bluuebunny/crossref_metadata_2025 huggingface dataset:
Operational AOD Retrieval at Subkilometer Resolution Using OceanSat‐2 OCM Over Land: SAER Algorithm, Uncertainties, Validation & Inter‐Sensor Comparison
Authors: Mishra Manoj K. , Misra Arundhati , Kumar Raj
Published: June 2023

The ocean color monitor (OCM) sensor onboard OceanSat‐2 is providing data in visible and near Infrared (NIR) bands. Due to the limited spectral coverage of OCM, the widely used dark‐target and deep‐blue aerosol algorithms cannot be adapted. Here, a new aerosol optical depth (AOD) retrieval algorithm for OCM (or similar sensors) over land, termed Space Applications Center AErosol Retrieval (SAER) is described. It utilizes two blue bands for the AOD inversion and, Red and NIR band to characterize the surface in visible bands without assuming red and NIR bands transparent to aerosols. Unlike the dark‐target algorithm, the SAER algorithm can retrieve AOD over bright arid and urban areas too. The uncertainty analysis of SAER suggests a theoretically expected error (EE) envelope of ±(0.06 + 0.26 × AOD) for typical retrieval conditions. OCM AOD over land is retrieved operationally for the first time over Indian and neighboring countries' landmass at the finest spatial resolution of 0.007°. The SAER algorithm is validated against in‐situ AOD measurements during the years 2016–2018 at 21 Aerosol Robotic Network stations located in south‐Asia. Overall validation using 1900 match‐up points shows correlations exceeding 0.8 with 74% of retrievals within EE. The retrievals over cropland, grassland, and mixed land cover types show high (low) correlation (bias), while over bright urban areas somewhat low (high) correlation (bias) is observed. Excluding monsoon season, OCM AOD retrievals show good performance over the year. The performance of MODerate Resolution Imaging Spectroradiometer dark‐target and OCM AOD, against common in‐situ, is close to each other. The study shows that OCM AOD can be used for air quality monitoring/modeling at high spatial resolution.
Statistical Decomposition and Machine Learning to Clean In Situ Spaceflight Magnetic Field Measurements
Authors: Finley M. G. , Bowen T. A. , Pulupa M. , Koval A. , Miles D. M.
Published: June 2023

Robust in situ magnetic field measurements are critical to understanding the various mechanisms that couple mass, momentum, and energy throughout our solar system. However, the spacecraft on which magnetometers are often deployed contaminate the magnetic field measurements via onboard subsystems including reaction wheels and magnetorquers. Two magnetometers can be deployed at different distances from the spacecraft to determine an approximation of the interfering field for subsequent removal, but constant data streams from both magnetometers can be impractical due to power and telemetry limitations. Here we propose a method to identify and remove time‐varying magnetic interference from sources such as reaction wheels using statistical decomposition and convolutional neural networks, providing high‐fidelity magnetic field data even in cases where dual‐sensor measurements are not constantly available. For example, a measurement interval from the Parker Solar Probe outboard magnetometer experienced a 95.1% reduction in reaction wheel interference following application of the proposed technique.
Efficacy, safety and pharmacokinetics of Unecritinib (TQ-B3101) for patients with ROS1 positive advanced non-small cell lung cancer: a Phase I/II Trial
Authors: Lu Shun , Pan Hongming , Wu Lin , Yao Yu , He Jianxing , Wang Yan , Wang Xiuwen , Fang Yong , Zhou Zhen , Wang Xicheng , Cai Xiuyu , Yu Yan , Ma Zhiyong , Min Xuhong , Yang Zhixiong , Cao Lejie , Yang Huaping , Shu Yongqian , Zhuang Wu , Cang Shundong , Fang Jian , Li Kai , Yu Zhuang , Cui Jiuwei , Zhang Yang , Li Man , Wen Xinxuan , Zhang Jie , Li Weidong , Shi Jianhua , Xu Xingxiang , Zhong Diansheng , Wang Tao , Zhu Jiajia
Published: June 2023

This phase I/II trial characterized the tolerability, safety, and antitumor activities of unecritinib, a novel derivative of crizotinib and a multi-tyrosine kinase inhibitor targeting ROS1, ALK, and c-MET, in advanced tumors and ROS1 inhibitor-naive advanced or metastatic non-small cell lung cancer (NSCLC) harboring ROS1 rearrangements. Eligible patients received unecritinib 100, 200, and 300 mg QD, and 200, 250, 300, and 350 mg BID in a 3 + 3 design during dose escalation and 300 and 350 mg BID during expansion. Phase II trial patients received unecritinib 300 mg BID in continuous 28-day cycles until disease progression or unacceptable toxicity. The primary endpoint was the objective response rate (ORR) per independent review committee (IRC). Key secondary endpoints included intracranial ORR and safety. The ORR of 36 efficacy evaluable patients in the phase I trial was 63.9% (95% CI 46.2%, 79.2%). In the phase II trial, 111 eligible patients in the main study cohort received unecritinib. The ORR per IRC was 80.2% (95% CI 71.5%, 87.1%) and the median progression-free survival (PFS) per IRC was 16.5 months (95% CI 10.2, 27.0). Additionally, 46.9% of the patients who received recommended phase II dose of 300 mg BID experienced grade 3 or higher treatment-related adverse events. Treatment-related ocular disorders and neurotoxicity occurred in 28.1% and 34.4% of patients, respectively, but none was grade 3 or higher. Unecritinib is efficacious and safe for ROS1 inhibitor-naive patients with ROS1-positive advanced NSCLC, particularly patients with brain metastases at baseline, strongly supporting that unecritinib should become one of the standards of care for ROS1-positive NSCLC.

ClinicalTrials.gov identifier: NCT03019276 and NCT03972189.
MiR-146a-5p deficiency in extracellular vesicles of glioma-associated macrophages promotes epithelial-mesenchymal transition through the NF-κB signaling pathway
Authors: Xu Chao , Wang Pan , Guo Haiyan , Shao Chuan , Liao Bin , Gong Sheng , Zhou Yanghao , Yang Bingjie , Jiang Haotian , Zhang Gang , Wu Nan
Published: June 2023

Glioma-associated macrophages (GAMs) are pivotal chains in the tumor immune microenvironment (TIME). GAMs mostly display M2-like phenotypes with anti-inflammatory features related to the malignancy and progression of cancers. Extracellular vesicles derived from immunosuppressive GAMs (M2-EVs), the essential components of the TIME, greatly impact the malignant behavior of GBM cells. M1- or M2-EVs were isolated in vitro, and human GBM cell invasion and migration were reinforced under M2-EV treatment. Signatures of the epithelial-mesenchymal transition (EMT) were also enhanced by M2-EVs. Compared with M1-EVs, miR-146a-5p, considered the key factor in TIME regulation, was deficient in M2-EVs according to miRNA-sequencing. When the miR-146a-5p mimic was added, EMT signatures and the invasive and migratory abilities of GBM cells were correspondingly weakened. Public databases predicted the miRNA binding targets and interleukin 1 receptor-associated kinase 1 (IRAK1) and tumor necrosis factor receptor-associated factor 6 (TRAF6) were screened as miR-146a-5p binding genes. Bimolecular fluorescent complementation and coimmunoprecipitation confirmed interactions between TRAF6 and IRAK1. The correlation between TRAF6 and IRAK1 was evaluated with immunofluorescence (IF)-stained clinical glioma samples. The TRAF6-IRAK1 complex is the switch and the brake that modulates IKK complex phosphorylation and NF-κB pathway activation, as well as the EMT behaviors of GBM cells. Furthermore, a homograft nude mouse model was explored and mice transplanted with TRAF6/IRAK1-overexpressing glioma cells had shorter survival times while mice transplanted with glioma cells with miR-146a-5p overexpression or TRAF6/IRAK1 knockdown lived longer. This work indicated that in the TIME of GBM, the deficiency of miR-146a-5p in M2-EVs enhances tumor EMT through disinhibition of the TRAF6-IRAK1 complex and IKK-dependent NF-κB signaling pathway providing a novel therapeutic strategy targeting the TIME of GBM.
NADPH oxidase mediated oxidative stress signaling in FLT3-ITD acute myeloid leukemia
Authors: Chen Yongfeng , Zou Zhenyou , Găman Mihnea-Alexandru , Xu Linglong , Li Jing
Published: June 2023

The internal tandem duplication of the juxtamembrane domain of the FMS-like tyrosine kinase 3 (FLT3-ITD) is the most common genetic change in acute myeloid leukemia (AML), and about 30% of all AMLs harbor a FLT3-ITD mutation. Even though FLT3 inhibitors have displayed encouraging effects in FLT3-ITD-mutated AML, the extent of the clinical response to these compounds is cut short due to the rapid development of drug resistance. Evidence has shown that FLT3-ITD triggered activation of oxidative stress signaling may exert a pivotal role in drug resistance. The downstream pathways of FLT3-ITD, including STAT5, PI3K/AKT, and RAS/MAPK, are considered to be major oxidative stress signaling pathways. These downstream pathways can inhibit apoptosis and promote proliferation and survival by regulating apoptosis-related genes and promoting the generation of reactive oxygen species (ROS) through NADPH oxidase (NOX) or other mechanisms. Appropriate levels of ROS may promote proliferation, but high levels of ROS can lead to oxidative damage to the DNA and increase genomic instability. In addition, post-translational modifications of FLT3-ITD and changes in its subcellular localization can affect downstream signaling which may also be one of the mechanisms leading to drug resistance. In this review, we summarized the research progress on NOX mediated oxidative stress signaling and its relationship with drug resistance in FLT3-ITD AML, and discuss the possible new targets in FLT3-ITD signal blocking to reverse drug resistance in FLT3-ITD-mutated AML.
Differentiation of IL-26+ TH17 intermediates into IL-17A producers via epithelial crosstalk in psoriasis
Authors: Fries Anissa , Saidoune Fanny , Kuonen François , Dupanloup Isabelle , Fournier Nadine , Guerra de Souza Ana Cristina , Haniffa Muzlifah , Ma Feiyang , Gudjonsson Johann E. , Roesner Lennart , Li Yang , Werfel Thomas , Conrad Curdin , Gottardo Raphael , Modlin Robert L. , Di Domizio Jeremy , Gilliet Michel
Published: June 2023

Interleukin (IL)-26 is a TH17 cytokine with known antimicrobial and pro-inflammatory functions. However, the precise role of IL-26 in the context of pathogenic TH17 responses is unknown. Here we identify a population of blood TH17 intermediates that produce high levels of IL-26 and differentiate into IL-17A-producing TH17 cells upon TGF-β1 exposure. By combining single cell RNA sequencing, TCR sequencing and spatial transcriptomics we show that this process occurs in psoriatic skin. In fact, IL-26+ TH17 intermediates infiltrating psoriatic skin induce TGF-β1 expression in basal keratinocytes and thereby promote their own differentiation into IL-17A-producing cells. Thus, our study identifies IL-26-producing cells as an early differentiation stage of TH17 cells that infiltrates psoriatic skin and controls its own maturation into IL17A-producing TH17 cells, via epithelial crosstalk involving paracrine production of TGF-β1.
Nuclear lamina strain states revealed by intermolecular force biosensor
Authors: Danielsson Brooke E. , George Abraham Bobin , Mäntylä Elina , Cabe Jolene I. , Mayer Carl R. , Rekonen Anna , Ek Frans , Conway Daniel E. , Ihalainen Teemu O.
Published: June 2023

Nuclear lamins have been considered an important structural element of the nucleus. The nuclear lamina is thought both to shield DNA from excessive mechanical forces and to transmit mechanical forces onto the DNA. However, to date there is not yet a technical approach to directly measure mechanical forces on nuclear lamins at the protein level. To overcome this limitation, we developed a nanobody-based intermolecular tension FRET biosensor capable of measuring the mechanical strain of lamin filaments. Using this sensor, we were able to show that the nuclear lamina is subjected to significant force. These forces are dependent on nuclear volume, actomyosin contractility, functional LINC complex, chromatin condensation state, cell cycle, and EMT. Interestingly, large forces were also present on nucleoplasmic lamins, indicating that these lamins may also have an important mechanical role in the nucleus. Overall, we demonstrate that the nanobody-based approach allows construction of biosensors for complex protein structures for mechanobiology studies.
Innovative design of minimal invasive biodegradable poly(glycerol-dodecanoate) nucleus pulposus scaffold with function regeneration
Authors: Wang Lizhen , Jin Kaixiang , Li Nan , Xu Peng , Yuan Hao , Ramaraju Harsha , Hollister Scott J. , Fan Yubo
Published: June 2023

Minimally invasive biodegradable implants with regeneration have been a frontier trend in clinic. Degeneration of nucleus pulposus (NP) is irreversible in most of spine diseases, and traditional spinal fusion or discectomy usually injure adjacent segments. Here, an innovative minimally invasive biodegradable NP scaffold with function regeneration inspired by cucumber tendril is developed using shape memory polymer poly(glycerol-dodecanoate) (PGD), whose mechanical property is controlled to the similar with human NP by adjusting synthetic parameters. The chemokine stromal cell-derived factor-1α (SDF-1α) is immobilized to the scaffold recruiting autologous stem cells from peripheral tissue, which has better ability of maintaining disc height, recruiting autologous stem cells, and inducing regeneration of NP in vivo compared to PGD without chemokine group and hydrogel groups significantly. It provides an innovative way to design minimally invasive implants with biodegradation and functional recovery, especially for irreversible tissue injury, including NP, cartilage and so on.
Drug reinforcement impairs cognitive flexibility by inhibiting striatal cholinergic neurons
Authors: Gangal Himanshu , Xie Xueyi , Huang Zhenbo , Cheng Yifeng , Wang Xuehua , Lu Jiayi , Zhuang Xiaowen , Essoh Amanda , Huang Yufei , Chen Ruifeng , Smith Laura N. , Smith Rachel J. , Wang Jun
Published: June 2023

Addictive substance use impairs cognitive flexibility, with unclear underlying mechanisms. The reinforcement of substance use is mediated by the striatal direct-pathway medium spiny neurons (dMSNs) that project to the substantia nigra pars reticulata (SNr). Cognitive flexibility is mediated by striatal cholinergic interneurons (CINs), which receive extensive striatal inhibition. Here, we hypothesized that increased dMSN activity induced by substance use inhibits CINs, reducing cognitive flexibility. We found that cocaine administration in rodents caused long-lasting potentiation of local inhibitory dMSN-to-CIN transmission and decreased CIN firing in the dorsomedial striatum (DMS), a brain region critical for cognitive flexibility. Moreover, chemogenetic and time-locked optogenetic inhibition of DMS CINs suppressed flexibility of goal-directed behavior in instrumental reversal learning tasks. Notably, rabies-mediated tracing and physiological studies showed that SNr-projecting dMSNs, which mediate reinforcement, sent axonal collaterals to inhibit DMS CINs, which mediate flexibility. Our findings demonstrate that the local inhibitory dMSN-to-CIN circuit mediates the reinforcement-induced deficits in cognitive flexibility.
Photoredox-catalyzed diastereoselective dearomative prenylation and reverse-prenylation of electron-deficient indole derivatives
Authors: Chang Xuexue , Zhang Fangqing , Zhu Shibo , Yang Zhuang , Feng Xiaoming , Liu Yangbin
Published: June 2023

Prenylated and reverse-prenylated indolines are privileged scaffolds in numerous naturally occurring indole alkaloids with a broad spectrum of important biological properties. Development of straightforward and stereoselective methods to enable the synthesis of structurally diverse prenylated and reverse-prenylated indoline derivatives is highly desirable and challenging. In this context, the most direct approaches to achieve this goal generally rely on transition-metal-catalyzed dearomative allylic alkylation of electron-rich indoles. However, the electron-deficient indoles are much less explored, probably due to their diminished nucleophilicity. Herein, a photoredox-catalyzed tandem Giese radical addition/Ireland–Claisen rearrangement is disclosed. Diastereoselective dearomative prenylation and reverse-prenylation of electron-deficient indoles proceed smoothly under mild conditions. An array of tertiary α-silylamines as radical precursors is readily incorporated in 2,3-disubstituted indolines with high functional compatibility and excellent diastereoselectivity (>20:1 d.r.). The corresponding transformations of the secondary α-silylamines provide the biologically important lactam-fused indolines in one-pot synthesis. Subsequently, a plausible photoredox pathway is proposed based on control experiments. The preliminary bioactivity study reveals a potential anticancer property of these structurally appealing indolines.
Accelerating the prediction and discovery of peptide hydrogels with human-in-the-loop
Authors: Xu Tengyan , Wang Jiaqi , Zhao Shuang , Chen Dinghao , Zhang Hongyue , Fang Yu , Kong Nan , Zhou Ziao , Li Wenbin , Wang Huaimin
Published: June 2023

The amino acid sequences of peptides determine their self-assembling properties. Accurate prediction of peptidic hydrogel formation, however, remains a challenging task. This work describes an interactive approach involving the mutual information exchange between experiment and machine learning for robust prediction and design of (tetra)peptide hydrogels. We chemically synthesize more than 160 natural tetrapeptides and evaluate their hydrogel-forming ability, and then employ machine learning-experiment iterative loops to improve the accuracy of the gelation prediction. We construct a score function coupling the aggregation propensity, hydrophobicity, and gelation correctorCg, and generate an 8,000-sequence library, within which the success rate of predicting hydrogel formation reaches 87.1%. Notably, the de novo-designed peptide hydrogel selected from this work boosts the immune response of the receptor binding domain of SARS-CoV-2 in the mice model. Our approach taps into the potential of machine learning for predicting peptide hydrogelator and significantly expands the scope of natural peptide hydrogels.
Availability and use of Standards in vaccine development
Authors: Avumegah Michael Selorm , Mattiuzzo Giada , Särnefält Anna , Page Mark , Makar Karen , Lathey Janet , Kim June , Yimer Solomon Abebe , Craig Danielle , Knezevic Ivana , Bernasconi Valentina , Kristiansen Paul A. , Kromann Ingrid
Published: June 2023

Reference materials are critical in assay development for calibrating and assessing their suitability. The devasting nature of the COVID-19 pandemic and subsequent proliferation of vaccine platforms and technologies has meant that there is even a greater need for standards for immunoassay development, which are critical to assess and compare vaccines’ responses. Equally important are the standards needed to control the vaccine manufacturing processes. Standardized vaccine characterization assays throughout process development are essential for a successful Chemistry, Manufacturing and Controls (CMC) strategy. In this perspective paper, we advocate for reference material incorporation into assays and their calibration to International Standards from preclinical vaccine development through control testing and provide insight into why this is necessary. We also provide information on the availability of WHO international antibody standards for CEPI-priority pathogens.
A validated test has been developed for assessment of manual small incision cataract surgery skills using virtual reality simulation
Authors: Hutter Daniel E. , Wingsted Line , Cejvanovic Sanja , Jacobsen Mads Forslund , Ochoa Luis , González Daher Karla Pamela , la Cour Morten , Konge Lars , Thomsen Ann Sofia Skou
Published: June 2023

This study investigates the validity evidence of metrics used for the assessment of surgical skills for Manual Small Incision Cataract Surgery (MSICS) in a virtual reality simulator. MSICS surgery is a low-cost, low-technology cataract surgery technique, which is widely used in low- and middle-income countries. However, there is a lack of cataract surgeons globally, and efficient and evidence-based training of new surgeons is needed. In order to investigate the validity of simulator metrics, we included three groups of participants: (1) MSICS novices who were ophthalmologists with no cataract surgery experience, (2) MSICS novices who were experienced phacoemulsification cataract surgeons, but with no MSICS experience, and (3) experienced phacoemulsification and MSICS surgeons. The evaluation included 11 steps of the MSICS procedure, and all simulator metrics for those steps were reviewed. Of the 55 initial metrics, 30 showed high positive discriminative ability. A test passing score of 20 out of 30 was established, and one of 15 novices with no MSICS experience (mean score 15.5) and 7 out of 10 experienced MSICS surgeons (mean score 22.7) passed the test. We have developed and established validity evidence for a test for MSICS skills in a virtual reality simulator for future use in proficiency-based training and evidence-based testing of training interventions.
Generalized neural closure models with interpretability
Authors: Gupta Abhinav , Lermusiaux Pierre F. J.
Published: June 2023

Improving the predictive capability and computational cost of dynamical models is often at the heart of augmenting computational physics with machine learning (ML). However, most learning results are limited in interpretability and generalization over different computational grid resolutions, initial and boundary conditions, domain geometries, and physical or problem-specific parameters. In the present study, we simultaneously address all these challenges by developing the novel and versatile methodology of unified neural partial delay differential equations. We augment existing/low-fidelity dynamical models directly in their partial differential equation (PDE) forms with both Markovian and non-Markovian neural network (NN) closure parameterizations. The melding of the existing models with NNs in the continuous spatiotemporal space followed by numerical discretization automatically allows for the desired generalizability. The Markovian term is designed to enable extraction of its analytical form and thus provides interpretability. The non-Markovian terms allow accounting for inherently missing time delays needed to represent the real world. Our flexible modeling framework provides full autonomy for the design of the unknown closure terms such as using any linear-, shallow-, or deep-NN architectures, selecting the span of the input function libraries, and using either or both Markovian and non-Markovian closure terms, all in accord with prior knowledge. We obtain adjoint PDEs in the continuous form, thus enabling direct implementation across differentiable and non-differentiable computational physics codes, different ML frameworks, and treatment of nonuniformly-spaced spatiotemporal training data. We demonstrate the new generalized neural closure models (gnCMs) framework using four sets of experiments based on advecting nonlinear waves, shocks, and ocean acidification models. Our learned gnCMs discover missing physics, find leading numerical error terms, discriminate among candidate functional forms in an interpretable fashion, achieve generalization, and compensate for the lack of complexity in simpler models. Finally, we analyze the computational advantages of our new framework.
The multi-mode acoustic gravitational wave experiment: MAGE
Authors: Campbell William M. , Goryachev Maxim , Tobar Michael E.
Published: June 2023

The Multi-mode Acoustic Gravitational wave Experiment (MAGE) is a high frequency gravitational wave detection experiment. In its first stage, the experiment features two near-identical quartz bulk acoustic wave resonators that act as strain antennas with spectral sensitivity as low as 6.6 × 10−21 [strain]/$$\sqrt{\text {Hz}}$$

Hz

in multiple narrow bands across MHz frequencies. MAGE is the successor to the initial path-finding experiments; GEN 1 and GEN 2. These precursor runs demonstrated the successful use of the technology, employing a single quartz gravitational wave detector that found significantly strong and rare transient features. As the next step to this initial experiment, MAGE will employ further systematic rejection strategies by adding an additional quartz detector such that localised strains incident on just a single detector can be identified. The primary goals of MAGE will be to target signatures arising from objects and/or particles beyond that of the standard model, as well as identifying the source of the rare events seen in the predecessor experiment. The experimental set-up, current status and future directions for MAGE are discussed. Calibration procedures of the detector and signal amplification chain are presented. The sensitivity of MAGE to gravitational waves is estimated from knowledge of the quartz resonators. Finally, MAGE is assembled and tested in order to determine the thermal state of its new components.
Effects of propolis-loaded nanoliposomes fortification in extender on buffalo semen cryopreservation
Authors: Abdelnour Sameh A. , Hassan Mahmoud A. E. , Shehabeldin Ahmed. M. , Omar Mohamed. E. A. , Khalil Wael A. , Aman Reham Mokhtar
Published: June 2023

Buffalo sperm is sensitive to cryoinjuries, thus improving sperm cryoresistance is a critical approach for wide spreading the assisted reproductive technologies in buffalo. The intention of this work was to assess the effect of propolis-loaded in nanoliposomes (PRNL) supplementation of semen extender on semen quality, antioxidant status and some apoptotic genes of cryopreserved buffalo semen. PRNL were prepared using cholesterol (Chol) as well as soybean lecithin and their physicochemical properties were characterized. Egyptian buffalo bulls (4–6 years) were involved, and the semen samples were collected using the artificial vagina method. Buffalo semen was pooled (n = 25 ejaculates) and cryopreserved in tris extender containing PRNL at 0 (PRNL0), 2 (PRNL2), 4 (PRNL4) and 6 µg/mL (PRNL6), respectively. The PRNL had a size of 113.13 nm and a negative zeta potential (− 56.83 mV). Sperm progressive motility, viability, membrane integrity, abnormalities, chromatin damage, redox status, apoptosis status, and apoptotic genes were investigated after post-thawed buffalo semen. Using 2 or 4 µg/mL PRNL significantly increased sperm progressive motility, viability, and membrane integrity, while sperm abnormalities and the percentage of chromatin damages were the lowest in PRNL2 group. Moreover, the PRNL2 group exhibited the best results for all antioxidative activities (TAC, SOD, GPx and CAT) with significantly higher levels than the other groups (P < 0.05). The levels of ROS and MDA were significantly lower in the PRLN2 compared with other groups. The sperm caspase 3 enzyme activities showed the lowest values in PRNL2 groups followed by PRNL4 and PRNL6 groups with significant differences compared with the control. Adding 2 µg/mL PRNL to freezing media significantly reduced apoptotic genes such as Bax and Caspase 3 in sperm, while significantly increase in Bcl2 expression compared with the control (P < 0.001). The expression of Bcl2, Caspase 3 and Bax genes in sperm were not affected by the 6 µg/mL PRNL addition (P > 0.05). The electron micrography descriptions exemplified that the fortification of 2 or 4 µg/mL PRNL maintained the acrosomal and plasma membrane integrities as well as sustained the ultrastructure integrity of the cryopreserved buffalo spermatozoa when compared with control group, whereas the 6 µg/mL of PRNL demonstrated highest injury to the acrosome and plasma membranes. Results show supplementation of the buffalo freezing extender with 2 or 4 µg/mL of PRNL enhanced post-thawed sperm quality via boosting the antioxidant indices, diminishing the oxidative stress and apoptosis as well as maintained the ultrastructure integrity of frozen-thawed buffalo sperm.
Lipoxygenase inhibitory synthetic derivatives of methyl gallate regulate gene expressions of COX-2 and cytokines to reduce animal model arthritis
Authors: Sharanya C.S. , Abhithaj J. , Arun K.G. , Eeda Koti Reddy , Bhat Vignesh , Variyar E.J. , Sabu A. , Haridas M.
Published: June 2023

Mammalian lipoxygenases (LOXs) are involved in the biosynthesis of mediators of anaphylactic reactions and have been implicated in cell maturation, the pathogenesis of bronchial asthma, atherosclerosis, rheumatoid arthritis, cardiovascular diseases, Alzheimer’s disease and osteoporosis. Hence LOX inhibition in chronic conditions can lead to reducing the disease progression, which can be a good target for treating these diseases. The present study deals with designing methyl gallate derivatives and their anti-inflammatory effect by in silico, in vitro and in vivo methods. Designed derivatives were docked against LOX enzyme, and molecular dynamic simulations were carried out. Following the synthesis of derivatives, in vitro LOX inhibition assay, enzyme kinetics and fluorescence quenching studies were performed. One of the derivatives of methyl gallate (MGSD 1) was demonstrated as an anti-inflammatory agent for the treatment of rheumatoid arthritis in the animal model. Amelioration of Freund’s complete adjuvant (FCA)-induced arthritis by methyl gallate and its derivative with a concentration of 10–40 mg.kg−1 has been assessed in vivo in a 28-day-long study. TNF-α and COX-2 gene expression were also studied. Methyl gallate synthetic derivatives (MGSDs) inhibited LOX with an IC50 of 100 nM, 304 nM, and 226 nM for MGSD 1, MGSD 2, and MGSD 3, respectively. Fluorescence quenching methods also prove their binding characteristics, and 200 ns simulations studies showed that the RMSDs for the entire complex were less than 2.8 Å. The in vivo results showed that methyl gallate was required approximately five times diclofenac for the same level of effect, and the synthesised (MGSD 1) compound required only approximately 1/12 of diclofenac for the same level of effect in in-vivo studies. The preeminent expression of COX-2 and TNF-α genes was significantly decreased after the treatment of the methyl gallate derivative. Hence, the in vivo results showed that the referenced synthetic derivative might have more arthritis-reducing properties than the parent compound methyl gallate and is more potent than the standard drug diclofenac, with no apparent induced toxicity.
Spatio-temporal modelling of routine health facility data for malaria risk micro-stratification in mainland Tanzania
Authors: Thawer Sumaiyya G. , Golumbeanu Monica , Lazaro Samwel , Chacky Frank , Munisi Khalifa , Aaron Sijenunu , Molteni Fabrizio , Lengeler Christian , Pothin Emilie , Snow Robert W. , Alegana Victor A.
Published: June 2023

As malaria transmission declines, the need to monitor the heterogeneity of malaria risk at finer scales becomes critical to guide community-based targeted interventions. Although routine health facility (HF) data can provide epidemiological evidence at high spatial and temporal resolution, its incomplete nature of information can result in lower administrative units without empirical data. To overcome geographic sparsity of data and its representativeness, geo-spatial models can leverage routine information to predict risk in un-represented areas as well as estimate uncertainty of predictions. Here, a Bayesian spatio-temporal model was applied on malaria test positivity rate (TPR) data for the period 2017–2019 to predict risks at the ward level, the lowest decision-making unit in mainland Tanzania. To quantify the associated uncertainty, the probability of malaria TPR exceeding programmatic threshold was estimated. Results showed a marked spatial heterogeneity in malaria TPR across wards. 17.7 million people resided in areas where malaria TPR was high (≥ 30; 90% certainty) in the North-West and South-East parts of Tanzania. Approximately 11.7 million people lived in areas where malaria TPR was very low (< 5%; 90% certainty). HF data can be used to identify different epidemiological strata and guide malaria interventions at micro-planning units in Tanzania. These data, however, are imperfect in many settings in Africa and often require application of geo-spatial modelling techniques for estimation.
Alterations in choroidal vascular structures due to serum levels of vascular endothelial growth factor in patients with POEMS syndrome
Authors: Yokouchi Hirotaka , Nagasato Daisuke , Mitamura Yoshinori , Egawa Mariko , Tabuchi Hitoshi , Misawa Sonoko , Kuwabara Satoshi , Baba Takayuki
Published: June 2023

A higher serum vascular endothelial growth factor (VEGF) level can cause choroidal thickening in the choroid of patients with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. We aimed to determine whether fluctuations in serum VEGF levels affect choroidal vascular structures in patients with POEMS syndrome. This retrospective observational case series examined 17 left eyes of 17 patients with POEMS syndrome. Enhanced depth imaging optical coherence tomography (EDI-OCT) images were obtained, and serum VEGF levels were measured at baseline and 6 months after transplantation with dexamethasone (n = 6), thalidomide (n = 8), or lenalidomide (n = 3). EDI-OCT images were binarized using ImageJ software, and we calculated the areas of the whole choroid and the luminal and stromal areas. Subsequently, we determined whether the choroidal vascular structure had changed significantly between baseline and 6 months after treatment. Six months after treatment, serum VEGF levels and the whole choroid, luminal, and stromal areas had decreased significantly compared to the baseline values (all, P < 0.001). The mean luminal area to the whole choroidal area ratio at 6 months after treatment was 0.70 ± 0.03, which was significantly smaller than the ratio at baseline (0.72 ± 0.03; P < 0.001). Whole choroid and luminal area fluctuations were significantly positively correlated with fluctuations in serum VEGF levels (r = 0.626, P = 0.007 and r = 0.585, P = 0.014, respectively). Choroidal thickening induced by VEGF might be caused by increases in the choroidal vessel lumen area. These results may offer insights into the pathogenesis of POEMS syndrome and the role of serum VEGF in choroidal vascular structure, which may apply to other ocular diseases.
Automated COVID-19 detection with convolutional neural networks
Authors: Dumakude Aphelele , Ezugwu Absalom E.
Published: June 2023

This paper focuses on addressing the urgent need for efficient and accurate automated screening tools for COVID-19 detection. Inspired by existing research efforts, we propose two framework models to tackle this challenge. The first model combines a conventional CNN architecture as a feature extractor with XGBoost as the classifier. The second model utilizes a classical CNN architecture with a Feedforward Neural Network for classification. The key distinction between the two models lies in their classification layers. Bayesian optimization techniques are employed to optimize the hyperparameters of both models, enabling a “cheat-start” to the training process with optimal configurations. To mitigate overfitting, transfer learning techniques such as Dropout and Batch normalization are incorporated. The CovidxCT-2A dataset is used for training, validation, and testing purposes. To establish a benchmark, we compare the performance of our models with state-of-the-art methods reported in the literature. Evaluation metrics including Precision, Recall, Specificity, Accuracy, and F1-score are employed to assess the efficacy of the models. The hybrid model demonstrates impressive results, achieving high precision (98.43%), recall (98.41%), specificity (99.26%), accuracy (99.04%), and F1-score (98.42%). The standalone CNN model exhibits slightly lower but still commendable performance, with precision (98.25%), recall (98.44%), specificity (99.27%), accuracy (98.97%), and F1-score (98.34%). Importantly, both models outperform five other state-of-the-art models in terms of classification accuracy, as demonstrated by the results of this study.
Functional outcome in patients with traumatic or hemorrhagic brain injuries undergoing decompressive craniectomy versus craniotomy and 6-month rehabilitation
Authors: Pingue Valeria , Franciotta Diego
Published: June 2023

Decompressive craniectomy (DC) and craniotomy (CT) to treat increased intracranial pressure after brain injury are common but controversial choices in clinical practice. Studying a large cohort of patients with traumatic brain injury (TBI) and hemorrhagic stroke (HS) on rehabilitation pathways, we aimed to determine the impact of DC and CT on functional outcome/mortality, and on seizures occurrence. This observational retrospective study included patients with either TBI, or HS, who underwent DC or CT, consecutively admitted to our unit for 6-month neurorehabilitation programs between January 1, 2009 and December 31, 2018. Neurological status using Glasgow Coma Scale (GCS), and rehabilitation outcome with Functional Independence Measure, both assessed at baseline and on discharge, post-DC cranioplasty, prophylactic antiepileptic drug use, occurrence of early/late seizures, infectious complications, and death during hospitalization were evaluated and analyzed with linear and logistic regression models. Among 278 patients, DC was performed in 98 (66.2%) with HS, and in 98 (75.4%) with TBI, whilst CT in 50 (33.8%) with HS, and in 32 (24.6%) with TBI. On admission, GCS scores were lower in patients treated with CT than in those with DC (HS, p = 0.016; TBI, p = 0.024). Severity of brain injury and older age were the main factors affecting functional outcome, without between-group differences, but DC associated with worse functional outcome, independently from severity or type of brain injury. Unprovoked seizures occurred post-DC cranioplasty more frequently after HS (OR = 5.142, 95% CI 1.026–25.784, p = 0.047). DC and CT shared similar risk of mortality, which associated with sepsis (OR = 16.846, 95% CI 5.663–50.109, p < 0.0001), or acute symptomatic seizures (OR = 4.282, 95% CI 1.276–14.370, p = 0.019), independently from the neurosurgery procedures. Among CT and DC, the latter neurosurgical procedure is at major risk of worse functional outcome in patients with mild-to-severe TBI, or HS undergoing an intensive rehabilitation program. Complications with sepsis or acute symptomatic seizures increase the risk of death.
Assessing physical abilities of sarcopenia patients using gait analysis and smart insole for development of digital biomarker
Authors: Kim Shinjune , Park Seongjin , Lee Sangyeob , Seo Sung Hyo , Kim Hyeon Su , Cha Yonghan , Kim Jung-Taek , Kim Jin-Woo , Ha Yong-Chan , Yoo Jun-Il
Published: June 2023

The aim of this study is to compare variable importance across multiple measurement tools, and to use smart insole and artificial intelligence (AI) gait analysis to create variables that can evaluate the physical abilities of sarcopenia patients. By analyzing and comparing sarcopenia patients with non sarcopenia patients, this study aims to develop predictive and classification models for sarcopenia and discover digital biomarkers. The researchers used smart insole equipment to collect plantar pressure data from 83 patients, and a smart phone to collect video data for pose estimation. A Mann–Whitney U was conducted to compare the sarcopenia group of 23 patients and the control group of 60 patients. Smart insole and pose estimation were used to compare the physical abilities of sarcopenia patients with a control group. Analysis of joint point variables showed significant differences in 12 out of 15 variables, but not in knee mean, ankle range, and hip range. These findings suggest that digital biomarkers can be used to differentiate sarcopenia patients from the normal population with improved accuracy. This study compared musculoskeletal disorder patients to sarcopenia patients using smart insole and pose estimation. Multiple measurement methods are important for accurate sarcopenia diagnosis and digital technology has potential for improving diagnosis and treatment.
Connectivity alteration in thalamic nuclei and default mode network-related area in memory processes in mesial temporal lobe epilepsy using magnetoencephalography
Authors: Ishizaki Tomotaka , Maesawa Satoshi , Nakatsubo Daisuke , Yamamoto Hiroyuki , Torii Jun , Mutoh Manabu , Natsume Jun , Hoshiyama Minoru , Saito Ryuta
Published: June 2023

This work aimed to investigate the involvement of the thalamic nuclei in mesial temporal lobe epilepsy (MTLE) and identify the influence of interictal epileptic discharges on the neural basis of memory processing by evaluating the functional connectivity (FC) between the thalamic nuclei and default mode network-related area (DMNRA) using magnetoencephalography. Preoperative datasets of nine patients with MTLE with seizure-free status after surgery and those of nine healthy controls were analyzed. The FC between the thalamic nuclei (anterior nucleus [ANT], mediodorsal nucleus [MD], intralaminar nuclei [IL]), hippocampus, and DMNRA was examined for each of the resting, pre-spike, spike, and post-spike periods in the delta to ripple bands using magnetoencephalography. The FC between the ANT, MD, hippocampus, and medial prefrontal cortex increased in the gamma to ripple bands, whereas the FC between the ANT, IL, and DMNRA decreased in the delta to beta bands, compared with that of the healthy controls at rest. Compared with the rest period, the pre-spike period had significantly decreased FC between the ANT, MD, and DMNRA in the ripple band. Different FC changes between the thalamic nuclei, hippocampus, and DMNRA of specific connections in a particular band may reflect impairment or compensation in the memory processes.
Telomere-related prognostic biomarkers for survival assessments in pancreatic cancer
Authors: Chen Shengyang , Hu Shuiquan , Zhou Baizhong , Cheng Bingbing , Tong Hao , Su Dongchao , Li Xiaoyong , Chen Yanjun , Zhang Genhao
Published: June 2023

Human telomeres are linked to genetic instability and a higher risk of developing cancer. Therefore, to improve the dismal prognosis of pancreatic cancer patients, a thorough investigation of the association between telomere-related genes and pancreatic cancer is required. Combat from the R package “SVA” was performed to correct the batch effects between the TCGA-PAAD and GTEx datasets. After differentially expressed genes (DEGs) were assessed, we constructed a prognostic risk model through univariate Cox regression, LASSO-Cox regression, and multivariate Cox regression analysis. Data from the ICGC, GSE62452, GSE71729, and GSE78229 cohorts were used as test cohorts for validating the prognostic signature. The major impact of the signature on the tumor microenvironment and its response to immune checkpoint drugs was also evaluated. Finally, PAAD tissue microarrays were fabricated and immunohistochemistry was performed to explore the expression of this signature in clinical samples. After calculating 502 telomere-associated DEGs, we constructed a three-gene prognostic signature (DSG2, LDHA, and RACGAP1) that can be effectively applied to the prognostic classification of pancreatic cancer patients in multiple datasets, including TCGA, ICGC, GSE62452, GSE71729, and GSE78229 cohorts. In addition, we have screened a variety of tumor-sensitive drugs targeting this signature. Finally, we also found that protein levels of DSG2, LDHA, and RACGAP1 were upregulated in pancreatic cancer tissues compared to normal tissues by immunohistochemistry analysis. We established and validated a telomere gene-related prognostic signature for pancreatic cancer and confirmed the upregulation of DSG2, LDHA, and RACGAP1 expression in clinical samples, which may provide new ideas for individualized immunotherapy.
The impact of bilateral anodal transcranial direct current stimulation of the premotor and cerebellar cortices on physiological and performance parameters of gymnastic athletes: a randomized, cross-over, sham-controlled study
Authors: Anoushiravani Sajjad , Alizadehgoradel Jaber , Iranpour Asgar , Yousefi Bilehsavar Omid , Pouresmali Asghar , Nitsche Michael A. , Salehinejad Mohammad Ali , Mosayebi-Samani Mohsen , Zoghi Maryam
Published: June 2023

Professional sports performance relies critically on the interaction between the brain and muscles during movement. Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique which modulates cortical excitability and can be used to improve motor performance in athletes. The present study aimed to investigate the effect of bilateral anodal tDCS (2 mA, 20 min) over the premotor cortex or cerebellum on motor and physiological functions and peak performance of professional gymnastics athletes. Seventeen professional gymnastics athletes participated in a randomized, sham-controlled, crossover study. In this study, we assessed the efficacy of two anodal tDCS protocols (2 mA, 20 min) with stimulation over the bilateral premotor cortex or cerebellum with the return electrodes placed over the opposite supraorbital areas. Power speed, strength coordination, endurance, static and dynamic strength, static and dynamic flexibility, and rating of perceived exertion were measured before and immediately after tDCS interventions (bilateral anodal tDCS over premotor cortices, anodal tDCS over the cerebellum, and sham tDCS). Additionally, physiological muscle performance parameters, including maximum voluntary isometric contraction (MVIC) of upper body muscles, were assessed during tDCS. Bilateral anodal tDCS over the premotor cortex, compared to anodal tDCS over the cerebellum and sham tDCS conditions, significantly improved power speed, strength coordination, and static and dynamic strength variables of professional gymnastics athletes. Furthermore, bilateral anodal tDCS over the cerebellum, compared to sham tDCS, significantly improved strength coordination. Moreover, bilateral premotor anodal tDCS significantly increased MVIC of all upper body muscles during stimulation, while anodal tDCS over the cerebellum increased MVIC in only some muscles. Bilateral anodal tDCS over the premotor cortex, and to a minor degree over the cerebellum, might be suited to improve some aspects of motor and physiological functions and peak performance levels of professional gymnastics athletes.

Clinical Trial Registration ID: IRCT20180724040579N2.
Introduction to Green Sample Preparation
Authors: Canpolat Gurbet , Dolak İbrahim , Hussain Chaudhery Ghazanfar , Keçili Rüstem , Hussain Chaudhery Mustansar
Published: June 2023

Preparation of samples is a critical stage in the analytical procedure that has benefited significantly from advances in green chemistry. Green sample preparation entails eliminating the use of toxic solvents and minimizing energy requirements throughout the procedure. This chapter gives an overview of green extraction processes, as well as a brief introduction to their theoretical foundations and a look at how they can be used in the fields of analytical and bioanalytical research, with a special focus on food, environmental, and biological matrices.
Molecularly Imprinted Polymers in Green Sample Preparation
Authors: Díaz-Álvarez M. , Martín-Esteban A.
Published: June 2023

The use of molecularly imprinted polymers in sample preparation is nowadays well-established thanks to their ability to provide unprecedented selectivity during extraction and clean-up steps. However, both their synthesis and subsequent use are far from being considered green. Accordingly, in the present chapter, the greenness of the different steps and strategies for the preparation and use of molecularly imprinted polymers in sample preparation is critically reviewed, and recent alternatives to make the use of molecularly imprinted polymers more sustainable are provided.