bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hordeum vulgare CYP76M57 catalyzes C2 shortening of tryptophan side chain by C–N bond rearrangement in gramine biosynthesis
Authors: Ishikawa Erika , Kanai Shion , Shinozawa Akihisa , Hyakutake Mami , Sue Masayuki 
Published: January 2024

SUMMARYThe indole alkaloid gramine, 3‐(dimethylaminomethyl)indole, is a defensive specialized metabolite found in some barley cultivars. In its biosynthetic process, the tryptophan (Trp) side chain is shortened by two carbon atoms to produce 3‐(aminomethyl)indole (AMI), which is then methylated by N‐methyltransferase (HvNMT) to produce gramine. Although side chain shortening is one of the crucial scaffold formation steps of alkaloids originating from aromatic amino acids, the gene and enzyme involved in the Trp–AMI conversion reactions are unknown. In this study, through RNA‐seq analysis, 35 transcripts were shown to correlate with gramine production; among them, an uncharacterized cytochrome P450 (CYP) gene, CYP76M57, and HvNMT were identified as candidate genes for gramine production. Transgenic Arabidopsis thaliana and rice overexpressing CYP and HvNMT accumulate AMI, N‐methyl‐AMI, and gramine. CYP76M57, heterologously expressed in Pichia pastoris, was able to act on Trp to produce AMI. Furthermore, the amino group nitrogen of Trp was retained during the CYP76M57‐catalyzed reaction, indicating that the C2 shortening of Trp proceeds with an unprecedented biosynthetic process, the removal of the carboxyl group and Cα and the rearrangement of the nitrogen atom to Cβ. In some gramine‐non‐accumulating barley cultivars, arginine 104 in CYP76M57 is replaced by threonine, which abolished the catalytic activity of CYP76M57 to convert Trp into AMI. These results uncovered the missing committed enzyme of gramine biosynthesis in barley and contribute to the elucidation of the potential functions of CYPs in plants and undiscovered specialized pathways.
Universally defining Z$\mathbb {Z}$ in Q$\mathbb {Q}$ with 10 quantifiers
Authors: Daans Nicolas 
Published: January 2024

AbstractWe show that for a global field , every ring of ‐integers has a universal first‐order definition in with 10 quantifiers. We also give a proof that every finite intersection of valuation rings of has an existential first‐order definition in with 3 quantifiers.
Dietary sodium alters aldosterone's effect on renal sodium transporter expression and distal convoluted tubule remodelling
Authors: Mutchler Stephanie M. , Hasan Mahpara , Murphy Carolyn P. , Baty Catherine J. , Boyd‐Shiwarski Cary , Kirabo Annet , Kleyman Thomas R. 
Published: January 2024

AbstractAldosterone is responsible for maintaining volume and potassium homeostasis. Although high salt consumption should suppress aldosterone production, individuals with hyperaldosteronism lose this regulation, leading to a state of high aldosterone despite dietary sodium consumption. The present study examines the effects of elevated aldosterone, with or without high salt consumption, on the expression of key Na+ transporters and remodelling in the distal nephron. Epithelial sodium channel (ENaC) α‐subunit expression was increased with aldosterone regardless of Na+ intake. However, ENaC β‐ and γ‐subunits unexpectedly increased at both a transcript and protein level with aldosterone when high salt was present. Expression of total and phosphorylated Na+Cl− cotransporter (NCC) significantly increased with aldosterone, in association with decreased blood [K+], but the addition of high salt markedly attenuated the aldosterone‐dependent NCC increase, despite equally severe hypokalaemia. We hypothesized this was a result of differences in distal convoluted tubule length when salt was given with aldosterone. Imaging and measurement of the entire pNCC‐positive tubule revealed that aldosterone alone caused a shortening of this segment, although the tubule had a larger cross‐sectional diameter. This was not true when salt was given with aldosterone because the combination was associated with a lengthening of the tubule in addition to increased diameter, suggesting that differences in the pNCC‐positive area are not responsible for differences in NCC expression. Together, our results suggest the actions of aldosterone, and the subsequent changes related to hypokalaemia, are altered in the presence of high dietary Na+.
imageKey points
Aldosterone regulates volume and potassium homeostasis through effects on transporters in the kidney; its production can be dysregulated, preventing its suppression by high dietary sodium intake.
Here, we examined how chronic high sodium consumption affects aldosterone's regulation of sodium transporters in the distal nephron.
Our results suggest that high sodium consumption with aldosterone is associated with increased expression of all three epithelial sodium channel subunits, rather than just the alpha subunit.
Aldosterone and its associated decrease in blood [K+] lead to an increased expression of Na‐Cl cotransporter (NCC); the addition of high sodium consumption with aldosterone partially attenuates this NCC expression, despite similarly low blood [K+].
Upstream kinase regulators and tubule remodelling do not explain these results.
Sacrificial Powder Pressure Control for Infiltration of Microscale Binder Jet Printed Metal Parts
Authors: Davis Henry D. , Harkness James G. , Kohls Isa M. , Jensen Brian D. , Vanfleet Richard , Crane Nathan B. , Davis Robert C. 
Published: January 2024

Abstract
High-temperature microfluidic devices (such as gas chromatography microcolumns) have traditionally been fabricated using photolithography, etching, and wafer bonding which allow for precise microscale features but lack the ability to form complex 3D designs. Metal additive manufacturing could enable higher complexity microfluidic designs if reliable methods for fabrication are developed, but forming small negative features is challenging—especially in powder-based processes. In this paper, the formation of sealed metal microchannels was demonstrated using stainless-steel binder jetting with bronze infiltration. To create small negative features, bronze infiltrant must fill the porous part produced by binder jetting without filling the negative features. This was achieved through sacrificial powder infiltration (SPI), wherein sacrificial powder reservoirs (pore size ∼60 µm) are used to control infiltrant pressure. With this pressure control, the infiltrant selectively filled the small pores between particles in the printed part (pore size ∼3 µm) while leaving printed microchannels (700 µm and 930 µm) empty. To develop the SPI method, a pore filling study was performed in this stainless-steel/bronze system with 370 µm, 650 µm, and 930 µm microchannel segments. This study enabled SPI process design on these length scales by determining variations in pore filling across a sample and preferential filling between different sized pores.
Data-Driven Global Sensitivity Analysis of Variable Groups for Understanding Complex Physical Interactions in Engineering Design
Authors: Dolar Tuba , Lee Doksoo , Chen Wei 
Published: January 2024

Abstract
In engineering design, global sensitivity analysis (GSA) is used for analyzing the effects of inputs on the system response and is commonly studied with analytical or surrogate models. However, such models fail to capture nonlinear behaviors in complex systems and involve several modeling assumptions. Besides model-focused methods, a data-driven GSA approach, rooted in interpretable machine learning, would also identify the relationships between system components. Moreover, a special need in engineering design extends beyond performing GSA for input variables individually, but instead evaluating the contributions of variable groups on the system response. In this article, we introduce a flexible, interpretable artificial neural network model to uncover individual as well as grouped global sensitivity indices for understanding complex physical interactions in engineering design problems. The proposed model allows the investigation of the main effects and second-order effects in GSA according to functional analysis of variance (FANOVA) decomposition. To draw a higher-level understanding, we further use the subset decomposition method to analyze the significance of the groups of input variables. Using the design of a programmable material system (PMS) as an example, we demonstrate the use of our approach for examining the impact of material, architecture, and stimulus variables as well as their interactions. This information lays the foundation for managing design space complexity, summarizing the relationships between system components, and deriving design guidelines for PMS development.
Development of a Novel Tendon-Sheath-Driven Upper Limb Exoskeleton With Elastic Joints for Assisting Surgeon-Performing Microlaryngoscopic Surgery
Authors: Wang Zhengyu , Song Wenjun , Bian Wenjie , Li Ziqian , Jia Zirui , Yu Xiang 
Published: January 2024

Abstract
When performing microlaryngoscopic surgery, surgeons must maintain their arm positions for a long time, which can cause arm soreness and affect the success rate of surgery. In this study, a novel tendon-sheath-driven upper limb exoskeleton with elastic joints (TULEE) is proposed and developed to support the arms of doctors wearing the TULEE. The functional requirements of the TULEE were proposed according to the needs of microlaryngoscopic surgery, and the overall structure of the TULEE was designed. Then, the positive kinematics of the TULEE were derived based on the D–H transformation matrices, and the accuracy of the positive kinematic control was verified experimentally. The reachable workspace of the wrist joint of the TULEE was analyzed, and the dexterous workspace of the wrist was analyzed by using the condition number of the Jacobian matrix. The control strategy of the TULEE was proposed based on the principle of admittance control. Finally, an experimental prototype of the TULEE was built, and the feasibility of the control strategy was verified by a servo control experiment testing a single joint and a combined control experiment testing multiple joints. Through simulated surgical experiments, it was verified that TULEE can follow the wearer's arm movement, provide assistance for the wearer's arm movement in the following control mode, and lock the joint rotation angle in the steady-state control mode to reduce external disturbances and reduce the risk of unsuccessful surgery.
Associations Between Intersecting Sociodemographic Characteristics and Device-Measured Physical Activity Among Children and Adolescents Living in the United States
Authors: Brown Denver M.Y. , Summerville Bryce , Fairclough Stuart J. , Mielke Gregore I. , Tyler Richard 
Published: January 2024

Background: Despite robust evidence demonstrating sociodemographic characteristics may underly some of the disparities in physical activity observed among children and adolescents, the often-overlooked nexus of potential interactions between these characteristics warrants further exploration. This study explored the intersectionality of gender, race/ethnicity, parental education, and household income in relation to device-measured physical activity volume and intensity in a nationally representative sample of US children and adolescents. Methods: Cross-sectional data from 3 cycles of the US National Health and Nutrition Survey (2011–2012; 2012 National Youth Fitness Survey; and 2013–2014) were used. A total of 6116 participants (49% female) between 3 and 17 years of age wore an accelerometer on their nondominant wrist for 7 days. Monitor-independent movement summary units were used to represent physical activity volume and intensity. A Social Jeopardy Index was created to represent increasing levels of intersecting social disadvantages based on combinations of gender, race/ethnicity, parental education, and household income-to-poverty ratio tertiles. Generalized linear regression models were computed. Results: The results showed social disadvantages become increasingly evident among children and adolescents during the most intense 60 minutes of daily physical activity (B = −48.69 [9.94] SE, P < .001), but disparities in total volume were not observed (B = 34.01 [44.96] SE, P = .45). Conclusions: Findings suggest that patterns of physical activity behavior may differ based on intersecting sociodemographic characteristics—more socially disadvantaged children and adolescents appear to accumulate activity at lighter intensities. Collecting contextual information about device-measured physical activity represents an important next step for gaining insight into these sociodemographic differences.
Differential interferon responses to influenza A and B viruses in primary ferret respiratory epithelial cells
Authors: Rowe Thomas , Davis William , Wentworth David E. , Ross Ted 
Published: January 2024

ABSTRACT

Influenza B viruses (IBV) cocirculate with influenza A viruses (IAV) and cause periodic epidemics of disease, yet antibody and cellular responses following IBV infection are less well understood. Using the ferret model for antisera generation for influenza surveillance purposes, IAV resulted in robust antibody responses following infection, whereas IBV required an additional booster dose, over 85% of the time, to generate equivalent antibody titers. In this study, we utilized primary differentiated ferret nasal epithelial cells (FNECs) which were inoculated with IAV and IBV to study differences in innate immune responses which may result in differences in adaptive immune responses in the host. FNECs were inoculated with IAV (H1N1pdm09 and H3N2 subtypes) or IBV (B/Victoria and B/Yamagata lineages) and assessed for 72 h. Cells were analyzed for gene expression by quantitative real-time PCR, and apical and basolateral supernatants were assessed for virus kinetics and interferon (IFN), respectively. Similar virus kinetics were observed with IAV and IBV in FNECs. A comparison of gene expression and protein secretion profiles demonstrated that IBV-inoculated FNEC expressed delayed type-I/II IFN responses and reduced type-III IFN secretion compared to IAV-inoculated cells. Concurrently, gene expression of Thymic Stromal Lymphopoietin (
TSLP
), a type-III IFN-induced gene that enhances adaptive immune responses, was significantly downregulated in IBV-inoculated FNECs. Significant differences in other proinflammatory and adaptive genes were suppressed and delayed following IBV inoculation. Following IBV infection,
ex vivo
cell cultures derived from the ferret upper respiratory tract exhibited reduced and delayed innate responses which may contribute to reduced antibody responses
in vivo
.

IMPORTANCE
Influenza B viruses (IBV) represent nearly one-quarter of all human influenza cases and are responsible for significant clinical and socioeconomic impacts but do not pose the same pandemic risks as influenza A viruses (IAV) and have thus received much less attention. IBV accounts for greater severity and deaths in children, and vaccine efficacy remains low. The ferret can be readily infected with human clinical isolates and demonstrates a similar course of disease and immune responses. IBV, however, generates lower antibodies in ferrets than IAV following the challenge. To determine whether differences in initial innate responses following infection may affect the development of robust adaptive immune responses, ferret respiratory tract cells were isolated, infected with IAV/IBV, and compared. Understanding the differences in the initial innate immune responses to IAV and IBV may be important in the development of more effective vaccines and interventions to generate more robust protective immune responses.
A prospective study of nanopore-targeted sequencing in the diagnosis of central nervous system infections
Authors: Fu Yu , Gu Jihong , Chen Liang-Jun , Xiong Mengyuan , Zhao Jin , Xiao Xiao , Zhou Junying , Li Zhiqiang , Li Yirong 
Published: January 2024

ABSTRACT

Central nervous system (CNS) infections are a leading cause of death in patients. Nanopore-targeted sequencing (NTS) has begun to be used for pathogenic microbial detection. This study aims to evaluate the ability of NTS in the detection of pathogens in cerebrospinal fluid (CSF) through a prospective study. Fifty CSF specimens collected from 50 patients with suspected CNS infections went through three methods including NTS, metagenomic next-generation sequencing (mNGS), and microbial culture in parallel. When there was an inconsistency between NTS results and the results of the mNGS, the 16S rDNA gene was amplified followed by Sanger sequencing to further verify pathogens detected by NTS. Among 50 CSF specimens, 76% were NTS-positive, which is lower than mNGS (94.0%), yet higher than microbial culture (16.0%). The overall validation rate, diagnostic accordance rate (DAR), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of NTS were 86.7%, 50.0%, 71.0%, 15.8%, 57.9%, and 25.0%, respectively. In the CSF total nucleated cell (TNC) number ≤10 cells/µL, DAR, specificity, and PPV were 20%, 11.1%, and 11.1%, whereas in that with CSF TNC number >10 cells/µL, DAR, sensitivity, specificity, PPV, and NPV were 57.5%, 70.0%, 20.0%, 72.4%, and 18.2%, respectively. Although NTS has a higher microbial detection rate than microbial culture, it should combine CSF TNC result to evaluate the value of NTS for the diagnosis of CNS infections.

IMPORTANCE
This study aims to prospectively evaluate the ability of nanopore-targeted sequencing (NTS) in the detection of pathogens in cerebrospinal fluid (CSF). It was the first time combining mNGS and microbial culture to verify the NTS-positive results also using 16S rDNA amplification with Sanger sequencing. Although microbial culture was thought to be the gold standard for pathogens detection and diagnosis of infectious diseases, this study suggested that microbial culture of CSF is not the most appropriate way for diagnosing central nervous system (CNS) infection. NTS should be recommended to be used in CSF for diagnosing CNS infection. When evaluating the value of NTS for diagnosis of CNS infections, the results of CSF TNC should be combined, and NTS-positive result is observed to be more reliable in patients with CSF TNC level >10 cells/μL.
Survival outcomes for congenital heart disease from Southern Malaysia: results from a congenital heart disease registry
Authors: Mat Bah Mohd Nizam , Kasim Aina Salwa , Sapian Mohd Hanafi , Alias Emieliyuza Yusnita 
Published: January 2024

ObjectiveLimited population-based studies are available on the survival of congenital heart disease (CHD) from lower- and middle-income countries. Therefore, we evaluated the survival from birth until 15 years and associated factors for mortality.MethodsThis population-based cohort study included all children with CHD registered in the Pediatric Cardiology Clinical Information System born between 2006 and 2020 in Johor, Malaysia. The mortality rate was calculated, and Cox proportional hazard regression analysis was used to determine factors associated with mortality. The Kaplan-Meier analysis was used to estimate the survival rates at 1, 5, 10 and 15 years.ResultsThere were 5728 patients with CHD studied, with 1543 (27%) lesions resolved spontaneously, 322 (5.6%) were treated with comfort care, 1189 (21%) required no intervention, and 2674 (47%) needed surgery or intervention. The overall mortality rate was 15%, with a median age of death of 3.7 months (IQR 0.9–9.8 months). Preoperative/intervention death was observed in 300 (11%), and 68 (3.2%) children died within 30 days of surgery or intervention. The overall estimated survival at 1, 5, 10 and 15 years was 88%, 85%, 84% and 83%, respectively. The independent factors associated with mortality were male gender, associated syndrome or extra-cardiac defect, pulmonary hypertension, antenatal diagnosis and severe lesions.ConclusionsEight out of 10 patients with CHDs survived up to 15 years of age. However, 10% of CHDs who require intervention die before the procedure. Thus, improving congenital cardiac surgery and enhancing the overall healthcare system are crucial to improve survival.
Atypical Wernicke’s encephalopathy without mental status changes following bariatric surgery in an adolescent patient
Authors: Akbar Asra , Lowther Jason , Creeden Sean , Frese William 
Published: January 2024

Morbid obesity is a systemic disease which can result in chronic complications, including hypertension, diabetes mellitus, depression, osteoarthritis and low self-esteem in the adolescent population.Bariatric surgery can be indicated to treat more severe forms of obesity, but these procedures are not without long-term risks. Therefore, adequate preoperative and postoperative care, which includes preoperative psychosocial evaluation for compliance, ongoing nutrition counselling and vitamin and micronutrient supplementation, is required for all patients, especially adolescent patients, who generally may not comply with medical therapies and/or be able to developmentally fully appreciate or comprehend the health consequences of their behaviours, prior to as well as after bariatric surgery to prevent complications.Thiamine pyrophosphate, an active form of thiamine (also known as vitamin B1, a water-soluble vitamin), which functions as a coenzyme in glucose and energy metabolism, is one such vitamin that requires supplementation postoperatively. It is mandatory for glucose to be administered concomitantly with thiamine, as glucose alone can precipitate Wernicke’s encephalopathy (WE) in thiamine-deficient individuals. WE is a medical emergency, with a mortality rate of up to 20%. WE is best understood as a classic triad of mental confusion, gait ataxia and eye movement abnormalities, and atypical WE or Wernicke’s syndrome (WS) is seen when the classic triad is not present. Cases that meet some, but do not necessarily meet all three criteria, are referred to as atypical WE or WS which can lead to delayed diagnosis. Atypical WE has an incidence of 19% which can lead to misdiagnosis of a preventable medical emergency with fatal complications.The following case reviews the consequences of post-bariatric thiamine supplementation therapy non-adherence and resulting in a deficiency in an adolescent patient.