bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective observational pilot study of the T2Resistance panel in the T2Dx system for detection of resistance genes in bacterial bloodstream infections
Authors: Walsh Thomas J. , Mencacci Antonella , Paggi Riccardo , Douka Evangelia , Vrettou Charikleia , Smith Roger , Guzman Oscar 
Published: March 2024

ABSTRACT

Early initiation of antimicrobial therapy targeting resistant bacterial pathogens causing sepsis and bloodstream infections (BSIs) is critical for a successful outcome. The T2Resistance Panel (T2R) detects the following resistance genes within organisms that commonly cause BSIs directly from patient blood samples:

bla
KPC

,

bla
CTXM-14/15

,

bla
NDM
/bla
/IMP
/bla
VIM

,

bla
AmpC

,

bla
OXA

,
vanA
,
vanB
, and
mec
A/
mec
C. We conducted a prospective study in two major medical centers for the detection of circulating resistance genes by T2R in patients with BSIs. T2R reports were compared to antimicrobial susceptibility testing (AST), phenotypic identification, and standard molecular detection assays. Among 59 enrolled patients, 25 resistance genes were identified:

bla
KPC

(
n
= 10),

bla
NDM
/bla
/IMP
/bla
VIM

(
n
= 5),

bla
CTXM-14/15

(
n
= 4),

bla
AmpC

(
n
= 2), and
mec
A/
mec
C (
n
= 4). Median time-to-positive-T2R in both hospitals was 4.4 hours [interquartile range (IQR): 3.65–4.97 hours] in comparison to that for positive blood cultures with final reporting of AST of 58.34 h (IQR: 45.51–111.2 hours;
P
< 0.0001). The sensitivity of T2R to detect the following genes in comparison to AST was 100% for
bla
CTXM-14/15
,
bla
NDM

/bla
/

IMP
/bla
VIM
,
bla
AmpC
,
mec
A/
mec
C and 87.5% for bla
KPC
. When monitored for the impact of significant antimicrobial changes, there were 32 events of discontinuation of unnecessary antibiotics and 17 events of escalation of antibiotics, including initiation of ceftazidime/avibactam in six patients in response to positive T2R results for

bla
KPC

. In summary, T2R markers were highly sensitive for the detection of drug resistance genes in patients with bacterial BSIs, when compared with standard molecular resistance detection systems and phenotypic identification assays while significantly reducing by approximately 90% the time to detection of resistance compared to standard methodology and impacting clinical decisions for antimicrobial therapy.

IMPORTANCE
This is the first reported study to our knowledge to identify key bacterial resistance genes directly from the bloodstream within 3 to 5 hours in patients with bloodstream infections and sepsis. The study further demonstrated a direct effect in modifying initial empirical antibacterial therapy in response to T2R signal to treat resistant bacteria causing bloodstream infections and sepsis.
Precipitation of Ag-Pb-Zn ores of the Poshan vein deposit in the Qinling orogen (central China) by dilution of magmatic hydrothermal fluids
Authors: Chai Ming-Chun , Li Jian-Wei , Xia Xiao-Ping , Fan Gao-Hua , Fu Wei 
Published: March 2024

Abstract
Constraints on the source, nature, and evolution of ore-forming fluids are crucial for better understanding the ore genesis and mechanisms that lead to metal precipitation. Here, we present results of in situ analysis for quartz oxygen isotopes and sulfide sulfur isotopes, combined with apatite U-Pb age and fluid inclusion data, to provide insights into the source and evolution of ore fluids of the Poshan Ag-Pb-Zn vein deposit in the Qinling orogen, central China. Quartz-carbonate-sulfide veins at Poshan are hosted in lower Paleozoic metavolcanic-sedimentary rocks and structurally controlled by fracture zones associated with the Heqianzhuang anticline. The Ag-Pb-Zn mineralization consists of three stages, which are represented by quartz-pyrite-arsenopyrite (stage I), quartz-carbonate-sulfide-silver minerals (stage II), and quartz-calcite ± native silver (stage III). Apatite texturally associated with galena from stage II has a U-Pb age of 125 ± 14 Ma (2σ; mean square of weighted deviates [MSWD] = 0.9), which suggests that the Poshan deposit formed in the Early Cretaceous and thus significantly postdated the Paleozoic and early Mesozoic orogenic deformation of the Qinling orogen. Aqueous-carbonic fluid inclusions from stages I and II have similar total homogenization temperatures of 263–347 °C and calculated salinities of 1.2–5.1 wt% NaCl equivalent, whereas the values for liquid-dominated aqueous inclusions from stage III are 211–245 °C and 0.5–3.0 wt% NaCl equivalent. Five quartz generations are recognized from the three paragenetic stages, including Qz-1 and Qz-2 from stage I, Qz-3 and Qz-4 from stage II, and Qz-5 from stage III. Based on in situ secondary ion mass spectrometry oxygen isotopic analysis of the five quartz generations (Qz-1 to Qz-5), the calculated δ18Ofluid values for the ore fluids are 7.8‰ to 9.2‰ (mean 8.3‰), −3.2‰ to 8.7‰ (mean 5.6‰), −3.5‰ to 7.4‰ (mean 4.6‰), −4.5‰ to 7.6‰ (mean −0.2‰), and −6.4‰ to 1.4‰ (mean −3.8‰). The oxygen isotopic data and trend among the five quartz generations are best interpreted to represent magmatically derived ore fluid being diluted by modified meteoric water to cause mineralization. Fluid mixing is considered to be the principal mechanism that led to Ag-Pb-Zn precipitation at Poshan. Sulfides coexisting with the quartz generations have δ34SV-CDT values of −1.7‰ to 4.4‰, with no systematic variations among different paragenetic stages. These data, combined with apatite U-Pb age and geologic relations, provide additional evidence for a magmatic origin of the Poshan Ag-Pb-Zn deposit, as inferred from the oxygen isotopes. This study highlights the role of fluid dilution in triggering Ag-Pb-Zn deposition, and sheds light on the origin of silver-polymetallic deposits in orogenic belts.
A temporal dissection of late Quaternary volcanism and related hazards within the Rio Grande rift and along the Jemez lineament of New Mexico, USA
Authors: Zimmerer Matthew J. 
Published: March 2024

Abstract
New 40Ar/39Ar ages, combined with selected ages from published studies, provide detailed insight into the late Quaternary (&lt;500 ka) eruptive history and related hazards of the Rio Grande rift and Jemez lineament of New Mexico, USA. Most eruptions in the region during this time were within monogenetic volcanic fields, which largely produced cinder cones and mafic lava flows. 40Ar/39Ar ages of mafic groundmass determined using the high-sensitivity ARGUS VI multicollector mass spectrometer are significantly more precise, by as much as an order of magnitude, than prior 40Ar/39Ar dates. The high-precision data permit more rigorous interpretation of age spectra and isochrons, leading to a greater confidence in assigning eruption ages, and thus allowing more accurate and thorough calculations of eruptive rates and repose periods. For most fields, comprehensive dating identifies a greater number of late Quaternary eruptions than previously known and, for some fields, determines younger-than-previously established ages for the last eruptive events. Repose periods in the fields range from too short to measure with the 40Ar/39Ar method to a few hundred thousand years, which suggests that all 12 fields in the rift and lineament with late Quaternary activity should be considered dormant rather than extinct, with the possibility of future eruptions. Average recurrence intervals for these fields during the late Quaternary range from 16.5 k.y. to 170.8 k.y. Many fields display peak periods of activity where rates spike to a recurrence interval of 5 k.y. or less. At the scale of the entire rift and lineament, 75 late Quaternary eruptions were dated, yielding an average recurrence interval of 6.5 k.y., which is a minimum estimate considering the likelihood of undated eruptions (either not studied or buried). During the last 100 k.y., the volcanic record is better preserved, and the recurrence interval is 3.2 k.y., which indicates that the current hiatus of 3.9 ± 1.2 k.y. is typical for the region. Since ca. 36 ka, the average recurrence interval decreased to 2.3 k.y., which suggests a slight increase in recent activity. When ages are compared to vent locations, a previously unrecognized migrational pattern is observed in nearly all of the fields studied. Migration vectors vary from 1.0 cm/yr to 4.0 cm/yr, and always with an eastward component—similar to migration patterns at some other late Cenozoic fields throughout the American Southwest. Volcanic migration is attributed to a combination of mechanisms including asthenospheric convection along the margin of the Colorado Plateau, North American plate motion over partial mantle melt, and extensional tectonics. Developing similar high-precision chronologies for other Quaternary fields throughout southwestern North America will be necessary to better understand the volcanic hazards of the region.
Pliocene subsurface fluid flow driven by rapid erosional exhumation of the Colorado Plateau, southwestern USA
Authors: Bailey Lydia R. , Reiners Peter W. , Ferguson Grant , McIntosh Jennifer , Kim Ji-Hyun , Hemming Sidney 
Published: March 2024

Abstract
Erosion may modify the architecture of subsurface flow systems by removing confining units and changing topography to influence patterns of fluid circulation or by inducing gas exsolution from subsurface fluids, influencing compositional and buoyancy patterns in flow systems. Here, we examine the geologic record of subsurface flow in the sedimentary rocks of the Paradox Basin in the Colorado Plateau (southwestern USA), including the distribution and ages of Fe- and Mn-oxide deposits and bleached, former red-bed sandstones. We compare our results to those of previous geo- and thermochronology studies that documented as much as 2 km of erosional exhumation at ca. 3–4 Ma and Fe-and Mn-oxide precipitation at 3.6 Ma along fault zones in the region.
We used (U-Th)/He and K-Ar dating to document two new records of subsurface flow of reduced fluids between 3 and 4 Ma. The first is precipitation of Mn-oxides along the Moab fault (Utah, USA) at 3.9 ± 0.2 Ma. The second is clay mineralization associated with laterally extensive bleaching in the Curtis Formation, which we dated using K-Ar illite age analysis to 3.60 ± 0.03 Ma. The coincidence of the timing of bleaching, Fe- and Mn-oxide formation in multiple locations, and erosional exhumation at 3–4 Ma raises the question of how surface erosion may have induced a phase of fluid flow in the subsurface. We suggest that recent erosion of the Colorado Plateau created steep topographic gradients that enhanced regional groundwater flow, whereby meteoric water circulation flushed reduced fluids toward discharge zones. Dissolved gases, transported from hydrocarbon reservoirs, also may have been exsolved by rapid depressurization.
New geochemical and geochronological insights on forearc magmatism across the Sanak-Baranof belt, southern Alaska: A tale of two belts
Authors: Wackett Adrian A. , Smith Diane R. , Davidson Cameron , Garver John I. 
Published: March 2024

Abstract
The Sanak-Baranof belt includes a series of near-trench plutons that intrude the outboard Chugach–Prince William terrane over ~2200 km along the southern Alaskan margin. We present new petrological, geochronological, and geochemical data for comagmatic microgranitoid enclaves and granitoid rocks from the Crawfish Inlet (ca. 53–47 Ma) and Krestof Island (ca. 52 Ma) plutons on Baranof and Krestof Islands, as well as the Mount Stamy (ca. 51 Ma) and Mount Draper (ca. 54–53 Ma) plutons and associated mafic rocks that intrude the Boundary block at Nunatak Fiord near Yakutat, Alaska, USA. These data suggest that intrusion of the Sanak-Baranof belt plutons is actually a tale of two distinct belts: a western belt with crystallization ages that young systematically from west to east (63–56 Ma) and an eastern belt with crystallization ages ranging from 55 to 47 Ma, but with no clear age progression along the margin. Hf isotope analyses of magmatic zircon from the western Sanak-Baranof belt become increasingly evolved toward the east with εHft = 9.3 ± 0.7 on Sanak Island versus εHft = 5.1 ± 0.5 for the Hive Island pluton in Resurrection Bay. The Hf isotope ratios of eastern Sanak-Baranof belt rocks also vary systematically with age but in reverse, with more evolved ratios in the oldest plutons (εHft = +4.7 ± 0.7) and more primitive ratios in the youngest plutons (εHft = +13.7 ± 0.7). We propose that these findings indicate distinct modes of origin and emplacement histories for the western and eastern segments of the Sanak-Baranof belt, and that the petrogenesis of eastern Sanak-Baranof belt plutons (emplaced subsequent to 57–55 Ma) was associated with an increasing mantle component supplied to the youngest eastern Sanak-Baranof belt magmas. These plutons reveal important information about offshore plate geometries and a dynamic period of plate reorganization ca. 57–55 Ma, but a clearer picture of the tectonic setting that facilitated these Sanak-Baranof belt intrusions cannot be resolved until the magnitude and significance of lateral translation of the Chugach–Prince William terrane are better understood.
High-Mg andesites and Nb-enriched basalts in the Dulate arc, East Junggar (NW China): Evidence of ocean ridge subduction
Authors: Qin Zhen , Tao Huifei , Qu Yongqiang , Wu Tao , Li Zhongping 
Published: March 2024

Abstract
The Dulate arc, located in East Junggar (NW China) in the southern Central Asian orogenic belt, records a Devonian magmatic arc evolution, offering a window to understanding the orogenic processes of the Central Asian orogenic belt. Here we present new geochemical and isotopic data for Late Devonian high-Mg andesite (HMA) and Nb-enriched basalt (NEB) suites from the Qiakuerte area, East Junggar. The HMA samples are typical subduction-related volcanic rocks. They have SiO2 contents ranging from 53.30 to 54.59 wt%, high MgO (5.0–5.26 wt%), and high Mg# values (~55) and show enrichments in large ion lithophile elements (LILEs) and depletions in high field strength elements (HFSEs). The HMA samples have high (La/Yb)N ratios and Sr/Y (~6.5 and 50–59, respectively) with no Eu anomalies. The HMA samples have high Na2O (~3.3 wt%) and low K2O (~2.5 wt%) and Th (~2.4 ppm) contents, combined with positive εNd(t) and low (87Sr/86Sr)i values. These characteristics suggest that the samples were formed mainly through interactions between subducted oceanic melts and mantle peridotites. Compared to normal arc basalts, the NEB samples have higher concentrations of Nb (~20 ppm), higher primitive mantle–normalized Nb/La (0.50–0.58), and higher ratios of Nb/U (9.4–14.6). The NEB samples also have positive εNd(t) and low (87Sr/86Sr)i values, indicating that their source was mantle wedge that had been metasomatized by slab melt. Considering the widespread presence of A-type granites, the abnormally high heat flow, and the tectonic characteristics of East Junggar, we conclude that a slab window created by the subduction of an ocean ridge was responsible for the melting of slab and the formation of the NEB-HMA suites. These processes may have also played a key role in the tectonic evolution processes of East Junggar during the Late Devonian.
Evaluating the effectiveness of spatial training for introductory geology students
Authors: Klyce Annie , Ryker Katherine 
Published: March 2024

Abstract
Spatial skills, which represent the ability to visualize and imagine manipulating objects in one’s mind, are necessary for success in the science, technology, engineering, and mathematics (STEM) fields and are particularly relied upon by geoscientists. Although scholars recognize the importance of these skills, explicit training is inconsistently offered throughout courses. Furthermore, the relationship between spatial training and students’ perspectives on STEM fields is underexplored. To address this, we developed a case study that included over 700 students enrolled in introductory geology classes over three semesters. These students were randomly divided into control and experimental groups; the experimental group completed 10 spatial training assignments, and the control group completed the course as usual. We relied on situated expectancy-value theory to interpret changes in students’ perceptions of both the course and science overall, and asked the following research questions: (1) Do students who complete the spatial training assignments (i.e., the experimental group) have a statistically significant improvement in their final course grade, self-efficacy, and/or value when compared to the control group? (2) If so, what are the effect sizes of these changes? (3) Is there a minimum number of trainings that need to be completed to achieve this effect? (4) Is there a maximum number of spatial training assignments where we stop seeing improvement (ceiling effect)?
We surveyed all students enrolled using 38-question pre- and post-assessments of their self-efficacy, defined as a belief in their ability to succeed, and value. We found that between the control and experimental groups, there were significant differences in students’ pre- to post-changes in perception of science self-efficacy, class self-efficacy, and class value. We found non-significant between-group differences in final grade and science value. We interpret this to mean that using weekly spatial training assignments could increase students’ perceived self-efficacy in their introductory geology course as well as in science more broadly, potentially having ripple effects that support students’ long-term engagement with the sciences.
Findings suggest that practitioners should include explicit spatial training in their courses to improve students’ perceptions of the course and science overall. Building on this work may include describing to students the purpose of spatial training (which was deliberately avoided in this study) and outlining the research that supports the relationship between spatial skills and success in STEM fields. Future directions may also include longitudinal tracking of spatial and related skill development throughout students’ college careers.
Structure and provenance of the Cretaceous Pingshanhu Basin in the Hexi Corridor: Implications for Mesozoic tectonics in the northern Tibetan Plateau
Authors: Liu Wenyou , Wu Chen , Li Jie , Zhang Cunhui , Jiang Tian , Zuza Andrew V. , Haproff Peter J. , Chen Xuanhua , Yue Yahui 
Published: March 2024

Abstract
The construction of Earth’s largest highland, the Tibetan Plateau, is generally considered to have been generated by the Cenozoic India-Asia collision. However, the extent to which high topography existed prior to the Cenozoic remains unclear. The Hexi Corridor foreland basin of the northern Tibetan Plateau is an ideal region in which to investigate this history, given its widespread exposure of Early Cretaceous sedimentary sequences. In this study, we examined the Early Cretaceous strata in the northern Hexi Corridor to understand the relationships between pre-Cenozoic sedimentation and tectonic deformation and constrain the late Mesozoic tectonic setting of the adjacent Qilian Shan and Alxa blocks bordering the northern Tibetan Plateau. Results of sandstone petrology analyses, paleocurrent observations, and U-Pb geochronology suggest that the oldest Early Cretaceous sediments deposited in the northern Hexi Corridor were sourced from the southern Alxa block during the earliest Cretaceous. By the late Early Cretaceous, Hexi Corridor sediments were sourced from both the southern Alxa block to the north and the Qilian Shan to the south. Sandstone petrologic results indicate that the northern Hexi Corridor experienced a tectonic transition from contraction to extension during the Early Cretaceous. These findings suggest that the northern Tibetan Plateau region was partially uplifted to a high elevation during the late Mesozoic before the India-Asia collision.
Function of mast cell and bile-cholangiocarcinoma interplay in cholangiocarcinoma microenvironment
Authors: Shi Anda , Liu Zengli , Fan Zhongqi , Li Kangshuai , Liu Xingkai , Tang Yongchang , Hu Jiaming , Li Xingyong , Shu Lizhuang , Zhao Liming , Huang Lingling , Zhang Zhiyue , Lv Guoyue , Zhang Zongli , Xu Yunfei 
Published: March 2024

Objective
The correlation between cholangiocarcinoma (CCA) progression and bile is rarely studied. Here, we aimed to identify differential metabolites in benign and malignant bile ducts and elucidate the generation, function and degradation of bile metabolites.

Design
Differential metabolites in the bile from CCA and benign biliary stenosis were identified by metabonomics. Biliary molecules able to induce mast cell (MC) degranulation were revealed by in vitro and in vivo experiments, including liquid chromatography-mass spectrometry (MS)/MS and bioluminescence resonance energy transfer assays. Histamine (HA) receptor expression in CCA was mapped using a single-cell mRNA sequence. HA receptor functions were elucidated by patient-derived xenografts (PDX) in humanised mice and orthotopic models in MC-deficient mice. Genes involved in HA-induced proliferation were screened by CRISPR/Cas9.

Results

Bile HA was elevated in CCA and indicated poorer prognoses. Cancer-associated fibroblasts (CAFs)-derived stem cell factor (SCF) recruited MCs, and bile N,N-dimethyl-1,4-phenylenediamine (DMPD) stimulated MCs to release HA through G protein-coupled receptor subtype 2 (MRGPRX2)-Gαq signalling. Bile-induced MCs released platelet-derived growth factor subunit B (PDGF-B) and angiopoietin 1/2 (ANGPT1/2), which enhanced CCA angiogenesis and lymphangiogenesis. Histamine receptor H1 (HRH1) and HRH2 were predominantly expressed in CCA cells and CAFs, respectively. HA promoted CCA cell proliferation by activating HRH1-Gαq signalling and hastened CAFs to secrete hepatocyte growth factor by stimulating HRH2-Gαs signalling. Solute carrier family 22 member 3 (SLC22A3) inhibited HA-induced CCA proliferation by importing bile HA into cells for degradation, and
SLC22A3
deletion resulted in HA accumulation.

Conclusion
Bile HA is released from MCs through DMPD stimulation and degraded via SLC22A3 import. Different HA receptors exhibit a distinct expression profile in CCA and produce different oncogenic effects. MCs promote CCA progression in a CCA-bile interplay pattern.
Network-based screening identifies sitagliptin as an antitumor drug targeting dendritic cells
Authors: Ng Ian-Ian , Zhang Jiaqi , Tian Tingzhong , Peng Qi , Huang Zheng , Xiao Kaimin , Yao Xiyue , Ng Lui , Zeng Jianyang , Tang Haidong 
Published: March 2024

BackgroundDendritic cell (DC)-mediated antigen presentation is essential for the priming and activation of tumor-specific T cells. However, few drugs that specifically manipulate DC functions are available. The identification of drugs targeting DC holds great promise for cancer immunotherapy.MethodsWe observed that type 1 conventional DCs (cDC1s) initiated a distinct transcriptional program during antigen presentation. We used a network-based approach to screen for cDC1-targeting therapeutics. The antitumor potency and underlying mechanisms of the candidate drug were investigated in vitro and in vivo.ResultsSitagliptin, an oral gliptin widely used for type 2 diabetes, was identified as a drug that targets DCs. In mouse models, sitagliptin inhibited tumor growth by enhancing cDC1-mediated antigen presentation, leading to better T-cell activation. Mechanistically, inhibition of dipeptidyl peptidase 4 (DPP4) by sitagliptin prevented the truncation and degradation of chemokines/cytokines that are important for DC activation. Sitagliptin enhanced cancer immunotherapy by facilitating the priming of antigen-specific T cells by DCs. In humans, the use of sitagliptin correlated with a lower risk of tumor recurrence in patients with colorectal cancer undergoing curative surgery.ConclusionsOur findings indicate that sitagliptin-mediated DPP4 inhibition promotes antitumor immune response by augmenting cDC1 functions. These data suggest that sitagliptin can be repurposed as an antitumor drug targeting DC, which provides a potential strategy for cancer immunotherapy.