bluuebunny/crossref_metadata_2025 huggingface dataset:
A Fresh View of the Asian‐Australian Monsoon Complexity: The Intertropical Convective Cell (ITCC) Framework
Authors: Cheng Tat Fan , Lu Mengqian , Wang Bin , Dai Lun
Published: January 2024

The monsoon holds great significance in Asian‐Australian civilization. Recent studies realized the link between the monsoon onset and the seasonal migration of the Intertropical Convergence Zone (ITCZ). However, no clear ITCZ band is observed in the Asian‐Australian sector due to the strong influence of topography. Instead, there exists a large‐scale (∼1,500 km) tropical convective cell––a perennial system that we hereafter coin as the “intertropical convective cell (ITCC).” Using ERA5 reanalysis and satellite‐based outgoing longwave radiation products, here we show by objective detection and tracking that the ITCC exhibits eight phases during its seasonal migration along the Asian‐Maritime land bridge. Particularly, its sudden northward jump in boreal spring coincides well with the earliest (abrupt) onset of the Asian rainy season, while its equatorward retreat heralds the overall (gradual) monsoon withdrawal. These findings demonstrate the close link of the ITCC behavior to the spring‐fall asymmetry of the monsoon. Dynamically, the off‐equatorial ITCC features a monsoon regime with a cross‐equatorial overturning circulation, differing markedly from its equatorial regime with two weak overturning cells on each side. Further budget analyses prove our hypothesis that the north‐south charging gradient of the moist static energy determines the ITCC's spring‐fall asymmetric propagation, illuminating the physical origin of the spring‐fall asymmetry in the monsoon. Our results demonstrate the usefulness of the ITCC framework in understanding the Asian‐Australian monsoon complexity in a fresh and holistic manner. The framework will facilitate monsoon diagnosis, modeling and subseasonal‐to‐seasonal forecasting in the Asian‐Australian sector.
The Relationship Between the Saharan Air Layer, Convective Environmental Conditions, and Precipitation in Puerto Rico
Authors: Miller P. W. , Ramseyer C.
Published: January 2024

The Saharan Air Layer (SAL) is a hot, dry, and dust‐laden feature that advects large concentrations of dust across the Atlantic annually to destination regions in the Americas and Caribbean. However, recent work has suggested the SAL may be a contributing factor to high‐impact drought in the Caribbean basin. While the SAL's characteristic dust loadings have been the focus of much previous research, fewer efforts have holistically engaged the co‐evolution of the dust plume, its associated convective environment, and resultant rainfall in Caribbean islands. This study employs a self‐organizing map (SOM) classification to identify the common trans‐Atlantic dust transport typologies associated with the SAL during June and July 1981–2020. Using the column‐integrated dust flux, termed integrated dust transport (IDT), from MERRA‐2 reanalysis as a SAL proxy, the SOM resolved two common patterns which resembled trans‐Atlantic SAL outbreaks. During these events, the convective environment associated with the SAL, as inferred by the Gálvez‐Davison Index, becomes less conducive to precipitation as the SAL migrates further away from the west African coast. Simultaneously, days with IDT patterns grouped to the SAL outbreak typologies demonstrate island‐wide negative precipitation anomalies in Puerto Rico. The SOM's most distinctive SAL outbreak pattern has experienced a statistically significant increase during the 40‐year study period, becoming roughly 10% more frequent over that time. These results are relevant for both climate scientists and water managers wishing to better anticipate Caribbean droughts on both the long and short terms.
Patterns of Alluviation in Mixed Bedrock‐Alluvial Channels: 2. Controls on the Formation of Alluvial Patches
Authors: Cho Jongseok , Nelson Peter A.
Published: January 2024

Understanding the development and spatial distribution of alluvial patches in mixed bedrock‐alluvial rivers is necessary to predict the mechanisms of the interactions between sediment transport, alluvial cover, and bedrock erosion. This study aims to analyze bedrock alluviation patterns using a 2D morphodynamic model, and to use the model results to better understand the mechanisms responsible for alluvial patterns observed experimentally. A series of simulations are conducted to explore how alluvial patterns in mixed bedrock‐alluvial channels form and evolve for different channel slopes and antecedent sediment layer thicknesses. In initially bare bedrock low‐slope channels, sediment cover increases with increasing sediment supply because areas of Froude‐subcritical flow enable sediment deposition, while in steep‐slope channels the flow remains fully supercritical and the model predicts so‐called runaway alluviation. For channels initially covered with sediment, the model predicts a slope‐dependent sediment supply threshold above which sediment cover increases with increasing sediment supply, and below which the bedrock becomes fully exposed. For a given sediment supply, the fraction of bedrock exposure and average alluvial thickness converge toward the equilibrium value regardless of the initial cover thickness as long as it exceeds a minimum threshold. Steep channels are able to maintain a continuous strip of sediment under sub‐capacity sediment supply conditions by achieving a balance between increased form drag as bedforms develop and reduced surface roughness as the portion of alluvial cover decreases. In lower‐slope channels, alluvial patches are distributed sporadically in regions of the subcritical flow.
Impact of Increased Horizontal Resolution of an Ocean Model on Carbon Circulation in the North Pacific Ocean
Authors: Tsujino H. , Nakano H. , Sakamoto K. , Urakawa L. S. , Toyama K. , Kosugi N. , Kitamura Y. , Ishii M. , Nishikawa S. , Nishikawa H. , Sugiyama T. , Ishikawa Y.
Published: January 2024

The impact of resolving western boundary currents and mesoscale eddies on a carbon circulation simulation for the North Pacific Ocean is investigated to evaluate the merits of using high‐resolution ocean biogeochemical models for climate projections. Simulations by a 100‐km resolution global ocean biogeochemical model with and without embedding a 10‐km resolution model in the North Pacific Ocean are compared. The major improvement in the high‐resolution simulation is the representation of the Kuroshio, its extension current, and the recirculation gyres formed to its south and north, resulting in a proper representation of the North Pacific subtropical mode water (STMW) and an increase in storage of the anthropogenic CO2 (Canth) in STMW by about two‐thirds. The larger storage rate in STMW is caused by supply of a larger amount of warm surface water containing rich Canth to the formation region by the intensified Kuroshio. A huge buoyancy loss from this warm water results in the increased formation of STMW that occupies a vast area in the western subtropical gyre. The surface uptake of Canth in the formation region of STMW is slightly increased but is largely comparable to that of the low‐resolution model. Moreover, there is no structural difference in Canth uptake in other parts of the subtropical region. Thus, the improvement of Canth distribution can be understood as a redistribution of water mass in the subtropical gyre by the improved circulation. The present assessment motivates the use of a high horizontal resolution ocean model in next‐generation projection experiments with carbon cycles.
Exploring hematopoiesis in zebrafish using forward genetic screening
Authors: Song Hyemin , Shin Unbeom , Nam Uijeong , Lee Yoonsung
Published: January 2024

Zebrafish have emerged as a powerful animal model for investigating the genetic basis of hematopoiesis. Owing to its close genetic and developmental similarities to humans, combined with its rapid reproduction and extensive genomic resources, zebrafish have become a versatile and efficient platform for genetic studies. In particular, the forward genetic screening approach has enabled the unbiased identification of novel genes and pathways related to blood development, from hematopoietic stem cell formation to terminal differentiation. Recent advances in mutant gene mapping have further expanded the scope of forward genetic screening, facilitating the identification of previously unknown genes and pathways relevant to hematopoiesis. In this review, we provide an overview of the zebrafish forward screening approach for hematopoietic gene discovery and highlight the key genes and pathways identified using this method. This review emphasizes the importance of zebrafish as a model system for understanding the genetic basis of hematopoiesis and its associated disorders.
Efficacy and safety of esaxerenone (CS-3150) in primary hypertension: a meta-analysis
Authors: Sun Ran , Li Yali , Lv Lei , Zhang Weiliang , Guo Xiaoxia
Published: January 2024

This study aimed to assess the efficacy and safety of esaxerenone (CS-3150) in treating primary hypertension. PubMed (Medline), Cochrane Central Register of Controlled Trials (CENTRAL), and Embase databases were searched for articles published until April 18, 2023. The outcomes included were diastolic blood pressure (DBP), systolic blood pressure (SBP), 24 h DBP, 24 h SBP, and adverse events. The meta-analysis was conducted using RevMan 5.3. This study included three trials. CS-3150 5 mg had a greater effect on lowering the SBP, DBP, 24 h SBP, and 24 h DBP than either CS-3150 2.5 mg or eplerenone 50 mg. In contrast, CS-3150 2.5 mg and eplerenone 50 mg showed no significant difference in lowering DBP, SBP, 24 h DBP, and 24 h SBP. Moreover, adverse events occurred at comparable rates in the three groups. CS-3150 (especially CS-3150 5 mg) is an effective and safe treatment for primary hypertension; which can reduce blood pressure and alleviate hypertensive symptoms.
Enhanced peripheral levels of BDNF and proBDNF: elucidating neurotrophin dynamics in cocaine use disorder
Authors: Pettorruso Mauro , Miuli Andrea , Clemente Katia , Mancusi Gianluca , Migliara Giuseppe , Di Carlo Francesco , Pernaci Giulia , Di Crosta Teresa , Santorelli Mario , d’Andrea Giacomo , De Risio Luisa , Ciavarella Mariaceleste , Baccolini Valentina , Di Meo Ilenia , Cataldo Ivana , Sensi Stefano L. , Martinotti Giovanni
Published: January 2024

Brain-derived neurotrophic factor (BDNF) and its precursor, proBDNF, are known to significantly contribute to brain homeostasis, neuroplasticity, and neuronal remodeling. Although these neurotrophins are thought to have opposing roles, both play a critical part in shaping long-lasting behavioral changes following substance use. In this context, our study sought to explore the implications of these neurotrophins in the pathophysiology of cocaine use disorder (CUD). We conducted a case-control study, which included 28 individuals seeking treatment for CUD and 38 matched healthy participants. We measured peripheral neurotrophin concentrations via an enzyme-linked immunosorbent assay. Additionally, all participants were screened for cocaine-associated pathways (e.g., cocaine intake, craving intensity), along with associated psychopathological data. Our findings highlighted an increased concentration of BDNF and proBDNF in CUD individuals when compared to healthy controls (BDNF: 18092.80 ± 6844.62 vs. 11334.42 ± 5061.85 pg/ml, p < 0.001; proBDNF: 87.03 ± 33.23 vs. 55.70 ± 23.26 ng/ml, p < 0.001). We further corroborated the relationship between neurotrophin levels and CUD using a linear regression model. Nevertheless, there was no significant difference in the proBDNF to BDNF ratio between the two groups. Interestingly, our study also demonstrated the influence of factors like usage of psychotropic medications, history of psychiatric hospitalizations, and psychiatric diagnoses on neurotrophin dynamics. In conclusion, our study underscores the significance of neurotrophin fluctuations in CUD. The observed increase in BDNF and proBDNF levels could play a pivotal role in driving craving and relapse risk. Thus, a nuanced understanding of these neurobiological underpinnings in CUD might contribute to the development of more targeted and effective therapeutic strategies.
Transcriptomic analysis identifies B-lymphocyte kinase as a therapeutic target for desmoplastic small round cell tumor cancer stem cell-like cells
Authors: Magrath Justin W. , Flinchum Dane A. , Hartono Alifiani B. , Sampath Shruthi Sanjitha , O’Grady Tina M. , Baddoo Melody , Haoyang Liang , Xu Xiaojiang , Flemington Erik K. , Lee Sean B.
Published: January 2024

Desmoplastic small round cell tumor (DSRCT) is an aggressive pediatric cancer caused by the EWSR1-WT1 fusion oncoprotein. The tumor is refractory to treatment with a 5-year survival rate of only 15–25%, necessitating the development of novel therapeutics, especially those able to target chemoresistant subpopulations. Novel in vitro cancer stem cell-like (CSC-like) culture conditions increase the expression of stemness markers (SOX2, NANOG) and reduce DSRCT cell line susceptibility to chemotherapy while maintaining the ability of DSRCT cells to form xenografts. To gain insights into this chemoresistant model, RNA-seq was performed to elucidate transcriptional alterations between DSRCT cells grown in CSC-like spheres and normal 2-dimensional adherent state. Commonly upregulated and downregulated genes were identified and utilized in pathway analysis revealing upregulation of pathways related to chromatin assembly and disassembly and downregulation of pathways including cell junction assembly and extracellular matrix organization. Alterations in chromatin assembly suggest a role for epigenetics in the DSRCT CSC-like state, which was further investigated with ATAC-seq, identifying over 10,000 differentially accessible peaks, including 4444 sphere accessible peaks and 6,120 adherent accessible peaks. Accessible regions were associated with higher gene expression, including increased accessibility of the CSC marker SOX2 in CSC-like culture conditions. These analyses were further utilized to identify potential CSC therapeutic targets, leading to the identification of B-lymphocyte kinase (BLK) as a CSC-enriched, EWSR1-WT1-regulated, druggable target. BLK inhibition and knockdown reduced CSC-like properties, including abrogation of tumorsphere formation and stemness marker expression. Importantly, BLK knockdown reduced DSRCT CSC-like cell chemoresistance, making its inhibition a promising target for future combination therapy.
15-Lipoxygenase promotes resolution of inflammation in lymphedema by controlling Treg cell function through IFN-β
Authors: Zamora A. , Nougué M. , Verdu L. , Balzan E. , Draia-Nicolau T. , Benuzzi E. , Pujol F. , Baillif V. , Lacazette E. , Morfoisse F. , Galitzky J. , Bouloumié A. , Dubourdeau M. , Chaput B. , Fazilleau N. , Malloizel-Delaunay J. , Bura-Rivière A. , Prats A. C. , Garmy-Susini B.
Published: January 2024

Lymphedema (LD) is characterized by the accumulation of interstitial fluid, lipids and inflammatory cell infiltrate in the limb. Here, we find that LD tissues from women who developed LD after breast cancer exhibit an inflamed gene expression profile. Lipidomic analysis reveals decrease in specialized pro-resolving mediators (SPM) generated by the 15-lipoxygenase (15-LO) in LD. In mice, the loss of SPM is associated with an increase in apoptotic regulatory T (Treg) cell number. In addition, the selective depletion of 15-LO in the lymphatic endothelium induces an aggravation of LD that can be rescued by Treg cell adoptive transfer or ALOX15-expressing lentivector injections. Mechanistically, exogenous injections of the pro-resolving cytokine IFN−β restores both 15-LO expression and Treg cell number in a mouse model of LD. These results provide evidence that lymphatic 15-LO may represent a therapeutic target for LD by serving as a mediator of Treg cell populations to resolve inflammation.
AI co-pilot bronchoscope robot
Authors: Zhang Jingyu , Liu Lilu , Xiang Pingyu , Fang Qin , Nie Xiuping , Ma Honghai , Hu Jian , Xiong Rong , Wang Yue , Lu Haojian
Published: January 2024

The unequal distribution of medical resources and scarcity of experienced practitioners confine access to bronchoscopy primarily to well-equipped hospitals in developed regions, contributing to the unavailability of bronchoscopic services in underdeveloped areas. Here, we present an artificial intelligence (AI) co-pilot bronchoscope robot that empowers novice doctors to conduct lung examinations as safely and adeptly as experienced colleagues. The system features a user-friendly, plug-and-play catheter, devised for robot-assisted steering, facilitating access to bronchi beyond the fifth generation in average adult patients. Drawing upon historical bronchoscopic videos and expert imitation, our AI–human shared control algorithm enables novice doctors to achieve safe steering in the lung, mitigating misoperations. Both in vitro and in vivo results underscore that our system equips novice doctors with the skills to perform lung examinations as expertly as seasoned practitioners. This study offers innovative strategies to address the pressing issue of medical resource disparities through AI assistance.
A stratospheric precursor of East Asian summer droughts and floods
Authors: Zhang Ruhua , Zhou Wen , Tian Wenshou , Zhang Yue , Zhang Junxia , Luo Jiali
Published: January 2024

East Asian floods and droughts in summer show a typical dipole pattern with a north-south oscillation centered near 30°N, called the southern drought–northern flood (SDNF) pattern, which has caused significant economic losses and casualties in the past three decades. However, effective explanations and predictions are still challenging, making suitable disaster prevention more difficult. Here, we find that a key predictor of this dipole pattern is the Quasi-Biennial Oscillation (QBO, tropical winds above 10 km). The QBO can modulate precipitation in East Asia, contributing the largest explained variation of this dipole pattern. A QBO-included statistical model can effectively predict summer floods and droughts at least three months in advance and explain at least 75.8% of precipitation variation. More than 30% of the SDNF pattern is attributed to the QBO in July-August 2020 and 2021. This result suggests a good prospect for using the tropical mid- to upper atmosphere in seasonal forecasts for summer.
Thermal Hall effects due to topological spin fluctuations in YMnO3
Authors: Kim Ha-Leem , Saito Takuma , Yang Heejun , Ishizuka Hiroaki , Coak Matthew John , Lee Jun Han , Sim Hasung , Oh Yoon Seok , Nagaosa Naoto , Park Je-Geun
Published: January 2024

The thermal Hall effect in magnetic insulators has been considered a powerful method for examining the topological nature of charge-neutral quasiparticles such as magnons. Yet, unlike the kagome system, the triangular lattice has received less attention for studying the thermal Hall effect because the scalar spin chirality cancels out between adjacent triangles. However, such cancellation cannot be perfect if the triangular lattice is distorted. Here, we report that the trimerized triangular lattice of multiferroic hexagonal manganite YMnO3 produces a highly unusual thermal Hall effect under an applied magnetic field. Our theoretical calculations demonstrate that the thermal Hall conductivity is related to the splitting of the otherwise degenerate two chiralities of its 120˚ magnetic structure. Our result is one of the most unusual cases of topological physics due to this broken Z2 symmetry of the chirality in the supposedly paramagnetic state of YMnO3, due to strong topological spin fluctuations with the additional intricacy of a Dzyaloshinskii-Moriya interaction.
Operando formation of highly efficient electrocatalysts induced by heteroatom leaching
Authors: Liu Cong , Mei Bingbao , Shi Zhaoping , Jiang Zheng , Ge Junjie , Xing Wei , Song Ping , Xu Weilin
Published: January 2024

Heterogeneous nano-electrocatalysts doped with nonmetal atoms have been studied extensively based on the so-called dopant-based active sites, while little attention has been paid to the stability of these dopants under working conditions. In this work, we reveal significantly, when the redox working potential is too low negatively or too high positively, the active sites based on these dopants actually tend to collapse. It means that some previously observed “remarkable catalytic performance” actually originated from some unknown active sites formed in situ. Take the Bi-F for the CO2RR as an example, results show that the observed remarkable activity and stability were not directly from F-based active sites, but the defective Bi sites formed in situ after the dopant leaching. Such a fact is unveiled from several heteroatom-doped nanocatalysts for four typical reactions (CO2RR, HER, ORR, and OER). This work provides insight into the role of dopants in electrocatalysis.
Rydberg electron stabilizes the charge localized state of the diamine cation
Authors: Reimann Marc , Kirsch Christoph , Sebastiani Daniel , Kaupp Martin
Published: January 2024

A previous controversial discussion regarding the interpretation of Rydberg spectra of gaseous dimethylpiperazine (DMP) as showing the co-existence of a localized and delocalized mixed-valent DMP+ radical cation is revisited. Here we show by high-level quantum-chemical calculations that an apparent barrier separating localized and delocalized DMP+ minima in previous multi-reference configuration-interaction (MRCI) calculations and in some other previous computations were due to unphysical curve crossings of the reference wave functions. These discontinuities on the surface are removed in state-averaged MRCI calculations and with some other, orthogonal high-level approaches, which do not provide a barrier and thus no localized minimum. We then proceed to show that in the actually observed Rydberg state of neutral DMP the 3s-type Rydberg electron binds more strongly to a localized positive charge distribution, generating a localized DMP* Rydberg-state minimum, which is absent for the DMP+ cation. This work presents a case where interactions of a Rydberg electron with the underlying cationic core alter molecular structure in a fundamental way.
Gene therapy with bidridistrogene xeboparvovec for limb-girdle muscular dystrophy type 2E/R4: phase 1/2 trial results
Authors: Mendell Jerry R. , Pozsgai Eric R. , Lewis Sarah , Griffin Danielle A. , Lowes Linda P. , Alfano Lindsay N. , Lehman Kelly J. , Church Kathleen , Reash Natalie F. , Iammarino Megan A. , Sabo Brenna , Potter Rachael , Neuhaus Sarah , Li Xiaoxi , Stevenson Herb , Rodino-Klapac Louise R.
Published: January 2024

Limb-girdle muscular dystrophy 2E/R4 is caused by mutations in the β-sarcoglycan (SGCB) gene, leading to SGCB deficiency and consequent muscle loss. We developed a gene therapy approach based on functional replacement of the deficient SCB protein. Here we report interim results from a first-in-human, open-label, nonrandomized, phase 1/2 trial evaluating the safety and efficacy of bidridistrogene xeboparvovec, an adeno-associated virus-based gene therapy containing a codon-optimized, full-length human SGCB transgene. Patients aged 4–15 years with confirmed SGCB mutations at both alleles received one intravenous infusion of either 1.85 × 1013 vector genome copies kg−1 (Cohort 1, n = 3) or 7.41 × 1013 vector gene copies kg−1 (Cohort 2, n = 3). Primary endpoint was safety, and secondary endpoint was change in SGCB expression in skeletal muscle from baseline to Day 60. We report interim Year 2 results (trial ongoing). The most frequent treatment-related adverse events were vomiting (four of six patients) and gamma-glutamyl transferase increase (three of six patients). Serious adverse events resolved with standard therapies. Robust SGCB expression was observed: Day 60 mean (s.d.) percentage of normal expression 36.2% (2.7%) in Cohort 1 and 62.1% (8.7%) in Cohort 2. Post hoc exploratory analysis showed preliminary motor improvements using the North Star Assessment for Limb-girdle Type Muscular Dystrophies maintained through Year 2. The 2-year safety and efficacy of bidridistrogene xeboparvovec support clinical development advancement. Further studies are necessary to confirm the long-term safety and efficacy of this gene therapy. ClinicalTrials.gov registration: NCT03652259.
Image restoration of degraded time-lapse microscopy data mediated by near-infrared imaging
Authors: Gritti Nicola , Power Rory M. , Graves Alyssa , Huisken Jan
Published: January 2024

Time-lapse fluorescence microscopy is key to unraveling biological development and function; however, living systems, by their nature, permit only limited interrogation and contain untapped information that can only be captured by more invasive methods. Deep-tissue live imaging presents a particular challenge owing to the spectral range of live-cell imaging probes/fluorescent proteins, which offer only modest optical penetration into scattering tissues. Herein, we employ convolutional neural networks to augment live-imaging data with deep-tissue images taken on fixed samples. We demonstrate that convolutional neural networks may be used to restore deep-tissue contrast in GFP-based time-lapse imaging using paired final-state datasets acquired using near-infrared dyes, an approach termed InfraRed-mediated Image Restoration (IR2). Notably, the networks are remarkably robust over a wide range of developmental times. We employ IR2 to enhance the information content of green fluorescent protein time-lapse images of zebrafish and Drosophila embryo/larval development and demonstrate its quantitative potential in increasing the fidelity of cell tracking/lineaging in developing pescoids. Thus, IR2 is poised to extend live imaging to depths otherwise inaccessible.
Design of complicated all-α protein structures
Authors: Sakuma Koya , Kobayashi Naohiro , Sugiki Toshihiko , Nagashima Toshio , Fujiwara Toshimichi , Suzuki Kano , Kobayashi Naoya , Murata Takeshi , Kosugi Takahiro , Tatsumi-Koga Rie , Koga Nobuyasu
Published: January 2024

A wide range of de novo protein structure designs have been achieved, but the complexity of naturally occurring protein structures is still far beyond these designs. Here, to expand the diversity and complexity of de novo designed protein structures, we sought to develop a method for designing ‘difficult-to-describe’ α-helical protein structures composed of irregularly aligned α-helices like globins. Backbone structure libraries consisting of a myriad of α-helical structures with five or six helices were generated by combining 18 helix–loop–helix motifs and canonical α-helices, and five distinct topologies were selected for de novo design. The designs were found to be monomeric with high thermal stability in solution and fold into the target topologies with atomic accuracy. This study demonstrated that complicated α-helical proteins are created using typical building blocks. The method we developed will enable us to explore the universe of protein structures for designing novel functional proteins.
Auto-detection of the coronavirus disease by using deep convolutional neural networks and X-ray photographs
Authors: Hussein Ahmad MohdAziz , Sharifai Abdulrauf Garba , Alia Osama Moh’d , Abualigah Laith , Almotairi Khaled H. , Abujayyab Sohaib K. M. , Gandomi Amir H.
Published: January 2024

The most widely used method for detecting Coronavirus Disease 2019 (COVID-19) is real-time polymerase chain reaction. However, this method has several drawbacks, including high cost, lengthy turnaround time for results, and the potential for false-negative results due to limited sensitivity. To address these issues, additional technologies such as computed tomography (CT) or X-rays have been employed for diagnosing the disease. Chest X-rays are more commonly used than CT scans due to the widespread availability of X-ray machines, lower ionizing radiation, and lower cost of equipment. COVID-19 presents certain radiological biomarkers that can be observed through chest X-rays, making it necessary for radiologists to manually search for these biomarkers. However, this process is time-consuming and prone to errors. Therefore, there is a critical need to develop an automated system for evaluating chest X-rays. Deep learning techniques can be employed to expedite this process. In this study, a deep learning-based method called Custom Convolutional Neural Network (Custom-CNN) is proposed for identifying COVID-19 infection in chest X-rays. The Custom-CNN model consists of eight weighted layers and utilizes strategies like dropout and batch normalization to enhance performance and reduce overfitting. The proposed approach achieved a classification accuracy of 98.19% and aims to accurately classify COVID-19, normal, and pneumonia samples.
Optimization, characterization, and cytotoxicity studies of novel anti-tubercular agent-loaded liposomal vesicles
Authors: Obiedallah Manar M. , Mironov Maxim A. , Belyaev Danila V. , Ene Antoaneta , Vakhrusheva Diana V. , Krasnoborova Svetlana Yu. , Bershitsky Sergey Y. , Shchepkin Daniil V. , Minin Artem S. , Ishmetova Rashida I. , Ignatenko Nina K. , Tolshchina Svetlana G. , Fedorova Olga V. , Rusinov Gennady L.
Published: January 2024

The treatment of tuberculosis is still a challenging process due to the widespread of pathogen strains resistant to antibacterial drugs, as well as the undesirable effects of anti-tuberculosis therapy. Hence, the development of safe and effective new anti-antitubercular agents, in addition to suitable nanocarrier systems, has become of utmost importance and necessity. Our research aims to develop liposomal vesicles that contain newly synthesized compounds with antimycobacterial action. The compound being studied is a derivative of imidazo-tetrazine named 3-(3,5-dimethylpyrazole-1-yl)-6-(isopropylthio) imidazo [1,2-b] [1,2,4,5] tetrazine compound. Several factors that affect liposomal characteristics were studied. The maximum encapsulation efficiency was 53.62 ± 0.09. The selected liposomal formulation T8* possessed a mean particle size of about 205.3 ± 3.94 nm with PDI 0.282, and zeta potential was + 36.37 ± 0.49 mv. The results of the in vitro release study indicated that the solubility of compound I was increased by its incorporation in liposomes. The free compound and liposomal preparation showed antimycobacterial activity against Mycobacterium tuberculosis H37Rv (ATCC 27294) at MIC value 0.94–1.88 μg/ml. We predict that the liposomes may be a good candidate for delivering new antitubercular drugs.
A pilot optical coherence tomography angiography classification of retinal neovascularization in retinopathy of prematurity
Authors: Chen Xi , Imperio Ryan , Viehland Christian , Patel Pujan R. , Tran-Viet Du , Mangalesh Shwetha , Prakalapakorn S. Grace , Freedman Sharon F. , Izatt Joseph A. , Toth Cynthia A. ,   BabySTEPS Group
Published: January 2024

Extraretinal neovascularization is a hallmark of treatment-requiring retinopathy of prematurity (ROP). Optical coherence tomography angiography (OCTA) offers vascular flow and depth information not available from indirect ophthalmoscopy and structural OCT, but OCTA is only commercially available as a tabletop device. In this study, we used an investigational handheld OCTA device to study the vascular flow in and around retinal neovascularization in seven preterm infants with treatment-requiring ROP and contrasted them to images of vascular flow in six infants of similar age without neovascular ROP. We showed stages of retinal neovascularization visible in preterm infants from 32 to 47 weeks postmenstrual age: Intraretinal neovascularization did not break through the internal limiting membrane; Subclinical neovascular buds arose from retinal vasculature with active flow through the internal limiting membrane; Flat neovascularization in aggressive ROP assumed a low-lying configuration compared to elevated extraretinal neovascular plaques; Regressed neovascularization following treatment exhibited decreased vascular flow within the preretinal tissue, but flow persisted in segments of retinal vessels elevated from their original intraretinal location. These findings enable a pilot classification of retinal neovascularization in eyes with ROP using OCTA, and may be helpful in detailed monitoring of disease progression, treatment response and predicting reactivation.
Copper-catalyzed synthesis of pyrazolo[1,5-a]pyrimidine based triazole-linked glycohybrids: mechanistic insights and bio-applications
Authors: Tiwari Ghanshyam , Khanna Ashish , Tyagi Rajdeep , Mishra Vinay Kumar , Narayana Chintam , Sagar Ram
Published: January 2024

Hybrid molecules maintain their stronghold in the drug market, with over 60% of drug candidates in pharmaceutical industries. The substantial expenses for developing and producing biologically privileged drugs are expected to create opportunities for producing hybrid molecule-based drugs. Therefore, we have developed a simple and efficient copper-catalyzed approach for synthesizing a wide range of triazole-linked glycohybrids derived from pyrazolo[1,5-a]pyrimidines. Employing a microwave-assisted copper-catalyzed approach, we developed a concise route using various 7-O-propargylated pyrazolo[1,5-a]pyrimidines and 1-azidoglycosides. This strategy afforded a series of twenty-seven glycohybrids up to 98% yield with diverse stereochemistry. All were achieved within a remarkably shortened time frame. Our investigation extends to evaluating the anticancer potential of these synthesized triazole-linked pyrazolo[1,5-a] pyrimidine-based glycohybrids. In-vitro assays against MCF-7, MDA-MB231, and MDA-MB453 cell lines reveal intriguing findings. (2R,3S,4S,5R,6R)-2-(acetoxymethyl)-6-(4-(((5-(4-chlorophenyl)pyrazolo[1,5-a]pyrimidin-7-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate emerges as a standout with better anticancer activity against MDA-MB231 cells (IC50 = 29.1 µM), while (2R,3R,4S,5R,6R)-2-(acetoxymethyl)-6-(4-(((5-(4-chlorophenyl)pyrazolo[1,5-a]pyrimidin-7-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate demonstrates the best inhibitory effects against MCF-7 cells (IC50 = 15.3 µM) in all derived compounds. These results align with our docking analysis and structure–activity relationship (SAR) investigations, further validating the in-vitro outcomes. This work not only underscores the synthetic utility of our devised protocol but also highlights the promising potential of these glycohybrids as candidates for further anticancer therapeutic exploration.
The mitochondrial DNA common deletion as a potential biomarker of cancer-associated fibroblasts from skin basal and squamous cell carcinomas
Authors: Fontana Gabriele A. , MacArthur Michael R. , Rotankova Nadezhda , Di Filippo Michela , Beer Hans-Dietmar , Gahlon Hailey L.
Published: January 2024

Cancer-associated fibroblasts (CAFs) are components of the tumor microenvironment and represent appealing therapeutic targets for translational studies. Conventional protein-based biomarkers for CAFs have been reported to be limited in their specificity, rendering difficult the identification of CAFs from normal fibroblasts (NFs) in clinical samples and dampening the development of CAF-targeted therapies to treat cancer. In this study, we propose the mitochondrial RNA and the mitochondrial DNA (mtDNA) common deletion (CD) as novel indicators of CAF identity. We found that cancer-activation correlated with decreased levels of the mtDNA CD, a condition not due to altered mitochondria count or cellular redox state, but potentially linked to the generalized overexpression of mtDNA maintenance genes in CAFs. Decreased mtDNA CD content in CAFs was associated with moderate to strong overexpression of mtDNA-encoded genes and to slightly improved mitochondrial function. We identified similar patterns of upregulation of mtDNA-encoded genes in independent single-cell RNA seq data obtained from squamous cell carcinoma (SCC) patients. By using the identified nucleic acids-based indicators, identification of CAFs from NFs could be improved, leading to potential therapeutic benefits in advancing translational and clinical studies.
The nascent polypeptide-associated complex subunit Egd1 is required for efficient selective mitochondrial degradation in budding yeast
Authors: Tian Yuan , Okamoto Koji
Published: January 2024

Selective degradation of dysfunctional or excess mitochondria is a fundamental process crucial for cell homeostasis in almost all eukaryotes. This process relies on autophagy, an intracellular self-eating system conserved from yeast to humans and is thus called mitophagy. Detailed mechanisms of mitophagy remain to be fully understood. Here we show that mitochondrial degradation in budding yeast, which requires the pro-mitophagic protein Atg32, is strongly reduced in cells lacking Egd1, a beta subunit of the nascent polypeptide-associated complex acting in cytosolic ribosome attachment and protein targeting to mitochondria. By contrast, loss of the sole alpha subunit Egd2 or the beta subunit paralogue Btt1 led to only a partial or slight reduction in mitophagy. We also found that phosphorylation of Atg32, a crucial step for priming mitophagy, is decreased in the absence of Egd1. Forced Atg32 hyperphosphorylation almost completely restored mitophagy in egd1-null cells. Together, we propose that Egd1 acts in Atg32 phosphorylation to facilitate mitophagy.
Deep learning-based optic disc classification is affected by optic-disc tilt
Authors: Nam Youngwoo , Kim Joonhyoung , Kim Kyunga , Park Kyung-Ah , Kang Mira , Cho Baek Hwan , Oh Sei Yeul , Kee Changwon , Han Jongchul , Lee Ga-In , Kang Min Chae , Lee Dongyoung , Choi Yeeun , Yun Hee Jee , Park Hansol , Kim Jiho , Cho Soo Jin , Chang Dong Kyung
Published: January 2024

We aimed to determine the effect of optic disc tilt on deep learning-based optic disc classification. A total of 2507 fundus photographs were acquired from 2236 eyes of 1809 subjects (mean age of 46 years; 53% men). Among all photographs, 1010 (40.3%) had tilted optic discs. Image annotation was performed to label pathologic changes of the optic disc (normal, glaucomatous optic disc changes, disc swelling, and disc pallor). Deep learning-based classification modeling was implemented to develop optic-disc appearance classification models with the photographs of all subjects and those with and without tilted optic discs. Regardless of deep learning algorithms, the classification models showed better overall performance when developed based on data from subjects with non-tilted discs (AUC, 0.988 ± 0.002, 0.991 ± 0.003, and 0.986 ± 0.003 for VGG16, VGG19, and DenseNet121, respectively) than when developed based on data with tilted discs (AUC, 0.924 ± 0.046, 0.928 ± 0.017, and 0.935 ± 0.008). In classification of each pathologic change, non-tilted disc models had better sensitivity and specificity than the tilted disc models. The optic disc appearance classification models developed based all-subject data demonstrated lower accuracy in patients with the appearance of tilted discs than in those with non-tilted discs. Our findings suggested the need to identify and adjust for the effect of optic disc tilt on the optic disc classification algorithm in future development.
Preparation and characterization of gelatin/chitosan nanocomposite reinforced by NiO nanoparticles as an active food packaging
Authors: Momtaz Mahdieh , Momtaz Elham , Mehrgardi Masoud A. , Momtaz Fatemeh , Narimani Tahmineh , Poursina Farkhondeh
Published: January 2024

Food packaging with antibacterial properties has attracted much attention recently. In this study, nickel oxide nanoparticles (NiONPs) were synthesized by co-precipitation and then gelatin/chitosan polymer films (GEL/CS) with different percentages of NiONPs, bio-nanocomposites, were prepared by casting. Morphology, crystal microstructure, molecular interactions and thermal stabilities of the NPs and the composite films were characterized by FESEM, XRD, FTIR and TGA, respectively. The bio-nanocomposite films exhibited excellent barrier, thermal and mechanical properties by addition of an optimized content of NPs. For example, the tensile strength (TS) of the GEL/CS film without NPs was 23.83 MPa and increased to 30.13 MPa by incorporation of 1% NPs. The antibacterial properties and toxicity of the films were investigated. These films show good antibacterial behavior against Gram-positive (Staphylococcus aureus) bacteria compared to Gram-negative (Escherichia coli) bacteria. Furthermore, the films were found to be non-toxic to fibroblast cells that came into contact with the films, with a survival rate of more than 88%. Therefore, these films can be applied for food packaging due to their excellent mechanical, barrier, and antibacterial properties.
ITGB1 and DDR activation as novel mediators in acquired resistance to osimertinib and MEK inhibitors in EGFR-mutant NSCLC
Authors: De Rosa Caterina , De Rosa Viviana , Tuccillo Concetta , Tirino Virginia , Amato Luisa , Papaccio Federica , Ciardiello Davide , Napolitano Stefania , Martini Giulia , Ciardiello Fortunato , Morgillo Floriana , Iommelli Francesca , Della Corte Carminia Maria
Published: January 2024

Osimertinib is a third-generation tyrosine kinase inhibitor clinically approved for first-line treatment of EGFR-mutant non-small cell lung cancer (NSCLC) patients. Although an impressive drug response is initially observed, in most of tumors, resistance occurs after different time and an alternative therapeutic strategy to induce regression disease is currently lacking. The hyperactivation of MEK/MAPKs, is one the most common event identified in osimertinib-resistant (OR) NSCLC cells. However, in response to selective drug pressure, the occurrence of multiple mechanisms of resistance may contribute to treatment failure. In particular, the epithelial-to-mesenchymal transition (EMT) and the impaired DNA damage repair (DDR) pathways are recognized as additional cause of resistance in NSCLC thus promoting tumor progression. Here we showed that concurrent upregulation of ITGB1 and DDR family proteins may be associated with an increase of EMT pathways and linked to both osimertinib and MEK inhibitor resistance to cell death. Furthermore, this study demonstrated the existence of an interplay between ITGB1 and DDR and highlighted, for the first time, that combined treatment of MEK inhibitor with DDRi may be relevant to downregulate ITGB1 levels and increase cell death in OR NSCLC cells.
Using optical emission spectroscopy in atmospheric conditions to track the inflight reduction of plasma sprayed TiO2−x feedstock for thermoelectric applications
Authors: Mauer Georg , Gildersleeve V Edward J.
Published: January 2024

Thermal spray deposition (specifically Atmospheric Plasma Spraying, APS) is a well-established surface coating technology with a broad scope of applications (i.e., insulative coatings, tribological coatings, anti-corrosion coatings, etc.). In addition, there is a constant drive to introduce the APS process into new and emerging fields. One such niche application for APS would be sub-stoichiometric TiO2−x coatings with enhanced thermoelectric performance (compared to the bulk material). The APS process in this context has a unique ability—given the use of hydrogen as a plasma gas—to reduce TiO2−x material during processing. However, to this point, there is neither a reliable nor self-consistent method to assess (nor control by parametric optimization) the inflight reduction of molten oxide particles during processing. This study shows that using Optical Emission Spectroscopy (OES), it can be possible—even in atmospheric conditions—to identify characteristic emission peaks associated with the inflight reduction of TiO2 during APS. Using this OES data, the input spray processing parameters and their influence on coating microstructure and the degree of inflight reduction of the material will be shown. Results suggest under equilibrium conditions only a minimal amount of hydrogen gas is needed in the plasma to fulfill the TiO2 reduction.
Diurnal retinal and choroidal gene expression patterns support a role for circadian biology in myopia pathogenesis
Authors: Stone Richard A. , Tobias John W. , Wei Wenjie , Schug Jonathan , Wang Xia , Zhang Lixin , Iuvone P. Michael , Nickla Debora L.
Published: January 2024

The prevalence of myopia (nearsightedness) is increasing to alarming levels, but its etiology remains poorly understood. Because both laboratory and clinical findings suggest an etiologic role for circadian rhythms in myopia development, we assayed gene expression by RNA-Seq in retina and choroid at the onset of unilateral experimental myopia in chick, isolating tissues every 4 h during a single 24-h period from myopic and contralateral control eyes. Occluded versus open eye gene expression differences varied considerably over the 24-h sampling period, with some occurring at multiple times of day but with others showing differences at only a single investigated timepoint. Some of the genes identified in retina or choroid of chick myopia were previously identified as candidate genes for common human myopia. Like differentially expressed genes, pathways identified by Gene Set Enrichment Analysis also varied dramatically by sampling time. Considered with other laboratory data, human genetic and epidemiology data, these findings further implicate circadian events in myopia pathogenesis. The present results emphasize a need to include time of day in mechanistic studies of myopia and to assess circadian biology directly in trying to understand better the origin of myopia and to develop more effective therapies.
Two-phase simulation of entropy optimized mixed convection flow of two different shear-thinning nanomaterials in thermal and mass diffusion systems with Lorentz forces
Authors: Suresha S. , Khan Umair , Soumya D. O. , Venkatesh P. , Gasmi Hatem , Sunitha M. , Zaib Aurang , Al-Naghi Ahmed , Karoui Hatem , Ishak Anuar , Ojok Walter
Published: January 2024

This research compares the momentum, thermal energy, mass diffusion and entropy generation of two shear thinning nanofluids in an angled micro-channel with mixed convection, nonlinear thermal radiation, temperature jump boundary condition and variable thermal conductivity effects. The $$RKF 45$$

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approach was used to solve the Buongiorno nonlinear governing model. The effect of different parameters on the flow, energy, concentration, and entropy generating fields have been graphically illustrated and explained. The hyperbolic tangent nanoliquid has a better velocity than the Williamson nanofluid. The Williamson nanofluid has higher thermal energy and concentration than the hyperbolic tangent nanoliquid in the microchannel. The Grashof number, both thermal and solutal, increases the fluid flow rate throughout the flow system. The energy of the nanoliquid is reduced by the temperature jump condition, while the energy field of the nanoliquid is enhanced by the improving thermal conductivity value. The nanoliquids concentration rises as the Schmitt number rises. The irreversibility rate of the channel system is maximized by the variable thermal conductivity parameter.