bluuebunny/crossref_metadata_2025 huggingface dataset:
2018-2019 human seasonal H3N2 influenza A virus spillovers into swine with demonstrated virus transmission in pigs were not sustained in the pig population
Authors: Powell Joshua D. , Thomas Megan N. , Anderson Tavis K. , Zeller Michael A. , Gauger Phillip C. , Vincent Baker Amy L.
Published: November 2024

Human seasonal H3 clade 3C3a influenza A viruses (IAV) were detected four times in U.S. pigs from commercial swine farms in Michigan, Illinois, and Virginia in 2019. To evaluate the relative risk of this spillover to the pig population, whole genome sequencing and phylogenetic characterization were conducted, and the results revealed that all eight viral gene segments were closely related to 2018–2019 H3N2 human seasonal IAV. Next, a series of
in vitro
viral kinetics, receptor binding, and antigenic characterization studies were performed using a representative A/swine/Virginia/A02478738/2018(H3N2) (SW/VA/19) isolate. Viral replication kinetic studies of SW/VA/19 demonstrated less efficient replication curves than all 10 swine H3N2 viruses tested but higher than three human H3N2 strains. Serial passaging experiments of SW/VA/19 in swine cells did not increase virus replication, but changes at HA amino acid positions 9 and 159 occurred. In swine transmission studies, wild-type SW/VA/19 was shed in nasal secretions and transmitted to all indirect contact pigs, whereas the human seasonal strain A/Switzerland/9715293/2013(H3N2) from the same 3C3a clade failed to transmit. SW/VA/19 induced minimal macroscopic and microscopic lung lesions. Collectively, these findings demonstrate that these human seasonal H3N2 3C3a-like viruses did not require reassortment with endemic swine IAV gene segments for virus shedding and transmission in pigs. Limited detections in the U.S. pig population in the subsequent period of time suggest a yet-unknown restriction factor likely limiting the spread of these viruses in the U.S. pig population.

IMPORTANCE

Interspecies human-to-swine IAV transmission occurs globally and contributes to increased IAV diversity in pig populations. We present data that a swine isolate from a 2018–2019 human-to-swine transmission event was shed for multiple days in challenged and contact pigs. By characterizing this introduction through bioinformatic, molecular, and animal experimental approaches, these findings better inform animal health practices and vaccine decision-making. Since wholly human seasonal H3N2 viruses in the United States were not previously identified as being transmissible in pigs (i.e., reverse zoonosis), these findings reveal that the interspecies barriers for transmission to pigs may not require significant changes to all human seasonal H3N2, although additional changes may be required for sustained transmission in swine populations.
Genome sequence of
Trueperella pyogenes
isolates from liver abscesses in feedlot cattle
Authors: Gruninger Robert J. , Zaheer Rahat , Stuart-Edwards Matthew , Zovoilis Athanasios , McAllister Tim A.
Published: November 2024

High-grain diets promote polymicrobial liver infections in cattle, commonly involving the bacterium
Trueperella pyogenes
. We have isolated
T. pyogenes
from the purulent material of abscesses and sequenced their genomes. These data enhance our understanding of the mechanisms underlying liver abscess development in cattle.
Nuclear pore complexes undergo Nup221 exchange during blood-stage asexual replication of
Plasmodium
parasites
Authors: Blauwkamp James , Ambekar Sushma V. , Hussain Tahir , Mair Gunnar R. , Beck Josh R. , Absalon Sabrina
Published: November 2024

Plasmodium
parasites, the causative agents of malaria, undergo closed mitosis without breakdown of the nuclear envelope. Unlike closed mitosis in yeast,
Plasmodium berghei
parasites undergo multiple rounds of asynchronous nuclear divisions in a shared cytoplasm. This results in a multinucleated organism prior to the formation of daughter cells within an infected red blood cell. During this replication process, intact nuclear pore complexes (NPCs) and their component nucleoporins play critical roles in parasite growth, facilitating selective bi-directional nucleocytoplasmic transport and genome organization. Here, we utilize ultrastructure expansion microscopy to investigate
P. berghei
nucleoporins at the single nucleus level throughout the 24-hour blood-stage replication cycle. Our findings reveal that these nucleoporins are distributed around the nuclei and organized in a rosette structure previously undescribed around the centriolar plaque, responsible for intranuclear microtubule nucleation during mitosis. By adapting the recombination-induced tag exchange system to
P. berghei
through a single plasmid tagging system, which includes the tagging plasmid as well as the Cre recombinase, we provide evidence of NPC formation dynamics, demonstrating Nup221 turnover during parasite asexual replication. Our data shed light on the distribution of NPCs and their homeostasis during the blood-stage replication of
P. berghei
parasites.

IMPORTANCE

Malaria, caused by
Plasmodium
species, remains a critical global health challenge, with an estimated 249 million cases and over 600,000 deaths in 2022, primarily affecting children under five. Understanding the nuclear dynamics of
Plasmodium
parasites, particularly during their unique mitotic processes, is crucial for developing novel therapeutic strategies. Our study leverages advanced microscopy techniques, such as ultrastructure expansion microscopy, to reveal the organization and turnover of nuclear pore complexes (NPCs) during the parasite’s asexual replication. By elucidating these previously unknown aspects of NPC distribution and homeostasis, we provide valuable insights into the molecular mechanisms governing parasite mitosis. These findings deepen our understanding of parasite biology and may inform future research aimed at identifying new targets for anti-malarial drug development.
A comprehensive two-hybrid analysis to explore the
Legionella pneumophila
effector–effector interactome
Authors: Mount Harley O'Connor , Urbanus Malene L. , Sheykhkarimli Dayag , Coté Atina G. , Laval Florent , Coppin Georges , Kishore Nishka , Li Roujia , Spirohn-Fitzgerald Kerstin , Petersen Morgan O. , Knapp Jennifer J. , Kim Dae-Kyum , Twizere Jean-Claude , Calderwood Michael A. , Vidal Marc , Roth Frederick P. , Ensminger Alexander W.
Published: November 2024

Legionella pneumophila
uses over 300 translocated effector proteins to rewire host cells during infection and create a replicative niche for intracellular growth. To date, several studies have identified
L. pneumophila
effectors that indirectly and directly regulate the activity of other effectors, providing an additional layer of regulatory complexity. Among these are “metaeffectors,” a special class of effectors that regulate the activity of other effectors once inside the host. A defining feature of metaeffectors is direct, physical interaction with a target effector. Metaeffector identification, to date, has depended on phenotypes in heterologous systems and experimental serendipity. Using a multiplexed, recombinant barcode-based yeast two-hybrid technology we screened for protein–protein interactions among all
L. pneumophila
effectors and 28 components of the Dot/Icm type IV secretion system (>167,000 protein combinations). Of the 52 protein interactions identified by this approach, 44 are novel protein interactions, including 10 novel effector–effector interactions (doubling the number of known effector–effector interactions).

IMPORTANCE

Secreted bacterial effector proteins are typically viewed as modulators of host activity, entering the host cytosol to physically interact with and modify the activity of one or more host proteins in support of infection. A growing body of evidence suggests that a subset of effectors primarily function to modify the activities of other effectors inside the host. These “effectors of effectors” or metaeffectors are often identified through experimental serendipity during the study of canonical effector function against the host. We previously performed the first global effector-wide genetic interaction screen for metaeffectors within the arsenal of
Legionella pneumophila
, an intracellular bacterial pathogen with over 300 effectors. Here, using a high-throughput, scalable methodology, we present the first global interaction network of physical interactions between
L. pneumophila
effectors. This data set serves as a complementary resource to identify and understand both the scope and nature of non-canonical effector activity within this important human pathogen.
Performance of UF-5000 in rapidly screening out urinary tract infection, predicting Gram-negative bacteria infection
Authors: Lu Wei , Li Zhaoxing , Zhang Tong , Li Yan , Zhu Huange , Zhao Ya , Lei Ke , Guo Zhi , Zhang Jing , Guo Juan , Zhang Lei
Published: November 2024

Urine culture is the gold standard for identifying microorganisms in urine. However, the process is time-consuming and usually takes days to get the results, which impedes timely treatment. This study aimed to evaluate the performance of UF-5000 in excluding bacterial urinary tract infection (UTI) and detecting the presence of Gram-negative bacteria. A total of 1,522 urine specimens were subjected to routine urine analysis and culture. Bacteria, white blood cell counts, and UF-5000 bacteria information flags were compared with urine culture. Bacteria forward scatter (B_FSC), and bacteria fluorescent light intensity (B_FLH) parameters were assessed to determine the optimal angle for discriminating bacterial growth patterns, which was verified in the validation cohort. The optimal cut-off values were 42.2/µL and 100.2/µL to rule out UTI for bacteria at ≥10
4
CFU/mL and ≥10
5
CFU/mL, respectively. The agreement of UF-5000 bacterial classification and urine culture was fair (Kappa = 0.227). Regarding the discrimination of bacterial groups, “Gram Neg?” was associated with a specificity of 94.0% and a positive predictive value of 87.2% in the detection of Gram-negative bacteria. By estimating the B_FSC and B_FLH parameters, the best angle was 28° for distinguishing Gram-negative and Gram-positive bacteria. Among the 136 urine specimens with the low angle pattern (<28°) in the validation cohort, 127 specimens were confirmed to contain Gram-negative bacteria. The UF-5000 analyzer is a suitable and rapid tool to exclude negative urine specimens, and bacterial information flags for Gram-negative bacteria could be trusted by clinicians.

IMPORTANCE

The strength of our study relied on being the first study assessing the bacteria forward scatter (B_FSC) and bacteria fluorescent light intensity (B_FLH) research parameters with a UF-5000 urine analyzer and establishing the best angle for distinguishing Gram-negative and Gram-positive bacteria. When the bacterial scatter plot angle is less than 28°, the possibility of Gram-negative bacterial infection is more than 80%. Meanwhile, we find that UF-5000 bacterial information flags have a significant advantage in detecting Gram-negative bacteria with a specificity of over 90% and a positive predictive value of over 80%.
Development of a Panel of Biomarkers for Differential Diagnosis of Multiple Sclerosis
Authors: Ovchinnikova L. A. , Dzhelad S. S. , Simaniv T. O. , Zakharova M. N. , Lomakin Y. A. , Gabibov A. G. , Illarioshkin S. N.
Published: November 2024

Demyelinating diseases are a group of heterogeneous pathologies that affect the nervous system and reduce the quality of life. One of such diseases is multiple sclerosis (MS), an inflammatory autoimmune neurodegenerative disease of the central nervous system (CNS). At the initial stages, MS can mimic some infectious, neoplastic, genetic, metabolic, vascular, and other pathologies. Accurate differential diagnosis of this disease is important to improve the quality of life of patients and reduce possible irreversible damage to the central nervous system. In this work, we confirmed the possibility of using our previously proposed candidate panel of MS biomarkers to distinguish MS from neuromyelitis optica spectrum disorder (NMOSD) and amyotrophic lateral sclerosis (ALS). We have shown that our proposed panel (SPTAN1601-644 + PRX451-494 + PTK6301-344 + LMP1285-330) allows us to distinguish MS from ALS (AUC = 0.796) and NMOSD (AUC = 0.779).
The Central American Seaway: do Magdalena River flocculates mimic deep water neodymium?
Authors: Montes Camilo , Bayona German
Published: November 2024

A common assumption in the interpretation of seawater neodymium isotopes is that the signal is a mixture of distally advected waters. A review of the local palaeogeography and bedrock Nd isotopic compositions (
n
 = 712) of the largest drainage basins of the Caribbean Sea shows: (1) unradiogenic sedimentary and crystalline sequences in the cratonic-derived eastern Andes, (2) very radiogenic sequences in the western Andes and Panama Isthmus and (3) intermediate values between them (Cauca River drainage basin). These local signatures can be matched to the Miocene–Pliocene record of Ocean Drilling Project sites ODP-998, 999 and 1000, dating the arrival of major inter-Andean drainages to the Caribbean Sea. The birth of the Atrato River at 15 Ma, following closure of the Central American Seaway, delivered very radiogenic Nd isotopes to the Caribbean Sea (
ε
Nd
 = +5.5), while the arrival of Magdalena River waters at 11 Ma brought very unradiogenic values (
ε
Nd
 ≪ −8). Later excavation of the Cauca River canyon at ∼7 Ma added a moderately radiogenic source (
ε
Nd
 = +1.9), modulating Magdalena River signatures to the Caribbean Sea. Flocculates forming in tropical deltas and estuarine environments carried these signals in hyperpicnal flows to slowly mixing Caribbean bottom waters, mimicking distally advected water.
Scalable Experimental Bounds for Entangled Quantum State Fidelities
Authors: Aktar Shamminuj , Bärtschi Andreas , Badawy Abdel-Hameed A. , Eidenbenz Stephan
Published: November 2024

Estimating the state preparation fidelity of highly entangled states on noisy intermediate-scale quantum (NISQ) devices is important for benchmarking and application considerations. Unfortunately, exact fidelity measurements quickly become prohibitively expensive, as they scale exponentially as
O
(3

N

for
N
-qubit states, using full state tomography with measurements in all Pauli bases combinations. However, Somma  et al.established that the complexity could be drastically reduced when looking at
fidelity lower bounds
for states that exhibit symmetries, such as Dicke states and GHZ states. These bounds must still be tight enough for larger states to provide reasonable estimations on NISQ devices.

For the first time and more than 15 years after the theoretical introduction, we report meaningful lower bounds for the state preparation fidelity of all Dicke states up to
N
=10 and all GHZ states up to
N
=20 on Quantinuum H1 ion-trap systems using efficient implementations of recently proposed scalable circuits for these states. Our achieved lower bounds match or exceed previously reported exact fidelities on superconducting systems for much smaller states. Furthermore, we provide evidence that for large Dicke states

\(\left|\smash{D_{N/2}^{N}} \right\rangle\)

, we may resort to a GHZ-based approximate state preparation to achieve better fidelity. This work provides a path forward to benchmarking entanglement as NISQ devices improve in size and quality.
Dynamic Buffer Management in Massively Parallel Systems: The Power of Randomness
Authors: Pham Minh , Yuan Yongke , Li Hao , Mou Chengcheng , Tu Yicheng , Xu Zichen , Meng Jinghan
Published: November 2024

Massively parallel systems, such as Graphics Processing Units (GPUs), play an increasingly crucial role in today’s data-intensive computing. The unique challenges associated with developing system software for massively parallel hardware to support numerous parallel threads efficiently are of paramount importance. One such challenge is the design of a dynamic memory allocator to allocate memory at runtime. Traditionally, memory allocators have relied on maintaining a global data structure, such as a queue of free pages. However, in the context of massively parallel systems, accessing such global data structures can quickly become a bottleneck even with multiple queues in place. This paper presents a novel approach to dynamic memory allocation that eliminates the need for a centralized data structure. Our proposed approach revolves around letting threads employ random search procedures to locate free pages. Through mathematical proofs and extensive experiments, we demonstrate that the basic random search design achieves lower latency than the best-known existing solution, Ouroboros, in most situations. Furthermore, we develop more advanced techniques and algorithms to tackle the challenge of warp divergence and further enhance performance when free memory is limited. Building upon these advancements, our mathematical proofs and experimental results affirm that these advanced designs can yield an order of magnitude improvement over the basic design and consistently outperform the state-of-the-art by up to two orders of magnitude. To illustrate the practical implications of our work, we integrate our memory management techniques into two GPU algorithms: a hash join and a group-by. Both case studies provide compelling evidence of our approach’s pronounced performance gains.
Multimodal Sentiment Analysis for the Malay Language: New Corpus using CNN-based Framework
Authors: Taylor Serena , Fauzi Fariza
Published: November 2024

Sentiment analysis in the Malay language has traditionally focused on text-based data. Malay is the native language of Malaysia and other surrounding countries. While text-based sentiment analysis has shown good performance, it often lacks accuracy due to the absence of the speaker's affective state and intentions, which can lead to misinterpretations. Multimodal sentiment analysis addresses these shortcomings and has demonstrated improved performance in various prediction tasks. Unfortunately, there has been little research in this area for the Malay language, due to a lack of corpus and baseline studies. This paper introduces a new Malay Multimodal Sentiment Corpus, ‘MyMSC’, with annotations at both the multimodal and unimodal text levels. It contains 1208 segments covering political and social topics. The corpus development processes are described in detail, along with the necessary guidelines and considerations. This paper proposes a CNN-based framework with a late fusion method as the baseline model. Experiments with the proposed model demonstrate that the multimodal approach (F1 score = 0.77) outperforms the unimodal approach (F1 score = 0.68), validating the contribution of multimodality to classification performance. The differences between the two types of annotations and their impact are further elaborated. The full corpus is available at
https://github.com/serenaroseaini/MyMSC
.
End-To-End Latency of Cause-Effect Chains: A Tutorial
Authors: Günzel Mario , Teper Harun , Brüggen Georg von der , Chen Jian-Jia
Published: November 2024

In many applications of cyber-physical systems, a sequence of tasks is necessary to perform a certain functionality. For example, from a sensor to an actuator, the first task reads the sensor value (cause), the second task processes the data, and the third task produces an output for the actuator (an effect is triggered). For such scenarios, the
end-to-end
timing properties (the so-called end-to-end latency) of the sequence of tasks (the so-called cause-effect chain) are of importance. This tutorial recaps different metrics for the end-to-end latency of cause-effect chains, and summarizes fundamental properties and existing analytical results in a systematic manner. To that end, this tutorial has a special focus on the reaction time (how fast can a reaction be in the worst case) and the data age (how old is the data source of an actuation in the worst case). The goal of this tutorial is to provide a systematic view of the fundamental end-to-end timing properties of cause-effect chains and offer an outlook of possible research directions in the near future. Furthermore, we extend the proof of one fundamental property in the literature to comply with the current state-of-the-art definition of end-to-end latencies.
On Hill’s Worst-Case Guarantee for Indivisible Bads
Authors: Li Bo , Moulin Herve , Sun Ankang , Zhou Yu
Published: November 2024

We evaluate the fairness of a rule allocating among agents with equal rights by computing their utility for a hypothetical worst-case share, which only depends on their own valuation and the number of agents. For indivisible goods, Budish proposed the
maximin share
: the least utility of a bundle in the best partition of the objects; unfortunately maximin share is not always satisfiable. Earlier, Hill proposed the worst maximin share over all utilities with the same largest possible single-object value. More conservative than maximin share, it is guaranteed to be satisfiable for any possible profile of utilities and its computation is elementary, whereas it is NP-hard to compute maximin share. We apply Hill’s approach to the allocation of indivisible bads (objects with disutilities) and compute in closed form the worst-case minimax share for a given value of the worst single bad. We show that the worst-case minimax share is close to the original minimax share and that its monotonic closure is the best guaranteed share for all allocation instances with a common upper bound on the value of the worst single bad.
CompARe: Design and Development of a Gamified Augmented Reality Learning Environment for Cultural Heritage Sites
Authors: Souropetsis Markos , Kyza Eleni A.
Published: November 2024

Understanding cultural heritage by visiting cultural sites is vital to individuals and communities across the world. It is, therefore, important to create authentic learning situations where students can experience and meaningfully learn about cultural heritage; however, authentic learning in situ can be a challenge. Learning during educational field trips at cultural sites is often not well supported, while students’ interest and motivation to learn are not always activated, which ultimately impacts the learning experience during the visit. Furthermore, students may be distracted by off-task activities and by the novelty effect of the setting during the field trip and may find it difficult to dedicate themselves to the learning activities. Augmented and virtual reality technologies and approaches such as gamification have created new contexts for location-based, technology-enhanced learning, which can help address some of the challenges faced during educational field trips. This article describes the design and validation of CompARe, a gamified augmented reality learning environment (LE) created to support student learning while visiting a cultural heritage site. The CompARe LE is built around an inquiry-based scenario in which students, working in groups, take on the role of art historians and are asked to date an important wall mosaic by visiting four digital hotspots located throughout the site. CompARe was developed and validated using a design-based methodology. We present two case studies of upper elementary students using CompARe and discuss the affordances and challenges of the learning experience. We conclude with lessons learned about the effectiveness of the CompARe learning approach and discuss future steps.
Transformative Therapies for Depression: Postpartum Depression, Major Depressive Disorder, and Treatment-Resistant Depression
Authors: Richardson Elizabeth , Patterson Riah , Meltzer-Brody Samantha , McClure Robert , Tow Amanda
Published: November 2024

Depressive disorders present an enormous global public health burden. A notable treatment gap exists between the prevalence of depression and our ability to provide rapid-acting, effective treatment that achieves remission. Brexanolone and zuranolone, the first US Food and Drug Administration–approved drugs for postpartum depression, signify a critical advancement in addressing the unmet needs of a vulnerable patient population. Psilocybin shows promise for treatment-resistant depression and for those who have struggled to find relief with existing treatments. This review discusses transformative therapies that represent significant advancements in postpartum depression, major depressive disorder, and treatment-resistant depression.
Tm@C82: Calculated Isomeric Populations
Authors: Slanina Zdeněk , Uhlík Filip , Akasaka Takeshi , Lu Xing , Adamowicz Ludwik
Published: November 2024

Relative equilibrium populations of the four potential-energy-lowest IPR (isolated-pentagon-rule) isomers of Tm@C82 under high synthetic temperatures are calculated using the Gibbs energy based on molecular characteristics from the density functional theory calculations at the B3LYP/6-31G*∼SDD level. Tm@C
2v
(9)-C82 and Tm@C

s
(6)-C82 are concluded as the most populated species. The calculations agree with available observations.
Early-Stage Techno-Economic Evaluation of Electrochemical Nitrogen Reduction to Ammonia Based on Catalyst Performance
Authors: Rix Michael J. , Mitsos Alexander
Published: November 2024

The direct electrochemical reduction of nitrogen offers a promising alternative to produce ammonia, an important chemical and potential energy carrier. While current research focuses on developing and improving catalysts for this reaction, studies evaluating the process and establishing catalyst performance targets remain limited. We performed a techno-economic analysis to evaluate the process based on the performance of the nitrogen reduction reaction catalyst. As a result, we identify catalyst performance targets: minimal performance levels as a combination of cell potential, Faraday efficiency, and current density required to reach cost parity with benchmark prices. The minimal catalyst performance levels are illustrated via curves that relate the required current density to the Faraday efficiency. For a competitive process, current densities and Faraday efficiencies above 100mAcm−2 and 60 %, respectively, are required. Although some catalyst development studies report sufficiently high Faraday efficiencies, the current densities are well below the required. Contrary to the literature’s emphasis on maximizing the Faraday efficiency, our results underscore the need for higher current densities at sufficiently high Faraday efficiencies. Although parameters such as electricity or benchmark prices change the absolute values of the required catalyst performance, the primary conclusions remain unchanged. This analysis provides clear guidance for future catalyst development.
Solar Radiation Prediction Based on TCN‐N‐BEATS Sequence Modeling
Authors: He Ruiyu , Tang Xin , Fang Li , Zhou Ying , Chen Yuanjun , Xiong Junjie , Chen Xiangru
Published: November 2024

Solar radiation prediction research is a key area of interest in the realm of solar energy utilization and has garnered significant attention in recent times. In order to realize accurate prediction of solar radiation and make solar radiation prediction better serve photovoltaic (PV) power generation, this study proposes a solar radiation prediction method based on sequence model, which integrates two kinds of neural networks, namely, temporal convolutional network (TCN) and neural basis expansion analysis (N‐BEATS). First, the dataset is preprocessed using Pearson’s correlation coefficient, outlier detection, and normalized to obtain valid and relevant data; second, the features of TCN feature extraction and N‐BEATS flexible extension are integrated to predict the solar radiation; then, the model’s hyperparameters are fine‐tuned using the grid search algorithm to ensure precise predictions; and last, the correctness of the method is verified by comparing the error metrics and the running time. Empirical findings indicate that the TCN‐N‐BEATS sequence model has high prediction accuracy and short time overhead, and it has certain application value in solar radiation prediction, and the model could offer valuable insights for predicting solar radiation.
Evaluating Emission Reduction Policies along an Urban Arterial Highway Using the AIMSUN Model
Authors: Okebe Meshack W. , Abuodha Silvester O. , Ochieng Meshack O. A.
Published: November 2024

The rapid growth of cities and the increasing traffic congestion have made vehicle emissions worse, especially in developing countries. Governments worldwide are now relying on regulations and policies to manage and reduce these emissions effectively. This change in approach towards emission control is also happening in developing nations. In this study, the effects of these policy measures are quantified using a calibrated integrated traffic and emission model (AIMSUN), and two hypothetical scenarios were analyzed: one scenario is where electric vehicles (EVs) replace traditional internal combustion EVs (ICEVs) in the study area and another scenario is assuming strict implementation of Euro 4/IV emission standards. The results showed that shifting towards a higher proportion of EVs leads to significant reductions in emissions but requires increased battery consumption, highlighting the trade‐off between reducing emissions and higher energy demand. Implementing Euro 4/IV standards could considerably reduce emissions, especially from motorcycles and trucks. It suggests that focusing on these categories with a phased implementation approach could bring significant environmental benefits. Policymakers in developing countries should adopt a rounded approach instead of implementing strict policies. It is crucial for them to carefully weigh the pros and cons of policy instruments before making any decisions. This study shows how traffic micro‐simulation modeling coupled with emission models can be used in evidence‐based decision‐making.
Study on the Effect of Soil Type and Salinity on Water–Soil Characteristic Curves of Saline Soils Based on the Vapor Balance Technique
Authors: Zhao Tianyu , Li Lunji , Zhang Huyuan , An Liang , Liu Wanming , Wang Yingchun
Published: November 2024

The soil–water characteristic curve (SWCC) describes the relationship between water content and soil suction, which is an important tool for determining the engineering properties of unsaturated soil. By measuring SWCC through vapor equilibrium technique, which could obtain soil suction up to 309 MPa, this paper explored the influences of the soil type and salt content on SWCC of saline soil. The experimental results illustrate that fine‐grained saline soil had a good water‐holding capacity, which had a higher air entry value and slower dehydrate rate. The study also brings out the observation that salt had negligible influence on soil suction and parameters effecting SWCC in low suction range; however, this effects was slight until it disappeared with the suction increasing.
Genetically Predicted Immune Cells Mediate the Association Between Gut Microbiota and Gastroesophageal Reflux Disease
Authors: Wang Jia , Fei Bojian , Wang Chao
Published: November 2024

Background: Recent evidence increasingly acknowledges the close interrelationship between immunity and gut microbiota (GM) in humans. Furthermore, previous studies have demonstrated a strong correlation between GM and gastroesophageal reflux disease (GERD). However, the specific impact of GM on immune factors in GERD remains largely unexplored. Therefore, we conducted the Mendelian randomization (MR) analysis to investigate the precise causal relationships and underlying mechanisms linking GM, immunity, and GERD.

Method: We employed the mediation MR utilizing summary statistics derived from Genome‐Wide Association Study (GWAS) data to investigate the causal effects of 207 taxa and 205 bacterial pathways on GERD. The analysis concentrated on 731 immune cell traits as potential mediators. The inverse variance weighted (IVW) approach was the primary analytical method. To ensure robustness, we employed additional MR methods, including Bayesian weighted MR (BWMR), MR‐Egger, Weighted Median, Weighted Mode, and Simple Mode. Furthermore, a series of sensitivity analyses, such as the Cochran’s Q test, leave‐one‐out test, MR‐Egger intercept analysis, and MR‐PRESSO test, were conducted to ensure the reliability and consistency of the findings.

Results: The study identified three taxa and eight bacterial pathways that exhibited a negative correlation with GERD. Mediation MR analyses indicated that four bacterial pathways influence GERD through four immune cell types acting as mediators. For instance, the “arginine, ornithine, and proline interconversion” pathway was implicated in reducing the risk of GERD via “PDL‐1 on CD14‐ CD16+ monocyte” cells, with a total effect of −0.0484 and a mediation effect of −0.0093. Sensitivity analyses provided additional validation for the reliability of the MR findings.

Conclusion: Our study contributes evidence to the close causal relationship between the GM and GERD, emphasizing the possible role of immune cells as mediators. Future research should focus on developing microbiome‐oriented therapeutic approaches for managing GERD.
Unveiling the Thermo‐Hygrometric Influence of Summer Sea and Estuarine Breezes (SEBs) in Lisbon (Portugal)
Authors: Reis Cláudia , Lopes António , Nouri A. Santos , Vasconcelos João
Published: November 2024

Local wind, such as sea breezes, play a crucial role in cooling coastal cities. This study presents new insights about the thermo‐hygrometric influence of the Tagus and Atlantic Ocean breezes (sea and estuarine breezes [SEBs]) in Lisbon’s urban climate (Portugal). SEB events were identified in the summer of 2022 according to a wind rotation criterion: the interruption of prevailing North and Northwest (Nortada) winds during the morning, the wind shift to Northeast/East/Southeast and, sometimes, to further South/Southwest/West (rotation between 22.6° and 292.5°) and the return of the regional flow at late afternoon. Additionally, air temperature and absolute humidity anomalies (ΔT/Haurb) were calculated according to the distance to the riverfront area. Results show that SEB occurred on 37 (31%) out of 120 days, mainly in July (43%) and August (32%), between, on average, 10:00 AM and 4:00 PM, and average wind speeds of 3.4 m/s. According to the daily thermo‐hygrometric cycle, the areas up to 4 km of the Tagus estuary were, on average, cooler than northern Lisbon during SEB events, especially the areas up to 500 m (average ΔTurb reached −1.7°C). Additionally, there was a significant increase in the moisture content during SEB hours across the city but especially close to the riverfront area: the areas up to 500 m registered, on average, ΔHaurb of 4.2 g/m3 on SEB events (12:00 PM) against 2.1 g/m3 during typical Nortada days. This research is a starting point for a future delimitation and preservation of SEB penetration zones in Lisbon to address outdoor thermal discomfort during summer.
Gastric Cancer Risk among Immigrants and Socioeconomic Groups in the Netherlands
Authors: Mülder Duco T. , van de Schootbrugge - Vandermeer Hilliene J. , O’Mahony James F. , Sun Dianqin , Han Weiran , Verhoeven Rob H.A. , van Loo Marlon , van de Veerdonk Wessel , Spaander Manon C.W. , Lansdorp-Vogelaar Iris
Published: November 2024

Background:

Identification of groups at a high risk of gastric cancer could facilitate targeted screening in countries with a low gastric cancer incidence. Our aim was to identify such high-risk groups based on individual-level population data on migration history and socioeconomic status (SES) in the Netherlands.

Methods:

In this retrospective cohort study, patient data from the Netherlands Cancer Registry were linked to demographic data of Statistics Netherlands in the period 2010 to 2022. Gastric cancer incidence rates in the 14 largest immigrant populations were compared with those born in the Netherlands. Odds ratios (OR) were computed per birthplace and controlled for age, sex, and SES. Additionally, we investigated gastric cancer risk among second-generation immigrants and by SES.

Results:

Immigrant populations at a significantly higher gastric cancer risk compared with the general population were identified. Specifically, foreign-born first-generation immigrants from Bosnia–Herzegovina (OR, 2.42), Turkey (OR, 2.22), and China (OR, 1.92) showed elevated risk. Whereas low SES increased the odds of developing gastric cancer, first-generation immigrants remained at higher risk even after controlling for SES. Second-generation immigrants did not have a significantly higher risk of developing gastric cancer.

Conclusions:

Certain first-generation immigrants remain at an elevated risk for gastric cancer despite migration to a low-risk region. Identification of these high-risk groups should be used to facilitate targeted gastric cancer prevention.

Impact:

Potential benefits of targeted Helicobacter pylori test-and-treat policy in immigrant populations should be explored in clinical and modeling studies. Primary care physicians should be cognizant of high-risk groups, facilitating the early detection of cancer within these populations.
Personalized MRD Assessment in Perisurgical ctDNA for Prognostic Prediction in Hepatocellular Carcinoma
Authors: Hu Jie , Tang Haoran , Jia Can-Can , Zhang Xiang-Yu , Xu Ying , Tan Jin-Peng , Fan Jia , Jia Shidong , Zhou Jian
Published: November 2024

Purpose:

Detecting residual disease is a critical clinical requirement in the perisurgical management of patients with resectable hepatocellular carcinoma (HCC). Previous studies focused on specific genomic regions exhibiting limited sensitivity and failed to meet the minimal residual disease (MRD) testing threshold. We introduce a next-generation sequencing–based assay, informed by baseline samples, facilitating MRD detection in hepatectomized patients with HCC and offering prognostic predictions.

Experimental Design:

This study involved 88 patients with HCC who underwent surgical resections from January 2016 to May 2016 in Zhongshan Hospital, Fudan University. Tumor and normal tissue samples were collected during surgery, whereas plasma samples were obtained both before surgery and up to 7 days after surgery. Using a next-generation sequencing–based personalized ctDNA assay, we analyzed the MRD in both presurgical and postsurgical blood samples and its correlation with prognosis.

Results:

With a median follow-up period of 80.7 months, our findings demonstrated significant correlations between presurgical ctDNA tumor fractions, postsurgical plasma MRD status, and both recurrence-free survival and overall survival. Postsurgical MRD status emerged as the most significant risk factor for cancer recurrence (HR = 2.162; 95% confidence interval, 1.09–4.30; P = 0.027) compared with other clinical characteristics in multivariate Cox regression analysis. Notably, MRD status showed potential as a prognostic indicator among clinically low-recurrent-risk patients, such as those with Barcelona Clinic Liver Cancer stages 0 to A or China Liver Cancer Staging stages I to II.

Conclusions:

Evaluating personalized MRD provided crucial prognostic insights into recurrence-free survival and overall survival. It efficiently identified patients at high risk of recurrence, even among those initially perceived as low-risk cases.
Inflammatory Stress Determines the Need for Chemotherapy in Patients with HER2-Positive Esophagogastric Adenocarcinoma Receiving Targeted Therapy and Immunotherapy
Authors: Tintelnot Joseph , Paschold Lisa , Goekkurt Eray , Schultheiss Christoph , Matschl Urte , Santos Cruz Mariana , Bauer Marcus , Wickenhauser Claudia , Thuss-Patience Peter , Lorenzen Sylvie , Ettrich Thomas J. , Riera-Knorrenschild Jorge , Jacobasch Lutz , Kretzschmar Albrecht , Kubicka Stefan , Al-Batran Salah-Eddin , Reinacher-Schick Anke , Pink Daniel , Bokemeyer Carsten , Sinn Marianne , Lindig Udo , Hinke Axel , Hegewisch-Becker Susanna , Stein Alexander , Binder Mascha
Published: November 2024

Anti–PD-1, trastuzumab, and chemotherapy are used in the treatment of patients with advanced HER2-positive esophagogastric adenocarcinoma, but long-term survival remains limited. In this study, we report extended follow-up data from the INTEGA trial (NCT03409848), which investigated the efficacy of the anti–PD-1 nivolumab, trastuzumab, and FOLFOX chemotherapy (FOLFOX arm) in comparison with a chemotherapy-free regimen involving nivolumab, trastuzumab, and the anti–CTLA-4 ipilimumab (Ipi arm) in the first-line setting for advanced disease. The 12-month overall survival (OS) showed no statistical difference between the arms, with 57% OS (95% confidence interval, 41%–71%) in the Ipi arm and 70% OS (95% confidence interval, 54%–82%) in the FOLFOX arm. Crossing of the survival curves indicated a potential long-term benefit for some patients within the Ipi arm, but early progressors in the Ipi arm underlined the need for biomarker-guided strategies to optimize treatment selection. To this end, metabolomic and cytokine analyses demonstrated elevated levels of normetanephrine, cortisol, and IL6 in immunotherapy-unresponsive patients in the Ipi arm, suggesting a role for systemic inflammatory stress in modulating antitumor immune responses. Patients with this signature also showed an increased neutrophil to lymphocyte ratio that persisted in the Ipi arm, but not in the FOLFOX arm, and strongly correlated with survival. Furthermore, a low neutrophil to lymphocyte ratio characterized patients benefiting from immunotherapy and targeted therapy without the need for additional chemotherapy. These data suggest that patient selection based on inflammatory stress–driven immune changes could help customize first-line treatment in patients with advanced HER2-positive esophagogastric adenocarcinoma to potentially improve long-term survival.
Assessment of Coronary Microvascular Dysfunction by Angiography-Based Index of Microcirculatory Resistance: An Indirect Meta-Analysis
Authors: Wen Wei , Chi Yi , Liu Mingwang , Xie Beili , Gao Mengjie , Jiang Lulian , Zhang Yiqing , Chen Keji , Zhao Fuhai
Published: November 2024

Introduction: There is a lack of consensus on diagnosing coronary microvascular dysfunction (CMD) using the angiography-based index of microcirculatory resistance (Angio-IMR) due to the absence of evidence. This study aimed to explore the efficacy of Angio-IMR in diagnosing CMD. Methods: A systematic search was conducted in PubMed, Embase, Scopus, and the Cochrane Library for studies primarily focusing on Angio-IMR diagnosing CMD, using IMR as the gold standard. The primary results were pooled sensitivity, specificity, and the area under the curve (AUC). Results: A total of 15 studies involving 2,202 individuals and 2,330 vessels were included in our study, Angio-IMR demonstrated high performance in predicting IMR with overall pooled sensitivity and specificity of 0.84 (95% confidence interval (CI): 0.81–0.87) and 0.87 (95% CI: 0.83–0.99), respectively, and AUC = 0.91 (95% CI: 0.89–0.94). This indicates that Angio-IMR has good diagnostic characteristics. Subgroup analysis by indirect meta-analysis showed higher sensitivity in the rest state. However, there is no significant difference in sensitivity and specificity between the hyperemic and rest states when using the AccuIMR system. Furthermore, sensitivity and specificity were more pronounced in the group without coronary pressure monitoring compared to the group with monitoring. Conclusion: Angio-IMR is an alternative tool to identify CMD.
Prediction of bone mineral density based on computer tomography images using deep learning model
Authors: Li Jujia , Zhang Ping , Xu Jingxu , Zhang Ranxu , Ren Congcong , Yang Fan , Li Qian , Dong Yanhong , Zhao Jian , Huang Chencui
Published: November 2024

Introduction
The problem of population aging is intensifying worldwide. Osteoporosis has become an important cause affecting the health status of older populations. However, the diagnosis of osteoporosis and people's understanding of it are seriously insufficient. We aim to develop a deep learning model to automatically measure bone mineral density (BMD) and improve the diagnostic rate of osteoporosis.
Methods
The images of 801 subjects with 2080 vertebral bodies who underwent abdominal paired computer tomography (CT) and quantitative computer tomography (QCT) scanning was retrived from June 2020 to January 2022. The BMD of T11-L4 vertebral bodies was measured by QCT. Developing a multi-stage deep learning-based model to simulate the segmentation of the vertebral body and predict BMD. The subjects were randomly divided into training dataset, validation dataset and test dataset. Analyze the fitting effect between the BMD measured by the model and the standard BMD by QCT. Accuracy, precision, recall and f1- score were used to analyze the diagnostic performance according to categorization criterion measured by QCT.
Results
410 males (51.2%) and 391 females (48.8%) were included in this study. Among them, there were 154 (19.2%) males and 118 (14.7%) females aged 23-44; 182 (22.7%) males and 205 (25.6%) females aged 45-64; 74 (9.2%) males and 68 (8.5%) females aged 65-84. The number of vertebral bodies in the training dataset, the validation dataset, and the test dataset was 1433, 243, 404, respectively. In each dataset, the BMD of males and females decreases with age. There was a significant correlation between the BMD measured by the model and QCT, with the coefficient of determination (r2) 0.95-0.97. The diagnostic accuracy based on the model in the three datasets was 0.88, 0.91, and 0.91, respectively.
Conclusion
The proposed multi-stage deep learning-based model can achieve automatic measurement of vertebral BMD and performed well in the prediction of osteoporosis.
Recent Advances in the Understanding of Gonadotrope Lineage Differentiation in the Developing Pituitary
Authors: Le Ciclé Charles , Cohen-Tannoudji Joëlle , L’Hôte David
Published: November 2024

Background: The pituitary gland is a vital endocrine organ regulating body homoeostasis through six hormone-secreting cell types. Among these, pituitary gonadotrope cells are essential for reproductive function. Throughout pituitary ontogenesis, gonadotrope cells differentiate in a stepwise process, involving both morphogenic cues and transcription factors, which drives specification of progenitor cells into specialised endocrine cells. It is crucial to understand the mechanisms underlying gonadotrope differentiation, as developmental defects and abnormalities in this process can lead to many reproductive pathologies. Summary: This review offers a detailed overview of the latest advances in gonadotrope cell differentiation. We addressed this question with a specific focus on three important aspects of gonadotrope differentiation: the identification of the progenitor population giving rise to gonadotrope cells, the early mechanisms that initiate Nr5a1 expression and thus gonadotrope fate commitment, and finally, the mechanisms driving the formation of physical and functional gonadotrope networks. Key Messages: Overall, this review aimed to provide new insights into three aspects of the gonadotrope differentiation process by reconsidering pioneering studies in the light of data gained from latest technological developments. Firstly, we re-investigated the long debated developmental trajectory of pituitary gonadotrope cells. Secondly, we reported new regulatory mechanisms of Nr5a1 expression, focusing on the involvement of ERα. Finally, we highlighted the molecular and cellular mechanisms driving gonadotrope network formation during embryogenesis, a process that seems essential for regulation of gonadotrope activity.