bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteostatic tuning underpins the evolution of novel multicellular traits
Authors: Montrose Kristopher , Lac Dung T. , Burnetti Anthony J. , Tong Kai , Bozdag G. Ozan , Hukkanen Mikaela , Ratcliff William C. , Saarikangas Juha
Published: March 2024

The evolution of multicellularity paved the way for the origin of complex life on Earth, but little is known about the mechanistic basis of early multicellular evolution. Here, we examine the molecular basis of multicellular adaptation in the multicellularity long-term evolution experiment (MuLTEE). We demonstrate that cellular elongation, a key adaptation underpinning increased biophysical toughness and organismal size, is convergently driven by down-regulation of the chaperone Hsp90. Mechanistically, Hsp90-mediated morphogenesis operates by destabilizing the cyclin-dependent kinase Cdc28, resulting in delayed mitosis and prolonged polarized growth. Reinstatement of Hsp90 or Cdc28 expression resulted in shortened cells that formed smaller groups with reduced multicellular fitness. Together, our results show how ancient protein folding systems can be tuned to drive rapid evolution at a new level of biological individuality by revealing novel developmental phenotypes.
Crosstalk involving two-component systems in
Staphylococcus aureus
signaling networks
Authors: Ali Liaqat , Abdel Aziz May H.
Published: March 2024

Staphylococcus aureus
poses a serious global threat to human health due to its pathogenic nature, adaptation to environmental stress, high virulence, and the prevalence of antimicrobial resistance. The signaling network in
S. aureus
coordinates and integrates various internal and external inputs and stimuli to adapt and formulate a response to the environment. Two-component systems (TCSs) of
S. aureus
play a central role in this network where surface-expressed histidine kinases (HKs) receive and relay external signals to their cognate response regulators (RRs). Despite the purported high fidelity of signaling, crosstalk within TCSs, between HK and non-cognate RR, and between TCSs and other systems has been detected widely in bacteria. The examples of crosstalk in
S. aureus
are very limited, and there needs to be more understanding of its molecular recognition mechanisms, although some crosstalk can be inferred from similar bacterial systems that share structural similarities. Understanding the cellular processes mediated by this crosstalk and how it alters signaling, especially under stress conditions, may help decipher the emergence of antibiotic resistance. This review highlights examples of signaling crosstalk in bacteria in general and
S. aureus
in particular, as well as the effect of TCS mutations on signaling and crosstalk.
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

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

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

New 40Ar/39Ar ages, combined with selected ages from published studies, provide detailed insight into the late Quaternary (<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

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

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

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

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

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.
Fusarium falciformeeumycetoma: a diagnostic challenge of a neglected tropical disease
Authors: Badarol Hisham Noralwani , Abdul Rhani Shaharuddin , Mohd Ali Razana , Masri Siti Norbaya
Published: March 2024

Eumycetoma, a subcutaneous infection caused by various fungi with pathognomonic discharging grain, is rarely reported in Malaysia. This case concerns a eumycetoma infection in an immunocompetent man who presented with progressive left foot swelling complicated with pustules, sinuses and pale grain discharge for the past year after recurrent thorn pricks. Histological findings of the grain and tissue showed foci of septate fungal hyphae. Tissue culture yielded no growth. Amplification and sequencing of the rDNA internal transcribed spacer 1 (ITS1), ITS4 and large subunit regions of the tissue identified the causative agent asFusarium falciforme, highlighting the role of molecular diagnostic method in identifying fungal species in eumycetoma. The patient was treated with surgical excision and oral itraconazole with excellent improvement. However, he presented again with recurrence after defaulting therapy.F. falciformehas been implicated in causing diseases in crops and sea turtles. Therefore, the One Health approach should be adopted to manage this emerging species.
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

Background

Dendritic 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.

Methods

We 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.

Results

Sitagliptin, 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.

Conclusions

Our 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.
Cerebral visual impairment: genetic diagnoses and phenotypic associations
Authors: Shaw Emogene , Flitcroft Ian , Bowman Richard , Baker Kate
Published: March 2024

Background

Cerebral visual impairment (CVI) is the most common form of paediatric visual impairment in developed countries. CVI can arise from a host of genetic or acquired causes, but there has been limited research to date on CVI in the context of genetic disorders.

Methods

We carried out a retrospective analysis of genotypic and phenotypic data for participants with CVI within the DECIPHER database and 100 000 Genomes Project (100KGP).

Results

158 individuals with CVI were identified across both cohorts. Within this group, pathogenic or likely pathogenic sequence variants in 173 genes were identified. 25 of these genes already have known associations with CVI, while the remaining 148 are candidate genes for this phenotype. Gene ontology analysis of the CVI gene sets from both DECIPHER and 100KGP suggests that CVI has a similar degree of genetic heterogeneity to other neurodevelopmental phenotypes, and a strong association with genetic variants converging on ion channels and receptor functions. Individuals with a monogenic disorder and CVI have a higher frequency of epilepsies and severe neurodisability than individuals with a monogenic disorder but not CVI.

Conclusion

This study supports the availability of genetic testing for individuals with CVI alongside other neurodevelopmental difficulties. It also supports the availability of ophthalmological screening for individuals with genetic diagnoses linked to CVI. Further studies could elaborate on the links between specific genetic disorders, visual maturation and broader neurodevelopmental characteristics.
The development and initial validation of IgG4-related disease damage index: a consensus report from Chinese IgG4-RD Consortium
Authors: Peng Linyi , Li Jingna , Zhou Jiaxin , Fei Yunyun , Dong lingli , Liu Yan-Ying , Zhang Dingding , Wang Yanhong , Chi Shuhong , Wang Fang , Hou Yunxia , Hong Xiaoping , Sun Hongsheng , Ye Yujin , Che Nan , Zhang Rong , Liu Changyan , Ji Zongfei , Sun Wenjia , Zhao Cheng , Ma Ning , Lai Yamin , Li Mengtao , Zhao Yan , Zeng Xiaofeng , Lu Liwei , Zhang Wen
Published: March 2024

Objective

To develop and conduct an initial validation of the Damage Index for IgG4-related disease (IgG4-RD DI).

Methods

A draft of index items for assessing organ damages in patients with IgG4-RD was generated by experts from the Chinese IgG4-RD Consortium (CIC). The preliminary DI was refined using the Delphi method, and a final version was generated by consensus. 40 IgG4-RD cases representing four types of clinical scenarios were then selected, each with two time points of assessment for at least 3 years of follow-up. 48 rheumatologists from 35 hospitals nationwide were invited to evaluate organ damage using the CIC IgG4-RD DI. The intraclass correlation coefficient (ICC) and the Kendall-W coefficient of concordance (KW) were used to assess the inter-rater reliability. The criterion validity of IgG4-RD DI was tested by calculating the sensitivity and specificity of raters.

Results

IgG4-RD DI is a cumulative index consisting of 14 domains of organ systems, including a total of 39 items. The IgG4-RD DI was capable of distinguishing stable and increased damage across the active disease subgroup and stable disease subgroup. In terms of scores at baseline and later observations by all raters, overall consistency in scores at baseline and later observations by all raters was satisfactory. ICC at the two time points was 0.69 and 0.70, and the KW was 0.74 and 0.73, respectively. In subgroup analysis, ICC and KW in all subgroups were over 0.55 and 0.61, respectively. The analysis of criterion validity showed a good performance with a sensitivity of 0.86 (95% CI 0.82 to 0.88), a specificity of 0.79 (95% CI 0.76 to 0.82) and an area under the curve of 0.88 (95% CI 0.85 to 0.91).

Conclusion

The IgG4-RD DI is a useful approach to analyse disease outcomes, and it has good operability and credibility. It is anticipated that the DI will become a useful tool for therapeutic trials and studies of prognosis in patients with IgG4-RD.
Modelling permafrost distribution using the temperature at top of permafrost model in the boreal forest environment of Whatì, NT
Authors: Vegter Scott , Bonnaventure Philip P. , Daly Seamus , Kochtitzky Will
Published: March 2024

Current permafrost models in Canadian boreal forests are generally of low spatial resolution as they cover regional or continental scales. This study aims to understand the viability of creating a temperature at the top of permafrost (TTOP) model on a local scale in the boreal wetland environment of Whatì, Northwest Territories from short-term field-collected temperature data. The model utilizes independent variables of vegetation, topographic position index, and elevation, with the dependent variables being ground surface temperature collected from 60 ground temperature nodes and 1.5 m air temperature collected from 10 temperature stations. In doing this, the study investigates the relationship vegetation and disturbance have on ground temperature and permafrost distribution. The model predicts that 31% of the ground is underlain by permafrost, based on a mean annual temperature at TTOP of <0 °C. This model shows an accuracy of 62.5% when compared to cryotic assessment sites (CAS). Most inaccuracies, showing the limitations of the TTOP model, came from peat plateaus that had been burned in the most recent forest fire in 2014. These resulted in out-of-equilibrium permafrost and climatic conditions that TTOP cannot handle well. Commonly, permafrost mapping places Whatì in the extensive discontinuous zone, estimating that between 50% and 90% of the ground is underlain by permafrost. The study shows that a climatically driven TTOP model calibrated with CAS can be used to illustrate ground temperature heterogeneity from short-term data in boreal forest wetland environments. However, this approach likely underestimates permafrost extent and is perhaps not the best-suited modelling choice for near-surface permafrost, which is currently out of equilibrium with the current climate.
Generalization of the Thwaites integral method for laminar boundary-layers due to moving continuous surfaces
Authors: Awais Muhammad , Mahmood Ahmer
Published: March 2024

In this study, attention has been given towards the development of an approximate method for the boundary-layer flows involving no pressure gradient (the flows due to moving continuous surfaces in a still fluid). The integral method devised in this study is an extension of the existing Thwaites integral method; applicable to boundary-layer flows over the stationary surfaces of finite length (which, in general, involve the pressure gradient because of the presence of external potential flow, except for the case of uniform external flow). The existing Thwaites integral method does not give an acceptable approximation for the flows over moving continuous surfaces in a quiescent fluid, involving no pressure gradient. Therefore, the extension of the existing Thwaites integral method, proposed in this study, will make it applicable to the flows due to moving continuous surfaces in a stationary fluid (involving no pressure gradient), also. With the combination of the two, the existing, and the extended Thwaites integral method, the generalized Thwaites integral method is proposed, applicable to the boundary-layer flows whether involving a pressure gradient or not.
The computational orthogonal shifted Legendre–Galerkin approach for handling fractional delay differential problems via adapting fractional M-derivative
Authors: Sweis Hind , Arqub Omar Abu
Published: March 2024

This paper presents a numerical procedure for handling delay fractional differential problems where the derivative is defined using the M-fractional approach. The proposed scheme modus operandi is based on the shifted Legendre–Galerkin procedure, which is a powerful tool for solving complex differential models of generalized fractional derivatives. The method involves constructing a series of Legendre polynomials that form the basis functions for approximating the solution of the required problem. The coefficients of the series are obtained after solving an algebraic system of linear types that results from the application of the Galerkin practice. The numerical accuracy and convergence assessment are also presented together with various results. Simulations-based analyses are realized to validate the truthfulness and exactness of the process. The results manifest that the M-derivatives and the Galerkin practice provide alternative innovative approaches for handling M-delay fractional problems. Several keynotes and future recommendations are exhibited at the last with some selected references.
Resurgence and self-completion in renormalized gauge theories
Authors: Maiezza Alessio , Vasquez Juan Carlos
Published: March 2024

Under certain assumptions and independent of the instantons, we show that the logarithm expansion of dimensional regularization in quantum field theory needs a nonperturbative completion to have a renormalization group flow valid at all energies. Then, we show that such nonperturbative completion has the analytic properties of the renormalons, which we find with only a marginal reference to diagrammatic calculations. We demonstrate that renormalon corrections necessarily lead to analyzable functions, namely, resurgent transseries. A detailed analysis of the resurgent properties of the renormalons is provided. The self-consistency of the theory requires these nonperturbative contributions to render the running coupling well defined at any energy, thus with no Landau pole. We illustrate the point within the case of quantum electrodynamics (QED). This way, we explicitly realize the correspondence between the nonperturbative Landau pole scale and the renormalons. What is seen as a Landau pole in perturbation theory is cured by the nonperturbative, resurgent contributions.
On the geometry of two state models for the colored Jones polynomial
Authors: Kaiser Uwe , Mishra Rama
Published: March 2024

Using the flow property of the [Formula: see text]-matrix defining the colored Jones polynomial, we establish a natural bijection between the set of states on the part arc-graph of a link projection and the set of states on a corresponding bichromatic digraph, called arc-graph, as defined by Garoufalidis and Loebl [A non-commutative formula for the colored Jones function, Math. Ann. 336 (2006) 867–900]. We use this to give a new and essentially elementary proof for the knot state-sum formula in [S. Garoufalidis and M. Loebl, A non-commutative formula for the colored Jones function, Math. Ann. 336 (2006) 867–900]. We will show that the state-sum contributions of states on the part arc-graph defined by the universal [Formula: see text]-matrix of [Formula: see text] correspond, under our bijection of sets of states, to the contributions in [S. Garoufalidis and M. Loebl, A non-commutative formula for the colored Jones function, Math. Ann. 336 (2006) 867–900]. This will show that the two state models are in fact not essentially distinct. Our approach will also extend the formula of Garoufalidis and Loebl to links. This requires some additional nontrivial observations concerning the geometry of states on the part arc-graphs. We will discuss in detail the computation of the arc-graph state-sum, in particular for [Formula: see text]-braid closures.
Dominance of polarization modes and absorption on self-focusing of laser beams in collisionless magnetized plasma
Authors: Vhanmore B. D. , Rajmane S. P. , Sadale S. B. , Patil S. D. , Shinde H. M. , Kamble R. J. , Takale M. V.
Published: March 2024

This work investigates the polarization modes i.e., Extraordinary (E-mode) and Ordinary (O-mode) on self-focusing of higher-order mode of elegant Hermite-cosh-Gaussian (EHChG) laser beams within collisionless magnetized plasma medium. In this study, the authors have taken transverse electromagnetic (TEM) mode with mode indices (0, 4) and explored. The ponderomotive force is primarily responsible for the dielectric constant’s nonlinearity in this context. Also, WKB and paraxial approximations via the parabolic wave equation approach are used to establish the general form of differential equations for beam-width parameters in both transverse dimensions of the beam. In this paper, the authors have theoretically investigated the dominance of polarization modes and absorption coefficient on self-focusing. The final results show good enhancement of laser propagation through collisionless plasma medium.
Complete CMC-1 surfaces in hyperbolic space with arbitrary complex structure
Authors: Alarcón Antonio , Castro-Infantes Ildefonso , Hidalgo Jorge
Published: March 2024

We prove that every open Riemann surface [Formula: see text] is the complex structure of a complete surface of constant mean curvature [Formula: see text] ([Formula: see text]‒1) in the three-dimensional hyperbolic space [Formula: see text]. We go further and establish a jet interpolation theorem for complete conformal [Formula: see text]‒1 immersions [Formula: see text]. As a consequence, we show the existence of complete densely immersed [Formula: see text]‒1 surfaces in [Formula: see text] with arbitrary complex structure. We obtain these results as application of a uniform approximation theorem with jet interpolation for holomorphic null curves in [Formula: see text] which is also established in this paper.
Numerical methods for fractional Fokker–Planck equation with multiplicative Marcus Lévy noises
Authors: Shang Wenpeng , Cheng Xiujun , Li Xiaofan , Wang Xiao
Published: March 2024

The Fokker–Planck equation (FPE) is an important deterministic tool for investigating stochastic dynamical systems. In this paper, we consider the space-time fractional FPE driven by multiplicative Marcus Lévy noises. Efficient numerical schemes are presented to solve the equations. Stability and convergence of the methods are also discussed. We give some numerical experiments to validate our schemes, and examine the effects of parameters on solutions. Additionally, we analyze the maximal likely trajectories and the critical time for the change of the most probability location.
Estimates of constants in the limit theorems for chaotic dynamical systems
Authors: Bunimovich Leonid A. , Su Yaofeng
Published: March 2024

In a vast area of probabilistic limit theorems for dynamical systems with chaotic behaviors always only functional form (exponential, power, etc.) of the asymptotic laws and of convergence rates were studied. However, for basically all applications, e.g., for computer simulations, development of algorithms to study chaotic dynamical systems numerically, as well as for design and analysis of real (e.g., in physics) experiments, the exact values (or at least estimates) of constants (parameters) of the functions, which appear in the asymptotic laws and rates of convergence, are of primary interest. In this paper, we provide such estimates of constants (parameters) in the central limit theorem, large deviations principle, law of large numbers and the rate of correlations decay for strongly chaotic dynamical systems.
A proof of the additivity of rough integral
Authors: Ito Yu
Published: March 2024

On the basis of fractional calculus, we introduce an explicit formulation of the integral of controlled paths along Hölder rough paths in terms of Lebesgue integrals for fractional derivatives. The additivity with respect to the interval of integration, a fundamental property of the integral, is not apparent under the formulation because the fractional derivatives depend heavily on the endpoints of the interval of integration. In this paper, we provide a proof of the additivity of the integral under the formulation. Our proof seems to be simpler than those provided in previous studies and is suitable for utilizing the fractional calculus approach to rough path analysis.
Binary robustness of random attractors for 2D-Ginzburg–Landau equations with Wong–Zakai noise
Authors: Li Yangrong , Wang Fengling
Published: March 2024

Consider a non-autonomous 2D-Ginzburg–Landau equation driven by Wong–Zakai noise or white noise, respectively, we first show the existence of pullback random attractors, which are random compact attracting sets indexed by two parameters: the size of Wong–Zakai noise and the current time. We then establish the robustness of the attractors when both parameters are simultaneously convergent. An essential difficulty arises from the possible loss of the convergence of solutions and only part convergence of solutions is available, which is a new phenomenon for 2D-GL equation distinguishing with the 1D case. So, by using part joint-convergence, regularity, eventual local-compactness and recurrence, we establish a binary robustness theorem of pullback random attractors and apply it to the weakly dissipative stochastic equation.
Dynamical behaviors of an impulsive stochastic neural field lattice model
Authors: Zeng Tianhao , Mi Shaoyue , Li Dingshi
Published: March 2024

This paper is concerned with the asymptotic behaviors of the solutions of an impulsive stochastic neural field lattice model driven by nonlinear noise. We first show the existence and uniqueness of weak pullback mean random attractors for the impulsive stochastic systems. Then by the properties of Markov processes, the existence of evolution system of measures for the impulsive stochastic systems is established. To this end, we employ the idea of uniform estimates on the tails of the solutions to show the tightness of a family of distributions of the solutions of the lattice systems.
Optimization of YOLOv7 Based on PConv, SE Attention and Wise-IoU
Authors: Zhigang Liu , Baoshan Sun , Kaiyu Bi
Published: March 2024

With the rapid development of deep learning technology, object detection algorithms have made significant breakthroughs in the field of computer vision. However, due to the complexity and computational requirements of deep Convolutional Neural Network (CNN), these models face many challenges in practical applications, especially on resource-constrained edge devices. To address this problem, researchers have proposed many lightweight methods that aim to reduce the model size and computational complexity while maintaining high performance. The popularity of mobile devices and embedded systems has led to an increasing demand for lightweight models. However, existing lightweight methods often lead to accuracy loss, limiting their feasibility in practical applications. Therefore, how to realize the light weight of the model while maintaining high accuracy has become an urgent problem to be solved. To address this challenge, this paper proposes a lightweight YOLOv7 method based on PConv, Squeeze-and-Excitation (SE) attention mechanism and Wise-IoU (WIoU), which we refer to as YOLOv7-PSW. PConv can effectively reduce the number of parameters and computational complexity. The SE can help the model focus on important feature information, thereby improving performance. WIoU is introduced to measure the similarity between the detection box and the Ground Truth, so that the model can effectively reduce the False Positive rate. By applying these advanced techniques to the YOLOv7, we achieve a lightweight model while maintaining a high detection accuracy. Experimental results on PASCAL VOC dataset show that YOLOv7-PSW performs better than the original YOLOv7 on object detection tasks. The number of parameters is reduced by 12.3%, FLOPs is reduced by 18.86%, and the accuracy is improved by about 0.5%. While the detection accuracy is not decreased or even slightly improved, the number of FLOPs and parameters is greatly reduced, which realizes lightweight to a certain extent. The proposed method can provide new ideas and directions for the subsequent research on lightweight object detection, and is expected to promote its application on edge devices. Meanwhile, YOLOv7-PSW can also be applied to other computer vision tasks to improve its performance and efficiency. In summary, the proposed YOLOv7-PSW lightweight method realizes the light weight of the model while maintaining high accuracy. This is of great significance for promoting the application of object detection algorithms on edge devices.