bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep Learning-Based Recognition of Different Thyroid Cancer Categories Using Whole Frozen-Slide Images
Authors: Zhu Xinyi , Chen Cancan , Guo Qiang , Ma Jianhui , Sun Fenglong , Lu Haizhen
Published: July 2022

Introduction: The pathological rare category of thyroid is a type of lesion with a low incidence rate and is easily misdiagnosed in clinical practice, which directly affects a patient’s treatment decision. However, it has not been adequately investigated to recognize the rare, benign, and malignant categories of thyroid using the deep learning method and recommend the rare to pathologists.

Methods: We present an empirical decision tree based on the binary classification results of the patch-based UNet model to predict rare categories and recommend annotated lesion areas to be rereviewed by pathologists.

Results: Applying this framework to 1,374 whole-slide images (WSIs) of frozen sections from thyroid lesions, we obtained an area under a curve of 0.946 and 0.986 for the test datasets with and without WSIs, respectively, of rare types. However, the recognition error rate for the rare categories was significantly higher than that for the benign and malignant categories (p < 0.00001). For rare WSIs, the addition of the empirical decision tree obtained a recall rate and precision of 0.882 and 0.498, respectively; the rare types (only 33.4% of all WSIs) were further recommended to be rereviewed by pathologists. Additionally, we demonstrated that the performance of our framework was comparable to that of pathologists in clinical practice for the predicted benign and malignant sections.

Conclusion: Our study provides a baseline for the recommendation of the uncertain predicted rare category to pathologists, offering potential feasibility for the improvement of pathologists’ work efficiency.
Nano-Metal–Organic Framework Decorated With Pt Nanoparticles as an Efficient Theranostic Nanoprobe for CT/MRI/PAI Imaging-Guided Radio-Photothermal Synergistic Cancer Therapy
Authors: Ma Yingjian , Mao Jing , Qin Haojie , Liang Pan , Huang Wenpeng , Liu Chenchen , Gao Jianbo
Published: July 2022

The multifunctional theranostic nanoplatforms, which can realize changing the contrasts of medical images and enhance cancer therapies simultaneously, have attracted tremendous attention from chemists and medicine in past decades. Herein, a nanoscale metal–organic framework-based material was first synthesized and then decorated with platinum (NMOF545@Pt) successfully for multimodal imaging-guided synergistic cancer therapy. The obtained NMOF545@Pt is advantageous in shortening the longitudinal relaxation time (T1), enhancing photoacoustic effects, and elevating X-ray absorption efficiently. Thus, the enchantments of tripe imaging modalities, computed tomography (CT)/magnetic resonance imaging (MRI)/photoacoustic imaging (PAI), were realized with NMOF545@Pt administration simultaneously and can be cleared from the mice. Meanwhile, in vitro and in vivo experiments demonstrate that the synthesized NMOF545@Pt can dramatically increase photothermal therapy (PTT) and radiotherapy (RT) efficacy. Convincing evidence proves that tumor growth can be wholly inhibited without noticeable side effects or organ damage. The results demonstrated the promise of multifunctional nanocomposites NMOF545@Pt to improve biomedical imaging and synergistic tumor treatments.
Arvcf Dependent Adherens Junction Stability is Required to Prevent Age-Related Cortical Cataracts
Authors: Martin Jessica B. , Herman Kenneth , Houssin Nathalie S. , Rich Wade , Reilly Matthew A. , Plageman Timothy F.
Published: July 2022

The etiology of age-related cortical cataracts is not well understood but is speculated to be related to alterations in cell adhesion and/or the changing mechanical stresses occurring in the lens with time. The role of cell adhesion in maintaining lens transparency with age is difficult to assess because of the developmental and physiological roles that well-characterized adhesion proteins have in the lens. This report demonstrates that Arvcf, a member of the p120-catenin subfamily of catenins that bind to the juxtamembrane domain of cadherins, is an essential fiber cell protein that preserves lens transparency with age in mice. No major developmental defects are observed in the absence of Arvcf, however, cortical cataracts emerge in all animals examined older than 6-months of age. While opacities are not obvious in young animals, histological anomalies are observed in lenses at 4-weeks that include fiber cell separations, regions of hexagonal lattice disorganization, and absence of immunolabeled membranes. Compression analysis of whole lenses also revealed that Arvcf is required for their normal biomechanical properties. Immunofluorescent labeling of control and Arvcf-deficient lens fiber cells revealed a reduction in membrane localization of N-cadherin, β-catenin, and αN-catenin. Furthermore, super-resolution imaging demonstrated that the reduction in protein membrane localization is correlated with smaller cadherin nanoclusters. Additional characterization of lens fiber cell morphology with electron microscopy and high resolution fluorescent imaging also showed that the cellular protrusions of fiber cells are abnormally elongated with a reduction and disorganization of cadherin complex protein localization. Together, these data demonstrate that Arvcf is required to maintain transparency with age by mediating the stability of the N-cadherin protein complex in adherens junctions.
The Ubiquitin-Proteasome System in Apoptosis and Apoptotic Cell Clearance
Authors: Yuan Lei , Li Peiyao , Zheng Qian , Wang Hui , Xiao Hui
Published: July 2022

Ubiquitination, a critical post-translational modification of proteins, refers to the covalent attachment of ubiquitin to the substrate and is involved in various biological processes such as protein stability regulation, DNA damage repair, and apoptosis, among others. E3 ubiquitin ligases are essential enzymes of the ubiquitin pathway with high substrate specificity and precisely regulate specific proteins’ turnover. As one of the most well-studied forms of programmed cell death, apoptosis is substantially conserved across the evolutionary tree. The final critical stage in apoptosis is the removal of apoptotic cells by professional and non-professional phagocytes. Apoptosis and apoptotic cell clearance are crucial for the normal development, differentiation, and growth of multicellular organisms, as well as their association with a variety of inflammatory and immune diseases. In this review, we discuss the role of ubiquitination and deubiquitination in apoptosis and apoptotic cell clearance.
Dysregulation of BMP, Wnt, and Insulin Signaling in Fragile X Syndrome
Authors: Song Chunzhu , Broadie Kendal
Published: July 2022

Drosophila models of neurological disease contribute tremendously to research progress due to the high conservation of human disease genes, the powerful and sophisticated genetic toolkit, and the rapid generation time. Fragile X syndrome (FXS) is the most prevalent heritable cause of intellectual disability and autism spectrum disorders, and the Drosophila FXS disease model has been critical for the genetic screening discovery of new intercellular secretion mechanisms. Here, we focus on the roles of three major signaling pathways: BMP, Wnt, and insulin-like peptides. We present Drosophila FXS model defects compared to mouse models in stem cells/embryos, the glutamatergic neuromuscular junction (NMJ) synapse model, and the developing adult brain. All three of these secreted signaling pathways are strikingly altered in FXS disease models, giving new mechanistic insights into impaired cellular outcomes and neurological phenotypes. Drosophila provides a powerful genetic screening platform to expand understanding of these secretory mechanisms and to test cellular roles in both peripheral and central nervous systems. The studies demonstrate the importance of exploring broad genetic interactions and unexpected regulatory mechanisms. We discuss a number of research avenues to pursue BMP, Wnt, and insulin signaling in future FXS investigations and the development of potential therapeutics.
Boron-Doped Pine-Cone Carbon With 3D Interconnected Porosity for Use as an Anode for Potassium-Ion Batteries With Long Life Cycle
Authors: Lu Jian-Fang , Li Ke-Chun , Lv Xiao-Yan , Kuai Hong-Xiang , Su Jing , Wen Yan-Xuan
Published: July 2022

Potassium-ion batteries (KIBs) have received widespread attention as an alternative to lithium-ion batteries because of their low cost and abundance of potassium. However, the poor kinetic performance and severe volume changes during charging/discharging due to the large radius of potassium leading to low capacity and rapid decay. Therefore, development of anode materials with sufficient space and active sites for potassium ion deintercalation and desorption is necessary to ensure structural stability and good electrochemical activity. This study prepared boron-doped pine-cone carbon (BZPC) with 3D interconnected hierarchical porous in ZnCl2 molten-salt by calcination under high temperature. The hierarchical porous structure promoted the penetration of the electrolyte, improved charge-carrier diffusion, alleviated volume changes during cycling, and increased the number of micropores available for adsorbing potassium ions. In addition, due to B doping, the BZPC material possessed abundant defects and active centers, and a wide interlayer distance, which enhanced the adsorption of K ions and promoted their intercalation and diffusion. When used as the anode of a KIB, BZPC provided a high reversible capacity (223.8 mAh g−1 at 50 mA g−1), excellent rate performance, and cycling stability (115.9 mAh g−1 after 2000 cycles at 1 A g−1).
Acaricides Resistance in Ticks: Selection, Diagnosis, Mechanisms, and Mitigation
Authors: Obaid Muhammad Kashif , Islam Nabila , Alouffi Abdulaziz , Khan Alam Zeb , da Silva Vaz Itabajara , Tanaka Tetsuya , Ali Abid
Published: July 2022

Ticks are blood-feeding ecto-parasites that have a cosmopolitan distribution in tropical and subtropical regions of the world. Ticks cause economic losses in the form of reduced blood, meat and dairy products, as well as pathogen transmission. Different acaricides such as organochlorines, organophosphates, formamidines (e.g. amitraz), synthetic pyrethroids, macrocyclic lactones, fipronil, and fluazuron are currently used sequentially or simultaneously to control tick infestations. Most acaricide treatments now face increasingly high chances of failure, due to the resistance selection in different tick populations against these drugs. Acaricide resistance in ticks can be developed in different ways, including amino acid substitutions that result in morphological changes in the acaricide target, metabolic detoxification, and reduced acaricide entry through the outer layer of the tick body. The current literature brings a plethora of information regarding the use of different acaricides for tick control, resistance selection, analysis of mutations in target sites, and resistance mitigation. Alternatives such as synergistic use of different acaricides, plant-derived phytochemicals, fungi as biological control agents, and anti-tick vaccines have been recommended to avoid and mitigate acaricide resistance. The purpose of this review was to summarize and discuss different acaricides applied for tick control, their mechanisms of action and resistance selection, genetic polymorphisms in their target molecules, as well as the approaches used for diagnosis and mitigation of acaricide resistance, specifically in Rhipicephalus microplus ticks.
Promoting Techno-Scientific Biomedical Communication in Russia: Pro-government Non-profit Organizations
Authors: Marchenko Alexander N. , Bykov Ilya A.
Published: July 2022

The rapidly expanding e-health market tends to reinvent the roles of science, entrepreneurship, and state. However, the results of such reinvention remain unclear. This study investigates the decade-long history (2011–2021) of the promotion of techno-scientific biomedical communication by pro-government non-profit organizations in Russia. In 2021, the World Bank pointed out that digital technologies have played a critical role in the pandemic in Russia and Russia's economic recovery is gathering pace. Thus, Russia tends to correspond to many other emerging health markets. We compare texts from non-profit organizations' websites and Facebook accounts with official state actions and the national mass media health agenda. The instruments that were used for text mining were topic modeling with latent Dirichlet allocation and an algorithm for keyphrase relationship visualization. The results revealed that promotion started no later than 2011 as a general private initiative in health. Throughout the state reforms and geopolitical crisis of 2014, in 2017–2019 digitalization was finally chosen as a model for the healthcare system. Simultaneously, the idea of digital reform for the health system was disseminated by the mass media. The pandemic drew attention to this communication, but it did not create significant change. Pro-government non-profit organizations continue to promote new directions for biomedical communication in Russia.
Percutaneous Retrieval of Left Atrial Appendage Closure Devices in Patients With Atrial Fibrillation: A Case Report
Authors: Wang Saihua , Zhang Juhua , Hao Shuwen , Zhu Luoning , Ning Zhongping , Zhao Zhihong
Published: July 2022

Left atrial appendage closure (LAAC) devices can be inadvertently released into unfavorable locations, which may allow them to migrate to a different position within the left atrial appendage or embolize from the heart into the aorta. In such instances, it can be challenging to remove the LAAC device. Here, we present two cases in which patients with atrial fibrillation experienced LAAC device exposure at an inappropriate site because of interventional operator error and device mismatch: (a) the LAAC device was dislodged into the aortic arch and retrieved percutaneously from the femoral artery route, and (b) in the left atrium, which was dislodged into the left atrium and retrieved via atrial transseptal puncture of the femoral vein.
A Perspective on a Quality Management System for AI/ML-Based Clinical Decision Support in Hospital Care
Authors: Bartels Richard , Dudink Jeroen , Haitjema Saskia , Oberski Daniel , van ‘t Veen Annemarie
Published: July 2022

Although many artificial intelligence (AI) and machine learning (ML) based algorithms are being developed by researchers, only a small fraction has been implemented in clinical-decision support (CDS) systems for clinical care. Healthcare organizations experience significant barriers implementing AI/ML models for diagnostic, prognostic, and monitoring purposes. In this perspective, we delve into the numerous and diverse quality control measures and responsibilities that emerge when moving from AI/ML-model development in a research environment to deployment in clinical care. The Sleep-Well Baby project, a ML-based monitoring system, currently being tested at the neonatal intensive care unit of the University Medical Center Utrecht, serves as a use-case illustrating our personal learning journey in this field. We argue that, in addition to quality assurance measures taken by the manufacturer, user responsibilities should be embedded in a quality management system (QMS) that is focused on life-cycle management of AI/ML-CDS models in a medical routine care environment. Furthermore, we highlight the strong similarities between AI/ML-CDS models and in vitro diagnostic devices and propose to use ISO15189, the quality guideline for medical laboratories, as inspiration when building a QMS for AI/ML-CDS usage in the clinic. We finally envision a future in which healthcare institutions run or have access to a medical AI-lab that provides the necessary expertise and quality assurance for AI/ML-CDS implementation and applies a QMS that mimics the ISO15189 used in medical laboratories.
Chemical Weathering of the Mekong River Basin With Implication for East Asian Monsoon Evolution During the Late Quaternary: Marine Sediment Records in the Southern South China Sea
Authors: Sang Pham Nhu , Liu Zhifei , Colin Christophe
Published: July 2022

Clay mineralogy, major-element geochemistry, and Sr-Nd isotopic compositions from Core MD05-2896 collected in the southern South China Sea have been utilized to investigate the discrimination of sediment provenance and to reconstruct a history of chemical weathering in the Mekong River basin over the last 45 ka. The results display that the clay mineral assemblage of the core is characterized by abundant smectite (27%–56%) and illite (18%–32%), with moderate kaolinite (13%–23%) and chlorite (11%–18%), and the 87Sr/86Sr ratio and εNd value narrowly vary in the ranges of 0.7232–0.7272 and from –10.9 to –9.6, respectively. According to clay mineralogy and Sr-Nd isotopic compositions, the Mekong River is the main terrigenous sedimentary source to the southern South China Sea, with no detectable change over the time span of the study, despite having strong sea-level fluctuations. Clay mineralogy and elemental geochemistry analyses reveal that higher smectite/(illite + chlorite), smectite/kaolinite, TiO2/K2O, and SiO2/K2O ratios during Marine Isotope Stage (MIS) 3 and 1 suggest enhanced chemical weathering, whereas lower values of these ratios during MIS 2 indicate weakened chemical weathering. These proxies reveal a close relationship with the available climate records of the East Asian monsoon evolution, implying that the chemical weathering in the Mekong River basin has been strongly controlled by the East Asian monsoon rainfall.
Multifractal Features of Particle-Size Distribution and Their Relationships With Soil Erosion Resistance Under Different Vegetation Types in Debris Flow Basin
Authors: Li Songyang , Gao Ruoyun , Huang Maowei , Yang Liusheng , Yu Hang , Yu Chenhui , Tian Xue , Li Jian , Lin Yongming
Published: July 2022

Understanding the influence of vegetation types on soil particle-size distribution (PSD) is essential to evaluate the effects of sediment control by vegetation restoration. In this work, we studied the effects of different vegetation types, including bare land, meadow, shrub and forest on soil PSD in Jiangjiagou gully, Yunnan province, China. A total of 60 soil samples were collected and analyzed for soil particle size distribution using the laser diffraction method. Fractal theory was used to calculate multifractal parameters. The volume fraction of silt particles in shrub and forest is significantly higher than that in bare land, meadow, whereas the total volume fraction of sand particles in bare land and meadow exceed that in shrub and forest. The soil particle size distribution along soil layers has no significant difference in each vegetation type. The volumetric fractal dimension is significantly higher in forest and shrub than in bare land and grassland, but there is no significant difference between forest and shrub. In addition, soil erosion resistance exhibits significant differences of forest > shrub > grassland > bare land. Multifractal parameters are highest in bare land except for multifractal spectrum values (f (αmax) and f (αmin)) and the maximum value of singularity index (αmin). All generalized dimensions spectra curves of the PSD are sigmoidal, whereas the singular spectrum function shows an asymmetric upward convex curve. Furthermore, soil erosion resistance has significant relationships with multifractal parameters. Our results suggest that multifractal parameters of the soil PSD can predict its anti-ability to erosion. This study also provides an important insight for the evaluation of soil structure improvement and the effects of erosion control by vegetation restoration in dry-hot valley areas.
Student Teachers’ Video-Assisted Collaborative Reflections of Socio-Emotional Experiences During Teaching Practicum
Authors: Näykki Piia , Laitinen-Väänänen Sirpa , Burns Eila
Published: July 2022

This study explores video as a tool for student teachers in reflecting upon their own teaching practice. The particular interest is in exploring, what kind of socio-emotional experiences did the student teachers describe during the video-assisted collaborative reflection and what benefits student teachers experienced through the video-assisted collaborative reflections? The study implements a video-observation model (Participatory and Empowering Video Analysis- model, PEVA™) developed for a professional teacher education programme and investigates the model from student teachers’ perspective. The participants are student teachers in an international professional teacher education programme (n = 24) at a university of applied sciences. Student teachers video recorded their own teaching sessions displaying their work in different roles: teacher-led content specific instructions, group working sessions and individual student guidance and tutoring sessions. Student teachers were advised to annotate their own videos with a video-reflection tool by focussing on socio-emotional interactions, non-verbal elements of interaction and moments, where students felt successful and empowered. In addition to self-reflection, videos were viewed and annotated by a peer student and a teacher educator. After the phases of reviews and annotations (self-,peer-, and teacher annotations), an hour-long collaborative reflective feedback discussion was held either face-to-face or online. These sessions were facilitated by the teacher educator, involving the videoed student and the reviewing peer. Video annotation data was transcribed, and, in addition, the student teachers’ reflective writings (54 pages) and teacher educators’ notes of the reflective feedback sessions (20 pages) were used as data. The results of this study indicate that student teachers viewed the video reflection process as helpful in making socio-emotional experiences visible and tangible. The video annotation tool was recognised as useful for indicating socio-emotional experiences and making them more concrete thus resources for reflection. A combination of own, peer’s and teachers’ annotations functioned as a collaborative tool for increasing awareness of different socio-emotional experiences. By observing videos of their own teaching as well as teaching videos of their peers, student teachers were able to evaluate teaching situations holistically and observe connections of their own socio-emotional behaviours to their students.
Statistical Power of Piecewise Regression Analyses of Single-Case Experimental Studies Addressing Behavior Problems
Authors: Wilbert Jürgen , Börnert-Ringleb Moritz , Lüke Timo
Published: July 2022

In intervention research, single-case experimental designs are an important way to gain insights into the causes of individual changes that yield high internal validity. They are commonly applied to examine the effectiveness of classroom-based interventions to reduce problem behavior in schools. At the same time, there is no consensus on good design characteristics of single-case experimental designs when dealing with behavioral problems in schools. Moreover, specific challenges arise concerning appropriate approaches to analyzing behavioral data. Our study addresses the interplay between the test power of piecewise regression analysis and important design specifications of single-case research designs. Here, we focus on the influence of the following specifications of single-case research designs: number of measurement times, the initial frequency of the behavior, intervention effect, and data trend. We conducted a Monte-Carlo study. First, simulated datasets were created with specific design conditions based on reviews of published single-case intervention studies. Following, data were analyzed using piecewise Poisson-regression models, and the influence of specific design specifications on the test power was investigated. Our results indicate that piecewise regressions have a high potential of adequately identifying the effects of interventions for single-case studies. At the same time, test power is strongly related to the specific design specifications of the single-case study: Few measurement times, especially in phase A, and low initial frequencies of the behavior make it impossible to detect even large intervention effects. Research designs with a high number of measurement times show robust power. The insights gained are highly relevant for researchers in the field, as decisions during the early stage of conceptualizing and planning single-case experimental design studies may impact the chance to identify an existing intervention effect during the research process correctly.
Prognostic Factors of Small Non-Functional Pancreatic Neuroendocrine Tumors and the Risk of Lymph Node Metastasis: A Population-Level Study
Authors: Tan Qingquan , Wang Xing , Li Yichen , Liu Yingyi , Liu Xubao , Ke Nengwen
Published: July 2022

Background

Small non-functional neuroendocrine tumors (NF-PNETs) are a heterogeneous subset of tumors with controversy regarding their optimal management. We aimed to analyze the prognostic factors of patients with small NF-PNETs and create a risk score for lymph node metastasis (LNM).

Methods

Data of 751 patients with NF-PNETs ≤ 2 cm were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate survival analysis was performed to analyze the prognostic factors. Logistic regression was used to identify risk factors for LNM.

Results

Of the 751 patients, 99 (13.2%) were confirmed to have LNM. In multivariate survival analysis, LNM (hazard ratio [HR], 2.12; 95% CI, 1.04–4.32, p = 0.040) was independently associated with disease-specific survival. Logistic regression identified that tumor location in the head of the pancreas (odds ratio [OR], 4.33; 95% CI, 2.75–6.81; p < 0.001), size ≥ 1.5–2 cm (OR, 1.84; 95% CI, 1.17–2.87; p = 0.009), and grade III–IV (OR, 7.90; 95% CI, 1.79–34.90; p = 0.006) were independent risk factors of LNM. According to the OR value, the risk of LNM was scored as follows: a score of 1 for tumors located in the body/tail of the pancreas and 4 for those located in the head; a score of 1 for tumors <1 cm and 2 for those ≥1.5–2 cm; and a score of 1 for tumors with grade I–II and 8 for those with grade III–IV. Finally, the median score for this cohort was 4, with an interquartile range of 3–6. Therefore, patients were classified as three groups based on the risk score system: a total score of 1–3 for low risk, 4–6 for intermediate risk (OR, 2.98; 95% CI, 1.59–5.60; p = 0.001), and 7–14 for high risk (OR, 8.94; 95% CI, 4.50–17.7; p < 0.001), with an incidence of LNM 5.0%, 13.5%, and 31.8%, respectively (p < 0.001).

Conclusion

Surgical resection with regional lymphadenectomy is recommended for small NF-PNETs with malignant potential of LNM. A risk score for LNM based on tumor grade, location, and size may preoperatively predict LNM of small NF-PNETs and guide clinical practice.
Assessing the Diet of a Predator Using a DNA Metabarcoding Approach
Authors: Wang Qiaoyun , Wang Zichen , Zheng Kaidan , Zhang Peng , Shen Limin , Chen Wanli , Fan Pengfei , Zhang Lu
Published: July 2022

The diet of top predators is vital information needed to determine their ecological function and for their conservation management. However, the elusive habit and low population density of many predators constrains determination of their diets. While the morphological identification of scat contents is the traditional method, DNA metabarcoding has lately proven a more efficient and accurate method of identifying prey taxa. We applied DNA metabarcoding to analyzing the diet of the Eurasian otter (Lutra lutra), a top predator in freshwater ecosystems, using 12S and 16S rRNA mitochondrial primers target vertebrate prey. Diet did not vary among different data removal thresholds of 0.1, 1, 3, and 5%, comprising fishes (>90%), amphibians and birds (>2%), and occasionally mammals (<2%). Both 12S and 16S primers revealed similar otter diets, indicating that a single set of primers with a higher threshold is cost-effective for detecting the main prey taxa. Using 12S primers and a 5% threshold, we found no seasonal variation of otter diet in the Tangjiahe National Nature Reserve. A different prey community was found outside the reserve, which resulted in different prey composition for otters. However, prey taxon richness was not different between otters in- and outside the reserve. Otters preferred Schizothorax spp., the largest-sized fish species in the reserve, whereas they mainly preyed on Triplophysa bleekeri, a small-sized fish species, outside the reserve. Otters’ flexible feeding strategy reflect their high adaptability. However, greater human disturbance outside the reserve may present significant challenges to otters by altering prey communities and reducing prey profitability. Combining fecal DNA metabarcoding and local fish survey will provide opportunities for more detailed studies on the impact of different levels of human disturbances on prey communities and otters.
BTN3A2 Expression Is Connected With Favorable Prognosis and High Infiltrating Immune in Lung Adenocarcinoma
Authors: Lin Yuansheng , Zhou Hao , Li Shengjun
Published: July 2022

Background: Butyrophilin subfamily 3 member A2 (BTN3A2) is an important mediator in immune activation, and it is reported to be linked to many cancer progresses. However, the relation with infiltrating immune and prognosis of BTN3A2 in lung adenocarcinoma are not clear.

Methods: In our study, we checked the mRNA expression and protein expression profile of BTN3A2 in lung adenocarcinoma (LUAD) and its relation to clinical outcomes using TIMER and UALCAN databases. In addition, we analyzed the survival of BTN3A2 in LUAD using the Kaplan–Meier Plotter database and PrognoScan database. Moreover, we analyzed gene set enrichment analysis (GSEA) of the BTN3A2. Next, we explored the relation of BTN3A2 expression with the immune infiltration by TIMER. At last, in order to enrich the regulatory mechanism of BTN3A2, we used miRarbase, starbase, and miRDB databases to look for miRNA targets of BTN3A2.

Results: The mRNA along with the protein expression of BTN3A2 in the LUAD group was lower than that in the normal group. In addition, high BTN3A2 expression was connected with good first progression (FP) and overall survival (OS) in LUAD. Then, the GSEA analysis demonstrated that T-cell receptor signaling cascade, B-cell receptor signaling cascade, natural killer cell–mediated cytotoxicity, immune receptor activity, immunological synapse, and T-cell activation were enriched differentially in the BTN3A2 high expression phenotype of LUAD. Moreover, BTN3A2 expression is a remarkable positive correlation with invading levels of tumor purity, B cells, neutrophils, CD4+ T cells, dendritic cells, macrophages, and CD8+ T cells in LUAD, and B cells and dendritic cells were linked with a good prognosis of LUAD. To further enrich the possible regulatory mechanisms of BTN3A2, we analyzed the miRNA targets. The results showed that hsa-miR-17-5p may be miRNA targets of BTN3A2.

Conclusion: Taking together, we provide evidence of BTN3A2 as possible prognosis biomarkers of LUAD. In addition, high BTN3A2 expression in LUAD may influence the prognosis because of immune invasion. Moreover, our findings provide a potential mechanism that hsa-miR-17-5p may be miRNA targets of BTN3A2.
Artificial Intelligence, Healthcare, Clinical Genomics, and Pharmacogenomics Approaches in Precision Medicine
Authors: Abdelhalim Habiba , Berber Asude , Lodi Mudassir , Jain Rihi , Nair Achuth , Pappu Anirudh , Patel Kush , Venkat Vignesh , Venkatesan Cynthia , Wable Raghu , Dinatale Matthew , Fu Allyson , Iyer Vikram , Kalove Ishan , Kleyman Marc , Koutsoutis Joseph , Menna David , Paliwal Mayank , Patel Nishi , Patel Thirth , Rafique Zara , Samadi Rothela , Varadhan Roshan , Bolla Shreyas , Vadapalli Sreya , Ahmed Zeeshan
Published: July 2022

Precision medicine has greatly aided in improving health outcomes using earlier diagnosis and better prognosis for chronic diseases. It makes use of clinical data associated with the patient as well as their multi-omics/genomic data to reach a conclusion regarding how a physician should proceed with a specific treatment. Compared to the symptom-driven approach in medicine, precision medicine considers the critical fact that all patients do not react to the same treatment or medication in the same way. When considering the intersection of traditionally distinct arenas of medicine, that is, artificial intelligence, healthcare, clinical genomics, and pharmacogenomics—what ties them together is their impact on the development of precision medicine as a field and how they each contribute to patient-specific, rather than symptom-specific patient outcomes. This study discusses the impact and integration of these different fields in the scope of precision medicine and how they can be used in preventing and predicting acute or chronic diseases. Additionally, this study also discusses the advantages as well as the current challenges associated with artificial intelligence, healthcare, clinical genomics, and pharmacogenomics.
The Pea R2R3-MYB Gene Family and Its Role in Anthocyanin Biosynthesis in Flowers
Authors: Yang Yating , Yuan Zhuo , Ning Conghui , Zhao Baoling , Wang Ruoruo , Zheng Xiaoling , Liu Yu , Chen Jianghua , He Liangliang
Published: July 2022

Pea (Pisum sativum L.) is one of the most important legume crops in the world, and it has attracted great attention for its high nutritive values. Recently, the crop breeding program has been focused on the crop metabolic engineering (i.e., color, flavor, nutrition) to improve the quality of crop. As a major group of transcription factors forming the ternary MYB–bHLH–WD repeat protein (MBW) complex to regulate the anthocyanin biosynthesis pathway, members of R2R3-MYB gene family have always been the focus of research targets to improve the valuable metabolic product of crops. Until now, few report about the R2R3-MYB gene family of pea has been released. In this study, we identified 119 R2R3-MYB genes in the assembled pea genome (Version 1a), of which 111 were distributed across 14 chromosomes. Combining with the 126 R2R3-MYB protein sequences of Arabidopsis, we categorized 245 R2R3-MYB proteins into 36 subgroups according to sequence similarity and phylogenetic relationships. There was no member from subgroup 12, 15 and 29 existing in pea genome, whereas three novel subgroups were found in pea and named as N1-N3. Further analyses of conserved domains and Motifs, gene structures, and chromosomal locations showed that the typical R2 and R3 domains were present across all R2R3-MYB proteins, and Motif 1, 2, and 3 were identified in most members. Most of them had no more than two introns. Additionally, 119 pea R2R3-MYB genes did not experience large-scale duplication events. Finally, we concluded that several candidate genes may be responsible for the spatiotemporal accumulation of anthocyanins in pea petals. PsMYB116 was predominantly expressed in the dorsal petals to presumably activate the anthocyanin biosynthesis pathway, while PsMYB37 and PsMYB32 may positively regulates the anthocyanin accumulation in the lateral petals. This study not only provides a good reference to further characterize the diverse functions of R2R3-MYB genes but also helps researchers to understand the color formation of pea flowers.
Early Response Assessment in Advanced Stage Melanoma Treated with Combination Ipilimumab/Nivolumab
Authors: Ma Vincent T. , Chamila Perera Alahendra A. , Sun Yilun , Sitto Merna , Waninger Jessica J. , Warrier Govind , Green Michael D. , Fecher Leslie A. , Lao Christopher D.
Published: July 2022

Background

Standard combination ipilimumab/nivolumab (I/N) is given as 4 induction doses for advanced stage melanoma followed by nivolumab single-agent maintenance therapy. While many patients receive less than 4 doses due to immune-related toxicities, it is unclear if fewer doses of I/N may still provide long term clinical benefit. Our aim is to determine if response assessment after 1 or 2 doses of I/N can predict long-term survival and assess if fewer doses of I/N can lead to similar survival outcomes.

Methods

We performed a retrospective analysis on a cohort of patients with advanced melanoma who w0ere treated with standard I/N. Cox regression of progression-free survival (PFS) and overall survival (OS) models were performed to assess the relationship between response after 1 or 2 doses of I/N and risk of progression and/or death. Clinical benefit response (CBR) was assessed, defined as SD (stable disease) + PR (partial response) + CR (complete response) by imaging. Among patients who achieved a CBR after 1 or 2 doses of I/N, a multivariable Cox regression of survival was used to compare 1 or 2 vs 3 or 4 doses of I/N adjusted by known prognostic variables in advanced melanoma.

Results

199 patients were evaluated. Patients with CBR after 1 dose of I/N had improved PFS (HR: 0.16, 95% CI 0.08-0.33; p<0.001) and OS (HR: 0.12, 0.05-0.32; p<0.001) compared to progressive disease (PD). Patients with CBR (vs PD) after 2 doses of I/N also had improved PFS (HR: 0.09, 0.05-0.16; p<0.001) and OS (HR: 0.07, 0.03-0.14; p<0.001). There was no survival risk difference comparing 1 or 2 vs 3 or 4 doses of I/N for PFS (HR: 0.95, 0.37-2.48; p=0.921) and OS (HR: 1.04, 0.22-4.78; p=0.965).

Conclusions

Early interval imaging with response during induction with I/N may be predictive of long-term survival in advanced stage melanoma. CBR after 1 or 2 doses of I/N is associated with favorable survival outcomes, even in the setting of fewer I/N doses received. Further studies are warranted to evaluate if electively administering fewer combination I/N doses despite tolerance in select patients may balance the benefits of therapy while decreasing toxicities.
The Culture Dish Surface Influences the Phenotype and Dissociation Strategy in Distinct Mouse Macrophage Populations
Authors: Song Qiaoling , Zhang Yazhuo , Zhou Mingming , Xu Yuting , Zhang Qianyue , Wu Lihong , Liu Shan , Zhang Minghui , Zhang Lei , Wu Zhihua , Peng Weixun , Liu Xutao , Zhao Chenyang
Published: July 2022

The nature of the culture dish surface and the technique used to detach adherent cells could very likely influence the cell viability and cell membrane protein integrity of harvested macrophages. Several previous studies assessed the detachment efficacies of enzymatic and non-enzymatic methods for harvesting the single cell suspensions of macrophages, but a comprehensive study assessing different dissociation methods and culture conditions for detaching functionally different macrophage populations has not yet been reported. In this study,viathe well-established GM-CSF and M-CSF differentiated bone marrow derived macrophage models (GM-BMDMs and M-BMDMs), we compared four commonly used enzymatic (trypsin and accutase) and non-enzymatic (PBS and EDTA) dissociation methods along with necessary mechanical detaching steps (scraping and pipetting) to evaluate the viable cell recovery and cell surface marker integrality of GM-BMDMs and M-BMDMs cultured on standard cell culture dish (TC dish), or on culture dish (noTC dish) that was not conditioned to enhance adherence. The data showed that accutase yielded a better recovery of viable cells comparing with PBS and EDTA, especially for tightly adherent GM-BMDMs on TC dishes, with a relatively higher level of detected cell membrane marker F4/80 than trypsin. An additional gradient centrifugation-based dead cell removal approach could increase the proportion of viable cells for TC cultured GM-BMDMs after accutase dissociation. Furthermore, transcriptome analysis was performed to evaluate the putative influence of culture dishes. At steady state, BMDMs cultured on noTC dishes exhibited more proinflammatory gene expression signatures (e.g. IL6, CXCL2 and ILlβ) and functions (e.g. TNF and IL17 signaling pathways). Similar inflammatory responses were observed upon LPS challenge regardless of culture conditions and differentiation factors. However, in LPS treated samples, the difference of gene expression patterns, signaling pathways and molecular functions between TC and noTC cultured BMDMs were largely dependent on the types of growth factors (M-CSF and GM-CSF). This observation might provide valuable information forin vitromacrophage studies.
The Contribution of Neutrophils and NETs to the Development of Type 1 Diabetes
Authors: Petrelli Alessandra , Popp Sarah K. , Fukuda Riho , Parish Christopher R. , Bosi Emanuele , Simeonovic Charmaine J.
Published: July 2022

Type 1 diabetes (T1D) is an autoimmune disease resulting from the destruction of insulin-producing beta cells in pancreatic islets. T lymphocytes are the claimed pathogenic effectors but abnormalities of other immune cell types, including neutrophils, also characterize T1D development. During human T1D natural history, neutrophils are reduced in the circulation, while accumulate in the pancreas where release of neutrophil extracellular traps (NETs), or NETosis, is manifest. Recent-onset T1D patients also demonstrate activated circulating neutrophils, associated with a unique neutrophil gene signature. Neutrophils can bind to platelets, leading to the formation of platelet-neutrophil aggregates (PNAs). PNAs increase in the circulation during the development of human T1D and provide a mechanism for neutrophil activation and mobilization/recruitment to the pancreas. In non-obese diabetic or NOD mice, T1D autoimmunity is accompanied by dynamic changes in neutrophil numbers, activation state, PNAs and/or NETosis/NET proteins in the circulation, pancreas and/or islets. Such properties differ between stages of T1D disease and underpin potentially indirect and direct impacts of the innate immune system in T1D pathogenesis. Supporting the potential for a pathogenic role in T1D, NETs and extracellular histones can directly damage isolated islets in vitro, a toxicity that can be prevented by small polyanions. In human T1D, NET-related damage can target the whole pancreas, including both the endocrine and exocrine components, and contribute to beta cell destruction, providing evidence for a neutrophil-associated T1D endotype. Future intervention in T1D could therefore benefit from combined strategies targeting T cells and accessory destructive elements of activated neutrophils.
Essential Oils From Five Local Plants: An Alternative Larvicide for Anopheles gambiae s.l. (Diptera: Culicidae) and Aedes aegypti (Diptera: Culicidae) Control in Western Burkina Faso
Authors: Balboné Mahamoudou , Soma Dieudonné Diloma , Namountougou Moussa , Drabo Samuel Fogné , Konaté Hamadou , Toe Oumarou , Bayili Koama , Meda Georges Benson , Dabiré Roch Kounbobr , Gnankine Olivier
Published: July 2022

Introduction

Malaria and dengue are two main vector-borne infectious diseases transmitted by Anopheles gambiae and Aedes aegypti, respectively, in tropical and subtropical regions. The concern for environmental safety and the increasing development of resistance to the chemical in main arthropod vectors raises interest in the search for botanicals such as essential oils (EOs) that can be used in vector control.

Methods

Larvicidal bioassays were performed according to the WHO standard methods using Ae. aegypti and An. gambiae larvae collected from Bobo-Dioulasso and in the Kou Valley (VK), respectively, two areas located in Houet Province of western Burkina Faso. Kisumu and Bora bora, the susceptible strains of An. gambiae and Ae. aegypti, respectively, were used as controls. OEs extracted from leaves of five aromatic plants, Cymbopogon citratus, Cymbopogon nardus, Eucalyptus camaldulensis, Lippia multiflora, and Ocimum americanum, naturally growing in Burkina Faso were tested. The pyriproxyfen was used as a positive control.

Results

As a result, the lethal concentrations (LC50) for Ae. aegypti from Bobo-Dioulasso and An. gambiae from VK ranged from 41.9 to 103.8 ppm and 39.5 to 138.1 ppm, respectively. As for LC90 values, they ranged from 74.6 to 311.3 ppm for Ae. aegypti from Bobo-Dioulasso and from 90.2 to 328.9 ppm for An. gambiae from VK. Among the EOs tested, L. multiflora showed the highest activity against all the strains of An. gambiae and Ae. aegypti larvae. No difference in terms of LC50 values was found between L. multiflora and pyriproxyfen used as a positive control on An. gambiae larvae. It is not the case for Aedes aegypti populations, where pyriproxyfen remains the most toxic. Overall, An. gambiae populations were the most susceptible to EOs tested as compared to Ae. aegypti populations.

Conclusion

Our study furthers our knowledge of the larvicidal activity of EOs in the western part of Burkina and opens new avenues in their putative use in vector control strategies.
Association of Exercise With Vascular Function in Patients With CKD: A Meta-Analysis of Randomized Controlled Trials
Authors: Wang Huan , Xie Dengpiao , Wu Lisheng , Zhao Liangbin
Published: July 2022

Background and Aim

Vascular function is associated with an increased risk of cardiovascular events in patients with chronic kidney disease (CKD). Whether exercise improves vascular function in such patients remains controversial. This study aimed to conduct a meta-analysis on the effect of exercise training on the vascular function of patients with CKD.

Methods

Embase, the Cochrane Central Register of Controlled Trials, and Medline were searched from inception until November 15, 2021. The terms exercise, CKD, dialysis, kidney transplant, and randomized controlled trial (RCT) were searched alone or in combination. RCTs were included when studies compared exercise with active control, usual care, or no intervention, and the studies reported vascular function on patients with CKD.

Results

This meta-analysis included 18 RCTs with 817 patients. Exercise training was significantly associated with decreased pulse wave velocity weighted mean difference (WMD), −0.56; 95% confidence interval (CI), −1.02 to −0.09, P = 0.02 and augmentation index (WMD, −3.26; 95% CI, −5.46 to −1.05, P = 0.004). It was also significantly associated with improved peak VO2 (WMD, 2.64; 95% CI, 1.94–3.35, P < 0.00001), general health (WMD, 7.03; 95% CI, 0.65–13.42, P = 0.03), and vitality (WMD, 9.1; 95% CI, 2.50–15.69, P = 0.007).

Conclusions

The meta-analysis suggested that exercise training improved vascular function in patients with CKD. An exercise program should be considered as one of the management strategies for vascular dysfunction in patients with CKD. Further studies are needed to demonstrate that exercise training improves cardiovascular diseases in patients with CKD.