bluuebunny/crossref_metadata_2025 huggingface dataset:
Gender and racialisation of pharmaceutical sector leaders in Canada: a cross-sectional study
Authors: Satgunanathan Kasthuri , Workentin Aine , Woods Hannah , Sabir Areesha , Persaud Nav
Published: November 2023

Objective/design

Lacking diversity in pharmaceutical leadership positions could contribute to inequities in medicine access. The objective of this cross-sectional study was to determine the gender and racial identities of individuals who hold leadership positions in the Canadian pharmaceutical sector.

Participants

We compiled a list of all Canadian governmental bodies, pharmaceutical companies and insurance providers. We identified individuals who were part of the leadership team, including executives and members of the board of directors.

Primary outcome measures

The main outcomes of the study were the racialisation and gender of the individuals in leadership positions. The gender and racialisation of an individual were determined by reviewing their name, pronouns and institutional profile through internet searches. Two members of the research team performed the assessment and a third reviewer resolved disagreements.

Results

We identified 957 individuals holding leadership positions within the pharmaceutical sector, including 280 drug evaluation committee members, 12 governmental executive officers, 273 insurance company executive and board members and 392 executive and board members. Reviewers identified a total of 375 (39.2% of 957) women holding leadership roles, with most of these positions being held by governmental leaders (52.4% of 292) and a minority by insurance (37.0% of 273) and pharmaceutical (30.9% of 392) leaders. There were a total of 157 (16.4% of 957) racialised leaders, with most of these positions being held by governmental (18.5% of 292) and pharmaceutical (18.1% of 392) leaders, and a minority in insurance companies (11.7% of 273). Across the pharmaceutical sector, there were a total of 48 (5.0% of 957) racialised women and 327 (34.2% of 957) white women.

Conclusions

Leaders within the Canadian pharmaceutical sector are mostly white men, and racialised women hold few leadership roles. Public policy should recognise that these institutions are mostly led by white men and reasons for this disparity could be explored.
Evaluating the balance of benefits and harms in chronic pain clinical trials: prioritizing individual participants over individual outcomes
Authors: Nishtar Mahd , Mark Remington , Langford Dale J , McDermott Michael P , Markman John D , Evans Scott R , France Fallon O , Park Meghan , Sharma Sonia , Turk Dennis C , Dworkin Robert H , Gewandter Jennifer S
Published: November 2023

Background

Randomized clinical trials (RCTs) generally assess efficacy and safety separately, with the conclusion of whether a treatment is beneficial based solely on the efficacy endpoint. However, assessing and combining efficacy and safety domains, using a single composite outcome measure, can provide a more comprehensive assessment of the overall effect of a treatment. Furthermore, composite outcomes can incorporate information regarding the relationship between the individual outcomes. In fact, such outcomes have been suggested in the clinical trials literature for at least 15 years.

Objectives

To (1) identify whether recent primary publications of chronic pain RCTs from major pain journals included a composite outcome measure of benefits and harms and (2) discuss the potential benefits of such outcomes in various stages of treatment development, including as outcome measures in RCTs, and to support decisions of Data and Safety Monitoring Boards and ordering of treatments in the context of treatment guidelines.

Evidence review

RCTs published in 6 major pain journals published between 2016 and 2021 that investigated interventions for chronic pain were reviewed.

Findings

Of 73 RCTs identified, only 2 included a composite outcome measure of benefits and harms. Both of these articles compared 2 active treatments.

Conclusions

Composite outcomes of benefits and harms are underutilized in chronic pain RCTs. The advantages and challenges of using such outcomes are discussed.
Genetic diversity and positive signatures of selection in indigenous cattle breeds of Iran
Authors: Ameri Nader Forough , Moradian Hasan , Koshkoiyeh Ali Esmailizadeh , Montazeri Mahdiyeh , Madabi Elaheh Rostamzadeh , Fozi Masood Asadi
Published: November 2023

Animal domestication, climate changes over time, and artificial selection have played significant roles in shaping the genome structure of various animal species, including cattle. These processes have led to the emergence of several indigenous cattle breeds with distinct genetic characteristics. This study focused on unraveling the genetic diversity and identifying candidate genomic regions in eight indigenous cattle breeds of Iran. The data consisted of ∼777 962 single nucleotide polymorphisms (SNPs) of 89 animals from Iranian indigenous cattle scattered throughout the country. We employed various methods, including integrated haplotype score, FST, and cross-population composite likelihood ratio, to conduct a genome scan for detecting selection signals within and between cattle populations. Average observed heterozygosity across the populations was 0.36, with a range of 0.32–0.40. In addition, negative and low rates of inbreeding (FIS) in the populations were observed. The genome-wide analysis revealed several genomic regions that harbored candidate genes associated with production traits (e.g., MFSD1, TYW5, ADRB2, BLK, and CRTC3), adaptation to local environmental constraints (CACNA2D1, CXCL3, and GRO1), and coat color (DYM). Finally, the study of the reported quantitative trait loci (QTL) regions in the cattle genome demonstrated that the identified regions were associated with QTL related to important traits such as milk composition, body weight, daily gain, feed conversion, and residual feed intake. Overall, this study contributes to a better understanding of the genetic diversity and potential candidate genes underlying important traits in Iranian indigenous cattle breeds, which can inform future breeding and conservation efforts.
The Early Jurassic sequence of Lyme Regis, Dorset, England and its place in the history of geology and palaeontology
Authors: Sharpe Tom
Published: November 2023

The cliffs and foreshore at Lyme Regis on the Dorset coast expose a sequence of Early Jurassic marine limestones and mudstones of the Blue Lias Formation and the overlying Charmouth Mudstone Formation, the lowest units of the Hettangian–Aalenian Lias Group. Known for its fossils since at least the mid-seventeenth century, this coastal section became famous in the early nineteenth century for the bones of ‘fossil crocodiles’. Many of the most significant discoveries were made by a family of fossil dealers whose best-known member was Mary Anning (1799–1847). Anning and her family recovered the first scientifically described ichthyosaurs, the first complete plesiosaur and the first British pterosaur to be identified. Anning's finds from Lyme Regis formed the basis of the pioneering palaeoenvironmental reconstruction
Duria antiquior
. Her geologist friends, some with close personal associations to the town, did much to publicize her discoveries and contribute to both her fame and that of the locality. This famous coastal section, with its important historical associations with a key period in the development of geology and the source of so many significant discoveries in the early nineteenth century, now lies within the Jurassic Coast UNESCO World Heritage Site.
Synthetic Communities of Gut Microbes for Basic Research and Translational Approaches in Animal Health and Nutrition
Authors: Jennings Susan A.V. , Clavel Thomas
Published: November 2023

Microbes and animals have a symbiotic relationship that greatly influences nutrient uptake and animal health. This relationship can be studied using selections of microbes termed synthetic communities, or SynComs. SynComs are used in many different animal hosts, including agricultural animals, to investigate microbial interactions with nutrients and how these affect animal health. The most common host focuses for SynComs are currently mouse and human, from basic mechanistic research through to translational disease models and live biotherapeutic products (LBPs) as treatments. We discuss SynComs used in basic research models and findings that relate to human and animal health and nutrition. Translational use cases of SynComs are discussed, followed by LBPs, especially within the context of agriculture. SynComs still face challenges, such as standardization for reproducibility and contamination risks. However, the future of SynComs is hopeful, especially in the areas of genome-guided SynCom design and custom SynCom-based treatments.
Lipid Quality Control and Ferroptosis: From Concept to Mechanism
Authors: Li Zhipeng , Lange Mike , Dixon Scott J. , Olzmann James A.
Published: November 2023

Cellular quality control systems sense and mediate homeostatic responses to prevent the buildup of aberrant macromolecules, which arise from errors during biosynthesis, damage by environmental insults, or imbalances in enzymatic and metabolic activity. Lipids are structurally diverse macromolecules that have many important cellular functions, ranging from structural roles in membranes to functions as signaling and energy-storage molecules. As with other macromolecules, lipids can be damaged (e.g., oxidized), and cells require quality control systems to ensure that nonfunctional and potentially toxic lipids do not accumulate. Ferroptosis is a form of cell death that results from the failure of lipid quality control and the consequent accumulation of oxidatively damaged phospholipids. In this review, we describe a framework for lipid quality control, using ferroptosis as an illustrative example to highlight concepts related to lipid damage, membrane remodeling, and suppression or detoxification of lipid damage via preemptive and damage-repair lipid quality control pathways.
Control Co-Design of Wind Turbines
Authors: Pao Lucy Y. , Pusch Manuel , Zalkind Daniel S.
Published: November 2023

Wind energy is recognized worldwide as cost-effective and environmentally friendly, and it is among the fastest-growing sources of electrical energy. To further decrease the cost of wind energy, wind turbines are being designed at ever-larger scales. To expand the deployment of wind energy, wind turbines are also being designed on floating platforms for placement in deep-water locations offshore. Both larger-scale and floating wind turbines pose challenges because of their greater structural loads and deflections. Complex, large-scale systems such as modern wind turbines increasingly require a control co-design approach, whereby the system design and control design are performed in a more integrated fashion. This article reviews recent developments in control co-design of wind turbines. We provide an overview of wind turbine design objectives and constraints, issues in the design of key wind turbine components, modeling of the wind turbine and environment, and controller coupling issues. Wind turbine control functions and the integration of control design in co-design are detailed with a focus on co-design compatible control approaches.
A Control Framework for Ocean Wave Energy Conversion Systems: The Potential of Moments
Authors: Faedo Nicolás , Ringwood John V.
Published: November 2023

The control of wave energy converters (WECs) to maximize power capture is a challenging problem. In particular, the nature of the wave excitation, which is in general panchromatic (or multi-sinusoidal), presents a reciprocating energy source that needs to be rectified through some means. In addition, the development of suitable control-oriented models is also challenging, requiring correct representation of system hydrodynamics and power take-off (PTO) components, while also lending themselves to control synthesis and real-time computational performance, along with a challenging optimal control problem. This article presents a moment-based mathematical framework for the formulation and solution of WEC control. It shows that moments are ideally suited to WEC control in terms of their ability to accurately characterize the nature of the wave excitation force (and the consequent evolutions in the system variables) while also gracefully including hydrodynamic and PTO nonlinearities as well as a natural extension to WEC arrays. Model reduction, to mold the system model into a control-friendly form, is also a feature of this framework.
Progress and Prospects of MXene-Based Hybrid Composites for Next-Generation Energy Technology
Authors: S Chetana , Mohd Abdah Muhammad Amirul Aizat , Thakur Vikas N. , Govinde Gowda M. S. , Choudhary Priyvart , Sriramoju Jagadeesh Babu , Rangappa Dinesh , Malik Sumira , Rustagi Sarvesh , Khalid Mohammad
Published: November 2023

MXenes are an emerging class of two-dimensional transition metal carbides and nitrides with metallic conductivity and hydrophilic surfaces. The discovery of MXenes has opened new possibilities for developing advanced hybrid composites for energy storage and conversion applications. This review summarizes recent advances in developing MXene-based hybrid composites, including their synthesis, characterization, and electrochemical performance. The heterostructure of MXenes with nanocarbons, metal oxides, polymers, and other nanomaterials can overcome the limitations of pristine MXenes and lead to enhanced lithium/sodium-ion storage, pseudocapacitive performance, and electrocatalytic activity. Various fabrication techniques have been employed to synthesize MXene composites with controlled nanostructures, morphology, and interfacial properties. Characterization by microscopy, spectroscopy, and electrochemical methods has shed light on structure-property relationships in these materials. As electrode materials, properly designed MXene hybrids have achieved high specific capacity, excellent rate capability, and long-term stability. The review also discusses strategies for further improving MXene composite energy storage performance, as well as emerging applications such as thermoelectrics and photocatalysis. Continued research to understand interfacial effects and optimize MXene heterostructures holds promise for developing next-generation energy storage technologies.
Lanthanum Sulfide Nanorods Modified Glassy Carbon Electrode as Non-Enzymatic Biosensor for Xanthine
Authors: Javeed Zainab , Ibrahim Muhammad , Iqbal Muhammad Faisal , Nawaz Rahat , Hussain Dilshad , Ayub Muhammad , Ashiq Muhammad Naeem , Majeed Saadat , Najam-ul-Haq Muahmmad , Fatima Batool
Published: November 2023

Xanthine detection is crucial for the diagnosis of metabolic disorders like xanthinuria and gout. Xanthinuria is due to xanthine stones in the urinary tract. Earlier detection of xanthine levels in human blood can minimize the risks. In this research, a non-enzymatic xanthine sensor is fabricated by depositing different concentrations of lanthanum sulfide nanoparticles on a glassy carbon electrode (GCE). Lanthanum sulfide (La2S3) nanorods are synthesized by a simple hydrothermal method and characterized by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDS). The effect of pH, scan rates, and xanthine concentration on the peak current is examined. La2S3-modified GCE shows good conductivity, a large surface area, fast electron transfer, and promising sensing capability for xanthine detection. The highest anodic peak for xanthine is observed at a 1 mV s−1 scan rate. The la2S3-based sensor exhibits a limit of detection (LOD) of 1.2 μM and xanthine recovery of up to 99.3%. The designed sensing system demonstrates the potential for xanthine detection in blood serum samples. The proposed sensor exhibits excellent efficiency due to fast electron transfer and good stability of La2S3 nanorods.
Demonstration of Feasibility Using Ionic Liquid as Electrolyte for Electrochemical Deposition and Recovery of Silver from Silver Oxide
Authors: Huang Shiao-Chen , Yu Chia-Lin , Lee Chien-Liang , Chen Po-Yu
Published: November 2023

Silver oxide (Ag₂O) is soluble in the hydrophobic protic amide-type ionic liquid (IL), protonated-betaine bis((trifluoromethyl)sulfonyl)amide ([Hbet][TFSA]). Cyclic voltammetric behavior of Ag(I) showed a single redox couple, and NMR spectra implied that Ag⁺ might be coordinated with the [TFSA] anions in more extent than with the deprotonated [Hbet] ions (i.e. [bet]; a Zwitterion). By changing the scan rates and cycle numbers of potential scan utilized for the cyclic voltammetric electrodeposition, different particle sizes and distribution densities of silver nanoparticles (AgNPs) could be electrodeposited on glassy carbon disc electrode (GCE), which showed activities towards the electrochemical reduction of nitrate and oxidation of hydrazine, respectively, in alkaline solutions. The high faradic efficiencies (F.E.) of Ag electrodeposition using the contents of Ag₂O coin batteries as the Ag source implied that it may be possible to develop a process for recovering Ag from spent Ag₂O coin batteries based on the electrochemical system reported here.
Grey Interest Chain Identification and Control Model for Government Investment Engineering Projects Based on Node Identification
Authors: Deng Lin , Wu Yaping , Chen Xianjun , Li Tian , Chen Yun
Published: November 2023

In the bidding process of government investment engineering projects, collusion between the government and bidders occurs repeatedly, which seriously affects the quality of engineering projects and the effectiveness of the government investment. Therefore, it is necessary to analyze and discuss the collusion between the government and bidders in government investment engineering projects, so as to provide a healthy and sustainable environment for the government investment engineering bidding market. There are two main types of collusion in engineering bidding: horizontal collusion and vertical collusion, and this paper focuses on the vertical collusion process in the engineering bidding process. A conceptual framework of the grey interest chain based on three stages of benefit creation, benefit distribution, and benefit realization was established, 15 major nodes in the grey interest chain were identified, and a grey interest chain control model was constructed, which further identified and classified the nodes into four levels: key nodes, important nodes, general nodes, and unimportant nodes. Finally, through the application of the model in the case, measures such as establishing a cracking mechanism for grey resource integration, increasing the supervision of grey interest chain, and strengthening post-bid audit are proposed. Measures such as including the preparation of bidding documents into the work assessment system and entrusting consulting units or third parties to prepare bidding documents are proposed to establish a crack mechanism for grey resource integration. In the benefit distribution stage, the penalties for the government and the bidders can be appropriately increased, the responsibilities of enterprises and project leaders can be implemented in the system on a reciprocal basis, and a perfect reputation mechanism information can be established. At the stage of benefit realization, the bidding system should be improved and post-bid audit should be strengthened to increase the difficulty of grey benefit realization. This paper will provide a reference for the prevention and governance of vertical collusion in bidding and tendering.
Surface Roughness Evaluation of Resin Composites after Finishing and Polishing Using 3D-Profilometry
Authors: Vinagre Alexandra , Barros Catarina , Gonçalves Joana , Messias Ana , Oliveira Filipe , Ramos João
Published: November 2023

The purpose of this study was to evaluate the effect of two finishing and polishing methods on the surface roughness of different resin composites. Twenty-two disk-shaped specimens of five resin composites Zirconfill® (ZF), Filtek™ Supreme XTE (FS), Brilliant EverGlow™ (BG), Ceram.X® Duo (CD), and Harmonize™ (HA) were prepared for each one using a silicon mold. Both surfaces of each specimen were first grinded with 600-grit silicon carbide paper in a moistened environment. The polishing methods used included the two-step Enhance® and PoGo® polishing system (E/P) or the four-step SwissFlex® discs (SFD). Surface roughness was evaluated using a noncontact 3D-optical profilometer. Surface morphology was examined by scanning electron microscopy. Data were analyzed using two-way analysis of variance and pairwise comparisons with Tukey’s test (

α
=
0.050

). Surface roughness was affected by both the type of resin composite (

p
<
0.001

) and the finishing and polishing system (

p
<
0.001

), with a significant interaction between these two factors (

p
=
0.025

). The E/P system produced smoother surfaces than the SFD system (

p
<
0.001

). For the E/P system, the highest mean roughness value was obtained with ZF and was statistically different from all other composites, whereas inhomogeneous results among resin composites could be found for the SFD system. Surface roughness was material-dependent, and the polishability of the resin composites was best accomplished using the E/P system. Within each F/P system studied, BG showed the lowest average surface roughness and ZF registered the highest.
The Assessment of Different Dietary Selenium Resources on Reproductive Performance, Spawning Indicators, and Larval Production of Red Tilapia (Oreochromis mossambicus × O. niloticus) Broodfish
Authors: Naiel Mohammed A. E. , Eissa El-Sayed H. , Abd El-Aziz Yasmin M. , Saadony Saadea , Abd Elnabi Heba E. , Sakr Salah El-Sayed
Published: November 2023

This trial aimed to investigate whether dietary selenium form influenced the reproductive performance of red tilapia broodfish. Four experimental broodstock diets were prepared employing two types of selenium. The first diet was free of additives and acted as the control diet. While the other three formulated diets were supplemented with conventional selenium sources (sodium selenite, Na2SeO3; 1 mg/kg), selenium nanoparticles (NPSe, 1 mg/kg), or a combination of them (0.5 mg Na2SeO3/kg + 0.5 mg NPSe/kg), respectively. Twelve cement ponds (each 24 m2) were subjected to fish brooder experimental groups. Each pond received six prespawning females (mean initial weight, 60.9 ± 0.4 g) and two males (mean weight 80.3 ± 0.8 g) of red tilapia. Each formulated diet was supplied to three broodfish cement ponds, and the reproductive traits of 18 adult female fish were monitored over 25 weeks. The findings showed that female fish fed NPSe-enriched diets had significantly higher viscera, liver, and gonad weight than other experimental groups. At the same time, the highest levels of LH, progesterone, and estradiol-17β, as well as the lowest levels of FSH, were detected in fish fed the NPSe diet, followed by those on the Na2SeO3 + NPSe and Na2SeO3 diets, respectively. Furthermore, the diameter, weight, and volume of eggs, as well as the number and weight of larvae in red tilapia brooder fish fed the various dietary selenium forms, increased markedly (

P
<
0.001

). Female red tilapia broodfish given selenium-based diets enhanced all spawning performance indicators (particularly total spawned egg per pond or fish and initial spawning interval) when compared to a control group fed an unsupplemented diet. Besides, as compared to other treatment groups, the spawning frequency of each female fish fed NPSe-supplemented diets (alone or in combination with Na2SeO3) was considerably (

P
<
0.001

) promoted. The fish group fed NPSe alone or mixed with Na2SeO3 had a well-developed stroma structure, many mature vitellogenic and postvitellogenic oocytes, and a remarkable intensity of mature spermatozoa in the testis. In conclusion, incorporating NPse into red tilapia broodstock diets might be a safe and efficient way to enhance reproductive function and fry production.
Benchmarking Water-Limited Yield Potential and Yield Gaps of Shiraz in the Barossa and Eden Valleys
Authors: Bonada Marcos , Petrie Paul R. , Phogat Vinod , Collins Cassandra , Sadras Victor O.
Published: November 2023

Background and Aims. Vineyard performance is impacted by water availability including the amount and seasonality of rainfall, evapotranspiration, and irrigation volume. We benchmarked water-limited yield potential (Yw), calculated yield gaps as the difference between Yw and actual yield, and explored the underlying environmental and management causes of these gaps. Methods and Results. The yield and its components in two sections of 24 Shiraz vineyards were monitored during three vintages in the Barossa zone (GI). The frequency distribution of yield was L-shaped, with half the vineyards below 5.2 t·ha−1, and an extended tail of the distribution that reached 24.9 t·ha−1. The seasonal ratio of actual crop evapotranspiration and reference evapotranspiration was below 0.48 in 85% of cases, with a maximum of 0.65, highlighting a substantial water deficit in these vineyards. A boundary function relating actual yield and seasonal rainfall was fitted to quantify Yw. Yield gaps increased with an increasing vine water deficit, as quantified by the carbon isotope composition of the fruit. The yield gap was smaller with higher rainfall before budburst, putatively favouring early-season vegetative growth and allocation to reproduction, and with higher rainfall between flowering and veraison, putatively favouring fruit set and berry growth. The gap was larger with higher rainfall and lower radiation between budburst and flowering. The yield gap increased linearly with vine age between 6 and 33 yr at a rate of 0.3 t·ha−1·yr−1. The correlation between yield gap and yield components ranked bunch weight ≈ berries per bunch > bunch number > berry weight; the minimum to close the yield gap was 185,000 bunches ha−1, 105 g bunch−1, 108 berries bunch−1, and 1.1 g berry−1. Conclusions. Water deficit and vine age were major causes of yield gaps. Irrigation during winter and spring provides an opportunity to improve productivity. The cost of dealing with older, less productive vines needs to be weighed against the rate of increase in yield gap with vine age. Significance of the Study. A boundary function to estimate water-limited yield potential returned viticulturally meaningful yield gaps and highlighted potential targets to improve vineyard productivity.
Detection of Clostridium perfringens Using Novel Methods Based on Recombinase-Aided Amplification Assay-Assisted CRISPR/Cas12a System
Authors: Xiao Xingxing , Zhang Qingxun , Wu Sihong , Li Yi , Zhong Zhenyu , Guo Qingyun , Li Junfang , Meng Qinghui , Cheng Zhibin , Duan Jianbin , Wang Xiaoqiong , He Hongxuan , Bai Jiade , Lou Yongliang
Published: November 2023

Clostridium perfringens is a highly versatile pathogen of humans and animals. Rapid and sensitive detection methods for C. perfringens are urgently needed for the timely implementation of control. In this study, to provide novel promising methods for the detection of C. perfringens, two rapid, sensitive, and instrument-free C. perfringens detection methods based on recombinase-aided amplification (RAA) assay and clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 12a (CRISPR/Cas12a) system were developed depending on fluorescence signal (RAA-CRISPR/Cas12a-FL) and lateral flow strip (RAA-CRISPR/Cas12a-LFS), respectively. The limit of detection of the RAA-CRISPR/Cas12a-FL and RAA-CRISPR/Cas12a-LFS methods is 2 copies and 20 copies of C. perfringens genomic DNA per reaction, respectively, and the whole process can be completed in 1 hr. Moreover, these two methods show no cross-reactivity with nontarget bacteria, which were used as a negative control to evaluate the specificity of two developed methods in the detection of C. perfringens and have 100% consistent with real-time polymerase chain reaction tests for 12 clinical samples collected from 2 Chinese Milu at Beijing Milu Ecological Research Center and 6 spiked samples from human blood and stool. Overall, the constructed C. perfringens detection methods, RAA-CRISPR/Cas12a-FL and RAA-CRISPR/Cas12a-LFS, have great potential as a novel detection scheme for the early diagnosis of C. perfringens infection in humans and animals.
Integrative Analysis of Clinical and Bioinformatics Databases to Reveal the Role of Peripheral Innate Immunity in Kawasaki Disease
Authors: Ba Hongjun , Zhang Lili , Peng Huimin , Lin Jixun , Qin Youzhen , Wang Yao
Published: November 2023

Kawasaki disease (KD) is an immune-response disorder with unknown etiology. KD is an acute systemic immune vasculitis caused by infectious factors that can be complicated by coronary artery lesions. Innate immune cells are closely associated with KD onset, but we know little regarding the expression of immunity-related genes (IRGs) and the possible immune regulatory mechanisms involved in KD. In this study, we analyzed public single-cell RNA sequencing (scRNA-seq) and microarray data of peripheral blood mononuclear cells from normal controls and KD patients. The results of scRNA-seq revealed myeloid cells, T cells, B cells, NK cells, erythrocytes, platelets, plasma cells, hematopoietic stem cells, and progenitor cells in the peripheral blood of patients with KD. In particular, myeloid cells were expanded and heterogeneous. Further analysis of the myeloid cell population revealed that monocytes in KD exhibited higher expression of the inflammatory genes S100A8, S100A9, and S100A12; furthermore, CD14+CD16+ monocyte clusters were associated with inflammatory responses. Microarray data revealed that activation of the innate immune response contributed to KD development and progression. Differential expression and weighted gene coexpression network analysis identified 48 differentially expressed IRGs associated with response to intravenous immunoglobulin, currently the most effective treatment of KD, although numerous patients are resistant. Protein–protein interaction analysis identified ten hub genes (IL1R1, SOCS3, IL1R2, TLR8, IL1RN, CCR1, IL1B, IL4R, IL10RB, and IFNGR1) among the IRGs. In addition, the expressions of IL1R1, SOCS3, CCR1, IL1B, and IL10RB were validated in Chinese KD patients using the real-time reverse transcriptase-polymerase chain reaction. Finally, we found that the neutrophil/lymphocyte ratio could be used as a biomarker to predict responsiveness to intravenous immunoglobulin in KD. In conclusion, our data highlight the importance of innate immunity in KD pathogenesis and its potential in predicting treatment response.
The Impact of Microscopic Pore Network Characteristics on Movable Fluid Properties in Tight Oil Reservoir
Authors: Gao Jie , Wang Hu , Ding Xiaojun , Yuchi Qingxiao , Ren Qiang , Ning Bo , Nan Junxiang
Published: November 2023

The fluid flow behavior, generally referred to as seepage, could determine the hydrocarbon and brine movement behavior. Movable fluid property, as one of the vital parameters for seepage characteristic evaluation, was generally used for tight oil reservoirs’ fluid flow ability assessment. The nuclear magnetic resonance technique was used to experiment with movable fluid percentage and movable fluid porosity, which can provide a realistic assessment of the amount of fluid that can flow in the porous media. Other techniques were also used to analyze the main factors in regulating the differences in movable fluid parameters. However, the research about fluid flow behavior was generally based on traditional methods, while the seepage characteristics from the pore-scale view are still a myth. To promote this process, in this study, core samples obtained from the Chang 7 reservoir of the Triassic Yanchang Formation in the Longdong region of Ordos Basin, China, were tested. The results show that the average movable fluid percentage and average movable fluid porosity of the total 16 core samples are 36.01% and 2.77%, respectively. The movable fluid exists mainly in the midlarge pores with the corresponding

T

2

relaxation time over 10 ms.

T

2

distributions mainly present four typical patterns: (1) bimodal distribution with similar amplitudes of the two peaks (occupying 6.25%), (2) bimodal distribution with higher right peak and lower left peak (occupying 18.75%), (3) bimodal distribution with higher left peak and lower right peak (occupying 56.25%), and (4) unimodal distribution (occupying 18.75%). Pore structure heterogeneity is closely related to the movable fluid parameters; the movable fluid parameters exhibit a relatively good correlation with core throat radius as well as permeability. There is an obvious difference between the movable fluid parameters and the microscopic characteristic factors in tight oil reservoirs due to the difference in physical properties, clay mineral content, microcracks, and pore structure characteristics. This research has provided a new perspective for the movable fluid property evaluation, and the relevant results can give some advice for the oil field development.
Antimicrobial Efficiency of Hypochlorous Acid and Its Effect on Some Properties of Alginate Impression Material
Authors: Khalaf Bayan S. , Abass Shorouq M. , Al-Khafaji Aseel Mohammed , Issa Moamin I.
Published: November 2023

Dental clinicians and professionals need an affordable, nontoxic, and effective disinfectant against infectious microorganisms when dealing with the contaminated dental impressions. This study evaluated the efficiency of hypochlorous acid (HOCl) as an antimicrobial disinfectant by spraying technique for the alginate impression materials, compared with sodium hypochlorite, and its effect on dimensional stability and reproduction of details. HOCl with a concentration of 200 ppm for 5 and 10 min was compared with the control group (no treatment) as a negative control and with sodium hypochlorite (% 0.5) as a positive control. Candida albicans, Staphylococcus aureus, and Pseudomonas aeruginosa were selected to assess the antimicrobial activity with the colony forming unit test in addition to the dimensional stability and reproduction of details tests. The results revealed that HOCl had significant antimicrobial activity against all tested microorganisms and experimental time. Interestingly, HOCl showed no impact on the dimensional stability of alginate impression material. HOCl could be an effective antimicrobial agent for alginate impression material without interfering with their surface details and dimensional stability.
A Machine Learning-Based Classification of Immunogenic Cell Death Regulators and Characterisation of Immune Microenvironment in Acute Ischemic Stroke
Authors: Wang Mengying , Wei Guolian , Gu Shaorui , Huo Zhengyuan , Han Xue
Published: November 2023

Immunogenic cell death (ICD) regulators exert a crucial part in quite a few in numerous biological processes. This study aimed to determine the function and diagnostic value of ICD regulators in acute ischemic stroke (AIS). 31 significant ICD regulators were identified from the gene expression omnibus (GEO) database in this work (the combination of the GSE16561 dataset and the GSE37587 dataset in the comparison of non-AIS and AIS patients). The random forest model was applied and 15 potential ICD regulators were screened to forecast the probability of AIS. A nomogram, on the basis of 11 latent ICD regulators, was performed. The resolution curve analysis indicated that patients can gain benefits from the nomogram. The consensus clustering approach was applied, and AIS patients were divided into 2 ICD clusters (cluster A and cluster B) based on the identified key ICD regulatory factors. To quantify the ICD pattern, 181 ICD-related dissimilarly expressed genes (DEGs) were selected for further investigation. The expression levels of NFKB1, NFKB2, and PARP1 were greater in gene cluster A than in gene cluster B. In conclusion, ICD regulators exerted a crucial part in the progress of AIS. The investigation made by us on ICD patterns perhaps informs prospective immunotherapeutic methods for AIS.
Characterizing Adverse Events of Biologic Treatment of T2 Disease: A Disproportionality Analysis of the FDA Adverse Event Reporting System
Authors: Stack Taylor J. , Kim Sulgi , Lamb Meredith M. , Mohammad Ibtisam , Zeatoun Abdullah , Lopez Erin , Klatt-Cromwell Cristine , Thorp Brian D. , Ebert Jr. Charles S. , Senior Brent A. , Kimple Adam J. , Alicea Daniel
Published: November 2023

Introduction: Over the last 3 years, the FDA has approved dupilumab, omalizumab, and mepolizumab for the treatment of CRSwNP; however, adverse events of these biologics have not been described in post-marketing surveillance trials. By utilizing the FDA Adverse Event Reporting System (FAERS), this study describes and compares biologic-associated adverse events in T2 disease. Methods: This case-non-case study assessed disproportionate reporting rates using reporting odds ratios (RORs). RORs and p values for biologic-associated AEs were categorized and compared among dupilumab, omalizumab, and mepolizumab. This analysis included AEs associated with all treatment indications. Relative AE rates and outcomes were calculated. Results: There were a total of 112,560, 24,428, and 18,741 unique AE reports associated with dupilumab, omalizumab, and mepolizumab, respectively. Omalizumab had the strongest association with anaphylaxis (ROR = 20.80, 95% confidence interval [CI]: 18.58, 23.29). Dupilumab had large relative proportions and positive signals in the ophthalmologic category (7.76%, ROR = 6.20, 95% CI: 6.06, 6.35), such as with blurry vision (ROR = 3.80, CI: 3.52, 4.12) and visual impairment (ROR = 1.98, CI: 1.80, 2.19). Dupilumab was the only biologic associated with injection-site reactions (7.98%, ROR = 8.17, 95% CI: 7.98, 8.37). Discussion/Conclusion: This is the first large-scale comparative analysis of the AE profiles of dupilumab, omalizumab, and mepolizumab. Our data suggest possible relations between dupilumab and ophthalmologic and injection-site AEs. Omalizumab was the only biologic with a positive anaphylaxis signal. This FAERS investigation suggests important AE differences among these biologics.
Infectious Disease Screening prior to Systemic Immunomodulatory Therapy in Hidradenitis Suppurativa: Consensus Guidelines from the Asia-Pacific Hidradenitis Suppurativa Foundation
Authors: Kozera Emily K. , Porter Martina , Paek So Yeon , Mintoff Dillon , McMeniman Erin , Oon Hazel H. , Chandran Nisha Suyien , Glasenhardt Katalin , Ring Hans Christian , Frew John W.
Published: November 2023

Background: Current infectious disease screening recommendations for hidradenitis suppurativa (HS) are adopted from recommendations in chronic plaque psoriasis. No HS-specific guidelines for infectious disease screening prior to immunomodulatory therapy have been developed. Objectives: The aim of the study was to establish an expert Delphi consensus of recommendations regarding infectious disease screening prior to systemic immunomodulatory therapy in HS. Methods: Participants were identified via recent publications in the field and were sent a questionnaire regarding infectious diseases encountered in the setting of HS, and opinions regarding infectious disease screening prior to various systemic immunomodulatory therapies. All questions were informed by a systematic literature review regarding infections exacerbated or precipitated by immunomodulatory therapy. Questionnaire responses were followed by round-table discussion with a core group of 8 experts followed by a final round of questionnaires resulting in achievement of consensus. Results: 44 expert HS physicians from 12 countries on 5 continents participated in the development of the expert consensus recommendations. Consensus recommendations include screening for hepatitis B, hepatitis C and tuberculosis in all individuals with HS prior to therapy. All immunomodulatory therapies (biologic and systemic immunosuppressant therapy) should be preceded by infectious disease screening including patient and location-specific considerations for endemic local diseases and high-risk activities and occupations. Clinical assessment has a significant role in determining the need for laboratory screening in the setting of many uncommon or tropical diseases such as leprosy, leishmaniasis and strongyloidiasis. Conclusions: The presented consensus recommendations are the first specifically developed for pre-treatment infectious disease screening in HS.
Improved Post-Traumatic Stress Disorder Symptoms and Related Sleep Disturbances after Initiation of Medical Marijuana Use: Evidence from a Prospective Single Arm Pilot Study
Authors: Vaddiparti Krishna , Liu Yiyang , Bottari Sarah , Boullosa Carly Crump , Zhou Zhi , Wang Yan , Williamson John , Cook Robert L.
Published: November 2023

Introduction: Post-traumatic stress disorder (PTSD) is a debilitating disorder experienced by a subgroup of individuals following a life-threatening trauma. Several US states have passed laws permitting the medical use of marijuana (MMJ) by individuals with PTSD, despite very little scientific indication on the appropriateness of marijuana as a therapy for PTSD. This prospective pilot study of adults with confirmed PTSD in Florida (FL) investigated whether PTSD symptoms, sleep quality, affect, and general physical and mental health/well-being improved post-initiation of MMJ treatment. Methods: Participants, N = 15, were recruited from two MMJ clinics in Gainesville and Jacksonville, FL. To be eligible, participants had to be 18 years of age or older, not currently on MMJ, and willing to abstain from recreational marijuana, if using any, until the State Medical Cannabis Card was obtained, screen positive for PTSD. Participants were assessed at baseline (pre-MMJ initiation) and 30 and 70 days post-MMJ initiation using the Pittsburgh Sleep Quality Index (PSQI), PTSD Checklist for DSM-5 (PCL-5), Positive and Negative Affect Schedule (PANAS), PROMIS Global Health V1.2, and semi-structured marijuana and other substance use assessment. Results: PTSD symptom severity as measured by total PCL-5 score improved significantly at 30- and 70-day follow-ups. Similarly, statistically significant reductions in nightmares were reported at 30- and 70-day follow-ups. Corresponding improvements in sleep were noticed with participants reporting increased duration of sleep hours, sleep quality, sleep efficiency, and total PSQI score. Likewise, negative affect and global mental health improved significantly at follow-up. According to the post hoc analyses, the most statistically significant changes occurred between baseline and 30-day follow-up. The exception to this pattern was nightmares, which did not show significant improvement until day 70. Conclusion: The findings of this study highlight the potential of MMJ in improving patient outcomes for those with PTSD, particularly concerning sleep disturbances, which often do not respond to currently available treatments.
Modulation of Intestinal Motility in an Adolescent Rat Model of Irritable Bowel Syndrome
Authors: Kyodo Reiko , Kudo Takahiro , Ito Natsuki , Tokita Kazuhide , Arai Nobuyasu , Sato Masamichi , Ikuse Tamaki , Jimbo Keisuke , Ohtsuka Yoshikazu , Shimizu Toshiaki
Published: November 2023

Introduction: The pathophysiology of irritable bowel syndrome (IBS) remains unknown. This study aimed to evaluate colonic motility and serotonin system response to restraint stress (RS) among adolescent rats who underwent neonatal maternal separation (NMS) to clarify the features of pathogenesis in adolescents with IBS. Methods: Male rats were exposed to NMS as chronic stress, and a normally handled (NH) group was used as control. Four groups were created by adding RS as acute stress treatment to the NMS and NH groups. To realize the RS treatment, the subjects were restrained for 1 h at the age of 5 weeks, and hourly fecal pellet discharge was determined. After euthanization and proximal colon intestinal tissue collection, 5-hydroxytryptamine (5-HT) and 5-hydroxytryptamine receptor 3 (5-HT3R) concentrations, enterochromaffin (EC) cell density, and the expression of mRNA-encoding slc6a4 were examined. Results: The amount of fecal pellet discharge during RS increased significantly in the RS and NMS+RS groups compared with that in the NH and NMS groups, respectively. The 5-HT concentration in the intestinal tissue of rats in the RS and NMS groups increased significantly compared with that of rats in the NH group. EC cell density also increased significantly in the NMS and NMS+RS groups compared with that in the NH and RS groups. However, combined stress did not result in any significant differences in the expression of 5-HT3R and mRNA-encoding slc6a4. Conclusions: The combination of juvenile and acute stress effectively induced increased 5-HT concentration or EC cell density via the 5-HT pathway in the proximal colon of adolescent rats.
A Homozygous Missense Variant in HSD17B4 Identified in Two Different Families
Authors: Özkan Kart Pınar , Sahin Yavuz , Yıldız Nihal , Cebi Alper Han , Esenulku Gulnur , Cansu Ali
Published: November 2023

Background: Perrault syndrome is an inherited disorder with clinical findings that differ according to sex. It is characterized by a variable age of onset and sensorineural hearing loss in both sexes, as well as ovarian dysfunction in females with a 46,XX karyotype. Although it is a rare autosomal recessive syndrome, with approximately 100 affected individuals reported in the literature, it shows both genotypic and phenotypic variations. Mutations in the HSD17B4 gene have been identified as one of the genetic causes of Perrault syndrome. Case Presentation: A female case and a male case from two different unrelated families with a new variant in the HSD17B4 gene, which were not previously described in the literature and were accompanied by hearing loss, skeletal anomalies, and neurological symptoms, were presented. Conclusion: We defined Perrault syndrome cases in Turkey caused by a novel mutation in HSD17B4. Whole-exome sequencing is a useful diagnostic technique with varying clinical results due to genetic and phenotypic heterogeneity.
QTc interval prolongation independently associates with FGF23 and predicts mortality in predialysis CKD.
Authors: Sikaneta Tabo , Ho Natalie , Bellasi Antonio , Mahdav Sara , Taskapan Hulya , Svendrovski Anton , Makanjee Bhavanesh , Roberts Jason , Wu George , Nathoo Bharat , Tam Paul
Published: November 2023

Introduction: QTc interval prolongation is increasingly frequent as CKD advances and predicts death in dialysis. However, predictors and mortality-risk in predialysis CKD are understudied. FGF23 induces left ventricular hypertrophy (LVH) which is associated with QTc interval prolongation and death, suggesting a possible pathway from FGF23 to death that entails LVH and QTc prolongation. We looked for links between FGF23 and prolonged QTc intervals mediated by LVH, and for deaths associated with QTc prolongation in a prospective observational cohort of patients with predialysis CKD.

Methods: Participants underwent protocolized baseline and semi-annual FGF23 testing, baseline and study end echocardiograms, and baseline and annual electrocardiograms over three years.

Results: 2,254 participants (34.1% female; mean age 68.7 years; mean glomerular filtration rate 41.4 ml/min/m2) enrolled. Baseline LVH (left ventricular mass index >131 g/m2 (>100 g/m2 if female)) was present in 10.8% and prolonged QTc intervals (>=500 ms) in 1.5%. One hundred thirty-eight (6.1%) participants died during the study. In generalized mixed effects regression, each unit increase in the natural log of FGF23 - but not LVH - predicted an odds ratio of 1.76 (1.15, 2.70, p=0.009) for prolonged QTc intervals independently of 15 other covariates. Mediation analysis showed that only 13% of FGF23's total effect on prolonged QTc intervals was mediated by LVH. Patients with prolonged QTc intervals had higher unadjusted (log rank p<0.001) and adjusted (hazard ratio 3.15 (1.38, 7.16, p=0.006)) mortality rates than those with QTc intervals <500 ms.

Conclusions: QTc interval prolongation ≥500 ms was prospectively associated with FGF23 independently of LVH, and with a tripling of mortality-risk in patients with predialysis CKD.