bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and antifungal susceptibility profile of uncommon yeast species at Fattouma Bourguiba University Hospital in Tunisia
Authors: Belgacem Sameh , Chebil Wissal , Ben Salem Safa , Babba Oussama , Mastouri Maha , Babba Hamouda
Published: July 2024

Despite the severe impact of uncommon yeast fungal infections and the pressing need for more research on the topic, there are still few studies available on the identification, epidemiology, and susceptibility profile of those pathogens. The aims of the current study were to define the profile of uncommon yeast species at Fattouma Bourguiba University Hospital using phenotypic, molecular, and proteomic methods and to study their antifungal susceptibility profile. Pre-identified uncommon yeast species were collected from 2018 to 2021. These isolates were further identified using phenotypic methods (ID32C® system and Vitek2® YST), matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), and sequencing. The antifungal susceptibility profile was studied using the reference CLSI broth microdilution method. In total, 30 strains were collected during the study period. Referring to the sequencing, the most isolated uncommon species were Saprochaete capitata, Candida lusitaniae, Candida kefyr, Candida inconspicua, and Candida guilliermondii. A total of 90% of isolates were correctly identified by MALDI-TOF MS compared to 76.7% and 63.3% by ID32® C and VITEK® 2 YST, respectively. The isolated species showed variable responses to antifungals. Candida guilliermondii showed increased azole minimum inhibitory concentrations. Misidentification of uncommon yeast species was common using commercial phenotypic methods. The high percentage of concordance of MALDI-TOF results with sequencing highlights its high performance and usefulness as a routine diagnosis tool.
Extended GeV γ-ray emission around the massive star forming region of the W3 complex
Authors: Wu Qi-Hang , Sun Xiao-Na , Yang Rui-Zhi , Ge Ting-Ting , Liang Yun-Feng , Liang En-Wei
Published: July 2024

We analyse the GeV γ-ray emission from the W3 complex using about 14 years of Pass 8 data recorded by the Fermi Large Area Telescope (Fermi-LAT). We resolve the γ-ray emissions around W3 into two components: an elliptical Gaussian overlapping with the molecular gas and a point-like source near the cluster W3 Main. The pion-bump feature of SED for the elliptical Gaussian together with the better fitting result of pion decay model favour the hadronic origin. We further argue that the cosmic rays (CRs) could originate from the interactions between cluster winds and the shock produced by the SNR HB3. The point-like source positionally coincident with the star cluster W3 Main indicates it may be directly powered by near clusters, while its fainter γ-ray emissions below 10 GeV are possibly due to the shelter from dense gas making the low-energy CRs incapable of penetrating the dense materials. Meanwhile, we cannot rule out that the γ-ray emissions originate from the interaction of accelerated protons in SNR with the ambient gas.
Entrainment of hot gas into cold streams: the origin of excessive star formation rates at cosmic noon
Authors: Aung Han , Mandelker Nir , Dekel Avishai , Nagai Daisuke , Semenov Vadim , van den Bosch Frank C
Published: July 2024

We explore the evolution of cold streams from the cosmic web that feed galaxies through their shock-heated circumgalactic medium (CGM) at cosmic noon, $z\simeq 1-5$. In addition to the hydrodynamical instabilities and radiative cooling that we have incorporated in earlier works, we embed the stream and the hot CGM in the gravitational potential of the host dark matter halo, deriving equilibrium profiles for both. Self-gravity within the stream is tentatively ignored. We find that the cold streams gradually entrain a large mass of initially hot CGM gas that cools in the mixing layer and condenses onto the stream. This entrainment, combined with the acceleration down the gravitational potential well, typically triples the inward cold inflow rate into the central galaxy, compared to the original rate at the virial radius, which makes the entrained gas the dominant source of gas supply to the galaxy. The potential sources for the hot gas to be entrained are recycled enriched gas that has been previously ejected from the galaxy, and fresh virial-shock-heated gas that has accumulated in the CGM. This can naturally elevate the star formation rate in the galaxy by a factor of $\sim 3$ compared to the gas accretion rate onto the halo, thus explaining the otherwise puzzling observed excess of star formation at cosmic noon. When accounting for self-shielding of dense gas from the ultraviolet background, we find that the energy radiated from the streams, originating predominantly from the cooling of the entrained gas, is consistent with observed Lyman-$\alpha$ blobs around galaxies.
The Thousand-Pulsar-Array programme on MeerKAT – XV. A comparison of the radio emission properties of slow and millisecond pulsars
Authors: Karastergiou A , Johnston S , Posselt B , Oswald L S , Kramer M , Weltevrede P
Published: July 2024

We use data from the MeerTime project on the MeerKAT telescope to ask whether the radio emission properties of millisecond pulsars (MSPs) and slowly rotating, younger pulsars (SPs) are similar or different. We show that the flux density spectra of both populations are similarly steep, and the widths of MSP profiles obey the same dependence on the rotational period as slow pulsars. We also show that the polarization of MSPs has similar properties to slow pulsars. The commonly used pseudo-luminosity of pulsars, defined as the product of the flux density and the distance squared, is not appropriate for drawing conclusions about the relative intrinsic radio luminosity of SPs and MSPs. We show that it is possible to scale the pseudo-luminosity to account for the pulse duty cycle and the solid angle of the radio beam, in such a way that MSPs and SPs do not show clear differences in intrinsic luminosity. The data therefore support common emission physics between the two populations in spite of orders of magnitude difference in their period derivatives and inferred, surface, dipole magnetic field strengths.
Deep learning insights into non-universality in the halo mass function
Authors: Guo Ningyuan , Lucie-Smith Luisa , Peiris Hiranya V , Pontzen Andrew , Piras Davide
Published: July 2024

The abundance of dark matter haloes is a key cosmological probe in forthcoming galaxy surveys. The theoretical understanding of the halo mass function (HMF) is limited by our incomplete knowledge of the origin of non-universality and its cosmological parameter dependence. We present a deep-learning model which compresses the linear matter power spectrum into three independent factors which are necessary and sufficient to describe the $z=0$ HMF from the state-of-the-art Aemulus emulator to sub-per cent accuracy in a wCDM$+N_\mathrm{eff}$ parameter space. Additional information about growth history does not improve the accuracy of HMF predictions if the matter power spectrum is already provided as input, because required aspects of the former can be inferred from the latter. The three factors carry information about the universal and non-universal aspects of the HMF, which we interrogate via the information-theoretic measure of mutual information. We find that non-universality is captured by recent growth history after matter-dark-energy equality and $N_{\rm eff}$ for $M\sim 10^{13} \, \mathrm{M_\odot }\, h^{-1}$ haloes, and by $\Omega _{\rm m}$ for $M\sim 10^{15} \, \mathrm{M_\odot }\, h^{-1}$. The compact representation learnt by our model can inform the design of emulator training sets to achieve high emulator accuracy with fewer simulations.
Towards a holistic magnetic braking model – II: explaining several long-term internal- and surface-spin properties of solar-like stars and the Sun
Authors: Sarkar Arnab , Eggenberger Patrick , Yungelson Lev , Tout Christopher A
Published: July 2024

We extend our model of magnetic braking (MB), driven by an α–Ω dynamo mechanism, from fully convective M-dwarfs (FCMDs) to explain the surface and internal spin $P_\mathrm{spin}$ evolution of partly convective dwarfs (PCDs) starting from the disc-dispersal stage to the main-sequence turn-off. In our model, the spin of the core is governed by shear at the core-envelope boundary while the spin of the envelope is governed by MB and shear. We show that (1) the most massive FCMDs experience a stronger spin-down than PCDs and less massive FCMDs, (2) the stalled spin-down and enhanced activity of K-dwarfs and the pile-up of G-dwarfs older than a few Gyr are stellar-structure and MB-dependent, and weakly dependent on core-envelope coupling effects, (3) our expression of the core-envelope convergence time-scale $\tau _{\text{converge}}(M_\ast , P_{\text{spin}})$ between a few 10 to 100 Myr strongly depends on stellar structure but weakly on MB strength and shear, such that fast and massive rotators achieve corotation earlier, (4) our estimates of the surface magnetic fields are in general agreement with observations and our wind mass loss evolution explains the weak winds from the solar analog $\pi ^1$ UMa, and (5) with our model the massive young Sun hypothesis as a solution to the faint young Sun problem can likely be ruled out, because the maximum mass lost by winds from our Sun with our model is about an order of magnitude smaller than required to solve the problem.
Targeting HTR2B suppresses nonfunctioning pituitary adenoma growth and sensitizes cabergoline treatment via inhibiting Gαq/PLC/PKCγ/STAT3 axis
Authors: Lin Shaojian , Wang Liangbo , Han Changxi , Dai Yuting , Li Changsheng , Liu Yanting , Zhang Bo , Huang Ning , Zhang Anke , Zhang Tao , Wang Yu , Xie Jing , Tang Hao , Cheng Yijun , Yao Hong , Lou Meiqing , Xue Li , Wu Zhe Bao
Published: July 2024

Background

Managing nonfunctioning pituitary adenomas (NFPAs) is difficult due to limited drug treatments. Cabergoline’s (CAB) effectiveness for NFPAs is debated. This study explores the role of HTR2B in NFPAs and its therapeutic potential.

Methods

We conducted screening of bulk RNA-sequencing data to analyze HTR2B expression levels in NFPA samples. In vitro and in vivo experiments were performed to evaluate the effects of HTR2B modulation on tumor growth and cell cycle regulation. Mechanistic insights into the HTR2B-mediated signaling pathway were elucidated using pharmacological inhibitors and molecular interaction assays.

Results

Elevated HTR2B expression was detected in NFPA samples, which was associated with increased tumor survival. Inhibition of HTR2B activity resulted in the suppression of tumor growth through modulation of the G2M cell cycle. The inhibition of HTR2B with PRX-08066 was found to block STAT3 phosphorylation and nuclear translocation by interfering with the Gαq/PLC/PKC pathway. A direct interaction between PKC-γ and STAT3 was critical for STAT3 activation. CAB was shown to activate pSTAT3 via HTR2B, reducing its therapeutic potential. However, the combination of an HTR2B antagonist with CAB significantly inhibited tumor cell proliferation in HTR2B-expressing pituitary tumor cell lines, a xenografted pituitary tumor model, and patient-derived samples. Analysis of patient-derived data indicated that a distinct molecular pattern characterized by upregulated HTR2B/PKC-γ and downregulated BTG2/GADD45A may benefit from combination treatment with CAB and PRX-08066.

Conclusions

HTR2B is a potential therapeutic target for NFPAs, and its inhibition could improve CAB efficacy. A dual therapy approach may be beneficial for NFPA patients with high HTR2B expression.
Pan-cancer integrative analyses dissect the remodeling of endothelial cells in human cancers
Authors: Li Jinhu , Wang Dongfang , Tang Fei , Ling Xinnan , Zhang Wenjie , Zhang Zemin
Published: July 2024

Therapeutics targeting tumor endothelial cells (TECs) have been explored for decades, with only suboptimal efficacy achieved, partly due to an insufficient understanding of the TEC heterogeneity across cancer patients. We integrated single-cell RNA-seq data of 575 cancer patients from 19 solid tumor types, comprehensively charting the TEC phenotypic diversities. Our analyses uncovered underappreciated compositional and functional heterogeneity in TECs from a pan-cancer perspective. Two subsets, CXCR4+ tip cells and SELE+ veins, represented the prominent angiogenic and proinflammatory phenotypes of TECs, respectively. They exhibited distinct spatial organization patterns, and compared to adjacent non-tumor tissues, tumor tissue showed an increased prevalence of CXCR4+ tip cells, yet with SELE+ veins depleted. Such functional and spatial characteristics underlie their differential associations with the response of anti-angiogenic therapies and immunotherapies. Our integrative resources and findings open new avenues to understand and clinically intervene in the tumor vasculature.
Implementation of an Approach to Equitable Allocation of SARS-CoV-2 Monoclonal Antibodies for Preexposure Prophylaxis: Experience From a Single Medical Center
Authors: Hamilton Keith W , Hua Elvis , Dutcher Lauren , Fernandez Lynch Holly , Junker Paul , Doucette Abigail G , Werner Danielle , Kannel Ethan Z , Civitello Thomas , Gabriel Peter , Ahya Vivek N , Jacobs Dina A , Garfall Alfred , Pratz Keith , Degnan Kathleen O , Blumberg Emily A , Capozzi Donna , Craig Ethan , Takach Patricia , Payne Aimee S , Geara Abdallah , Koenig Helen , Holzman Lawrence , Tebas Pablo
Published: July 2024

Background

During the COVID-19 pandemic, SARS-CoV-2 monoclonal antibodies for preexposure prophylaxis (SMA-PrEP) offered patients who were immunocompromised another option for protection. However, SMA-PrEP posed administrative, operational, and ethical challenges for health care facilities, resulting in few patients receiving them. Although the first SMA-PrEP medication, tixagevimab and cilgavimab, had its authorization revoked due to compromised in vitro efficacy, new SMA-PrEP medications are currently completing clinical trials. This article provides an operational framework for administrative organization, patient identification and prioritization, equitable medication allocation, medication ordering and administration, and patient tracking.

Methods

A retrospective cohort study evaluating our hospital's SMA-PrEP administration strategy was performed. Multivariable logistic regression was used to examine factors associated with receipt of SMA-PrEP.

Results

Despite the barriers in administering this medication and the scarcity of resources, our hospital was able to administer at least 1 dose of SMA-PrEP to 1359 of 5902 (23.0%) eligible patients. Even with the steps taken to promote equitable allocation, multivariable logistic regression demonstrated that there were still differences by race, ethnicity, and socioeconomic status. As compared with patients who identified as Black, patients who identified as White (odds ratio [OR], 1.85; 95% CI, 1.46–2.33), Asian (OR, 1.59; 95% CI, 1.03–2.46), and Hispanic (OR, 1.53; 95% CI, 1.02–2.44) were more likely to receive SMA-PrEP. When compared with patients with low socioeconomic status, patients with high socioeconomic status (OR, 1.37; 95% CI, 1.05–1.78) were more likely to be allocated SMA-PrEP.

Conclusions

Despite efforts to mitigate health care disparities, differences by race/ethnicity and socioeconomic status still arose in patients receiving SMA-PrEP.
Understanding variants of unknown significance and classification of genomic alterations
Authors: Pavlick Dean C , Frampton Garrett M , Ross Jeffrey R
Published: July 2024

Despite recent efforts to issue clinical guidelines outlining strategies to define the pathogenicity of genomic variants, there is currently no standardized framework for which to make these assertions. This review does not present a step-by-step methodology, but rather takes a holistic approach to discuss many aspects which should be taken into consideration when determining variant pathogenicity. Categorization should be curated to reflect relevant findings within the scope of the specific medical context. Functional characterization should evaluate all available information, including results from literature reviews, different classes of genomic data repositories, and applicable computational predictive algorithms. This article further proposes a multidimensional view to infer pathogenic status from many genomic measurements across multiple axes. Notably, tumor suppressors and oncogenes exhibit fundamentally different biology which helps refine the importance of effects on splicing, mutation interactions, copy number thresholds, rearrangement annotations, germline status, and genome-wide signatures. Understanding these relevant datapoints with thoughtful perspective could aid in the reclassification of variants of unknown significance (VUS), which are ambiguously understood and currently have uncertain clinical implications. Ongoing assessments of VUS examining these relevant biological axes could lead to more accurate classification of variant pathogenicity interpretation in diagnostic oncology.
Genomic, immunologic, and prognostic associations of TROP2 (TACSTD2) expression in solid tumors
Authors: Morgenstern-Kaplan Dan , Kareff Samuel A , Trabolsi Asaad , Rodriguez Estelamari , Krause Harris , Ribeiro Jennifer R , Tan Heng , Antonarakis Emmanuel S , Lou Emil , Nagasaka Misako , Algaze Sandra , Lenz Heinz-Josef , Liu Stephen V , Halmos Balazs , Hoon Dave S B , Seeber Andreas , Ma Patrick C , El-Deiry Wafik S , Vanderwalde Ari M , Lopes Gilberto
Published: July 2024

Background

TROP2 (TACSTD2) expression is associated with decreased overall survival (OS) in some solid tumors, and the TROP2-targeting antibody-drug conjugate (ADC) sacituzumab govitecan has been approved in breast and urothelial carcinomas. We aimed to explore the multi-omic landscape associated with TACSTD2 gene expression in various solid tumors to identify patients most likely to benefit from this approach.

Methods

Breast (N = 11 246), colorectal (N = 15 425), hepatocellular (N = 433), pancreatic (N = 5488), and urothelial (N = 4125) tumors were stratified into quartiles by TACSTD2 gene expression, analyzed by next-generation DNA sequencing, whole transcriptome sequencing, and immunohistochemistry at Caris Life Sciences (Phoenix, AZ). Survival data were obtained from insurance claims, and Kaplan-Meier estimates were calculated for molecularly defined cohorts.

Results

Several pathogenic mutations were associated with TACSTD2-high tumors, including TP53 in breast, colorectal (CRC), pancreatic, and hepatocellular cancers; KRAS in pancreatic and CRC cancers; ARID1A and FGFR3 in urothelial cancer; and CTNNB1 in hepatocellular cancer. TACSTD2-low breast tumors were enriched for copy number amplifications in CCND1 and FGF/R family member genes. TACSTD2 high was generally associated with more immune cell infiltration and greater T-cell inflammation scores. Patients with TACSTD2-high breast, CRC, and pancreatic cancers demonstrated a significantly shorter OS than TACSTD2-low tumors. This was restricted to CRC with microsatellite stable tumors and patients with pancreatic cancer with KRAS-mutant tumors. Patients with breast cancer with TACSTD2-high tumors also experienced significantly worse OS following immune checkpoint inhibitors.

Conclusions

TACSTD2 expression is associated with key driver alterations and a more active immune microenvironment, suggesting possible combinatorial strategies with TROP2-targeting ADCs plus immunotherapy in various solid tumors.
It is time to rethink randomized clinical trial approaches
Authors: Stewart David J
Published: July 2024

This letter to the editor comments on the recently published editorial by Fojo, LaRose, and Bates, and agrees that changes are needed in clinical research approaches.
Drivers of the natural long-term rate of interest (and why the economy hasn’t tanked)
Authors: Ademmer Martin , Rush Jamie
Published: July 2024

Long-term borrowing costs have been on a path of near continuous decline for the last several decades, with huge consequences for asset values, government finances, borrowers and savers. To shed light on why, we have estimated a global model that brings together an extensive set of drivers of the natural rate of interest for 12 advanced economies, using data spanning half a century. We find that slower growth and the age structure of the population accounted for about half of the three percentage point decline in the real natural rate for the USA between 1970 and a trough in the mid-2010s. Global spillovers account for a bit more than a third of the decline. Our model suggests the natural rate in the USA has climbed more than half a percentage point since the trough, partly reflecting extraordinary fiscal stimulus in the USA. Rather than on overnight rates, our model is estimated on 10-year borrowing costs. That is because monetary policy has increasingly relied on squeezing the whole yield curve to support demand. Importantly, when viewed through a longer-term lens, US monetary policy does not look as tight as it does when looking at short-term rates alone. This may help to explain why the economy has been so resilient to the post-pandemic hiking cycle.
Experimental Constraints on the Storage Conditions and Differentiation of High-Ti Basalts from the Panzhihua and Hongge Layered Intrusions, SW China
Authors: Wang Dachuan , Hou Tong , Botcharnikov Roman , Haselbach Sarah , Pohl Florian , Almeev Renat R , Klügel Andreas , Wang Meng , Qin Jingyi , Zhang Zhaochong , Holtz Francois
Published: July 2024

High-Ti basalts are commonly believed to represent parental magmas leading to the formation of mafic-ultramafic layered intrusions, such as Late Permian Panzhihua and Hongge in the Emeishan Large Igneous Province (SW China). Consequently, elucidation of the crystallisation and crustal differentiation of high-Ti basalts is critical for our understanding of the petrogenesis of these layered intrusions and the associated oxide ore mineralisation. Here, we present the results of crystallisation experiments carried out in internally heated pressure vessels using a primitive high-Ti basaltic composition. The experiments were conducted at 100 and 300 MPa, in the temperature interval of 950–1200 °C and with water activities (aH2O) from 0 to 1. The oxygen fugacity (fO2) was controlled and varied from FMQ −1 to FMQ +3.3 log units (FMQ corresponds to fayalite-quartz-magnetite buffer). The main mineral phases are olivine, clinopyroxene and plagioclase, accompanied by Cr-Fe-Ti-oxides, orthopyroxene, apatite and amphibole, depending on the conditions. Redox conditions primarily influence the stability fields of Cr-Fe-Ti oxides. Clinopyroxene, orthopyroxene and amphibole are pressure-dependent and have larger stability fields under high pressure conditions. The olivine→orthopyroxene and olivine→amphibole peritectic reactions are observed. Comparisons of phase equilibria between this study and experiments conducted with parental magma of Skaergaard layered intrusion demonstrate the effect of bulk system composition. For instance, ilmenite crystallisation is determined not only by intrinsic parameters such as fO2 but also by additional compositional parameters (e.g. melt Ti, Fe, Al and Mg content). Although COMAGMAT and MELTS modelling results generally reproduce the crystallisation sequence, only the stability field of clinopyroxene and its composition are perfectly modelled. The comparison of experimental results with the rocks from the lowest units of Panzhihua and Hongge layered intrusions are applied to constrain storage conditions in the magma reservoirs. Compared to Hongge, we conclude that the Panzhihua magma chamber was probably located at a shallower depth (~3–6 km), that magma crystallisation started at lower temperatures (~1125–1100 °C), higher fO2 (~FMQ + 1 to FMQ + 2) and that its initial melt H2O content was lower (~0.5–1 wt. %).
Effects of firebricks for industrial process heat on the cost of matching all-sector energy demand with 100% wind–water–solar supply in 149 countries
Authors: Jacobson Mark Z , Sambor Daniel J , Fan Yuanbei F , Mühlbauer Andreas
Published: July 2024

Refractory bricks are bricks that can withstand high temperatures without damage to their structures. They have been used to insulate kilns, furnaces, and other hot enclosures for thousands of years. Firebricks are refractory bricks that can, with one composition, store heat, and with another, insulate the firebricks that store the heat. Because firebricks are made from common materials, the cost per kilowatt-hour-thermal of a firebrick storage system is less than one-tenth the cost per kilowatt-hour-electricity of a battery system. It has thus been hypothesized that using excess renewable electricity to produce and store industrial process heat in firebricks can provide a low-cost source of continuous heat for industry. Here, it is hypothesized further that, upon a transition to 100% clean, renewable energy worldwide, using firebricks to store industrial process heat can reduce electricity generator, electricity storage, and low-temperature heat storage needs, thereby reducing overall energy cost. Both hypotheses are tested across 149 countries combined into 29 world regions. Results suggest, relative to a base case with no firebricks, using firebricks may reduce, among all 149 countries, 2050 battery capacity by ∼14.5%, annual hydrogen production for grid electricity by ∼31%, underground low-temperature heat storage capacity by ∼27.3%; onshore wind nameplate capacity by ∼1.2%, land needs by ∼0.4%, and overall annual energy cost by ∼1.8%. In sum, the use of firebricks for storing industrial process heat appears to be a remarkable tool in reducing the cost of transitioning to clean, renewable energy across all energy sectors.
Neuroimage Analysis Methods and Artificial Intelligence Techniques for Reliable Biomarkers and Accurate Diagnosis of Schizophrenia: Achievements Made by Chinese Scholars Around the Past Decade
Authors: Du Yuhui , Niu Ju , Xing Ying , Li Bang , Calhoun Vince D
Published: July 2024

Background and Hypothesis

Schizophrenia (SZ) is characterized by significant cognitive and behavioral disruptions. Neuroimaging techniques, particularly magnetic resonance imaging (MRI), have been widely utilized to investigate biomarkers of SZ, distinguish SZ from healthy conditions or other mental disorders, and explore biotypes within SZ or across SZ and other mental disorders, which aim to promote the accurate diagnosis of SZ. In China, research on SZ using MRI has grown considerably in recent years.

Study Design

The article reviews advanced neuroimaging and artificial intelligence (AI) methods using single-modal or multimodal MRI to reveal the mechanism of SZ and promote accurate diagnosis of SZ, with a particular emphasis on the achievements made by Chinese scholars around the past decade.

Study Results

Our article focuses on the methods for capturing subtle brain functional and structural properties from the high-dimensional MRI data, the multimodal fusion and feature selection methods for obtaining important and sparse neuroimaging features, the supervised statistical analysis and classification for distinguishing disorders, and the unsupervised clustering and semi-supervised learning methods for identifying neuroimage-based biotypes. Crucially, our article highlights the characteristics of each method and underscores the interconnections among various approaches regarding biomarker extraction and neuroimage-based diagnosis, which is beneficial not only for comprehending SZ but also for exploring other mental disorders.

Conclusions

We offer a valuable review of advanced neuroimage analysis and AI methods primarily focused on SZ research by Chinese scholars, aiming to promote the diagnosis, treatment, and prevention of SZ, as well as other mental disorders, both within China and internationally.
Evaluating Reduced Blood Monitoring Frequency and the Detection of Hematological Abnormalities in Clozapine-Treated Patients With Schizophrenia: A Chart Review Study From the COVID-19 Pandemic
Authors: Thai Helen , Preobrazenski Nicholas , Hsieh TiChen , Robertson Carrie , Owoeye Olabisi
Published: July 2024

Background and Hypothesis

In response to Health Canada’s March 2020 directive, patients on clozapine for over 12 months were allowed to extend hematological testing intervals from 4 to 8 weeks during the COVID-19 pandemic. We hypothesized that this change would not affect the timely detection of hematological abnormalities in patients with severe mental illness.

Study Design

A chart review was conducted of patients at the Royal Ottawa who were prescribed clozapine from March 2019 to March 2021. We analyzed clinical and hematological data from electronic health records and Clozaril Support and Assistance Network database to compare occurrences of hematological abnormalities [leukopenia (white blood cell count <3.5 × 109/L) and agranulocytosis (absolute neutrophil count <0.5 × 109/L)] from March 17, 2020 to March 16, 2021, between standard and extended monitoring protocols using binomial logistic and zero-inflated negative binomial regressions.

Study Results

Of 621 patients, 196 were on extended blood monitoring, and 425 followed standard blood monitoring. Clozapine dose did not differ between groups (standard: 370 ± 201 mg; extended: 352 ± 172 mg; P = .14, ds = 0.10). Clozapine treatment duration up to March 2021 was 12.6 ± 8.3 years, with the extended group (10 ± 7.9 years) having a significantly (P < .01, ds = 0.50) shorter duration than the standard (14 ± 8.2 years). Extended monitoring did not significantly impact likelihood of detecting hematological abnormalities (OR = 0.83, 95% CI [0.58,1.41], P = .55) after controlling for age, sex, total bloodwork, and other psychotropics associated with neutrophil counts (ie, valproate, olanzapine). No patient on the extended regimen developed agranulocytosis.

Conclusions

Reducing blood monitoring frequency in patients on clozapine for more than 12 months did not compromise detection of hematological abnormalities.
US AI data centers and deployment challenges for small modular reactors: proposed regulatory policy recommendations
Authors: Hemphill Thomas A
Published: July 2024

Global demand by cloud vendors, financial institutions, and telecommunication companies for commercially owned and operated data centers is accelerating in recent years. Given this increase in energy supply required to meet US artificial intelligence (AI) technology consumer demand, the paper addresses state-of-the-art traditional data centers and their capacity transition to process AI technologies. Subsequently, the paper explains the potential for small modular (nuclear) reactors—and specifically a subset, micro modular reactors (MMRs)—to generate the increasing energy demanded for AI processing capabilities, including the potential of quantum computing, through 2035 and beyond. Lastly, the paper identifies a primary regulatory policy challenge—the federal regulatory construction review/permitting process—that hinders an environmentally sustainable source of nuclear energy to power such AI data centers and offers policy recommendations to assist in meeting this federal regulatory policy challenge and encourages the deployment of MMR technologies.
Signaling virtue or vulnerability? The changing impact of EMU on government bond spreads
Authors: Barta Zsófia , Baccaro Lucio , Johnston Alison
Published: July 2024

Do bond-spreads of developed countries behave differently under different exchange-rate regimes? Focusing on the experience of European monetary integration, we find that the impact of exchange-rate regimes on spreads depends on the macroeconomic context. When inflation counted as the greatest risk to bondholdings, Economic and Monetary Union (EMU) was advantaged over flexible and fixed exchange rates, because of its in-built inflation-control mechanisms. Since debt-sustainability became the primary risk, exchange-rate rigidity has been a liability because it constrains governments’ response to adverse shocks. Employing a moving-window analysis for 12 EMU-members plus 10 ‘comparators’, we find that inflation was penalized under flexible and fixed exchange-rate regimes, but not under EMU. From the early 2010s on, inflation carried no penalty under any exchange-rate regime. Debt and deficit did not affect spreads until the late 2000s. Since then, EMU-members incurred larger and more prolonged spreads penalties for deficits and debt than countries in other exchange-rate regimes.
Advances in the study of the relationship between gut microbiota and erectile dysfunction
Authors: Su Quanxin , Tang Qizhen , Ma Chuanyu , Wang Kenan
Published: July 2024

Introduction

In recent years, in-depth research has revealed that gut microbiota has an inseparable relationship with erectile dysfunction (ED) in men.

Objectives

(1) To review the correlation between gut microbiota and ED from the perspective of its impact on men’s mental health, metabolism, immunity, and endocrine regulation and (2) to provide reference to further explore the pathogenesis of ED and the improvement of clinical treatment plans.

Methods

PubMed was used for the literature search to identify publications related to ED and gut microbiota.

Results

Gut microbiota may induce depression and anxiety through the microbiota-gut-brain axis, leading to the occurrence of psychological ED. It may also cause vascular endothelial dysfunction and androgen metabolism disorder by interfering with lipid metabolism, immunity, and endocrine regulation, leading to the occurrence of organic ED.

Conclusion

Gut microbiota and its metabolites play an important role in the occurrence and development of ED. As a new influencing factor of ED, gut microbiota disorder is expected to become a target for treatment.
Knockdown of circ_0076305 decreases the paclitaxel resistance of non-small cell lung cancer cells by regulating TMPRSS4 via miR-936
Authors: Su Lin , Gou Jiaxue , Zhou Chunyan , Li Jieping , Wu Jing , Shen Lili , Jia Yimin
Published: July 2024

Background

Paclitaxel (PTX) is a commonly used as a chemotherapeutic drug for non-small cell lung cancer (NSCLC). Exploring the underlying mechanism of PTX resistance is of great significance for NSCLC treatment.

Methods

The expression levels of RNA and protein were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot assays. The targeted relationship was confirmed by dual-luciferase reporter assay and RNA-pull down assay. The PTX resistance and cell proliferation were assessed by cell counting kit-8 (CCK-8) assay and 5-Ethynyl-2′-deoxyuridine (EDU) assay, respectively. Cell migration and invasion were analyzed by transwell assays. Cell apoptosis was analyzed by flow cytometry, and cell glycolysis was analyzed using the commercial kits. The role of circular RNA_0076305 (circ_0076305) in regulating the PTX sensitivity in vivo was explored in xenograft tumor model.

Results

Circ_0076305 was up-regulated in PTX-resistant NSCLC tissues and cells. Mechanically, circ_0076305 bound to microRNA-936 (miR-936), and miR-936 targeted transmembrane serine protease 4 (TMPRSS4). Circ_0076305 could up-regulate TMPRSS4 expression by sponging miR-936 in NSCLC cells. miR-936 knockdown or TMPRSS4 overexpression reversed the anti-tumor effects of circ_0076305 knockdown in NSCLC cells with PTX treatment. Circ_0076305 silencing increased the PTX sensitivity of xenograft tumors in vivo.

Conclusion

Circ_0076305 silencing promoted PTX sensitivity by targeting miR-936/TMPRSS4 axis in NSCLC cells.
L-carnitine: A novel approach in management of acute cholinesterase inhibitor insecticide poisoning
Authors: Ragab Hisham Elsayed , El-Banna Asmaa , Elshaer Noha Selim , Azzaz Omnia
Published: July 2024

Cholinesterase inhibitors (ChEIs) insecticide poisoning is a serious global health concern that results in hundreds of thousands of fatalities each year. Although inhibition of the cholinesterase enzyme is the main mechanism of ChEI poisoning, oxidative stress is considered the mechanism underlying the related complications. The study aimed to assess the oxidative status of the patients with ChEI insecticide poisoning and the role of L-carnitine as adjuvant therapy in their management. Human studies on the efficacy and safety of L-carnitine in treating insecticide poisoning are limited despite its growing research interest as a safe antioxidant. This prospective study was conducted on eighty patients with acute ChEIs insecticide poisoning admitted to Alexandria Poison Center, Alexandria Main University Hospital, Egypt. Patients were allocated into two equal groups randomly. The L-carnitine (LC) group received the conventional treatment (atropine & toxogonin) and LC and the standard treatment (ST) group received the standard treatment only. Outcome measures were fatality rate, the total administered dose of atropine & toxogonin, length of hospital stay, and the requirement for ICU admission or mechanical ventilation. The study results revealed that malondialdehyde (MDA) significantly decreased in the LC group. Cholinesterase enzyme levels increased significantly after treatment in the LC group than in the ST group. The LC group needed lower dosages of atropine and toxogonin than the ST group. Also, the LC group showed no need for ICU admission or mechanical ventilation. The study concluded that LC can be considered a promising adjuvant antioxidant treatment in acute ChEIs pesticide poisoning.
The role of reactive oxygen species in regulation of the plasma membrane H+-ATPase activity in Masson pine (Pinus massoniana Lamb.) roots responding to acid stress
Authors: Zhou Sijie , Wang Wenxin , Wang Ping , Ma Huiyan , Li Wenhui
Published: July 2024

To understand the role of reactive oxygen species (ROS) in regulation of the plasma membrane (PM) H+-ATPase in acid-stressed Masson pine roots, different acidity (pH 6.6 as the control, pH 5.6 and pH 4.6) of simulated acid rain (SAR) added with and without external chemicals (H2O2, enzyme inhibitors and ROS scavenger) was prepared. After 30 days of SAR exposure, the plant morphological phenotype attributes, levels of cellular ROS and lipid peroxidation, enzymatic activities of antioxidants, PM nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and PM H+-ATPase activity in pine seedlings were measured. Compared with the control, the growth of pine seedlings exposed to SAR in the presence or absence of H2O2 was well-maintained, but the application of Na3VO4, 1,3-dimethyl-2-thiourea, N, N-dimethylthiourea (DMTU) and diphenyleneiodonium chloride (DPI) caused a substantial growth inhibition. In addition, SAR exposure, SAR with H2O2 treatment, and SAR with Na3VO4 treatment increased the cellular H2O2 content, O2− content and malondialdehyde (MDA) content, while the use of DMTU and DPI lead to relatively low levels. Similarly, the enzymatic activities of antioxidants, PM NADPH oxidase and PM H+-ATPase in acid stressed pine seedlings elevated with the increasing acidity. A significant stimulation of these enzymatic activities obtained from SAR with H2O2 treatment was observed, whereas which decreased obviously with the addition of Na3VO4, DMTU and DPI (P < 0.05). Moreover, a positive correlation was found between plant morphological attributes and the PM H+-ATPase activity (P < 0.05). Besides, the PM H+-ATPase activity positively correlated with the cellular ROS contents and the enzymatic activities of antioxidants and PM NADPH oxidase (P < 0.05). Therefore, the PM H+-ATPase is instrumental in the growth of pine seedlings resisting to acid stress by enhancing its activity. The process involves the signaling transduction of cellular ROS and coordination with PM NADPH oxidase.
Field Evaluation of Fluazinam Fungicide in Dollar Spot Populations Confirmed In Vitro Insensitivity
Authors: Shi Xiaojing , Min Soonhong , Jung Geunhwa
Published: July 2024

Fluazinam, a fungicide widely used in agriculture and turf management, was traditionally thought to pose a low risk of resistance. However, our in vitro sensitivity test conducted in 2021 revealed reduced sensitivity to fluazinam in dollar spot, highlighting the need for more vigilant field monitoring. In 2022 and 2023, we evaluated the field responses of four Clarireedia jacksonii isolates with varying in vitro sensitivity to fluazinam. Fluazinam was used at both a full labeled rate (0.5 oz/1,000 ft2) and a half-rate (0.25 oz/1,000 ft2) to evaluate the effectiveness in isolate-inoculated plots in the field. In 2022, both natural and sensitive isolates showed significantly better control compared to insensitive isolates under both half- and full-rate treatments. However, in 2023, half-rate fluazinam demonstrated limited control under high disease pressure, providing relative disease control of dollar spot less than 45% across all treatments. In contrast, full-rate fluazinam maintained significantly better control of natural and sensitive isolates compared with insensitive isolates. Our results, showing that in vitro insensitivity leads to field insensitivity under inoculated conditions, suggest the development of fluazinam insensitivity in the C. jacksonii population. This highlights the need for judicious use of fluazinam and the establishment of continuous resistance monitoring. Furthermore, the loss of control observed when fluazinam was applied at half-rates under high disease pressure highlights the importance of careful fungicide use.
Novel Sources of Resistance to Bacterial Leaf Blight in the USDA Brassica rapa Collection
Authors: Kaur Khushwinder , Wechter W. Patrick , Farnham Mark W. , Robinson Shane M. , Branham Sandra E.
Published: July 2024

Bacterial leaf blight, caused by Pseudomonas cannabina pv. alisalensis ( Pcal), is a devastating disease that has spread worldwide over the past 20 years. Pcal can infect all Brassica crops and leads to yield losses of Brassica leafy greens across the southeastern United States every year. There are no commercial cultivars of turnip greens with resistance to Pcal and no effective bactericides available. We report the first identification of resistant sources in Brassica rapa L. against bacterial leaf blight caused by Pcal. The United States Department of Agriculture (USDA) accessions of B. rapa (275 accessions) were screened through multiple tests in greenhouse trials. The three commercial cultivars tested exhibited an intermediate response across all tests and retests. Three accessions (Ames 7572, PI 649171, and PI 649183) with significant resistance were identified in the B. rapa germplasm collection. The identified accessions are an important source for development of B. rapa cultivars resistant to Pcal and introgression of the resistant loci into B. napus cultivars.
Antiretroviral drug dolutegravir induces inflammation at the mouse brain barriers
Authors: Huang Chang , Hoque Md. Tozammel , Qu Qing Rui , Henderson Jeffrey , Bendayan Reina
Published: July 2024

Integrase strand transfer inhibitors (INSTIs) based antiretroviral therapy (ART) is currently used as first‐line regimen to treat HIV infection. Despite its high efficacy and barrier to resistance, ART‐associated neuropsychiatric adverse effects remain a major concern. Recent studies have identified a potential interaction between the INSTI, dolutegravir (DTG), and folate transport pathways at the placental barrier. We hypothesized that such interactions could also occur at the two major blood–brain interfaces: blood‐cerebrospinal fluid barrier (BCSFB) and blood–brain barrier (BBB). To address this question, we evaluated the effect of two INSTIs, DTG and bictegravir (BTG), on folate transporters and receptor expression at the mouse BCSFB and the BBB in vitro, ex vivo and in vivo. We demonstrated that DTG but not BTG significantly downregulated the mRNA and/or protein expression of folate transporters (RFC/SLC19A1, PCFT/SLC46A1) in human and mouse BBB models in vitro, and mouse brain capillaries ex vivo. Our in vivo study further revealed a significant downregulation in Slc19a1 and Slc46a1 mRNA expression at the BCSFB and the BBB following a 14‐day DTG oral treatment in C57BL/6 mice. However, despite the observed downregulatory effect of DTG in folate transporters/receptor at both brain barriers, a 14‐day oral treatment of DTG‐based ART did not significantly alter the brain folate level in animals. Interestingly, DTG treatment robustly elevated the mRNA and/or protein expression of pro‐inflammatory cytokines and chemokines (Cxcl1, Cxcl2, Cxcl3, Il6, Il23, Il12) in primary cultures of mouse brain microvascular endothelial cells (BBB). DTG oral treatment also significantly upregulated proinflammatory cytokines and chemokine (Il6, Il1β, Tnfα, Ccl2) at the BCSFB in mice. We additionally observed a downregulated mRNA expression of drug efflux transporters (Abcc1, Abcc4, and Abcb1a) and tight junction protein (Cldn3) at the CP isolated from mice treated with DTG. Despite the structural similarities, BTG only elicited minor effects on the markers of interest at both the BBB and BCSFB. In summary, our current data demonstrates that DTG but not BTG strongly induced inflammatory responses in a rodent BBB and BCSFB model. Together, these data provide valuable insights into the mechanism of DTG‐induced brain toxicity, which may contribute to the pathogenesis of DTG‐associated neuropsychiatric adverse effect.
The Mean Delta Method: Quantifying Assessor Stringency and Leniency and Identifying Outliers in Workplace-Based Assessments
Authors: Dewhirst Sebastian , Cheung Warren J. , Wood Timothy , Szabo Nora D. , Frank Jason R.
Published: July 2024

Assessor stringency and leniency (ASL)—an assessor’s tendency to award low or high scores—has a significant effect on workplace-based assessments. Outliers on this spectrum have a disproportionate effect. However, no method has been published for quantifying ASL or identifying outlier stringent or lenient assessors using workplace-based assessment data. The authors propose the mean delta method, which compares the scores that an assessor awards to trainees with those trainees’ mean scores. This novel, simple method can be used to quantify ASL and identify outlier assessors without requiring specialized statistical knowledge or software. As a worked example, the mean delta method was applied to a set of end-of-shift assessments completed in a large Canadian academic emergency department from July 1, 2017, to May 31, 2018, and used to examine the net effect of ASL on learners’ assessment scores. A total of 3,908 assessments were completed by 99 assessors for 151 trainees, with a median (interquartile range) of 37 (12–39) completed assessments per trainee. Using cutoff values of 1.5 and 2 standard deviations, a total of 11 and 3 outlier assessors were identified, respectively. Moreover, ASL changed overall scores by more than the mean difference between years of training for nearly 1 in 4 learners. The mean delta method was able to quantify ASL and identify outlier lenient and stringent assessors. It was also used to quantify the net effect of ASL on individual trainees. This method could be used to further study outlier assessors, to identify assessors who may benefit most from targeted coaching and feedback, and to measure changes in assessors’ tendencies over time or with specific intervention.