bluuebunny/crossref_metadata_2025 huggingface dataset:
KHSRP ameliorates acute liver failure by regulating pre-mRNA splicing through its interaction with SF3B1
Authors: Li Mingxuan , Fang Qian , Xiao Pingping , Yin Zhinang , Mei Guangbo , Wang Cheng , Xiang Ying , Zhao Xuejun , Qu Lihua , Xu Tian , Zhang Jiaxi , Liu Kejun , Li Xiaoqing , Dong Huifen , Xiao Ruijing , Zhou Rui
Published: August 2024

Acute liver failure (ALF) is characterized by the rapidly progressive deterioration of hepatic function, which, without effective medical intervention, results in high mortality and morbidity. Here, using proteomic and transcriptomic analyses in murine ALF models, we found that the expression of multiple splicing factors was downregulated in ALF. Notably, we found that KH-type splicing regulatory protein (KHSRP) has a protective effect in ALF. Knockdown of KHSRP resulted in dramatic splicing defects, such as intron retention, and led to the exacerbation of liver injury in ALF. Moreover, we demonstrated that KHSRP directly interacts with splicing factor 3b subunit 1 (SF3B1) and enhances the binding of SF3B1 to the intronic branch sites, thereby promoting pre-mRNA splicing. Using splicing inhibitors, we found that Khsrp protects against ALF by regulating pre-mRNA splicing in vivo. Overall, our findings demonstrate that KHSRP is an important splicing activator and promotes the expression of genes associated with ALF progression by interacting with SF3B1; thus, KHSRP could be a possible target for therapeutic intervention in ALF.
NLRP4 renders pancreatic cancer resistant to olaparib through promotion of the DNA damage response and ROS-induced autophagy
Authors: Xiao Mingming , Yang Jing , Dong Mingwei , Mao Xiaoqi , Pan Haoqi , Lei Yalan , Tong Xuhui , Yu Xiaoning , Yu Xianjun , Shi Si
Published: August 2024

Olaparib has been approved as a therapeutic option for metastatic pancreatic ductal adenocarcinoma patients with BRCA1/2 mutations. However, a significant majority of pancreatic cancer patients have inherent resistance or develop tolerance to olaparib. It is crucial to comprehend the molecular mechanism underlying olaparib resistance to facilitate the development of targeted therapies for pancreatic cancer. In this study, we conducted an analysis of the DepMap database to investigate gene expression variations associated with olaparib sensitivity. Our findings revealed that NLRP4 upregulation contributes to increased resistance to olaparib in pancreatic cancer cells, both in vitro and in vivo. RNA sequencing and Co-IP MS analysis revealed that NLRP4 is involved in the DNA damage response and autophagy pathway. Our findings confirmed that NLRP4 enhances the capacity for DNA repair and induces the production of significant levels of reactive oxygen species (ROS) and autophagy in response to treatment with olaparib. Specifically, NLRP4-generated mitochondrial ROS promote autophagy in pancreatic cancer cells upon exposure to olaparib. However, NLRP4-induced ROS do not affect DNA damage. The inhibition of mitochondrial ROS using MitoQ and autophagy using chloroquine (CQ) may render cells more susceptible to the effects of olaparib. Taken together, our findings highlight the significant roles played by NLRP4 in the processes of autophagy and DNA repair when pancreatic cancer cells are treated with olaparib, thereby suggesting the potential therapeutic utility of olaparib in pancreatic cancer patients with low NLRP4 expression.
BRG1 promotes progression of B-cell acute lymphoblastic leukemia by disrupting PPP2R1A transcription
Authors: Kang Qian , Ma Dan , Zhao Peng , Chai Xiao , Huang Yi , Gao Rui , Zhang Tianzhuo , Liu Ping , Deng Bo , Feng Cheng , Zhang Yan , Lu Yinghao , Li Yanju , Fang Qin , Wang Jishi
Published: August 2024

Despite advancements in chemotherapy and the availability of novel therapies, the outcome of adult patients with B-cell acute lymphoblastic leukemia (B-ALL) remains unsatisfactory. Therefore, it is necessary to understand the molecular mechanisms underlying the progression of B-ALL. Brahma-related gene 1 (BRG1) is a poor prognostic factor for multiple cancers. Here, the expression of BRG1 was found to be higher in patients with B-ALL, irrespective of the molecular subtype, than in healthy individuals, and its overexpression was associated with a poor prognosis. Upregulation of BRG1 accelerated cell cycle progression into the S phase, resulting in increased cell proliferation, whereas its downregulation facilitated the apoptosis of B-ALL cells. Mechanistically, BRG1 occupies the transcriptional activation site of PPP2R1A, thereby inhibiting its expression and activating the PI3K/AKT signaling pathway to regulate the proto-oncogenes c-Myc and BCL-2. Consistently, silencing of BRG1 and administration of PFI-3 (a specific inhibitor targeting BRG1) significantly inhibited the progression of leukemia and effectively prolonged survival in cell-derived xenograft mouse models of B-ALL. Altogether, this study demonstrates that BRG1-induced overactivation of the PPP2R1A/PI3K/AKT signaling pathway plays an important role in promoting the progression of B-ALL. Therefore, targeting BRG1 represents a promising strategy for the treatment of B-ALL in adults.
TREM2-dependent activation of microglial cell protects photoreceptor cell during retinal degeneration via PPARγ and CD36
Authors: Zhou Wenchuan , He Jincan , Shen Guiyan , Liu Ya , Zhao Peiquan , Li Jing
Published: August 2024

Retinal degeneration is a collection of devastating conditions with progressive loss of vision which often lead to blindness. Research on retinal microglial cells offers great therapeutic potential in deterring the progression of degeneration. This study explored the mechanisms underlying the TREM2-mediated protective function of activated microglial cells during retinal degeneration. N-methyl-N-nitrosourea (MNU)-induced retinal degeneration was established in C57BL/6 J (WT) and Trem2 knockout (Trem2−/−) mice. We discovered that MNU treatment led to the concurrent processes of photoreceptor apoptosis and microglia infiltration. A significant upregulation of disease-associated microglia signature genes was observed during photoreceptor degeneration. Following MNU treatment, Trem2−/− mice showed exacerbated photoreceptor cell death, decreased microglia migration and phagocytosis, reduced microglial PPARγ activation and CD36 expression. Pharmaceutical activation of PPARγ promoted microglial migration, ameliorated photoreceptor degeneration and restored CD36 expression in MNU-treated Trem2−/− mice. Inhibition of CD36 activity worsened photoreceptor degeneration in MNU-treated WT mice. Our findings suggested that the protective effect of microglia during retinal degeneration was dependent on Trem2 expression and carried out via the activation of PPARγ and the consequent upregulation of CD36 expression. Our study linked TREM2 signaling with PPARγ activation, and provided a potential therapeutic target for the management of retinal degeneration.
TRIP13 regulates progression of gastric cancer through stabilising the expression of DDX21
Authors: Zhang Guanghui , Yang Rui , Wang Baiyan , Yan Qiujin , zhao Peiyuan , Zhang Jiaming , Su Weiyu , Yang Lianhe , Cui Hongjuan
Published: August 2024

GC (Gastric cancer) is one of the most common malignant tumours, with over 95% of gastric cancer patients being adenocarcinoma and most gastric cancer patients having no apparent symptoms in the early stages. Finding biomarkers for early screening of gastric cancer and exploring new targets for gastric cancer treatment are urgent problems to be solved in the treatment of gastric cancer, with significant clinical outcomes for the survival rate of gastric cancer patients. The AAA+ family ATPase thyroid hormone receptor-interacting protein 13 (TRIP13) has been reported to play an essential role in developing various tumours. However, the biological function and molecular mechanism of TRIP13 in gastric cancer remain unclear. This study confirms that TRIP13 is highly expressed in gastric cancer tissue samples and that TRIP13 participates in the proliferation, migration, invasion in vitro, and tumourigenesis and metastasis in vivo of gastric cancer cells. Mechanistically, this study confirms that TRIP13 directly interacts with DDX21 and stabilises its expression by restraining its ubiquitination degradation, thereby promoting gastric cancer progression. Additionally, histone deacetylase 1 (HDAC1) is an upstream factor of TRIP13, which could target the TRIP13 promoter region to promote the proliferation, migration, and invasion of gastric cancer cells. These results indicate that TRIP13 serve is a promising biomarker for the treating of gastric cancer patients, and the HDAC1-TRIP13/DDX21 axis might provide a solid theoretical basis for clinical treatment of gastric cancer patients.
Missense BICD2 variants in fetuses with congenital arthrogryposis and pterygia
Authors: Masuda Layla , Hasegawa Akihiro , Kamura Hiromi , Hasegawa Fuyuki , Yamamura Michihiro , Taniguchi Kosuke , Ito Yuki , Hata Kenichiro , Samura Osamu , Okamoto Aikou
Published: August 2024

Type 2 spinal muscular atrophy with lower extremity dominance (SMALED2) is caused by bicaudal D cargo adaptor 2 (BICD2) variants. However, the SMALED2 genotype and phenotype correlation have not been thoroughly characterized. We identified de novo heterozygous BICD2 missense variants in two fetuses with severe, prenatally diagnosed multiple arthrogryposis congenita. This report provides further insights into the genetics of this rare disease.
Observation of nonlinear thermoelectric effect in MoGe/Y3Fe5O12
Authors: Arisawa Hiroki , Fujimoto Yuto , Kikkawa Takashi , Saitoh Eiji
Published: August 2024

Thermoelectric effects refer to the voltage generation from temperature gradients in condensed matter. Although various power generators are made from them, all the known effects, such as Seebeck effect, require macroscopic temperature gradients; since the sign of the generated voltage is reversed by reversing the temperature gradient, the net voltage disappears when the temperature distribution fluctuates temporarily or spatially with a macroscopic temperature gradient of zero. It is impossible to utilize such temperature fluctuations in the conventional thermoelectric effects, a situation which limits their application. Here we report the observation of a second-order nonlinear thermoelectric effect; we develop a method to measure nonlinear thermoelectricity and observe that a superconducting MoGe film on Y3Fe5O12 generates a voltage proportional to the square of the applied temperature gradient. The nonlinear thermoelectric generation demonstrated here provides a way for making power generators that produce electric power from temperature fluctuations.
Structure prediction of alternative protein conformations
Authors: Bryant Patrick , Noé Frank
Published: August 2024

Proteins are dynamic molecules whose movements result in different conformations with different functions. Neural networks such as AlphaFold2 can predict the structure of single-chain proteins with conformations most likely to exist in the PDB. However, almost all protein structures with multiple conformations represented in the PDB have been used while training these models. Therefore, it is unclear whether alternative protein conformations can be genuinely predicted using these networks, or if they are simply reproduced from memory. Here, we train a structure prediction network, Cfold, on a conformational split of the PDB to generate alternative conformations. Cfold enables efficient exploration of the conformational landscape of monomeric protein structures. Over 50% of experimentally known nonredundant alternative protein conformations evaluated here are predicted with high accuracy (TM-score > 0.8).
Polarity transitions of narrow bipolar events in thundercloud tops reaching the lower stratosphere
Authors: Liu Feifan , Neubert Torsten , Chanrion Olivier , Lu Gaopeng , Wu Ting , Lyu Fanchao , Lyu Weitao , Köhn Christoph , Li Dongshuai , Zhu Baoyou , Lei Jiuhou
Published: August 2024

Blue corona discharges are often generated in thunderclouds penetrating into the stratosphere and are the optical manifestation of narrow bipolar events (NBEs) observed in radio signals. While their production appears to depend on convection, the cause and nature of such discharges are not well known. Here we show the observations by a lightning detection array of unusual amounts of 982 NBEs during a tropical storm on the coastline of China. NBEs of negative polarity are predominantly observed at the cloud top reaching the stratosphere, and positive NBEs are primarily at lower altitudes. We find that the dominant polarity changes with the typical time of development of thunderstorm cells, suggesting that the polarity depends on the phase of the storm cells. Furthermore, we find that the lightning jump of negative NBEs is associated with above-anvil cirrus plumes of ice crystals and water vapor in the lower stratosphere. We propose that variations in updrafts induce changes in the altitude and charge concentrations of the cloud layers, which lead to the polarity transition. Our results have implications for studies of the chemical perturbations of greenhouse gas concentrations by corona discharges at the tropopause.
Proteomic changes in Alzheimer’s disease associated with progressive Aβ plaque and tau tangle pathologies
Authors: Pichet Binette Alexa , Gaiteri Chris , Wennström Malin , Kumar Atul , Hristovska Ines , Spotorno Nicola , Salvadó Gemma , Strandberg Olof , Mathys Hansruedi , Tsai Li-Huei , Palmqvist Sebastian , Mattsson-Carlgren Niklas , Janelidze Shorena , Stomrud Erik , Vogel Jacob W. , Hansson Oskar
Published: August 2024

Proteomics can shed light on the dynamic and multifaceted alterations in neurodegenerative disorders like Alzheimer’s disease (AD). Combining radioligands measuring β-amyloid (Aβ) plaques and tau tangles with cerebrospinal fluid proteomics, we uncover molecular events mirroring different stages of AD pathology in living humans. We found 127 differentially abundant proteins (DAPs) across the AD spectrum. The strongest Aβ-related proteins were mainly expressed in glial cells and included SMOC1 and ITGAM. A dozen proteins linked to ATP metabolism and preferentially expressed in neurons were independently associated with tau tangle load and tau accumulation. Only 20% of the DAPs were also altered in other neurodegenerative diseases, underscoring AD’s distinct proteome. Two co-expression modules related, respectively, to protein metabolism and microglial immune response encompassed most DAPs, with opposing, staggered trajectories along the AD continuum. We unveil protein signatures associated with Aβ and tau proteinopathy in vivo, offering insights into complex neural responses and potential biomarkers and therapeutics targeting different disease stages.
High-speed aerial grasping using a soft drone with onboard perception
Authors: Ubellacker Samuel , Ray Aaron , Bern James M. , Strader Jared , Carlone Luca
Published: August 2024

Contrary to the stunning feats observed in birds of prey, aerial manipulation and grasping with flying robots still lack versatility and agility. Conventional approaches using rigid manipulators require precise positioning and are subject to large reaction forces at grasp, which limit performance at high speeds. The few reported examples of high-speed aerial grasping rely on motion capture systems, or fail to generalize across environments and grasp targets. We describe the first example of a soft aerial manipulator equipped with a fully onboard perception pipeline, capable of robustly localizing and grasping visually and morphologically varied objects. The proposed system features a novel passively closed tendon-actuated soft gripper that enables fast closure at grasp, while compensating for position errors, complying to the target-object morphology, and dampening reaction forces. The system includes an onboard perception pipeline that combines a neural-network-based semantic keypoint detector, a state-of-the-art robust 3D object pose estimator, and a fixed-lag smoother to estimate the pose of known objects. The resulting pose estimate is passed to a minimum-snap trajectory planner, tracked by an adaptive controller that fully compensates for the added mass of the grasped object. Finally, a finite-element-based controller determines optimal gripper configurations for grasping. Experiments on three different targets confirm that our approach enables dynamic, high-speed, and versatile grasping, all of which are necessary capabilities for tasks such as rapid package delivery or emergency relief. We demonstrate fully onboard vision-based grasps of a variety of objects, in both indoor and outdoor environments, and up to speeds of 2.0 m/s—the fastest vision-based grasp reported in the literature. Finally, we take a major step in expanding the utility of our platform beyond stationary targets, by demonstrating motion-capture-based grasps of targets moving up to 0.3 m/s, with relative speeds up to 1.5 m/s.
Life cycle assessment methods for investigating novel food packaging systems
Authors: Bremenkamp Ina , Sousa Gallagher Maria J.
Published: August 2024

The high volume of plastic waste generated and its potential harm to wildlife and ecosystems are negative consequences of poor end-of-life food packaging management.
An electrochemical biosensor equipped with a logic circuit as a smart automaton for two-miRNA pattern detection
Authors: Xie Benting , Du Shimao , Gao Hejun , Zhang Juan , Fu Hongquan , Liao Yunwen
Published: August 2024

Detecting multiple targets in complex cellular and biological environments yields more reliable results than single-label assays.
NIR light-triggered bursting of double-emulsion drops (DEDs) for microdroplet generation
Authors: Lu Zhaoze , Yu Jian , Wang Kaihua , Cheng Wei , Hou Likai
Published: August 2024

This work presents a method for generating micro-droplets in several micron by using a near-infrared (NIR) light-triggered double emulsion drop (DED) bursting.
Sr4Al14O25:Li+,Mn4+ phosphor-in-glass film: erosion behavior and luminescence property
Authors: Liu Yunzheng , Yang Haoyu , Jiang Haohui , Ma Daoyuan , Fang Wenfa , Xia Libin
Published: August 2024

At present, phosphor-in-glass is regarded as a superior encapsulation material substituting for organic materials to resolve the poor thermal stability of WLEDs.
Single-molecule force spectroscopy shows that side chain interactions govern the mechanochemical response of polypeptide α-helices and prevent the formation of β-sheets
Authors: Asano Marie , Sluysmans Damien , Willet Nicolas , Bonduelle Colin , Lecommandoux Sébastien , Duwez Anne-Sophie
Published: August 2024

AFM single-molecule experiments on poly(l-glutamic acid) and poly(l-lysine) show that hydrophobic side chain interactions stabilize α-helices and inhibit the formation of a metastable β-sheet-like structure under mechanical deformation.
Illuminating the multiple Lewis acidity of triaryl-boranes via atropisomeric dative adducts
Authors: Kovács Benjámin , Földes Tamás , Szabó Márk , Dorkó Éva , Kótai Bianka , Laczkó Gergely , Holczbauer Tamás , Domján Attila , Pápai Imre , Soós Tibor
Published: August 2024

The emergence of a peculiar molecular phenomenon, the single-centered, but multiple Lewis acidity, is uncovered among Lewis acidic boranes with appropriate steric crowding and symmetry design.
Rationally engineering a binary SnS0.5Se0.5/carbon nest-coated Si nanosphere for a high-performance lithium-ion battery anode
Authors: Zhang Hui , Tao Kehao , Zeng Xiangbing , Chen Chengbing , Zhu Yajun , Han Tianli , Li Jinjin , Liu Jinyun
Published: August 2024

A nanohybrid composed of core-nest structured Si@SnS0.5Se0.5/carbon is developed using silicon as the core and SnS0.5Se0.5/carbon as a binary nest, displaying a high performance, which is significant for engineering many energy-storage composites.
Breakthrough in the large area photoanode fabrication process: high concentration precursor solution with solvent mixing and one step spin coating for high PEC performance of BiVO4
Authors: Lee Hoyoung , Kang Gil-Seong , Lim Hanyi , Han Hyobin , Kim Tae Woo , Choi Jun-Hyuk , Choi Dae-Geun , Jung Joo-Yun , Jeong Jun-Ho , Park Jong Hyeok , Lee Jihye
Published: August 2024

In this study, we present a streamlined method to fabricate high-efficiency BiVO4 films using one-step spin coating, suitable for large-scale production, enabling cost-effective BiVO4 photoanodes that generate high current under sunlight.
Interlayer-release synthesis of Cu single atoms anchored on a heterogeneous photocatalyst for constructing Cu–Ov–Fe bimetallic active sites with ultrafast kinetics of activation of H2O2
Authors: Chen Changdong , Shang Yan , Shao Shihui , Wang Wei , Zhu Jiahao , Gao Ying , Chen Lei , Wang Fangfang
Published: August 2024

Ovs act as electron trap sites, directly driving the photoelectrons towards adjacent bimetallic active sites through Ov-metal pathways.
Optical constants manipulation of formamidinium lead iodide perovskites: ellipsometric and spectroscopic twigging
Authors: Khan Mohd Taukeer , Haris Muhammed P. U. , Alhouri Baraa , Kazim Samrana , Ahmad Shahzada
Published: August 2024

Unraveling the knowledge of the complex refractive index and photophysical properties of the perovskite layer is paramount to uncovering the physical process that occurs in a perovskite solar cell under illumination.
Highly conductive flat grains of cesium lead bromide perovskites via additive engineering with methylammonium bromide
Authors: Pathak Chandra Shakher , Aloysius Deepak , Gupta Satyajit , Mukhopadhyay Sabyasachi , Edri Eran
Published: August 2024

Methylammonium bromide yields highly conductive flat grains of cesium lead bromide perovskites.
Anti‐sloshing control: Flatness‐based trajectory planning and tracking control with an integrated extended state observer
Authors: Viet Khanh Nguyen , Duc Minh Do , Duc Thanh Cao , Nguyen Tung Lam
Published: August 2024

The phenomenon of sloshing causes a significantly negative impact on a wide range of industries. A time‐optimal flatness‐based trajectory planning and Lyapunov‐based model predictive control (LMPC) is proposed for trajectory tracking of a transmitting cylindrical container filled with liquid. Firstly, this research presents an equivalent discrete model based on a mass‐spring‐damper system. Subsequently, after the flatness of the adopted non‐linear model for 2D is established, time‐optimal trajectories are introduced. A control method called LMPC is shown to solve the problem of orbital tracking, which allows setting limits for state variables. In addition, to ensure system performance, a linear extended state observer (LESO) is integrated to cope with system uncertainties. Finally, the efficiency of the proposed approach for liquid sloshing suppression and tracking is illustrated by simulations.
Generation of dual‐mode PS‐OAM beams using a Vivaldi antenna array
Authors: Li Na , Feng Guirong , Jiao Lingling , Li Ping , Shi Xiaowei
Published: August 2024

The paper proposes a single antenna that can generate dual‐mode plane spiral orbital angular momentum (PS‐OAM) beams. Six Vivaldi antennas placed in a tangential circular array make up the antenna, and the antenna is etched onto a substrate material and has a flat design, allowing for easy integration with other system components. The neighbouring ports of the antenna elements have phase differences, so phase‐shifting in the feeding network is unnecessary. When fed with the same phase and amplitude, the antenna can produce PS‐OAM beams with mode +1 at 7 GHz and mode +2 at 14 GHz, and the measured purity is 80.6% and 63%, respectively. The method may provide a new way to produce multi‐mode orbital angular momentum.
Distributed optimization control strategy for distribution network based on the cooperation of distributed generations
Authors: Hua Dong , Liu Suisheng , Liu Yiqing , Le Jian , Zhou Qian
Published: August 2024

Aiming to improve the voltage distribution and realize the proportional sharing of active and reactive power in the distribution network (DN), this article proposes a distributed optimal control strategy based on the grouping cooperation mechanism of the distributed generation (DG). The proposed strategy integrates the local information of the DG and the global information of the DN. Considering the high resistance/reactance ratio of DN, distributed optimization control strategies for node voltage control and active power management are developed with the consensus variable of active utilization rate. And distributed strategy for reactive power management is proposed with a consensus variable of reactive utilization rate. The convergence of the distributed control system for each group is proved. The validity and robustness of the proposed strategy are verified by several simulations in the IEEE 33‐bus system.
Two metamorphic cycles recorded by monazite in eclogite-facies gneisses (Southern Armorican Massif, France): A Cambro-Ordovician continental crust involved in eo-Variscan subduction
Authors: Bosse Valérie , Godard Gaston , Devidal Jean Luc , Mallens Julie , Shea Thomas
Published: August 2024

We present U-Th/Pb data obtained for xenotime and monazite from the polycyclic eclogite-facies para- and ortho-gneisses of the Les Essarts Unit (Vendée, southern Armorican Massif, France), which have recorded an HT-LP cycle ending with a first retrogression and a subsequent HP eclogite-facies metamorphism similar to that of the neighbouring eclogites. Some paragneisses and orthogneisses are only slightly deformed and retrogressed, showing the structure of nebulitic migmatite or metagranite, respectively; both show well-preserved complex coronitic and pseudomorphic microstructures, due to the eclogite-facies metamorphism. Monazite I and xenotime crystallised during the HT stage providing an opportunity to date the early HT metamorphic event in the paragneiss and the emplacement of granite in the orthogneiss. U/Pb ages obtained from monazite I and xenotime of the cordierite-bearing migmatitic paragneisses range between 510 and 480 Ma (Late Cambrian-Early Ordovician). These ages may correspond to the crystallisation and/or re-equilibration of monazite and xenotime during the prograde stage of the HT cycle, close to the T peak. Consistent monazite and xenotime U/Pb ages around 496 Ma in the orthogneiss represent the age of the granite protolith. During subsequent HP overprint in the gneisses, numerous coronas developed at the expense of the early HT parageneses, in particular plagioclase. In both paragneiss and orthogneiss, monazite I in contact with HT plagioclase reacted to form apatite + zoisite + monazite II coronas. The small monazite II crystals could be dated in a paragneiss sample and gave a lower intercept age of 395 ± 9 Ma, interpreted as the age of the eclogite-facies HP metamorphism. This age is in agreement with those obtained in HP metamorphic rocks of the Upper Allochthon Unit of the Iberian-Armorican Arc (Bragança, Cabo-Ortegal, Audierne) representing the first evidence of convergence in the Variscan cycle.
S2k-Leitlinie Klinische Ernährung in der Hepatologie
Authors: Plauth Mathias , Bechmann Lars , Grajecki Donata , Gundling Felix , Kramer Ludwig , Kremer Andreas E. , Rau Monika , Schneider Andrea , Tacke Frank , van Thiel Ingo
Published: August 2024

Ziel Sowohl Über- als auch Unterernährung spielen für die Prognose von
Patienten mit Leberkrankheiten eine bedeutende Rolle. Bei chronischer
Leberkrankheit besteht häufig eine Mangelernährung mit gestörter
Körperzusammensetzung, allerdings zeigt sich in den letzten Jahren ein Wandel
des klinischen Spektrums mit Zunahme von Adipositas und sarkopener Adipositas.
In der klinischen Praxis wird das Potenzial der Ernährungstherapie als
metabolisches Management einer Leberkrankheit oft unterschätzt und nicht
ausgeschöpft. Mit der Aktualisierung dieser Leitlinie sollen umfassende aktuelle
und evidenzbasierte Empfehlungen für die Ernährungstherapie von Patienten mit
Lebererkrankungen gegeben werden.

Methoden Frühere Leitlinien der Deutschen und der Europäischen
Gesellschaften für Ernährungsmedizin (DGEM, ESPEN) zur Ernährung von Patienten
mit Lebererkrankungen wurden entsprechend den Prinzipien der AWMF
(Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften)
und ÄZQ (Ärztliche Zentralstelle für Qualitätssicherung) aktualisiert und
vollständig überarbeitet und erweitert.

Ergebnisse Die vorliegende Leitlinie umfasst 110 im
Konsentierungsverfahren ermittelte Aussagen und Empfehlungen zum
ernährungsmedizinischen metabolischen Management leberkranker Patienten im
Hinblick auf pathophysiologische Grundlagen, Indikationsstellung und
Durchführung einer Ernährungstherapie sowie ihrer Ergebnisse. Empfehlungen
werden für die Krankheitsbilder akutes Leberversagen (ALV), alkoholassoziierte
Lebererkrankung (ALD), metabolische Dysfunktion-assoziierte Fettleberkrankheit
(MASLD), Leberzirrhose (LZ), Lebertransplantation und Operation sowie
ernährungsbedingte Leberschädigung (NALI) gegeben.

Schlussfolgerung Bei Patienten mit chronischer Lebererkrankung liegt
häufig ein prognostisch ungünstiger metabolischer Status vor mit gestörter
Körperzusammensetzung und Mangelernährung oder Adipositas; diese Patientengruppe
profitiert von einem evidenzbasierten ernährungsmedizinischen metabolischen
Management. Bei Patienten mit akutem Leberversagen ist die Datenlage wesentlich
unsicherer, da nur wenige Studiendaten für diese schwere, aber seltene
Erkrankung vorliegen.
Electroconvulsive Therapy Versus Aripiprazole Addition to Clozapine
in Patients with Clozapine-Resistant Symptoms (EMECLO): A Protocol of a
Single-Blind, Multicenter, Randomized-Controlled Feasibility
Trial
Authors: den Toom Manouk , Blanken Laura , Horn Inge , Veerman Selene , van der Vlugt-Molenaar Joris J. B. , de Koning Mariken B. , Bogers Jan , Enterman John , de Jonge Martin , Cianci Daniela , Frederix Gerardus W. J. , de Haas Hans J. , Storosum Bram W. , Veereschild Mike , Javadzadeh Martin , Schulte Peter F. J. , Cohen Dan , van Os Jim , Cahn Wiepke , de Haan Lieuwe , Zantvoord Jasper B. , Luykx Jurjen J.
Published: August 2024

Background Currently, guidance on the most effective treatment for
patients with clozapine-resistant schizophrenia-spectrum disorders (SSD) is
lacking. While augmentation strategies to clozapine with aripiprazole and
electroconvulsive therapy (ECT) have been demonstrated to be effective in
patients with clozapine-resistant schizophrenia spectrum disorders (CRS),
head-to-head comparisons between these addition strategies are unavailable. We
therefore aim to examine the feasibility of a larger randomized, single-blind
trial comparing the effectiveness, cost-effectiveness, and safety of
aripiprazole addition vs. ECT addition in CRS.

Methods In this multi-center, randomized, single-blind feasibility study,
the feasibility of recruiting 20 participants with CRS who will be randomized to
either aripiprazole or bilateral ECT addition will be assessed. The main
endpoint is the number of patients willing to be randomized. The number of
screened individuals and reasons to decline participation will be recorded.
Effects will be estimated for the benefit of the foreseen larger trial. To that
end, differences between both arms in symptom severity will be assessed using
blinded video assessments. In addition, tolerability (e. g., cognitive
functioning), safety, quality of life, recovery, and all-cause discontinuation
will be compared. The follow-up period is 16 weeks, after which non-responders
will be given the option to switch to the other treatment.

Discussion Strengths of this feasibility trial include maintaining
blinding with video assessment, a possibility to switch groups in case of
non-response, and a broad set of outcome measures. Identification of factors
contributing to non-participation and drop-out will generate valuable
information on trial feasibility and may enhance recruitment strategies in a
follow-up RCT.

Trial registration The study has been approved by the Medical Research
Ethics Committee of the Amsterdam University Medical Center, location AMC, and
was registered on 1 May 2022 in the EU Clinical Trials Register (EudraCT) under
the trial name ‘EMECLO’ (2021–006333–19).
Can Opportunistic Use of Computed Tomography Help Reveal the Association Between Hepatic Steatosis and Disease Severity in Hospitalized COVID-19 Patients?
Authors: Parlak Ayşe Eda , Erdem Toslak Iclal , Turkoglu Selcuk Nursel
Published: August 2024

To measure hepatic steatosis (HS) in hospitalized COVID-19 patients using unenhanced chest computed tomography (CT) imaging and to evaluate the relationship between disease severity and prognosis in adult patients.

This retrospective study included 152 consecutive hospitalized COVID-19 patients with a positive reverse transcriptase polymerase chain reaction (RT-PCR) test. The COVID-19 Reporting and Data System (CO-RADS) and the chest CT score were evaluated. HS measurements were performed based on CT images using a single region of interest placed on the right liver lobe (segments V-VII). HS was defined as a liver attenuation value <40 Hounsfield units. Data were collected and compared with the patients’ prognostic parameters.

Of the 152 inpatients, 137 patients (90.1%) had a CT score ≥3 and 109 patients (71.7%) had a CO-RADS score ≥4, 43 (28.2%) had HS. All patients with HS (100%) and 94/109 (86.2%) patients without HS had a CT score ≥3. There was a statistically significant difference between the two groups in terms of chest CT score (p=0.006). There was no statistically significant difference between the two groups in terms of CO-RADS score (p=0.291). The median CRP levels were significantly increased in patients with HS compared to patients without HS (p=0.023). There was no significant difference in ICU hospitalization and mortality due to the presence of HS (p>0.05).

The current study revealed significantly higher chest CT scores in COVID-19 patients with HS measured on CT compared to those without HS. Opportunistic use of CT images for the detection of HS can be considered as an adjunctive tool in the risk analysis of COVID-19 patients hospitalized due to COVID-19 pneumonia.

The severity of COVID-19 disease is increased in hospitalized patients with hepatosteatosis compared to patients with a normal liver. Density measurements for the evaluation of HS using opportunistic CT applications can be considered as an adjunctive tool in the prognostic evaluation of hospitalized patients with COVID-19 pneumonia.
Association Study Between DRD2, DRD3 Genetic Polymorphisms and
Adverse Reactions in Chinese Patients on Amisulpride Treatment
Authors: Qu Kankan , He Yanan , Zhang Zhongdong , Cao Yeli , Qin Qiyun , Zhou Zhenhe , Zhen Lili
Published: August 2024

Objective To determine if the cardiac function and “endocrinium” of
Chinese patients are associated with dopamine D2 (DRD2)
(rs6276) and DRD3 (rs6280, rs963468) genetic
polymorphisms when treated with amisulpride.

Methods This study enrolled 148 patients with schizophrenia who took
amisulpride orally for 8 weeks. DRD2 (rs6276) and DRD3 (rs6280,
rs963468) genetic polymorphisms were detected with TaqMan-MGB allelic
discrimination.

Results Analysis by multivariate covariance analysis (MANCOVA) showed that
after adjusting for age, gender, and the baseline level, the increase in the
level of aspartate aminotransferase (AST) and creatine kinase (CK) in the
rs6276 AG group was higher than that in the AA and GG groups.
Similarly, the changed estradiol (E2) level in rs6276 GG and
rs963468 GG groups was higher than that in the other two groups.
Adjusting for covariates, the increased triglyceride (TG) level in rs6276
GG and rs963468 GG groups was the highest among their different genotype
groups. The increase in the level of “AST” in the rs6280 TT group was
higher than that in the CC and CT groups upon adjusting for covariates.
Similarly, MANCOVA showed that the increase in the level of “CK” in the
rs6280 CT group was higher than that in the CC and CT groups.
Besides, the increased level of “PRL” in the rs6280 CC group and
rs963468 GG group was higher than that in their other two genotypes
groups.

Conclusion
DRD2 (rs6276) and DRD3 (rs6280,
rs963468) polymorphisms can affect amisulpride tolerability since they
are associated with the observed adverse reactions, including cardiac
dysfunction and endocrine disorders in Chinese patients with schizophrenia.
A Phase 1b PK/PD Study to Demonstrate Antigen Elimination with RLYB212, a Monoclonal Anti-HPA-1a Antibody for FNAIT Prevention
Authors: Geisen Christof , Fleck Erika , Schäfer Stephan Martin Gastón , Walter Carmen , Braeuninger Susanne , Jensen Jens Søndergaard , Sheridan Douglas , Patki Kiran , Armstrong Róisín , Skogen Bjørn , Behrens Frank , Seifried Erhard , Kjeldsen-Kragh Jens , Kjær Mette , Köhm Michaela
Published: August 2024

Background Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a rare bleeding disorder of the fetus/newborn caused by development of maternal alloantibodies against fetal human platelet antigens (HPAs), predominantly HPA-1a. Currently there are no treatments available to prevent maternal alloimmunization to HPAs or FNAIT.

Methods This proof-of-concept study (EudraCT Number: 2021-005380-49) was designed to assess the ability of subcutaneous (SC) RLYB212, a monoclonal anti-HPA-1a antibody, to eliminate HPA-1a-positive platelets in an antigen challenge model of a 30 mL fetal–maternal hemorrhage. Subjects were randomized to receive a single SC dose of RLYB212 or placebo on day 1 in a single-blinded manner, followed by transfusion of 10 × 109 HPA-1a-positive platelets on day 8.

Results Four subjects received 0.09 mg SC RLYB212, five received 0.29 mg SC RLYB212, and two received placebo. RLYB212 achieved rapid elimination of HPA-1a-positive platelets in a concentration-dependent manner, with concentrations as low as 3.57 ng/mL meeting the prespecified proof-of-concept criterion of ≥90% reduction in platelet elimination half-life versus placebo. Following HPA-1a-positive platelet transfusion, a rapid decline was observed in the concentration of RLYB212 over a period of 2 to 24 hours, corresponding to the time needed for RLYB212 to bind to ∼10% of HPA-1a on cell surfaces. RLYB212 was well tolerated with no reports of drug-related adverse events.

Conclusion The data from this study are consistent with preclinical efficacy data and support the potential use of RLYB212 as a prophylactic treatment for FNAIT that prevents maternal HPA-1a alloimmunization during at-risk pregnancies.
Shear Stress Promotes Remodeling of Platelet Glycosylation via Upregulation of Platelet Glycosidase Activity: One More Thing
Authors: Roka-Moiia Yana , Lewis Sabrina , Cleveland Estevan , Italiano Joseph E. , Slepian Marvin J.
Published: August 2024

Background Mechanical circulatory support (MCS) is a mainstay of therapy for advanced and end-stage heart failure. Accompanied by systemic anticoagulation, contemporary MCS has become less thrombogenic, with bleeding complications emerging as a major cause of readmission and 1-year mortality. Shear-mediated platelet dysfunction and thrombocytopenia of undefined etiology are primary drivers of MCS-related bleeding. Recently, it has been demonstrated that deprivation of platelet surface glycosylation is associated with the decline of hemostatic function, microvesiculation, and premature apoptosis. We test the hypothesis that shear stress induces remodeling of platelet surface glycosylation via upregulation of glycosidase activity, thus facilitating platelet count decline and intense microvesiculation.

Methods Human gel-filtered platelets were exposed to continuous shear stress in vitro. Platelets and platelet-derived microparticles (PDMPs) were quantified via flow cytometry using size standard fluorescent nanobeads. Platelet surface glycosylation and NEU1 expression were evaluated using lectin- or immune-staining and multicolor flow cytometry; lectin blotting was utilized to verify glycosylation of individual glycoproteins. Platelet neuraminidase, galactosidase, hexosaminidase, and mannosidase activities were quantified using 4-methylumbelliferone-based fluorogenic substrates.

Results We demonstrate that shear stress promotes selective remodeling of platelet glycosylation via downregulation of 2,6-sialylation, terminal galactose, and mannose, while 2,3-sialylation remains largely unchanged. Shear-mediated deglycosylation is partially attenuated by neuraminidase inhibitors, strongly suggesting the involvement of platelet neuraminidase in observed phenomena. Shear stress increases platelet NEU1 surface expression and potentiates generation of numerous NEU1+ PDMPs. Platelets exhibit high basal hexosaminidase and mannosidase activities; basal activities of platelet neuraminidase and galactosidase are rather low and are significantly upregulated by shear stress. Shear stress of increased magnitude and duration promotes an incremental decline of platelet count and immense microvesiculation, both being further exacerbated by neuraminidase and partially attenuated by neuraminidase inhibition.

Conclusion Our data indicate that shear stress accumulation, consistent with supraphysiologic conditions of device-supported circulation, promotes remodeling of platelet glycosylation via selective upregulation of platelet glycosidase activity. Shear-mediated platelet deglycosylation is associated with platelet count drop and increased microvesiculation, thus offering a direct link between deglycosylation and thrombocytopenia observed in device-supported patients. Based on our findings, we propose a panel of molecular markers to be used for reliable detection of shear-mediated platelet deglycosylation in MCS.
From Filters to Scalpels—Understanding Perceptions of Facial Asymmetry: An AAFPRS Survey
Authors: Abraham-Aggarwal Kiran , Chen Xiaoxuan , Parsa Keon M. , Frodel John L.
Published: August 2024

Facial asymmetries can significantly affect patient satisfaction post-surgery. Social media can impact a patient's perception of their asymmetries. To gather insights into the practices, perceptions, and approaches concerning facial asymmetry among facial plastic surgeons. The aim of this study was to understand the impact of social media on perceptions of facial asymmetry. This is an American Academy of Facial Plastic and Reconstructive Surgeons (AAFPRS) survey consisting of 46 questions that sought to understand facial plastic surgeons' perceptions of facial asymmetry, their consultation process, their patients' perspectives on their own facial asymmetries, and patient satisfaction. The survey was distributed to 1,269 members of AAFPRS across community hospitals, private practices, and academic hospitals. Sixty-seven members completed the survey. The survey revealed that 31% (21) of surgeons face challenges in managing patient expectations regarding facial asymmetry. In addition, 12% (8) of surgeons felt that patients did not initially recognize their own asymmetries. Eighty-seven percent (58) of surgeons emphasize the natural occurrence of asymmetry during consultations to set realistic expectations. This study emphasizes the need for thorough patient education during initial consultations to align expectations with achievable outcomes. Surgeons should explain the natural occurrence of asymmetry clearly and use digital imaging to show patients realistic previews of surgical results.
Split Dorsal Nasal Flap: A Modification to Expand Its Utilization
Authors: Macielak Robert J. , Schmidtman Daniel C. , Recker Chelsey A. , Hamilton Grant S.
Published: August 2024

Nasal reconstruction presents the facial plastic surgeon with a complex problem given its functional and aesthetic importance. The dorsal nasal flap is a composite rotational flap of the glabella and nasal dorsum that can be used for nasal dorsum and tip defects of medium to large sizes. Given its composite nature, this flap can be split into its constituent parts—the epidermis and dermis and the subcutaneous tissue and superficial musculoaponeurotic system—without flap loss. This case series describes this technique and various potential applications within nasal reconstruction.
Characterizing Hearing Outcomes Following Treatment of Cerebellopontine Angle Meningiomas
Authors: Papazian Michael , Cottrell Justin , Pan Lydia , Kay-Rivest Emily , Friedmann David R. , Jethanamest Daniel , Kondziolka Douglas , Pacione Donato , Sen Chandranath , Golfinos John G. , Roland J. Thomas , McMenomey Sean O.
Published: August 2024

Objectives To characterize treatment and hearing outcomes for cerebellopontine angle (CPA) meningiomas with inherent risks of hearing loss and identify predictors of hearing loss for surgically treated lesions.

Design Retrospective chart review.

Setting Tertiary care medical center.

Participants Adult patients with CPA meningiomas impinging upon cranial nerve VIII and/or pretreatment hearing loss managed with microsurgery or stereotactic radiosurgery (SRS) with Gamma Knife at our center between 2012 and 2023.

Main Outcome Measures Hearing preservation rate was determined from analysis of patients with pretreatment serviceable hearing for whom hearing-preserving treatment was attempted. Surgical patients were further analyzed using multivariable Cox proportional hazards regression models to identify factors predictive of postoperative hearing loss.

Results We identified 80 patients with CPA meningiomas meeting inclusion criteria who were managed with either microsurgery (43, 54%) or radiosurgery (37, 46%). Following SRS, hearing was preserved in 88% of cases. Following microsurgery, hearing was preserved in 71% of patients—all patients who lost hearing had tumors involving the internal auditory canal (IAC). Among surgical patients only, multivariable analysis accounting for preoperative hearing, recurrence status, lesion size, and patient age, the preoperative imaging finding that the CPA meningioma surrounded the vestibulocochlear nerve was significantly associated with hearing loss (hazard ratio: 10.3, 95% confidence interval: 1.3–81.4, p = 0.02).

Conclusion Most patients with meningiomas of the CPA can experience preservation of hearing, even when there is risk of hearing loss based on pretreatment evaluation. IAC invasion and surrounding of eighth nerve by tumor may portend poorer hearing outcomes in surgically managed patients.
Precision Medicine in Angelman Syndrome
Authors: Manssen Lena , Krey Ilona , Gburek-Augustat Janina , von Hagen Cornelia , Lemke Johannes R. , Merkenschlager Andreas , Weigand Heike , Makowski Christine
Published: August 2024

Angelman syndrome (AS) is a rare neurogenetic disorder caused by a loss of function of UBE3A on the maternal allele. Clinical features include severe neurodevelopmental delay, epilepsy, sleep disturbances, and behavioral disorders. Therapy currently evolves from conventional symptomatic, supportive, and antiseizure treatments toward alteration of mRNA expression, which is subject of several ongoing clinical trials.

This article will provide an overview of clinical research and therapeutic approaches on AS.