Computer vision is a rapidly developing field that focuses on highly sophisticated picture analysis, manipulation, and comprehension. Its objective is to analyze what is happening in front of a camera and utilize that understanding to control a computer or robotic system or to present users with fresh visuals that are more enlightening or appealing than the original camera images. Computer vision technologies make it feasible for new user interfaces, augmented reality gaming, biometrics, automobile, photography, movie creation, Web search, and many more applications. This essay seeks to explain how computer vision can be utilized to play blackjack successfully.

Abstract: Endoglin (ENG) is a causative gene of type 1 hereditary hemorrhagic telangiectasia (HHT1). HHT1 patients have arteriovenous malformations (AVMs) in multiple organs, including the brain. In mice, Eng deletion induced by R26RCreER or SM22aCre leads to AVM development in the brain and other organs. We have reported that the severity of brain AVM in mice with activin receptor-like kinase 1 (Alk1, an HHT2 causative gene) mutation is correlated with the number of Alk1 negative endothelial cells (ECs). We hypothesized that increase of Eng negative ECs will enhance AVM severity. To increase EC Eng deletion, we used a codon improved cre (icre), which is more potent in recombination of floxed alleles than the wild type (WT) cre. R26RCreER;Eng^f/f mice that have Rosa promoter driving and tamoxifen (TM) inducible WT cre expression globally and PdgfbiCreER;Eng^f/f that have Pdgfb promoter driving and TM inducible icre expression in ECs were treated with 3 intra-peritoneal injections of TM (2.5 mg/25g of body weight) to delete Eng globally or in the ECs. AAV-VEGF was stereotactically injected into the brain to induce brain focal angiogenesis and brain AVM. We found that iCre caused more Eng deletion in the brain indicated by lower level of Eng proteins (p<0.001) and fewer Eng positive ECs (p=0.01) than mice with WT cre. Mice with iCre mediated Eng deletion have more abnormal vessels (p=0.02), CD68⁺ macrophages (p=0.002), and hemorrhage (p=0.04), and less vascular pericyte and smooth muscle coverage than mice with WT cre. In addition, arteriovenous shunts were detected in the intestines of icre mice, a phenotype that have not been detected in WT cre mice before. RNAseq analysis showed that 8 out of the 10 top upregulated pathways identified by Gene Ontology (GO) analysis are related to the inflammation. Therefore, increase of Eng deletion in ECs exacerbates AVM severity, which is associated with enhanced inflammation. Strategies that can reduce Eng negative ECs could be used to develop new therapies to reduce AVM severity for HHT1 patients.

Lipids have not traditionally been considered likely candidates for catalyzing reactions in biological systems. However, there is significant evidence that aggregates of amphiphilic compounds are capable of catalyzing reactions in synthetic organic chemistry. Here we demonstrate the potential for the hydrophobic region of a lipid bilayer to provide an environment suitable for catalysis by means of a lipozyme, or lipid aggregate capable of speeding up a chemical reaction. By bringing organic molecules into the non-polar or hydrophobic region of a lipid bilayer, reactions can be catalyzed by collections of small, nonpolar or amphiphilic molecules. We demonstrate this concept by the ester hydrolysis of calcein-AM to produce a fluorescent product, which is a widely used assay for esterase activity in cells. The reaction was first carried out in a two phase octanol-water system with the organic phase containing the cationic amphiphiles cetyltrimethylammonium bromide (CTAB) or octadecylamine. The octanol was then replaced with DOPC added to the water in the form of vesicles, where the reaction was also found to be carried out. The reaction was monitored using quantitative fluorescence which revealed catalytic turnover numbers on a scale of 10−4s−1 for each system, which is comparable to some slow enzymes. The reaction product was characterized by 1H-NMR measurements which were consistent with ester hydrolysis. The implications of thinking about lipid aggregates as catalytic entities are discussed in the context of biochemistry, pharmacology and synthetic biology.

Smith-Magenis syndrome is a complex neurobehavioral genetic disorder. The spectrum of SMS phenotype is broad but commonly includes craniofacial, neurobehavioral, and otolaryngologic features. While the etiology of SMS is commonly attributed to one copy interstitial deletion in the 17p11.2 region (90-95% of cases), variants identified by sequence analysis in RAI1 have also been reported in 5-10% of cases. The phenotypic spectrum of patients with RAI1 sequence alterations is not clear. In this study, we report a 9-year-old male with global cognitive and psychomotor developmental delay, musculoskeletal and cardiovascular abnormalities, and dysmorphic craniofacial features. Whole genome quad analysis of the proband, unaffected parent, and unaffected brother identified a novel de novo RAI1:c.2736delC variant. This is the first report of this variant in the literature. This report also highlights the details of the genome analysis and this patient's phenotypic spectrum.

One of the relevant goals in forging technologies is simplifying the existing process and developing new processes that can retain the original or very close to the original dimensions and billet shape after the end of the deformation cycle. This study attempts to develop a forging equipment design that provides alternating cyclic loading; the alternate cyclic forging (ACF) method is proposed. To preliminary evaluate the ACF and study the plastic deformation behavior, numerical simulation via finite element modeling (FEM) was conducted using DEFORM-3D. The main attention was paid to the metal flow characteristics, effective strain and stress distribution, and the forging load. The ACF results in non-uniform metal flow with the formation of diagonal and vortex flows were demonstrated. Maximum effective strains and stresses zones are localized at two points of the billet contact with the surface of the tooling container and at two points of the interface between the punches. It was also assumed that reducing the contact area between the punch and the billet using separate semi-cylindrical punches can reduce the forging load. Preliminary finite element analysis (FEA) results of the proposed process after four successive steps of the deformation cycle confirmed the feasibility of its general implementation.

New antimicrobial approaches are essential to counter antimicrobial resistance. The drug development pipeline is exhausted with emergence of resistance resulting in unsuccessful trials. The lack of an effective drug developed from the conventional drug portfolio has mandated the introspection into the list of potentially effective unconventional alternate antimicrobial molecules. Alternate therapies, that are clinically explicable forms include monoclonal antibodies, antimicrobial peptides, aptamers and phages. Clinical diagnostics optimizes the drug delivery. In the era of diagnostic-based applications, it is logical to draw diagnostic based treatment for infectious diseases. Selection criteria of alternate therapeutics in infectious disease include detection, monitoring of response and resistance mechanism identification. Integrating these diagnostic applications is disruptive to the traditional therapeutic development. The challenges and mitigation methods need to be noted. Applying the goals of clinical pharmacokinetics that include enhancing efficacy and decreasing toxicity of drug therapy this review analyses the strong correlation of alternate antimicrobial therapeutics in infectious diseases. The relationship between drug concentration and the resulting effect defined by the pharmacodynamic parameters are also analyzed. This review analyzes the perspectives of aligning diagnostic initiatives into the use of alternate therapeutics with a particular focus on companion diagnostic applications in infectious diseases.

Current sampling methods for detecting the presence of the invasive freshwater hydrozoan Craspedacusta sowerbii rely mainly on visual confirmation of the medusa stage. Confirming the presence of the polyp stage is equally important to observing medusae since typical late summer/early fall occurrences or observations of medusae are sporadic though becoming more frequent. The polyp stage is important as it is the organism’s primary stage and is present throughout the year depending on water temperatures. Therefore, sampling methods for the polyp stage are commonly the collection of substrates such as rocks, plants or pieces of wood in a given body of water and can be cumbersome to examine. Based on preliminary culturing of the polyp stage on glass and plastic microscope slides in the lab, we designed a novel sampling methodology based on submerging 4 substrate types (small glass petri dishes, Hester-Dendy plates, plastic and glass microscope slides) to confirm the presence of C. sowerbii polyps in the field. We tested this method in various lakes in the Illinois-Indiana region (USA). The sampling method we designed was effective in that C. sowerbii polyps (and sometimes colonies) were found on both plastic and glass slides. While this method can be sufficient for detection of the polyp stage, it also shows significant potential for improvement; we highlight water flow and competition and predation from other organisms as significant factors influencing the collection of C. sowerbii polyps for future methodologies.

Hereditary Hemorrhagic Telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is a rare and inherited vascular disorder, characterized by the development of arteriovenous malformations (AVMs) in various organs and telangiectasia (small AVM) in the mucocutaneous. The majority of HHT patients have haploinsufficiency of genes involved in the transforming growth factor-beta (TGFβ) signaling pathway, including endoglin (ENG), activin receptor-like kinase 1 (ALK1, also known as ACVRL1), or SMAD4. Active angiogenesis is also required for telangiectasia and AVM development. Anti-angiogenic strategies have been tested in patients and animal models extensively. However, the exact mechanisms for telangiectasia and AVM development remain unclear. In this review, we discuss recent advances in identifying disease mechanisms, and potential therapeutic targets.

We present a new analytical method to find the asymptotic stable equilibria states based on the Markov chain technique. We reveal this method on the SIR-type epidemiological model that we developed for viral diseases with long-term immunity memory pandemic. This is a large-scale model containing 15 nonlinear ODE equations, and classical methods have failed to analytically obtain its equilibria. The proposed method is used to conduct a comprehensive analysis by a stochastic representation of the dynamics of the model, followed by finding all asymptotic stable equilibrium states of the model for any values of parameters and initial conditions.

Epilepsy is one of the most prevalent and serious brain disorders, affecting 70 million people worldwide. Antiseizure medications (ASMs) though relieve symptoms and prevent the occurrence of future seizures in epileptic patients have limited effect on epileptogenesis. Addressing the multifaceted nature of epileptogenesis and its association with Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated neuroinflammation requires a comprehensive understanding of the underlying mechanisms for development of targeted therapeutic strategies beyond conventional antiseizure treatments. Several types of NLRP3 inhibitors have been developed and their effect has been validated both in vitro and in vivo models of epileptogenesis. In this review, we discuss the advances in understanding the regulatory mechanisms of NLRP3 activation as well as progress made and challenges facing in the development of NLRP3 inhibitors for the treatment of epilepsy.

In patients with heart failure, the evaluation of left ventricular (LV) diastolic function is vital, offering crucial insights into hemodynamic impact and prognostic accuracy. Echocardiography stands as the primary imaging modality for diastolic function assessment, and using it effectively requires a profound understanding of the underlying pathology. This review covers four main topics: first, the fundamental driving forces behind each phase of normal diastolic dynamics, along with the physiological basis of two widely used echocardiographic assessment parameters, E/e' and mitral annulus early diastolic velocity (e'); second, the intricate functional relationship between the left atrium and LV in patients with varying degrees of LV diastolic dysfunction (LVDD); third, the role of stress echocardiography in diagnosing LVDD and the significance of parameter changes in this context; and fourth, the clinical utility of evaluating diastolic function from echocardiography images across diverse cardiovascular care areas.

Purpose: Investigation for the co-occurrence of two unrelated genetic disorders of muscular dystrophy and Prader-Willi syndrome (PWS) (OMIM # 176270) using joint whole genome sequencing (WGS). Methods: Trio WGS joint analysis was performed to investigate the genetic etiology in a proband with PWS, prolonged muscular hypotonia associated hyperCKemia, and early-onset obesity. The parents were unaffected. Results: Results showed maternal isodisomy uniparental disomy (UPD) in chromosome 15 expanding from 15q11.2 to 15q22.2, including PWS regions at 15q11.2-15q13. Maternal heterodisomy was detected from 15q22.2 to 15q26.3. A pathogenic variant, NM_000070.3(CAPN3):c.550del (p.Thr184fs), was identified at 15q15.1 in a heterozygous state in the mother that was homozygous in the proband due to maternal isodisomy. Conclusion: This is the first study of the concurrent molecular etiology of PWS and calpainopathy (OMIM # 253600) in the same patient. This report highlights the utility of joint analysis and need for the assessment of autosomal recessive disease in regions of isodisomy in patients with complex and unexplained phenotype.

This retrospective study assesses the efficacy and tolerability of anti-CGRP therapy in adolescents and young adults (ages 12-21) with migraines and chronic daily headaches unresponsive to standard treatments. Migraines severely affect school performance, self-esteem, psychological well-being, and cognitive health in this demographic, who are also sensitive to the side effects of conventional medications often prescribed off-label and face high insurance denial rates. Medication overuse, including analgesics, triptans, and NSAIDs, is prevalent due to treatment failures. Elevated plasma CGRP levels during migraines suggest that anti-CGRP therapies, which have shown success in adults, might benefit this age group. Over three years, patients at a specialized headache center were evaluated for the impact of anti-CGRP treatments, including monoclonal antibodies (erenumab, fremanezumab, galcanezumab) and small molecule CGRP receptor antagonists (ubrogepant, rimegepant, atogepant), either alone or in combination with OnabotulinumtoxinA. The study found significant improvements in migraine management, especially among older adolescents, with reduced rescue medication use and emergency visits. Longer treatment courses and combination therapy with traditional medications were more effective than monotherapy, reducing migraine intensity and frequency. Adverse effects were minimal, and no significant medication interactions were noted. Anti-CGRP therapy demonstrates substantial potential in improving outcomes for this age group with chronic and episodic migraines.

Out-of-hospital cardiac arrest (OHCA) represents a significant global public health burden, characterized by low survival and few established diagnostic tools to guide intervention. OHCA presents with a wide variety of etiologies in a heterogeneous population, posing a clinical challenge to care teams. In this review, we describe evolving research focused on diagnostic approaches to OHCA following resuscitation, including electrocardiography, coronary angiography, computed tomography, ultrasonography, and serologic biomarker assessment. These diagnostic tools have been employed in post-resuscitative efforts for diagnosing ischemic and non-ischemic cardiac, respiratory, neurologic, vascular, traumatic, and metabolic causes of arrest.

Alzheimer’s disease (AD) is a progressive irreversible neurodegenerative disorder that represents a major global public health concern. Traditionally, AD is diagnosed using cerebrospinal fluid biomarker analysis or brain imaging modalities. Recently, less burdensome, more widely available blood biomarker (BBM) assays for amyloid-beta (Aβ42/40) and phosphorylated-tau concentrations have been found to accurately identify the presence/absence of brain amyloid plaques and tau tangles and have helped to streamline AD diagnosis. However, few BBMs have been rigorously analytically validated. Herein, we report the analytical validation of a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantifying plasma phosphorylated-tau217 (p-tau217) and non-phosphorylated-tau217 (np-tau217) peptide concentrations. We combined the p-tau217/np-tau217 concentrations ratio (%p-tau217) and the previously validated LC-MS/MS assay for plasma Ab42/40 into a new multiple analyte blood test and algorithm (PrecivityAD2™) that identifies brain amyloid status based on brain amyloid positron emission tomography. We found: (a) the %p-tau217 assay is precise, accurate, sensitive, linear over a wide analytical measurement range, and free from carryover and interference; (b) the pre-analytical specimen collection, processing, storage and shipping conditions that maintain plasma tau peptide stability; and (c) using the measured analytical imprecision for plasma Aβ42/40 and p-tau217/np-tau217 levels in a worst-case scenario model, the PrecivityAD2 test algorithm for amyloid pathology classification changed for only 3.5% of participants from brain amyloid positive to negative, or negative to positive. The plasma sample preparation and LC-MS/MS methods underlying the PrecivityAD2 test are suitable for use in the clinical laboratory and valid for the test’s intended purpose: to aid in the diagnostic evaluation of individuals aged 55 and older with signs or symptoms of mild cognitive impairment or dementia.

This paper represents a groundbreaking paradigm shift in network optimization. Departing from traditional static methodologies, this innovative approach harnesses the power of Generative Artificial Intelligence (AI) and Large Language Models (LLMs) to optimize cloud networks dynamically. By integrating advanced AI algorithms, this framework continuously adapts and evolves, ensuring optimal real-time performance. This dynamic optimization enhances efficiency and resilience, allowing cloud networks to adjust seamlessly to changing demands and conditions. Through the fusion of cutting-edge technology and adaptive intelligence, this approach heralds a new era in network optimization, empowering organizations to achieve unprecedent-ed levels of agility and scalability in their cloud infrastructures.

Reducing fertilizer-N rate, applying nitrification inhibitor (NI), and incorporating straw are widely recommended to improve N use efficiency of crops and decrease N losses. However, how these practices affect crop N uptake by regulating the fertilizer-N fate during the growing season is not well understood. We conducted a field 15N tracer study to explore the effectiveness of reduced N application, NI, and straw incorporation on fertilizer-N fates for maize cultivation in Northeast China. The following six treatments were used: 1) no N fertilization (control); 2) 200 kg urea-N ha−1 (100%N); 3) 200 kg urea-N ha−1 and 2400 kg dry-straw ha−1 (100%N+S); 4) 160 kg urea-N ha−1 (80%N, i.e., 20% reduction of N fertilization); 5) 160 kg urea-N ha−1 and nitrification inhibitor (Nitrapyrin) (80%N+NI); 6) 160 kg urea-N ha−1, nitrification inhibitor and 2400 kg dry-straw ha−1 (80%N+NI+S). Our results showed that the five N fertilization treatments yielded 16%–25% more grain and 39%–60% more crop N uptake than the control receiving no N fertilizer, but the differences among the five treatments were not statistically significant. In contrast to plant growth, changes in fertilizer-N fates in soil and plant pools were more pronounced. Compared with the 100%N treatment, 20% fertilizer-N reduction (80%N) decreased 15N concentration in topsoil and plant pools but increased the proportion of plant 15N recovery at harvesting (N use efficiency, NUE15N, 60% vs. 50%) (P &lt; 0.05). Nitrapyrin co-application (80%N+NI) delayed soil nitrification and increased soil 15N retention at harvesting (52% vs. 36%), thereby decreasing NUE15N significantly (P &lt; 0.05). Straw incorporation (100%N+S) decreased fertilizer-N retention compared with NI co-application because it promoted NUE15N significantly (P &lt; 0.05). The combined application of NI and straw (80%N+NI+S) was more conducive to fertilizer-N retention in soil. Our findings demonstrate that NI and straw additions are efficient strategies for stabilizing fertilizer-N in soils and potentially minimizing N loss; however, their effects on NUE15N vary and the related mechanism must be further clarified in long-term trials.

Objective: To develop an algorithm that accurately identifies children with Down syndrome (DS) using administrative data. Methods: We identified a cohort of children born 2000-2017, enrolled in a state Medicaid program, who either had DS coded on the birth certificate or had a diagnosis listed using an International Classification of Diseases (ICD) code (suspected DS), and who received care at a comprehensive academic medical center in the United States. Children with suspected DS were defined as having DS if they had a) karyotype confirmed DS indicated on their birth certificate; b) karyotype pending DS indicated on their birth certificate (or just DS if test type was not specified) and at least two healthcare encounters for DS during the first 6 years of life; or c) at least three healthcare encounters for DS, with the first and last encounter separated by at least 30 days, during the first six years of life. Positive predictive value (PPV) of the algorithm and 95% confidence interval (CI) were reported. Results: Of the 411 children with suspected DS, 354 (86.1%) were defined as having DS by the algorithm. According to medical chart review, the algorithm correctly identified 347 children with DS (PPV=98%, 95%CI: 96.0%-99.0%). Of the 57 children the algorithm defined as not having DS, 50 (97.7%, 95%CI: 76.8%-93.9%) were confirmed not having DS by medical chart review. Conclusions: An algorithm that accurately identifies individuals with DS using birth certificate data and/or ICD codes provides a valuable tool to study DS using administrative data.

Prostate cancer (PCa) ranks as the second most fatal and sixth most prevalent cancer among males globally. This study focuses on leveraging deep learning networks to detect the Gleason grading of prostate cancer from histopathology images stained with Hematoxylin and Eosin (H&amp;E). Six pathologists annotated the images, resulting in six distinct labels for each input image. A common ground truth label was established through majority voting approach. Subsequently, the dataset was trained using architectures: UNeT, UNeT++, DeepLabV3, DeepLabV3+, and GAN based segmentation network. Notably, GAN based network demonstrated superior performance, achieving an F1-score of 0.872 and a Jaccard Index of 0.777, outperforming the other architectures considered in this study.

With the increasing use of data-driven modeling methods new approaches to complex problems in the field of wind energy can be addressed. Topics reviewed through literature include wake modeling, performance monitoring and controls applications, condition monitoring and fault detection, and other data-driven research. Literature shows the advantages of data-driven methods reduce computational expense or complexity, particularly in the cases of wake modeling and controls, as well as various data-driven methodologies’ aptitude for predictive modeling and classification, as in the cases of fault detection and diagnosis. Significant work exists for fault detection while less work is found for controls applications. A methodology for creating data-driven wind turbine models for arbitrary performance parameters is proposed. Results are presented utilizing the methodology to create wind turbine models relating active adaptive twist to steady-state rotor thrust as a performance parameter of interest. Resulting models are evaluated by comparing root-mean-square-error (RMSE) on both the training and validation data sets, with Gaussian Process Regression (GPR), deemed an accurate model for this application. The resulting model undergoes particle swarm optimization to determine the optimal aerostructure twist shape at a given wind speed with respect to the modeled performance parameter, aerodynamic thrust load. The optimization process shows an improvement of 3.15% in thrust loading for the 10 MW reference turbine, and 2.66% for the 15 MW reference turbine.

LC-SPIK is a liver cancer-specific isoform of Serine Protease Inhibitor Kazal and has been proposed as a new biomarker for the detection of HCC given its unique 3-D structure which differs from normal pancreatic SPIK. An ELISA technology based on its unique structure was developed to use LC-SPIK as an effective biomarker for the clinical diagnosis of HCC. AFP, the most widely used biomarker for HCC surveillance currently, suffers from poor clinical performance, especially in the detection of early-stage HCC. In one case-control study, which included 164 HCC patients and 324 controls, LC-SPIK had an AUC of 0.87 compared to only 0.70 for AFP in distinguishing HCC from liver disease controls (cirrhosis, HBV/HCV). LC-SPIK also performed significantly better than AFP for the 81 patients with early-stage HCC (BCLC stage 0 and A), with an AUC of 0.85 compared to only 0.61 for AFP. Cirrhosis is the major risk factor for HCC, about 80% of patients with newly diagnosed HCC have preexisting cirrhosis. LC-SPIK’s clinical performance was also studied in HCC patients with viral and non-viral cirrhosis including cirrhosis caused by nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). In a total of 163 viral cirrhosis patients with 93 HCC patients (50 early-stage), LC-SPIK had an AUC of 0.85, while AFP had an AUC of 0.70. For patients with early-stage HCC, LC-SPIK had a similar AUC of 0.83, while AFP had an AUC of only 0.60. For 120 patients with nonviral cirrhosis, including 62 HCC (23 early-stage) patients, LC-SPIK had an AUC of 0.84 while AFP had an AUC of only 0.72. For the 23 patients with early-stage HCC, LC-SPIK had a similar AUC of 0.83, while the AUC for AFP decreased to 0.65. All these results suggest that LC-SPIK has significantly better performance in the detection of HCC than AFP in all etiologies of liver diseases. In addition, LC-SPIK accurately detected the presence of HCC in 71%-91% of HCC patients with false-negative AFP test results in viral associated HCC and non-viral associated HCC.

Nucleosomes are non-uniformly distributed across eukarytic genomes, with stretches of ‘open’ chromatin strongly associated with transcriptionally active promoters and enhancers. Understanding chromatin accessibility patterns in normal tissue and how they are altered in pathologies can provide critical insights to development and disease. With the advent of high-throughput sequencing, a variety of strategies have been devised to identify open regions across the genome, including DNase-seq, MNase-seq, FAIRE-seq, ATAC-seq, and NicE-seq. However, the broad application of such methods to FFPE (formalin-fixed paraffin embedded) tissues has been curtailed by the major technical challenges imposed by highly fixed and damaged genomic material. Here we review the most common approaches for mapping open chromatin regions, recent optimizations to overcome the challenges of working with FFPE tissue, and a brief overview of a typical data pipeline with analysis considerations.

MicroRNAs, short non-protein coding RNAs, are overexpressed in GCTs. Circulating levels of germ cell tumor (GCT)- associated miRNAs, such as miR-371a-3p, can be utilized as efficient and cost-effective alternatives in diagnosing and managing patients presenting with GCTs. This quality of miRNAs has demonstrated favorable performance characteristics as a reliable blood-based biomarker with high diagnostic accuracy compared to current serum tumor markers (STMs) including α-fetoprotein (AFP), beta human chorionic gonadotropin (β-hCG), and lactate dehydrogenase (LDH). The conventional STMs exhibit limited specificity and sensitivity. Potential clinical implications of miRNAs include impact on de-escalating or intensifying treatment, detecting recurrence at earlier stages, and lessening the necessity of cross-sectional imaging or invasive tissue biopsy for non-teratomatous GCTs. Here we also highlight the outstanding issues that must be addressed prior to clinical implementation. Standards for measuring circulating miRNAs and determining ideal cutoff values are essential for integration into current clinical guidelines.

Fibrosis is a ubiquitous pathology, and prior studies have indicated that various artemisinin (ART) derivatives (including artesunate (AS), artemether (AM), and dihydroartemisinin (DHA)) can reduce fibrosis in vitro and in vivo. The medicinal plant, Artemisia annua L., is the natural source of ART and is widely used, especially in underdeveloped countries, to treat a variety of diseases including malaria, while A. afra contains no ART but is also antimalarial. Using human dermal fibroblasts (CRL-2097), we compared the effects of A. annua and A. afra tea infusions, ART, AS, AM, DHA, and a liver metabolite of ART, deoxyART (dART), on fibroblast viability and expression of key fibrotic marker genes after 1 and 4 days of treatment. AS, DHA, and Artemisia tea significantly reduced fibroblast viability at 1 and 4 d post-treatment. After 4 d post treatment, AS, DHA, and A. afra tea downregulated ACTA2, and upregulated MMP3, with other genes either being unaffected or differentially affected. ART and AM had no significant effect on either fibroblast viability or fibrotic gene expression. Although A. annua contains ART, it had a significantly greater anti-fibrotic effect than ART alone. Immunofluorescent staining for smooth muscle α-actin (α-SMA) correlated well with transcriptional responses of drug-treated fibroblasts. Together, proliferation, qPCR, and immunofluorescence results show that treatment with ART, AS, DHA, and the two Artemisia teas yield differing responses, including those related to fibrosis, in human dermal fibroblasts.

Dynamic systems which underly controlled systems are expected to increase in complexity as robots, devices, and connected networks become more intelligent. While classical stable systems converge to a stable point (a sink), another type of stability is to consider a stable path rather than a single point. Such stable paths can be made of saddles which draw in trajectories from certain regions, and then push the trajectory toward the next saddle point. These are chains of saddles are called stable heteroclinic channels (SHCs), and can be used in robotic control to represent time sequences. While we have previously shown that each saddle is visualizable as a trajectory waypoint in phase space, how to increase the fidelity of the trajectory was unclear. In this paper, we hypothesized that the waypoints can be individually modified to locally vary fidelity. Specifically, we expected that increasing the saddle value (ratio of saddle eigenvalues) causes the trajectory to slow to more closely approach a particular saddle. Combined with other parameters that control speed and magnitude, a system expressed with an SHC can be modified locally, point by point, without disrupting the rest of the path, supporting their use in motion primitives. However, even more complex trajectory shape modifications are possible. While some combinations can enable a trajectory to better reach into corners, other combinations can rotate, distort and round the trajectory in the region of a corner. In our example, modifying select saddle values produced a 32% decrease in the trajectory error of a complex trajectory produced using this system. This is an effect not visible in previous 1D studies, that can lead to different learnable and tunable representations of dynamic systems.

The influence of climate conditions and stable design on horses housed in single stalls can have significant effects, especially in regions with tropical savannah climates. A recent study observed variations in autonomic responses in horses housed in different stable designs during the summer, but there is limited information about their conditions during the monsoon. This study investigated the stable microenvironment and autonomic regulation of horses housed in different stable archi-tectures during the monsoon in a tropical savannah environment. Twenty-two horses were allo-cated to one of three stable architectures, each with varying stable microenvironments. The findings reveal that the heart rate variability (HRV) was lower in horses in a stable with a solid external wall and lower volume-to-horse ratio compared to those in a stable with a solid external wall but a higher volume-to-horse ratio or one without a solid external wall. Additionally, the study found that stable microenvironments and HRV modulation were correlated with stable architecture. Autonomic responses differed among horses in different stable architectures, indicating that stable microen-vironments and, to some extent, volume-to-horse ratio play a role in horses’ autonomic regulation. The findings have implications for improvements in housing and welfare in tropical savannah environments.

With advancements in remote sensing technology and affordable design, uncrewed aerial systems (UAS), commonly known as drones, have become prevalent in both civil and military applications, such as agriculture, public safety, and aerial imaging. However, the rise in unlawful UAS activities, such as non-compliance with legal standards and potential terrorist attacks, has raised significant public concern, necessitating effective detection and mitigation solutions. Despite the growing importance of this issue, comprehensive and detailed examinations of existing counter-UAS solutions are lacking. To address this gap, this study conducts a bibliometric analysis and scoping review of the current literature to identify key topics and emerging trends in counter-UAS approaches. Utilizing co-word and social network analyses, the study identifies strong and weak connections between selected keywords from academic articles. This study summarizes the limitations and potential opportunities within counter-UAS research, suggesting an increasing focus on multisensory fusion and machine-learning approaches for drone detection and mitigation. Additionally, areas such as swarm drone operations, UAS traffic management (UTM), and UAS networks are identified as important but promising fields for further investigation. The findings of this study provide a foundation for enhancing air and ground safety through improved counter-UAS applications.

Long-range HNCO NMR spectra for proteins show crosspeaks due to 1JNC, 2JNC, 3JNCg and h3JNC couplings. The h3JNC couplings are transmitted through hydrogen bonds and are correlated to hydrogen bond lengths. We collected long-range HNCO data at a series of temperatures for four protein states. P22i and CUS-3i are six-stranded beta-barrel I-domains from phages P22 and CUS-3 that share less than 40% sequence identity. The cis and trans states of the C-terminal domain from pore-forming toxin hemolysin ΙΙ (HlyIIC) arise from isomerization of a single G404-P405 peptide bond. For P22i and CUS-3i the hydrogen bonds detected by NMR agree with those observed in the corresponding domains from cryoEM structures of the two phages. Hydrogen bond lengths derived from the h3JNC couplings, however, are poorly conserved between the distantly related CUS-3i and P22i domains and show differences even between the cis and trans states of HlyIIC. This is consistent with hydrogen bond lengths being determined by local differences in structure rather than the overall folding topology. With increasing temperature hydrogen bonds typically show an apparent increase in length, which has been attributed to protein thermal expansion. Some hydrogen bonds are invariant with temperature, however, while others show apparent decreases in length suggesting they become stabilized with increasing temperature. Considering the data for the three proteins in this study and previously published data for ubiquitin and GB3, lowered protein folding stability and cooperativity correlates with a larger range of temperature responses for hydrogen bonds. This suggests a partial uncoupling of hydrogen bond energetics from global unfolding cooperativity as protein stability decreases.

The general synthesis of boron-containing cyclic compounds (boracycles) necessitates toxic organotin precursors or highly reactive boron halides. Here we report the synthesis of seven- and five-membered boracycles utilizing arylboronic acid pinacol esters (ArBpins) as stable boron sources. Grignard reagents generated from 2,2′-dibromodibenzyl or 2,2′-dibromobiphenyl reacted with ArBpins, where Ar = 9-anthryl (Anth), 2,4,6-trimethylphenyl (Mes), 2,4,6-triisopropylphenyl (Tip), to give 10,11-dihydro-5H-dibenzo[b,f]borepins or dibenzoborole derivatives. This Bpin-based method was successfully applied to a one-shot double boracycle formation, providing a dihydrodibenzoborepin–anthracene–dihydrodibenzoborepin triad molecule in a good yield. The dihydrodibenzoborepin bearing the Anth group was directly converted to the unsaturated borepin by NBS/AIBN. All products were characterized by NMR, HRMS, and in some cases, single-crystal X-ray diffraction analysis. Additionally, the photophysical properties of the products are also reported.

This paper presents a wideband dual-polarized dipole antenna structure operating at 1.7-3.8 GHz (76.4%). For a traditional 4G dipole antenna which covers the band 1.71 GHz- 2.69 GHz, it’s difficult to maintain the satisfactory impedance matching and normal stable radiation patterns within the 5G sub-6 GHz band 3.3-3.8 GHz, which mainly due to the fixed antenna height is no longer a quarter-wavelength. To solve this, a connected-ring-shaped metasurface structure is proposed and deployed to operate as an artificial magnetic conductor (AMC). As a result, stable antenna radiation patterns are obtained within the whole band 1.7-3.8 GHz. For verification, this wideband dipole antenna using AMC is implemented and tested. The measured results show that the proposed antenna has an impedance bandwidth of 80.7% (1.7-4.0 GHz). It has an average measured in-band realized gain of 7.0±1.0 dBi and a stable 70∘±5∘ half power beam width (HPBW) within the 4G/5G-sub 6GHz bands 1710-2690 MHz and 3300-3800 MHz.

Since the discovery of transposable elements (TEs) in Maize in the 1940s by Barbara McClintock [1] transposable elements have been described as junk, as selfish elements with no benefit to the host, and more recently as major determinants of genome structure and genome evolution. TEs are DNA sequences that are capable of moving to new sites in the genome and make additional copies while doing so. To limit the propagation of TEs, host silencing mechanisms are directed at transposon-encoded genes that are required for mobilization. The mutagenic properties of TEs, the potential of TEs to form new genes and affect gene expression, together with the host silencing mechanisms shape eukaryotic genomes and drive genome evolution. While TEs constitute more than half of the genome in many higher eukaryotes, transposable elements in the nematode C. ele-gans form a relatively small proportion of genome, about 15% [2]. Genetic studies of transposon silencing and the discovery of RNAi in C. elegans, propelled C. elegans to the forefront of studies of RNA-based mechanisms that silence TEs. Here, I will review the transposable elements that are present and active in the C. elegans genome, and the host defense mechanisms that silence these elements.

Introduction: In the recent years alternate day dosing has been recommended in iron deficieny treatment. The aim of this study is to compare the efficacy and side effects of oral iron treatments given daily 1x1, alternate day 1x1 and 2x1 alternate day dosing in iron deficieny anemia patients. Methods: A total of 52 patients with a diagnosis of iron deficiency anemia with serum ferritin level of 25 µg/L or less were included in this retrospective study. Statistical analyzes were done with SPSS V.25. Results: The patients included in our study were between the ages of 18-51. All of the patients included in the study were female. A statistically significant increase was found between 0-14 days(p<0.001), 14-28 days(p<0.001) and 0-28 days(p<0.001) hemoglobin values in all patients. There was no statistically significant difference between 0-14 days (p=0.397) and 0-28 days(p=0.310) ferritin values in all patients. A statistically significant difference was found between 14-28 days(p<0.001) ferritin values. When the rate of change of hemoglobin and ferritin values between the groups was compared and no statistically significant difference was observed between the groups. The rate of change of ferritin values for 14-28 days was significant (p=0.012). There was no significant difference in the frequency of symptoms in the 14th day and 28th day controls for each group (p>0.05). The incidence of metallic taste and bloating symptoms was found to be statistically significant in the third control in the group with 2x1 drug use alternate day (p=0.094). Discussion: The only difference in efficacy was observed in ferritin values between 14th and 28th days. The increase in ferritin values was higher in the group that used 1x1 oral iron every day. However, since no difference was observed between the groups in terms of ferritin and hemoglobin values on days 0 and 28, all three groups were considered equally efficient. Side effects were mainly gastrointestinal side effects. Since the group that received 2x1 oral treatment alternate day had a statistically significantly higher rate of side effects, the patients’ treatment tolerance will be lower compared to the other groups. In conlusion, there is no difference in efficacy and side effects between the patient groups receiving 1x1 daily and 1x1 alternate day oral iron therapy, so 1x1 use alternate day is the most appropriate treatment method for oral iron therapy in terms of patient tolerance, adherence to treatment and pharmacoeconomics.

Entanglement is one of the most striking features in quantum systems. Today, quantum entanglement plays a vital role in quantum technology, the non-classical correlation of quantum entanglement is an important resource for quantum communication and quantum computing. Entanglement can be divided into two categories: between multi-particle systems and between various degrees of freedom in a single-particle system (intraparticle entangled states). This work first analogized the distinctions and connections between two kinds of entangled states. Then it designed three types of entanglement-swapping methods based on Bell state joint measurement, cross-Kerr medium, and linear optical elements for intraparticle entangled states by analogizing the entanglement swapping between multiple particles. Intraparticle entanglement swapping can be applied in super quantum dense encoding, quantum information transmission, and quantum teleportation. This work is beneficial for promoting the development of quantum information technologies.

Prostate Cancer remains a prevalent health concern, emphasizing the critical need for early diagnosis and precise treatment strategies to mitigate mortality rates. Accurate prediction of cancer grade is paramount for timely interventions. This paper introduces an approach to prostate cancer grading, framing it as a classification problem. Leveraging ResNet models on multi-scale patch-level digital pathology and the Diagset dataset, the proposed method demonstrates notable success, achieving an accuracy of 0.999 in identifying clinically significant prostate cancer. The study contributes to the evolving landscape of cancer diagnostics, offering a promising avenue for improved grading accuracy and, consequently, more effective treatment planning. By integrating innovative deep-learning techniques with comprehensive datasets, our approach presents a step forward in the pursuit of personalized and targeted cancer care.

The chiral optical Tamm state (COTS) is a special localized state at the interface of a handedness-preserving mirror and a structurally chiral medium such as a cholesteric liquid crystal or a chiral sculptured thin film. The spectral behavior of COTS, observed as reflection resonances, is described by the temporal coupled-mode theory. Mode coupling is different for two circular light polarizations because COTS has a helix structure replicating that of the cholesteric. The mode coupling for co-handed circularly polarized light exponentially attenuates with the cholesteric layer thickness since the COTS frequency falls into the stop band. Cross-handed circularly polarized light freely goes through the cholesteric layer and can excite COTS when reflected from the handedness-preserving mirror. The coupling in this case is proportional to anisotropy of the cholesteric and theoretically it is only anisotropy of magnetic permittivity that can ultimately cancel this coupling. These two couplings being equal results in a polarization crossover (the Kopp--Genack effect) for which a linear polarization is optimal to excite COTS. The corresponding cholesteric thickness and scattering matrix for COTS are generally described by simple expressions.

Cancer diagnosis and classification are pivotal for effective patient management and treatment planning. In this study, we present a comprehensive approach utilizing ensemble deep learning techniques to analyze breast cancer histopathology images. Our datasets are based on two widely employed datasets from different centers for two different tasks: BACH and BreakHis. Within the BACH Dataset, we deployed an ensemble strategy incorporating VGG16 and ResNet50 architec-tures to achieve precise classification of breast cancer histopathology images. Introducing a novel image patching technique, to preprocess a high-resolution image, which facilitates focused analysis of localized regions of interest. The annotated BACH dataset encompasses 400 WSIs across four distinct classes: Normal, Benign, In Situ Carcinoma, and Invasive Carcinoma. In addition, we employed the BreakHis dataset, utilizing VGG16, ResNet34, and ResNet50 models to classify mi-croscopic images into eight distinct categories (four benign and four malignant). For both models we leveraged a five-fold cross-validation approach for rigorous training and testing. Preliminary ex-perimental results indicate a Patch classification accuracy of 95.31% (on BACH dataset) and WSI image classification accuracy of 98.43% (BreakHis). This research significantly contributes to on-going endeavors in harnessing artificial intelligence to advance breast cancer diagnosis, potentially fostering improved patient outcomes and alleviating healthcare burdens.

Cancer cells are believed to be recognized and controlled by the immune system of the host, especially the adaptive immune system. Cancers may be initiated by a single gene defect in stem cells or regenerating cells during the replacement of old or injured tissue cells, and additional gene defect(s) then occur. To compensate for missing proteins intracellular homeostasis systems, such as proteostasis, may work with activation of new genes. The risk or predisposing factors in cancers may be related to the number of tissue cell renewals (the turnover time) and the probability of gene defect(s). Oncological symptoms may be associated with substances that are derived from antigens expressed on cancer cells and those derived from damaged cancer cells with corresponding immune reactions. In patients with cancers or other conditions, inadequate immune components to control these substances may result in chronic inflammatory or autoimmune diseases. Cancer cells communicate with host cells, including the immune cells such as T cells, for survival and proliferation and may need assistance from immune cells against intracellular infections or physicochemical insults. T cell-based immune therapeutics have been developed and clinically used in some cancers, especially in advanced cancers. We further discuss the oncogenesis, pathophysiology of cancers, and unresolved issues in tumor immunology and reinterpret the effectiveness of T cell-based therapies under the protein-homeostasis-system hypothesis.

In case of the maximally rotating Black Holes (BH) through Kerr-Neumann frames, or as described in Boyer-Lindquist coordinates metrics, the rotation axis of the BHs inputs a frame dragging effect i.e., relativistically a Lens-Thirring Precession that accelerates the photon trajectories oscillates with a shaped induced rotations through the ring singularity, between alternate universes, as a means of an induced geodesics that takes a sharp turning points back and forth provided, in the prograde photon sphere, due to magnetorotational instability, the path tracing of a photons circulates as a smooth fiber bundles over the event horizon curves, that when gets interpolate between mixed trajectories behaves as a geodesics and thus forms a smooth Jacobi-fields through Jacobi-lines by mutual intersection of geodesics over the photon sphere which when somehow gets leaked inside the event horizon, then gets sucked in with not sufficient escape velocity for retardation and trapped in the compact singularity, oscillating back and forth through alternate universes.

To clarify effects of weathered coal humic acid on water-stable aggregates and pore characteristics of reclaimed cambisol, this research analyzed the evolution characteristics of soil aggregates and pores. Effects of different humic acid dosages (0, 1%, 3%, and 5% by weight) and application period (1 year, 2 years, and 3 years) on soil aggregates and organic carbon components in soil water-stable aggregates were investigated. The results showed that water-stable macroaggregates (&gt;0.25 mm) had the highest content in the first year; but in the third year, water-stable microaggregates (0.053–0.25 mm) had the highest content, and silt and clay (&lt;0.053 mm) were at a maximum. In the third year of 5% treatment, mean weight and geometric mean diameters were the largest, soil structure was the most stable, and TOC and water-stable microaggregates (0.053–0.25 mm) in soil had the highest proportions. For 5% treatment, the majority of irregular pores were independent in the first year, and number of pores decreased in the second year, but average pore volume increased, forming robust connected pores. In the third year, the number of elongated and irregular pores increased. In the third year of 5% treatment, most pores were irregular and of size &gt;100 μm, and soil structure was the most stable.

Contrasting results have suggested that the prevalence and intensity of post abortion emotional distress (PAD) either diminishes rapidly or persists over time. Few studies have followed women for longer than five years. This study examines retrospective population data on 226 ever aborting U.S. women aged 41-45, at an average of 20 years following the abortion, with extensive measures of PAD. Most post abortive women (55.2%) experienced little or no distress from their abortion(s) and 74.6% were confident it had been the right decision, but 44.8% reported moderate (20.7%) to high (24.1%) distress related to their abortion(s), including 37.7% who reported negative emotions; 31.2% “frequent feelings of loss, grief or sadness;” 24.6% “frequent thoughts, dreams, or flashbacks;” 23.2% for whom thoughts and feelings about their abortion “negatively interfered with life, work, or relationships.” Time since the abortion (mean 20 years, range 0-31 years) was not correlated with PAD (r = -.02, p .71). For the minority of women who experienced it, PAD did not diminish but persisted for decades. An estimated 7.5 million U.S. women currently experience persistent high PAD. Further research to specify risk factors and possible interventions for postabortion distress would be of value for this group of women.

A structure based analysis of the pion’s decay path reveals that neutrinos can show up in three eigenstates. It requires a proper understanding of the nature of charged leptons, such as why the loss of binding energy stops the lepton generation at the tauon level. The analysis quantifies this binding energy in terms of the weak interaction strength as embodied by the weak interaction boson and the strength of the energetic background field as embodied by the Higgs boson. Next to this it is shown that a reconstruction of Fermi’s neutrino theory allows a quantitative assessment of the Fermi constant straightforwardly from the weak interaction strength. The article ends with the conclusion that neutrino oscillation is not a physical phenomenon, but, instead, a measurement interpretation induced from projecting the statistical behaviour of a multi-particle ensemble onto a single particle.

Tomato brown rugose fruit virus (ToBRFV) is an emerging tobamovirus infecting tomatoes and peppers. Due to its ability to trigger seed contamination, efficient mechanical transmission, and to break the popular resistance genes (Tm-1, Tm-2 and Tm-22), the virus has resulted in a global pandemic on greenhouse tomato production in recent years despite the implementation of strict hygiene and disinfection measures. The objective of this study was to evaluate whether ToBRFV can be transmissible through recirculating hydroponic systems and search for effective approach to contain its spread under such circumstances. We not only detected the presence of ToBRFV in the runoff water solutions collected from ToBRFV-infected tomato greenhouses, but also demonstrated the infectivity of detected virus through initiating ToBRFV infection on tomato plants using bioassay. We then conducted treatment using cold plasma-generated ozone on ToBRFV-contaminated water reservoir and further assessed the efficacy of the treatment to inac-tivate the virus. Results showed the effectiveness of the cold-plasma ozone treatment was de-pendent on the ozone concentrations (0.1 mg/L to 1.0 mg/L), the periods of exposure (24 min to 72 min), and the relative virus titers (1:100 to 1:10,000 - dilution of virus-infected tissue extract), demonstrating the cold-plasma ozone treatment could offer a promising solution to cope with the potential ToBRFV spread through a recirculating hydroponic system in a greenhouse.

We report the case of a 44-year-old woman who suffered gastric perforation after receiving bag-valve-mask (BVM) ventilation in the setting of alcohol intoxication. She had a markedly distended abdomen and cold, dusky lower extremities upon arrival to the emergency department. Imaging revealed a large volume intraabdominal accumulation of air with compression of the aorta. Needle decompression relieved symptoms of lower extremity arterial insufficiency. However, the patient quickly decompensated and subsequent exploratory laparotomy confirmed gastric rupture. A subtotal gastrectomy was performed but the patient ultimately passed on post-operative day two due to multi-organ dysfunction. Although BVM ventilation is commonplace in both the hospital and field, there is a lack of awareness of the serious complications of abdominal air accumulation due to their rareness in the adult population. Checking for abdominal distention during resuscitation ought to be routine in all patients. Signs of arterial insufficiency accompanying abdominal distention, once confirmed by diagnostic imaging that shows extensive pneumoperitoneum, are indicators of having reached a life-threatening level of air accumulation, calling for immediate needle decompression and exploratory laparotomy.

The motor protein Prestin found in the outer hair cells (OHCs) of the inner ear is responsible for producing high sensitivity and sharp frequency selectivity for mammalian hearing. Some studies have suggested that Prestin could serve as a serological biomarker for cochlear damage since OHCs are highly vulnerable to damage from various sources of insults. However, the reported data are inconsistent and lack appropriate negative controls. To investigate this further, we measured Prestin quantities in the bloodstream using ELISA kits from different companies. Wildtype (WT) mice were exposed to different ototoxic treatments, including noise exposure and ototoxic reagents that kill OHCs rapidly. Prestin-knockout (KO) mice were used as a negative control. Our data show that some ELISA kits were not able to detect Prestin specifically. The ELISA kit that could detect Prestin protein from cochlear homogenates failed to detect Prestin in the bloodstream despite significant damage to OHCs in cochleae. Furthermore, the optical densities of samples, which correlate to Prestin quantities, were significantly influenced by hemolysis in the samples. In conclusion, Prestin from OHCs is not a sensitive and reliable serological biomarker for detecting cochlear damage in mice.

Brain aging causes a wide variety of changes at molecular and cellular levels, leading to the decline of cognitive functions and increased vulnerability to neurodegenerative disorders. The research aimed at understanding the aging of the brain has made much progress in recent decades. Technological innovations such as single-cell RNA-sequencing (scRNA-seq), proteomic analyses, and spatial transcriptomic analyses have facilitated the research on the dynamic changes occurring within neurons, glia, and other cells along with their impacts on intercellular communication during aging. In this review, we introduce recent trends of how neurons and glia change during aging and discuss the impact of the brain microenvironment such as the blood-brain barrier (BBB).

This study aimed to evaluate the effect of three yeast strains, Pichia guilliermondii (Levica 27), Candida norvegensis (Levazoot 15), and a commercial product (Levucell® SC 10) containing Saccharomyces cerevisiae, on in vitro rumen fermentation of two substrates: corn stover and a total mixed ration (TMR). Samples were taken 24 hours post-fermentation to measure pH, ammonia nitrogen (NH3-N), gas production, and volatile fatty acid (VFA) concentrations. The addition of yeasts did not affect gas production at 24 hours for either diet. For pH, differences between yeast strains were noted when TMR was used. The lowest NH3-N concentration (6.1 mM) was recorded with corn stover, showing similar results across strains. Conversely, NH3-N levels with TMR ranged from 47 mM to 66 mM. The inclusion of all three yeast strains increased the molar concentrations of total VFA, as well as acetic (C2), propionic (C3), and butyric (C4) acids in the rumen fluid. The C2:C3 ratio remained unchanged with corn stover but decreased with the inclusion of Levica 27 and Levazoot 15 in the TMR. With the commercial product Levucell® SC 10, this ratio was comparable to the control treatment. In conclusion, Levica 27 and Levazoot 15 demonstrated a stimulatory effect on in vitro rumen fermentation for the evaluated diets, evidenced by increased VFA concentrations.

Little in the scholarly economics literature is directed specifically to the performance of sta­ble value funds, although they occupy a leading place among retirement investment vehicles. They are currently offered in more than one-third of all defined contribution plans in the USA, with more than $800 billion of assets under management. This paper rigorously ex­amines their performance throughout the entire period since their inception in 1973. We produce a composite index of stable value returns. We next conduct mean-variance analysis, Sharpe and Sortino ratio analysis, stochastic dominance analysis, and optimal multi-period portfolio composition analysis. Our evidence suggests that stable value funds dominate (on average) two major asset classes based on a historical analysis, and that they often occupy a significant position in optimized portfolios across a broad range of risk aversion levels. We discuss factors that contributed to stable value funds’ past performance and whether they can continue to perform well into the future. We also discuss considerations regarding whether or not to include stable value as an element in target date funds within defined con­tribution pension plans.

The paper focuses on the admissibility problem of descriptor fractional-order systems (DFOSs). The alternate admissibility criteria are addressed for DFOSs with order in (0,2) which involve a non-strict linear matrix inequality (LMI) method and a strict LMI method, respectively. The forms of non-strict and strict LMIs are brand-new and distinguished with the existing literature, which fill the gaps of studies for admissibility. These approaches are available to the order in (0,2) without separating the order ranges into (0,1) and [1,2). In addition, a method involved least real decision variables in terms of strict LMIs is derived which is more convenient to process the practical solution. Three numerical examples are given to illustrate the validity of proposed results.

While there is overwhelming evidence for dark matter (DM) in galaxies and galaxy clusters, all searches for DM particles have so far proved negative. It is not even clear whether only one particle is involved or a combination or particles, their masses not precisely predicted. This non-detectability raises the possible relevance of modified gravity theories – MOND, MONG, etc. Here we consider a specific modification of Newtonian gravity (MONG) which involves gravitational self-energy, leading to modified equations whose solutions imply flat rotation curves and limitations of sizes of clusters. The results are consistent with current observations including that involving large spirals. This modification could also explain the current Hubble tension. We also consider effects of dark energy (DE) in terms of a cosmological constant.

The emergence of antimicrobial resistance (AMR) Candida auris presents a formidable global health challenge, causing severe healthcare-associated infections with high mortality rates. Its ability to colonize surfaces and resist standard disinfectants undermines traditional hygiene practices, prompting an urgent need for novel strategies. Ultraviolet C (UVC) light offers a promising approach due to its rapid and broad-spectrum germicidal efficacy. This review comprehensively examines the current knowledge of UVC LED technology in combating C. auris, highlighting its effectiveness, limitations, and potential applications in healthcare hygiene. UVC light has potent activity against C. auris, including multidrug-resistant (MDR) strains. UVC can reduce C. auris on contaminated surfaces, aiding in transmission prevention. This review explores implementation strategies, including mobile UVC systems for targeted disinfection of high-risk areas and equipment, integration into air handling units (AHUs) to continuously disinfect recirculating air, and incorporation into water treatment systems. Current limitations in our understanding of UVC safety and effectiveness necessitate further research to optimize application protocols and ensure treatment safety while maintaining efficacy against C. auris. Integrating UVC disinfection technology into infection control programs holds promise for strengthening hygiene practices that will curb the global spread of C. auris and improve patient outcomes.

This study investigates the effect of scaffold architecture on bone regeneration, focusing on 3D-printed polylactic acid-bioceramic calcium phosphate (PLA-bioCaP) composite scaffolds in rabbit femoral condyle critical defects. To assess their influence on bone healing and scaffold performance, we explored two distinct scaffold designs, alternate and helical laydown patterns. The scaffolds were meticulously characterized for pore size, strut thickness, porosity, pore accessibility, and mechanical properties. The in vivo efficacy of these scaffolds was evaluated using a rabbit femoral condyle critical defect model. Our findings indicate that both scaffold architectures are biocompatible and support bone formation. The helical scaffolds, characterized by larger pore sizes and higher porosity, demonstrated significantly greater bone regeneration than the alternate structures. However, their lower mechanical strength presented limitations for use in load-bearing sites. This study highlights the importance of scaffold architecture in bone tissue engineering and underscores the need to balance porosity and mechanical strength for optimal bone regeneration. The findings provide crucial insights for the design of 3D- printed scaffolds in clinical applications, particularly in the context of critical-sized bone defects. The study also outlines potential areas for future research, including exploring hybrid scaffold designs to achieve optimal porosity without compromising mechanical integrity.

Pharmaceutical packaging is very crucial in as much as it plays the role of enhancing the stability, efficacy as well as safety of the produced medicine through the material used in packaging. It is important to note that cGMP Chapters 661 and 671 are focused on explaining how one should assess the quality of container materials in the sphere of pharmaceuticals. These chapters encompass a number ofmatters among them being Plastic and glass containers and performance testing; they serve as a resource that aids in assuring all standards are met with profound proficiency. Following this, the performance of two core chapters of USP known as Chapter 661 on “Containers—Glass” and Chapter 671 on “Containers—Performance Testing” will be dealt with in a step-by-step manner in the following paper while providing a comprehensive review of both at the same time. Understanding and legal obedience to these rules, as stipulated in the above-mentioned chapter, are indispensable for almost all the parties involved in the production of the drugs, together with the policies and legislation on the same. Thus, the purpose of this paper is to describe and discuss the major aspects of the understanding, application, requirements and evaluation procedures depending on the USP Chapters 661 and 671 in the sphere of the pharmaceutical market.

The many-body problem in quantum physics originates from the difficulty of describing the non-trivial correlations encoded in the exponential complexity of the many-body wave function. Motivated by the Giuseppe Carleo's work titled solving the quantum many-body problem with artificial neural networks [Science, 2017, 355: 602], we focus on finding the NNQS approximation of the unknown ground state of a given Hamiltonian $H$ in terms of the best relative error and explore the influences of sum, tensor product, local unitary of Hamiltonians on the best relative error. Besides, we illustrate our method with some examples.

Rabbit hemorrhagic disease virus disease 2 (RHDV2) emerged in the United States in 2018 and has spread in both domestic and wild rabbits nationwide. The virus has a high mortality rate and can spread rapidly between infected individuals. Vaccination against RHDV2 provides the best protection against disease and should be considered by all rabbit owners. Here, we investigate the duration of immunity provided by vaccination with the Medgene Platform conditionally licensed commercial vaccine 6 months following the initial series. Rabbits received either the vaccination or a placebo and were challenged with RHDV2 6 months later. All vaccinated rabbits survived challenge whereas 18/19 non-vaccinated controls succumbed to infection within 10 or fewer days post-challenge. These results demonstrate lasting immunity following vaccination with the Medgene RHDV2 vaccine.

With continuous increase in integration of the semiconductor devices, the requirements on size accuracy and surface quality of the etched lead frame are higher. The etchant is a key factor on etching process and etched surface quality, while effects of the difference in etchants on microscopic etched surface morphology of the Cu alloy have not been directly studied. In this study, the aqua regia, acidic FeCl3 and CuCl2 solutions were used as etchants, and the CuCrSn alloy specimens with different microstructure were etched and characterized. The results show that the etching rate in aqua regia is high, and the grain orientation, grain boundary (GB) and dislocation have significant influence on the local etching rate. The preferential etching of some atomic planes forms steps between grains with different orientations, and the preferential etching around the GB and dislocation group forms grooves, resulting in high surface roughness. For etching of the FeCl3 and CuCl2 etchants, the steps and grooves become blurred, and almost invisible on the surface etched by the CuCl2 etchant, thus the surface roughness is much lower. The CuCrSn alloy surface etched by the aqua regia is clean, with little Cr-rich particles, while high density Cr-rich particles are remained on the surfaces etched with the FeCl3 and CuCl2 etchants. For the same kind of etchant, the ion concentration can affect the etching mechanism and etching surface morphology.

In the sphere of urban renewal in historic districts, preserving and innovatively reinterpreting traditional architectural styles remains a primary research focus. However, the modernization and adaptive reuse of traditional buildings often necessitate changes in their functionality. To cater to the demands of tourism in historic districts, many traditional residential buildings require conversion to commercial use, resulting in a mismatch between their external form and internal function. This study explores an automated approach to transform traditional residences into commercially viable designs, offering an efficient and scalable solution for the modernization of historic architecture. We developed a methodology based on diffusion models, focusing on a dataset of nighttime shopfront facades. By training a Low-Rank adaptation (LoRA) model and integrating the ControlNet model, we enhanced the accuracy and stability of generated images. The methodology’s performance was validated through qualitative and quantitative assessments, optimizing batch size, repetition, and learning rate configurations. These evaluations confirmed the method’s effectiveness. Our findings significantly advance the modern commercial style transformation of historical architectural facades, providing a novel solution that maintains aesthetic and functional integrity, thereby fostering breakthroughs in traditional de-sign thinking and exploring new possibilities for the preservation and commercial adaptation of historical buildings.

We present a new method of estimating fitness of countries and complexity of products by exploiting a non-linear non-homogeneous map applied to the publicly available information on the goods exported by a country. The non homogeneous terms guarantee both convergence and stability. After a suitable rescaling of the relevant quantities, the non homogeneous terms are eventually set to zero so that this new method is parameter free. This new map reproduces the findings of the method proposed by Tacchella et al. [1], and allows for an approximate analytic solution in case of actual binarized matrices based on the Revealed Comparative Advantage (RCA) indicator. This solution is connected with a new quantity describing the neighborhood of nodes in bipartite graphs, representing in this work the relations between countries and exported products. Moreover, we define the new indicator of country net-efficiency quantifying how a country efficiently invests in capabilities able to generate innovative complex high quality products. Eventually, we demonstrate analytically the local convergence of the algorithm.

The gut-brain axis (GBA) represents a complex, bidirectional communication network that intri-cately connects the gastrointestinal tract with the central nervous system (CNS). Understanding and intervening in this axis opens a pathway for therapeutic advancements. In light of this, the current review assesses the effectiveness of neuromodulation techniques in treating neurological and gastrointestinal disorders by modulating the GBA, involving key elements such as gut micro-biota, neurotrophic factors, and proinflammatory cytokines. Through a comprehensive literature review encompassing PubMed, Google Scholar, Web of Science, and the Cochrane Library, and analyzing 182 relevant articles, this research highlights how neuromodulation can positively impact the management of functional gastrointestinal disorders (FGIDs), chronic pain, inflammation, and a range of GI disorders like Crohn's disease and ulcerative colitis. Despite existing challenges, the ability of neuromodulation to adjust disrupted neural pathways, alleviate pain, and mitigate in-flammation is significant in improving the quality of life for patients, thereby offering exciting prospects for future advancements in patient care.

Robin's criterion states that the Riemann hypothesis is true if and only if the inequality $\sigma(n) < e^{\gamma } \cdot n \cdot \log \log n$ holds for all natural numbers $n > 5040$, where $\sigma(n)$ is the sum-of-divisors function of $n$ and $\gamma \approx 0.57721$ is the Euler-Mascheroni constant. We show that the Robin inequality is true for all natural numbers $n > 5040$ that are not divisible by some prime between $2$ and $1771559$. We prove that the Robin inequality holds when $\frac{\pi^{2}}{6} \cdot \log\log n' \leq \log\log n$ for some $n>5040$ where $n'$ is the square free kernel of the natural number $n$. The possible smallest counterexample $n > 5040$ of the Robin inequality implies that $q_{m} > e^{31.018189471}$, $1 < \frac{(1 + \frac{1.2762}{\log q_{m}}) \cdot \log(1.006479799241)}{\log \log n}+ \frac{\log N_{m}}{\log n}$, $(\log n)^{\beta_{n}} < 1.000208229291\cdot\log(N_{m})$ and $n < (1.006479799241)^{m} \cdot N_{m}$, where $N_{m} = \prod_{i = 1}^{m} q_{i}$ is the primorial number of order $m$, $q_{m}$ is the largest prime divisor of $n$ and $\beta_{n} = \prod_{i = 1}^{m} \frac{q_{i}^{a_{i}+1}}{q_{i}^{a_{i}+1}-1}$ when $n$ is an Hardy-Ramanujan integer of the form $\prod_{i=1}^{m} q_{i}^{a_{i}}$. By combining these results, we present a proof of the Riemann hypothesis. This work is an expansion and refinement of the article "Robin's criterion on divisibility", published in The Ramanujan Journal.

The P versus NP problem is a fundamental question in computer science. It asks whether problems whose solutions can be quickly verified can also be quickly solved. Here, "quickly" refers to computational time that grows proportionally to the size of the input (polynomial time). While the problem's roots trace back to a 1955 letter from John Nash, its formalization is attributed to Stephen Cook and Leonid Levin. Despite extensive research, a definitive answer remains elusive. Closely tied to this is the concept of NP-completeness. If a single NP-complete problem could be solved efficiently, it would imply that all problems in NP can be solved efficiently, proving that P equals NP. This work posits that MONOTONE ONE-IN-THREE 3SAT, a notoriously difficult NP-complete problem, can be solved efficiently, thereby establishing the equivalence of P and NP.

A prime gap is the difference between consecutive prime numbers. The $n^{\text{th}}$ prime gap, denoted $g_{n}$, is calculated by subtracting the $n^{\text{th}}$ prime from the $(n+1)^{\text{th}}$ prime: $g_{n}=p_{n+1}-p_{n}$. Oppermann's conjecture is a prominent unsolved problem in pure mathematics concerning prime gaps. Despite verification for numerous primes, a general proof remains elusive. If true, the conjecture implies that prime gaps grow at a rate bounded by $g_{n}<{\sqrt {p_{n}}}$. This note presents a proof of Oppermann's conjecture using the square root function on inequalities involving prime numbers. This proof simultaneously establishes Andrica's, Legendre's, and Brocard's conjectures.

Let $\Psi(n) = n \cdot \prod_{q \mid n} \left(1 + \frac{1}{q} \right)$ denote the Dedekind $\Psi$ function where $q \mid n$ means the prime $q$ divides $n$. Define, for $n \geq 3$; the ratio $R(n) = \frac{\Psi(n)}{n \cdot \log \log n}$ where $\log$ is the natural logarithm. Let $N_{n} = 2 \cdot \ldots \cdot q_{n}$ be the primorial of order $n$. A trustworthy proof for the Riemann hypothesis has been considered as the Holy Grail of Mathematics by several authors. The Riemann hypothesis is a conjecture that the Riemann zeta function has its zeros only at the negative even integers and complex numbers with real part $\frac{1}{2}$. There are several statements equivalent to the famous Riemann hypothesis. We show if the inequality $R(N_{n+1}) < R(N_{n})$ holds for $n$ big enough, then the Riemann hypothesis is true. In this note, we prove that $R(N_{n+1}) < R(N_{n})$ always holds for $n$ big enough.

Around $1637$, Pierre de Fermat famously scribbled, and claimed to have a proof for, his statement that equation $a^{n} + b^{n} = c^{n}$ has no positive integer solutions for exponents $n>2$. The theorem stood unproven for centuries until Andrew Wiles' groundbreaking work in $1994$, with a notable caveat: Wiles' proof, while successful, relied on modern tools far beyond Fermat's claimed approach in terms of complexity. The present work potentially offers a solution which is closer in spirit to Fermat's original idea.

The Riemann hypothesis is the assertion that all non-trivial zeros are complex numbers with real part $\frac{1}{2}$. It is considered by many to be the most important unsolved problem in pure mathematics. There are several statements equivalent to the famous Riemann hypothesis. Robin's criterion states that the Riemann hypothesis is true if and only if the inequality $\sigma(n) < e^{\gamma} \cdot n \cdot \log \log n$ holds for all natural numbers $n > 5040$, where $\sigma(n)$ is the sum-of-divisors function of $n$, $\gamma \approx 0.57721$ is the Euler-Mascheroni constant and $\log$ is the natural logarithm. We require the properties of superabundant numbers, that is to say left to right maxima of $n \mapsto \frac{\sigma(n)}{n}$. In this note, using Robin's criterion on superabundant numbers, we prove that the Riemann hypothesis is true.

Background: This study aimed to investigate the impact of the COVID-19 pandemic on breast reconstruction trends in the United States, focusing on implant-based and autologous techniques, as well as the timing of reconstruction (immediate vs. delayed). Methods: A retrospective analysis of data from the American Society of Plastic Surgeons' National Plastic Surgery Statistics from 2015 to 2022 was conducted. Annual trends in breast reconstruction procedures were analyzed, comparing the pre-pandemic (2015-2019) and pandemic (2020-2022) periods. Results: The total number of breast reconstructions increased from 106,338 in 2015 to 151,641 in 2022. The proportion of implant-based reconstructions decreased from 81.41% pre-pandemic to 76.51% during the pandemic (p < 0.001), with a notable rise in direct-to-implant procedures from 10.37% to 19.12% (p < 0.001). Autologous reconstructions increased from 18.59% to 23.49% (p < 0.001). Among autologous techniques, DIEP flaps remained the most popular. Immediate reconstruction rates increased from 72.61% pre-pandemic to 75.57% during the pandemic, while delayed recon-struction rates decreased from 27.39% to 24.43% (p < 0.001). Conclusions: The COVID-19 pandemic has significantly influenced breast reconstruction trends in the United States, with a shift towards autologous techniques, particularly DIEP flaps, and an in-crease in immediate reconstructions. These changes may reflect adaptations in surgical practice and decision-making processes in response to the unique challenges posed by the pandemic. Further research is needed to assess the long-term outcomes and patient satisfaction associated with these trends.

This review explores the crucial role of glycosphingolipids (GSLs) in the context of cardiovascular diseases (CVD), focusing on their biosynthesis, metabolic pathways, and implications for clinical outcomes. GSLs are pivotal in regulating a myriad of cellular functions that are essential for heart health and disease progression. Highlighting findings from both human cohorts and animal models, this review emphasizes the potential of GSLs as biomarkers and therapeutic targets. We advocate for more detailed mechanistic studies to deepen our understanding of GSL functions in cardiovascular health, which could lead to innovative strategies for diagnosis, treatment, and personalized medicine in cardiovascular care.

This study aimed to determine shifts in microbial populations regarding richness and diversity from the daily use of a popular over-the-counter nasal spray. In addition, the finding of nasal commensal bacterial species that overlap with the oral microbiome may prove to be potential probiotics for the “gateway microbiomes.” Nasal swab samples were obtained before and after using the most popular over-the-counter (OTC) nasal spray in 10 participants aged 18–48. All participants were healthy volunteers with no significant medical histories. The participants were randomly assigned a number by randomizing software and consisted of five men and five women. The sampling consisted of placing a nasal swab atraumatically into the nasal cavity. The samples were preserved and sent to Northwestern University Sequencing Center for whole-genome deep sequencing. After 21 days of OTC nasal spray use twice daily, the participants returned for further nasal microbiome sampling. The microbial analysis included all bacteria, archaea, viruses, molds, and yeasts via deep sequencing for species analysis. The Northwestern University Sequencing Center utilized artificial intelligence analysis to determine shifts in species and strains following nasal spray use that resulted in changes in diversity and richness.

Vascular rings are a rare congenital anomaly of the aortic arch in which a ring-shaped structure forms surrounding the trachea and/or esophagus, potentially causing compression. We describe the case of a 14-month-old female patient with failure to thrive secondary to dysphagia, and a vascular ring formed by a right aortic arch, an aberrant left subclavian artery, and a left liga-mentum arteriosum. Surgical repair involved ligamentum arteriosum division, Kommerell’s di-verticulum obliteration, and left subclavian artery re-implantation into the left carotid artery. Endoscopy and EndoFLIPTM evaluated intraoperative improvement in esophageal narrowing and impedance, respectively. Postoperative period was uneventful and follow-up visits demonstrated dysphagia resolution and a patent re-implanted left subclavian artery.

Sustainable water resource management in Bangladesh's Gumti River Basin faces challenges from climate change, urbanization, and population growth. This study aimed to calibrate and validate the HEC-HMS model for the Gumti River to enhance flood prediction and water resource planning. The model was set up using precipitation, temperature, and discharge data from 2019-2021, with SRTM elevation data for catchment delineation. Manual calibration was performed for 2019-2020, followed by validation for 2021, using parameters such as Muskingum routing and SCS Curve Number. Model performance was evaluated using R², Nash-Sutcliffe efficiency (NSE), RSR, and PBIAS metrics. Results showed satisfactory to good performance, with R² values of 0.64 and 0.68 for calibration and validation, respectively. NSE values were within the satisfactory range, while PBIAS indicated very good performance with slight underestimation. The study concludes that the calibrated HEC-HMS model provides a reliable tool for simulating the Gumti River's hydrology, though there's room for improvement. Integration with flood frequency analysis, water quality monitoring, and climate change projections is recommended for comprehensive water resource management, alongside the implementation of Sustainable Water Resource Management principles and community engagement strategies.

In this work we looked for a stable and accurate procedure to perform feature selection in datasets with a much higher number of predictors than individuals, as in Genome-Wide Association Studies. Due to the instability in feature selection when many potential predictors are measured, a variable selection procedure is proposed that combines several replications of shrinkage regression models. A weighted formulation is used to define the final predictors. The procedure is applied to investigate Single Nucleotide Polymorphisms (SNPs) predictors associated to Alzheimer’s disease in the Alzheimer’s disease Neuroimaging Initiative (ADNI) dataset. Two data scenarios are investigated: one considering only the set of SNPs and another with the covariates age, sex, educational level and APOE4 genotype. The SNP rs2075650 and the APOE4 genotype are given as risk factors for AD, which is in line with the literature, and other four new SNPs are pointed, opening new hypotheses for in vivo analyses. These experiments demonstrate the potential of the new method for stable feature selection.

Generative Adversarial Networks (GANs) are powerful models for generative tasks but face significant challenges such as instability, mode collapse, and inefficient convergence. This paper introduces a theoretical framework leveraging Fermi-Dirac statistics, Ruppeiner geometry, phase transition dynamics, and graph theory to address these issues. The proposed theorems provide a robust mathematical foundation for enhancing GAN stability, diversity, and convergence. Experimental validation on the MNIST dataset demonstrates that the application of these theorems results in improved Inception Scores, reduced Fr´echet Inception Distances, and stable training dynamics, as indicated by Ruppeiner curvature analysis. The findings suggest that these theoretical insights offer a comprehensive solution to the persistent challenges in GAN training, paving the way for more reliable and effective generative models.

The purpose of this paper is to build a new bridge between category theory and a generalized probability theory known as noncommutative probability or quantum probability, which was originated as a mathematical framework for quantum theory, in terms of states as linear functional defined on category algebras. We clarify that category algebras can be considered as generalized matrix algebras and that the notions of state on category as linear functional defined on category algebra turns out to be a conceptual generalization of probability measures on sets as discrete categories. Moreover, by establishing a generalization of famous GNS (Gelfand-Naimark-Segal) construction, we obtain a representation of category algebras of †-categories on certain generalized Hilbert spaces which we call semi-Hilbert modules over rigs.

The recent growth of wearable medical device technology in the form of fitness trackers, smart watches, smartphone apps, and patient monitoring systems has created people-generated health data (PGHD) that may benefit medical science with large amounts of continuous real-world data. The prevalence of these devices speaks to their broad popularity and user-friendliness and may lead us one day to a more fully “connected healthcare system.” Meanwhile, data security, confidentiality, and privacy issues have emerged in these hackable systems. Despite the promise of anonymized data, data can sometimes be re-identified, but even without that step, data breaches may reveal information (name, address, date of birth, social security number, and so on) sufficient for identity theft. Clinicians are often asked about the utility and value of wearable devices or monitors, but most are unaware that data from these systems may be transmitted, stored, and even sold without the user’s specific knowledge. Despite the confidentiality of medical information, cybersecurity surrounding wearables and monitors remains relatively lax, making them comparatively easy targets for cyber-villains. It is also important that efforts be taken to make PGHD more secure, since medical data may have great value to telehealth applications and AI-physician assistants. Clinicians should take an active role in informing patients about both risks and benefits of wearables and similar devices.

Rice provides ~20% of human dietary energy and, for many people, a similar share of their protein. Rice cultivation, however, produces significant greenhouse gas (GHG) emissions, comparable to those from the aviation sector. The main GHG from rice production is methane, mostly a result of conventional rice cultivation (CRC) keeping rice fields continuously flooded during the crop cycle. There is extensive evidence that alternate wetting and drying (AWD) of rice fields substantially reduces methane emissions. AWD is one component of the System of Rice Intensification (SRI), an agroecological approach to the management of plants, water, soil and nutrients practiced by millions of farmers in both lowland irrigated rice and upland rainfed cultivation. Thirteen countries have included SRI in their Nationally Determined Contributions to GHG reduction or climate change mitigation. This article reviews 16 field studies of the net reduction in GHG emissions from the adoption of AWD, eight from the adoption of SRI, and two that compared SRI and AWD. Where available, the review includes data on yield and therefore on carbon dioxide-equivalent GHG emissions per kilogram of rice produced. The evidence indicates that AWD and SRI offer a similar and substantial reduction (~35–41%) in GHG emissions per hectare compared with conventional rice cultivation. However, SRI offers ~66% greater yield than CRC, and therefore greater reduction in emissions per kilogram of rice, ~54% more than AWD. The limited data directly comparing SRI and AWD support this finding. SRI also appears to have greater potential to sequester carbon in the soil. SRI lowers rice farmers’ costs of production, adds to their income and can make climate-friendly methods more attractive. Both AWD and SRI are greatly preferable to current conventional practices, but SRI offers opportunities to contribute to food security while directly addressing the drivers of climate change.

Background and Objectives. To examine trends in the links between induced abortion and subsequent mental health problems for U.S. women approaching completed fertility. Materials and Methods. Panel data on a nationally-representative cohort of 3,842 ever-pregnant women assessed at mean ages of 15, 22, 28 and 37 years from the National Longitudinal Study of Adolescent to Adult Health (Add Health) were examined for pregnancy outcome-related mental health disorders, with extensive adjustment for confounders including sociodemographic dif-ferences, mental health history, and unwanted pregnancies. Outcomes were defined using pub-lished diagnostic criteria or validated index for depression, anxiety disorder, post-traumatic stress disorder (PTSD), and suicide ideation (affective problems); alcohol abuse, drug abuse, opioid abuse, and cannabis abuse (substance abuse problems); and summary counts of affective problems, substance abuse problems and total disorders. Results were adjusted for abortion under-reporting using cross-wave analysis. Results. The relative risk of mental health disorder with exposure to induced abortion followed an inverted “V” pattern as women aged to midlife, increasing from Wave III (age 22; IRR 1.41) to Wave IV (age 28; IRR 1.67), then dropping sharply by Wave V (age 37; IRR 1.20). The population at-tributable fraction of mental health disorder due to abortion dropped from 18.1% at Wave IV to 8.0% at Wave V. Unlike previous Waves, at Wave V mental health risk was more strongly reduced by exposure to childbirth (IRR 0.70, 95% CI .63, .78, p < .001). Reduced relative metrics at Wave V were not due to reduced prevalence of mental health disorders for ever-aborting women, which increased from Wave IV to Wave V by 1.7%, but increased much more, by 20.5%, for never-aborting women. Conclusion. At midlife approaching completed fertility, differential negative psychological out-comes for ever-aborting U.S. women remained elevated but reduced from younger ages.

Beaches are among the habitats most frequented by migratory birds for breeding and/or wintering. However, threats such as human pressure and sea level rise can reduce the availability of these habitats for different species. The presence of alternative areas, such as salt pans and brackish habitats, is essential for many migratory shorebird populations. This study addresses the post-breeding dispersal of the Kentish plover (Charadrius alexandrinus) in the Iberian Peninsula by analysing C and N isotopes in feathers. The study was conducted at six locations along the Iberian coast, which were categorized in three areas: NW Atlantic coast, the Atlantic coast of Andalusia and the Mediterranean coast. Although linear mixed models did not reveal any significant effects of sex or coastal area on isotopic levels, the variability in the data suggests different habitat-use strategies in the post-reproductive period. Birds from the northwest of the Iberian Peninsula exhibit greater fidelity to a single habitat type, i.e. coastal beaches, while populations from the Mediterranean coast and the Atlantic coast of Andalusia show different individual dispersal strategies, occupying coastal habitats and freshwater wetlands. The lack of alternative habitats for the northwest Iberian population, the reduction in available habitat due to rising sea levels and human pressure together pose a serious threat to the survival of this species, already with an unfavourable conservation status.

Previous reviews by the authors [1, 2] indicate the continuing development and improvement of thermal protective systems through the introduction of polymer nanocomposites into polymer matrix composites. These materials perform as thermal protective systems for a variety of aerospace applications, such as thermal protection systems (TPS), solid rocket motors (SRM) nozzles, internal insulation of SRM, leading edges of hypersonic vehicles, and missile launch structures. A summary of the most recent, global technical research is presented. Polymeric resin systems continue to emphasize phenolic resins and other materials. New high-temperature organic resins based on phthalonitrile (PN), and polysiloxane are described and extend the increased temperature range of resin matrix systems.

Accidental arterial embolization of hyaluronic acid (HA) fillers can lead to severe complications, including skin ischemia, blindness, and stroke. Currently, the intra-arterial dispersal and fragmentation behavior of HA gels is unknown but is critical to our understanding of the pathomechanism of these injuries. This work introduces the Pulsatile Unit for the Laboratory Simulation of Arterioembolic Restrictions (PULSAR) and evaluates the intravascular behavior of different HA gels. The fragmentation and dispersal behaviors of four HA gels with distinct rheological properties were evaluated via high-resolution videography and ImageJ particle size and morphology analysis. The gels' elastic modulus (G'), loss modulus (G''), tan(δ), and HA concentration were subsequently correlated with their intra-arterial behaviors. This study effectively confirms the extensive fragmentation of HA gels upon arterial inoculation, with particle sizes ranging from &lt;50 µm to &gt;1 mm. Gel particle size and morphology correlate most significantly with tan(δ). Conversely, arterial flow rates do not significantly influence gel fragmentation behavior, though the probability of proximal, macrovascular obstruction is affected. Overall, this study validates the PULSAR model for simulation of arterial dynamics and the testing of intravascular filler kinematics. The findings highlight the importance of gel viscoelasticity and flow parameters in determining particle size, dispersibility, and occlusive potential.

Background: Mental health has a special relevance in adolescence. Therefore, this study aimed to analyze the possible association between emotional distress and suicidal ideation among adolescents. Methods: The article presents the results of a survey of secondary school students (N=1419) in the city of Tarragona, Spain. The aim of the analysis was to verify the existence of an association between suicidal ideation and risk factors such as emotional distress and low self-esteem. All the data were also analysed to determine the existence of statistically significant differences between girls and boys. Bivariate analyses were performed with chi-square, point-biserial coefficient and non-parametric tests for independent groups. Logistic regression analysis was also performed to calculate the probability of suicidal ideation. Results: These analyses showed that both emotional distress and low self-esteem increase the likelihood of suicidal ideation among adolescents. This was more evident among boys with high levels of emotional distress. Conclusion: Schools should develop suicide ideation prevention programs for adolescents based on situations that cause emotional distress.

Logic gates made of pairs of NPN and PNP bipolar transistors, similar to CMOS logic gates, have been proposed and patented long ago but did not find any practical application until now. Other bipolar technologies (TTL, TTL-S, ECL), once the technologies of choice for digital systems, were abandoned and superseded by CMOS. In this paper it is shown that now, when truly com-plementary pairs of bipolar transistors can be made, properly biased bipolar gates similar to CMOS gates are feasible, can be thermally stable and find practical applications.

Due to the linear property around an acetylenic carbon, the introduction of such an atom to a small cycle would result in high ring strain. Currently, the smallest isolated rings are five-membered, including metallacycloalkynes and metallapentalynes. Both types contain at least one unusual small bond angle around the acetylenic carbon, thus exhibiting abnormal reactivities. This feature article gives a comprehensive overview on these two kind complexes. The synthesis and reactivities are extensively described, the source of stability is presented, and the future prospect is discussed. The article aims to provide a better development for the chemical diversity of five-membered metallacycloalkynes and metallapentalynes.

In dry season paddy farming, the alternate wetting and drying (AWD) irrigation improves water productivity, paddy production, and has the potential to decrease greenhouse gas (GHG) such as methane (CH4) and nitrous oxide (N2O) emissions when compared to continuous flooding (CF). However, there is a lack of research in Bangladesh on the effects of water management on CH4 and N2O emissions. During November 2017–April 2018, participatory on-farm trials were conducted at Feni and Chattogram districts of Bangladesh. Total 105 farmers comprising 20-hectare of land (62 farmers at Feni and 43 farmers at Chattogram district, each location having 10 hectare of land). We compared irrigation water and cost reductions, paddy yield, and CH4 and N2O emissions from paddy fields irrigated using AWD and CF irrigation methods. The CH4 and N2O emissions were determined using the Cool Farm Beta-3 methodology, and the global warming potential (GWP) was estimated using the Intergovernmental Panel on Climate Change-2014 standard approach. The mean results of randomly selected 30 farmers from two locations (15 of each) showed that AWD remarkably decreased irrigation water consumption by about 24% and increased water productivity by 224%. We estimated 23% savings for irrigation costs in AWD. By this time, AWD improved paddy production by 3% over CF. The AWD irrigation resulted in a 47% reduction in cumulative CH4 emissions having a lower CH4 emission factor (0.74 kg ha-1 day-1) than CF (1.39 kg ha-1 day-1). There was no obvious difference in N2O emission between AWD and CF. When compared to CF, AWD decreased the overall GWP by 27% and lowered the GHG intensity by 42%. The CH4 and N2O emissions did not differ substantially between Feni and Chattogram.

Introduction This study was conducted to validate the findings of a prior study published in JDD in September 2023, which reported that a topical firming and toning body lotion (FTB – SkinMedica®, Allergan Aesthetics, an AbbVie Company, Irvine, CA) upregulated several genes in a UV irradiated 3D full-thickness human skin model, outperforming other products, including TransFORM Body Treatment with TriHex Technology® (ATF – Alastin Skincare®, a Galderma company Fort Worth, Texas, USA ). Given the unique response reported for FTB, we conducted this study to assess the reproducibility of these results and explore gene expression at multiple time points, along with validating protein expression in an ex vivo model. Materials and Methods Experiments were conducted using an ex vivo model with photodamaged skin from facelift patients, under an Institutional Review Board approved study. Skin samples were processed, cultured in transwells with Skin Media, and treated daily with either TransFORM or FTB for 7 days. A control group was left untreated. Gene expression was assessed using RT-PCR on days 1 and 3, immunofluorescence after 3 and 7 days of treatment. Skin samples were fixed, paraffin-embedded, sectioned, and stained with an anti-tropoelastin antibody. Fluorescence detection and imaging were conducted to assess protein expression changes. Results Gene expression data from our study and the initial study showed a few similarities but multiple discrepancies. In particular, as opposed to results previously reported at only the 24-hour time point, additional time points showed complete reversal of many of these results. For example, COL1A1 expression at 24 hours was similar for FTB in both studies but differed for TransFORM which showed higher levels at 24 hours. However, at day 3, COL1A1 expression decreased markedly for FTB and was sustained for TransFORM. Other genes, such as COL3A1, COL5, ELN, VEGFC, ATG7, ATG12, BECN1, POMP, PSMB5, and PSMB6, exhibited varying expression patterns between the studies and across different time points. From a translational perspective, histological analysis showed that TransFORM enhanced elastin fiber presence in the dermal-epidermal junction (DEJ) more effectively than FTB at both day 3 and day 7. FTB-treated samples maintained a gap in the DEJ, while TransFORM-treated samples exhibited increased cellular proliferation and DEJ undulation, indicative of a healthier regenerative response. Conclusion This study highlights the problems of examining data and drawing conclusions using a single point of examination. In addition, when a study reports positive results for only 1 product among a range of 8 competitive products, further questioning is essential to exclude the possibility of the experimental model favoring that particular product. The additional 3-day timepoint and further translational examination of histological changes, paints a completely different picture to that reported in the prior publication TransFORM outperformed FTB in most gene expression and histological parameters when assessed over multiple time points in a physiologically relevant ex vivo model.

Background: Regular moderate-vigorous intensity exercise is recommended for adults as it can improve longevity and reduce health risks associated with a sedentary lifestyle. However, there are barriers to achieving intense exercise that may be addressed using virtual reality (VR) as a tool to promote exercise intensity and adherence, particularly through visual feedback and competition. The purpose of this work is to compare visual feedback and competition within fully-immersive VR to enhance exercise intensity and user experience of exercise for young adults; and to describe and compare visual attention during each of the conditions. Methods: Young adults (21- 34 years old) bicycled in three 5-minute VR conditions (visual feedback, self-competition and competition against others). Exercise intensity (cycling cadence and % of maximum heart rate) and visual attention (derived from a wearable eye tracking sensor) were measured continuously. User experience was measured by an intrinsic motivation questionnaire, perceived effort and participant preference. A repeated measures ANOVA with paired t-test post-hoc tests was conducted to detect differences between conditions. Results: Participants exercised at a higher intensity and had higher intrinsic motivation in the two competitive conditions compared to visual feedback. Further, participants preferred the competitive conditions and only reached a vigorous exercise intensity during self-competition. Visual exploration was higher in visual feedback compared to self-competition. Conclusion: For young adults bicycling in VR, competition promoted higher exercise intensity and motivation compared to visual feedback.

The Rényi entropy functional was optimised for the novel findings of this investigation under various conditions. Their research's findings suggest that the complete spectrum of Lévy stable distributions is covered by generalised t-distributions. Additionally, an exposition was undertaken to prove that the Lévy distribution generalizes Tsallisian distribution, rather than the reverse. The current study is a strong generalization of an existing research work in the literature.

Structural hydroxide groups in layered magnesium-aluminum double hydroxides were partially replaced by fluoride ions. Fluorinated and fluorine-free materials were used as hosts for two dyes, carminic acid and hydroxyl naphthol blue, resulting in a hybrid pigment color palette. Additionally, the pigments were protected with a magnesium hydroxide phase to prevent the color from fading over time. The color properties of the pigments were significantly influenced by the host of dye, since the presence of fluorine directly influences the acid-base properties of the layered double hydroxides. Finally, the pigments were successfully applied to prepare colored creams.

Most existing data synthesis methods are designed to tackle problems such as dataset imbalance, data anonymization and insufficient sample size. There is a lack of effective synthesis methods for the limited number of datasets which contain a large of features and unknown noise to expand the size of the dataset. We propose a data synthesis method, named Adaptive Subspace Interpolation for Sample Optimization (ASISO). The idea is to divide the original feature space into several subspaces with an equal number of samples, and then perform interpolation for the samples in the adjacent subspaces. This method can adaptively adjust the size of the dataset containing unknown noise, and the expanded data typically contain minimal error with actual. Moreover, it adjusts the structure of the samples, which can significantly reduce the proportion of samples with large errors. In addition, the hyperparameters of this method have an intuitive explanation and usually require little calibration. Experimental results on artificial data and benchmark data sets demonstrate that ASISO is a robust and stable method to optimize samples.

Even though materialistic atoms are having independent existence in this current accelerating universe, they are not allowing scientists and engineers to explore the secrets of gravity at atomic scale. This may be due to incomplete unification paradigm, inadequacy of known physics and technological difficulties etc. In this challenging scenario, one fundamental question to be answered is: Is Newtonian gravitational constant having a physical existence? We would like to suggest that, it’s a man created empirical constant and is having no physical existence. Clearly speaking, it’s not real but virtual. For understanding the secrets of large scale gravitational effects, scientists consider it as a physical constant. In the same way, each atomic interaction can be allowed to have its own gravitational constant. With further study, their magnitudes can be refined for a better understanding of the nature. Thinking in this way, we tried to fit the Newtonian gravitational constant. It’s estimated value seems to be 6.679855x10^(-11) m3/kg/sec2. Proceeding further, the famous radiation constants can be shown to be complex or secondary physical constants. By considering proton neutron stability, nuclear binding energy, nuclear charge radii, neutron life time, Fermi’s weak coupling constant and strong coupling constant, we are trying to understand the validity of the proposed three atomic gravitational constants. It needs further study.

In this short communication, we conducted first-principles calculations to explore the stability of boron monochalcogenides (BX, X=S, Se or Te), as a new class of two-dimensional (2D) materials. We predicted BX monolayers with two different atomic stacking sequences of ABBA and ABBC, referred in this work to 2H and 1T, respectively. Analysis of phonon dispersions confirm the dynamical stability of BX nanosheets with the both 2H and 1T atomic lattices. Ab-initio molecular dynamics simulations reveal the outstanding thermal stability of all predicted monolayers at high temperatures over 1500 K. BX structures were found to exhibit high elastic modulus and tensile strengths. It was found that BS and BTe nanosheets can show high stretchability, comparable to that of the graphene. It was found that all predicted monolayers exhibit semiconducting electronic character, in which 2H structures present lower band-gaps as compared with 1T lattices. The band-gap values were found to decrease from BS to BTe. According to the HSE06 results, 1T-BS and 2H-BTe show respectively, the maximum (4.0 eV) and minimum (2.06 eV) electronic band-gaps. This investigation introduces boron monochalcogenides as a novel class of 2D semiconductors with remarkable thermal, dynamical and mechanical stability.

This review paper presents a comprehensive synthesis of current knowledge on the contamination of water systems by polycyclic aromatic hydrocarbons (PAHs). PAHs, organic contaminants characterized by two or more fused aromatic rings, are notably problematic due to their persistence, bioaccumulation, and significant health risks. The review commences with an examination of various sources of PAHs in aquatic environments, encompassing both anthropogenic activities, such as industrial discharges, urban runoff, and oil spills, and natural phenomena including volcanic eruptions and wildfires. Subsequently, the discussion shifts to the distribution patterns of PAHs within different aquatic ecosystems, with an analysis of factors that influence their transport. Considerable focus is placed on the entry mechanisms of PAHs into water systems and their interactions with diverse environmental matrices. Additionally, the ecotoxicological effects of PAHs on aquatic life are scrutinized, with particular emphasis on molecular, individual, and ecosystemic impacts. This includes an exploration of PAH bioaccumulation in aquatic organisms and their potential mutagenic and carcinogenic consequences. The review further addresses the challenges associated with detecting and quantifying PAHs in aquatic settings, reflecting on the advancements in analytical methodologies and the complexities introduced by their varied physicochemical properties. The paper concludes with a summary of existing regulatory frameworks and guidelines governing PAH contamination in water systems, underscoring the imperative for global collaboration in the monitoring and management of PAH pollution.

With the rapid development of new energy vehicles and the digital electronics industry, the demand for lithium has surged, necessitating advanced lithium extraction technologies. Electrochemical methods, noted for their high selectivity and efficiency in extracting target ions from liquid sources in an environmentally friendly manner, have become increasingly vital. These methods are versatile, applicable in scenarios such as lithium extraction from saline lakes, mother liquor separation, and lithium enrichment. They include electrochemical deintercalation, electrochemical ion pumps, and electrodialysis, each offering unique benefits and challenges depending on the application context. This review provides a detailed exploration of the research progress in lithium extraction using electrochemical methods and discusses future prospects for these technologies, emphasizing their potential to meet the growing demand for lithium.

In this paper, we propose a quantitative definition of emergence from the density matrix framework as a state of knowledge of the system and its generalized probability formulation, in order to detect emergent properties. We propose the use of a descriptor based on the difference of von Neumann entropy, to calculate if subsystems of systems have inner correlations by defining emergent systems in terms of emergent information.

We investigate a new fundamental property of infectious diseases with natural adaptive immunity that weakens over time. Numerical experiments with a model of the Covid-19 epidemic in Moscow have demonstrated that when the reproduction number R0 is about 4, a qualitative change (bifurcation) occurs in the behavior of the virus-human system. Below this value, the long-term forecast tends to undamped oscillations; above it, the forecast shows damped oscillations: the amplitudes of epidemic waves decrease gradually, with a constant, very high background level of morbidity that keeps the natural immunity near 100%. To confirm this result analytically, we use an original modification of the Euler-Lotka renewal equation, which describes the dynamics of infected patients distributed by disease duration (time since infection) and accounts for immunity. To construct a bifurcation diagram, which illustrates the dependence of the equilibrium stability on the parameter R0, we linearize the equation in the vicinity of the equilibrium point and examine its numerical approximation (discrete form). This approximation can be interpreted as a Leslie model, with the matrix elements dependent on the parameter R0. By examining the roots of the corresponding Lotka polynomial, we can assess the stability of the equilibrium point. For the bifurcation diagram, we use the functions obtained from the simulation of the Covid-19 epidemic in Moscow. However, observations of the epidemic in other cities and countries support the primary finding of our study regarding the attenuation of epidemic waves.

The region of Eastern Europe & Turkey contributed to the SISAL (Speleothem Isotopes Synthesis and AnaLysis) global database with stable carbon- and oxygen isotope time-series from 18 entities from 14 cave systems. The currently available oldest record from this region is the ABA-2 flowstone record (Abaliget Cave; Hungary) reaching back to MIS 6. The temporal distribution of the compiled 18 entities points out a ~20-kyr-long period, centering around 100 ka, lacking speleothem stable isotope record in the region. The regional subset of SISAL_v1 records displays a continuous coverage for the past ~90 kyr for both δ¹⁸O and δ¹³C, with a mean temporal resolution of ~12 yr for the Holocene, and >50 yr for the pre-Holocene period. The highest temporal resolution both for the Holocene and the pre-Holocene was achieved in the So-1 record (Sofular Cave; Turkey). Assessing the data, an important split was found regarding the climatic interpretation of speleothem δ¹⁸O. While the oxygen isotope composition of more continental formations is thought to reflect mainly temperature variations and changes in moisture transport trajectories, it may strongly reflect fluctuations of precipitation amount in the southern part of the region. Variations of δ¹³C primarily interpreted as humidity changes reflecting dry/wet periods across the region. Elevation gradients from three non-overlapping time periods from the region - for the last 5kyr - indicated systematically prevailing elevational gradients around -0.26‰ 100m^-1 in δ¹⁸O. The regional comparison of SISAL_v1 speleothem δ¹⁸O and the temporal distribution of coarsely crystalline cryogenic cave carbonate occurrences back to 45ka does not appear to confirm the finding that occurrence of the latter coincides with the warming from stadial to interstadial conditions.

We assessed the impact of social determinants of health (SDOH) and psychosocial factors on screening behavior in a nationally representative sample of women in the US. A retrospective population-level cross-sectional sample was extracted from the 2022 Health Information National Trends Survey. Descriptive statistics were conducted for demographic characteristics and covariates. Population-based estimates with 95% confidence intervals (95% CI) were produced for Pap testing behaviors across study years. We used logistic regression models to assess Pap testing differences based on SDOH and psychosocial factors, adjusting for covariates, with a significance level of 0.05 for hypothesis testing. Women (n=2,224) with a mean age of 46.96 participated in the study. Our study found that 90% of women were interested in cervical cancer screening, with an 80% actual screening rate. Screening rates differed by age group and rurality. SDOH and psychosocial factors were associated with participants’ interest in screening and in actual screening behavior. The impacts of SDOH and psychosocial factors on screening behavior were 3% and 1%, respectively. The SDOH and psychosocial factors are associated with the uptake of cervical cancer screening among women in the United States. Policies must be directed at bridging the gap created by these SDOHs.

Pancreatic ductal adenocarcinoma (PDAC) is the fifth leading cause of cancer-related death in and presents the lowest 5-year survival rate for any form of cancer in the US. Only 20% of PDAC patients are suitable for surgical resection and adjuvant chemotherapy which remains the only curative treatment. Chemotherapeutic and genetherapy treatments are associated with adverse effects and lack specificity/efficacy. In this study we assess the oncolytic potential of immuno-oncolytic tanapoxvirus (TPV) recombinants expressing mouse monocyte chemoattractant protein (mMCP-1 or mCCL2), and mouse interleukin (mIL)-2, in human pancreatic BxPc-3 cells, using immunocompromised and CD-3+ T-cell reconstituted mice. Intratumoral treatment with TPV/∆66R/mCCL2 and TPV/∆66R/mIL-2 resulted in regression of BxPc-3 xenograft volume as compared to control in immunocompromised mice; mCCL-2 expressing TPV OV resulted in significant difference from control at p

Introduction: Lower respiratory tract infections, including pneumonia, are one of the leading causes of child mortality, especially in low-resource settings. Current guidelines rely on clinical signs for diagnosis, leading to over-prescription of antibiotics, which in turn contribute to antimicrobial resistance. Lung point of care ultrasound (L-POCUS) offers potential to improve diagnostic accuracy and reduce unnecessary antibiotic use, but lacks standardized guidelines for diagnosis and management of paediatric pneumonia. Methods and Analysis: This study utilizes a modified Delphi process to develop expert consensus guidelines for L-POCUS interpretation in paediatric pneumonia that would constitute a framework for effective guidelines for judicious antibiotic prescribing. The 5-stage iterative process includes: i) creation of a literature summary and conceptual framework, ii) first round of online surveys for expert feedback, iii) virtual meetings to discuss survey results and refine guidelines, iv) second round of online surveys, v) final analysis and development of consensus guidelines. A panel of 12-15 experts, chosen for their paediatric POCUS experience, geographic diversity, and gender balance, will participate. Consensus will be defined as ≥75% agreement. Ethics and Dissemination: Participation is voluntary, with consent obtained at the start and the option to withdraw at any time. The protocol was approved by the Ethics Commission of Bern, Switzerland. Findings will be disseminated through open access publication.

Diffuse midline gliomas are among the deadliest human cancers and have had little progress in treatment in the last 50 years. Cell cultures of these tumors have been developed recently, but it is unknown the degree to which such cultures retain the characteristics of the source tumors. DNA methylation profiling offers a powerful tool to look at genome-wide epigenetic changes that are biologically meaningful and can help assess the similarity of cultured tumor cells to their in vivo progenitors. Paraffinized diagnostic tissue from three diffuse intrinsic pontine gliomas with H3 K27M mutations was compared with subsequent passages of neurosphere cell cultures from those tumors. Each cell line was passaged 3-4 times and analyzed with DNA methylation arrays and standard algorithms that provided comparison of diagnostic classification and cluster analysis. All samples tested maintained high classifier scores and clustered within the reference group of H3 K27M-mutant diffuse midline gliomas. There was a gain of 1q in all cell lines, with two cell lines initially manifesting the gain of 1q only during culture. In vitro cell cultures of H3 K27M-mutant gliomas maintain high degrees of similarity in DNA methylation profiles to their source tumor, confirming their fidelity even with some chromosomal changes.

Background/Objectives: Concurrent opioid (OPI) and benzodiazepine (BZD) use may exacerbate falls/fractures risk compared to no use or use alone. Yet, patients may need concurrent OPI-BZD use for co-occurring conditions (e.g., pain and anxiety). Therefore, we examined the association between longitudinal OPI-BZD dosing patterns and subsequent injurious falls risk. Methods: We conducted a retrospective cohort study including non-cancer fee-for-service Medicare beneficiaries initiating OPI and/or BZD in 2016-2018. We identified OPI-BZD use patterns during the 3 months following OPI and/or BZD initiation (i.e., trajectory period) using group-based multi-trajectory models. We estimated time to first injurious fall within 3 months post-trajectory period using inverse-probability-of-treatment-weighted Cox proportional hazards models. Results: Among 622,588 beneficiaries (age≥65=84.6%, female=58.1%, White=82.7%; having injurious falls=0.45%), we identified 13 distinct OPI-BZD trajectories: Group(A):Very-low OPI-only (early discontinuation)(44.9% of the cohort); (B):Low OPI-only (rapid decline)(15.1%); (C):Very-low OPI-only (late discontinuation)(7.7%); (D):Low OPI-only (gradual decline)(4.0%); (E):Moderate OPI-only (rapid decline)(2.3%); (F):Very-low BZD-only (late discontinuation)(11.5%); (G):Low BZD-only (rapid decline)(4.5%); (H):Low BZD-only (stable) (3.1%); (I):Moderate BZD-only (gradual decline)(2.1%); (J):Very-low OPI (rapid decline)/Very-low BZD (late discontinuation)(2.9%); (K):Very-low OPI (rapid decline)/Very-low BZD (increasing)(0.9%); (L):Very-low OPI (stable)/Low BZD (stable)(0.6%); and (M):Low OPI (gradual decline)/Low BZD (gradual decline)(0.6%). Compared with Group(A), 6 trajectories had increased 3-month injurious fall risks: (C): HR, 95%CI=1.78, 1.58-2.01; (D): 2.24, 1.93-2.59; (E): 2.60, 2.18-3.09; (H): 2.02, 1.70-2.40; (L): 2.73, 1.98-3.76; and (M): 1.96, 1.32-2.91. Conclusions: Our findings suggest that 3-month injurious fall risk varied across OPI-BZD trajectories, highlighting the importance of considering both dose and duration when assessing fall risks of OPI-BZD use among older adults.

In our investigation of the time evolution of energy states Einstein’s interpretation from more than a century ago is found to have greater internal consistency than that of non-relativistic quantum mechanics. We choose to align more closely with his methods by abandoning the non-relativistic Hamiltonian method, which has been the standard for nearly a century, in favor of a relativistically correct Lagrangian method. Integral equations of motion for the absorption and emission of radiation are derived that underlie and anticipate the differentially motivated Schrödinger equation. This new interpretation applies to a large volume of experimental evidence of both classical and quantum mechanical origin. Among the examples discussed in support are Planck’s law describing black body radiation, matrix mechanics, the function of the simplest quantum mechanical system an electron cyclotron, chaos theory, and evolutionary biology.