bluuebunny/crossref_metadata_2025_split huggingface dataset:
Infection biology of
Salmonella enterica
Authors: Han Jing , Aljahdali Nesreen , Zhao Shaohua , Tang Hailin , Harbottle Heather , Hoffmann Maria , Frye Jonathan G. , Foley Steven L. 
Published: January 2024

ABSTRACT

Salmonella enterica
is the leading cause of bacterial foodborne illness in the USA, with an estimated 95% of salmonellosis cases due to the consumption of contaminated food products.
Salmonella
can cause several different disease syndromes, with the most common being gastroenteritis, followed by bacteremia and typhoid fever. Among the over 2,600 currently identified serotypes/serovars, some are mostly host-restricted and host-adapted, while the majority of serotypes can infect a broader range of host species and are associated with causing both livestock and human disease.
Salmonella
serotypes and strains within serovars can vary considerably in the severity of disease that may result from infection, with some serovars that are more highly associated with invasive disease in humans, while others predominantly cause mild gastroenteritis. These observed clinical differences may be caused by the genetic make-up and diversity of the serovars.
Salmonella
virulence systems are very complex containing several virulence-associated genes with different functions that contribute to its pathogenicity. The different clinical syndromes are associated with unique groups of virulence genes, and strains often differ in the array of virulence traits they display. On the chromosome, virulence genes are often clustered in regions known as
Salmonella
pathogenicity islands (SPIs), which are scattered throughout different
Salmonella
genomes and encode factors essential for adhesion, invasion, survival, and replication within the host. Plasmids can also carry various genes that contribute to
Salmonella
pathogenicity. For example, strains from several serovars associated with significant human disease, including Choleraesuis, Dublin, Enteritidis, Newport, and Typhimurium, can carry virulence plasmids with genes contributing to attachment, immune system evasion, and other roles. The goal of this comprehensive review is to provide key information on the
Salmonella
virulence, including the contributions of genes encoded in SPIs and plasmids during
Salmonella
pathogenesis.
Brucella
targets the host ubiquitin-specific protease,
Usp8
, through the effector protein, TcpB, for facilitating infection of macrophages
Authors: Joshi Kiranmai , Mazumdar Varadendra , Nandi Binita Roy , Radhakrishnan Girish K. 
Published: January 2024

ABSTRACT

Brucella
species are Gram-negative intracellular bacterial pathogens that cause the worldwide zoonotic disease brucellosis.
Brucella
can infect many mammals, including humans and domestic and wild animals.
Brucella
manipulates various host cellular processes to invade and multiply in professional and non-professional phagocytic cells. However, the host targets and their modulation by
Brucella
to facilitate the infection process remain obscure. Here, we report that the host ubiquitin-specific protease, USP8, negatively regulates the invasion of
Brucella
into macrophages through the plasma membrane receptor, CXCR4. Upon silencing or chemical inhibition of USP8, the membrane localization of the CXCR4 receptor was enriched, which augmented the invasion of
Brucella
into macrophages. Activation of USP8 through chemical inhibition of 14-3-3 protein affected the invasion of
Brucella
into macrophages.
Brucella
suppressed the expression of
Usp8
at its early stage of infection in the infected macrophages. Furthermore, we found that only live
Brucella
could negatively regulate the expression of
Usp8
, suggesting the role of secreted effector protein of
Brucella
in modulating the gene expression. Subsequent studies revealed that the
Brucella
effector protein, TIR-domain containing protein from
Brucella
, TcpB, plays a significant role in downregulating the expression of
Usp8
by targeting the cyclic-AMP response element-binding protein pathway. Treatment of mice with USP8 inhibitor resulted in enhanced survival of
B. melitensis,
whereas mice treated with CXCR4 or 14-3-3 antagonists showed a diminished bacterial load. Our experimental data demonstrate a novel role of
Usp8
in the host defense against microbial intrusion. The present study provides insights into the microbial subversion of host defenses, and this information may ultimately help to develop novel therapeutic interventions for infectious diseases.
Overlap reduction function for pulsar timing arrays in an expanding Universe
Authors: Zhu Qing-Hua 
Published: January 2024

AbstractSince it was confirmed two decades ago that the expansion of the Universe is accelerating, it would be of theoretical interests to figure out what is the influence from cosmological constant on detection of stochastic gravitational wave background. This paper studies the overlap reduction functions in de-Sitter space-time for a pair of one-way tracking gravitational wave detectors. It is shown to be non-trivial in an expanding Universe, because the propagation of light along line of sight also has effect on the response of GW detectors. It is found that the expansion of the Universe can enhance the value of magnitude of the overlap reduction functions, when the detector pairs are close to each other. For nanohertz gravitational waves, this effect can dominate the values of overlap reduction functions when the galactic pulsar pairs are separated by milliarcsecond.
Adipocyte Precursor-Derived NRG1 Promotes Resistance to FGFR Inhibition in Urothelial Carcinoma
Authors: Hosni Sana , Kilian Viola , Klümper Niklas , Gabbia Daniela , Sieckmann Katharina , Corvino Dillon , Winkler Anja , Saponaro Miriam , Wörsdörfer Karin , Schmidt Doris , Hahn Oliver , Zanotto Ilaria , Bertlich Marina , Toma Marieta , Bald Tobias , Eckstein Markus , Hölzel Michael , Geyer Matthias , Ritter Manuel , Wachten Dagmar , De Martin Sara , Alajati Abdullah 
Published: January 2024

Abstract

Aberrations of the fibroblast growth factor receptor (FGFR) family members are frequently observed in metastatic urothelial cancer (mUC), and blocking the FGF/FGFR signaling axis is used as a targeted therapeutic strategy for treating patients. Erdafitinib is a pan-FGFR inhibitor, which has recently been approved by the FDA for mUC with FGFR2/3 alterations. Although mUC patients show initial response to erdafitinib, acquired resistance rapidly develops. Here, we found that adipocyte precursors promoted resistance to erdafitinib in FGFR-dependent bladder and lung cancer in a paracrine manner. Moreover, neuregulin 1 (NRG1) secreted from adipocyte precursors was a mediator of erdafitinib resistance by activating human epidermal growth factor receptor 3 (ERBB3; also known as HER3) signaling, and knockdown of NRG1 in adipocyte precursors abrogated the conferred paracrine resistance. NRG1 expression was significantly downregulated in terminally differentiated adipocytes compared with their progenitors. Pharmacologic inhibition of the NRG1/HER3 axis using pertuzumab reversed erdafitinib resistance in tumor cells in vitro and prolonged survival of mice bearing bladder cancer xenografts in vivo. Remarkably, data from single-cell RNA sequencing revealed that NRG1 was enriched in platelet-derived growth factor receptor-A (PDGFRA) expressing inflammatory cancer-associated fibroblasts, which is also expressed on adipocyte precursors. Together, this work reveals a paracrine mechanism of anti-FGFR resistance in bladder cancer, and potentially other cancers, that is amenable to inhibition using available targeted therapies.

Significance:
Acquired resistance to FGFR inhibition can be rapidly promoted by paracrine activation of the NRG1/HER3 axis mediated by adipocyte precursors and can be overcome by the combination of pertuzumab and erdafitinib treatment.
See related commentary by Kolonin and Anastassiou, p. 648
Pulmonary Hypertension Induces Serotonin Hyperreactivity and Metabolic Reprogramming in Coronary Arteries via NOX1/4-TRPM2 Signaling Pathway
Authors: Huang Yan-Zhen , Wu Ji-Chun , Lu Gui-Feng , Li Hui-Bin , Lai Su-Mei , Lin Yi-Chen , Gui Long-Xin , Sham James S.K. , Lin Mo-Jun , Lin Da-Cen 
Published: January 2024

BACKGROUND:

Clinical evidence revealed abnormal prevalence of coronary artery (CA) disease in patients with pulmonary hypertension (PH). The mechanistic connection between PH and CA disease is unclear. Serotonin (5-hydroxytryptamine), reactive oxygen species, and Ca
2+
signaling have been implicated in both PH and CA disease. Our recent study indicates that NOXs (NADPH [nicotinamide adenine dinucleotide phosphate] oxidases) and TRPM2 (transient receptor potential cation channel subfamily M member 2) are key components of their interplay. We hypothesize that activation of the NOX-TRPM2 pathway facilitates the remodeling of CA in PH.

METHODS:
Left and right CAs from chronic hypoxia and monocrotaline-induced PH rats were collected to study vascular reactivity, gene expression, metabolism, and mitochondrial function. Inhibitors or specific siRNA were used to examine the pathological functions of NOX1/4-TRPM2 in CA smooth muscle cells.

RESULTS:

Significant CA remodeling and 5-hydroxytryptamine hyperreactivity in the right CA were observed in PH rats. NOX1/4-mediated reactive oxygen species production coupled with TRPM2-mediated Ca
2+
influx contributed to 5-hydroxytryptamine hyperresponsiveness. CA smooth muscle cells from chronic hypoxia-PH rats exhibited increased proliferation, migration, apoptosis, and metabolic reprogramming in an NOX1/4-TRPM2–dependent manner. Furthermore, the NOX1/4-TRPM2 pathway participated in mitochondrial dysfunction, involving mitochondrial DNA damage, reactive oxygen species production, elevated mitochondrial membrane potential, mitochondrial Ca
2+
accumulation, and mitochondrial fission. In vivo knockdown of NOX1/4 alleviated PH and suppressed CA remodeling in chronic hypoxia rats.

CONCLUSIONS:
PH triggers an increase in 5-hydroxytryptamine reactivity in the right CA and provokes metabolic reprogramming and mitochondrial disruption in CA smooth muscle cells via NOX1/4-TRPM2 activation. This signaling pathway may play an important role in CA remodeling and CA disease in PH.
Multifocal, Asymmetric Bilateral Primary Aldosteronism Cannot be Excluded by Strong Adrenal Vein Sampling Lateralization: An International Retrospective Cohort Study
Authors: Turcu Adina F. , Tezuka Yuta , Lim Jung Soo , Salman Zara , Sehgal Kartik , Liu Haiping , Larose Stéphanie , Parksook Wasita Warachit , Williams Tracy Ann , Cohen Debbie L. , Wachtel Heather , Zhang Jinghong , Dorwal Pranav , Satoh Fumitoshi , Yang Jun , Lacroix André , Reincke Martin , Giordano Tom J. , Udager Aaron M. , Vaidya Anand , Rainey William E. 
Published: January 2024

BACKGROUND:
Primary aldosteronism (PA) has been broadly dichotomized into unilateral and bilateral forms. Adrenal vein sampling (AVS) lateralization indices (LI) ≥2 to 4 are the standard-of-care to recommend unilateral adrenalectomy for presumed unilateral PA. We aimed to assess the rates and characteristics of residual PA after AVS-guided adrenalectomy.

METHODS:
We conducted an international, retrospective, cohort study of patients with PA from 7 referral centers who underwent unilateral adrenalectomy based on LI≥4 on baseline and/or cosyntropin-stimulated AVS. Aldosterone synthase (CYP11B2) immunohistochemistry and next generation sequencing were performed on available formalin-fixed paraffin-embedded adrenal tissue.

RESULTS:

The cohort included 283 patients who underwent AVS-guided adrenalectomy, followed for a median of 326 days postoperatively. Lack of PA cure was observed in 16% of consecutive patients, and in 22 patients with lateralized PA on both baseline and cosyntropin-stimulated AVS. Among patients with residual PA postoperatively, 73% had multiple CYP11B2 positive areas within the resected adrenal tissue (versus 23% in those cured), wherein
CACNA1D
mutations were most prevalent (63% versus 33% in those cured). In adjusted regression models, independent predictors of postoperative residual PA included Black versus White race (odds ratio, 5.10 [95% CI, 1.45–17.86]), AVS lateralization only at baseline (odds ratio, 8.93 [95% CI 3.00–26.32] versus both at baseline and after cosyntropin stimulation), and CT-AVS disagreement (odds ratio, 2.75 [95% CI, 1.20–6.31]).

CONCLUSIONS:
Multifocal, asymmetrical bilateral PA is relatively common, and it cannot be excluded by robust AVS lateralization. Long-term postoperative monitoring should be routinely pursued, to identify residual PA and afford timely initiation of targeted medical therapy.
Violations of physical and psychological expectations in the human adult brain
Authors: Liu Shari , Lydic Kirsten , Mei Lingjie , Saxe Rebecca 
Published: January 2024

Abstract
After seeing one solid object apparently passing through another, or a person taking the long route to a destination when a shortcut was available, human adults classify those events as surprising. When tested on these events in violation-of-expectation (VOE) experiments, infants look longer at the same outcomes, relative to similar but expected outcomes. What cognitive processes underlie these judgments from adults, and perhaps infants' sustained attention to these events? As one approach to test this question, we used functional magnetic resonance imaging (fMRI) to scan the brains of human adults (total N = 49, 22 female, mean age of 26 years) while they viewed stimuli that were originally designed to test for physical and psychological expectations in infants. We examined non-mutually exclusive candidates for the processes underlying the VOE effect, including domain-general processes, like visual prediction error and curiosity, and domain-specific processes, like prediction error with respect to distinctively physical and psychological expectations (objects are solid; agents behave rationally). Early visual regions did not distinguish between expected and unexpected events from either domain. By contrast, multiple demand regions, involved in goal-directed attention, responded more to unexpected events in both domains, providing evidence for domain-general goal-directed attention as a mechanism for VOE. Left supramarginal gyrus (LSMG) was engaged during physical prediction and responded preferentially to unexpected events from the physical domain, providing evidence for domain-specific physical prediction error. Thus, in adult brains, violations of physical and psychological expectations involve domain-specific, and domain-general, though not purely visual, computations.
Rescuing missing data in connectome-based predictive modeling
Authors: Liang Qinghao , Jiang Rongtao , Adkinson Brendan D. , Rosenblatt Matthew , Mehta Saloni , Foster Maya L. , Dong Siyuan , You Chenyu , Negahban Sahand , Zhou Harrison H. , Chang Joseph , Scheinost Dustin 
Published: January 2024

Abstract
Recent evidence suggests brain-phenotype predictions may require very large sample sizes. However, as the sample size increases, missing data also increase. Conventional methods, like complete-case analysis, discard useful information and shrink the sample size. To address the missing data problem, we investigated rescuing these missing data through imputation. Imputation is substituting estimated values for missing data to be used in downstream analyses. We integrated imputation methods into the Connectome-based Predictive Modeling (CPM) framework. Utilizing four open-source datasets—the Human Connectome Project, the Philadelphia Neurodevelopmental Cohort, the UCLA Consortium for Neuropsychiatric Phenomics, and the Healthy Brain Network (HBN)—we validated and compared our framework with different imputation methods against complete-case analysis for both missing connectomes and missing phenotypic measures scenarios. Imputing connectomes exhibited superior prediction performance on real and simulated missing data compared to complete-case analysis. In addition, we found that imputation accuracy was a good indicator for choosing an imputation method for missing phenotypic measures but not informative for missing connectomes. In a real-world example predicting cognition using the HBN, we rescued 628 individuals through imputation, doubling the complete case sample size and increasing the variance explained by the predicted value by 45%. In conclusion, our study is a benchmark for state-of-the-art imputation techniques when dealing with missing connectome and phenotypic data in predictive modeling scenarios. Our results suggest that improving prediction performance can be achieved by strategically addressing missing data through effective imputation methods rather than resorting to the outright exclusion of participants. Our results suggest that rescuing data with imputation, instead of discarding participants with missing information, improves prediction performance.
Old Comedy and Athenian Power
Authors: Lazar Leah 
Published: January 2024

Abstract
In this article, jumping off from Geoffrey de Ste. Croix’s treatment of Aristophanes and the Megarian Decree, I argue that Old Comedy is an underutilised category of evidence for the study of the popular intellectual history of Athens. My particular focus here is the Athenian empire: how does Old Comedy present Athenian power and what does this comic presentation tell us about how at least some ordinary Athenians understood it? Can one popular Athenian imaginary of the empire be constructed through analysis of Aristophanes and his contemporaries? I will argue that Old Comedy, taken as a corpus, presents a very Athenian empire, that is to say one focused on Athens and its exploitation of others. The comic poets, therefore, likely assumed parochialism and myopia on the part of their audience, but also significant topical interest in the mechanisms of Athenian power, particularly those which brought revenue to Athens. This impression of highly topical engagement with the empire is corroborated by bringing Comedy into dialogue with other sources, in particular the epigraphic record.
Investigating Multidecadal Trends in Ice Cover and Subsurface Temperatures in the Laurentian Great Lakes Using a Coupled Hydrodynamic–Ice Model
Authors: Cannon David , Wang Jia , Fujisaki-Manome Ayumi , Kessler James , Ruberg Steve , Constant Steve 
Published: January 2024

Abstract
While changing lake surface conditions have received significant research scrutiny, changes in subsurface conditions, including stratification and heat content, remain largely unexplored. In this work, we highlight changes in thermal structure, stratification dynamics, and ice characteristics in the Laurentian Great Lakes (Lakes Superior, Huron, Michigan, Erie, and Ontario) as simulated between 1979 and 2021. Three-dimensional lake hydrodynamics and ice cover were modeled using the Finite Volume Community Ocean Model (FVCOM) coupled with the Los Alamos sea ice model (CICE). Analysis revealed significant increases in surface (0.4°–0.6°C decade−1) and subsurface (0.1°–0.4°C decade−1) temperatures as well as dramatic losses in ice cover (1%–8% decade−1) and ice volume (0–3 km3 decade−1) over the last 40 years. Estimated surface heating rates were strongest during the summer and fall, while subsurface warming was most rapid during the nearly isothermal winter and spring. Intensified (decreased) summer (winter) stratification led to shifts in lake turnover dynamics, with delayed fall turnover dates (2–6 days decade−1) and earlier spring overturn dates (2–9 days decade−1). Modeled surface temperatures (LST), bottom temperatures (LBT), and annual averaged ice cover (AAIC) were used to estimate low-frequency climate signals, which were highly correlated with the Atlantic multidecadal oscillation. Warming trends fit to residual climate signals (LST: 0.1°C decade−1; LBT: 0.03°C decade−1; AAIC: −1% decade−1), calculated by removing low-frequency variability from the raw climate signal, were lower than those fit to associated low-frequency components, suggesting that recent climate change in the Great Lakes may be strongly influenced by natural multidecadal climate variability.
Impact of Low Bone Mineral Content Index on Cardiovascular Outcomes in Patients With Coronary Artery Disease Undergoing Percutaneous Coronary Intervention
Authors: Itagaki Tadashi , Ueki Yasushi , Sunohara Daisuke , Aoki Moeko , Nomoto Fumika , Takamatsu Toshifumi , Mochidome Tomoaki , Miura Takashi , Kasai Toshio , Kuwahara Koichiro , Ikeda Uichi 
Published: January 2024

The prognostic value of bone mineral content (BMC) for the clinical outcomes of patients with coronary artery disease (CAD) remains unknown. The present study evaluated the association between BMC index (BMCI) and cardiovascular events between January 2020 to June 2021, in consecutive patients (n = 257) with CAD undergoing percutaneous coronary intervention (PCI) at the Nagano Municipal Hospital. BMCI was measured using bioelectrical impedance analysis and calculated as the BMC divided by height squared. Patients were classified as low (<0.918) or high BMCI (≥0.918) groups according to the receiver operating characteristics curve analysis for the primary endpoint, major adverse cardiovascular events (MACE), including cardiovascular death, spontaneous myocardial infarction, stroke, and any revascularization. During a median follow-up of 744 days, the low BMCI group (n = 152) had an increased risk of MACE compared with the high group (n = 105) (19.7 vs 6.7%, P = .004). A low BMCI was significantly associated with MACE in the multivariable Cox and the Inverse Probability of Treatment Weighting analyses (hazard ratio: 3.16, 95% confidence interval: 1.15-8.67, P = .025). In conclusion, among patients with CAD undergoing PCI, BMCI was a predictor for cardiovascular events. Further research is required to determine whether medical interventions for BMC can improve patient prognosis.
Determinants of Health Expenditure during Extreme Climate Events: An Ex-post Analysis of Households in Rural Odisha of India
Authors: Sahu Santosh Kumar , Narayanan K. , Semetko Holli A. 
Published: January 2024

This study is an ex-post analysis of household health expenditure for rural India in the presence of climate shock. Primary data from Odisha state, located on the east coast of India, are collected for empirical analysis. We have also used information from focus group discussions at the village level and the primary data. Further, an adaptive response measure is created to understand household spending behaviour on health better. Econometric techniques such as regression and propensity score matching explain sample households’ ex-post-health spending behaviour. Our findings indicate that mitigation and adaptation strategies must be heterogeneous among villages classified as near or far from the coast. Social status matters in the health spending behaviour of households. Hence, a particular focus must be given to socially backward castes or classes in designing health policies and information at the state and national levels. JEL Codes: D31, I18, Q54, Q56