bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hippo pathway in non-small cell lung cancer: mechanisms, potential targets, and biomarkers
Authors: Liang Hongge , Xu Yan , Zhao Jing , Chen Minjiang , Wang Mengzhao 
Published: March 2024

AbstractLung cancer is the primary contributor to cancer-related deaths globally, and non-small cell lung cancer (NSCLC) constitutes around 85% of all lung cancer cases. Recently, the emergence of targeted therapy and immunotherapy revolutionized the treatment of NSCLC and greatly improved patients’ survival. However, drug resistance is inevitable, and extensive research has demonstrated that the Hippo pathway plays a crucial role in the development of drug resistance in NSCLC. The Hippo pathway is a highly conserved signaling pathway that is essential for various biological processes, including organ development, maintenance of epithelial balance, tissue regeneration, wound healing, and immune regulation. This pathway exerts its effects through two key transcription factors, namely Yes-associated protein (YAP) and transcriptional co-activator PDZ-binding motif (TAZ). They regulate gene expression by interacting with the transcriptional-enhanced associate domain (TEAD) family. In recent years, this pathway has been extensively studied in NSCLC. The review summarizes a comprehensive overview of the involvement of this pathway in NSCLC, and discusses the mechanisms of drug resistance, potential targets, and biomarkers associated with this pathway in NSCLC.
The potential key role of choroidal non-perfusion and rod degeneration in the pathogenesis of macular neovascularization type 3
Authors: Haj Najeeb Bilal , Schmidt-Erfurth Ursula 
Published: March 2024

AbstractMacular neovascularization type 3 (MNV3) is a multifactorial disease with distinct epidemiological, clinical, pathomorphological and topographical characteristics. This review of the literature discusses the latest experimental and clinical outcomes that could explain the pathogenesis of retinal neovascularization. Although patients with MNV3 are usually older than those with MNV1 or 2, their lesions do not coexist with, precede, or follow other types in the same eye. The regional distribution of MNV3 lesions is characterized as confined to the parafoveal macula without any involvement of the rod-free foveal area. Focal outer retinal atrophy and choroidal non-perfusion are the main structural features that occur prior to the development of retinal neovascularization. Also, histological and experimental studies of MNV3 and other non-neovascular age-related macular degeneration diseases complicated with MNV3-like lesions strongly suggest rod degeneration contributes to the pathogenesis. Therefore, the retinal neovascularization in MNV3 has a different pathogenesis from the choroidal neovascularization in MNV1 and 2 and emerging evidence indicates that choroidal non-prefusion and rod degeneration play a key role in the pathogenesis of MNV3. Accordingly, we suggest a sequence of pathological events that start with choroidal non-perfusion due to advanced age followed by hypoxia of the outer retina at the parafoveal area. This induces a remarkable degeneration of rods that triggers the growth of retinal neovascularization due to the imbalance of the angiogenic factors in the outer retina.
Synthesis of meta-carbonyl phenols and anilines
Authors: Zhao Bao-Yin , Jia Qiong , Wang Yong-Qiang 
Published: March 2024

AbstractPhenols and anilines are of extreme importance for medicinal chemistry and material science. The development of efficient approaches to prepare both compounds has thus long been a vital research topic. The utility of phenols and anilines directly reflects the identity and pattern of substituents on the benzenoid ring. Electrophilic substitutions remain among the most powerful synthetic methods to substituted phenols and anilines, yet in principle achieving ortho- and para-substituted products. Therefore, the selective preparation of meta-substituted phenols and anilines is the most significant challenge. We herein report an efficient copper-catalyzed dehydrogenation strategy to exclusively synthesize meta-carbonyl phenols and anilines from carbonyl substituted cyclohexanes. Mechanistic studies indicate that this transformation undergoes a copper-catalyzed dehydrogenation/allylic hydroxylation or amination/oxidative dehydrogenation/aromatization cascade process.
Ferroelectric compute-in-memory annealer for combinatorial optimization problems
Authors: Yin Xunzhao , Qian Yu , Vardar Alptekin , Günther Marcel , Müller Franz , Laleni Nellie , Zhao Zijian , Jiang Zhouhang , Shi Zhiguo , Shi Yiyu , Gong Xiao , Zhuo Cheng , Kämpfe Thomas , Ni Kai 
Published: March 2024

AbstractComputationally hard combinatorial optimization problems (COPs) are ubiquitous in many applications. Various digital annealers, dynamical Ising machines, and quantum/photonic systems have been developed for solving COPs, but they still suffer from the memory access issue, scalability, restricted applicability to certain types of COPs, and VLSI-incompatibility, respectively. Here we report a ferroelectric field effect transistor (FeFET) based compute-in-memory (CiM) annealer for solving larger-scale COPs efficiently. Our CiM annealer converts COPs into quadratic unconstrained binary optimization (QUBO) formulations, and uniquely accelerates in-situ the core vector-matrix-vector (VMV) multiplication operations of QUBO formulations in a single step. Specifically, the three-terminal FeFET structure allows for lossless compression of the stored QUBO matrix, achieving a remarkably 75% chip size saving when solving Max-Cut problems. A multi-epoch simulated annealing (MESA) algorithm is proposed for efficient annealing, achieving up to 27% better solution and ~ 2X speedup than conventional simulated annealing. Experimental validation is performed using the first integrated FeFET chip on 28nm HKMG CMOS technology, indicating great promise of FeFET CiM array in solving general COPs.
A fast-acting lipid checkpoint in G1 prevents mitotic defects
Authors: Köberlin Marielle S. , Fan Yilin , Liu Chad , Chung Mingyu , Pinto Antonio F. M. , Jackson Peter K. , Saghatelian Alan , Meyer Tobias 
Published: March 2024

AbstractLipid synthesis increases during the cell cycle to ensure sufficient membrane mass, but how insufficient synthesis restricts cell-cycle entry is not understood. Here, we identify a lipid checkpoint in G1 phase of the mammalian cell cycle by using live single-cell imaging, lipidome, and transcriptome analysis of a non-transformed cell. We show that synthesis of fatty acids in G1 not only increases lipid mass but extensively shifts the lipid composition to unsaturated phospholipids and neutral lipids. Strikingly, acute lowering of lipid synthesis rapidly activates the PERK/ATF4 endoplasmic reticulum (ER) stress pathway that blocks cell-cycle entry by increasing p21 levels, decreasing Cyclin D levels, and suppressing Retinoblastoma protein phosphorylation. Together, our study identifies a rapid anticipatory ER lipid checkpoint in G1 that prevents cells from starting the cell cycle as long as lipid synthesis is low, thereby preventing mitotic defects, which are triggered by low lipid synthesis much later in mitosis.
Pulse potential mediated selectivity for the electrocatalytic oxidation of glycerol to glyceric acid
Authors: Chen Wei , Zhang Liang , Xu Leitao , He Yuanqing , Pang Huan , Wang Shuangyin , Zou Yuqin 
Published: March 2024

AbstractPreventing the deactivation of noble metal-based catalysts due to self-oxidation and poisonous adsorption is a significant challenge in organic electro-oxidation. In this study, we employ a pulsed potential electrolysis strategy for the selective electrocatalytic oxidation of glycerol to glyceric acid over a Pt-based catalyst. In situ Fourier-transform infrared spectroscopy, quasi-in situ X-ray photoelectron spectroscopy, and finite element simulations reveal that the pulsed potential could tailor the catalyst’s oxidation and surface micro-environment. This prevents the overaccumulation of poisoning intermediate species and frees up active sites for the re-adsorption of OH adsorbate and glycerol. The pulsed potential electrolysis strategy results in a higher glyceric acid selectivity (81.8%) than constant-potential electrocatalysis with 0.7 VRHE (37.8%). This work offers an efficient strategy to mitigate the deactivation of noble metal-based electrocatalysts.
Autophagy formation, microtubule disorientation, and alteration of ATG8 and tubulin gene expression under simulated microgravity in Arabidopsis thaliana
Authors: Yemets Alla , Shadrina Ruslana , Blume Rostyslav , Plokhovska Svitlana , Blume Yaroslav 
Published: March 2024

AbstractAutophagy plays an important role in plant growth and development, pathogen invasion and modulates plant response and adaptation to various abiotic stress stimuli. The biogenesis and trafficking of autophagosomes involve microtubules (MTs) as important actors in the autophagic process. However, initiation of autophagy in plants under microgravity has not been previously studied. Here we demonstrate how simulated microgravity induces autophagy development involving microtubular reorganization during period of autophagosome formation. It was shown that induction of autophagy with maximal autophagosome formation in root cells of Arabidopsis thaliana is observed after 6 days of clinostating, along with MT disorganization, which leads to visible changes in root morphology. Gradual decrease of autophagosome number was indicated on 9th and 12th days of the experiment as well as no significant re-orientation of MTs were identified. Respectively, analysis of α- and β-tubulins and ATG8 gene expression was carried out. In particular, the most pronounced increase of expression on both 6th and 9th days in response to simulated microgravity was detected for non-paralogous AtATG8b, AtATG8f, AtATG8i, and AtTUA2, AtTUA3 genes, as well as for the pair of β-tubulin duplicates, namely AtTUB2 and AtTUB3. Overall, the main autophagic response was observed after 6 and 9 days of exposure to simulated microgravity, followed by adaptive response after 12 days. These findings provide a key basis for further studies of cellular mechanisms of autophagy and involvement of cytoskeletal structures in autophagy biogenesis under microgravity, which would enable development of new approaches, aimed on enhancing plant adaptation to microgravity.
Turning alterations detected by mobile health technology in idiopathic REM sleep behavior disorder
Authors: Zatti Cinzia , Pilotto Andrea , Hansen Clint , Rizzardi Andrea , Catania Marcello , Romijnders Robbin , Purin Leandro , Pasolini Maria P. , Schaeffer Eva , Galbiati Andrea , Ferini-Strambi Luigi , Berg Daniela , Maetzler Walter , Padovani Alessandro 
Published: March 2024

AbstractIdiopathic REM sleep Behavior Disorder (iRBD) is a condition at high risk of developing Parkinson’s disease (PD) and other alpha-synucleinopathies. The aim of the study was to evaluate subtle turning alterations by using Mobile health technology in iRBD individuals without subthreshold parkinsonism. A total of 148 participants (23 persons with polysomnography-confirmed iRBD without subthreshold parkinsonism, 60 drug-naïve PD patients, and 65 age-matched controls were included in this prospective cross-sectional study. All underwent a multidimensional assessment including cognitive and non-motor symptoms assessment. Then a Timed-Up-and-Go test (TUG) at normal and fast speed was performed using mobile health technology on the lower back (Rehagait®, Hasomed, Germany). Duration, mean, and peak angular velocities of the turns were compared using a multivariate model correcting for age and sex. Compared to controls, PD patients showed longer turn durations and lower mean and peak angular velocities of the turns in both TUGs (all p ≤ 0.001). iRBD participants also showed a longer turn duration and lower mean (p = 0.006) and peak angular velocities (p < 0.001) compared to controls, but only in the TUG at normal speed. Mobile health technology assessment identified subtle alterations of turning in subjects with iRBD in usual, but not fast speed. Longitudinal studies are warranted to evaluate the value of objective turning parameters in defining the risk of conversion to PD in iRBD and in tracking motor progression in prodromal PD.
Making drugs from T cells: The quantitative pharmacology of engineered T cell therapeutics
Authors: Kirouac Daniel C. , Zmurchok Cole , Morris Denise 
Published: March 2024

AbstractEngineered T cells have emerged as highly effective treatments for hematological cancers. Hundreds of clinical programs are underway in efforts to expand the efficacy, safety, and applications of this immuno-therapeutic modality. A primary challenge in developing these “living drugs” is the complexity of their pharmacology, as the drug product proliferates, differentiates, traffics between tissues, and evolves through interactions with patient immune systems. Using publicly available clinical data from Chimeric Antigen Receptor (CAR) T cells, we demonstrate how mathematical models can be used to quantify the relationships between product characteristics, patient physiology, pharmacokinetics and clinical outcomes. As scientists work to develop next-generation cell therapy products, mathematical models will be integral for contextualizing data and facilitating the translation of product designs to clinical strategy.
Biomimetic versus arbitrary motor control strategies for bionic hand skill learning
Authors: Schone Hunter R. , Udeozor Malcolm , Moninghoff Mae , Rispoli Beth , Vandersea James , Lock Blair , Hargrove Levi , Makin Tamar R. , Baker Chris I. 
Published: March 2024

AbstractA long-standing engineering ambition has been to design anthropomorphic bionic limbs: devices that look like and are controlled in the same way as the biological body (biomimetic). The untested assumption is that biomimetic motor control enhances device embodiment, learning, generalization and automaticity. To test this, we compared biomimetic and non-biomimetic control strategies for non-disabled participants when learning to control a wearable myoelectric bionic hand operated by an eight-channel electromyography pattern-recognition system. We compared motor learning across days and behavioural tasks for two training groups: biomimetic (mimicking the desired bionic hand gesture with biological hand) and arbitrary control (mapping an unrelated biological hand gesture with the desired bionic gesture). For both trained groups, training improved bionic limb control, reduced cognitive reliance and increased embodiment over the bionic hand. Biomimetic users had more intuitive and faster control early in training. Arbitrary users matched biomimetic performance later in training. Furthermore, arbitrary users showed increased generalization to a new control strategy. Collectively, our findings suggest that biomimetic and arbitrary control strategies provide different benefits. The optimal strategy is probably not strictly biomimetic, but rather a flexible strategy within the biomimetic-to-arbitrary spectrum, depending on the user, available training opportunities and user requirements.
In vitro and in vivo investigation of a thyroid hormone system-specific interaction with triazoles
Authors: Kadic Asya , Oles Patricia , Fischer Benjamin Christian , Reetz Anne Elisabeth , Sylla Boubacar Sidiki , Feiertag Katreece , Ritz Vera , Heise Tanja , Marx-Stoelting Philip , Tralau Tewes , Renko Kostja , Solano Marize de Lourdes Marzo 
Published: March 2024

AbstractAlterations in thyroid hormones (TH) and thyroid-stimulating hormone levels are frequently found following exposure to chemicals of concern. Dysregulation of TH levels can severely perturb physiological growth, metabolism, differentiation, homeostasis in the adult and developmental processes in utero. A frequently identified mode of action for this interaction is the induction of hepatic detoxification mechanisms (e.g. SULTs and UGTs), which lead to TH conjugation and elimination and therefore interfere with hormonal homeostasis, fulfilling the endocrine disruptors (EDs) definition. A short-term study in rats with dietary exposure to cyproconazole, epoxiconazole and prochloraz was conducted and hepatocyte hypertrophy, hepatic UGT activity and Phase 1/2 gene expression inductions were observed together with changes in TH levels and thyroid follicular hypertrophy and hyperplasia. To test for specific interaction with the thyroid hormone system, in vitro assays were conducted covering thyroidal I-uptake (NIS), TH transmembranal transport via MCT8 and thyroid peroxidase (TPO) function. Assays for iodothyronine deiodinases (DIO1–DIO3) and iodotyrosine deiodinase (DEHAL1) were included, and from the animal experiment, Dio1 and Dehal1 activities were measured in kidney and liver as relevant local indicators and endpoints. The fungicides did not affect any TH-specific KEs, in vitro and in vivo, thereby suggesting hepatic conjugation as the dominant MoA.
Multiple-pathways light modulation in Pleurosigma strigosum bi-raphid diatom
Authors: De Tommasi Edoardo , Rea Ilaria , Ferrara Maria Antonietta , De Stefano Luca , De Stefano Mario , Al-Handal Adil Y. , Stamenković Marija , Wulff Angela 
Published: March 2024

AbstractOrdered, quasi-ordered, and even disordered nanostructures can be identified as constituent components of several protists, plants and animals, making possible an efficient manipulation of light for intra- and inter- species communication, camouflage, or for the enhancement of primary production. Diatoms are ubiquitous unicellular microalgae inhabiting all the aquatic environments on Earth. They developed, through tens of millions of years of evolution, ultrastructured silica cell walls, the frustules, able to handle optical radiation through multiple diffractive, refractive, and wave-guiding processes, possibly at the basis of their high photosynthetic efficiency. In this study, we employed a range of imaging, spectroscopic and numerical techniques (including transmission imaging, digital holography, photoluminescence spectroscopy, and numerical simulations based on wide-angle beam propagation method) to identify and describe different mechanisms by which Pleurosigma strigosum frustules can modulate optical radiation of different spectral content. Finally, we correlated the optical response of the frustule to the interaction with light in living, individual cells within their aquatic environment following various irradiation treatments. The obtained results demonstrate the favorable transmission of photosynthetic active radiation inside the cell compared to potentially detrimental ultraviolet radiation.
The microcirculation in the first days of ICU admission in critically ill COVID-19 patients is influenced by severity of disease
Authors: Brouwer Fleur , Ince Can , Pols Jiska , Uz Zühre , Hilty Matthias Peter , Arbous Mendi Sesmu 
Published: March 2024

AbstractThe objective of this study was to investigate the relationship between sublingual microcirculatory parameters and the severity of the disease in critically ill coronavirus disease 2019 (COVID-19) patients in the initial period of Intensive Care Unit (ICU) admission in a phase of the COVID-19 pandemic where patients were being treated with anti-inflammatory medication. In total, 35 critically ill COVID-19 patients were included. Twenty-one critically ill COVID-19 patients with a Sequential Organ Failure Assessment (SOFA) score below or equal to 7 were compared to 14 critically ill COVID-19 patients with a SOFA score exceeding 7. All patients received dexamethasone and tocilizumab at ICU admission. Microcirculatory measurements were performed within the first five days of ICU admission, preferably as soon as possible after admission. An increase in diffusive capacity of the microcirculation (total vessel density, functional capillary density, capillary hematocrit) and increased perfusion of the tissues by red blood cells was found in the critically ill COVID-19 patients with a SOFA score of 7–9 compared to the critically ill COVID-19 patients with a SOFA score ≤ 7. No such effects were found in the convective component of the microcirculation. These effects occurred in the presence of administration of anti-inflammatory medication.
Deep learning-based forecasting of electricity consumption
Authors: Qureshi Momina , Arbab Masood Ahmad , Rehman Sadaqat ur 
Published: March 2024

AbstractBuilding energy management systems (BEMS) are integrated computerized systems that track and manage the energy use of many pieces of building-related machinery and equipment, including lighting, power systems, and HVAC systems. Modern buildings must have BEMSs in order to reduce energy usage while maintaining comfort. Not only for energy-saving purposes, BEMS is essential in enhancing the quality of the energy supply, which helps to gain a better understanding of how energy is used and the building's energy usage. When the dynamics of a building's energy usage are known, it is possible to determine which changes are most likely to reduce consumption. Numerous connected devices, operating modes, energy usage, and environmental factors can all be monitored and controlled in real-time using BEMS. Changing operating times and setting points to maximize comfort and efficiency is made simple by this. In this paper, we have primarily addressed the two significant issues of model optimization and electricity consumption forecasts. Future forecasting has been done using the LSTM based time series approach. We generated data on the amount of electricity consumed by a hospital facility and tested our suggested methodologies on actual data. The findings gained demonstrated that the strategies were successful with both types of data. On actual data, the trend in electricity consumption can be accurately predicted. Several model optimizers enhanced the suggested methods' performance as well. Our objective function gain accuracy result of 95%.
Association between DCP levels and kidney stone prevalence in US female adults based on NHANES data
Authors: Liu Heqian , Wang Jiawei , Tao Lingsong , Hao Yunwu 
Published: March 2024

AbstractOur study aimed to evaluate the correlation between levels of 2,4-DCP(2,4-Dichlorophenol) and 2,5-DCP(2,5-Dichlorophenol) and the prevalence of kidney stones in US female adults. Participants were chosen from the National Health and Nutrition Examination Survey database, spanning the years 2007–2016. Dose–response curves were analyzed using logistic regression, subgroup analyses, and other statistical methods to evaluate the relationship between 2,4-DCP and 2,5-DCP levels and the prevalence of kidney stones. The final study included 3220 participants aged over 20 years, with 252 females reporting a history of kidney stones. After accounting for all interfering variables, we found that every 0.1 ug/ml increase in 2.4-DCP correlated with a 1% rise in kidney stone prevalence (OR = 1.01, 95% CI 1.00, 1.01), whereas the same increase in 2.5-DCP was linked to a 27% growth in prevalence (OR = 1.27, 95% CI 1.01, 1.61). Sensitivity analysis was performed by triangulating 2,4-DCP and 2,5-DCP levels. The dose–response curves demonstrated a linear positive relationship between 2,4-DCP and 2,5-DCP levels and the risk of stone development. Our findings indicate a positive correlation between 2,4-DCP and 2,5-DCP levels and the prevalence of kidney stones in US female adults. This association is of clinical significance; however, a direct causal relationship cannot be definitively established.