bluuebunny/crossref_metadata_2025 huggingface dataset:
An extended supramolecular coordination compound produced from PbCl2 and N′-isonicotinoylpicolinohydrazonamide
Authors: Garcia-Santos Isabel , Iglesias-Pereiro Tamara , Labisbal Elena , Castiñeiras Alfonso , Eftekhari-Sis Bagher , Mahmoudi Ghodrat , Sagan Filip , Mitoraj Mariusz P. , Safin Damir A.
Published: January 2024

Novel complex [Pb(HL′)Cl2]·MeOH (1·MeOH) was synthesized from an equimolar reaction of N′-isonicotinoylpicolinohydrazonamide (HL) with PbCl2, where HL′ is a zwitterionic form of HL with the protonated 4-pyridyl and deprotonated amide nitrogen atoms.
Weakly antiferromagnetic vanillin and acetate bridged dinuclear Ni(ii) compound exhibiting catecholase-like activity and biological properties
Authors: Vernekar Beena K. , Harmalkar Nikita N. , Gaonkar Sanket K. , Sannigrahi Jhuma , Dhuri Sunder N.
Published: January 2024

A dinuclear Ni(ii) compound, [Ni2(μ-van)2(μ-OAc)(NCS)3(H2O)]·5H2O 1 with p-vanillin and acetato bridging ligands have been structurally characterized and tested for catecholase-like and biological activities.
Rapid plasma electrolytic oxidation preparation of sub-3 nm half-embedded intermetallic nanocatalysts for efficient selective hydrogenation
Authors: Li Mengyang , Cao Feng , Wang Mingran , Cao Yang , Wang Qianwei , Zhou Jun , Li Song , Qin Gaowu
Published: January 2024

Monodisperse sub-3 nm ordered intermetallic nanoparticles half-embedded in a porous MgO support layer on a Mg plate were prepared for the first time.
Correction: Silver/silver halide supported on mesoporous ceria particles and photo-CWPO degradation under visible light for organic compounds in acrylonitrile wastewater
Authors: Zhao Guozheng , Tan Qingwei , Li Changbo , Shang Liyan , Zhang Daihang , Lu Xuanxuan , Qiu Feng
Published: January 2024

Correction for ‘Silver/silver halide supported on mesoporous ceria particles and photo-CWPO degradation under visible light for organic compounds in acrylonitrile wastewater’ by Guozheng Zhao et al., RSC Adv., 2021, 11, 26791–26799, https://doi.org/10.1039/D1RA04465F.
Schizophrenia: Communication Disorders and Role of the Speech-Language Pathologist
Authors: Raina Shivani
Published: January 2024

Purpose:

This clinical focus article aims to provide a comprehensive overview of schizophrenia and understanding of communication disorders resulting from its psychopathology. Schizophrenia is a spectrum disorder with varying levels of symptom expression. It is characterized by positive and negative symptoms that can cause communication disorders of different severity levels. Communication difficulties manifest as a range of symptoms such as alogia, disorganized speech, and impaired social communication. These challenges may result in receptive and expressive language deficits that lead to misunderstandings, reduced social interactions, and difficulties expressing thoughts and emotions effectively. The purpose of this clinical focus article is to explore the role of the speech-language pathologist (SLP) in assessing and treating communication disorders presented in schizophrenia.

Conclusions:

In order to understand the role of the SLP in assessing and treating communication disorders in schizophrenia, it is imperative to understand the overall course, etiology, assessment, and treatment consideration of this condition. SLPs can provide services in the areas of social skills training and community-based intervention contexts.
Analysis and research of the causes and course of degradation of lithium batteries
Authors: Buriak Serhii , Gololobova Oksana , Havryliuk Volodymyr , Serdiuk Tetiana , Voznyak Oleh , Manachyn Ivan
Published: January 2024

Energy storage devices based on lithium technology are confidently leading the respective market due to their significant advantages over other technologies in the industry. Despite their relatively recent history of appearance, they managed to undergo many modifications of both physical and chemical components. One of the constant goals of all research in this field is the formation of knowledge about the degradation processes occurring inside a given chemical current source, and ways to influence them. Systematization and identification of the fundamental reasons for the decrease in the performance of lithium batteries still remains a topical issue of today, and therefore is considered in this article. And no matter how studied this issue looks, taking into account the existing many long-term experimental data of a huge number of scientists and a number of different types of companies, but still, optimization of work is impossible without identifying and eliminating as many destructive factors as possible in battery operation. The difficulty of this process lies also in the fact that, taking into account all the high-tech production processes in the world, there are no two identical lithium current sources. On the example of a single battery, the ability to maintain high performance, close to nominal, was demonstrated from a source that, due to its lifetime, should not have had them. The data obtained during the experiment, which confirmed the high performance, show once again that the issue of degradation of lithium current sources can and should be studied further.
Improving the System of Electricity Consumption Rationing
Authors: Arpul Serhii , Afanasov Andrii , Babyak Mykola , Vasyliev Viacheslav
Published: January 2024

The main tool for reducing energy consumption in train traction is the construction of such a system of electricity consumption rationing, which will allow to reliably analyse and forecast energy consumption. This requires the development of a scientifically based system for rationing electricity consumption in train traction and its widespread implementation in locomotive depots. The purpose of the study is to improve the system of technical rationing of electricity consumption by freight trains. To this end, an attempt was made to solve the following tasks: to determine tools for assessing the impact of operational factors on electricity consumption using information from samples of drivers’ route sheets by the method of statistical analysis; based on the conducted research, to propose an improved system of technical rationing of energy consumption in freight train traction. The proposed method of technical rationing allows for more accurate calculation of electricity consumption per trip and, as a result, provides a greater incentive effect for saving electricity by locomotive crews.
The passive safety system of a high-speed multiple-unit train
Authors: Sobolevska Maryna , Horobets Dmytro
Published: January 2024

The designing of modern high-speed multiple-unit trains in Ukraine should be carried out accounting for passive safety systems (PSSs) which include energy absorption devices (EADs). In the cases of trains collisions with obstacles these systems must automatically work to increase the passenger transportation safety, to reduce the risk of injury and death of passengers and service personnel, to minimize rolling stock damage. On the base of European experience in power head passive protection, a three-dimensional geometric model of the domestic power head frontal part with energy absorption devices containing cellular elements was developed. The protective devices for the power head and energy absorption devices installed in inter-car connections were proposed using the experience of development of the EP20 locomotive energy absorption device and results of its prototype crash test. The scientific methodology was developed to evaluation the EAD parameters. Finite-element models for studying the plastic deformation of EAD designs at impact and discrete-mass mathematical models for studying the dynamic loading of reference multiple-unit train vehicles in emergency collisions were developed in accordance with the DSTU EN 15227 requirements. As a research result, the parameters of the EAD designs have been obtained and compliance of the developed passive safety system with regulatory requirements has been proven.
The influence of the powers of executive authorities in the EU transport sector on environmental safety (on the example of some EU countries with the lowest number of transport accidents and incidents)
Authors: Gubina Ganna
Published: January 2024

Transport accidents and incidents are closely related to environmental safety. Ukraine became a candidate for EU membership. In addition, Ukrainian legislation must be reformed to speed up EU membership. One of the pressing problems is also the reduction of transport accidents and incidents in order to maintain environmental safety. To do this, it is necessary to analyze the powers of those executive authorities of the EU countries where the smallest number of transport accidents and incidents are observed in order to make the necessary changes to Ukrainian legislation. The author proposed recommendations.
Supervised Machine Learning Models for Forecasting Fuel Consumption by Vehicles During the Grain Crops Delivery
Authors: Kotenko Viktoriia , Onyshchuk Vasyl , Stelmashchuk Valerii
Published: January 2024

In the work possibilities of applying computational intelligence, namely machine learning models, in the grain crops delivery from agricultural enterprises to the elevator are analyzed. The expediency of using regression models of machine learning to forecast fuel consumption by vehicles during the grain crops delivery is established. Based on the historical data of the enterprise on the orders execution for the grain crops delivery, which include key factors influencing fuel consumption, the article forecasts fuel consumption by vehicles using such models: Generalized Linear Model, Neural Network Model, Decision Tree Model and Random Forest Model. The developed models were evaluated according to efficiency criteria, including mean absolute error, root mean square error, mean absolute percentage error, total time and training time. According to the modelling results, it is found that the most accurate and relatively fast forecast of fuel consumption by vehicles is obtained by applying the Random Forest model with MAPE 7.8 %.
Method for calculating the supply of transport and logistics services depending on the demand for freight transportation
Authors: Myronenko Viktor , Gaba Vasyl , Hrushevska Tetiana
Published: January 2024

The article examines the problems that arise in railway freight transportation when determining the optimal size of rolling stock fleet under seasonal fluctuations in the volume of transportation and ensuring a certain reserve of vehicles. In order to optimize the number of vehicles in the fleet, it is necessary to find a balance between undesirable expenses for maintaining wagons in periods of falling demand for them (surplus supply of transport and logistics services) and unearned income from their lack (deficit) in periods of maximum growth of transportation volumes. The methodology and example of calculating the fleet of freight wagons, the efficiency of their use and determining the optimal number of rolling stock and the need for a certain reserve of vehicles are presented. It is noted that the railway transport of Ukraine was and continues to be one of the main types of transport in the transportation of goods and passengers. However, considering the long operating time of the rolling stock, more than 70% of semi-wagons and more than 80% of grain wagons require replacement or extension of their service life due to capital repairs. The role of railways is especially critical in the current period of russia's war against Ukraine, due to the lack of air transport, river and sea transport and the insufficient capacity of highways and border railway stations. Determining the required number and optimizing the number of vehicles in the fleet can be carried out according to the calculation methodology, which is based on the analytical determination of the minimum of the objective function of the total operating costs associated with both the deficit and the surplus of vehicles compared to the demand for transport and logistics services. It has been established that the application of this calculation method allows to optimize the inventory and working fleet of wagons taking into account the different cost per day of shortage and surplus of the fleet of wagons (supply of transport services compared to their demand). Compared to traditional methods of calculation, the proposed method saves operational costs for maintaining the fleet of wagons in the amount of 2-5%.
The influence of the structure and properties of powder heat-resistant alloys on the features of 3D printing of products from them
Authors: Duriagina Zoia , Lemishka Ihor , Ovchynnykov Oleksandr , Yefanov Vladimir , Klimczyk Piotr
Published: January 2024

Methods of fractional analysis of powders based on heat-resistant nickel alloys, electron microscopy and elemental analysis, study of bulk density of powder fractions, as well as approaches of mathematical modeling of packing density were applied in the work. Spherical powders based on heat-resistant nickel alloys of two different fractions: 50...200 μm and ≤63 μm were studied. The morphology of the surface of spherical particles of powders based on heat-resistant nickel alloys of different fractional composition, as well as their granulometric characteristics, was researched. It is shown that as the fractional composition of powder fractions decreases, their homogeneity and bulk density increase. At the same time, it was established that more finely dispersed fractions are characterized by worse fluidity indicators. According to the simulation results, the optimal fractional composition of the powder for filling the previously specified volume was determined. It is shown that as the size of the investigated particles decreases, their packing density increases.
Ensuring the technological strength when welding the shaft with flange of auto-vehicles
Authors: Dzyubyk Andrij , Kachmar Roman , Dzyubyk Liudmyla , Porokhovskyi Yurii
Published: January 2024

In engineering, the use of highly loaded shafts with flanges is mainly intended for additional attaching of various technological equipment. At the same time, the shaft-flange fitting is performed using an annular weld. Next, parts such as gears, pulleys, bushings, etc. are mechanically attached to the flange. The work considers the achievement of the technological strength of the shaft-flange fit when using arc welding methods. It has been established that the emergence of dangerous defects such as weld cracks is possible. The cause for this is a number of structural, technological and metallurgical restrictions. It is shown that it is expedient to apply welding technological schemes that make it possible to minimize areas of structural heterogeneity. It is proposed to use a transition layer made of low-carbon material, which is characterized by high plastic properties. As a result, the creation of a barrier layer in the zone of structural heterogeneity is achieved. The plastic intermediate weld contributes to the partial relaxation of residual stresses of welding and increases the crack resistance of the welded joint as a whole.
An Eye Opener for a Blinding Disease—Orbital Infarction Syndrome
Authors: Kaushik Kavya S. , Acharya Ullas V. , Pandey Paritosh , Krupa Lakshmi
Published: January 2024

Orbital infarction syndrome (OIS) is a disease of rare occurrence owing to the rich orbital vascular anastomotic network. We describe a case of a middle-aged female who presented with an acute left middle cerebral artery (MCA) territory infarct with left terminal internal carotid artery and MCA occlusion, underwent emergency mechanical thrombectomy, and developed painful loss of vision shortly after diagnosed as OIS based on clinical and radiological findings. The rarity and severity of OIS, especially in the setting of mechanical thrombectomy, warrant radiologists to be aware of this entity to ensure preventive measures or aid in prompt diagnosis to institute timely treatment.
Ablation versus Radiation Segmentectomy for Small Liver Tumors
Authors: Ozen Merve , Patel Ronak K.
Published: January 2024

Hepatocellular carcinoma (HCC) is a liver malignancy that affects more than a million people worldwide with a complex multifactorial etiology. After the diagnosis of HCC is made, physicians establish management using the Barcelona Clinic Liver Cancer (BCLC) guidelines revolving around tumor stage, liver function, performance status, and patient preferences. According to recent updates to these guidelines, thermal ablation is the second-best curative option apart from surgical resection for small HCC (< 2 cm). While thermal ablation is standard of care, recent studies have suggested that radiation segmentectomy (RS) has similar outcomes, limited hepatotoxicity, and ultimately a cost-efficient approach. Although there is limited literature on RS, this article compares ablation techniques against radiation segmentectomy for small HCC tumors.
A Review of Resection and Surgical Ablation for Primary and Secondary Liver Cancers
Authors: White McKenzie J. , Jensen Eric H. , Brauer David G.
Published: January 2024

The surgical management of primary and secondary liver tumors is constantly evolving. Patient selection, particularly with regard to determining resectability, is vital to the success of programs directed toward invasive treatments of liver tumors. Particular attention should be paid toward determining whether patients are best served with surgical resection or ablative therapies. A multidisciplinary approach is necessary to provide optimal care to patients with liver malignancy.
How does the new environmental protection law affect the environmental social responsibility of enterprises in Chinese heavily polluting industries?
Authors: Wu Guoyong , Sun Mengmin , Feng Yanchao
Published: January 2024

In the new era of seeking for cleaner production and comfortable life, it is important and necessary to improve environmental social responsibility, especially for the heavily polluting industries. Against this backdrop, the Chinese government put forward the new environmental protection law in 2015, while the effect of it on the environmental social responsibility still remains as a black box, which forms the initial motivation of this essay. Treating the implementation of the new environmental protection law (NEPL) as a quasi-natural experiment, this essay employed the difference-in-differences model to explore its impact on the environmental social responsibility (ESR) of highly polluting enterprises. The results support that implementing the NEPL can enhance the level of environmental social responsibility by strengthening the end-of-pipe governance and green office level of enterprises, in contrast, the affection on the front-end governance is not significant. The results remain unchanged after various robustness tests, such as changing the time point of the policy, placebo test, and elimination of sample selection bias. Further research finds that the scale of corporate financing and the efficiency of capital use have different moderating effects on the effectiveness of the implementation of the NEPL policy. Mechanism analysis shows that the NEPL policy affects the level of corporate environmental social responsibility through the technological innovation crowding-out effect. In addition, heterogeneity analysis reveals that environmental regulation intensity has an “inverted U-shaped” effect on the ESR of businesses. Furthermore, non-state-owned companies and companies with higher levels of executive education have higher levels of environmental social responsibility. Finally, policy implications are provided to shed light on this essay’s theoretical and practical values.
The Wigner function of a semiconfined harmonic oscillator model with a position-dependent effective mass
Authors: Nagiyev S. M. , Jafarova A. M. , Jafarov E. I.
Published: January 2024

We propose a phase-space representation concept in terms of the Wigner function for a quantum harmonic oscillator model that exhibits the semiconfinement effect through its mass varying with the position. The new method is used to compute the Wigner distribution function exactly for such a semiconfinement quantum system. This method suppresses the divergence of the integrand in the definition of the quantum distribution function and leads to the computation of its analytical expressions for the stationary states of the semiconfined oscillator model. For this quantum system, both the presence and absence of the applied external homogenous field are studied. Obtained exact expressions of the Wigner distribution function are expressed through the Bessel function of the first kind and Laguerre polynomials. Furthermore, some of the special cases and limits are discussed in detail.
Semiclassical quantification of some two degree of freedom potentials: A differential Galois approach
Authors: Acosta-Humánez Primitivo , Lázaro J. Tomás , Morales-Ruiz Juan J. , Pantazi Chara
Published: January 2024

In this work we explain the relevance of the Differential Galois Theory in the semiclassical (or WKB) quantification of some two degree of freedom potentials. The key point is that the semiclassical path integral quantification around a particular solution depends on the variational equation around that solution: a very well-known object in dynamical systems and variational calculus. Then, as the variational equation is a linear ordinary differential system, it is possible to apply the Differential Galois Theory to study its solvability in closed form. We obtain closed form solutions for the semiclassical quantum fluctuations around constant velocity solutions for some systems like the classical Hermite/Verhulst, Bessel, Legendre, and Lamé potentials. We remark that some of the systems studied are not integrable, in the Liouville–Arnold sense.
Four-wave mixing with anti-parity-time symmetry in hot 85Rb vapor
Authors: Niu Ziqi , Jiang Yue , Wen Jianming , Zhang Chuanwei , Du Shengwang , Novikova Irina
Published: January 2024

We report an experimental demonstration of anti-parity-time symmetric optical four-wave mixing in thermal rubidium vapor, where the propagation of probe and stokes fields in a double-Λ scheme is governed by a non-Hermitian Hamiltonian. We are particularly interested in studying quantum intensity correlations between the two fields near the exceptional point, taking into account loss and accompanied Langevin noise. Our experimental measurements of classical four-wave mixing gain and the associated two-mode relative-intensity squeezing are in reasonable agreement with the theoretical predictions.
Performance-enhanced intrinsic polarization-sensitive organic photodetectors by molecular interaction modulation
Authors: Shao Zhimin , Yu Feng , Cen Guobiao , Gu Tianfu , Huang Xinyue , Wang Yufei , Cai Wanzhu , Mai Wenjie , Xu Xiaofeng , Qin Donghuan , Yang Renqiang , Hou Lintao
Published: January 2024

Polarization-sensitive organic photodetectors (OPDs) are increasingly paid attention for their broad application prospect. However, it is extremely difficult to achieve highly sensitive detection of polarized light for most organic semiconductor polymers with intrinsic isotropic amorphous behavior. In this study, the performance-enhanced intrinsic anisotropic all-polymer bulk heterojunctions (BHJs) are obtained by constructing molecular fluorination engineering in the fused-ring backbone of the acceptor polymer. The molecular orientation, alignment, and packing can be effectively optimized during the floating-film formation process without using any additives and post-treatments. The outstanding intrinsic polarization-sensitive photodetection performance with a very high photocurrent dichroic ratio of 3.73, a specific detectivity of 1.3 × 1011 Jones at 0 V, and a broad linear dynamic range of 120 dB is achieved for the optimum-fluorine-content self-assembly all-polymer organic BHJ film. The superiorities of self-powered capability, fast response, and high-contrast imaging demonstrate that the backbone fluorination for acceptor polymers is conducive to achieving excellent structural regularity and can endow the intrinsic polarization-sensitive all-polymer OPDs with more demanding polarized-light detection ability.
Avalanche dynamics of dislocations and cracks under tension in additively manufactured copper
Authors: Chen Yan , Gou Boyuan , He Dongdong , Ding Xiangdong , Sun Jun , Salje Ekhard K. H.
Published: January 2024

Acoustic emission, AE, spectroscopy identifies dislocation avalanches and crack propagation in high-purity Cu with self-stabilized dislocation networks. These samples were produced by additive manufacturing where thermal gradients form cellular structures. These structures confine avalanches of dislocation movements (∼confined dislocations) with an energy exponent ε = 1.82 ± 0.04. Free dislocation movement follows force-integrated mean-field behavior with ε = 1.6 ± 0.02. Additional crack propagation under tension exhibits a critical failure exponent of ε = 1.45 ± 0.01. These three mechanisms combine to generate sample failure under tension. We use this example to demonstrate how different avalanche mechanisms can be disentangled in AE spectroscopy of additive manufactured metal and how the specific self-stabilized dislocation networks influence these avalanche dynamics.
Strong polarization sensitivity in a two-dimensional MoS2/WSe2 heterojunction for self-powered photodetection
Authors: Zhang Xianjun , Qiu Dan , Zhou Pan , Hou Pengfei
Published: January 2024

Polarization-sensitive photodetectors have received considerable attention for their exceptional optoelectronic properties that depend on polarization. It is an excellent method to reduce energy consumption, system's sizes, and cost by constructing self-powered heterojunctions using the two-dimensional materials with asymmetry structure. In this report, we present a self-powered MoS2/WSe2 heterojunction capable of polarized photodetection. The heterojunction exhibits both photovoltaic and pyroelectric effects, which are correlated with the polarized signals. Interestingly, there is a 90° polarization angle between the photovoltaic and pyroelectric effects due to the introduction of in-plane structural polarization. The photovoltaic effect achieves the highest specific detectivity (D*) of about 5 × 1012 Jones when the light polarization is parallel to the in-plane structural polarization. Conversely, the pyroelectric effect dominates and yields the highest D* of about 6 × 109 Jones when the light polarization is perpendicular to the in-plane structural polarization. These findings demonstrate that the specific detectivity of the heterojunction can vary based on the orientation of the light polarization relative to the in-plane structural polarization due to distinct physical mechanisms. Moreover, the self-powered MoS2/WSe2 heterojunction enables simultaneous detection of optical power density and its change rate for polarized light. This study highlights the potential application of two-dimensional heterojunctions for polarization-sensitive self-powered photodetection in the future.
A two-terminal fault location method for gas switch prefire in linear transformer driver
Authors: Wan Zhenbo , Ding Weidong , Sun Fengju , Jiang Xiaofeng
Published: January 2024

Large-scale linear transformer drivers (LTDs) are composed of numerous high-power gas switches, and switch prefire is a frequent operational fault. To detect and locate the faulty switch accurately and efficiently, a two-terminal location method is proposed. A B-dot sensor is integrated on the gas switch’s shell to collect the discharging signal. All the B-dot sensors are connected in parallel through cables of equal length. The fault position can be determined by the time delay of the signals at the two terminals. A diode is inserted between the B-dot sensor’s coil and the cable core to ensure low-loss transmission of the signal. Two methods are applied in fault location, including time-of-arrival (TOA) and time reversal (TR). For the TOA method, an energy criterion and a phase criterion are applied and compared. The accuracy of the energy criterion is greatly influenced by the signal-to-noise ratio, while the phase criterion requires a reasonable estimate of the actual delay to account for the impact of phase periodicity. The TR method based on a precise simulation model is established, which demonstrates high precision in location. The TR method has been tested and validated on a single stage LTD module. Moreover, the location method for double switches prefire is discussed theoretically. The method proposed in this paper will be helpful to improve the efficiency of the commissioning, operation, and maintenance of the large-scale LTD devices.
Composite of carbon dots and TiNiSn thermoelectric materials: Initial investigation on the electrical and thermal transport properties
Authors: Yong Chao , Lei Ying , Ye Fan , Wang Nan , Li Yu , Liu Yinghui , Chen Zheng , Wang Dongsheng , Zhang Shaowu
Published: January 2024

TiNiCu0.025Sn0.99Sb0.01 is prepared using microwaves. However, an ultra-high electrical conductivity and electronic thermal conductivity are obtained by interstitial Cu and Sb doping, which could not effectively improve the ZT value. We introduce carbon dots (CDs) as a nano-second phase by ball milling to simultaneously optimize the thermoelectric properties. To our best knowledge, this is the first report on half-Heusler/CDs composites. Experimental results show that the introduction of nano-CDs optimizes the carrier concentration and mobility and dramatically improves the Seebeck coefficient through the energy filtering effect. The nano-CDs introduce more point defects, inhibit the grains growth, and form a specific carbon solid solution second phase in the matrix. The lattice thermal conductivity is reduced to the same level as TiNiSn at 1.96 W m−1 K−1 through the synergistic effect of point defects and phase and grain boundaries scattering, and the ZT value reaches a maximum of 0.63 at 873 K.
Macroscale controls determine the recovery of river ecosystem productivity following flood disturbances
Authors: Lowman Heili E. , Shriver Robert K. , Hall Robert O. , Harvey Judson W. , Savoy Philip , Yackulic Charles B. , Blaszczak Joanna R.
Published: January 2024

River ecosystem function depends on flow regimes that are increasingly modified by changes in climate, land use, water extraction, and flow regulation. Given the wide range of variation in flow regime modifications and autotrophic communities in rivers, it has been challenging to predict which rivers will be more resilient to flow disturbances. To better understand how river productivity is disturbed by and recovers from high-flow disturbance events, we used a continental-scale dataset of daily gross primary production time series from 143 rivers to estimate growth of autotrophic biomass and ecologically relevant flow disturbance thresholds using a modified population model. We compared biomass recovery rates across hydroclimatic gradients and catchment characteristics to evaluate macroscale controls on ecosystem recovery. Estimated biomass accrual (i.e., recovery) was fastest in wider rivers with less regulated flow regimes and more frequent instances of biomass removal during high flows. Although disturbance flow thresholds routinely fell below the estimated bankfull flood (i.e., the 2-y flood), a direct comparison of disturbance flows estimated by our biomass model and a geomorphic model revealed that biomass disturbance thresholds were usually greater than bed disturbance thresholds. We suggest that primary producers in rivers vary widely in their capacity to recover following flow disturbances, and multiple, interacting macroscale factors control productivity recovery rates, although river width had the strongest overall effect. Biomass disturbance flow thresholds varied as a function of geomorphology, highlighting the need for data such as bed slope and grain size to predict how river ecosystems will respond to changing flow regimes.
In Support of Breast-/Chestfeeding by People With HIV in High-Income Settings
Authors: Powell Anna , Agwu Allison
Published: January 2024

Given that HIV can be transmitted through breastfeeding, historically, breastfeeding among women with HIV in the US and other resource-rich settings was discouraged. Formula feeding was the mandated feeding option out of concern for breast-milk transmission of HIV, which occurred in 16–24% of cases pre-antiretroviral therapy (pre-ART) use. In January 2023, the US Department of Health and Human Services’ Perinatal Guidelines were revised to support shared decision-making for infant feeding choices. Updated clinical trials' data from resource-limited settings suggest the actual breastmilk HIV transmission rate in the context of maternal ART or neonatal postexposure prophylaxis is 0.3–1%. High-income countries are reporting more people with HIV breastfeeding their infants without cases of HIV transmission. We present the reasons for fully embracing breast-/chestfeeding as a viable, safe infant feeding option for HIV-exposed infants in high-income settings, while acknowledging unanswered questions and the need to continually craft more nuanced clinical guidance.
OP10 Efficacy and safety of upadacitinib in patients with moderately to severely active Crohn’s Disease: results from the U-ENDURE long-term extension
Authors: D'Haens G , Louis E , Loftus Jr. E V , Regueiro M , Jairath V , Magro F , Nakase H , Dubcenco E , Lacerda A P , Feng T , Duncan B , Wang T , Ford S , Anyanwu S I , Blumenstein I
Published: January 2024

Background

Upadacitinib (UPA) is an oral Janus kinase inhibitor approved for the treatment of moderately to severely active Crohn’s disease (CD).1 The U-ENDURE (NCT03345823) maintenance study and long-term extension (LTE) evaluate the long-term efficacy and safety of UPA maintenance therapy. Here, we report the results of the U-ENDURE LTE.

Methods

Patients (pts) completing the U-ENDURE 52-week (wk) maintenance study were eligible to participate in the LTE and continue their previously assigned treatment (placebo [PBO], UPA 15 mg [UPA15] once daily [QD], or UPA 30 mg [UPA30] QD; blinded until the last pt completed maintenance wk52). Clinical response, clinical remission, endoscopic response, endoscopic remission, as well as high-sensitivity C-reactive protein (hs-CRP) and faecal calprotectin (FCP) were evaluated as-observed up to wk48 of the LTE among pts (PBO [N = 89], UPA15 [N = 107], UPA30 [N = 173]); excluding pts who received open-label UPA30 rescue therapy. Safety was assessed in all pts (PBO [N = 223], UPA15 [N = 221], UPA30 [N = 229]) from wk0 of the maintenance study up to LTE wk204 (cut-off date: 01 Aug 2023).

Results

At LTE wk0, the SF/APS clinical remission rates were 73.0%, 78.3%, and 80.3% for PBO, UPA15, and UPA30, respectively (Figure 1A). Similar rates were reported at LTE wk0 for CDAI clinical remission (PBO 75.3%, UPA15 81.3%, UPA30 80.9%; Figure 1B) and clinical response (CR-100: PBO 79.5%, UPA15 84.9%, UPA30 84.4%). Rates of clinical remission were stable through wk48 of the LTE. Endoscopic response (PBO 32.9%, UPA15 59.6%, UPA30 66.5%) and remission rates (PBO 27.8%, UPA15 42.4%, UPA30 47.3%) at LTE wk0 were sustained through wk48 with UPA while decreased with PBO (Figure 1C-D). At LTE wk0, the mean [95% CI] change from induction BL in hs-CRP was 1.8 [–0.4, 4.1], –13.2 [–17.9, –8.6], and –12.8 [–16.8, –8.9] for PBO, UPA15, and UPA30, respectively; sustained through wk48. Similar results were observed with FCP (mean [95% CI] change from induction BL: PBO 126 [–103, 356], UPA15 –2946 [–4121, –1772], UPA30 –1871 [–2577, –1165]). Severe adverse events (AEs) and serious AEs were lower with UPA treatment compared with PBO (Table 1). The rates of most AEs of special interest were similar between UPA and PBO; however, numerically higher rates of herpes zoster, adjudicated gastrointestinal perforations, neutropenia, lymphopenia, creatine phosphokinase elevation, and hepatic disorders were reported in pts treated with UPA vs PBO (Table 1).

Conclusion

In pts completing wk48 of the LTE, sustained efficacy was observed in clinical and endoscopic endpoints with over 2 years of UPA treatment, while maintaining an overall positive safety profile in pts with CD.

Reference:

1. Loftus EV Jr, et al. N Engl J Med. 2023;388:1966–80
OP12 Mirikizumab improves fatigue, bowel urgency, and quality of life in patients with moderately to severely active Crohn’s Disease: Results from a phase 3 clinical trial
Authors: Travis S , Hisamatsu T , Fischer M , Dubinsky M , Jairath V , Chen M , Ferrante M , Peyrin-Biroulet L , Siegmund B , Hunter Gibble T , Lin Z , Protic M , Morris N , Ghosh S
Published: January 2024

Background

Mirikizumab (miri), an anti-IL-23p19 antibody, is approved for the treatment of ulcerative colitis and under development for Crohn’s disease (CD). We investigated how miri impacted fatigue, bowel urgency, and health-related quality of life (HRQoL) through 52 weeks in patients with moderately to severely active CD in the Phase 3 VIVID-1 study.

Methods

In the treat-through VIVID-1 (NCT03926130) study, patients (N=1065) with moderately to severely active CD and a Simple Endoscopic Score for CD (SES-CD) score ≥7 (or ≥4 for patients with isolated ileal disease) and failure to biologic and/or conventional therapy were randomized in a 6:3:2 ratio to receive miri (N=579) (a single 900mg intravenous (IV) dose at W0, W4, and W8 followed by a subcutaneous (SC) dose of 300 mg at W12 and then every 4 weeks), ustekinumab (N=287) (6mg/kg IV at W0 and SC dose of 90mg at W8 and then every 8 weeks), or PBO (N=199). At W12 PBO responders continued PBO to W52; PBO-non-responders received the same blinded miri regimen as described above. This analysis focuses on results in patients randomized to either miri or PBO. The change from baseline for Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Urgency Numeric Rating Scale (UNRS), and Inflammatory Bowel Disease Questionnaire (IBDQ) total and domain scores (bowel symptoms, systemic symptoms, emotional function, social function) were analyzed through W52. IBDQ response (≥16-point improvement from baseline) and remission (total score ≥ 170) rates were also analyzed at W12 and W52. For binary variables, adjusted risk differences were compared between miri and PBO using the Cochran-Mantel-Haenszel (CMH) test. For continuous variables, least squares mean changes from baseline were compared between treatment groups using ANCOVA.

Results

Significant improvement in mean change from baseline to W12 and W52 were observed with miri for FACIT-F, UNRS, and IBDQ total and domain scores (all p<0.000001 at W52) (Figure 1&2). Miri-treated patients showed improved UNRS scores versus PBO as early as W8 with statistical significance sustained to W52 (Figure 1B). At W12 and W52, a greater percentage of miri-treated patients achieved IBDQ response (W12: p<0.000001; W52: p<0.000001) and remission (W12: p<0.000001; W52: p<0.000001) compared to PBO (Figure 2A&B).

Conclusion

Treatment with miri resulted in improvements in fatigue, bowel urgency, and HRQoL at W12 and W52 in patients with moderately to severely active CD.
OP25 Dual activation of GCGR/GLP1R signaling ameliorates intestinal fibrosis via metabolic regulation of histone H3K9 lactylation in epithelial cells
Authors: Liu H , Hong Y , Wang X , Dong J , Li X , Shi Z , Wang J , Zhou L , Rieder F , Chen B , Chen M , Zhang Y , Mao R , Jiang X
Published: January 2024

Background

Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases, but no effective anti-fibrotic therapy is currently available. GCGR and GLP1R are both peptide hormone receptors involved in energy metabolism of epithelial cells. However, their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored.

Methods

Intestinal tissues from patients with Crohn’s Disease (CD) (n=20) were obtained. AAV9-Glp1r-shRNA, AAV9-Gcgr-shRNA or AAV9-NC-shRNA were used to transfect mice. Murine colons were analyzed by single-cell RNA sequencing (seq) and metabonomics. Glycolytic metabolism of epithelial cells was analyzed with bulk RNAseq and seahorse-XF technology, while lactylation levels were verified using antibodies against diverse forms of lactylated histones. Then a range of GCGR/GLP1R dual-target ultralong-acting peptides were synthesized, and their agonistic activities were assessed in HEK293 cells that stably expressed either human GLP1R or GCGR, using a cAMP response element-driven luciferase reporter. The antifibrotic activity of the leading peptide 1907B was functionally evaluated in vitro and in vivo.

Results

GCGR and GLP1R were reduced in the stenotic ileum of patients with CD as well as in the fibrotic colon of mice with chronic colitis. In the chronic model, Gcgr/Glp1r dual knockdown worsened the degree of fibrosis in mice, and increased glycolysis-related metabolites, with lactate exhibiting the most prominent alterations. In the TGFβ1-induced epithelial cell model, exogenous and endogenous lactate induced fibrotic genes expression and overwhelming histone lactylation in H3K9 (H3K9la). Further, cells overexpressing H3.1 (K9R) exhibited lower levels of fibrotic genes and proteins after treatment with lactate compared with the H3.1 WT group. Then 1907B, the leading GCGR/GLP1R dual-target peptide, normalized the ATP production rate of glycolysis, extracellular lactate, H3K9la levels of promoters related to fibrosis genes, and further ameliorated intestinal fibrosis in vivo.

Conclusion

We uncovered the role of GCGR/GLP1R in regulating EMT involved in intestinal fibrosis via histone lactylation. Simultaneously activating GCGR/GLP1R with the novel dual agonist 1907B holds promise as a treatment strategy for alleviating intestinal fibrosis.
OP32 TWIST1-mediated fibroblast activation protein (FAP)-expressing fibroblasts drives fibrosis in Crohn’s Disease
Authors: Ke B J , Abdurahiman S , Verstockt B , Biscu F , Zanella G , Zouzaf A , van Baarle L , De Simone V , Stakenborg M , Santhosh S , Verstockt S , De Hertogh G , Vermeire S , Matteoli G
Published: January 2024

Background

Stricturing Crohn’s disease (CD) is a distinct clinical phenotype, characterised by the development of fibrotic strictures within the GI tract. These strictures result from chronic inflammation, leading to the accumulation of collagen and scar tissue, causing narrowing of the affected intestinal segments. Due to a lack of anti-fibrotic medication, up to 70% of patients with CD will require surgery in their lifetime, while up to 40% of patients need repetitive resections within 10 years.

Methods

To understand inflammation-induced fibrosis, full-thickness ileal punch biopsies from CD patients (n=10) and colorectal cancer (CRC) patients (n=5) undergoing ileocecal resection (ICR), were profiled using single-cell RNA sequencing (scRNA-seq) on the 10x Genomics platform. Flow cytometry was performed to confirm scRNA-seq findings. Intestinal fibroblasts were cultured in the presence of NicheNet-predicted cytokines or supernatant of FACS-sorted myeloid cells. To confirm the pro-fibrotic role of TWIST1 in fibroblasts, both Harmine (TWIST1 inhibitor)-treated wild-type mice and COL1A2CrexTWIST1fl/fl mice were subjected to chronic dextran sulphate sodium (DSS)-induced colitis.

Results

Using scRNA-seq, we identified a specific subset of FAP-expressing fibroblasts enriched in fibrotic surgical CD specimens. Flow cytometry confirmed a significant increase of these cells in the inflamed and stenotic ileum, compared to proximal uninflamed ileum and unaffected control ileum from CRC patients undergoing ICR. Computational methods identified TWIST1 as a key transcription factor, mediating fibroblast activation and extracellular matrix (ECM)-regulatory phenotypes. Myeloid cell-derived inflammatory signals were predicted to induce this specific fibroblast activation, resulting in collagen deposition and tissue fibrosis. Intestinal fibroblasts cultured with inflammatory monocyte supernatant or pro-inflammatory cues expressed higher levels of TWIST1, FAP, and COL3A1. After inhibiting TWIST1 with Harmine, collagen expression and ECM accumulation were decreased in fibroblasts. In addition, in chronic DSS colitis, wild-type mice treated with Harmine showed a reduction in collagen deposition. COL1A2CrexTWIST1fl/fl mice showed improved disease activity, compared to their littermate controls.

Conclusion

Our findings suggest that TWIST1 serves as a central mediator in the activation of fibroblasts, promoting excessive collagen deposition in ileal CD. Targeting TWIST1 may reduce tissue remodelling and prevent fibrosis in CD.
DOP33 Distinct perturbances in metabolic pathways associate with disease progression in patients with Inflammatory Bowel Disease
Authors: Bourgonje A R , Ibing S , Argmann C , Sands B E , Dubinsky M , Jacobsen H A , Suarez-Farinas M , Mehandru S , Colombel J F , Ungaro R C
Published: January 2024

Background

Patients with inflammatory bowel diseases (IBD) exhibit distinct shifts in circulating metabolite levels that have been associated with clinical disease activity and disease phenotype. However, there are limited data on the impact of metabolomic changes on disease progression in IBD. We aimed to understand the association of circulating metabolite levels and related pathways with the risk of disease progression in patients with IBD.

Methods

We conducted an observational cohort study using the Mount Sinai Crohn’s and Colitis Registry (MSCCR). Patients were prospectively enrolled with baseline questionnaires and biospecimens that were then linked to longitudinal electronic health record data. A total of 1,456 serum metabolites were measured in 277 patients with UC and 375 patients with CD using untargeted metabolomics. Disease progression was defined as any new steroid or biological prescriptions, IBD-related hospitalizations, or surgery. Multivariable Cox proportional hazards regression models, adjusted for age, sex, smoking, biologic use, and surgery were used to explore metabolite associations with risk of disease progression. Metabolite set enrichment analysis (MSEA) was performed to identify underlying metabolic pathways associated with disease progression.

Results

During a median 2-year follow-up time (IQR 0.3-5.1 years), 375 patients (57.5%) had a disease progression event. Among CD, 151 metabolites significantly correlated with the composite outcome (FDR<0.1). Of these, 81 (53.6%) were linked to higher risk, mainly enriched in amino acids, purine, and pyrimidine metabolism, fibrinogen cleavage peptides, and bile acid pathways. Additionally, 70 (46.4%) metabolites associated with lower risk with enrichment in fatty acid metabolism, steroid biosynthesis, histidine, tryptophan, and antioxidant pathways. In CD, aspartate metabolism was most significantly associated with increased risk and linoleic metabolism with decreased risk. In UC, 84 metabolites were significantly associated with disease progression (FDR<0.1), with 29 (34.5%) associated with increased and 55 (65.5%) with decreased risk. Metabolic pathways linked to higher risk were sphingolipid, benzoate, hydrogen sulfide, polyamine, and tyrosine metabolism, while protective metabolites were enriched in branched-chain amino acid (BCAA), steroid biosynthesis, histidine, and phenylalanine pathways. In UC, sphingolipid metabolism was prominently associated with increased risk and BCAA metabolism with decreased risk.

Conclusion

Specific metabolites and metabolic pathways are associated with risk of disease progression in patients with IBD, highlighting potential prognostic metabolite biomarkers and pathways that may be important in modulating risk of disease progression.