risk of MACEs compared with men (hazard ratio [HR]: 0.84; 95% CI: 0.72-0.98; P = .024). Beyond that, stratified analysis of age and waiting time for KT showed that the risk of MACEs was significantly lower in women than in men among KTRs aged > 50 years (HR: 0.79; 95% CI: 0.62-1.0; P = .05) or waiting time for KT ≤ 6 years (HR: 0.85; 95% CI: 0.72-0.99; P = .04). Bayesian network indicated that age is an important determinant of cardiovascular outcomes in KTRs, regardless of gender. In Taiwan, women had a lower risk of adverse cardiovascular outcomes than men in KTRs aged > 50 years or with a waiting time for KT ≤ 6 years. Furthermore, age is an important independent determinant for the prognosis of KTRs.

G3BP2 promotes tumor progression and gemcitabine resistance in PDAC via regulating PDIA3-DKC1-hENT in a stress granules-dependent manner.

Pancreatic ductal adenocarcinoma (PDAC) is distinguished by its aggressive malignancy, limited treatment avenues and a tendency towards chemotherapy resistance, underscoring the critical need for advanced research to uncover new therapeutic approaches. Stress granules (SGs) that is implicated in cellular self-protection mechanism, along with its associated family molecules have shown pro-cancer effects and are closely related to tumor chemotherapy resistance. In this study we investigated the relationship between Ras GTPase-activating protein-binding proteins 2 (G3BP2), a core component of SGs, and the malignancy of PDAC as well as its resistance to the chemotherapy drug gemcitabine. Analyzing TCGA dataset revealed that the expression of G3BP1 and G3BP2 was significantly upregulated in PDAC compared with adjacent normal pancreatic tissues, and the high expression of G3BP2 rather than G3BP1 was significantly associated with poorer overall survival (OS) in PDAC patients. We demonstrated that knockdown of G3BP2 inhibited the proliferation and invasion of PANC-1 and CFPAC-1 cells in vitro and in vivo. By analyzing the differentially expressed genes in G3BP2 knockdown and overexpressed PANC-1 cells, we identified DKC1 that was associated with RNA stability and regulation as the target of G3BP2. We demonstrated that G3BP2 bound to PDIA3 mRNA and recruited them into SGs, increasing the stability of PDIA3 mRNA and attenuating its translation efficiency, thereby promoting DKC1 expression. Furthermore, DKC1 could bind to hENT mRNA and inhibited its expression, which enhanced gemcitabine resistance of PDAC. Therefore, we propose a novel mechanism wherein G3BP2 facilitates PDAC's resistance to chemotherapy by modulating PDIA3-DKC1-hENT in a SGs-dependent way, suggesting G3BP2 SGs a protentional therapeutic target for the treatment in PDAC.

A nationwide survey on the management of neonatal respiratory distress syndrome: insights from the MUNICH survey in 394 Chinese hospitals.

BACKGROUND: At present, preterm infants with respiratory distress syndrome (RDS) in China present higher mortality and morbidity rates than those in high-income countries. The aim of this nationwide survey was to assess the clinical management of RDS in China. METHODS: A nationwide cross-sectional survey to assess adherence to RDS management recommendations was performed. One neonatologist per hospital was randomly selected. The primary outcome was the key care of RDS management. RESULTS: Among the 394 participating hospitals, 88·3% were birthing centres. The number of doctors and nurses per bed were 0·27 and 0·72, respectively. Antenatal corticosteroids (any dose) were administered to 90% of the women at risk of preterm birth at < 34 weeks of gestation (90·0% inborn vs. 50·0% outborn, p < 0·001). The median fraction of inspired oxygen (FiO2) for initial resuscitation was 0·30 for babies born at ≤ 32 weeks of gestation and 0·25 for those born at > 32 weeks. T-piece resuscitators were available in 77·8% of delivery rooms (DRs) (tertiary hospitals: 82·5% vs. secondary hospitals: 63·0%, p < 0·001). Surfactant was used in 51·6% of the DRs. Less invasive surfactant administration (LISA) was used in 49·7% of the hospitals (tertiary hospitals: 55·3% vs. secondary hospitals: 31·5%, p < 0·001). Primary non-invasive ventilation was initiated in approximately 80·0% of the patients. High-frequency oscillation ventilation was primarily reserved for rescue after conventional mechanical ventilation (MV) failure. Caffeine was routinely used during MV in 59·1% of the hospitals. Bedside lung ultrasonography was performed in 54·3% of the health facilities (tertiary hospitals: 61·6% vs. secondary hospitals: 30·4%, p < 0·001). Qualified breast milk banks and Family Integrated Care (FICare) were present in 30·2% and 63·7% of the hospitals, respectively. CONCLUSIONS: Significant disparities in resource availability and guidelines adherence were evident across hospitals. Future strategies should address DR facilities and medication access, technical training, staff allocation, and ancillary facility development for a better management of RDS patients in China.

Self-templated fabrication of P-doped CoMoO4-Co3O4 hollow nanocages for the efficient oxygen evolution reaction.

Finding reservoir-rich and efficient electrocatalysts for the alkaline oxygen evolution reaction (OER) is crucial for further sustainable energy development. Despite the advantages of high earth abundance, easy availability, and tunable composition, transition-metal oxides are typically considered poor electrocatalysts for the OER. In this study, a composite P-doped CoMoO4-Co3O4 hollow nanocage is deliberately synthesized through a cation-exchange, pyrolysis, and phosphorization approach using an innovative self-template strategy with ZIF-67 as the sacrificial template. Hollow nanocages provide large surface areas and abundant active sites, enhancing electron transfer. Hybridization with other components increases the number of electrochemically reactive sites and optimizes the advantages of different element components. As a result, the P-CoMoO4-Co3O4 hollow nanocage catalyst demonstrates high OER performance, with an overpotential of 279 mV at a current density of 10 mA cm-2. Additionally, P-CoMoO4-Co3O4 catalysts exhibit good dispersibility and excellent long-term stability. Experimental findings and density functional theory (DFT) calculations indicate that the phosphorus-doping effect in various aspects contributes significantly to the superior catalytic activity of P-CoMoO4-Co3O4. This work provides a valuable method for designing cost-effective P doped Co-based bimetal oxide catalysts with outstanding OER performance for industrial applications.

Perovskite-silicon tandem solar cells with bilayer interface passivation.

Two-terminal monolithic perovskite-silicon tandem solar cells demonstrate huge advantages in power conversion efficiency (PCE) compared to their respective single-junction counterparts1,2. However, suppressing interfacial recombination at the wide-bandgap perovskite/electron transport layer interface, without compromising its superior charge transport performance, remains a significant challenge for perovskite-silicon tandem cells3,4. By exploiting the nanoscale discretely distributed LiF ultrathin layer followed by an additional deposition of diammonium diiodide molecule, we have devised a bilayer intertwined passivation strategy that combines efficient electron extraction with further suppression of nonradiative recombination. We constructed perovskite-silicon tandem devices on double-side textured Czochralski (CZ)-based silicon heterojunction cell, which featured a mildly-textured front surface and a heavily-textured rear surface, leading to simultaneously enhanced photocurrent and uncompromised rear passivation. The resulting perovskite-silicon tandem achieved an independently certified stabilized PCE of 33.89%, accompanied by an impressive fill factor (FF) of 83.0% and an open-circuit voltage (Voc) of nearly 1.97 volts. To our knowledge, this represents the first reported certified efficiency of a two-junction tandem solar cell exceeding the single-junction Shockley-Queisser limit of 33.7%.

CircRREB1 Mediates Metabolic Reprogramming and Stemness Maintenance to Facilitate Pancreatic Ductal Adenocarcinoma Progression.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal tumor with limited treatment options and poor patient survival. Circular RNAs (circRNAs) play crucial regulatory roles in the occurrence and development of various cancers, including PDAC. Here, using circRNA sequencing of diverse PDAC samples, we identified circRREB1 as an oncogenic circRNA that is significantly upregulated in PDAC and is correlated with an unfavorable patient prognosis. Functionally, loss of circRREB1 markedly inhibited glycolysis and stemness, while elevated circRREB1 elicited the opposite effects. Mechanistically, circRREB1 interacted with PGK1, disrupting the association between PTEN and PGK1 and increasing PGK1 phosphorylation to activate glycolytic flux. Moreover, circRREB1 promoted WNT7B transcription by directly interacting with YBX1 and facilitating its nuclear translocation, consequently activating the Wnt/ß-catenin signaling pathway to maintain PDAC stemness. Overall, these results highlight circRREB1 as a key regulator of metabolic and stemness properties of PDAC.

Hydration effect and molecular geometry conformation as critical factors affecting the longevity stability of G4-structure-based supramolecular hydrogels.

Nucleoside-derived supramolecular hydrogels based on G4-structures have been extensively developed in the biomedical sector and recognized for superior excellent biocompatibility and biodegradability. However, limited longevity and stability present a significant challenge. Chemical modifications in the molecular structure have been shown to enhance the longevity stability of G4-structure-based supramolecular hydrogels, but the precise way in which the molecular structure impacts the stability of the G4-structures and consequently affects the properties of the hydrogel remains to be elucidated. This issue represents a notable challenge in the field, which restricts their further applications to some extent. In this study, single crystals of Gd, αGd and αGd* were cultivated and compared with G. Notably, before this study, the single crystal structures of all natural nucleosides, with the exception of Gd, had been determined. The investigation into the molecular structure and supramolecular self-assembly properties of four guanosine analogs at the atomic scale revealed that the formation of G-quartets is critical for their ability to form hydrogels. The stability of the sugar ring geometry conformation (an intrinsic factor) and the disorder and strength of the hydration effect (extrinsic factors) are vital for maintaining the stability of the G4-structures. The rapid cooling changes the molecular geometry conformation, and the organic solvent changes the hydration effect, which can improve the longevity stability of G4-structure-based supramolecular hydrogels instead of chemical modifications. Consequently, the lifespan of the hydrogels was extended from 2 h to over one week. This advancement is expected to offer significant insights for future research in designing and developing G4-structure-based supramolecular hydrogels.

Adaptive roles of cytokinins in enhancing plant resilience and yield against environmental stressors.

Innovative agricultural strategies are essential for addressing the urgent challenge of food security in light of climate change, population growth, and various environmental stressors. Cytokinins (CKs) play a pivotal role in enhancing plant resilience and productivity. These compounds, which include isoprenoid and aromatic types, are synthesized through pathways involving key enzymes such as isopentenyl transferase and cytokinin oxidase. Under abiotic stress conditions, CKs regulate critical physiological processes by improving photosynthetic efficiency, enhancing antioxidant enzyme activity, and optimizing root architecture. They also reduce the levels of reactive oxygen species and malondialdehyde, resulting in improved plant performance and yield. CKs interact intricately with other phytohormones, including abscisic acid, ethylene, salicylic acid, and jasmonic acid, to modulate stress-responsive pathways. This hormonal cross-talk is vital for finely tuning plant responses to stress. Additionally, CKs influence nutrient uptake and enhance responses to heavy metal stress, thereby bolstering overall plant resilience. The application of CKs helps plants maintain higher chlorophyll levels, boost antioxidant systems, and promote root and shoot growth. The strategic utilization of CKs presents an adaptive approach for developing robust crops capable of withstanding diverse environmental stressors, thus contributing to sustainable agricultural practices and global food security. Ongoing research into the mechanisms of CK action and their interactions with other hormones is essential for maximizing their agricultural potential. This underscores the necessity for continued innovation and research in agricultural practices, in alignment with global goals of sustainable productivity and food security.

Effect of infarct location and volume on cognitive dysfunction in elderly patients with acute insular cerebral infarction.

BACKGROUND: The aging of the population has become increasingly obvious in recent years, and the incidence of cerebral infarction has shown an increasing trend annually, with high death and disability rates. AIM: To analyze the effects of infarct location and volume on cognitive dysfunction in elderly patients with acute insular cerebral infarction. METHODS: Between January 2020 and December 2023, we treated 98 cases of elderly acute insula, patients with cerebral infarction in the cerebral infarction acute phase (3-4 weeks) and for the course of 6 months in Montreal Cognitive Assessment Scale (MoCA) for screening of cognition. Notably, 58 and 40 patients were placed in the cognitive impairment group and without-cognitive impairment group, respectively. In patients with cerebral infarction, magnetic resonance imaging was used to screen and clearly analyze the MoCA scores of two groups of patients with different infarctions, the relationship between the parts of the infarction volume, and analysis of acute insula cognitive disorder in elderly patients with cerebral infarction and the relationship between the two. RESULTS: The number of patients with cognitive impairment in the basal ganglia and thalamus was significantly higher than that without cognitive impairment (P < 0.05). The total infarct volume in the cognitive impairment group was higher than that in the non-cognitive impairment group, and the difference was statistically significant (P < 0.05). The infarct volumes at different sites in the cognitive impairment group was higher than in the non-cognitive impairment group (P < 0.05). In the cognitive impairment group, the infarct volumes in the basal ganglia, thalamus, and mixed lesions were negatively correlated with the total MoCA score, with correlation coefficients of -0.67, -0.73, and -0.77, respectively. CONCLUSION: In elderly patients with acute insular infarction, infarction in the basal ganglia, thalamus, and mixed lesions were more likely to lead to cognitive dysfunction than in other areas, and patients with large infarct volumes were more likely to develop cognitive dysfunction. The infarct volume in the basal ganglia, thalamus, and mixed lesions was significantly negatively correlated with the MoCA score.

Epigenomic landscapes during prefrontal cortex development and aging in rhesus.

The prefrontal cortex (PFC) is essential for higher-level cognitive functions. How epigenetic dynamics participates in PFC development and aging is largely unknown. Here, we profiled epigenomic landscapes of rhesus monkey PFCs from prenatal to aging stages. The dynamics of chromatin states, including higher-order chromatin structure, chromatin interaction and histone modifications are coordinated to regulate stage-specific gene transcription, participating in distinct processes of neurodevelopment. Dramatic changes of epigenetic signals occur around the birth stage. Notably, genes involved in neuronal cell differentiation and layer specification are pre-configured by bivalent promoters. We identified a cis-regulatory module and the transcription factors (TFs) associated with basal radial glia development, which was associated with large brain size in primates. These TFs include GLI3, CREB5 and SOX9. Interestingly, the genes associated with the basal radial glia (bRG)-associated cis-element module, such as SRY and SOX9, are enriched in sex differentiation. Schizophrenia-associated single nucleotide polymorphisms are more enriched in super enhancers (SEs) than typical enhancers, suggesting that SEs play an important role in neural network wiring. A cis-regulatory element of DBN1 is identified, which is critical for neuronal cell proliferation and synaptic neuron differentiation. Notably, the loss of distal chromatin interaction and H3K27me3 signal are hallmarks of PFC aging, which are associated with abnormal expression of aging-related genes and transposon activation, respectively. Collectively, our findings shed light on epigenetic mechanisms underlying primate brain development and aging.

Building running-friendly cities: effects of streetscapes on running using 9.73 million fitness tracker data in Shanghai, China.

The association between built environment and physical activity has been recognized. However, how and to what extent microscale streetscapes are related to running activity remains underexplored, partly due to the lack of running data in large urban areas. Moreover, few studies have examined the interactive effects of macroscale built environment and microscale streetscapes. This study examines the main and interactive effects of the two-level environments on running intensity, using 9.73 million fitness tracker data from Keep in Shanghai, China. Results of spatial error model showed that: 1) the explanatory power of microscale streetscapes was higher than that of macroscale built environment with R2 of 0.245 and 0.240, respectively, which is different from the prior finding that R2 is greater for macroscale built environment than for microscale streetscape; 2) sky and green view indexes were positively associated with running intensity, whereas visual crowdedness had a negative effect; 3) there were negative interactions of land use Herfindahl-Hirschman index with sky and green view indexes, while a positive interaction was observed for visual crowdedness. To conclude, greener, more open and less visually crowded streetscapes, can promote running behavior and enhance the benefits of land use mix as well. The findings highlight the importance of streetscapes in promoting running behavior, instead of a supplement to macroscale built environment.

C2 pedicle screw insertion assisted by mobilization of the vertebral artery in cases with high-riding vertebral artery.

Objective: To describe the feasibility, safety and efficacy of mobilization of the vertebral artery for C2 pedicle screws in cases with the high-riding vertebral artery (HRVA).. Methods: During the period January 2020 to September 2022, fifteen patients underwent posterior occipitocervical fixation in our department. All patients had unilateral HRVA on at least one side that prohibited the insertion of C2 pedicle screws. There were 2 males and 13 females aged 47 ± 11.9 years (range: 17-64 years). After the correction of the vertical dislocation during the operation, the C2 pedicle screw insertion and occipitocervical fixation and fusion were performed using the vertebral artery mobilization technique. A routine three-dimensional reconstructed CT examination was executed to confirm the trajectory of C2 pedicle screws post-operation, and a CT angiography examination was performed when necessary. Neurological function was assessed using the Japanese Orthopedic Association (JOA) scale. The preoperative and postoperative JOA score and the main radiological measurements, including anterior atlantodental interval (ADI), the distance of odontoid tip above Chamberlain line, and clivus-canal angle (CCA), were collected and compared by paired t-test. Results: All 15 patients had atlas assimilation, among which 12 patients had C2-C3 fusion (Klippel-Feil syndrome). Mobilization of the HRVA was successfully completed, and C2 pedicle screws were then fulfilled after the vertebral artery was protected. There was no injury to the vertebral artery during the operation. Meanwhile, no severe surgical complications such as cerebral infarction or aggravated neurological dysfunction occurred during the perioperative period. Satisfactory C2 pedicle screw placement and reduction were reached in all 15 patients. All the patients achieved bone fusion 6 months after surgery. No looseness and shift of internal fixation or reduction loss was observed during the follow-up period. Compared to the preoperative, the postoperative JOA score and the main radiological measurements were remarkably improved and statistically significant. Conclusions: C2 pedicle screw insertion assisted by mobilization of the vertebral artery is safe and considerably effective, providing a choice for internal fixation in cases with high-riding vertebral arteries.

Enhanced De/hydrogenation Kinetics and Cycle Stability of Mg/MgH2 by the MnOx-Coated Ti2CTx Catalyst with Optimized Ti-H Bond Stability.

MXene based catalysts can significantly enhance hydrogenation and dehydrogenation (de/hydrogenation) kinetics of Mg/MgH2, but they suffer from uncontrollable catalysts-hydrogen bond strength and structural instability. Here, we propose Tx density control of MXene-based catalysts and MnOx coating as a promising solution. The MnOx@Ti2CTx-catalyzed Mg/MgH2 can release 5.97 wt % H2 at 300 °C in 3 min and 5.60 wt % H2 at 240 °C in 15 min with an activation energy of 75.57 kJ·mol-1. In addition, the samples showed excellent de/hydrogenation-cycle stability, and the degradation of hydrogen storage capacity is negligible even after 100 cycles. DFT calculations combined with XPS analysis showed that the Tx defect on the surface of the MnOx@Ti2CTx catalyst could optimize the strength of the Ti-H bond, accelerating both hydrogen dissociation and diffusion processes. The catalyst's surface properties were protected by the MnOx coating, achieving high chemical and catalytic stability. These findings offer a strategy for surface structure optimization and protection of MXene-based catalysts, realizing controllable catalyst-hydrogen bond strength.

Wavelet-based selection-and-recalibration network for Parkinson's disease screening in OCT images.

BACKGROUND AND OBJECTIVE: Parkinson's disease (PD) is one of the most prevalent neurodegenerative brain diseases worldwide. Therefore, accurate PD screening is crucial for early clinical intervention and treatment. Recent clinical research indicates that changes in pathology, such as the texture and thickness of the retinal layers, can serve as biomarkers for clinical PD diagnosis based on optical coherence tomography (OCT) images. However, the pathological manifestations of PD in the retinal layers are subtle compared to the more salient lesions associated with retinal diseases. METHODS: Inspired by textural edge feature extraction in frequency domain learning, we aim to explore a potential approach to enhance the distinction between the feature distributions in retinal layers of PD cases and healthy controls. In this paper, we introduce a simple yet novel wavelet-based selection and recalibration module to effectively enhance the feature representations of the deep neural network by aggregating the unique clinical properties, such as the retinal layers in each frequency band. We combine this module with the residual block to form a deep network named Wavelet-based Selection and Recalibration Network (WaveSRNet) for automatic PD screening. RESULTS: The extensive experiments on a clinical PD-OCT dataset and two publicly available datasets demonstrate that our approach outperforms state-of-the-art methods. Visualization analysis and ablation studies are conducted to enhance the explainability of WaveSRNet in the decision-making process. CONCLUSIONS: Our results suggest the potential role of the retina as an assessment tool for PD. Visual analysis shows that PD-related elements include not only certain retinal layers but also the location of the fovea in OCT images.

Medical image registration and its application in retinal images: a review.

Medical image registration is vital for disease diagnosis and treatment with its ability to merge diverse information of images, which may be captured under different times, angles, or modalities. Although several surveys have reviewed the development of medical image registration, they have not systematically summarized the existing medical image registration methods. To this end, a comprehensive review of these methods is provided from traditional and deep-learning-based perspectives, aiming to help audiences quickly understand the development of medical image registration. In particular, we review recent advances in retinal image registration, which has not attracted much attention. In addition, current challenges in retinal image registration are discussed and insights and prospects for future research provided.

Mussel-Inspired Polymer Binders for Organic Electrodes.

The development of polymer binders is necessary to meet the growing demands of modern energy storage technologies. While catechol-containing materials are proven successful in silicon anodes, their application in organic batteries remains unexplored. In this contribution, the synthesis of four polymers are described with nearly identical side chain composition but varying backbone structures. The materials are used to investigate the effect of polymer backbone structure on the binding abilities of catechol-containing materials. Comparative analysis with the commonly used polyvinylidene fluoride (PVDF) binder aims to address two critical questions: 1) Can catechol-rich polymers replace PVDF for use in organic cathodes? and 2) Does the choice of polymer backbone affect the performance of the battery?. The investigation reveals that supramolecular interactions, such as π-π stacking and coordination bonding, are pivotal features of catechol binders. Among the catechol-rich polymers, the polyacrylate binder stands out, likely attributed to its high flexibility. Additionally, introducing an oxygen atom into a catechol-rich polynorbornene enhances lithium-ion conductivity and rate performance. Overall, the findings highlight the viability of catechol-containing polymers as organic cathode binders, and that the choice of polymer backbone is a crucial factor for their use as lithium-ion battery binder materials.

Analysis of Risk Factors of Sarcopenia in Patients with Maintenance Hemodialysis and Its Correlation with Emotional Status and Quality of Life.

Objective: Sarcopenia is more common in maintenance hemodialysis (MHD) patients, and the aim of this study is to analyze the risk factors associated with sarcopenia in MHD patients, along with its correlation to emotional status and quality of life. Methods: This is a cross-sectional cohort study. A total of 111 MHD patients who were treated in the Department of Nephrology of our hospital were selected as the study subjects by convenience sampling. The quality of life and emotional status were evaluated by health survey scale (SF-36), self-rating anxiety scale (SAS) and self-rating depression scale (SDS). Regression analysis was used to explore the influencing factors of sarcopenia. Correlation analysis was used to investigate the correlation between sarcopenia and quality of life and emotional status. Results: The prevalence of sarcopenia was 59.8%. The results showed that age, gender, body mass index (BMI), dialysis time, economic status, marital status and pre-dialysis creatinine were significant factors affecting the development of sarcopenia in hemodialysis patients (p<0.05). The SF-36 total score was significantly lower in the sarcopenia group (72.05±12.28 vs 78.03±10.55) than in the non-sarcopenia group, but the anxiety scale score (52.97±4.67 vs 36.2±3.36) and depression scale score (57.67±4.58 vs 38.71±3.77) were significantly higher than those in the non-sarcopenia group (p< 0.001). Correlation analysis showed that sarcopenia was positively correlated with SAS and SDS scores and negatively correlated with SF-36 total score (p < 0.05). Conclusion: The risk of sarcopenia was higher among MHD patients who were older, male, single, with a longer MHD duration, lower economic status, lower BMI, comorbid diabetes and lower levels of creatinine.

Unveiling hierarchy and spatial distribution of O6-methylguanine-DNA methyltransferase promoter methylation in World Health Organization grade 2-3 gliomas.

This study investigated the role of O6-methylguanine-DNA methyltransferase promoter (MGMTp) methylation hierarchy and heterogeneity in grade 2-3 gliomas, focusing on variations in chemotherapy benefits and resection dependency. A cohort of 668 newly diagnosed grade 2-3 gliomas, with comprehensive clinical, radiological, and molecular data, formed the basis of this analysis. The extent of resection was categorized into gross total resection (GTR ≥100%), subtotal resection (STR >90%), and partial resection (PR ≤90%). MGMTp methylation levels were examined using quantitative pyrosequencing. Our findings highlighted the critical role of GTR in improving the prognosis for astrocytomas (IDH1/2-mutant and 1p/19q non-codeleted), contrasting with its lesser significance for oligodendrogliomas (IDH1/2 mutation and 1p/19q codeletion). Oligodendrogliomas demonstrated the highest average MGMTp methylation levels (median: 28%), with a predominant percentage of methylated cases (average methylation levels >20%). Astrocytomas were more common in the low-methylated group (10%-20%), while IDH wild-type gliomas were mostly unmethylated (<10%). Spatial distribution analysis revealed a decrement in frontal lobe involvement from methylated, low-methylated to unmethylated cases (72.8%, 59.3%, and 47.8%, respectively). In contrast, low-methylated and unmethylated cases were more likely to invade the temporal-insular region (19.7%, 34.3%, and 40.4%, respectively). Astrocytomas with intermediate MGMTp methylation were notably associated with temporal-insular involvement, potentially indicating a moderate response to temozolomide and underscoring the importance of aggressive resection strategies. In conclusion, our study elucidates the complex interplay of MGMTp methylation hierarchy and heterogeneity among grade 2-3 gliomas, providing insights into why astrocytomas and IDH wild-type lower-grade glioma might derive less benefit from chemotherapy.

Synthesis of Isotypic Giant Polymolybdate Cages for Efficient Photocatalytic C-C Coupling Reactions.

The construction of isotypic high-nuclearity inorganic cages with identical pristine parent structure and increasing nuclearity is highly important for molecular growth and structure-property relationship study, yet it still remains a great challenge. Here, we provide an in situ growth approach for successfully synthesizing a series of new giant hollow polymolybdate dodecahedral cages, Mo250, Mo260-I, and Mo260-E, whose structures are growth based on giant polymolybdate cage Mo240. Remarkably, they show two pathways of nuclear growth based on Mo240, that is, the growth of 10 and 20 Mo centers on the inner and outer surfaces to afford Mo250 and Mo260-I, respectively, and the growth of 10 Mo centers both on the inner and outer surfaces to give Mo260-E. To the best of our knowledge, this is the first study to display the internal and external nuclear growth of a giant hollow polyoxometalate cage. More importantly, regular variations in structure and nuclearity confer these polymolybdate cages with different optical properties, oxidative activities, and hydrogen atom transfer effect, thus allowing them to exhibit moderate to excellent photocatalytic performance in oxidative cross-coupling reactions between different unactivated alkanes and N-heteroarenes. In particular, Mo240 and Mo260-E with better comprehensive abilities can offer the desired coupling product with yield up to 92% within 1 h.

Driving Efficiency: Leveraging Model-Informed Approaches in 505(b)(2) Regulatory Actions.

Introduced by the Hatch-Waxman Amendments of 1984, 505(b)(2) applications permit the US Food and Drug Administration to rely, for approval of a new drug application, on information from studies not conducted by or for the applicant and for which the applicant has not obtained a right of reference. This pathway is designed to circumvent the unnecessary duplication of studies already conducted on a previously approved drug. It can lead to a considerably more efficient and expedited route to approval compared to a traditional development path. Model-informed drug development refers to the utilization of a diverse array of quantitative models in drug development to streamline the decision-making process. In this approach, diverse quantitative models that integrate knowledge of physiology, disease processes, and drug pharmacology are employed to address drug development challenges and guide regulatory decisions. Integration of these model-informed approaches into 505(b)(2) regulatory submissions and decision-making can further expedite the approval of new drugs. This article discusses some applications of model-informed approaches that were used to support 505(b)(2) drug development and regulatory actions. Specifically, various quantitative models such as population pharmacokinetic and exposure-response models have been employed to provide evidence of effectiveness, guide dosing in subgroups such as subjects with hepatic or renal impairment, and inform policies. These case study examples collectively underscore the significance of model-informed approaches in drug development and regulatory decisions associated with 505(b)(2) submissions.