bluuebunny/crossref_metadata_2025_split huggingface dataset:
Topical cyclosporine A cationic ophthalmic emulsion in paediatric vernal keratoconjunctivitis: pooled analysis of randomised NOVATIVE and VEKTIS trials
Authors: Leonardi Andrea , Doan Serge , Aragona Pasquale , Amrane Mourad , Ismail Dahlia , Montero Jesús , Németh János , Bremond-Gignac Dominique 
Published: December 2022

Abstract
Background/Objectives
Cyclosporine A cationic ophthalmic emulsion (CsA CE) was evaluated in paediatric and adolescent patients with vernal keratoconjunctivitis (VKC) in the NOVATIVE (NCT00328653) and VEKTIS (NCT01751126) trials. The similarity of these studies permitted pooled assessment of the effect of CsA CE on corneal damage as well as safety and tolerability.

Subjects/Methods
Pooled outcomes were assessed for the first 28 days of treatment. In NOVATIVE, 118 patients were randomised to 4 times daily (QID) CsA CE 0.05%, 0.1%, or vehicle eye drops. In VEKTIS, 169 patients were randomised to CsA CE 0.1% QID or twice daily (BID) or vehicle. For these analyses, treatment groups comprised: (1) pooled CsA CE 0.1% QID arms (high-dose; n = 96); (2) pooled CsA CE 0.05% QID arm from NOVATIVE and CsA CE 0.1% BID data from VEKTIS (low-dose; n = 93); and (3) pooled vehicle QID arms (vehicle; n = 98).

Results
Changes from baseline to day 28 (mean ± standard deviation) in corneal fluorescein staining (CFS) scores for CsA CE high-dose, low-dose, and vehicle groups were −1.6 ± 1.47 (95% CI: −0.9, −0.1; p = 0.0124 vs vehicle), −1.7 ± 1.39 (95% CI: −1.1, −0.3; p = 0.0015 vs vehicle), and −1.0 ± 1.55, respectively. Adverse events (AEs) of any type were reported in 37.5%, 34.4%, and 37.8% of the high-dose, low-dose, and vehicle groups, respectively. Most were mild or moderate in severity.

Conclusions
CsA CE significantly decreased corneal damage and was safe and well tolerated in patients with VKC. These data support CSA CE as a treatment option for the management of VKC.
Ligand recognition and activation of neuromedin U receptor 2
Authors: Zhao Wenli , Zhang Wenru , Wang Mu , Lu Minmin , Chen Shutian , Tang Tingting , Schnapp Gisela , Wagner Holger , Brennauer Albert , Yi Cuiying , Chu Xiaojing , Han Shuo , Wu Beili , Zhao Qiang 
Published: December 2022

AbstractNeuromedin U receptor 2 (NMU2), an emerging attractive target for treating obesity, has shown the capability in reducing food intake and regulating energy metabolism when activated. However, drug development of NMU2 was deferred partially due to the lack of structural information. Here, we present the cryo-electron microscopy (cryo-EM) structure of NMU2 bound to the endogenous agonist NmU-25 and Gi1 at 3.3 Å resolution. Combined with functional and computational data, the structure reveals the key factors that govern the recognition and selectivity of peptide agonist as well as non-peptide antagonist, providing the structural basis for design of novel and highly selective drugs targeting NMU2. In addition, a 25-degree rotation of Gi protein in reference to NMU2 is also observed compared in other structures of class A GPCR—Gi complexes, suggesting heterogeneity in the processes of G protein-coupled receptors (GPCRs) activation and G protein coupling.
Multiscale structural control of thiostannate chalcogels with two-dimensional crystalline constituents
Authors: Ha Thanh Duy Cam , Lee Heehyeon , Kang Yeo Kyung , Ahn Kyunghan , Jin Hyeong Min , Chung In , Kang Byungman , Oh Youngtak , Kim Myung-Gil 
Published: December 2022

AbstractChalcogenide aerogels (chalcogels) are amorphous structures widely known for their lack of localized structural control. This study, however, demonstrates a precise multiscale structural control through a thiostannate motif ([Sn2S6]4−)-transformation-induced self-assembly, yielding Na-Mn-Sn-S, Na-Mg-Sn-S, and Na-Sn(II)-Sn(IV)-S aerogels. The aerogels exhibited [Sn2S6]4−:Mn2+ stoichiometric-variation-induced-control of average specific surface areas (95–226 m2 g−1), thiostannate coordination networks (octahedral to tetrahedral), phase crystallinity (crystalline to amorphous), and hierarchical porous structures (micropore-intensive to mixed-pore state). In addition, these chalcogels successfully adopted the structural motifs and ion-exchange principles of two-dimensional layered metal sulfides (K2xMnxSn3-xS6, KMS-1), featuring a layer-by-layer stacking structure and effective radionuclide (Cs+, Sr2+)-control functionality. The thiostannate cluster-based gelation principle can be extended to afford Na-Mg-Sn-S and Na-Sn(II)-Sn(IV)-S chalcogels with the same structural features as the Na-Mn-Sn-S chalcogels (NMSCs). The study of NMSCs and their chalcogel family proves that the self-assembly principle of two-dimensional chalcogenide clusters can be used to design unique chalcogels with unprecedented structural hierarchy.
Glucose absorption drives cystogenesis in a human organoid-on-chip model of polycystic kidney disease
Authors: Li Sienna R. , Gulieva Ramila E. , Helms Louisa , Cruz Nelly M. , Vincent Thomas , Fu Hongxia , Himmelfarb Jonathan , Freedman Benjamin S. 
Published: December 2022

AbstractIn polycystic kidney disease (PKD), fluid-filled cysts arise from tubules in kidneys and other organs. Human kidney organoids can reconstitute PKD cystogenesis in a genetically specific way, but the mechanisms underlying cystogenesis remain elusive. Here we show that subjecting organoids to fluid shear stress in a PKD-on-a-chip microphysiological system promotes cyst expansion via an absorptive rather than a secretory pathway. A diffusive static condition partially substitutes for fluid flow, implicating volume and solute concentration as key mediators of this effect. Surprisingly, cyst-lining epithelia in organoids polarize outwards towards the media, arguing against a secretory mechanism. Rather, cyst formation is driven by glucose transport into lumens of outwards-facing epithelia, which can be blocked pharmacologically. In PKD mice, glucose is imported through cysts into the renal interstitium, which detaches from tubules to license expansion. Thus, absorption can mediate PKD cyst growth in human organoids, with implications for disease mechanism and potential for therapy development.
Effects of phytoplankton, viral communities, and warming on free-living and particle-associated marine prokaryotic community structure
Authors: Yeh Yi-Chun , Fuhrman Jed A. 
Published: December 2022

AbstractFree-living and particle-associated marine prokaryotes have physiological, genomic, and phylogenetic differences, yet factors influencing their temporal dynamics remain poorly constrained. In this study, we quantify the entire microbial community composition monthly over several years, including viruses, prokaryotes, phytoplankton, and total protists, from the San-Pedro Ocean Time-series using ribosomal RNA sequencing and viral metagenomics. Canonical analyses show that in addition to physicochemical factors, the double-stranded DNA viral community is the strongest factor predicting free-living prokaryotes, explaining 28% of variability, whereas the phytoplankton (via chloroplast 16S rRNA) community is strongest with particle-associated prokaryotes, explaining 31% of variability. Unexpectedly, protist community explains little variability. Our findings suggest that biotic interactions are significant determinants of the temporal dynamics of prokaryotes, and the relative importance of specific interactions varies depending on lifestyles. Also, warming influenced the prokaryotic community, which largely remained oligotrophic summer-like throughout 2014–15, with cyanobacterial populations shifting from cold-water ecotypes to warm-water ecotypes.
Photochemical diazidation of alkenes enabled by ligand-to-metal charge transfer and radical ligand transfer
Authors: Bian Kang-Jie , Kao Shih-Chieh , Nemoto David , Chen Xiao-Wei , West Julian G. 
Published: December 2022

AbstractVicinal diamines are privileged synthetic motifs in chemistry due to their prevalence and powerful applications in bioactive molecules, pharmaceuticals, and ligand design for transition metals. With organic diazides being regarded as modular precursors to vicinal diamines, enormous efforts have been devoted to developing efficient strategies to access organic diazide generated from olefins, themselves common feedstock chemicals. However, state-of-the-art methods for alkene diazidation rely on the usage of corrosive and expensive oxidants or complicated electrochemical setups, significantly limiting the substrate tolerance and practicality of these methods on large scale. Toward overcoming these limitations, here we show a photochemical diazidation of alkenes via iron-mediated ligand-to-metal charge transfer (LMCT) and radical ligand transfer (RLT). Leveraging the merger of these two reaction manifolds, we utilize a stable, earth abundant, and inexpensive iron salt to function as both radical initiator and terminator. Mild conditions, broad alkene scope and amenability to continuous-flow chemistry rendering the transformation photocatalytic were demonstrated. Preliminary mechanistic studies support the radical nature of the cooperative process in the photochemical diazidation, revealing this approach to be a powerful means of olefin difunctionalization.
Control of SARS-CoV-2 infection by MT1-MMP-mediated shedding of ACE2
Authors: Guo Xuanming , Cao Jianli , Cai Jian-Piao , Wu Jiayan , Huang Jiangang , Asthana Pallavi , Wong Sheung Kin Ken , Ye Zi-Wei , Gurung Susma , Zhang Yijing , Wang Sheng , Wang Zening , Ge Xin , Kwan Hiu Yee , Lyu Aiping , Chan Kui Ming , Wong Nathalie , Huang Jiandong , Zhou Zhongjun , Bian Zhao-Xiang , Yuan Shuofeng , Wong Hoi Leong Xavier 
Published: December 2022

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. Angiotensin-converting enzyme 2 (ACE2) is an entry receptor for SARS-CoV-2. The full-length membrane form of ACE2 (memACE2) undergoes ectodomain shedding to generate a shed soluble form (solACE2) that mediates SARS-CoV-2 entry via receptor-mediated endocytosis. Currently, it is not known how the physiological regulation of ACE2 shedding contributes to the etiology of COVID-19 in vivo. The present study identifies Membrane-type 1 Matrix Metalloproteinase (MT1-MMP) as a critical host protease for solACE2-mediated SARS-CoV-2 infection. SARS-CoV-2 infection leads to increased activation of MT1-MMP that is colocalized with ACE2 in human lung epithelium. Mechanistically, MT1-MMP directly cleaves memACE2 at M706-S to release solACE218-706 that binds to the SARS-CoV-2 spike proteins (S), thus facilitating cell entry of SARS-CoV-2. Human solACE218-706 enables SARS-CoV-2 infection in both non-permissive cells and naturally insusceptible C57BL/6 mice. Inhibition of MT1-MMP activities suppresses solACE2-directed entry of SARS-CoV-2 in human organoids and aged mice. Both solACE2 and circulating MT1-MMP are positively correlated in plasma of aged mice and humans. Our findings provide in vivo evidence demonstrating the contribution of ACE2 shedding to the etiology of COVID-19.
Targeting anti-apoptotic pathways eliminates senescent melanocytes and leads to nevi regression
Authors: Kohli Jaskaren , Ge Chen , Fitsiou Eleni , Doepner Miriam , Brandenburg Simone M. , Faller William J. , Ridky Todd W. , Demaria Marco 
Published: December 2022

AbstractHuman melanocytic nevi (moles) result from a brief period of clonal expansion of melanocytes. As a cellular defensive mechanism against oncogene-induced hyperplasia, nevus-resident melanocytes enter a senescent state of stable cell cycle arrest. Senescent melanocytes can persist for months in mice and years in humans with a risk to escape the senescent state and progress to melanoma. The mechanisms providing prolonged survival of senescent melanocytes remain poorly understood. Here, we show that senescent melanocytes in culture and in nevi express high level of the anti-apoptotic BCL-2 family member BCL-W but remain insensitive to the pan-BCL-2 inhibitor ABT-263. We demonstrate that resistance to ABT-263 is driven by mTOR-mediated enhanced translation of another anti-apoptotic member, MCL-1. Strikingly, the combination of ABT-263 and MCL-1 inhibitors results in synthetic lethality to senescent melanocytes, and its topical application sufficient to eliminate nevi in male mice. These data highlight the important role of redundant anti-apoptotic mechanisms for the survival advantage of senescent melanocytes, and the proof-of-concept for a non-invasive combination therapy for nevi removal.
Microporous organic nanotube assisted design of high performance nanofiltration membranes
Authors: Han Shuangqiao , Zhu Junyong , Uliana Adam A. , Li Dongyang , Zhang Yatao , Zhang Lin , Wang Yong , He Tao , Elimelech Menachem 
Published: December 2022

AbstractMicroporous organic nanotubes (MONs) hold considerable promise for designing molecular-sieving membranes because of their high microporosity, customizable chemical functionalities, and favorable polymer affinity. Herein, we report the use of MONs derived from covalent organic frameworks to engineer 15-nm-thick microporous membranes via interfacial polymerization (IP). The incorporation of a highly porous and interpenetrated MON layer on the membrane before the IP reaction leads to the formation of polyamide membranes with Turing structure, enhanced microporosity, and reduced thickness. The MON-modified membranes achieve a remarkable water permeability of 41.7 L m−2 h−1 bar−1 and high retention of boron (78.0%) and phosphorus (96.8%) at alkaline conditions (pH 10), surpassing those of reported nanofiltration membranes. Molecular simulations reveal that introducing the MONs not only reduces the amine molecule diffusion toward the organic phase boundary but also increases membrane porosity and the density of water molecules around the membrane pores. This MON-regulated IP strategy provides guidelines for creating high-permeability membranes for precise nanofiltration.
High-throughput first-principle prediction of collinear magnetic topological materials
Authors: Su Yunlong , Hu Jiayu , Cai Xiaochan , Shi Wujun , Xia Yunyouyou , Xu Yuanfeng , Xu Xuguang , Chen Yulin , Li Gang 
Published: December 2022

AbstractThe success of topological band theory and symmetry-based topological classification significantly advances our understanding of the Berry phase. Based on the critical concept of topological obstruction, efficient theoretical frameworks, including topological quantum chemistry and symmetry indicator theory, were developed, making a massive characterization of real materials possible. However, the classification of magnetic materials often involves the complexity of their unknown magnetic structures, which are often hard to know from experiments, thus, hindering the topological classification. In this paper, we design a high-throughput workflow to classify magnetic topological materials by automating the search for collinear magnetic structures and the characterization of their topological natures. We computed 1049 chosen transition-metal compounds (TMCs) without oxygen and identified 64 topological insulators and 53 semimetals, which become 73 and 26 when U correction is further considered. Due to the lack of magnetic structure information from experiments, our high-throughput predictions provide insightful reference results and make the step toward a complete diagnosis of magnetic topological materials.
Effects of population growth on Israel’s demand for desalinated water
Authors: Kramer Isaac , Tsairi Yaara , Roth Michael Buchdahl , Tal Alon , Mau Yair 
Published: December 2022

AbstractIn 2005, Israel began using desalination to augment limited natural water supplies. While desalination has helped Israel overcome chronic water shortages, high-population growth may test this approach. We examine how three population growth scenarios (low, medium, high) could affect water demand and supply by 2065. Our projections show that Israel will need to desalinate as much as 3.7 billion m3annually, compared to 0.5 billion m3in 2020. Meeting this demand could require the construction of 30 new desalination units. The effects of population growth on Israel’s water supply are likely to dwarf those of climate change. Increased desalination would, however, increase electricity demand, requiring over 11 TWh electricity annually. Population growth is also likely to challenge Israel’s wastewater management policies, producing more effluent than farmers will have the capacity to consume. The Israeli experience will provide important lessons for regions facing similar pressures.
Leukocyte CH25H is a potential diagnostic and prognostic marker for lung adenocarcinoma
Authors: Zhang Jun , Xu Lidong , Gao Jun , Li Jieyi , Zhao Xiaokai , Yang Pengmin , Ge Yujun , Guo Dawei , Liu Zhonghua , Wang Xiyong , Gu Wenchao , Wang Pengli , Hu Xun , Gong Ziying , Zhang Daoyun 
Published: December 2022

AbstractMetastasis, a major challenge during the treatment of lung cancer, causes deterioration in patient health outcomes. Thus, to address this problem, this study aimed to explore the role and contribution of Cholesterol 25-Hydroxylase (CH25H) as a potential diagnostic and prognostic marker in lung cancer. Online public databases were used to analyze the expression level, prognostic value, gene-pathway enrichment, and immune infiltration of CH25H in lung cancer patients. The Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) was used to analyze and detect the CH25H expression levels in leukocytes from lung cancer patients. The expression level of CH25H was significantly reduced in lung adenocarcinoma (LUAD), which is associated with a higher disease stage, but not in lung squamous cell carcinoma (LUSC). Kaplan–Meier survival analysis indicated that LUAD patients with low CH25H expression had a worse prognosis. Mechanistically, our results showed that in LUAD, CH25H may be a regulatory factor affecting the immune cell infiltration level, and the resultant tumor development. Experimental data showed that low expression of CH25H in leukocytes was significantly associated with LUAD metastasis (P < 0.01). Our study suggests that CH25H may function as a prognostic and risk stratification biomarker for LUAD.
Regionalization, constraints, and the ancestral ossification patterns in the vertebral column of amniotes
Authors: Verrière Antoine , Fröbisch Nadia B. , Fröbisch Jörg 
Published: December 2022

AbstractThe development of the vertebral column has been studied extensively in modern amniotes, yet many aspects of its evolutionary history remain enigmatic. Here we expand the existing data on four major vertebral developmental patterns in amniotes based on exceptionally well-preserved specimens of the early Permian mesosaurid reptile Mesosaurus tenuidens: (i) centrum ossification, (ii) neural arch ossification, (iii) neural arch fusion, and (iv) neurocentral fusion. We retrace the evolutionary history of each pattern and reconstruct the ancestral condition in amniotes. Despite 300 million years of evolutionary history, vertebral development patterns show a surprisingly stability in amniotes since their common ancestor. We propose that this stability may be linked to conservatism in the constraints posed by underlying developmental processes across amniotes. We also point out that birds, mammals, and squamates each show specific trends deviating from the ancestral condition in amniotes, and that they remain rather unchanged within these lineages. The stability of their unique patterns demonstrates a certain homogeneity of vertebral developmental constraints within these lineages, which we suggest might be linked to their specific modes of regionalization. Our research provides a framework for the evolution of axial development in amniotes and a foundation for future studies.
Electron energy loss spectroscopy database synthesis and automation of core-loss edge recognition by deep-learning neural networks
Authors: Kong Lingli , Ji Zhengran , Xin Huolin L. 
Published: December 2022

AbstractThe ionization edges encoded in the electron energy loss spectroscopy (EELS) spectra enable advanced material analysis including composition analyses and elemental quantifications. The development of the parallel EELS instrument and fast, sensitive detectors have greatly improved the acquisition speed of EELS spectra. However, the traditional way of core-loss edge recognition is experience based and human labor dependent, which limits the processing speed. So far, the low signal–noise ratio and the low jump ratio of the core-loss edges on the raw EELS spectra have been challenging for the automation of edge recognition. In this work, a convolutional-bidirectional long short-term memory neural network (CNN-BiLSTM) is proposed to automate the detection and elemental identification of core-loss edges from raw spectra. An EELS spectral database is synthesized by using our forward model to assist in the training and validation of the neural network. To make the synthesized spectra resemble the real spectra, we collected a large library of experimentally acquired EELS core edges. In synthesize the training library, the edges are modeled by fitting the multi-Gaussian model to the real edges from experiments, and the noise and instrumental imperfectness are simulated and added. The well-trained CNN-BiLSTM network is tested against both the simulated spectra and real spectra collected from experiments. The high accuracy of the network, 94.9%, proves that, without complicated preprocessing of the raw spectra, the proposed CNN-BiLSTM network achieves the automation of core-loss edge recognition for EELS spectra with high accuracy.
Combined effects of sepsis and extracorporeal membrane oxygenation on left ventricular performance in a murine model
Authors: Kayumov Mukhammad , Kim Dowan , Raman Sainath , MacLaren Graeme , Jeong In Seok , Cho Hwa Jin 
Published: December 2022

AbstractExtracorporeal membrane oxygenation (ECMO) may be a viable salvage therapy in selected patients with septic shock. As ECMO use increases, we studied left ventricular (LV) performance during sepsis with and without ECMO using a pressure–volume (PV) loop in a murine model and aimed to understand LV hemodynamics in septic shock with ECMO. The rats were divided into Group 1 (ECMO applied to healthy rats), Group 2 (ECMO for septic rats), Group 3 (Controls, n = 20) and Group 4 (Sepsis induction only, n = 20). The cardiac parameters include end-diastolic volume (EDV), end-systolic volume (ESV), end-diastolic pressure (EDP), and end-systolic pressure (ESP), ejection fraction (EF), end-systolic elastance (Ees), diastolic time constant (Tau) index, arterial elastance (Ea), pressure–volume area (PVA), stroke work (SW), and potential energy (PE). We compared the changes of parameters in all groups. A total of 74 rats were included in the analyses. After 2 h on ECMO, Group 2 was associated with significant increases in ESP, EDV, ESV, PVA, PE, and SW. The difference ratio of PE and PVA was significantly higher in Group 2 compared to Group 1 (P < 0.01). In conclusion, myocardial oxygen consumption was higher in septic shock with ECMO than in controls.