Quantized multi-task learning for context-specific representations of gene network dynamics.

While often represented as static entities, gene networks are highly context-dependent. Here, we developed a multi-task learning strategy to yield context-specific representations of gene network dynamics. We assembled a corpus comprising ~103 million human single-cell transcriptomes from a broad range of tissues and diseases and performed a two stage pretraining, first with non-malignant cells to generate a foundational model and then with continual learning on cancer cells to tune the model to the cancer domain. We performed multi-task learning with the foundational model to learn context-specific representations of a broad range of cell types, tissues, developmental stages, and diseases. We then leveraged the cancer-tuned model to jointly learn cell states and predict tumor-restricting factors within the colorectal tumor microenvironment. Model quantization allowed resource-efficient fine-tuning and inference while preserving biological knowledge. Overall, multi-task learning enables context-specific disease modeling that can yield contextual predictions of candidate therapeutic targets for human disease.

Unlocking the secrets of porous silicon formation: insights into magnesiothermic reduction mechanism using in situ powder X-ray diffraction studies.

The magnesiothermic reduction of SiO2 is an important reaction as it is a bulk method that produces porous Si for a wide range of applications directly from SiO2. While its main advantage is potential tunability, the reaction behavior and final product properties are heavily dependent on many parameters including feedstock type. However, a complete understanding of the reaction pathway has not yet been achieved. Here, using in situ X-ray diffraction analysis, for the first time, various pathways through which the magnesiothermic reduction reaction proceeds were mapped. Further, the key parameters and conditions that determine which pathways are favored were determined. It was discovered that the reaction onset temperatures can be as low as 348 ± 7 °C, which is significantly lower when compared to previously reported values. The onset temperature is dependent on the size of Mg particles used in the reaction. Further, Mg2Si was identified as a key intermediate rather than a reaction byproduct during the reduction process. Its rate of consumption is determined by the reaction temperature which needs to be >561 °C. These findings can enable process and product optimization of the magnesiothermic reduction process to manufacture and tune porous Si for a range of applications.

Feasibility and Advantages of Continuous Synthesis of Bioinspired Silica Using CO2 as an Acidifying Agent.

In this work, we present a method for the continuous synthesis of bioinspired porous silica (BIS) particles using carbon dioxide (CO2) as an acidifying agent. Typical BIS synthesis uses strong mineral acids (e.g., HCl) to initiate the hydrolysis and subsequent condensation reactions. The use of strong acids leads to challenges in controlling the reaction pH. The synthesis approach proposed in this work offers for the first time CO2 as an attractive alternative for the synthesis of BIS and demonstrates the continuous process. The developed method leverages the mild acidic and the self-buffering nature of the CO2 combined with additional options for controlling mass transfer rates to facilitate enhanced control of pH, which is crucial for controlling the properties of synthesized BIS. Proof of concept experiments conducted in continuous mode demonstrated a yield of over 70% and a surface area exceeding 500 m2/g. These results indicate the successful synthesis of BIS using CO2 with properties in the desired range. The enhanced pH control offered by this CO2-based process will facilitate the implementation of a sustainable and robust continuous process for BIS synthesis.

Molecular regulation of PPARγ/RXRα signaling by the novel cofactor ZFP407.

Cofactors interacting with PPARγ can regulate adipogenesis and adipocyte metabolism by modulating the transcriptional activity and selectivity of PPARγ signaling. ZFP407 was previously demonstrated to regulate PPARγ target genes such as GLUT4, and its overexpression improved glucose homeostasis in mice. Here, using a series of molecular assays, including protein-interaction studies, mutagenesis, and ChIP-seq, ZFP407 was found to interact with the PPARγ/RXRα protein complex in the nucleus of adipocytes. Consistent with this observation, ZFP407 ChIP-seq peaks significantly overlapped with PPARγ ChIP-seq peaks, with more than half of ZFP407 peaks overlapping with PPARγ peaks. Transcription factor binding motifs enriched in these overlapping sites included CTCF, RARα/RXRγ, TP73, and ELK1, which regulate cellular development and function within adipocytes. Site-directed mutagenesis of frequent PPARγ phosphorylation or SUMOylation sites did not prevent its regulation by ZFP407, while mutagenesis of ZFP407 domains potentially necessary for RXR and PPARγ binding abrogated any impact of ZFP407 on PPARγ activity. These data suggest that ZFP407 controls the activity of PPARγ, but does so independently of post-translational modifications, likely by direct binding, establishing ZFP407 as a newly identified PPARγ cofactor. In addition, ZFP407 ChIP-seq analyses identified regions that did not overlap with PPARγ peaks. These non-overlapping peaks were significantly enriched for the transcription factor binding motifs of TBX19, PAX8, HSF4, and ZKSCAN3, which may contribute to the PPARγ-independent functions of ZFP407 in adipocytes and other cell types.

Quality-by-Design Approach to Process Intensification of Bioinspired Silica Synthesis.

Characterizing nanomaterials is challenging due to their macromolecular nature, requiring suites of physicochemical analysis to fully resolve their structure. As such, their synthesis and scale-up are notoriously complex, especially when compared to small molecules or bulk crystalline materials, which can be provided a unique fingerprint from nuclear magnetic resonance (NMR) or X-ray diffraction (XRD) alone. In this study, we address this challenge by adopting a three-step quality-by-design (QbD) approach to the scale-up of bioinspired silica nanomaterials, demonstrating its utility toward synthesis scale-up and intensification for this class of materials in general. First, we identified material-specific surface area, pore-size distribution, and reaction yield as critical quality attributes (CQAs) that could be precisely measured and controlled by changing reaction conditions. We then identified the critical process parameters (CPPs) controlling bioinspired synthesis properties, exploring different process routes, incorporating commercial reagents, and optimizing reagent ratios, comparing silica properties against original CQA values to identify acceptable limits to each CPP. Finally, we intensified the synthesis by increasing reagent concentration while simultaneously incorporating the optimized CPPs, thereby modifying the bioinspired silica synthesis to make it compatible with existing manufacturing methods. We increased the specific yield from ca. 1.1 to 38 g/L and reduced the additive intensity from ca. 1 to 0.04 g/g product, greatly reducing both synthesis cost and waste production. These results identify a need for mapping the effects of critical process parameters on material formation pathways and CQAs to enable accelerated scale-up and transition from the lab to the market.

Congenital Transmesenteric Hernia With Closed-Loop Small Bowel Obstruction and Intestinal Gangrene in an Adult.

Internal hernias (IHs) are defined as the protrusion of the intestine through an aperture in the peritoneal ligament, mesentery, or the omentum, without traversing the fascial planes and leading to encapsulation of the protruded intestine within another compartment of an otherwise intact abdominal cavity. Internal hernias can be acquired or congenital. Congenital internal hernias resulting in small bowel obstruction are extremely rare, even more so in adults, occurring usually due to embryological or developmental defects, often undiagnosed, and requiring a high index of clinical suspicion. We report a rare case of a 22-year-old young adult with transmesenteric hernia of distal ileum through a congenital distal ileal mesenteric defect resulting in closed-loop small bowel obstruction and distal ileal gangrene, managed with resection and end-ileostomy, followed by stoma reversal one month later. It requires a high index of suspicion and remains a surgical emergency due to its predilection for intestinal gangrene and small bowel obstruction, with a high mortality rate due to delayed presentation and diagnosis.

Cannula Placement for Cerebral Protection Without Circulatory Arrest in Patients Undergoing Hemiarch Aortic Aneurysm Repair.

BACKGROUND: Aortic aneurysms involving the proximal aortic arch, which require hemiarch-type repair, typically require circulatory arrest with antegrade cerebral perfusion. Left carotid antegrade cerebral perfusion (LCP) via distal arch cannulation without circulatory arrest was used in this study's patient population. The goal was to assess the operative efficiency and clinical outcomes of using a distal arch cannulation technique that would not require any hypothermic circulatory arrest (HCA) time compared with more traditional brachiocephalic artery cannulation with right-sided unilateral antegrade cerebral perfusion (RCP) and HCA. METHODS: A single-center retrospective review of patients with replacement of the distal ascending aorta involving the proximal arch was performed. Patients with an intramural hematoma or dissection were excluded. Between January 2015 and December 2019, 68 adult patients had undergone a hemiarch repair because of aneurysmal disease. Analysis of baseline demographics, operative data, and clinical outcomes was performed. RESULTS: Comparing the 68 patients: 21 patients were treated with RCP (via brachiocephalic artery graft with HCA), and 47 patients were treated with LCP (via distal aortic arch cannulation with cross-clamp between the brachiocephalic and left common carotid arteries without HCA). Baseline characteristics and outcomes were evaluated for both groups. The LCP group was younger (LCP median [IQR] age, 60 [53-65] years vs RCP median [IQR] age, 67 [59-71] years]. Sex, race, body mass index, comorbidities, and ejection fraction were similar between the groups. Cardiopulmonary bypass time (LCP, 123 minutes vs RCP, 149 minutes) and unilateral cerebral perfusion time (LCP, 17 minutes vs RCP, 22 minutes) were longer in the RCP group. Bleeding, prolonged ventilatory support, kidney failure, and length of stay were similar. In-hospital mortality was 2% in the LCP group vs 0% in the RCP group. Stroke occurred in 2 patients (4.2%) in the LCP group and in 0% of the RCP group. Mortality at 6 months in the LCP and RCP groups was 3% and 10%, respectively. CONCLUSION: Distal arch cannulation with LCP without HCA is a reasonable and safe alternative strategy for patients requiring hemiarch replacement for aneurysmal disease. This technique may provide additional benefits by avoiding circulatory arrest in these complex cases.

Large Language Model-Based Neurosurgical Evaluation Matrix: A Novel Scoring Criteria to Assess the Efficacy of ChatGPT as an Educational Tool for Neurosurgery Board Preparation.

INTRODUCTION: Technological advancements are reshaping medical education, with digital tools becoming essential in all levels of training. Amidst this transformation, the study explores the potential of ChatGPT, an artificial intelligence model by OpenAI, in enhancing neurosurgical board education. The focus extends beyond technology adoption to its effective utilization, with ChatGPT's proficiency evaluated against practice questions from the Primary Neurosurgery Written Board Exam. METHODS: Using the Congress of Neurologic Surgeons (CNS) Self-Assessment Neurosurgery (SANS) Exam Board Review Prep questions, we conducted 3 rounds of analysis with ChatGPT. We developed a novel ChatGPT Neurosurgical Evaluation Matrix (CNEM) to assess the output quality, accuracy, concordance, and clarity of ChatGPT's answers. RESULTS: ChatGPT achieved spot-on accuracy for 66.7% of prompted questions, 59.4% of unprompted questions, and 63.9% of unprompted questions with a leading phrase. Stratified by topic, accuracy ranged from 50.0% (Vascular) to 78.8% (Neuropathology). In comparison to SANS explanations, ChatGPT output was considered better in 19.1% of questions, equal in 51.6%, and worse in 29.3%. Concordance analysis showed that 95.5% of unprompted ChatGPT outputs and 97.4% of unprompted outputs with a leading phrase were aligned. CONCLUSIONS: Our study evaluated the performance of ChatGPT in neurosurgical board education by assessing its accuracy, clarity, and concordance. The findings highlight the potential and challenges of integrating AI technologies like ChatGPT into medical and neurosurgical board education. Further research is needed to refine these tools and optimize their performance for enhanced medical education and patient care.

A Novel Method for Understanding the Mixing Mechanisms to Enable Sustainable Manufacturing of Bioinspired Silica.

Bioinspired silica (BIS) has received unmatched attention in recent times owing to its green synthesis, which offers a scalable, sustainable, and economical method to produce high-value silica for a wide range of applications, including catalysis, environmental remediation, biomedical, and energy storage. To scale-up BIS synthesis, it is critically important to understand how mixing affects the reaction at different scales. In particular, successful scale-up can be achieved if mixing time is measured, modeled, and kept constant across different production scales. To this end, a new image analysis technique was developed using pH, as one of the key parameters, to monitor the reaction and the mixing. Specifically, the technique involved image analysis of color (pH) change using a custom-written algorithm to produce a detailed pH map. The degree of mixing and mixing time were determined from this analysis for different impeller speeds and feed injection locations. Cross validation of the mean pH of selected frames with measurements using a pH calibration demonstrated the reliability of the image processing technique. The results suggest that the bioinspired silica formation is controlled by meso- and, to a lesser extent, micromixing. Based on the new data from this investigation, a mixing time correlation is developed as a function of Reynolds number-the first of a kind for green nanomaterials. Further, we correlated the effects of mixing conditions on the reaction and the product. These results provide valuable insights into the scale-up to enable sustainable manufacturing of BIS and other nanomaterials.

Recent Advances in Enabling Green Manufacture of Functional Nanomaterials: A Case Study of Bioinspired Silica.

Global specialty silica production is over 3 million tonnes per annum with diverse applications across sectors and an increasing demand for more complex material structures and surface chemistries. Commercial manufacturing of high-value silica nanomaterials is energy and resource intensive. In order to meet market needs and mitigate environmental impacts, new synthesis methods for these porous materials are required. The development of the bioinspired silica (BIS) product system, which is the focus of this review, provides a potential solution to this challenge. BIS is a versatile and greener route with the prospect of good scalability, attractive process economics and well controlled product materials. The potential of the system lies not only in its provision of specific lead materials but also, as itself, a rich design-space for the flexible and potentially predictive design of diverse sustainable silica nanomaterials. Realizing the potential of this design space, requires an integrative mind-set, which enables parallel and responsive progression of multiple and dependent research strands, according to need, opportunities, and emergent knowledge. Specifically, this requires development of detailed understanding of (i) the pathways and extent of material diversity and control, (ii) the influences and mechanisms of scale-up, and (iii) performance, economic and environmental characteristics and sensitivities. Crucially, these need to be developed for the system overall, which sits in contrast to a more traditional research approach, which focuses initially on the discovery of specific material leads at the laboratory scale, leaving scale-up, commercialization, and, potentially, pathway understanding to be considered as distinctly separate concerns. The intention of this review is to present important recent advances made in the field of BIS. Specifically, advances made along three research themes will be discussed: (a) particle formation pathways, (b) product design, and (c) scale-up and manufacture. These advances include first quantitative investigation of synthesis-product relationships, first structured investigation of mixing effects, preparation of a broad range of functionalized and encapsulated silica materials and continued industrial engagement and market research. We identify future challenges and provide an important foundation for the development of new research avenues. These include the need to develop comprehensive and predictive product design models, to understand markets in terms of product cost, performance and environmental considerations, and to develop capabilities enabling rapid prototyping and scale-up of desired nanomaterials.

A Comparison of Environmental Impact of Various Silicas Using a Green Chemistry Evaluator.

To answer questions surrounding the sustainability of silica production, MilliporeSigma's DOZN 2.0 Green Chemistry Evaluator was employed as it provides quantitative values based on the 12 principles of Green Chemistry. As a first study using DOZN 2.0 to evaluate the greenness of nanomaterials, a range of silica types were considered and their greenness scores compared. These included low- and high-value silicas, both commercial and emerging, such as precipitated, gel, fumed, colloidal, mesoporous, and bioinspired silicas. When surveying these different types of silicas, it became clear that while low value silicas have excellent greenness scores, high-value silicas perform poorly on this scale. This highlighted the tension between high-value silicas that are desired for emerging markets and the sustainability of their synthesis. The calculations were able to quantify the issues pertaining to the energy-intensive reactions and subsequent removal of soft templates for the sol-gel processes. The importance of avoiding problematic solvents during processes and particularly releasing them as waste was identified. The calculations were also able to compare the amount of waste generated as well as their hazardous nature. The effects of synthesis conditions on greenness scores were also investigated in order to better understand the relationship between the production process and their sustainability.

Facile Cellulase Immobilisation on Bioinspired Silica.

Cellulases are enzymes with great potential for converting biomass to biofuels for sustainable energy. However, their commercial use is limited by their costs and low reusability. Therefore, the scientific and industrial sectors are focusing on finding better strategies to reuse enzymes and improve their performance. In this work, cellulase from Aspergillus niger was immobilised through in situ entrapment and adsorption on bio-inspired silica (BIS) supports. To the best of our knowledge, this green effect strategy has never been applied for cellulase into BIS. In situ entrapment was performed during support synthesis, applying a one-pot approach at mild conditions (room temperature, pH 7, and water solvent), while adsorption was performed after support formation. The loading efficiency was investigated on different immobilisation systems by Bradford assay and FTIR. Bovine serum albumin (BSA) was chosen as a control to optimize cellulase loading. The residual activity of cellulase was analysed by the dinitro salicylic acid (DNS) method. Activity of 90% was observed for the entrapped enzyme, while activity of ~55% was observed for the adsorbed enzyme. Moreover, the supported enzyme systems were recycled five times to evaluate their reuse potential. The thermal and pH stability tests suggested that both entrapment and adsorption strategies can increase enzyme activity. The results highlight that the entrapment in BIS is a potentially useful strategy to easily immobilise enzymes, while preserving their stability and recycle potential.

Racial disparities in cardiac transplantation: Chronological perspective and outcomes.

BACKGROUND: The objective of this study was to evaluate annual heart transplant volumes and 3-year post-transplant outcomes since establishment of United Network for Organ Sharing (UNOS) database stratified by race. METHODS: The UNOS thoracic transplant database was evaluated for adult patients since 1987. The available database was then stratified by Race: Black, White and Other and era of transplant: group 1(1987-1991), group 2(1992-1996), group 3(1997-2001), group 4(2002-2006), group 5(2007-2011), group 6(2012-2016) and group 7(2017 and later). Demographic and clinical factors were evaluated. RESULTS: A total of 105,266 adults have been listed since 1987 and 67,824 have been transplanted. Of the transplanted patients 11,235 were Black, 48,786 White and 6803 were of Other race. The proportion of Black patients listed increased from 7% in 1987 to 13.4% in 1999 and 25% in 2019 and those transplanted increased from 5% in 1987 to 13.4% in 2001 and 26% in 2019. The survival of Black patients gradually improved. CONCLUSION: Historically, fewer Black patients received cardiac transplantation however, their access gradually improved over the years and account for over 25% of cardiac transplantations performed in recent years. The historically poor survival of Black patients has recently improved and became comparable to the rest.

Exploiting nanoscale effects enables ultra-low temperature to produce porous silicon.

The magnesiothermic reduction (MgTR) of silica has been recently shown to produce porous silicon which can be used in applications such as photocatalysis and energy storage. MgTR typically requires ≥650 °C to achieve meaningful conversions. However, high temperatures are detrimental to the highly desired porosity of silicon, while also raising doubts over the sustainability of the process. In this work we show for the first time that the onset temperature of the MgTR is dependent on the particle size of the feedstock silica. Using both in-house synthesised and commercial silica, we have shown that only particles ≤20 nm are able to trigger the reaction at temperatures as low as 380 °C, well below a previously reported cut-off temperature of 500 °C, producing porous, crystalline silicon. The decrease in temperature requirement from ≥650 °C to 380 °C achieved with little modification to the overall process, without any additional downstream processing, presents significant implications for sustainable and economical manufacturing of porous silicon.

Enabling scale-up of mesoporous silicon for lithium-ion batteries: a systematic study of a thermal moderator.

The volume expansion of silicon during cycling of a lithium-ion battery (LIB) leads to degradation and capacity loss. Porous silicon can address many of the issues faced by silicon active materials and has previously been shown to have excellent cyclability. Recently we have uncovered the mechanisms underpinning the pore evolution in magnesiothermic reduction (MgTR) of silica and further demonstrated that it has the potential to produce porous silicon in a scalable and economic manner [J. Mater. Chem. A, 2020, 8, 4938]. However, the scalability of MgTR is affected by the large excess heat produced during reaction. Although previous studies have shown that NaCl can be used as a thermal moderator to mitigate this issue, this has not been systematically investigated, leading to a lack of knowledge on scalability of MgTR. Here, by carefully investigating the roles of NaCl, we show that the NaCl ratio and reduction temperature are the critical factors for controlling scale-up and the product properties. We identified the upper temperature limit of NaCl as a thermal moderator. Further, we systematically showed how the amount of NaCl and the reduction temperature affect the porous properties of the product silicon. Our results have established pathways for scaling-up this method such that it can now be taken forward to target specific porous silicon properties.

Mimicking Biosintering: The Identification of Highly Condensed Surfaces in Bioinspired Silica Materials.

Interfacial interactions between inorganic surfaces and organic additives are vital to develop new complex nanomaterials. Learning from biosilica materials, composite nanostructures have been developed, which exploit the strength and directionality of specific polyamine additive-silica surface interactions. Previous interpretations of these interactions are almost universally based on interfacial charge matching and/or hydrogen bonding. In this study, we analyzed the surface chemistry of bioinspired silica (BIS) materials using solid-state nuclear magnetic resonance (NMR) spectroscopy as a function of the organic additive concentration. We found significant additional association between the additives and fully condensed (Q4) silicon species compared to industrial silica materials, leading to more overall Q4 concentration and higher hydrothermal stability, despite BIS having a shorter synthesis time. We posit that the polyfunctionality and catalytic activity of additives in the BIS synthesis lead to both of these surface phenomena, contrasting previous studies on monofunctional surfactants used in most other artificial templated silica syntheses. From this, we propose that additive polyfunctionality can be used to generate tailored artificial surfaces in situ and provide insights into the process of biosintering in biosilica systems, highlighting the need for more in-depth simulations on interfacial interactions at silica surfaces.

Degradation of Anthraquinone Dyes from Effluents: A Review Focusing on Enzymatic Dye Degradation with Industrial Potential.

Up to 84 000 tons of dye can be lost in water, and 90 million tons of water are attributed annually to dye production and their application, mainly in the textile and leather industry, making the dyestuff industry responsible for up to 20% of the industrial water pollution. The majority of dyes industrially used today are aromatic compounds with complex, reinforced structures, with anthraquinone dyes being the second largest produced in terms of volume. Despite the progress on decolorization and degradation of azo dyes, very little attention has been given to anthraquinone dyes. Anthraquinone dyes pose a serious environmental problem as their reinforced structure makes them difficult to degrade naturally. Existing methods of decolorization might be effective but are neither efficient nor practical due to extended time, space, and cost requirements. Attention should be given to the emerging routes for dye decolorization via the enzymatic action of oxidoreductases, which have already a strong presence in various other bioremediation applications. This review will discusses the presence of anthraquinone dyes in the effluents and ways for their remediation from dyehouse effluents, focusing on enzymatic processes.

The Prevalence Pattern of Locomotor Disability and its Impact on Mobility, Self-Care, and Interpersonal Skills in Rural Areas of Jodhpur District.

CONTEXT: Impact of disability is deleterious, affecting an individual's every aspect. Majority of disabled reside in rural areas of developing countries. Moreover, different types of disability add to its wide spectrum. All these make it a major health issue. AIMS: The aim of this study was to note the prevalence rate and pattern of locomotor disability in a rural population of Jodhpur District and to observe its impact on mobility, self-care, and interpersonal skills of disabled. SETTINGS: This study was carried out in rural field practice area of the Community and Family Medicine Department of tertiary care setup. DESIGN: This was a cross-sectional study. MATERIALS AND METHODS: House-to-house survey for a sample size of 1656 was conducted by a team of trained doctors, therapists, and anganwadi workers for identification of locomotor disability applying a pretested survey questionnaire. STATISTICAL ANALYSIS: SPSS version 22 was used for descriptive analysis of variables (frequency distribution), and the Chi-squared test was used for the association of sociodemographic factors with performance qualifier score. RESULTS: The prevalence rate of 2.08% for locomotor disability (male = 57% and female = 43%) was noted, with 31% from 40 to 60 years, 49% were illiterate, and 60% were from lower class. The main etiologies were cerebrovascular accident (25%) and cerebral palsy (23%). About 80% faced some difficulties in mobility domain, 57% in self-care, and 63% in interpersonal skills. Statistically significant association was seen for self-care domain with education level (P = 0.04) and for interpersonal skill domain with age groups and diagnosis (P = 0.022 and P = 0.035, respectively). CONCLUSION: The overall prevalence of locomotor disability in rural Jodhpur was 2.08%, higher for males and higher from 40 to 60 years. Most disabled were illiterate and were from low socioeconomic status. Self-care, mobility, and interpersonal skills were primarily affected and require proper intervention.