bluuebunny/crossref_metadata_2025 huggingface dataset:
Physico-chemical properties of oil from plums and prospects for its use
Authors: Davlyatov Azizbek , Xudayberdiyev Absalom , Khamdamov Anvar , Adashev Bekhzod , Madaminova Zilola
Published: February 2024

The article is devoted to the methods and results of the research conducted on the development of complex processing technology of plum fruit seeds from fruit seeds growing in the Republic of Uzbekistan. Obtaining a new type of oil for the food industry, nutritious food for livestock, poultry and fishing industries is described. Development of energy-efficient oil extraction technology using new types of equipment for extracting oil from fruit kernels and the role of non-traditional raw materials today and their wide use in practice are mentioned. Recommendations on the effective use of industrial secondary raw materials released from production enterprises, reducing the amount of waste released into the environment, and the results of research on the effectiveness of research on the measures taken in this regard are covered in detail.
Study of the influence of stratification on germination of sea buckthorn seeds (Hippophae rhamnoides L.) in the conditions of the Moscow region
Authors: Makarov Sergey , Orlova Elena , Zubik Inna , Kozlova Elena , Akhmetova Lilia
Published: February 2024

The article presents a comparative analysis of the influence of stratification methods on germination of sea buckthorn seeds (Hippophae rhamnoides L.) in autumn and spring sowing. In the fall sowing with natural stratification under snow, sprouts of H. rhamnoides seeds were more friendly, and the percentage of germination was higher than in the spring sowing with artificial stratification. At autumn sowing of seeds in H. rhamnoides seedlings, formation of many short roots was observed, which predicts more active development of the root system. The number of nodules on the roots of H. rhamnoides plants is formed depending on varietal characteristics and does not depend on the term and method of sowing. Lomonosovskaya, Rossiyanka, Studencheskaya varieties proved to be the most strongly growing in two variants of the experiment at fall sowing, and Trofimovskaya at spring sowing.
Characteristics of secondary dairy raw material obtained during dairy processing
Authors: Ubaydullaeva Nilufar B. , Maksumova Dilrabo Q. , Shosalimova Shaxzoda J. , Rifky Mohamed
Published: February 2024

This study focuses on by-products of dairy processing and the effectively utilization to reduce environmental problems. The existing traditional technology of producing sour cream, butter, natural cheeses and cottage cheese receives huge amount of by-products such as skim milk, buttermilk and whey is called “secondary dairy raw material”. Enzymatic hydrolysis of kappa-casein is the particular process that starts the coagulation of milk and the casein micelles’ characteristics change and become unstable and begin to combine. A 3-dimensional network of casein micelles eventually emerges as aggregation continues. The amount of nutrients and the chemical elements to be taken into consideration for further processing would lower the cost of manufacturing and increase corporate profit, according to tests conducted on the samples’ protein, lactose content, titratable acidity, and pH. It could be used as a product for functional purpose and processing of whey and the production of whey drinks which has dietary and therapeutic nutrition. They can significantly increase the biological value of nutrition and due to lipotropic and antioxidant components (phospholipids, choline, leucine, vitamin E and other substances) mitigate the manifestation of latent forms of vitamin deficiency. Therefore, whey should be more fully processed for food purposes.
Application of a modified mathematical model “consumer – resource” to justify the periods of treatment of potato late blight with fungicides
Authors: Gasratova Natalya , Pashkova Darya
Published: February 2024

Potato late blight is a harmful disease. Treatment of fields with fungicides is the main method of combating this phytopathology. The work presents a modified mathematical model “consumer - resource” - this is a system of partial differential equations, which contains a step function with the help of which fungicidal treatment can be successfully modeled. The system was solved numerically. Based on the modeling results, it is possible to successfully simulate the development of leaf damage during the growing season without and with fungicide treatment. Thus, knowing the duration of action of the drugs and assuming how intensively late blight will develop, it is possible to model different combinations of fungicides and spraying times. This circumstance can be successfully implemented into decision support systems for agricultural enterprises.
Evaluation of claims reserve methods: claims payment pattern and Stanard-buhlmann, case study at prévoir insurance company (agriculture Cambodia)
Authors: Srun Sovila , Kean Tak , Khim Chamroen , Rakitina Maria S. , Dmitrieva Irina A. , Ivanova Natalia A.
Published: February 2024

A claims reserve is money set aside for a claim that has been Reported But Not Settled (RBNS) or Incurred But Not Reported (IBNR). Claim reserves are crucial for the financial stability of insurance companies. Operationally, we can know the amount RBNS, but we don’t know the amount of IBNR. Therefore, actuarial literature has proposed numerous IBNR calculation methods, which are usually based on statistical concepts. However, the mutant and uncertain behavior of insurance environments for each insurance company does not make advisable to use a wide database across all insurance companies in Cambodia when calculating IBNR. As it is not advised by the regulator for any standard methodology of claim reserve calculation and each insurance company must define its own method based on its data and operational procedure. Prevoir (Kampuchea) Micro- Life Insurance in Cambodia, the first Micro Insurance licensed in Cambodia since 2011, has developed its methodology of claim reserve calculation by studying on claim settlement pattern and Stanard-buhlmann method. In this paper, we are going to share evaluation between the two methods after conducting experiment at Previor Insurance company. The Insurance company also operates in the agricultural insurance market.
Innovative technologies used on dairy farms
Authors: Khoroshailo Tatiana , Bachinina Ksenia , Tishchenko Alexander , Zdanovskaya Lidiya , Alekseeva Yulia
Published: February 2024

An analysis of milk production technologies on a dairy farm in the Krasnodar region is presented. Factors influencing the amount of milk produced are considered, such as cutting seams on the floors, installing the «Texas Gate», modernizing the ventilation system and water supply, and using the «Pennsylvania Sieve» when feeding cows. The priority directions of observations during the modernization of technical means to obtain competitive products are identified. The possibilities and feasibility of using methods of technological support for dairy cattle breeding based on innovative technologies are analyzed. It is shown that the tasks of managing dairy farms are multifaceted: from controlling individual machines to making decisions in conditions of limited information.
New approaches to training engineers for the oil and gas industry
Authors: Karachurina Regina F. , Gulin Denis A. , Burenina Irina V. , Sayfullina Sofiya F.
Published: February 2024

The article presents an analysis of trends in the development of education, analyzes new challenges in the oil and gas industry and educational activities, as well as existing problems in training engineering personnel, and examines benchmarks - advanced engineering schools in Russia and the world. The strategic direction is presented and the main aspects of training the engineering personnel of the future are considered. The basic principles of training engineering personnel in the fuel and energy complex are presented, and possible trajectories for the development of educational programs are presented. The characteristics of the competency model of engineers of the future are determined, including professional skills, soft and digital competencies for three categories of specialists in the oil and gas industry: a research engineer with project-based learning skills; an advanced technology engineer; an industrial and applied engineer.
Environmental constituent of the petrochemical complex sustainable development
Authors: Ponikarova Anna
Published: February 2024

This article studies the ongoing processes of environmental safety formation in the context of sustainable development of companies. It is hypothesized that during changes most companies in the petrochemical industry of the Republic of Tatarstan underestimate the need for a comprehensive modernization of the environmental component of sustainable development. In conditions of disturbances and uncertainty in the external environment it leads to increased entropy and loss of effectiveness of discrete measures to improve the environmental safety of enterprises. The study carried out an analysis with a depth of study of more than five years, which is characterized by the emergence of economic and social risks of a global nature and reveals the degree of their influence on the environmental safety of a complex strategically important for the republic. In conclusion, it is concluded that increasing systematicity in environmental safety management under conditions of uncertainty leads to an increase in the rate of sustainable development and the effect of production activities.
Methods of obtaining activated adsorbents based on gossypol tar and local bentonites and analysis of their physical parameters
Authors: Ochilov Golibjon , Boymatov Ismoiljon , Ganiyeva Nazokat
Published: February 2024

This article provides information on the methods of obtaining activated adsorbents based on oil-oil waste gossypol tar and local benonites and their various physical properties. In addition, the effect of temperature change on the yield of activated adsorbents from gossypol resin was analyzed. As a result, when Logon bentonite is modified with activated gossypol resin, the hydrophilic properties decrease and the hydrophobic properties increase. Compared to coke obtained from gossypol, it was known that the density of adsorbents obtained as a result of its modification with local bentonite increases. At the end of the study, it was concluded that by adding bentonite as a binder to gossypol resin, its strength increases several times.
Research of the synthesis of new acetylene aminoalcohols
Authors: Juraboev Fozil
Published: February 2024

The article describes the synthesis of acetylene amino alcohols based on secondary acetylene alcohol and amino compounds containing a hydroxyl group, the results of scientific research and their analysis to study the influence of factors such as temperature and catalyst on the yield of the product in the process. In the course of the work, a new type of acetylene amino alcohol was obtained with high efficiency as a result of the condensation reaction of ethanolamine (or diethanolamine) with hex-1-yn- 3-ol mediated by formaldehyde. Optimal conditions for carrying out synthesis processes have been determined. The mechanism of these chemical processes is explained on the basis of theoretical quantum chemical calculations of the reactivity of the starting substances.
Geochemistry of lanthanides in thermal waters of Issyk-Kul Lake Basin
Authors: Chelnokov George , Kharitonova Natalia , Lavrushin Vasilii , Bragin Ivan , Aidarkozhina Altyn
Published: February 2024

The distribution and abundance of lanthanides in thermal waters of the northern Tien Shan (Issyk-Kul lake basin) were studied. Waters are represented by three types: Na-Cl-SO4-HCO3, Na-Ca-Cl-SO4 and Na-Ca-Cl, demonstrates alkaline pH (7.3–9.7) and Eh from -260 to +98 mV. Discharge temperature varies from 15 to 50oC, and total dissolved solids from 0.2 to 13.0 g/l. It is established that lanthanides (or rare earth elements, REE) concentrations vary from 0.07 to 0.81 ppb, the maximal concentrations relate to a Na-Ca-Cl water type, which demonstrates the influence of reverse ion exchange. The total concentration of rare earth elements roughly increases as pH decreases, implying that the absolute abundance of REE is totally controlled by pH conditions. The ΣREE concentrations in groundwater exhibit a high positive correlation (R=0.8) with the total dissolved solids contents indicating that ΣREE are well related to the salinity of the thermal water samples. The major ions HCO3, SO4, Ca, K, and Mg have minor associations with REE. The geochemical and geological data suggest that the principal REE source of the thermal waters is bedrock mineralogy and lithology. The distribution and abundance of REE in thermal waters of Issyk-Kul basin were studied for the first time.
Development of a device for restoration of the flowability of caked fertilizers with justification of its design and operating parameters
Authors: Klyukanov Aleksey V. , Zolkin Alexander L. , Rudnev Sergey G. , Malova Natalia N. , Chistyakov Maksim S.
Published: February 2024

The article explores the possibility of use of a separate two-phase technology in agriculture to restore the flowability of caked mineral fertilizers. Flowability is one of the most important properties of fertilizers that determine their quality during storage and transportation. Flowability is understood as the property of a mineral fertilizer to flow freely under the influence of gravitational forces. Under certain environmental conditions, fertilizers may cake. To solve this problem in the preparation of fertilizers at agricultural enterprises, a new design of a preliminary grinder is proposed as a part of a two-phase technology. Based on the results of the experimental studies, the most rational design and operating parameters of the grinder have been determined. Practical recommendations on the possible use of the developed drum-type grinder for the destruction of other brittle materials in preparation for their introduction into the soil at agricultural enterprises are formulated.
Friction of fluoroplastic with steel in a hydraulic fluid medium when transient mode
Authors: Alisin Valery
Published: February 2024

The article considers the issues of experimental research of the antifriction properties of fluoroplastic seals of piston pump hydraulic systems in a transient friction mode. The statement about the influence of frictional heating on the tribological properties of the seal is substantiated. Model experiments are used to study the friction coefficients at the moment of changing the direction of the contacting surfaces movement and the transient period from the moment of starting from a standstill to the steadystate friction mode. The experiments were carried out under conditions of heating the hydraulic fluid to the maximum temperature. Particular attention is paid to the change in the friction coefficient with increasing load-speed characteristics. The limiting contact pressures that ensure trouble-free operation of a seal made of radiation-modified fluoroplastic have been determined.
Endophytic microorganisms of Aloe vera
Authors: Krynitskaya Alla , Aulan Aniurka Maria Panfet , Petukhova Elena , Kharina Maria , Kanarskaya Zosya
Published: February 2024

Aloe vera is one of the most commonly used plants in medical and pharmaceutical practice due to the large number of biologically active compounds it contains. At the same time, the internal gel of plants contains endophytic microorganisms that can increase the area of plants action. In the process of carrying out research work, the isolation and identification of microorganisms associated with the internal gel of Aloe vera was carried out. A method for aseptic shedding of microbial isolates from plant gel has been developed. Using the developed method, four microbial isolates were obtained. Morphological, cultural and physiological-biochemical analysis of the isolated microorganisms was carried out. Based on their characteristics, all isolated microorganisms can be attributed to the Actinobacteria class. Previously isolated bacteria can be identified as Arthrobacter spp. or Micrococcus spp. Additional research is required for more accurate identification. As a result of the research, the antimicrobial activity of two isolates against bacteria of the genus Bacillus was discovered.
Experimental study of variations in the reflection spectra of leaves and needles depending on the conditions for obtaining samples
Authors: Fedotov Yury , Ivanov Sergey , Belov Mikhail , Gorodnichev Victor
Published: February 2024

Experimental studies on variations in the reflectivity of coniferous and deciduous woody vegetation in the spectral range of 0.4-2.4 microns were carried out, depending on the conditions for obtaining samples. It is shown that for deciduous trees, variations in measurement data caused by the fact that samples were taken from different trees, different sides of the crown of one tree, from the shady and sunny sides of the crown, from branches located at different heights are small. At the same time, the use of averaging over 10-15 different samples of leaves taken from different trees (of the same species) makes these variations insignificant. For coniferous trees, variations in measurement data, even for needle samples from the same tree, can be significant.
OF2 # mit sekundärer Sinterung – konservative Therapie
Authors: Schnake Klaus John
Published: February 2024

Thorakolumbale OF 2 Frakturen betreffen eine Wirbelendplatte ohne oder mit nur geringer Beteiligung der Hinterkante. Sie können erfolgreich konservativ oder operativ behandelt werden. Als Hilfestellung zur Therapieentscheidung kann der OF-Score herangezogen werden. Eine Nachsinterung ist nicht unüblich und betrifft vor allem Patienten mit einem T-Score von <–3. Sie stellt jedoch ohne eine gleichzeitig auftretende klinische Verschlechterung keine Indikation zum operativen Vorgehen dar.
Evidenzen in der konservativen Wirbelsäulentherapie
Authors: Wiechert Karsten
Published: February 2024

Konservative Therapiemaßnahmen stellen die bevorzugte Behandlungsform für die überwiegende Zahl von Wirbelsäulenerkrankungen dar. Diese Übersichtarbeit fasst die Evidenzen unterschiedlicher Behandlungen von Rückenschmerzen zusammen. Berücksichtigung finden Nationale und internationale Leitlinien sowie Metanalysen zu den einzelnen Verfahren. Untersuchte Behandlungskategorien sind Medikamentöse Behandlungen, Physiotherapie und Trainingstherapie, physikalische Maßnahmen und Rehabilitation, Korsettbehandlungen, Infiltrationsbehandlungen, psychologische Interventionen sowie verschiedene Eigenübungsprogramme.

Die Evidenz bei der Mehrzahl der untersuchten Therapieformen ist gering bis moderat mit einzelnen Ausnahmen. Das Forschungspotenzial bei nichtoperativen Behandlungskonzepten ist groß.
Osteoporotische Wirbelkörperfrakturen im Alter – Neue Entwicklungen
Authors: Roigk Patrick , Abel Bastian , Rapp Kilian , Becker Clemens
Published: February 2024

Die Bedeutung der Wirbelkörperfrakturen, die zu einer Krankenhauseinweisung führen nimmt zu. Dieser Anstieg ist nicht nur demographisch bedingt. Die Fallzahlen der LWK-, BWK- und HWK Frakturen sind altersadjustiert in den letzten 15 Jahren um weit mehr als 100% angestiegen. Ein ähnlicher Anstieg wird auch für die Beckenfrakturen beobachtet. Im gleichen Zeitraum war die Zahl der Hüftfrakturen altersadjustiert leicht rückläufig. Hierfür gibt es bislang keine schlüssige/n Erklärungen. Die Epidemiologie deutet jedoch daraufhin, dass Osteoporose keine alleinige Erklärung hierfür bietet. Die häufigste Lokalisation der Frakturen ist die LWS gefolgt von der BWS und HWS. Die Zahl der LWS-Frakturen entspricht in etwa den Beckenfrakturen. Die beste Erklärung für diesen Trend bieten video- und sensorbasierte Daten, die zeigen, dass ältere und vor allem hochaltrige Patienten versuchen beim Sturz mit dem Gesäß aufzuprallen und dann häufig einen zweiten und dritten Aufprall im Bereich der Wirbelsäule haben. Der Hauptgrund ist vermutlich die lebenslange Erfahrung, dass die Muskulatur und die Weichteile der Beckenregion, den besten Schockabsorber bieten und im höheren Alter Abwehrreaktionen der Arme meist nicht mehr erfolgreich sind. Die Entwicklungen zeigen, dass die alterstraumatologische Versorgung nicht nur der Hüftfrakturen wichtig sind, sondern die Organisation der Versorgung der Wirbelkörperfrakturen eine hohe Priorität hat.
Kopfschmerz und Schlafmangel bei Kindern und Jugendlichen verstehen und behandeln
Authors: Sandach Julia , Klaas Maren , Arping Anna-Maria
Published: February 2024

Während der Schulzeit leidet eine große Anzahl von Kindern und Jugendlichen unter chronischen Kopfschmerzen und Schlafmangel. Aufgrund der Komplexität beider Gesundheitsprobleme ist es für Schulgesundheitspflegende und Erziehungsberechtigte nicht einfach, sich für die richtigen präventiven und therapeutischen Interventionen zu entscheiden. Welche Hilfsmittel sich für die Anamnese eignen und welche Möglichkeiten der Prävention und Therapie bestehen, beleuchtet der folgende Beitrag.
Salvage Reconstruction of Composite Defects of the Anterior Mandible, Floor of Mouth, and Lip
Authors: Khalid Farrukh A. , Ahmed Omar A. , Khurshid Almeotan P. , Mujahid Abdul M. , Ahmad Junaid , Saleem Muhammad , Yousaf Muhammad A. , Tarar Moazzam N. , Shahzad Farooq
Published: February 2024

Anterior mandible defects result in loss of support for the tongue, floor of the mouth and lower lip, resulting in impairment of airway, feeding, and speech. We treated four patients with these “Andy Gump” deformities. Reconstruction was performed with two free flaps: a fibula osteocutaneous flap for the anterior mandible and floor of the mouth, and a soft tissue free flap for the lip, chin, and anterior neck. The lower lip was suspended cranially with fascia or tendon grafts ± mini-temporalis turndown flaps. All flaps survived completely. All patients were tube feed-dependent before surgery; they all resumed an oral diet. All tracheostomies were decannulated. Lip competence was restored as evidenced by cessation of drooling. Speech improved from unintelligible to intelligible with frequent repetitions. Objective assessment was performed with the functional intraoral Glasgow scale; the mean FIGS score improved from 3.25 (range 3–4) to 11 (range 9–13). We conclude that composite anterior mandible and tongue defects have large tissue requirements that require multiple free flaps. Reconstruction leads to significant improvement in function.
Improvement of Shoulder Motion in Two-Stage Dual-Plane Implant-Based Breast Reconstruction followed by Radiation Therapy through Delayed Prepectoral Conversion
Authors: Park Jin Sol , Jin Ung Sik
Published: February 2024

Background Although prepectoral implant-based breast reconstruction has recently gained popularity, dual-plane reconstruction is still a better option for patients with poor-quality mastectomy skin flaps. However, shoulder morbidity is aggravated by subpectoral reconstruction, especially in irradiated patients. This study aimed to demonstrate shoulder exercise improvement in subpectoral reconstruction by delayed prepectoral conversion with an acellular dermal matrix (ADM) inlay graft technique at the time of expander-to-implant exchange after irradiation.

Methods Patients with breast cancer treated for expander-to-implant exchange after subpectoral expander insertion and subsequent radiotherapy between January 2021 and June 2022 were enrolled. An ADM inlay graft was inserted between the pectoralis major muscle and the previously inserted ADM. The ADM was sutured partially overlapping the pectoralis muscle from the medial side with the transition part, to the muscle border at the lateral side. Perioperative shoulder joint active range-of-motion (ROM) for forward flexion, abduction, and external rotation was also evaluated.

Results A total of 35 patients were enrolled in the study. Active shoulder ROM significantly improved from 163 degrees preoperatively to 176 degrees postoperatively in forward flexion, 153 to 175 degrees in abduction, and 69 to 84 degrees in external rotation. There was no difference in patient satisfaction regarding the final outcome between the conventional prepectoral reconstruction group and the study group.

Conclusion Shoulder exercises in irradiated patients who underwent subpectoral reconstruction were improved by delayed prepectoral conversion using an ADM inlay graft. It is recommended that subpectoral reconstruction not be ruled out due to concerns regarding muscle contracture and shoulder morbidity in radiation-planned patients with poor mastectomy skin flaps.
Utility of BioFire FilmArray Gastrointestinal Panel in the Diagnosis of Gastrointestinal Infections
Authors: Gupta Rama , Gupta Veenu , Sood Ajit , Singh Arshdeep , Chaudhary Jyoti , Gupta Menal , Aggarwal Manisha
Published: February 2024

Background Conventional diagnostic methods like culture and microscopy are time-consuming and have low diagnostic yield for gastrointestinal infections. New rapid molecular methods such as multiplex polymerase chain reaction (PCR) have recently been introduced for etiological diagnosis. The aim of this study was to evaluate the utility of the FilmArray gastrointestinal panel (GIP) in the diagnosis of gastrointestinal infections.

Materials and Methods This is a retrospective study performed in the microbiology department of a tertiary care hospital. Stool samples were received and processed according to the manufacturer's instructions by FilmArray GIP. Stool culture and routine microscopy were also performed.

Results The mean age of the 32 patients was 46 ± 24.2 years and with a male-to-female ratio of 1:1. Out of 32 stool samples received for testing by BioFire GIP, 23 samples (71.9%) were found to be positive for one or the other target. A total of 41 targets were detected from 23 positive patients, with predominant bacterial etiology (65.9%) followed by parasitic (31.7%) and viral (4.9%). Giardia lamblia was the most common (26.8%) target detected in all age groups. Additionally, in 56.5% of patients, more than one target was detected. The stool culture was positive in 2 of the 16 patients (12.5%).

Conclusion The FilmArray GIP showed very good diagnostic performance compared with culture for the diagnosis of gastrointestinal infections. Further studies are needed to determine whether multiplex PCR improves patient outcomes and reduces costs.
Homophily, selection, and choice in segregation models
Authors: Xu Bing , Clark William A. V. , Pak Maxwell
Published: February 2024

Schelling’s 1971 work on the dynamics of segregation showed that even a small degree of homophily, the desire to live among like neighbors, can lead to a starkly segregated population. One of the driving factors for this result is that the notion of homophily used is based on group identities that are exogenous and immutable. In contrast, we consider a homophily that arises from the desire to be with neighbors who are behaviorally similar, not necessarily those who have the same group identity. The distinction matters because behaviors are neither exogenous nor immutable but choices that can change as individuals adapt to their neighborhoods. We show that in such an environment, integration rather than segregation is the typical outcome. However, the tendency toward adaptation and integration can be impeded when economic frictions in the form of income inequality and housing cost are present.
Effect of Al-Sr-Y intermediate alloy on microstructure and mechanical properties of A356 alloy
Authors: Huang Zhongyue , Li Jing , Yuan Changwen , Wang Qihang , Yan Feng , Zu Fangqiu
Published: February 2024

In this experiment, an intermediate alloy (Al-3Sr-8Y) that can refine and modify A356 alloy simultaneously was developed, and the synergistic effect of Sr and Y on the microstructure and mechanical properties of A356 alloy was investigated. The results show that when the content of Al-3Sr-8Y intermediate alloy reaches 0.3 wt%, the morphology of α-Al dendrites is significantly refined and the secondary dendrite arm spacing (SDAS) was significantly reduced. Moreover, the morphology of eutectic Si transforms from acicular to small fibrous, and the average area and aspect ratio of eutectic Si decrease to 0.81 μm2, and 2.01. This change is caused by the twin plane re-entrant edge (TPRE) poisoning mechanism, where the addition of Al-3Sr-8Y can poison the intrinsic growth position of the Si phase, reduce the growth rate of the Si phase, promote isotropic growth, and achieve a highly branched morphology of the Si phase to form a fibrous structure. Due to the excellent synergistic effect of Sr and Y, the tensile strength and elongation of the alloy reached the maximum values of 303.5 MPa and 9.5% when 0.3 wt% Al-3Sr-8Y was added after heat treatment, which is an increase of 18.2% and 86.3% compared with the untreated A356 alloy, respectively.
High-order splitting finite element methods for the subdiffusion equation with limited smoothing property
Authors: Li Buyang , Yang Zongze , Zhou Zhi
Published: February 2024

In contrast with the diffusion equation which smoothens the initial data to

C
∞

C^\infty

for

t
>
0

t>0

(away from the corners/edges of the domain), the subdiffusion equation only exhibits limited spatial regularity. As a result, one generally cannot expect high-order accuracy in space in solving the subdiffusion equation with nonsmooth initial data. In this paper, a new splitting of the solution is constructed for high-order finite element approximations to the subdiffusion equation with nonsmooth initial data. The method is constructed by splitting the solution into two parts, i.e., a time-dependent smooth part and a time-independent nonsmooth part, and then approximating the two parts via different strategies. The time-dependent smooth part is approximated by using high-order finite element method in space and convolution quadrature in time, while the steady nonsmooth part could be approximated by using smaller mesh size or other methods that could yield high-order accuracy. Several examples are presented to show how to accurately approximate the steady nonsmooth part, including piecewise smooth initial data, Dirac–Delta point initial data, and Dirac measure concentrated on an interface. The argument could be directly extended to subdiffusion equations with nonsmooth source data. Extensive numerical experiments are presented to support the theoretical analysis and to illustrate the performance of the proposed high-order splitting finite element methods.
Energy diminishing implicit-explicit Runge–Kutta methods for gradient flows
Authors: Fu Zhaohui , Tang Tao , Yang Jiang
Published: February 2024

This study focuses on the development and analysis of a group of high-order implicit-explicit (IMEX) Runge–Kutta (RK) methods that are suitable for discretizing gradient flows with nonlinearity that is Lipschitz continuous. We demonstrate that these IMEX-RK methods can preserve the original energy dissipation property without any restrictions on the time-step size, thanks to a stabilization technique. The stabilization constants are solely dependent on the minimal eigenvalues that result from the Butcher tables of the IMEX-RKs. Furthermore, we establish a simple framework that can determine whether an IMEX-RK scheme is capable of preserving the original energy dissipation property or not. We also present a heuristic convergence analysis based on the truncation errors. This is the first research to prove that a linear high-order single-step scheme can ensure the original energy stability unconditionally for general gradient flows. Additionally, we provide several high-order IMEX-RK schemes that satisfy the established framework. Notably, we discovered a new four-stage third-order IMEX-RK scheme that reduces energy. Finally, we provide numerical examples to demonstrate the stability and accuracy properties of the proposed methods.
495 - Lebrikizumab reduces systemic inflammation in serum of patients with moderate-to-severe atopic dermatitis
Authors: Guttman-Yassky Emma , Okragly Angela , Sun Zhe , Mena Laura Rebeca , Hahn Nathan , Nickoloff Brian J , Siu Kimberly , Gallo Gaia , Wolf Eric , Eyerich Kilian , Aparici Monica , Benschop Robert J
Published: February 2024

Introduction

Lebrikizumab is an interleukin (IL)-13 inhibitor that has completed phase 3 studies. It demonstrated statistical superiority vs. placebo in patients with moderate-to-severe atopic dermatitis (AD) across all primary and key secondary endpoints at week 4 and week 16 of ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967).

Objectives

The objective of this analysis is to determine lebrikizumab’s impact on AD-relevant serum biomarkers in patients from these studies through week 16.

Methods

Protein biomarkers were determined in available serum samples from patients receiving lebrikizumab 250 mg every 2 weeks (n=72) or placebo (n=36) from both ADvocate1 and ADvocate2. Pre- and post-treatment biomarkers were compared to healthy controls (HC, n=30) which were age, sex, race, and ethnically matched. The analysis included biomarkers known to be elevated in AD. IL-13 was only measured at baseline because of lebrikizumab’s known interference with IL-13 measurement.

Results

At baseline, CCL13, CCL17, CCL22, total IgE, IL-5, IL-13, and periostin were elevated in patients with AD (p<0.001) with IL-13 measuring approximately 7-fold greater in the AD population vs. HC. In patients with AD, IL-4, CCL11, CXCL10, CCL2, and CCL4 were not elevated at baseline vs. HC.

At week 4, lebrikizumab significantly reduced levels of the key type 2 biomarkers, CCL13, CCL17, and periostin vs. placebo (p<0.01) with a trend toward levels consistent with HC (within 1.5-fold). At week 16, CCL13, CCL17, and periostin levels remained consistent with HC levels with CCL13 and periostin retaining statistically significant reductions vs. placebo (p<0.01).

Conclusions

In sum, selective targeting of IL-13 with lebrikizumab monotherapy reduced known molecular biomarkers of systemic type 2 inflammation in patients with moderate-to-severe AD.
518 - Interaction of sleep disturbance and nocturnal scratch in atopic dermatitis patients
Authors: Alexopoulos Christos , Kassim Alia , Christakis Yiorgos , Di Junrui , Thomas Kevin , Wicker Madisen , Kabiri Nina Shaafi , Lehan Walter , Auerbach Sanford , Northcott Carrie , Samuelsson John G
Published: February 2024

Introduction/Background

Itch, scratch and poor sleep are often cited as key symptoms of Atopic Dermatitis (AD). Although approximately 10-41% of children and 7-48% of adults in the general population experience sleep disturbances, this figure climbs to 47-80% in children with AD and 33-90% in adults with AD (Bawany et al., 2021). While great effort has been done to characterize and validate nocturnal scratch and sleep, the relationship between the two remains poorly characterized.

Objectives

We hypothesize that nocturnal scratch is the reason for the sleep disturbances in patients with AD. Literature suggests that these symptoms are linked, albeit not necessarily causal. Here we investigate the interaction between nocturnal scratch events and sleep disturbances in study participants with AD compared to a healthy cohort.

Methods

Patients with AD (n=185) and without AD (n=40) aged between 2 to 75 years were recruited across three different studies. Study participants spent the night in a qualified sleep lab while being under observation with thermal videography and polysomnography (PSG). The thermal videography was annotated for both scratch and non-scratch movements by two trained annotators independently with any conflicts being resolved by an arbitrator. The PSG was scored by a credentialed technologist in 30-s epochs per revised American Academy of Sleep Medicine scoring guidelines. The study participants also wore a wrist-worn accelerometer on both the left and right wrists.

Results

It was noted that sleep disturbances were associated with the observed scratch events, and that the temporal relationship between sleep disturbance and scratching seemed to differ between the AD and healthy cohorts. Surprisingly, however, it was also noted that within a few study participants with AD, scratch events occurred while the patient was in stable REM sleep, most often in the children with AD. Further investigation will provide additional information as to whether this was an artifact or in fact a true observation. We also present an overview of sleep, as well as nocturnal scratch and non-scratch movements in the AD and healthy cohorts, noting specifically how the behaviors differ between the groups, and over the course of the sleep opportunity, across sleep stages and sleep cycles, as well as their relationships to sleep disturbances.

Conclusions

Nocturnal scratching is often associated with sleep disturbances in AD; however, the causality is not always clear. Moreover, in some cases scratching was observed during stable REM sleep in AD, an observation that requires further investigation.
562 - Dupilumab treatment provides long-term improvement in itch in pediatric patients with moderate-to-severe atopic dermatitis over 1 year
Authors: Siegfried Elaine , Simpson Eric L , Boguniewicz Mark , Flohr Carsten , Eichenfield Lawrence F , Pinter Andreas , Ramien Michele , Gao Xing-Hua , Chen Zhen , Bates Lauren , Rossi Ana B
Published: February 2024

Introduction/Background

As symptoms of atopic dermatitis (AD) can wax and wane over time, disease control is better represented by consistency of response over a long treatment duration rather than at a single time point.

Objective

To evaluate the proportion of pediatric patients achieving and maintaining mild or no itch (defined by a SCORing Atopic Dermatitis (SCORAD) itch visual analog scale (VAS; 0-10 over last 3 days) score of lower than 4) across 5 visits during a 52-week open label extension trial of dupilumab.

Methods

Patients who previously participated in 16-week trials and were aged 0.5–5 years (LIBERTY AD PRESCHOOL; NCT03346434), 6–11 years (LIBERTY AD PEDs; NCT03345914), and 12–17 years (LIBERTY AD ADOL; NCT03054428), were subsequently enrolled in the phase 3, open-label extension trial, LIBERTY AD PED-OLE (NCT02612454). Patients were treated with 300 mg q4w or 200/300 mg q2w (body weight <60 or ≥60 kg, respectively). In this analysis, patients with a SCORAD itch VAS score of greater than 4 at OLE baseline, were assessed for the maintenance of SCORAD itch VAS lower than 4, at 5 timepoints: Weeks 4, 16, 28, 40, and 52.

Results

In 763 patients, 400 patients with a SCORAD itch VAS score of greater than 4 were assessed. Mild or no itch was achieved in at least 4 of 5 timepoints in most patients aged 0.5–5 years (55/110; 50%), 6–11 years (76/148; 51%), and 12–17 years (73/142; 51%). Across these age groups, over 65% maintained this response for at least 3 of 5 timepoints. Safety was consistent with the known dupilumab safety profile in patients with atopic dermatitis.

Conclusions

Most pediatric patients achieved improvement in itch, maintained during 1 year of treatment with dupilumab. Results were consistent for infants/preschoolers, children, and adolescents.
565 – Safety and pharmacokinetic profiles of a humanized monoclonal antibody TQH2722 targeting interleukin 4 receptor alpha (IL-4Rα) in health adult subjects
Authors: Lin Pingping , Sun Feifei , Xu Yi , Ban Rongxin , Jiang Xin , Fu Yao , Gao Xiaomeng , Cao Yu
Published: February 2024

Introduction/Background

TQH2722 is a humanized monoclonal antibody targeting interleukin 4 receptor alpha (IL4Rα) which leads to the dual-blockade of interleukin-4 (IL-4) and interleukin-13 (IL-13) signaling, inhibiting the T-helper cell type 2 immune pathway. Th2 inflammation is implicated in the pathobiology of diseases such as asthma and atopic dermatitis. We describe the safety and pharmacokinetic results from a first-in-human study in healthy subjects.

Objectives

To evaluate the safety, tolerability, pharmacokinetic characteristics, and immunogenicity of TQH2722 injection in healthy adult subjects.

Methods

This randomized, double-blind, placebo-controlled, ascending-dose phase I study (NCT05409326) was conducted in China. Each adult subject received a single subcutaneous (sc.) TQH2722 dose or placebo in single ascending-dose (SAD) cohorts, and 4 doses of TQH2722 or placebo administrated Q2W in multiple ascending-dose (MAD) cohorts. Pharmacokinetic samples were collected prior to first dose administration through 56 days after initial dosing in SAD cohorts. In the MAD cohorts, samples were collected before every administration until 56 days after last dosing.

Results

As of 28 September 2023, all subjects had completed the study, with the database locked while remaining unblinded. Sixty-six (66) healthy subjects were enrolled in this study. The SAD cohorts consisted of single doses of TQH2722 of 50 mg (n-4), 150 mg (n=10 active, 2 placebo), 300, 600, and 1200 mg cohorts, each receiving TQH2722 (n=8) or placebo (n=2). Ten subjects were enrolled in each of the 150 and 600 mg MAD cohorts receiving TQH2722 (n=8) or placebo (n=2). No dose-limiting toxicities or SAEs were observed and only 3 subjects experienced a grade 3 AE including 1 subject of increased triglycerides, 1 subject with increased creatine kinase and 1 subject with decreased blood potassium). All other AEs were of grade 1 or 2. The incidence and severity of AEs were not dose dependent. No SAEs or AEs led to treatment discontinuation. The pharmacokinetics of TQH2722 were indicative of an anti-receptor mAb in that TQH2722 exhibited nonlinear target-mediated clearance. Maximum serum concentration was reached after 2.78-6.75 days with the half-life of a single sc. administration of TQH2722 increasing by dose level, ranging between 4 and 18 days.

Conclusions

TQH2722 was safe and well tolerated in healthy volunteers. Injection site reactions and laboratory abnormalities were the most reported AEs, with grade 1-2 as the major severity. Most AEs resolved on their own. Single dosing showed non-linear increases of the drug exposure as the dosage increased. These data support further clinical development of TQH2722 as a therapeutic treatment for patients with Atopic Dermatitis and other related diseases mediated by Th2 inflammation.
566 - Efficacy of dupilumab treatment in atopic hand and foot dermatitis across morphological subtypes: results from a phase 3, randomized, double-blind, placebo-controlled trial
Authors: Worm Margitta , Simpson Eric L , Honari Golara , Soong Weily , Pinter Andreas , Masuda Koji , Shao Liyang , Dubost-Brama Ariane , Bansal Ashish , Korotzer Andrew , Rossi Ana B
Published: February 2024

Introduction/Background

Dupilumab has previously shown to significantly improve signs, symptoms, and quality of life in patients with moderate-to-severe atopic hand and foot dermatitis.

Objective

To investigate the efficacy of dupilumab across morphological subtypes in patients with moderate-to-severe atopic hand and foot dermatitis.

Methods

The phase 3, randomized, double-blind LIBERTY-AD-HAFT (NCT04417894) trial enrolled patients aged ≥12 years with moderate-to-severe (Investigator’s Global Assessment [IGA] score of 3/4) atopic hand and foot dermatitis. Patients were randomized to dupilumab monotherapy 300 mg every 2 weeks (q2w) in adults; 200/300 mg q2w in adolescents, or placebo for 16 weeks. This analysis reports the percent change from baseline in modified total lesion sign score (mTLSS) by hand and foot morphological subtypes: chronic dry fissured, hyperkeratotic (palmar/plantar), and other.

Results

133 patients enrolled into this study and were randomized to dupilumab (n = 67) or placebo (n = 66). Atopic hand and foot morphologies were reported in 3 categories: chronic dry fissured (n = 63), hyperkeratotic (palmar/plantar; n = 37), and other (n = 33) In the “other” category, dyshidrotic was the most frequent morphology (n = 13). mTLSS values were similar at baseline for all morphological subtypes. At Week 16, greater improvements were seen in the percent change from baseline (SE) in mTLSS for patients receiving dupilumab vs placebo in all categories: chronic dry fissured (−65.6% [5.1] vs −31.5% [6.2]), hyperkeratotic (palmar/plantar; −58.2% [7.6] vs −11.8% [7.7]), and other (−64.5% [11.6] vs −29.9% [9.0]). Safety was consistent with the known dupilumab safety profile in patients with atopic dermatitis.

Conclusions

The efficacy of dupilumab remains consistent across different hand and foot dermatitis morphologies and shows higher treatment benefit across subtypes compared with placebo.
537 - The distribution of thyroid disease by age in pediatric vitiligo
Authors: Silverberg Nanette B
Published: February 2024

Background

Thyroid disease is a comorbid autoimmune disorder linked to vitiligo.

Objective

To identify the age distribution of pediatric vitiligo cases in order to understand when screening should begin.

Methods

An IRB-exempt survey of pediatric vitiligo patients.

Results

Thyroid disease was reported in 14 children out of 205 children who specifically responded regarding presence of thyroid disease, Of the 14 children reporting sex with thyroid disease, 12 were female (85.7%) and 2 were unknown. Race/ ethnicity included 8 Caucasian (57.1%), Indian 2 (14.2%), Unknown 3 (21.4%), and Black 1 (7.1 %). Average age of diagnosis of thyroid disease in vitiligo patients (self-reported) was 9.7 years (Range 6 years-18 years).

Limitations

The survey design has limitations, and the number of reported cases is low overall.

Conclusion and Relevance

Thyroid disease appears uncommon as a comorbidity in pre-school children. All races may be at risk. The role of family history is unknown. Presentation is almost exclusively in girls. This data suggests that screening can be reserved for females and guided by age and symptoms.
High frequency oscillation network dynamics predict outcome in non-palliative epilepsy surgery
Authors: Lin Jack , Smith Garnett C , Gliske Stephen V , Zochowski Michal , Shedden Kerby , Stacey William C
Published: February 2024

High frequency oscillations are a promising biomarker of outcome in intractable epilepsy. Prior high frequency oscillation work focused on counting high frequency oscillations on individual channels, and it is still unclear how to translate those results into clinical care. We show that high frequency oscillations arise as network discharges that have valuable properties as predictive biomarkers. Here, we develop a tool to predict patient outcome before surgical resection is performed, based on only prospective information. In addition to determining high frequency oscillation rate on every channel, we performed a correlational analysis to evaluate the functional connectivity of high frequency oscillations in 28 patients with intracranial electrodes. We found that high frequency oscillations were often not solitary events on a single channel, but part of a local network discharge. Eigenvector and outcloseness centrality were used to rank channel importance within the connectivity network, then used to compare patient outcome by comparison with the seizure onset zone or a proportion within the proposed resected channels (critical resection percentage). Combining the knowledge of each patient’s seizure onset zone resection plan along with our computed high frequency oscillation network centralities and high frequency oscillation rate, we develop a Naïve Bayes model that predicts outcome (positive predictive value: 100%) better than predicting based upon fully resecting the seizure onset zone (positive predictive value: 71%). Surgical margins had a large effect on outcomes: non-palliative patients in whom most of the seizure onset zone was resected (‘definitive surgery’, ≥ 80% resected) had predictable outcomes, whereas palliative surgeries (<80% resected) were not predictable. These results suggest that the addition of network properties of high frequency oscillations is more accurate in predicting patient outcome than seizure onset zone alone in patients with most of the seizure onset zone removed and offer great promise for informing clinical decisions in surgery for refractory epilepsy.