bluuebunny/crossref_metadata_2025 huggingface dataset:
Intratumoral radiation dose heterogeneity augments antitumor immunity in mice and primes responses to checkpoint blockade
Authors: Jagodinsky Justin C. , Vera Jessica M. , Jin Won Jong , Shea Amanda G. , Clark Paul A. , Sriramaneni Raghava N. , Havighurst Thomas C. , Chakravarthy Ishan , Allawi Raad H. , Kim KyungMann , Harari Paul M. , Sondel Paul M. , Newton Michael A. , Crittenden Marka R. , Gough Michael J. , Miller Jessica R. , Ong Irene M. , Morris Zachary S.
Published: September 2024

Radiation therapy (RT) activates multiple immunologic effects in the tumor microenvironment (TME), with diverse dose-response relationships observed. We hypothesized that, in contrast with homogeneous RT, a heterogeneous RT dose would simultaneously optimize activation of multiple immunogenic effects in a single TME, resulting in a more effective antitumor immune response. Using high-dose-rate brachytherapy, we treated mice bearing syngeneic tumors with a single fraction of heterogeneous RT at a dose ranging from 2 to 30 gray. When combined with dual immune checkpoint inhibition in murine models, heterogeneous RT generated more potent antitumor responses in distant, nonirradiated tumors compared with any homogeneous dose. The antitumor effect after heterogeneous RT required CD4 and CD8 T cells and low-dose RT to a portion of the tumor. At the 3-day post-RT time point, dose heterogeneity imprinted the targeted TME with spatial differences in immune-related gene expression, antigen presentation, and susceptibility of tumor cells to immune-mediated destruction. At a later 10-day post-RT time point, high-, moderate-, or low-RT-dose regions demonstrated distinct infiltrating immune cell populations. This was associated with an increase in the expression of effector-associated cytokines in circulating CD8 T cells. Consistent with enhanced adaptive immune priming, heterogeneous RT promoted clonal expansion of effector CD8 T cells. These findings illuminate the breadth of dose-dependent effects of RT on the TME and the capacity of heterogeneous RT to promote antitumor immunity when combined with immune checkpoint inhibitors.
Modulation of
Vibrio cholerae
gene expression through conjugative delivery of engineered regulatory small RNAs
Authors: Menendez-Gil Pilar , Veleva Diana , Virgo Mollie , Zhang Jige , Ramalhete Rita , Ho Brian T.
Published: September 2024

The increase in antibiotic resistance in bacteria has prompted the efforts in developing new alternative strategies for pathogenic bacteria. We explored the feasibility of targeting
Vibrio cholerae
by neutralizing bacterial cellular processes rather than outright killing the pathogen. We investigated the efficacy of delivering engineered regulatory small RNAs (sRNAs) to modulate gene expression through DNA conjugation. As a proof of concept, we engineered several sRNAs targeting the type VI secretion system (T6SS), several of which were able to successfully knockdown the T6SS activity at different degrees. Using the same strategy, we modulated exopolysaccharide production and motility. Lastly, we delivered an sRNA targeting T6SS into
V. cholerae
via conjugation and observed a rapid knockdown of the T6SS activity. Coupling conjugation with engineered sRNAs represents a novel way of modulating gene expression in
V. cholerae
opening the door for the development of novel prophylactic and therapeutic applications.

IMPORTANCE

Given the prevalence of antibiotic resistance, there is an increasing need to develop alternative approaches to managing pathogenic bacteria. In this work, we explore the feasibility of modulating the expression of various cellular systems in
Vibrio cholerae
using engineered regulatory sRNAs delivered into cells via DNA conjugation. These sRNAs are based on regulatory sRNAs found in
V. cholerae
and exploit its native regulatory machinery. By delivering these sRNAs conjugatively along with a real-time marker for DNA transfer, we found that complete knockdown of a targeted cellular system could be achieved within one cell division cycle after sRNA gene delivery. These results indicate that conjugative delivery of engineered regulatory sRNAs is a rapid and robust way of precisely targeting
V. cholerae
.
Semantic search using protein large language models detects class II microcins in bacterial genomes
Authors: Kulikova Anastasiya V. , Parker Jennifer K. , Davies Bryan W. , Wilke Claus O.
Published: September 2024

Class II microcins are antimicrobial peptides that have shown some potential as novel antibiotics. However, to date, only 10 class II microcins have been described, and the discovery of novel microcins has been hampered by their short length and high sequence divergence. Here, we ask if we can use numerical embeddings generated by protein large language models to detect microcins in bacterial genome assemblies and whether this method can outperform sequence-based methods such as BLAST. We find that embeddings detect known class II microcins much more reliably than does BLAST and that any two microcins tend to have a small distance in embedding space even though they typically are highly diverged at the sequence level. In data sets of
Escherichia coli
,
Klebsiella
spp., and
Enterobacter
spp. genomes, we further find novel putative microcins that were previously missed by sequence-based search methods.

IMPORTANCE

Antibiotic resistance is becoming an increasingly serious problem in modern medicine, but the development pipeline for conventional antibiotics is not promising. Therefore, alternative approaches to combat bacterial infections are urgently needed. One such approach may be to employ naturally occurring antibacterial peptides produced by bacteria to kill competing bacteria. A promising class of such peptides are class II microcins. However, only a small number of class II microcins have been discovered to date, and the discovery of further such microcins has been hampered by their high sequence divergence and short length, which can cause sequence-based search methods to fail. Here, we demonstrate that a more robust method for microcin discovery can be built on the basis of a protein large language model, and we use this method to identify several putative novel class II microcins.
Establishment and evaluation of a rapid method for the detection of bacterial pneumonia in hospitalized patients via multiplex PCR–capillary electrophoresis (MPCE)
Authors: Wang Jie , Zhao Pei , Zhao Mengchuan , Zhang Duoxiao , Chen Shan , Liu Ying , Gao Yuan , Tie Yanqing , Feng Zhishan
Published: September 2024

Cost-effective molecular diagnostic techniques for bacterial pneumonia are limited. We designed primers for 13 bacteria, performed multiplex nucleic acid detection through fragment analysis to obtain pathogen identification results, and established a multiplex PCR–capillary electrophoresis (MPCE) method, which can simultaneously detect 13 pathogens associated with bacterial pneumonia. The sensitivity, specificity, and reproducibility of the MPCE assay were tested, and 420 clinical samples were used to assess the clinical detection ability of MPCE, with the culture method used as a reference. Samples with inconsistent results detected by the two methods were sent for Sanger sequencing. The minimum detection limit of MPCE for 13 bacteria was 6.0 × 10
3
cfu/mL~2.0 × 10
6
cfu/mL. No cross-reactivity was observed with other pathogens. The percentage of agreement for reproducibility analysis reached 100%. For the 420 sputum samples, when the culture method was used as the reference, the sensitivity of MPCE to 13 bacteria ranged from 80% to 100%. The specificity for 13 bacteria ranged from 67.1% to 100%. The percentage of agreement between the MPCE and the culture method ranged from 69.7% to 100%. There was no statistically significant difference (
P
> 0.05) in the detection of
Escherichia coli
,
Enterobacter cloacae complex
,
Staphylococcus aureus
, methicillin-resistant
S. aureus, Streptococcus pyogenes
,
Moraxella catarrhalis
, or
Legionella pneumophila
between the MPCE and the culture method. Clinical samples with negative cultures but positive MPCE results were validated by Sanger sequencing, and the results were consistent with those of MPCE. The MPCE method has high sensitivity and specificity for bacterial pneumonia, enabling the simultaneous and rapid detection of multiple pathogens. It is cost-effective and has potential for clinical application.

IMPORTANCE

This study successfully established a multiplex PCR–capillary electrophoresis detection system that can simultaneously detect 13 pathogens through a single detection method, significantly improving clinical efficiency. It is cost-effective and has potential for clinical application.
The First Discovery of Archean Dolerite Dikes in the Western Part of the Aldan Shield
Authors: Erofeeva K. G. , Larionova Yu. O. , Samsonov A. V.
Published: September 2024

Dolerite dikes were studied in the western part of the Aldan terrane, in the middle reaches of the Tokko River. These dolerite dikes form a swarm of submeridional trend about 1 km wide. The dolerites of the thickest dike preserve their primary textural and structural features and mineral composition: plagioclase + pigeonite + augite + titanomagnetite. Dolerite in the chilled margins and central parts of the dike are homogeneous in composition, corresponds to low-Mg tholeiites, has low contents of Ti and other HFSE, with weak enrichment in light REE and small negative Nb anomalies. Sm–Nd isotope data on magmatic minerals of dolerite from the central part of the dike yield a good linear regression in an isochron diagram that gives to an age of 2510 ± 64 Ma, which probably corresponds to the crystallization age of the basalt. Metadolerites in a thin dike retain plagioclase porphyritic structures, but the pyroxenes are completely replaced by amphibole and chlorite. The metadolerites are contrastingly different in low contents of MgO, Cr, and Ni and in higher contents of TiO2, Fe2O3, P2O5, Nb, and all REE. The differences in the composition of the dikes may be explained by the longterm (about 65%) crystallization differentiation of the initial melt and the emplacement of the residual melt from a shallow intermediate magma chamber via opening cracks. Such conditions probably may have existed in tectonically stable intraplate settings. The age of the dolerites of the dike swarm is comparable to that of the anorogenic granites of the Nelyuki complex (~2.4–2.5 Ga), which are widespread in the western part of Aldan granulite–gneiss terrane. Our data bridge some gaps in characteristics of intraplate anorogenic magmatism that occurred in the western Aldan Shield in the Late Archean and marked the final consolidation of a large block of Archean crust in the Chara–Olekma granite–greenstone area.
‘Going through the motions’; a rich account of the complexity of the anterior cruciate ligament reconstruction pathway, a UK qualitative study
Authors: Carter Hayley M , Beard David J , Leighton Paul , Moffatt Fiona , Smith Benjamin E , Webster Kate E , Logan Phillipa
Published: September 2024

Objectives

This study aimed to understand the lived experiences of patients on the anterior cruciate ligament reconstruction (ACLR) pathway up to 3 months before, 3 months after and 1 year after surgery. Study objectives were to explore (1) patient experiences of preoperative and postoperative treatment, (2) views of/involvement in prehabilitation and (3) sources and consistency of healthcare advice.

Design

Semi-structured interviews analysed using reflexive thematic analysis.

Setting

Midlands, England.

Participants

Purposive sample of 18 participants aged 18–45. Three identified as female and 15 as male. Participants’ ethnic origin was white (n=14), Indian (n=2), British Asian (n=1) and Pakistani (n=1). 10 participants were awaiting ACLR, six were 3months postsurgery and two were 1 year postsurgery.

Results

Participants gave a rich account of ACLR pathway experiences discussing negative impacts of the injury, difficulties with navigating the pathway and making decisions about surgery. Interacting with healthcare professionals and managing the variety of resources, advice and opinions were also highlighted as challenges. Participants reflected on their preoperative journey accounting a wide spectrum of expectations and realities of returning to work and physical activity postoperatively. Prehabilitation was perceived to offer an advantage to recovery, mental well-being, injury knowledge, postoperative rehabilitation and supports a faster return to physical activity. Five themes were identified:

Injury experience, impact and support.

Navigating the treatment pathway.

Sense making in the preoperative period.

Uncertainty, expectations and reality of the postsurgical period.

Balancing resources, advice and opinions.

Conclusion

This study has illuminated patient experiences of the National Health Service (NHS) ACLR pathway, novel to the evidence base.

The results highlight the perceived shortcomings in patient support. They also demonstrate the difficulty patients face when navigating the NHS system, communicating with clinicians, making decisions about treatment and managing conflicting sources of healthcare advice. These problems are more prominent than previously recognised in the literature.

Registration

ClinicalTrials.gov Identifier:NCT05529511.
Construction of a competency evaluation model for Clinical Research Coordinators in China: a study based on the Delphi method and questionnaire survey
Authors: Zhu Yanhong , Sun Xiang , Cai Maohang , Shi Jun , Li Xin
Published: September 2024

Purpose

As the number of clinical trials in China continues to grow, the assessment of competency of Clinical Research Coordinators (CRCs), who play a crucial role in clinical trials, has become an important and challenging topic. This study aims to construct a competency model for CRCs tailored to the Chinese context, in order to promote the standardisation and regulated development of the CRC industry.

Study design and setting

This study was conducted in China, engaging CRCs as the primary subjects. A competency evaluation model for CRCs was constructed through literature review, semi-structured interviews, Delphi expert consultation and the analytic hierarchy process. A questionnaire survey was distributed to a broad sample of CRCs across China to evaluate the model’s reliability and validity.

Results

The final model encompasses 4 core competency dimensions and 37 indicators, tailored to assess the competencies of CRCs in China. The questionnaire yielded an effective response rate of 81.83%, with high internal consistency(Cronbach’s α>0.7). Factor analysis confirmed the model’s structure, indicating good reliability and validity.

Conclusion

This study represents a pioneering effort in constructing a competency model specifically designed for Chinese CRCs, complemented by a robust and valid assessment scale. The findings bear significant implications for the recruitment, training, development and management of CRCs.
Road to Recovery: protocol for a mixed-methods prospective cohort study evaluating the impact of a new model of substance use care in a Canadian setting
Authors: Dennis Brittany B , Bowles Jeanette , Johnson Cheyenne , De Wolfe Travis , Mundel Erika , Fast Danya , Boyd Jade , Fleury Mathew , Bach Paxton , Fairbairn Nadia , Socías M Eugenia , Ti Lianping , Hayashi Kanna , DeBeck Kora , Milloy M J , Felicella Guy , Morgan Jeffrey , Eekhoudt Cameron R , McGrail Kimberlyn , Richardson Lindsey , Ryan Andrea , Mbuagbaw Lawrence , Guyatt Gordon , Nolan Seonaid
Published: September 2024

Introduction

The Road to Recovery (R2R) Initiative is an innovative model of substance use care that seeks to increase treatment capacity by creating approximately 100 new addiction treatment beds to provide on-demand addiction care in Vancouver, British Columbia, for patients with substance use disorders. The new model also coordinates the region’s existing clinical substance use services to support patients across a care continuum that includes traditional office-based addiction treatment and harm reduction services, early withdrawal management and more intensive abstinence-based treatment programming. To understand the impact of offering on-demand and coordinated substance use care, an observational cohort of individuals who access any R2R clinical service will be created to examine health and social outcomes over time.

Methods and analysis

This prospective mixed-methods study will invite individuals from Vancouver, Canada, who access substance use treatment through the R2R model of care to (1) complete a baseline and 12-month follow-up quantitative questionnaire that solicits sociodemographic, substance use and previous addiction treatment data and (2) provide consent to the use of participants’ personal identifiers to access health records for chart review and for annual linkage to select health and administrative databases to allow for ongoing (virtual) community follow-up over 5 years. Additionally, a purposive sample of cohort participants will be invited to participate in baseline and 12-month follow-up qualitative interviews to share their experiences accessing R2R and identify challenges and opportunities associated with the implementation of R2R.

Ethics and dissemination

The study was approved by the University of British Columbia Providence Health Care Research Ethics Board in September 2023. Results from the proposed study will be published in peer-reviewed journals, presented at national and international scientific conferences and disseminated through regular meetings with policymakers, individuals with lived and living experience, and other high-level stakeholders, academic presentations and lay media.
Managing heart failure in the longer term
Authors: Ahmed Fozia Z , Beezer Janine , Fuat Ahmet , Halliday Brian P , Ludman Andrew J , Pellicori Pierpaolo , Savage Henry Oluwasefunmi , Taylor Clare J , Cleland John GF
Published: September 2024

After initial diagnosis and treatment, patients presenting to hospital with acute heart failure (HF) are assessed and managed by the hospital HF team. Further investigations are carried out to confirm the diagnosis; existing guideline-directed medical therapies are optimised; and new treatments are initiated to stabilise the condition, manage symptoms, and reduce morbidity and mortality. A wide range of diagnostic tests and therapeutics are established for HF with reduced ejection fraction, while options for HF with preserved ejection fraction have been limited. However, repurposing of drugs originally developed for other conditions (eg, sodium-glucose co-transporter 2 inhibitors and glucagon-like receptor 1 antagonists) for use in people with heart failure and extended use of medications traditionally restricted to reduced ejection fraction, such as mineralocorticoid receptor antagonists (eg, spironolactone) and angiotensin-neprilysin inhibitors (eg, sacubitril–valsartan) in those with an EF>40% is challenging established practice and increasing the options for optimisation of long-term management of patients with HF, across the entire ejection fraction spectrum. Integral to the management of chronic HF is the need to consider approaches to identify deterioration between scheduled visits, including annual electrocardiography and N-terminal pro B-type natriuretic peptide monitoring in primary care. Remote monitoring, including alert-based monitoring for patients with implanted devices, may help to identify worsening HF or deterioration between scheduled clinic visits. Questions remain around optimal diuretic treatment (eg, infusion vs bolus dosing during periods of decompensation and converting to oral furosemide or bumetanide); use of beta blockers in HF patients with atrial fibrillation (AF) and midly reduced or normal ejection fraction; whether mineralocorticoid receptor antagonists should be used in HF patients with higher ejection fraction beyond the control of blood pressure, and the choice between spironolactone and eplerenone; how sacubitril–valsartan should be used in patients with ejection fraction>40%; in which setting drugs should be optimised following discharge, and whether cessation of medications is appropriate after recovery in ejection fraction.
Loop quantum gravity effects on electromagnetic properties of charged leptons
Authors: Melo J. P. S. , Neves M. J. , Paixão J. M. A. , Helayël-Neto J. A.
Published: September 2024

The efforts in this contribution consist in reassessing a modified Dirac equation that incorporates a $$\gamma ^0 \gamma _5$$

γ
0

γ
5

-Lorentz-symmetry violating (LSV) term induced as a Loop Quantum Gravity (LQG) effect. Originally, this equation has been applied and considered as a good scenario for describing a number of investigations on the flight time of cosmic neutrinos, which suggests that the speed, in vacuum, in connection with the geometry that describes a granular space-time, takes the energy-dependent form, e.g., $$v(E) =1 \pm E/E_{\text {\tiny LSV}}$$

v

(
E
)

=
1
±
E
/

E

LSV

, with $$E_{\text {\tiny LSV}} \approx 6,5 \times 10^{17}$$

E

LSV

≈
6
,
5
×

10
17

GeV for neutrinos. Once LQG provides a viable way to understand this picture consistently, we pursue an analysis of this effective Dirac equation to inspect some of its properties. These include: the derivation of the modified fermionic propagator, attainment of the Gordon decomposition of the vector current with minimal electromagnetic coupling to obtain information on the form factors, examination of the non-relativistic limit of the equation, evaluation of the spin- and velocity-dependent corrections to the Coulomb potential due to LQG effects, and the modified Hamiltonian in the low-relativistic regime. The study of the form factors may open up paths to set up bounds on the LQG parameters from the precision measurements of electromagnetic attributes of the charged leptons, such as their respective electric and magnetic dipole moments.
TPLAD: Template-Parsed Log Anomaly Detection for Electrical Database Systems
Authors: Li Hailong , Peng Xiao , Wang Di , An Siyao , Zhang Chentao , Shi Weining
Published: September 2024

In recent years, with the increasing complexity of software systems, logs have become crucial for system maintenance. Log-based anomaly detection plays a vital role in automatically detecting system anomalies through log analysis. However, current log-based anomaly detection approaches encounter significant practical challenges. Supervised methods often require a large amount of manually labeled training data, which can be time-consuming and costly to obtain. On the other hand, unsupervised and semi-supervised approaches may suffer from subpar performance, as they do not leverage historical anomalies to improve their detection capabilities. These challenges underscore the necessity for the development of more efficient and effective log-based anomaly detection methods. Database anomaly access detection is critical for ensuring the stability and security of database systems. We present a survey of existing log anomaly detection models and propose a novel approach, Template-Parsed Log Anomaly Detection (TPLAD) model, for automated anomaly detection in massive database log files. The proposed model combines the original log template with template parsing using code and text semantic representation. Experimental results demonstrate the effectiveness of the proposed approach in detecting abnormal database access patterns, including runtime errors, unauthorized access, and data leaks. The findings indicate that TPLAD model shows promise in enhancing database security and stability in business systems.
Non-classical correlations and coherence in a two-dimensional electron gas under the influence of Rashba spin–orbit coupling
Authors: Banouni C. , Bouafia Z. , Mansour M. , Ouchrif M.
Published: September 2024

This investigation delves into the dynamics of quantum correlations and coherence within a two-dimensional electron gas (2DEG) system, taking into account the influence of Rashba spin–orbit coupling (SOC). We utilize metrics such as logarithmic negativity ([Formula: see text]), local quantum uncertainty (LQU ([Formula: see text])), and relative entropy of coherence ([Formula: see text]) to specifically assess these quantum resources among electron spins within non-interacting electron gases. Our study investigates how the separation distance (R) between electrons and the intensity of Rashba SOC ([Formula: see text]), impact the behavior of quantum properties within the 2DEG system. We find that specific strengths of Rashba SOC can effectively regulate quantum correlations and coherence within this system. Particularly significant is our observation that optimal quantum indicators emerge when electron proximity is minimized, underscoring the substantial influence of electron distance on quantum characteristics. Conversely, as electron separation increases, these quantum metrics diminish. Therefore, by adjusting the Rashba parameter, we can enhance the resilience of these quantum measurements against increasing electron separations, providing valuable insights into the potential for controlling and manipulating quantum behavior in similar 2DEG systems.
Interior Crisis Route to Extreme Events in a Memristor-Based 3D Jerk System
Authors: Vivekanandan Gayathri , Kengne Léandre Kamdjeu , Chandrasekhar D. , Fozin Theophile Fonzin , Minati Ludovico
Published: September 2024

In dynamical systems, events that deviate significantly from usual or expected behavior are referred to as extreme events. This paper investigates the mechanism of extreme event generation in a 3D jerk system based on a generalized memristive device. In addition, regions of coexisting parallel bifurcation branches are explored as a way of investigating the multistability of the memristive system. The system is examined using bifurcation diagrams, Lyapunov exponents, time series, probability density functions of events, and inter-event intervals. It is found that extreme events occur via a period-doubling route and are due to an interior crisis that manifests itself as a sudden shift from low-amplitude to high-amplitude oscillations. Multistability is also identified when both control parameters and initial values are modified. Finally, an analog circuit based on the memristive jerk system is designed and experimentally realized. To our knowledge, this is the first time that extreme events have been reported in a memristive jerk system in particular and in jerk systems in general.
Digital Image Sensor Evolution and New Frontiers
Authors: Fossum Eric R. , Teranishi Nobukazu , Theuwissen Albert J.P.
Published: September 2024

This article reviews nearly 60 years of solid-state image sensor evolution and identifies potential new frontiers in the field. From early work in the 1960s, through the development of charge-coupled device image sensors, to the complementary metal oxide semiconductor image sensors now ubiquitous in our lives, we discuss highlights in the evolutionary chain. New frontiers, such as 3D stacked technology, photon-counting technology, and others, are briefly discussed.
Informing Endpoints for Clinical Trials of Geographic Atrophy
Authors: Lad Eleonora M. , Fleckenstein Monika , Holz Frank G. , Shen Liangbo , Priore Lucian V. Del , Silva Rufino , Staurenghi Giovanni , Waheed Nadia , Chakravarthy Usha
Published: September 2024

Geographic atrophy (GA), the non-neovascular advanced form of age-related macular degeneration, remains an important disease area in which treatment needs are currently unmet. Recent clinical trials using drugs that target the complement pathway have shown modest yet consistent reductions in GA expansion but without commensurate changes in measures of visual function. In this review, we summarize information from the wide range of studies describing the characteristics of GA morphology and enumerate the factors influencing the growth rates of lesions and the directionality of expansion. In addition, we review the relationship between GA growth and the various measures of vision that reflect changes in function. We consider the reasons for the discordance between the anatomical and functional endpoints in current use and discuss methods to align these key outcomes.
Retinal Connectomics: A Review
Authors: Sigulinsky Crystal L. , Pfeiffer Rebecca L. , Jones Bryan William
Published: September 2024

The retina is an ideal model for understanding the fundamental rules for how neural networks are constructed. The compact neural networks of the retina perform all of the initial processing of visual information before transmission to higher visual centers in the brain. The field of retinal connectomics uses high-resolution electron microscopy datasets to map the intricate organization of these networks and further our understanding of how these computations are performed by revealing the fundamental topologies and allowable networks behind retinal computations. In this article, we review some of the notable advances that retinal connectomics has provided in our understanding of the specific cells and the organization of their connectivities within the retina, as well as how these are shaped in development and break down in disease. Using these anatomical maps to inform modeling has been, and will continue to be, instrumental in understanding how the retina processes visual signals.
Rapid and Nondestructive Evaluation of Rice SPAD Value under Disease Stress Using Hyperspectral Imaging Sensors
Authors: Hu Xiaohui , Cao Yifei , Zhou Peng , Wu Yuqiang , Korohou Tchalla Wiyao
Published: September 2024

Leaf chlorophyll content is an important indicator of photosynthetic capacity and health status and plays a key role in monitoring plant growth. At present, research on chlorophyll content monitoring has mainly focused on establishing a relationship between vegetation index and chlorophyll content, which was composed of several hyperspectral wavelengths, resulting in the loss of effective information contained in certain wavelengths strongly associated with disease. Therefore, it was very important to select spectral wavelengths to reveal the hyperspectral response of chlorophyll content in diseased leaves. Fifty groups of rice leaves infected with bacterial leaf blight were studied, and hyperspectral images and soil plant analysis development (SPAD) values of disease‐stressed rice leaves were collected every 5 days from the first day after inoculation. A method for predicting the SPAD value of diseased rice leaves using random forest (RF) combined with a back‐propagation optimized neural network (BPNN) was proposed. The bird swarm algorithm (BSA) and the immune algorithm (IA) were used to solve the problems of information loss, local minimization, and slow convergence of the BPNN. The BPNN, BSA–BPNN, IA–BPNN, and BSA–IA–BPNN prediction models for the SPAD value of diseased rice leaves are established. The results show that the BSA–IA–BPNN model with characteristic wavelengths selected by RF achieved the best prediction effect, and the prediction sets R2, root‐mean‐square error, and relative error are 0.97%, 4.34%, and 3.33% respectively. The shortest prediction modeling time is 1.54 s, and the model exhibits the best stability. This study provides allegorical support and a theoretical basis for achieving rapid, nondestructive detection of the SPAD value of diseased rice leaves, provides an effective reference for estimating the SPAD value of diseased rice leaves in the field, and is of great importance for rice disease monitoring.
Brain Tumor Detection Using a Deep CNN Model
Authors: Ben Brahim Sonia , Dardouri Samia , Bouallegue Ridha
Published: September 2024

The diagnosis of brain tumors through magnetic resonance imaging (MRI) has become highly significant in the field of medical science. Relying solely on MR imaging for the detection and categorization of brain tumors demands significant time, effort, and expertise from medical professionals. This underscores the need for an autonomous model for brain tumor diagnosis. Our study involves the application of a deep convolutional neural network (DCNN) to diagnose brain tumors from MR images. The application of these algorithms offers several benefits, including rapid brain tumor prediction, reduced errors, and enhanced precision. The proposed model is built upon the state‐of‐the‐art CNN architecture VGG16, employing a data augmentation approach. The dataset utilized in this paper consists of 3000 brain MR images sourced from Kaggle, with 1500 images reported to contain tumors. Through training and testing, the pretrained CNN model achieves a precision and classification accuracy rate of 96%, and the loss is 1%. Moreover, it achieves an average precision, recall, and F1‐score of 98.7%, 97.44%, and 98.06%, respectively. These evaluation metric values demonstrate the effectiveness of the proposed solution.
A Paradigm Shift in Tumor Immunology: Th17 Cells and TGFβ in Intestinal Cancer Initiation
Authors: Wyatt Megan M. , Paulos Chrystal M.
Published: September 2024

Cancer remains one of the most complex challenges in modern medicine, with intricate relationships between immune responses and tumor development. This article examines a groundbreaking study by Fesneau and colleagues, published in Nature Immunology. This elegant body of work explores the link between chronic inflammation and cancer, particularly focusing on Th17 cells involved in intestinal cancer initiation. Th17 cells, known for their dual roles in immunity, can promote or inhibit tumor growth depending on their environment. This study reveals that a specific subset of Th17 cells, derived from IL17-producing cells, can transition to a tumorigenic state when TGFβ signaling is impaired. Surprisingly, TGFβ acts as a crucial regulatory factor, maintaining the balance between immune tolerance and tumorigenesis by preventing Th17 cells from becoming tumorigenic. This research highlights the potential for therapeutic interventions targeting TGFβ signaling to prevent cancer initiation under chronic inflammatory conditions. The findings have clinical implications for improving cancer immunotherapies, including immune checkpoint inhibitors and adoptive T-cell therapies, by enhancing the efficacy of treatments and mitigating the risk of tumorigenic transformations. Overall, this study provides insights into the mechanisms linking inflammation and cancer, paving the way for innovative strategies to harness the immunity in cancer treatment.
Data from Estrogen Receptor Blockade Potentiates Immunotherapy for Liver Metastases by Altering the Liver Immunosuppressive Microenvironment
Authors: Benslimane Yasmine , Amalfi Kevin , Lapin Sara , Perrino Stephanie , Brodt Pnina
Published: September 2024

Abstract
Liver metastases (LM) remain a major cause of cancer-related death and are a major clinical challenge. LM and the female sex are predictors of a poorer response to immunotherapy but the underlying mechanisms remain unclear. We previously reported on a sexual dimorphism in the control of the tumor microenvironment (TME) of colorectal carcinoma liver metastases (CRCLM) and identified estrogen as a regulator of an immunosuppressive TME in the liver. Here we aimed to assess the effect of estrogen deprivation on the cytokine/chemokine profile associated with CRCLM, using a multiplex cytokine array and the RNAscope technology, and its effects on the innate and adaptive immune responses in the liver. We also evaluated the benefit of combining the selective estrogen-receptor degrader Fulvestrant with immune checkpoint blockade for the treatment of CRCLM. We show that estrogen depletion altered the cytokine/chemokine repertoire of the liver, decreased macrophage polarization, as reflected in reduced accumulation of tumor infiltrating M2 macrophages and increased the accumulation of CCL5+/CCR5+ CD8+ T and NKT cells in the liver TME. Similar results were obtained in a murine pancreatic ductal adenocarcinoma model. Importantly, treatment with Fulvestrant also increased the accumulation of CD8+CCL5+, CD8+CCR5+ T and NK cells in the liver TME and enhanced the therapeutic benefit of anti-PD1 immunotherapy, resulting in a significant reduction in the outgrowth of LM. Taken together, our results show that estrogen regulates immune cell recruitment to the liver and suggest that inhibition of estrogen action could potentiate the tumor-inhibitory effect of immunotherapy in hormone-independent and immunotherapy-resistant metastatic cancer.
Significance:
The immune microenvironment of the liver plays a major role in controlling the expansion of hepatic metastases and is regulated by estrogen. We show that treatment of tumor-bearing mice with an estrogen receptor degrader potentiated an anti-metastatic effect of immunotherapy. Our results provide mechanistic insight into clinical findings and a rationale for evaluating the efficacy of combination anti-estrogen and immunotherapy for prevention and/or treatment of hepatic metastases in female patients.
Metastatic SMARCB1-Deficient Renal Medullary Carcinoma without Hemoglobinopathy with Durable and Dramatic Response to Pembrolizumab plus Lenvatinib: Case Report
Authors: McCamy William , Yousefiasl Maryam , Tretiakova Maria , Jagtiani Minal , Hall Evan
Published: September 2024

Introduction: Renal medullary carcinoma (RMC) is a rare form of renal cell carcinoma (RCC) that is typically associated with a loss of function in SMARCB1 and diagnosis of sickle cell or other hemoglobinopathy. In rare cases, this disease can be seen in patients without hemoglobinopathy and is classified as “SMARCB1-deficient RMC without hemoglobinopathy” or referred to as “RCC unclassified with medullary phenotype” in some of the literature. Platinum-based cytotoxic chemotherapy is currently the recommended first-line treatment for this rare disease. Case Presentation: Here we report a 53-year-old male who was diagnosed with metastatic SMARCB1-deficient RMC without hemoglobinopathy after presenting with left flank and abdominal pain. After initiating first-line pembrolizumab and lenvatinib systemic therapy, imaging showed regression at 6 weeks. To date, this patient continues to show a near complete response to this treatment regimen. Conclusion: To our knowledge, this is the first documented case of SMARCB1-deficient RMC without hemoglobinopathy to receive this treatment regimen and show such a response.
Senescent CD4+ T-Cell Phenotypes and Inflammatory Milieu in the Coronary and Systemic Circulation in ST-Elevation Myocardial Infarction: An Exploratory Study
Authors: Bocanegra-Zamora Fernanda , Espinosa-Bautista Fernanda , Jiménez-Rodríguez Gian M. , Masso Felipe , Paez Araceli , Gonzalez-Pacheco Hector , Patlán Mariana , Eid-Lidt Guering , Amezcua-Guerra Luis M.
Published: September 2024

Introduction: In ST-elevation myocardial infarction (STEMI), inflammation is pivotal, with early senescent CD4+CD28null cells implicated in its pathogenesis. However, the functional phenotype of these cells within the coronary circulation remains unclear. Methods: We examined CD4+ cell subpopulations in blood samples from the coronary sinus and vena cava of 24 STEMI patients and the cephalic vein of seven healthy controls. Results: Our findings revealed reduced CD4+ cell counts in STEMI patients compared to controls (1,998, 1,275–3,268 vs. 4,278, 3,595–4,449), alongside an increased proportion of CD4+ cells lacking CD28 expression (20.1 vs. 6.1%). These CD4+CD28null cells in STEMI predominantly exhibited a Th1 phenotype (47.8% vs. 6.6%). Intriguingly, no significant differences were detected in CD4+CD28null cells between coronary sinus and vena cava, and cytokine levels in these compartments remained similar. Conclusion: CD4+CD28null cells are increased in STEMI, mainly polarized toward a Th1 phenotype, and distributed equally between the different vascular beds.
Cannabinoids for the Treatment of Glaucoma: A Review
Authors: Joshi Neeraj , Mariam Haifa , Kamath Ashwin
Published: September 2024

Background: Glaucoma is an ocular disease with significant health burden. Despite the availability of many antiglaucoma drugs, a significant proportion of patients may experience worsening of the disease. Hence, there is a need for newer antiglaucoma drugs. Summary: Natural and synthetic derivatives of cannabis plants have been studied in the treatment of glaucoma since the 1970s. This review describes the potential mechanisms of the cannabinoids in the treatment of glaucoma, summarizes the findings of clinical studies describing the efficacy of these compounds, and describes the adverse effects observed with the various cannabinoid formulations evaluated in clinical studies of glaucoma in healthy volunteers and patients. The implications of these findings in terms of the potential clinical status of cannabinoids in the treatment of glaucoma and the challenges involved have also been described. Key Messages: Cannabinoids lower intraocular pressure. However, the effect is short-lived. There is also a lack of well-formulated ocular delivery system. The available evidence is inadequate to recommend the use of cannabinoids for the routine treatment of glaucoma.
Diagnosis, Approach, and Clinical Classification of Idiopathic Granulomatous Mastitis: Consensus Report
Authors: Emiroglu Mustafa , Akcan Alper , Velidedeoglu Mehmet , Girgin Sadullah , Aytac Ozgur , Canturk N. Zafer , Yilmaz Kerim Bora , Koksal Hande , Cabioglu Neslihan , Cetin Kenan , Gulluoglu Bahadır
Published: September 2024

Objective: The aim of the idiopathic granulomatous mastitis (IGM) consensus study was to evaluate the etiology, diagnostic steps, and differential diagnosis and propose a widely accepted clinical classification of this mysterious breast disease. Method: The organization of a national IGM consensus was decided by the joint evaluation of the Turkish Federation of Breast Diseases Societies, SENATURK, and the Society of Breast Surgery. First, a working group of 11 members was formed, and a survey and workshop were organized to reach a common consensus. The modified Delphi method was used in the consensus methodology. Voting rates of 80% and above were considered as acceptance. Results: The consensus was 45/50 (92%) that core needle biopsies are necessary for the diagnosis of IGM and 39/40 (97%) that a new clinical classification is needed. The proposed Turkish clinical classification of IGM was accepted by 94% in three rounds of voting. Conclusion: This disease should be considered etiologically idiopathic. Tissue diagnosis and pathological evaluation are recommended for treatment. The proposed IGM Turkey classification was strongly accepted.
Validação do analisador i-STAT® cartucho CG8+ para análise hemogasométrica
Authors: Faria Valéria Cristina de , Marins João Carlos Bouzas , Pereira Juscélia Cristina , Salles Samuel de Souza , Oliveira Gustavo Antonio de , Lima Luciana Moreira
Published: September 2024

The aim of this study was to compare values arterial blood gas values obtained by laboratory technical reference with values obtained by the i-STAT® CG8+ analyzer, in order to confirm their validity and thus extrapolate its applicability in academic research in the context of physical activity. Were collected 22 samples of blood from the radial artery of the non-dominant arm of patients admitted to the ITU of the Hospital São João Batista, located in Viçosa, Minas Gerais, in the period from February to March 2013. Were compared between the reference method Ciba Corning Gas System 278 and i-STAT® CG8+ portable analyzer the result of the following variables: pH; PO2 and PCO2 expressed in mmHg; HCO3, and TCO2 BE (base excess) expressed in mmol / L; sO2 and expressed as a percentage of saturation. The student t test, correlation test, and Bland-Altman analysis were used. For all blood parameters monitored in the comparison of mean values between the two methods, no significant difference was found for any of the variables. There was a significant correlation (p<0.0001) and strong, with all correlation coefficients (r) above 0.93, between the two methods for all variables. The Bland-Altman analysis showed that there was agreement between the two methods, with over 90% of the sample between the limits of agreement for all variables. The i-STAT® CG8+ analyzer presented acceptable validity in the resting situation by reference to the Ciba Corning 278 Gas System device, and its use is an excellent strategy for research in the area of sport and health sciences that require fast results in the resting situation and that ensure the effectiveness of decision making.
Sarcopenia em pessoas idosas: concordância entre métodos preditores
Authors: Araújo Sílvia Ribeiro Santos , Miranda Rogério Mariano de , Silva Bruno Rodrigues
Published: September 2024

Sarcopenia is a relevant clinical condition worldwide. Its prevalence ranges from 5% to 13% in the elderly aged 65 years and over. Over 80 years, this value can reach 50%, demonstrating the influence of age on the development of the disease. Its diagnosis is based on reduced muscle mass, associated with decreased strength and/or low muscle function. The gold standard for diagnosing the disease is Dual-energy X-ray absorptiometry, but it is inaccessible due to its high cost and diagnostic complexity. Thus, alternative methods for screening for sarcopenia, such as: sit and stand test (TSL), calf circumference (CP) and manual strength test (FPM), SARC-F questionnaire are applied. Defining methods suitable for the outpatient setting is essential for both screening and diagnosis of the disease. The present study aimed to analyze whether there is agreement between predictive methods used to estimate the existence of sarcopenia in the elderly. This is a cross-sectional study carried out with 27 healthy elderly people (23 women and 4 men). The predictive methods were measuring CP, FPM, TSL and Ishii Probability Score (ISHII). The agreement between the classifications was used the Kappa statistic. All predictive methods identified sarcopenic and non-sarcopenic individuals. There was no agreement in the combinations: CTS x FPM; TSL x FPM and; TSL x ISHII. As for the association between the CTS and TSL methods, there was a moderate agreement between the predicted values  (k=0.43; p=0.006). Conclusion: Different predictive methods promote different sarcopenia diagnoses. A moderate agreement was observed for the combination between CTS and TSL predictors. It should be noted that the association between different tests is an option to be evaluated.
Low‐Level Tragus Stimulation Attenuates Blood Pressure in Young Individuals With Hypertension: Results From a Small‐Scale Single‐Blind Controlled Randomized Clinical Trial
Authors: Mbikyo Muisha B. , Wang Ai , Ma Qun , Miao Linlin , Cui Nan , Yang Yiqing , Fu Haoran , Sun Yingxian , Li Zhao
Published: September 2024

Background

Hypertension is a significant risk factor for cardiovascular and chronic kidney diseases. Its management in young people remains limited. Device‐based therapies, such as low‐level tragus stimulation (LL‐TS), a noninvasive method that reduces sympathetic activity, have recently been explored for resistant hypertension.

Methods and Results

This trial involved patients with Grade 1 hypertension with no other medical history. LL‐TS (20 Hz, 1 mA, 1 h/day) was applied for 3 months on the tragus (Intervention group [IG]) or earlobe (Control group [CG]). Blood pressure and outcomes were assessed at the first, second, and third months. Among 40 patients, 21 were in IG and 19 in CG. Baseline systolic blood pressure was similar between IG (142.62±8.18 mm Hg) and CG (143.00±8.61 mm Hg),
P
=0.89. Post‐LL‐TS, systolic blood pressure showed significant reductions in IG compared with CG at the first (IG: 134.47±5.95 mm Hg, CG: 141.28±6.78 mm Hg,
P
=0.002), second (IG: 132.50±7.51 mm Hg, CG: 140.62±7.15 mm Hg,
P
=0.001), and third months (IG: 128.81±7.13 mm Hg, CG: 136.51±7.96 mm Hg,
P
=0.003). diastolic blood pressure also differed significantly: first month (IG: 85.34±5.81 mm Hg, CG: 89.74±6.32 mm Hg,
P
=0.03), second month (IG: 82.12±5.22 mm Hg, CG: 88.57±7.11 mm Hg,
P
=0.002), and third month (IG: 80.71±5.96 mm Hg, CG: 87.55±5.26 mm Hg,
P
=0.001). Heart rate was unchanged (
P
>0.05). Only 0.01% of IG subjects reported site irritation, with no serious adverse events.

Conclusions

LL‐TS led to significant blood pressure reductions in young patients with essential hypertension. Further larger trials are needed to confirm the safety and efficacy of LL‐TS.

Registration

URL:
https://www.chictr.org.cn/
; Unique identifier: ChiCTR2000038448.