bluuebunny/crossref_metadata_2025 huggingface dataset:
Direct hearing measurements in a baleen whale suggest ultrasonic sensitivity
Authors: Houser Dorian S. , Kvadsheim Petter H. , Kleivane Lars , Mulsow Jason , Ølberg Rolf A. , Harms Craig A. , Teilmann Jonas , Finneran James J.
Published: November 2024

Predicting and mitigating the impacts of anthropogenic ocean noise on marine animals is hindered by a lack of information on hearing in these species. We established a catch-and-release program to temporarily hold adolescent minke whales (
Balaenoptera acutorostrata
) for hearing tests during their summer migration. In 2023, two minke whales provided measures of the auditory brainstem response and data on the frequency range of their hearing. Results show that minke whales are sensitive to sound frequencies as high as 45 to 90 kilohertz. These tests provide information on the types of anthropogenic noise that could affect minke whales and potentially, other related baleen whale species.
Rapid in silico directed evolution by a protein language model with EVOLVEpro
Authors: Jiang Kaiyi , Yan Zhaoqing , Di Bernardo Matteo , Sgrizzi Samantha R. , Villiger Lukas , Kayabolen Alisan , Kim B. J. , Carscadden Josephine K. , Hiraizumi Masahiro , Nishimasu Hiroshi , Gootenberg Jonathan S. , Abudayyeh Omar O.
Published: November 2024

Directed protein evolution is central to biomedical applications but faces challenges such as experimental complexity, inefficient multiproperty optimization, and local maxima traps. Although in silico methods that use protein language models (PLMs) can provide modeled fitness landscape guidance, they struggle to generalize across diverse protein families and map to protein activity. We present EVOLVEpro, a few-shot active learning framework that combines PLMs and regression models to rapidly improve protein activity. EVOLVEpro surpasses current methods, yielding up to 100-fold improvements in desired properties. We demonstrate its effectiveness across six proteins in RNA production, genome editing, and antibody binding applications. These results highlight the advantages of few-shot active learning with minimal experimental data over zero-shot predictions. EVOLVEpro opens new possibilities for artificial intelligence–guided protein engineering in biology and medicine.
Shades of blue
Authors: Amigo Ignacio
Published: November 2024

Blue zones, supposed havens of longevity, have become a global brand. But skeptics think they rest on shaky science
Complete genome sequence of
Limosilactobacillus reuteri
LU150, a potential vitamin B
12
producer from the NORDBIOTIC collection
Authors: Szczepankowska A.K. , Cukrowska B. , Aleksandrzak-Piekarczyk T.
Published: November 2024

We performed whole-genome sequencing of
Limosilactobacillus reuteri
LU150, a human fecal isolate from the NORDBIOTIC collection. The genome consists of 2,039,406 bp with a GC content of 38.9%. The genetic content of LU150 suggests its probiotic potential.
Development and evaluation of a CRISPR/Cas12a-based diagnostic test for rapid detection and genotyping of HR-HPV in clinical specimens
Authors: Yin Lijuan , Zhao Ziqian , Wang Chunhua , Zhou Caihong , Wu Xiuzhen , Gao Baoxue , Wang Liangyuan , Man Shuli , Cheng Xinkuan , Wu Qiankun , Hu Siqi , Fan Hongxia , Ma Long , Xing Hui , Shen Liang
Published: November 2024

Persistent infection with high-risk human papillomavirus (HR-HPV) is the principal etiological factor of cervical cancer. Considering the gradual progression of cervical cancer, the early, rapid, sensitive, and specific identification of HPV, particularly HR-HPV types, is crucial in halting the advancement of the illness. Here, we established a rapid, highly sensitive, and specific HR-HPV detection platform, leveraging the CRISPR/Cas12a assay in conjunction with multienzyme isothermal rapid amplification. Our platform enables the detection and genotyping of 14 types of HR-HPV by using type-specific crRNAs. The outcomes of the detection can be interpreted either through a fluorescence reader or visually. Furthermore, we achieved one-tube multiplex detection of 14 HR-HPV types through the use of multiple amplifications and a crRNA pool. The detection sensitivity of this method is 2 copies/μL with no cross-reactivity, and the results can be obtained within 30 minutes. This method exhibited 100% clinical sensitivity and 100% clinical specificity when applied to 258 clinical specimens. Based on these findings, our CRISPR/Cas-based HR-HPV detection platform holds promise as a novel clinical detection tool, offering a visually intuitive and expedited alternative to existing HPV infection diagnostics and providing fresh perspectives for clinical cervical cancer screening.

IMPORTANCE

This study developed a novel high-risk human papillomavirus (HR-HPV) detection platform based on CRISPR/Cas12a technology. This platform not only enables the rapid, highly sensitive, and specific detection and genotyping of 14 types of HR-HPV but also achieves single-tube multiplex detection of 14 HR-HPV types through ingenious design. The outcomes of the detection can be interpreted either through a fluorescence reader or visually. To the best of our knowledge, this is the first paper to utilize CRISPR/Cas diagnostic technology for the simultaneous detection of 14 types of HPV and to evaluate its feasibility in clinical sample detection using a large number of clinical samples. We hope that this work will facilitate the rapid and accurate detection of HPV and promote the broader application of CRISPR/Cas diagnostic technology.
Adherence to cervical cancer screening in France: factors influencing the healthcare professionals’ decisions—a qualitative study
Authors: Mignot Stéphanie , Naiditch Nicolas , Llorens Justine , Fritel Xavier
Published: November 2024

Objective

To understand what leads to the non-adherence to the cervical cancer screening (CCS) recommendations during a consultation.

Design

For this qualitative study, in-depth semistructured interviews were carried out with French healthcare professionals. An interview guide was developed and tested. It included the following themes: CCS recommendations, patients’ profiles, relationship with patients, emotional work, over-screening and under-screening. Interviews were carried out until data saturation (no new data, theoretical diversity reached). The grounded theory was used for data analysis.

Participants

Gynaecologists, midwives and general practitioners (GPs). The sample diversity was achieved using the following criteria: place of work, type of healthcare profession, type of patients, private-sector or hospital professional.

Setting

Interviews were conducted between July and December 2022 in six regions in France.

Results

In-depth semistructured interviews were carried out with 15 midwives, 24 GPs and 11 gynaecologists from six French regions. Their analysis highlighted that the following factors contributed to the non-adherence to the CCS recommendation: burden of caring for family members for some women, adhesion to the principle of yearly screening by healthcare professionals and patients, need of negotiating the respect of the CCS recommendations, use of emotions, and arbitration to prioritise what is needed for good health maintenance. The search for mutual emotional comfort led some healthcare professionals to adopt attitudes towards the CCS that avoid positioning conflicts, even if this means departing from the recommendations.

Conclusion

CCS can be correctly performed if healthcare professionals and patients agree on the need of actively taking care of their health, which is difficult for women from lower sociocultural backgrounds. During the one-to-one meeting with their patients, healthcare professionals may find difficult to apply the CCS recommendations, although they know and agree with them.
Diagnostics for optimised dengue surveillance: a qualitative focus group study to investigate user experience and requirements in Thailand
Authors: Arkell Paul , Ketklao Sanhapon , Songjaeng Adisak , Mairiang Dumrong , Rodriguez-Manzano Jesus , Georgiou Pantelis , Holmes Alison , Ahmad Raheelah , Malasit Prida , Avirutnan Panisadee , Lawpoolsri Saranath
Published: November 2024

Objectives

Effective, real-time surveillance of dengue may provide early warning of outbreaks and support targeted disease-control intervention but requires widespread accurate diagnosis and timely case reporting. Research directing innovation in diagnostics for dengue surveillance is lacking. This study aimed to describe experience and requirements of relevant prospective users.

Design

A qualitative, focus group study was conducted.

Participants

Data were collected from 19 users of diagnostic technology who work across the Thai dengue surveillance system.

Data collection and analysis

Contextual knowledge, experience and needs were explored in focus groups. Discussions were translated, transcribed, analysed thematically and mapped to Consolidated Framework for Implementation Research domains.

Results

Participants expressed a need for rapid, accurate, serotype-specific tests which can be operated easily by non-expert users without laboratory equipment. They supported integration of diagnostics with surveillance systems and felt this would increase the quantity and speed of case reporting as well as provide healthcare professionals with up-to-date information about the number of cases locally, thereby aiding interpretation of test results. Concerns included those relating to data security and the cost of tests.

Conclusions

Engagement to understand prospective user experience and requirements can improve relevance and uptake of new technology, leading to system efficiencies. The present study highlights specific needs for accurate, serotype-specific, remote-connected diagnostics which are integrated with surveillance systems and support dengue case reporting at the point-of-care.
Immune microenvironment of Epstein-Barr virus (EBV)-negative compared to EBV-associated gastric cancers: implications for immunotherapy
Authors: McMiller Tracee L , Besharati Sepideh , Yarchoan Mark , Zhu Qingfeng , Ünsal-Kaçmaz Keziban , Xu Ke , Lee Junghwa , Bhaijee Feriyl , Engle Logan L , Taube Janis M , Berger Alan E , Anders Robert A , Topalian Suzanne L
Published: November 2024

Background

Gastric carcinomas (GC) are aggressive malignancies, and only ~15% of patients respond to anti-programmed cell death (ligand) 1 (PD-(L)1) monotherapy. However, Epstein-Barr virus (EBV)-associated GCs (~5–10% of GCs) often harbor PD-L1 and PD-L2 chromosomal amplifications and robust CD8+ T cell infiltrates, and respond at a high rate to anti-PD-1. The current study compares the tumor immune microenvironments (TiMEs) of EBV+ versus EBV(−) GCs.

Methods

Over 1000 cases of primary invasive GCs were screened to identify 25 treatment-naïve specimens for study (11 EBV+, 14 EBV(−)). Quantitative immunohistochemistry (IHC) was conducted for markers of immune cell subsets and co-regulatory molecules. Gene expression profiling (GEP) was performed on RNAs isolated from macrodissected areas of CD3+ T cell infiltrates abutting PD-L1+ stromal/tumor cells, using multiplex quantitative reverse transcriptase PCR for a panel of 122 candidate immune-related genes.

Results

IHC revealed that 17/25 GCs contained PD-L1+ stromal cells, with no significant difference between EBV+/- specimens; however, only 3/25 specimens (all EBV+) contained PD-L1+ tumor cells. CD8+ T cell densities were higher in EBV+ versus EBV(−) tumors (p=0.044). With GEP normalized to the pan-leukocyte markerPTPRC/CD45, EBV+ GCs overexpressedITGAE(CD103, marking intraepithelial T cells and a dendritic cell subset) and the interferon-inducible genesCXCL9andIDO1. In contrast, EBV(−) tumors overexpressed several functionally-related gene groups associated with myeloid cells (CD163,IL1A,NOS2, RIGI),immunosuppressive cytokines/chemokines (CXCL2,CXCR4,IL10, IL32),coinhibitory molecules (HAVCR2/TIM-3 andVSIR/VISTA), and adenosine pathway components (ENTPD1/CD39 andNT5E/CD73). Notably, compared with EBV+ GCs, EBV(−) GCs also overexpressed components of the cyclooxygenase 2 (COX-2)/prostaglandin E2 (PGE2) pathway associated with cancer-promoting inflammation, includingPTGS2/COX-2 (most highly upregulated gene, 32-fold, p=0.005); prostaglandin receptorsPTGER1(EP1; up 21-fold, p=0.015) andPTGER4(EP4; up twofold, p=0.022); and the major COX-2-inducing cytokineIL1B(up 11-fold, p=0.019). Consistent with these findings, COX-2 protein expression trended higher in EBV(−) versus EBV+ GCs (p=0.068).

Conclusions

While certain markers of immunosuppression are found in the GC TiME regardless of EBV status, EBV(−) GCs, which are much more common than EBV+ GCs, overexpress components of the COX-2/PGE2 pathway. These findings provide novel insights into the immune microenvironments of EBV+ and EBV(−) GC, and offer potential targets to overcome resistance to anti-PD-(L)1 therapies.
On the effectiveness of Brink–Axel hypothesis for stellar weak rate calculations of heavy nuclei
Authors: Farooq Fakeha , Nabi Jameel-Un , Shehzadi Ramoona
Published: November 2024

Earlier weak rate calculations relied on the Brink–Axel hypothesis (BAH), but the assumption requires validation against microscopic calculations for reliable nucleosynthesis modeling. We investigate the effectiveness of BAH in computing stellar weak rates of [Formula: see text]–decay and electron capture interactions in two sets of heavy neutron-rich nuclei: fp- and fpg-shell nuclei ([Formula: see text], [Formula: see text]) for post-silicon burning phases, and waiting-point nuclei ([Formula: see text], [Formula: see text]) for r-process. The impact of BAH is evaluated for allowed rates in the first set, and for unique first-forbidden and allowed rates in the second set. Our calculations used the proton–neutron quasi-particle random-phase approximation (pn-QRPA) model with two strength function prescriptions: one using state-by-state calculations and the other invoking the BAH, within stellar densities [Formula: see text][Formula: see text]g/cm3 and temperatures [Formula: see text][Formula: see text]GK of post-silicon burning phase of massive stars. Our study reveals significant deviations between BAH-invoked and microscopic [Formula: see text]–decay rates, with overestimation up to three orders of magnitude in allowed rates for fp/fpg-shell nuclei and for waiting-point nuclei exhibiting a stark difference in U1F rates up to four–five orders of magnitude, contrasting with relatively small deviations by up to an order of magnitude in electron capture rates. Our results suggest that application of BAH may lead to unrealistic weak stellar allowed (forbidden) [Formula: see text]-decay rates.
Modeling of charged anisotropic compact star with Tolman-IV ansatz
Authors: Awais M. , Azam M.
Published: November 2024

This research focuses on formulating a physical model for spherically symmetric system incorporating electromagnetic fields within the framework of [Formula: see text] gravity. To accomplish this, we investigate [Formula: see text] gravity’s field equations in the setting of anisotropic matter and solve these equations by choosing viable solution, i.e. Tolman-IV model. Matching conditions help us calculate the constants in terms of physical parameters. For this, we choose exterior geometry as Reissner–Nordström corresponding to charged anisotropic matter in the interior of spherically symmetric metric. To ensure that the obtained solution is physical viable and well-behaved, we rigorously examine the accessibility conditions (casualty conditions, TOV equations, adiabatic index, Harrison–Zeldovich–Novikov criterion and energy conditions) through graphically with software like Mathematica. Next, we implement this model to investigate various well-known compact objects, including LMC X-4 having mass [Formula: see text] and a radius of [Formula: see text] kilometers.
Remarks on the algebraic structure of (2,2) double forms
Authors: Goulart E. , Ottoni J. E.
Published: November 2024

In this paper, we study the algebraic features of covariant tensors of valence four containing two blocks of skew indices. After a rather general treatment, we specialize ourselves to four-dimensional spacetimes and discuss several complementary aspects of these objects. In particular, we focus our attention on the corresponding invariant subspaces and generalize previous relations such as the Ruse–Lanczos identity, the Bel–Matte decomposition and the Lovelock-like quadratic identities. We conclude pointing out some possible applications of the formalisms.
The prescribed Ricci curvature problem on five-dimensional nilpotent Lie groups
Authors: Foka Marius Landry , Mbatakou Salomon Joseph , Pefoukeu Romain Nimpa , Djiadeu Michel Bertrand Ngaha , Bouetou Thomas Bouetou
Published: November 2024

In this paper, using the Milnor-type theorem technique for each left-invariant symmetric [Formula: see text]-tensor field [Formula: see text] on a five-dimensional nilpotent Lie group, we determine whether it is possible or not to find a left-invariant Riemannian metric [Formula: see text] and a constant [Formula: see text] so that [Formula: see text], where [Formula: see text] is the Ricci curvature of [Formula: see text].
Compact objects in f(R,𝔏m) theory
Authors: Taṣer Dog̃ukan , Dog̃ru Melis Ulu , Kirezli Pınar , Aydn Hüseyin , Eraslan Erkan
Published: November 2024

In this study, it is aimed to investigate the Krori–Barua type compact stars within the scope of [Formula: see text] theory. In this context, first, the field equations are obtained by considering the [Formula: see text] model. Interestingly, the model offers chance to attain all components of matter without any restrictions. In addition, data sets from LMC X-4, EXO 1785-248 and Cen X-3 are used to analyze physical stability of the solutions. It is obtained that all conditions such as causality and stability. which indicate consistency between compact objects and [Formula: see text] theory are valid for the constructed model. We obtained that small values of [Formula: see text] in the [Formula: see text] function show significant effect on the consistency of the star models. Therefore, different [Formula: see text] values are considered for each star data set when graphing the physical states. Finally, necessary quantities of the model are defined, compared with the considered stars and discussed in detail.
Dust-fluid accelerating flat cosmological models in f(R,T,Lm)-gravity with observational constraints
Authors: Pradhan Anirudh , Zeyauddin M. , Dixit Archana , Krishnannair S.
Published: November 2024

In this paper, we investigate dust-fluid flat cosmological models in the recently proposed modified [Formula: see text]-gravity theory. We derive the field equations for the flat FLRW spacetime metric for the arbitrary function [Formula: see text], where [Formula: see text] is the Ricci curvature scalar, [Formula: see text] is the matter Lagrangian, [Formula: see text] is the trace of the energy–momentum tensor [Formula: see text], and [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text] are the model parameters. We solve these equations to obtain the Hubble function in terms of matter energy density parameters [Formula: see text], [Formula: see text], [Formula: see text], and Hubble constant [Formula: see text]. Then, we use the cosmic chronometer (CC) Hubble points dataset and the Pantheon dataset to do MCMC analysis of the Hubble function and find the best fit model parameters for the lowest [Formula: see text] values. Subsequently, we investigate the effective equation of state parameter [Formula: see text] and deceleration parameter [Formula: see text] for the present past epoch of the universe. We also perform analysis for energy conditions and statefinder parameters to discuss the different stages of the dark energy models.
Noether symmetries of Bianchi type II universe in modified teleparallel f(T) gravity
Authors: Ijaz Nitasha , Rubbab Qammar , Ramzan Muhammad , Hussain Fiaz
Published: November 2024

The aim of this paper is to explore Noether symmetries of Bianchi type II universe in the modified teleparallel [Formula: see text] gravity, where [Formula: see text] is a function of the torsion scalar [Formula: see text]. In a physical context, the selection of Noether symmetries provides constraints that are helpful in building conservation laws. Some of the well-known examples of such laws are the conservation of energy and momentum. In this study, initially, we explore certain classes of Bianchi type II universe considering linear as well as nonlinear [Formula: see text] gravity models. In view of such models, equations of motion of the [Formula: see text] gravity have been solved in twelve cases. In each of the cases, we apply the definition of Noether symmetry which tends to a set of nineteen equations. Upon solving these equations, we reach the fact that the Bianchi type II universe in the background of [Formula: see text] gravity admits only four Noether vector fields (NVFs). As a result, the physical entities which we observe are the conservation of linear and generalized momentum.
Lithofacies and depositional model of organic-rich lacustrine mudstone: A case study of the second member of the Eocene Liushagang Formation in the Weixinan Sag, Beibuwan Basin, China
Authors: Zhao Niubin , Ye Jiaren , Zhang Ronghu , Yang Baolin , Wang Ziling , Zhu Xiang , Liu Yiming
Published: November 2024

The mudstone in the second member of the Eocene Liushagang Formation is the most important oil and gas supply interval in the Weixinan Sag. Natural gamma curves (GR), Scanning electron microscope (SEM), X-ray diffraction (XRD) and the major and trace element analyses were used to investigate the lithofacies, tectonostratigraphic, palaeoenvironment, and influence of environmental factors on the lithofacies and to create a depositional model for the second member of the Eocene Liushagang Formation in the Weixinan Sag. The results show that organic- and clay-rich siliceous mudstone-dominated (LA1A) (in the bottom) and organic- and siliceous-rich clay mudstone-dominated (LA1B) (in the top) whose deposition thicknesses were respectively around 50 - 150 m and 40 – 80 m. For both deposition stages of the LA1A and LA1B, the overall trends were similar in that they were mainly characterized by an upward half cycle. The hidden mechanisms of organic matter enrichment can both be summarized as “high fault activity rate and tectonic subsidence rate, deep lacustrine facies, and extreme heat and anoxic environment”. However, the difference lied in the organic matter productivity conditions (LA1A> LA1B). This research proposes a model to explain the depositional processes of the second member of the Liushagang Formation, providing theoretical support for shale oil exploration in the exploration area while being crucial for understanding the lithofacies deposition mechanism of lacustrine mudstones in other areas. Besides, it may also serve as evidence for the study of the Eocene carbon cycle and extreme heat events in terrestrial and low latitude regions.
HammingMesh: A Network Topology for Large-Scale Deep Learning
Authors: Hoefler Torsten , Bonoto Tommaso , De Sensi Daniele , Di Girolamo Salvatore , Li Shigang , Heddes Marco , Goel Deepak , Castro Miguel , Scott Steve
Published: November 2024

Numerous microarchitectural optimizations unlocked tremendous processing power for deep neural networks that in turn fueled the ongoing AI revolution. With the exhaustion of such optimizations, the growth of modern AI is now gated by the performance of training systems, especially their data movement. Instead of focusing on single accelerators, we investigate data-movement characteristics of large-scale training at full system scale. Based on our workload analysis, we design HammingMesh, a novel network topology that provides high bandwidth at low cost with high job scheduling flexibility. Specifically, HammingMesh can support full bandwidth and isolation to deep learning training jobs with two dimensions of parallelism. Furthermore, it also supports high global bandwidth for generic traffic. Thus, HammingMesh will power future large-scale deep learning systems with extreme bandwidth requirements.
Cross-Domain HAR: Few-Shot Transfer Learning for Human Activity Recognition
Authors: Thukral Megha , Haresamudram Harish , Plötz Thomas
Published: November 2024

The ubiquitous availability of smartphones and smartwatches with integrated inertial measurement units (IMUs) enables straightforward capturing of human activities through collecting movement data. For specific applications of sensor-based human activity recognition (HAR), however, logistical challenges and burgeoning costs render especially the ground-truth annotation of such data a difficult endeavor, resulting in limited scale and diversity of datasets available for deriving effective HAR systems and less than ideal recognition capabilities. Transfer learning, i.e., leveraging publicly available labeled datasets to first learn useful representations that can then be fine-tuned using limited amounts of labeled data from a target domain, can alleviate some of the performance issues of contemporary HAR systems. Yet they can fail when the differences between source and target conditions are too large and/or only few samples from a target application domain are available—each of which are typical challenges in real-world human activity recognition scenarios. In this article, we present an approach for economic use of publicly available labeled HAR datasets for effective transfer learning. We introduce a novel transfer learning framework—Cross-Domain HAR—which follows the teacher-student self-training paradigm to more effectively recognize activities with very limited label information. It bridges conceptual gaps between source and target domains, including sensor locations and type of activities. Cross-Domain HAR enables substantial performance improvements over the state-of-the-art in sensor-based HAR scenarios. Through our extensive experimental evaluation on a range of benchmark datasets we specifically demonstrate the effectiveness of our approach for practically relevant few-shot activity recognition scenarios. We also present a detailed analysis into how the individual components of our framework affect downstream performance and provide practical suggestions for using the framework in real-world applications.
Dual Perspective of Label-Specific Feature Learning for Multi-Label Classification
Authors: Hang Jun-Yi , Zhang Min-Ling
Published: November 2024

Label-specific features work as an effective supervised feature manipulation strategy to account for distinct discriminative properties of each class label in multi-label classification. Existing approaches implement this strategy in its primal form, i.e., finding the most pertinent features specific to each class label and directly inducing classifiers on these features. Instead of such a straightforward implementation, a dual perspective for label-specific feature learning is investigated in this article. As a dual problem of existing primal one, we consider label-specific discriminative properties by identifying non-informative features for each class label and making the discrimination process immutable to variations of identified features. Accordingly, a perturbation-based approach
Dela
is presented, which endows classifiers with immutability on simultaneously identified non-informative features by solving a probabilistically relaxed expected risk minimization problem. Furthermore, we touch the realistic issue of label-specific feature learning in a weakly supervised scenario via extending
Dela
to accommodate to multi-label data with missing labels. Comprehensive experiments show that our approach outperforms the state-of-the-art counterparts.
Postsynaptic dopamine D3 receptors selectively modulate μ-opioid receptor-expressing GABAergic inputs onto CA1 pyramidal cells in the rat ventral hippocampus
Authors: Brown Kyle A. , Stramiello Michael , Clark Jason K. , Wagner John J.
Published: November 2024

We report that the activity of an inhibitory synapse on CA1 pyramidal cells in the rat ventral hippocampus is shaped by heterogeneous neuromodulators. Specifically, postsynaptic dopamine D3 receptors on ventral hippocampal CA1 pyramidal neurons are selectively targeted by an inhibitory input from µ-opioid receptor-expressing GABAergic terminals.
Investigating the Impact of Traditional Bullying and Cyberbullying on Suicidal Attempts in Chinese Youth: A Prospective Cohort Study
Authors: Li Sihong , Ni Xi , Luo Xuerong , Jin Xingyue , Song Lintong , Fan Tianqing , Zhang Leyin , Shen Yanmei
Published: November 2024

Aims: It is unknown whether bullying exposure is independently associated with suicide attempts incidence. This study aims to investigate the association between traditional bullying, cyberbullying, and subsequent risk of suicide attempts among Chinese adolescents.

Methods: In this prospective cohort study, 1162 participants (mean age, 12.59, 54.5% male) were recruited from November 2020 to December 2020 in Changsha Hunan Province. In total, 782 of them completed the follow‐up in May and June 2021 and were included in the final analysis. Logistic regression was utilized to calculate the odds ratio (OR) with 95% confidence intervals (95% CIs). Gender differences in these associations were further explored by stratified analysis.

Results: Adolescents who engaged in bullying perpetration (BP) and experienced cyberbullying victimization (CV) were significantly associated with an increased risk of suicide attempts in the 6‐month follow‐up even after adjusting for age, ethnicity, single child, depression, anxiety, and stress in the baseline (BP: adjusted OR [aOR] = 3.337, 95% CI: 1.463–7.611, p = 0.004; CV: aOR = 3.338, 95% CI: 1.468–7.590, p = 0.004). Furthermore, the association between BP and suicide attempts was found to be statistically significant only among male adolescents (aOR = 6.692, 95% CI: 1.566–28.601, p = 0.01), while CV was significantly associated with a heightened risk of suicide attempts among female adolescents (aOR = 4.452, 95% CI: 1.684–11.771, p = 0.003).

Conclusions: BP and CV were longitudinally associated with an increased risk of suicide attempts in Chinese youth, and these associations vary across genders.
Mechanical Experiments and ABAQUS Simulations of Fiber–Coal Gangue Stabilized Expansive Soil Under Freeze–Thaw Cycles
Authors: Zhang Yan , Jia Xiupeng , Wang Minglei
Published: November 2024

Considering the environmental protection and infrastructure needs for solid waste recycling and improvement of soil engineering properties, a fiber–gangue composite soil consolidation material is proposed to improve the mechanical properties of expansive soils and the workability to resist freeze–thaw (FT) cycling effects. The unconfined compressive strength (UCS) of the expansive soil was measured at varying FT cycles. Then, thermal–mechanical field simulation using Advanced Simulation for Engineering and Sciences (ABAQUS) numerical simulation software was conducted to analyze the stress–strain behavior of the model and compared with the UCS test results obtained during the laboratory test. After that, the microstructural characteristics of modified soil systems after FT cycles were carried out using scanning electron microscope (SEM) mapping to obtain the reinforcement mechanism. The investigation results indicate that the UCS of the modified expansive soil (MES) not only increased after experiencing 12 FT cycles, but also demonstrated a 20.1% reduction in UCS inhibition by the improver compared to plain‐expansive soil (PES). Therefore the addition of fiber–coal gangue composite effectively amends the effect of FT cycles on the UCS of expansive soil. UCS test results suggest that a reasonable 9 mm long 0.3% fiber and 20% coal gangue ratio of the composite modifier is advantageous to the soil’s mechanical properties. ABAQUS numerical simulations results the UCS strength of the specimens deteriorates gradually with the increase in the number of FT cycles, which is in agreement with the laboratory measured values. From the SEM observation, the PES samples were loose and the pores increased, while the coal gangue and the fibers of the incorporated expansive soil particles formed links between them, the structure was tight, the pores and cracks were reduced, and the compactness was improved.
Prevalence and Predictive Factors of Sickle Cell Emergencies Readmission in the Clinical Hematology Department of Dakar, Senegal
Authors: Diallo Alioune Badara , Seck Moussa , Touré Sokhna Aissatou , Keita Mohamed , Bousso Elimane Seydi , Faye Blaise Félix , Diop Saliou
Published: November 2024

Introduction: Sickle cell emergencies are the most common cause of hospitalization for patients with sickle cell disease (SCD). Hospital readmissions represent a considerable financial burden for healthcare systems and increase patient morbidity and mortality. The aim of this study was to assess the prevalence and predictive factors of sickle cell emergencies readmission.

Materials and Methods: We conducted a prospective, cross‐sectional, descriptive, and analytical study over a 4‐month period, including all adult patients admitted for an emergency related to SCD: vaso‐occlusive crisis (VOC), acute chest syndrome (ACS), severe anemia, infections, priapism, and stroke. Readmission was considered when the patient returned to the emergency within a period of <30 days, either due to recurrence, persistence of the same complication, or the occurrence of another acute complication related to SCD.

Results: We recorded 151 sickle cell emergencies for 112 patients, representing 0.33 emergencies/month/patient. Fifty‐eight cases of readmission were recorded, resulting in a readmission rate of 38.41%. Among these patients, 53 (91.37%) had two admissions, and 5 (8.62%) had three admissions. The median age of the patients was 28.41 years (16–70 years), and the sex ratio was 0.57. The SS sickle cell phenotype was predominant in 97 patients (86.61%). The reasons for readmission were VOC (82.75%), ACS (13.72%), and severe anemia (3.44%). The main factors that predicted readmission were the existence of professional activity, a low fetal hemoglobin (HbF) level, the existence of neutrophilia, lymphocytosis, and/or thrombocytosis (p values of 0.0084, 0.043, and 0.020 respectively).

Conclusion: The 30‐day readmission rate after a sickle cell emergency is high in our study. The main factors that predicted readmission were the existence of professional activity, a relatively low level of fetal Hb, the existence of neutrophilia, lymphocytosis, and/or thrombocytosis.
Effect of Serum Interleukin‐6 Concentration on the Prognosis After Radiotherapy for Patients With Hepatocellular Carcinoma
Authors: Hu Yong , Zhou Yongkang , Du Shisuo , Zhu Wenchao , Chen Yixing , Zeng Zhaochong
Published: November 2024

Objective: The aim of this study was to explore the association between interleukin‐6 (IL‐6) concentration before radiotherapy (RT) and the prognosis after RT for patients with hepatocellular carcinoma (HCC).

Methods: The clinical data for 101 patients with HCC who received RT from October 2016 to June 2021 were retrospectively analyzed. In these patients, the tumors were confined to the liver, and IL‐6 concentration was measured before RT. The survival rate was calculated using the Kaplan–Meier method, and the Cox proportional hazards regression model was used to explore the independent factors affecting the patients’ prognosis. X‐tile software was used to obtain the optimal cut‐off value of pre‐RT IL‐6 concentration (7.8 pg/mL) for overall survival (OS).

Results: The 1‐, 2‐, and 3‐year OS rates were 84.4%, 55.8%, and 34.7%, respectively, for patients with a pre‐RT IL‐6 concentration > 7.8 pg/mL versus 96.0%, 80.1%, and 80.1%, respectively, for those with a pre‐RT IL‐6 concentration ≤ 7.8 pg/mL. The OS rates of the two groups were significantly different (p < 0.001). The median progression‐free survival (PFS) time was 7.5 months versus 15.1 months for patients with pre‐RT IL‐6 concentrations > 7.8 pg/mL and ≤ 7.8 pg/mL, respectively (p = 0.001). Pre‐RT IL‐6 concentration was an independent prognostic factor of OS (hazard ratio [HR] = 3.421, 95% confidence interval [CI]: 1.477–7.927, p = 0.004). Pre‐RT IL‐6 concentration (HR = 2.235, 95% CI: 1.176–4.246, p = 0.014) and age (HR = 0.615, 95% CI: 0.383–0.987, p = 0.044) were independent prognostic factors for PFS.

Conclusions: The prognosis of HCC patients receiving RT was worse for those with a pre‐RT serum IL‐6 concentration > 7.8 pg/mL than those with a pre‐RT serum IL‐6 concentration ≤ 7.8 pg/mL. Pre‐RT IL‐6 concentrations may affect the prognosis of HCC patients.
A Potential Therapeutic Effect of Suxiao Jiuxin Pills in Treating Postacute Sequelae of COVID‐19: Case Report
Authors: Sun Li , Li Nannan , Li Huilin , Zhang Qingshan , Bao Shuai , Li Xiaolu
Published: November 2024

Postacute Sequelae of COVID‐19 Cardiovascular Syndrome (PASC‐CVS) refers to a broad spectrum of cardiovascular symptoms that manifest four weeks or more after infection with COVID‐19, which cannot be diagnosed as cardiovascular disease through standard examinations. Common symptoms include exercise intolerance and tachycardia, alongside persistent issues such as chest pain, chest tightness, and difficulty breathing. PASC‐CVS significantly affects patients’ quality of life; however, effective treatments for this condition are currently lacking. In this report, we present two cases of PASC‐CVS patients who experienced well‐controlled cardiovascular symptoms following treatment with Suxiao Jiuxin Pills. Our findings may offer a novel approach to the clinical management of PASC‐CVS.
A Small Device May Deliver King‐Sized Solutions for Patients With an Exacerbation of Cystic Fibrosis
Authors: Laird P. , MacKenzie G. , Gill F. , Burr C. , McKinnon E. , Cooper M. , Geelhoed E. , Schultz A.
Published: November 2024

Aim: The aim is to examine whether using a portable spring‐infusor device to deliver antibiotics compared with a standard infusion pump (SIP) translated to (i) improve health outcomes, (ii) reduce the length of stay (LoS), and (iii) reduce cost for treatment of exacerbations of cystic fibrosis (CF).

Methods: An observational cohort study was conducted between December 2020 and June 2022 with participants aged 8–19 years admitted for exacerbation of CF. An activity monitor was fitted to participants to measure physical activities for the final 5 days of hospital admission. LoS was measured (days). Group allocation was according to participant preference. Costs were compared between the two groups for LoS, pump cost, and preparation and administration of antibiotics.

Results:Twenty‐seven of 30 eligible participants were approached, and 22 consented. Data were captured for 16 participants (spring‐infusor n = 9): 10 female; mean (SD) age 14.5 (2.1) years. Average step count was negatively associated with age (rho = 0.50), and greater overall in participants using spring‐infusors (mean 5324 (SD 2873) steps) versus SIPs (4806 (3116) steps) ‐ mean (95% CI) increase in the spring‐infusor group of 3246 (54‐6438) for participants of the same age. LoS was longer on average in the SIP group, (mean (SD) LoS: 16.1 (4.3) versus 12.4 (1.7)). The estimated cost saving for a child using a spring‐infusor was AUS$12,000.

Conclusion:Results from the study suggest that children hospitalised for exacerbations of CF are more active if they receive antibiotics via a spring‐infusor device compared with a SIP, and have reduced hospital stay that results in cost saving to the hospital. What is already known? Spring‐infusors are small, portable, and mechanical devices to deliver intravenous antibiotics to patients. Spring‐infusors are preferred by patients with CF at Perth Children’s Hospital Physical activity in children with CF is recommended, including during hospital admissions to promote wellbeing, quality of life, and health outcomes. What this paper adds? Children hospitalised for exacerbations of CF may be more active if they receive antibiotics via a portable spring‐infusor device compared with a SIP. Children using spring‐infusors had reduced hospital stays that results in cost saving to the hospital. Children hospitalised for exacerbations of CF step on average, fewer than 5000 steps per day, which is well below recommendations.
High Resolution Ultrasound as a Neuroimaging Tool in Traumatic Peripheral Nerve Injuries
Authors: Amr Hanan A. A. , Ali Asmaa A. M. , Mohamed Hanaa M. R. , Azab Marwa A. M. A.
Published: November 2024

Traumatic peripheral nerve injury (TPNI) is quite common in various types of acral trauma. It mostly passes unnoticed at the time of the initial trauma. The patients are usually sent for an ultrasound (US) assessment about 4 weeks following the trauma, after the electrophysiological changes are established. This paper presents a 5‐year experience of US findings of TPNI through 60 cases, who were examined as an outpatient with clinical and electrodiagnostic (EDX) tests suggesting nerve injury. The study population includes 40 males, 20 females, and mean age 34.4 ± 16.3. Upper limb nerves were more affected than the lower ones, with no significant difference between the right and left sides. Mechanisms of injury include laceration in 53.4% of cases, 38.3% had history of traction injury and only 8.3% had history of compression/contusion injury. Regarding the severity grading of the injuries, long segments of thickened separate or matted fascicles (Grades I and II) was found in 27 (40.9%) nerves; partial disruption with interstitial neuroma (Grade III) in 15 (22.7%) nerves; complete disruption (neurotmesis) (Grade IV) in 24 (36.4%) case. The integrity of six repaired nerves was also assessed. Muscle states within the territory of the motor nerve were always assessed, 62.9% of cases had decreased muscle bulk, 28.6% had muscle atrophy, and the remaining was normal. EDX testing results of 44 out of 60 patients was severe in 14 cases (31.8%), moderate in 15 cases (34.1%), mild in 11 case (25%), and normal in four cases (9.1%). The purpose of this study is to demonstrate that the US is a convenient neuroimaging tool by which we can accurately determine the level and the degree of peripheral nerve damage to plan the appropriate treatment.
PTBP1 Lactylation Promotes Glioma Stem Cell Maintenance through PFKFB4-Driven Glycolysis
Authors: Zhou Zijian , Yin Xianyong , Sun Hao , Lu Jiaze , Li Yuming , Fan Yang , Lv Peiwen , Han Min , Wu Jing , Li Shengjie , Liu Zihao , Zhao Hongbo , Sun Haohan , Fan Hao , Wang Shan , Xin Tao
Published: November 2024

Long-standing evidence implicates glioma stem cells (GSC) as the major driver for glioma propagation and recurrence. GSCs have a distinctive metabolic landscape characterized by elevated glycolysis. Lactate accumulation resulting from enhanced glycolytic activity can drive lysine lactylation to regulate protein functions, suggesting that elucidating the lactylation landscape in GSCs could provide insights into glioma biology. Herein, we have demonstrated that global lactylation was significantly elevated in GSCs compared with differentiated glioma cells. Polypyrimidine tract–binding protein 1 (PTBP1), a central regulator of RNA processing, was hyperlactylated in GSCs, and SIRT1 induced PTBP1 delactylation. PTBP1-K436 lactylation supported glioma progression and GSC maintenance. Mechanistically, K436 lactylation inhibited PTBP1 proteasomal degradation by attenuating the interaction with TRIM21. Moreover, PTBP1 lactylation enhanced RNA-binding capacity and facilitated PFKFB4 mRNA stabilization, which further increased glycolysis. Together, these findings uncovered a lactylation-mediated mechanism in GSCs driven by metabolic reprogramming that induces aberrant epigenetic modifications to further stimulate glycolysis, resulting in a vicious cycle to exacerbate tumorigenesis.

Significance: Glycolysis-induced lactylation enhances the function of PTBP1 to promote glioma stem cell maintenance, indicating that PTBP1 lactylation could be a potential target for the development of innovative glioma therapies.
Midkine at the Crossroads of Aging and Cancer
Authors: Bai Huiru , Cai Shang
Published: November 2024

Aging in mammals, including humans, is marked by a multitude of molecular, cellular, and systemic changes that increase the risk of various diseases, including cancer. Although the link between aging and increased cancer incidence is well documented, the precise biological mechanisms driving tumor initiation remain less clear. In a recent issue of Cancer Cell, Yan and colleagues have identified midkine, a heparin-binding growth factor, as an age-related biomarker mediating both aging-related phenotypes and cancer development. Further exploration of these molecular dynamics, alongside the development of targeted drugs, holds great promise for reducing aging-related cancer incidence.
supplementary figure5 from TAK1 Promotes an Immunosuppressive Tumor Microenvironment through Cancer-Associated Fibroblast Phenotypic Conversion in Pancreatic Ductal Adenocarcinoma
Authors: Sheng Nan , Shindo Koji , Ohuchida Kenoki , Shinkawa Tomohiko , Zhang Bo , Feng Haimin , Yamamoto Takeo , Moriyama Taiki , Ikenaga Naoki , Nakata Kohei , Oda Yoshinao , Nakamura Masafumi
Published: November 2024

supplementary figure5 from TAK1 Promotes an Immunosuppressive Tumor Microenvironment through Cancer-Associated Fibroblast Phenotypic Conversion in Pancreatic Ductal Adenocarcinoma
Supplementary Data 1 from TAK1 Promotes an Immunosuppressive Tumor Microenvironment through Cancer-Associated Fibroblast Phenotypic Conversion in Pancreatic Ductal Adenocarcinoma
Authors: Sheng Nan , Shindo Koji , Ohuchida Kenoki , Shinkawa Tomohiko , Zhang Bo , Feng Haimin , Yamamoto Takeo , Moriyama Taiki , Ikenaga Naoki , Nakata Kohei , Oda Yoshinao , Nakamura Masafumi
Published: November 2024

clean Supplementary article
Pancreatic CAF-Derived Autotaxin Drives Autocrine CTGF Expression to Modulate Protumorigenic Signaling
Authors: Volat Fanny , Medhi Ragini , Maggs Lauren Z. , Deken Marcel A. , Price Alice , Andrews Lauren , Clark Jonathan , Taylor Diane , Carruthers Alan , Taylor-Smith Ewan , Pacheco Natalia , Rudge Simon A. , Fraser Amy , Lopez-Clavijo Andrea F. , Sousa Bebiana C. , Johnson Zoë , Di Conza Giusy , van der Veen Lars , Shah Pritom , Sandig Hilary , Sharpe Hayley J. , Farrow Stuart
Published: November 2024

Autotaxin (ATX), encoded by ENPP2, is a clinical target in pancreatic ductal adenocarcinoma (PDAC). ATX catalyzes the production of lysophosphatidic acid (LPA), an important regulator within the tumor microenvironment (TME), yet the protumorigenic action of the ATX/LPA axis in PDAC remains unclear. In this study, by interrogating patient samples and cell line datasets, we show that the PDAC TME, rather than cancer cells, is responsible for the majority of ENPP2 expression and highlight a key role for cancer-associated fibroblast (CAF)-derived ATX in autocrine and paracrine protumorigenic signaling. Using the clinical-stage ATX inhibitor, IOA-289, we identified connective tissue growth factor (CTGF), also known as CCN2, as a downstream mediator of ATX signaling in the PDAC CAF-derived cell line, 0082T. Genetic ablation or pharmacologic inhibition of ATX in 0082T CAFs reduced CTGF secretion via modulation of LPA/LPA receptor signaling. Despite the loss of ATX function, extracellular levels of LPA were paradoxically increased, indicating a role for ATX beyond its enzymatic activity and suggesting a role for its LPA chaperone function in the LPA/LPA receptor signaling in CAFs. As CAFs are the main source for CTGF in the PDAC TME, these findings suggest a role for ATX in promoting a protumorigenic microenvironment via modulation of CAF secretion not only via its LPA-producing activity but also via its LPA chaperone function, providing a potential mechanism for the antitumor effects of ATX inhibition.