bluuebunny/crossref_metadata_2025_split huggingface dataset:
Widefield imaging of rapid pan-cortical voltage dynamics with an indicator evolved for one-photon microscopy
Authors: Lu Xiaoyu , Wang Yunmiao , Liu Zhuohe , Gou Yueyang , Jaeger Dieter , St-Pierre François 
Published: October 2023

AbstractWidefield imaging with genetically encoded voltage indicators (GEVIs) is a promising approach for understanding the role of large cortical networks in the neural coding of behavior. However, the limited performance of current GEVIs restricts their deployment for single-trial imaging of rapid neuronal voltage dynamics. Here, we developed a high-throughput platform to screen for GEVIs that combine fast kinetics with high brightness, sensitivity, and photostability under widefield one-photon illumination. Rounds of directed evolution produced JEDI-1P, a green-emitting fluorescent indicator with enhanced performance across all metrics. Next, we optimized a neonatal intracerebroventricular delivery method to achieve cost-effective and wide-spread JEDI-1P expression in mice. We also developed an approach to correct optical measurements from hemodynamic and motion artifacts effectively. Finally, we achieved stable brain-wide voltage imaging and successfully tracked gamma-frequency whisker and visual stimulations in awake mice in single trials, opening the door to investigating the role of high-frequency signals in brain computations.
Clinically relevant atovaquone-resistant human malaria parasites fail to transmit by mosquito
Authors: Balta Victoria A. , Stiffler Deborah , Sayeed Abeer , Tripathi Abhai K. , Elahi Rubayet , Mlambo Godfree , Bakshi Rahul P. , Dziedzic Amanda G. , Jedlicka Anne E. , Nenortas Elizabeth , Romero-Rodriguez Keyla , Canonizado Matthew A. , Mann Alexis , Owen Andrew , Sullivan David J. , Prigge Sean T. , Sinnis Photini , Shapiro Theresa A. 
Published: October 2023

AbstractLong-acting injectable medications, such as atovaquone, offer the prospect of a “chemical vaccine” for malaria, combining drug efficacy with vaccine durability. However, selection and transmission of drug-resistant parasites is of concern. Laboratory studies have indicated that atovaquone resistance disadvantages parasites in mosquitoes, but lack of data on clinically relevant Plasmodium falciparum has hampered integration of these variable findings into drug development decisions. Here we generate atovaquone-resistant parasites that differ from wild type parent by only a Y268S mutation in cytochrome b, a modification associated with atovaquone treatment failure in humans. Relative to wild type, Y268S parasites evidence multiple defects, most marked in their development in mosquitoes, whether from Southeast Asia (Anopheles stephensi) or Africa (An. gambiae). Growth of asexual Y268S P. falciparum in human red cells is impaired, but parasite loss in the mosquito is progressive, from reduced gametocyte exflagellation, to smaller number and size of oocysts, and finally to absence of sporozoites. The Y268S mutant fails to transmit from mosquitoes to mice engrafted with human liver cells and erythrocytes. The severe-to-lethal fitness cost of clinically relevant atovaquone resistance to P. falciparum in the mosquito substantially lessens the likelihood of its transmission in the field.
Comprehensive profiling of neutralizing polyclonal sera targeting coxsackievirus B3
Authors: Álvarez-Rodríguez Beatriz , Buceta Javier , Geller Ron 
Published: October 2023

AbstractDespite their fundamental role in resolving viral infections, our understanding of how polyclonal neutralizing antibody responses target non-enveloped viruses remains limited. To define these responses, we obtained the full antigenic profile of multiple human and mouse polyclonal sera targeting the capsid of a prototypical picornavirus, coxsackievirus B3. Our results uncover significant variation in the breadth and strength of neutralization sites targeted by individual human polyclonal responses, which contrasted with homogenous responses observed in experimentally infected mice. We further use these comprehensive antigenic profiles to define key structural and evolutionary parameters that are predictive of escape, assess epitope dominance at the population level, and reveal a need for at least two mutations to achieve significant escape from multiple sera. Overall, our data provide a comprehensive analysis of how polyclonal sera target a non-enveloped viral capsid and help define both immune dominance and escape at the population level.
Next-generation CRISPR gene-drive systems using Cas12a nuclease
Authors: Sanz Juste Sara , Okamoto Emily M. , Nguyen Christina , Feng Xuechun , López Del Amo Víctor 
Published: October 2023

AbstractOne method for reducing the impact of vector-borne diseases is through the use of CRISPR-based gene drives, which manipulate insect populations due to their ability to rapidly propagate desired genetic traits into a target population. However, all current gene drives employ a Cas9 nuclease that is constitutively active, impeding our control over their propagation abilities and limiting the generation of alternative gene drive arrangements. Yet, other nucleases such as the temperature sensitive Cas12a have not been explored for gene drive designs in insects. To address this, we herein present a proof-of-concept gene-drive system driven by Cas12a that can be regulated via temperature modulation. Furthermore, we combined Cas9 and Cas12a to build double gene drives capable of simultaneously spreading two independent engineered alleles. The development of Cas12a-mediated gene drives provides an innovative option for designing next-generation vector control strategies to combat disease vectors and agricultural pests.
The decrease in ocean heat transport in response to global warming
Authors: Mecking Jennifer V. , Drijfhout Sybren S. 
Published: October 2023

AbstractThe ocean is taking up additional heat but how this affects ocean circulation and heat transport is unclear. Here, using coupled model intercomparison project phase 5/6 (CMIP5/6) climate projections, we show a future decrease in poleward ocean heat transport (OHT) across all Northern Hemisphere latitudes and south of 10° S. Most notably, the CMIP5/6 multimodel mean reduction in poleward OHT for the Atlantic at 26.5° N and Indo-Pacific at 20° S is 0.093–0.304 PW and 0.097–0.194 PW, respectively, dependent on scenario and CMIP phase. These changes in OHT are driven by decline in overturning circulation dampened by upper ocean warming. In the Southern Ocean, the reduction in poleward OHT at 55° S is 0.071–0.268 PW. The projected changes are stronger in CMIP6, even when corrected for its larger climate sensitivity. This is especially noticable in the Atlantic Ocean for the weaker forcing scenarios (shared socioeconomic pathway SSP 1-2.6/representative concentration pathways RCP 2.6), where the decrease is 2.5 times larger at 26.5° N due to a stronger decline in the Atlantic meridional overturning circulation.
Activation of human STING by a molecular glue-like compound
Authors: Li Jie , Canham Stephen M. , Wu Hua , Henault Martin , Chen Lihao , Liu Guoxun , Chen Yu , Yu Gary , Miller Howard R. , Hornak Viktor , Brittain Scott M. , Michaud Gregory A. , Tutter Antonin , Broom Wendy , Digan Mary Ellen , McWhirter Sarah M. , Sivick Kelsey E. , Pham Helen T. , Chen Christine H. , Tria George S. , McKenna Jeffery M. , Schirle Markus , Mao Xiaohong , Nicholson Thomas B. , Wang Yuan , Jenkins Jeremy L. , Jain Rishi K. , Tallarico John A. , Patel Sejal J. , Zheng Lianxing , Ross Nathan T. , Cho Charles Y. , Zhang Xuewu , Bai Xiao-Chen , Feng Yan 
Published: October 2023

AbstractStimulator of interferon genes (STING) is a dimeric transmembrane adapter protein that plays a key role in the human innate immune response to infection and has been therapeutically exploited for its antitumor activity. The activation of STING requires its high-order oligomerization, which could be induced by binding of the endogenous ligand, cGAMP, to the cytosolic ligand-binding domain. Here we report the discovery through functional screens of a class of compounds, named NVS-STGs, that activate human STING. Our cryo-EM structures show that NVS-STG2 induces the high-order oligomerization of human STING by binding to a pocket between the transmembrane domains of the neighboring STING dimers, effectively acting as a molecular glue. Our functional assays showed that NVS-STG2 could elicit potent STING-mediated immune responses in cells and antitumor activities in animal models.
Characterization of immune microenvironment in patients with HPV-positive and negative head and neck cancer
Authors: Wang Zhongqiu , Wang Qingxin , Tao Yuxuan , Chen Jingru , Yuan Zhiyong , Wang Peiguo 
Published: October 2023

AbstractHuman papillomavirus (HPV) status strongly predicts positive clinical outcomes in patients with head and neck squamous cell cancer (HNSCC); however, the potential reasons have not been fully elucidated. Here, we characterized the immune context in HPV+ and HPV− HNSCC by integrating scRNA-seq and bulk RNA-seq data. In scRNA-seq data, HPV + HNSCC displayed increased B cells, plasma cells, CD4+ effector T cells, and decreased macrophages and mast cells. This finding was validated using bulk-cell data. Plasma cells predicted improved survival, and macrophages were associated with survival disadvantage. 1403 upregulated and 1877 downregulated differential expressed genes (DEGs) were obtained. Gene Ontology and KEGG enrichment analysis showed these DEGs focused on cytokine-related activity. Transcriptional analysis of B and plasma cells revealed associations between B-cell surface marker FCER2 and improved survival. In vitro assays confirmed the ability of FCER2 to suppress cellular proliferation and migration of HPV + tumors. In conclusion, our analysis revealed a heterogeneous tumor immune environment (TME) for HPV+ and HPV− HNSCC. Further, FCER2+ B cells contribute to antitumor immunity.
Laser melting manufacturing of large elements of lunar regolith simulant for paving on the Moon
Authors: Ginés-Palomares Juan-Carlos , Fateri Miranda , Kalhöfer Eckehard , Schubert Tim , Meyer Lena , Kolsch Nico , Brandić Lipińska Monika , Davenport Robert , Imhof Barbara , Waclavicek René , Sperl Matthias , Makaya Advenit , Günster Jens 
Published: October 2023

AbstractThe next steps for the expansion of the human presence in the solar system will be taken on the Moon. However, due to the low lunar gravity, the suspended dust generated when lunar rovers move across the lunar soil is a significant risk for lunar missions as it can affect the systems of the exploration vehicles. One solution to mitigate this problem is the construction of roads and landing pads on the Moon. In addition, to increase the sustainability of future lunar missions, in-situ resource utilization (ISRU) techniques must be developed. In this paper, the use of concentrated light for paving on the Moon by melting the lunar regolith is investigated. As a substitute of the concentrated sunlight, a high-power CO2 laser is used in the experiments. With this set-up, a maximum laser spot diameter of 100 mm can be achieved, which translates in high thicknesses of the consolidated layers. Furthermore, the lunar regolith simulant EAC-1A is used as a substitute of the actual lunar soil. At the end of the study, large samples (approximately 250 × 250 mm) with interlocking capabilities were fabricated by melting the lunar simulant with the laser directly on the powder bed. Large areas of lunar soil can be covered with these samples and serve as roads and landing pads, decreasing the propagation of lunar dust. These manufactured samples were analysed regarding their mineralogical composition, internal structure and mechanical properties.
Comparing laser speckle contrast imaging and indocyanine green angiography for assessment of parathyroid perfusion
Authors: Mannoh Emmanuel A. , Baregamian Naira , Thomas Giju , Solόrzano Carmen C. , Mahadevan-Jansen Anita 
Published: October 2023

AbstractAccurate intraoperative assessment of parathyroid blood flow is crucial to preserve function postoperatively. Indocyanine green (ICG) angiography has been successfully employed, however its conventional application has limitations. A label-free method overcomes these limitations, and laser speckle contrast imaging (LSCI) is one such method that can accurately detect and quantify differences in parathyroid perfusion. In this study, twenty-one patients undergoing thyroidectomy or parathyroidectomy were recruited to compare LSCI and ICG fluorescence intraoperatively. An experimental imaging device was used to image a total of 37 parathyroid glands. Scores of 0, 1 or 2 were assigned for ICG fluorescence by three observers based on perceived intensity: 0 for little to no fluorescence, 1 for moderate or patchy fluorescence, and 2 for strong fluorescence. Speckle contrast values were grouped according to these scores. Analyses of variance were performed to detect significant differences between groups. Lastly, ICG fluorescence intensity was calculated for each parathyroid gland and compared with speckle contrast in a linear regression. Results showed significant differences in speckle contrast between groups such that parathyroids with ICG score 0 had higher speckle contrast than those assigned ICG score 1, which in turn had higher speckle contrast than those assigned ICG score 2. This was further supported by a correlation coefficient of -0.81 between mean-normalized ICG fluorescence intensity and speckle contrast. This suggests that ICG angiography and LSCI detect similar differences in blood flow to parathyroid glands. Laser speckle contrast imaging shows promise as a label-free alternative that overcomes current limitations of ICG angiography for parathyroid assessment.
InSAR-observed surface deformation in New Mexico’s Permian Basin shows threats and opportunities presented by leaky injection wells
Authors: Graves E. J. , Rinehart A. , Grapenthin R. , Angarita M. F. , Grigg J. 
Published: October 2023

AbstractKnowledge of aquifer dynamics, including groundwater storage changes, is key to effective groundwater resource and reservoir management. Resolving and accurate modeling of these processes requires knowledge of subsurface poroelastic properties and lateral heterogeneity within units of interest. Computationally demanding methods for determining lateral heterogeneity in poroelastic properties exist but remain difficult to practically employ. The InSAR-based detection of uplift over a New Mexico well with a casing breach provides an opportunity to determine poroelastic properties using a tractable 2D analytical plane strain solution for surface uplift created by a pressurized reservoir with overburden. Using a Bayesian inversion framework, we calculate poroelastic properties under deep (depth of well-screen) and shallow (depth of well-breach) conditions. We find that shallow injection is necessary to produce the observed deformation. However, pressure-varying forward solutions for uplift are required to reproduce the temporal evolution of deformation. For this we use realistic shallow poroelastic properties and well dynamics, which reflect the evolving injection conditions at the well breach as the casing further erodes. Analysis of individual interferograms or InSAR time series may provide insights into shallow subsurface heterogeneity or anomalous injection conditions at operating wells more rapidly than scheduled field inspections.
A neural signature of social support mitigates negative emotion
Authors: Pei Rui , Courtney Andrea L. , Ferguson Ian , Brennan Connor , Zaki Jamil 
Published: October 2023

AbstractSocial support can mitigate the impact of distressing events. Such stress buffering elicits activity in many brain regions, but it remains unclear (1) whether this activity constitutes a stable brain signature, and (2) whether brain activity can predict buffering across people. Here, we developed a neural signature that predicted social buffering of negative emotion in response to real life stressors. During neuroimaging, participants (n = 95) responded to stressful autobiographical memories either naturally, or by imagining a conversation with a peer. Using supervised dimensionality reduction and machine learning techniques, we identified a spatio-temporal neural signature that distinguished between these two trials. Activation of this signature was associated with less negative affect across trials, and people who most activated the signature reported more supportive social connections and lower loneliness outside the lab. Together, this work provides a behaviorally relevant neurophysiological marker for social support that underlies stress buffering.
Formulation of water pollutant discharge limits for malathion based on nonsensitive aquatic organism protection
Authors: Wei Yuxia , Liu Qingqing , Zhao Jian 
Published: October 2023

AbstractThe “Integrated Wastewater Discharge Standard” was implemented for water pollutant discharge in China’s pesticide industry, which has no control requirements for particular wastewater pollutants in the industry. In the standard, certain pollutants discharge limits are limited strictly or loosely, resulting in practical management implementation difficulties. In view of the highly selective targeting characteristics of organic pesticide active ingredients in fungicides, insecticides, and herbicides, a method for deriving discharge limits based on the water quality criteria for pesticides for the protection of nonsensitive species is established based on the idea of fully protecting aquatic organisms beyond sensitive objects. Through the use of malathion as an example, by screening its toxicity data in different species of aquatic organisms, the sequence point with the most significant change in the acute toxicity sensitivity of the species is taken as the variation point in the cumulative frequency of the sensitive and nonsensitive species to derive the water quality criteria, using the species sensitivity distribution method as the scientific basis for determining the discharge limits. After a comparative analysis of different simulation models, the sigmoid model, with the best fit, is selected to determine that the sensitive species hazard concentration (HCs) of malathion to aquatic organisms in China is 46.4 µg/L, and the discharge limit derived from the HCs based on the relationship between the environmental capacity and emissions is rounded to 250 µg/L. Studies showed that the relationship between the emissions limit derived from the water quality criteria for protecting nonsensitive species and malathion limit stipulated in the “Environmental Quality Standards for Surface Water” conforms to the corresponding relationship of the quality standard and discharge standard, which can be achieved by current pollution control technology, combined with water quality improvement. The discharge limit offers the advantages of technical accessibility and economic rationality.
Knowledge of recommended antibiotic treatments for community-acquired infections in general medical practice: a cross-sectional study in Occitanie region, France
Authors: Strazzulla Alessio , Ballarin Manuel , Postorino Maria Concetta , Lee Raphaël , Leroy Pierre , Castan Bernard , Diamantis Sylvain 
Published: October 2023

AbstractTo assess and analyse the knowledge of recommended antibiotic treatments, focusing on the appropriate drugs and treatment durations for the most common community-acquired infections in general medical practice in Occitanie region, France. A web-based survey was conducted over a 3-month period, from October, 2018 to January, 2019. All participants answered directly through the online platform. For the analysis of overtreatment risk, a score based system was adopted and two scores were produced: the duration score and the treatment score. 413 general practitioners completed the survey. The overall rate of concordance with guidelines in terms of both drug choice and treatment length was 2974/4956 (60%) answers. Diseases with at least 70% good answers included cystitis, group A streptococcal pharyngitis, and bacterial superficial skin infections. Diseases with fewer than 50% good answers included pyelonephritis, dog bite wounds, and community-acquired pneumonia in patients aged ≥ 65 years. Factors associated with the risk of overtreatment were age > 40 years, country setting and hospital employment. Knowledge of treatment durations is satisfactory with 60% of recommendations being met. However, varying levels were observed according to different diseases. This study highlighted a very high rate of adherence when recommendations were clear. In contrast, low levels of adherence were observed when recommendations were ambiguous or when conflicting guidelines existed.
Entropy analysis of nickel(II) porphyrins network via curve fitting techniques
Authors: Farooq Muhammad Talha , Jiarasuksakun Thiradet , Kaemawichanurat Pawaton 
Published: October 2023

AbstractNickel(II) porphyrins typically adopt a square planar coordination geometry, with the nickel atom located at the center of the porphyrin ring and the coordinating atoms arranged in a square plane. The additional atoms or groups coordinated to the nickel atom in nickel(II) porphyrins are called ligands. Porphyrins have been investigated as potential agents for imaging and treating cancer due to their ability to selectively bind to tumor cells and be used as sensors for a variety of analytes. Nickel(II) porphyrins are relatively stable compounds, with high thermal and chemical stability. They can be stored in a solid state or in solution without significant degradation. In this study, we compute several connectivity indices, such as general Randi’c, hyper Zagreb, and redefined Zagreb indices, based on the degrees of vertices of the chemical graph of nickel porphyrins. Then, we compute the entropy and heat of formation NiP production, among other physical parameters. Using MATLAB, we fit curves between various indices and the thermodynamic properties parameters, notably the heat of formation and entropy, using various linearity- and non-linearity-based approaches. The method’s effectiveness is evaluated using$$R^2$$R2, the sum of squared errors, and root mean square error. We also provide visual representations of these indexes. These mathematical frameworks might offer a mechanism to investigate the thermodynamical characteristics of NiP’s chemical structure under various circumstances, which will help us understand the connection between system dimensions and these metrics.
A spectroscopy based prototype for the noninvasive detection of diabetes from human saliva using nanohybrids acting as nanozyme
Authors: Roy Lopamudra , Mondal Susmita , Bhattacharyya Neha , Ghosh Ria , Banerjee Amrita , Singh Soumendra , Chattopadhyay Arpita , Ahmed Saleh A. , Jassas Rabab S. , Al-Rooqi Munirah M. , Moussa Ziad , Althagafi Ismail I. , Bhattacharya Debasish , Bhattacharya Kallol , Mallick Asim Kumar , Pal Samir Kumar 
Published: October 2023

AbstractThe recent prediction of diabetes to be a global pandemic invites a detection strategy preferably non-invasive, and bloodless to manage the disease and the associated complications. Here, we have synthesized chitosan polymer functionalized, organic–inorganic bio-compatible nano-hybrids of Mn3O4 nanoparticles, and characterized it by utilizing several optical methodologies for the structural characterization which shows the Michaelis Menten (MM) kinetics for glucose and alpha-amylase protein (well-known diabetes biomarkers). We have also studied the potentiality for the detection of alpha-amylase in human salivary secretion which is reported to be strongly correlated with uncontrolled hyperglycemia. Finally, we have developed a prototype for the measurement of glucose (LOD of 0.38 mg/dL, LOQ of 1.15 mg/dL) and HbA1c (LOD of 0.15% and LOQ of 0.45%) utilizing the basic knowledge in the study for the detection of uncontrolled hyperglycemia at the point-of-care. With the limited number of clinical trials, we have explored the potential of our work in combating the diabetic pandemic across the globe in near future.