bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantifying a stopover of killer whales preying on gray whales rounding the Alaska Peninsula
Authors: Durban JW , Matkin CO , Ellifrit DK , Andrews RD , Barrett-Lennard LG
Published: October 2023

Predation by killer whales Orcinus orca on recovering populations of baleen whales is being increasingly reported, but there have been no direct quantitative assessments of its importance, for either the predators or prey. We used photographic mark-recapture and satellite telemetry to assess the abundance and behavior of killer whales gathering to feed on gray whale Eschrichtius robustus calves and juveniles that were migrating around the Alaska Peninsula into the Bering Sea. We quantitatively describe this aggregation as a stopover, used in May and early June 2003-2008 by at least 197 different killer whales. Estimates of average stopover duration (1.8-3.6 wk) and annual abundance (89-128 killer whales) were variable and correlated with annual gray whale calf production (404-1528 calves). In years with more gray whale calves, killer whales spent more time at this geographic pinch point where they could presumably access adequate prey. In years with fewer calves, more killer whales used the study area but remained for a shorter time, presumably searching more widely when calves were scarcer. The presence of killer whales increased through May into early June, when satellite tags tracked northerly movements into the Bering Sea, and as far as 1620 km into the Chukchi Sea, likely following migrating gray whales. These data indicate focused and prolonged predation by killer whales on a recovered population of baleen whales and provide the first evidence of the importance of such predation in structuring killer whale populations and influencing their dynamics.
Through the Eyes of Attackers: A Comprehensive Analysis of Cybersecurity Strategies in International Relations
Authors: RUGİNA Juma Mdimu
Published: October 2023

In this interconnected global landscape, where technology forms the foundation of diplomatic interactions, understanding the complicated methodologies of cyber attackers has become of utmost importance. This study delves into the core of worldwide cybersecurity, introducing a unique viewpoint that involves an exploration of offensive tactics from the vantage point of those orchestrating attacks. Employing an interdisciplinary methodology, the research amalgamates case studies, expert publications, and the analysis of threat intelligence to decode the incentives, strategies, and aspirations of these digital assailants. By closely examining historical events like the Stuxnet incident, the investigation reveals the evolution of offensive cyber activities and their consequences in the international relations field. Through a comprehensive assessment of attack avenues, techniques, and the motivations driving attackers, this analysis brings to light the complicated interaction between cybersecurity, global politics, and the stability of nations. By anticipating emerging trends in cyber threats and delving into regional perspectives, this study offers a forward-focused outlook on the challenges and possibilities that lie on the horizon. Ultimately, this research emphasizes the pressing requirement for international collaboration, innovative policy development, and proactive measures to navigate the complex terrain of offensive cyber tactics and to ensure the preservation of the future landscape of international relations.
PENGEMBANGAN INSTRUMEN SOAL PILIHAN GANDA BERBANTU APLIKASI QUIZIZZ MATERI SISTEM PERNAPASAN PADA MANUSIA UNTUK PESERTA DIDIK KELAS VIII SMP
Authors: Riza Ardania  , Lina Arifah Fitriyah  , Nur Kuswanti
Published: October 2023

Abstract: The Covid-19 pandemic has caused the evaluation process to be different from before. This is due to the inability to meet face-to-face between teachers and students. One of the supporting applications that can be used is quizizz. This study aims to (1) describe the process of developing multiple-choice instruments with the help of quizizz applicaton. (2) describe the product developed after the validation process. This research is a development research using the ADDIE development model (Analyze, Design, Development, Implementation, and Evaluation). The question instrument developed consists of 20 multiple choice questions and is equipped with operating instructions for quizizz application. The development data obtained were analyzed descriptively and quantitatively. The results of the development of the multiple-choice instrument with the help of quizizz application after validation showed that the multiple-choice instrument was stated to be very good with a percentage of 99.3%. Based on the results of the expert test, the multiple-choice instrument assisted by theapplication quizizz can be applied to students.

Keywordsâ€‹: â€‹â€‹development, multiple choice question, quizizz.
Carpal bone replacement using personalized 3D printed tantalum prosthesis
Authors: Zhang Changgui , Chen Hao , Fan Huaquan , Xiong Ran , He Rui , Huang Chengjun , Peng Yang , Yang Pengfei , Chen Guangxing , Wang Fuyou , Yang Liu
Published: October 2023

Objective:Scaphoid and lunate fractures have a relatively high incidence rate. Traditional carpectomy and carpal arthrodesis in the treatment of carpal osteonecrosis will lead to many complications. Three-dimensional (3D) printed tantalum has good biocompatibility and can be designed to match the patient’s personalized anatomical carpal structure. This study aims to investigate carpal function and prosthesis-related conditions after carpal bone replacement using 3D printed tantalum prostheses.

Methods:From July 2020 to January 2022 at our center, seven patients with osteonecrosis of the carpus received carpal bone replacement using 3D printed tantalum prosthesis. The Disability of the Arm, Shoulder and Hand (DASH) score and patient satisfaction, as well as the Mayo Wrist Scores (Cooney method, modified Green, and O’Brien wrist score), were used to evaluate the preoperative and postoperative wrist function of patients. The Visual Analog Scale (VAS) pain scores were also recorded before and after surgery. The angles of flexion, dorsiflexion, ulnar deviation, and radial deviation were measured using an arthrometer. The grip strength and pinch strength of the operated hand after carpal bone replacement and the contralateral healthy carpus were measured using a dynamometer. Radiographs were taken to confirm the condition and complications of the tantalum prosthesis.

Results:All seven patients were followed for 19.6 ± 2.7 months. At the last follow-up, the grip strength of the operated wrist joint after carpal bone replacement was 33.4 ± 2.3 kg, the pinch strength was 8.9 ± 0.7 kg, the flexion was 54.6° ± 0.8°, the dorsiflexion was 54.7° ± 1.7°, the ulnar deviation was 34.6° ± 1.9°, and the radial deviation was 25.9° ± 0.8°, all of which showed no statistically significant difference with the contralateral healthy carpus (p> 0.05). There were significant differences in the VAS, DASH, and MAYO scores between the preoperative and the last follow-up (p< 0.01). Patients had reduced postoperative pain and improved wrist function and range of motion (ROM), and the tantalum prostheses were stable.

Conclusion:The 3D printed tantalum brings us new hope, not only for hip or knee replacement, but also for joint replacement of other complex anatomical structures, and patients with other irregular bone defects such as bone tumors and deformity, which could realize personalized treatment and precise medicine.
The emerging role of m6A modification of non-coding RNA in gastrointestinal cancers: a comprehensive review
Authors: Wang Meiqi , Liu Zhuo , Fang Xuedong , Cong Xianling , Hu Yue
Published: October 2023

Gastrointestinal (GI) cancer is a series of malignant tumors with a high incidence globally. Although approaches for tumor diagnosis and therapy have advanced substantially, the mechanisms underlying the occurrence and progression of GI cancer are still unclear. Increasing evidence supports an important role for N6-methyladenosine (m6A) modification in many biological processes, including cancer-related processes via splicing, export, degradation, and translation of mRNAs. Under distinct cancer contexts, m6A regulators have different expression patterns and can regulate or be regulated by mRNAs and non-coding RNAs, especially long non-coding RNAs. The roles of m6A in cancer development have attracted increasing attention in epigenetics research. In this review, we synthesize progress in our understanding of m6A and its roles in GI cancer, especially esophageal, gastric, and colorectal cancers. Furthermore, we clarify the mechanism by which m6A contributes to GI cancer, providing a basis for the development of diagnostic, prognostic, and therapeutic targets.
Recent advances in synthesizing and utilizing nitrogen-containing heterocycles
Authors: Ha Hyun-Joon
Published: October 2023

The use of organocatalysts and a pot economy has strengthened recent organic syntheses. Synthetic methodologies may be applicable in laboratory preparation or in the industrial production of valuable organic compounds. In most cases, synthetic challenges are overcome by highly efficient and environmentally benign organocatalysts in a pot-economical manner. This is exemplified by the recent synthesis of tetrahydropyridine-containing (−)-quinine.
An improved method for large scale generation and high-throughput functional characterization of human iPSC-derived microglia
Authors: Padmakumar Manisha , Biesmans Steven , Valadas Jorge S. , Detrez Jan R. , Gillet Gaëlle , Bresler Priscillia , Clénet Marie-Laure , Kadiu Irena
Published: October 2023

Neuroscience drug discovery has faced significant challenges due to restricted access to relevant human cell models and limited translatability of existing preclinical findings to human pathophysiology. Induced pluripotent stem cells (iPSCs) have emerged as a promising solution, offering the potential to generate patient-specific cell types, including in the recent years, iPSC-derived microglia (iMGL). Current methods rely on complex and time-consuming differentiation procedures, leading to considerable batch-to-batch variability consequently hindering the establishment of standardized and reproducible high-throughput functional screening approaches. Addressing these challenges is critical in ensuring the generation of homogenous iMGL populations with consistent functional properties. In this study we describe an improved high-yield protocol for generating iMGL, which allows for increased reproducibility and flexibility in the execution of high-throughput functional screens. We introduce a two-step process in embryoid bodie (EB) maintenance and a stop point allowing for cryopreservation at the hematopoietic progenitor cell (iHPC) stages. Furthermore, we demonstrate inter-operator robustness of this modified protocol in a range of high-throughput functional assays including phagocytosis, lysosomal acidification, chemotaxis, and cytokine release. Our study underscores the importance of quality control checks at various stages of iPSC-differentiation and functional assay set up, highlighting novel workarounds to the existing challenges such as limited yield, flexibility, and reproducibility, all critical in drug discovery.
Notable changes in geochemical and mineralogical characteristics of different phases of episyenitization: insights on the radioactive and shielding of the late phase
Authors: Taalab Sherif A. , Zakaly Hesham M. H. , Ivanov V. , Alrowaily Albandari W. , Awad Hamdy A. , Abed Neveen S. , Issa Shams A. M. , Eltohamy Amira M. , Ene Antoaneta
Published: October 2023

Kab Amiri granites are submitted to post-magmatic hydrothermal solutions through fracture and faults, causing several alteration processes. The most common processes are episyenitization, saussuritization, hematitization, sericitization, kaolinization, albitization, chloritization, silicification, and muscovitization. Kab Amiri granites are vuggy, with the vugs partially to completely refilled with new constituents. The least episyenitized granites have elevated amounts of Fe, P, Zr, Ni, U, Th, Ba, Y, Hf, Nb, and As, which are correlated with their mobilization from biotite, k-feldspar, plagioclase and metamict zircon. These elemental changes are related the partial albitization, muscovitization, desilicification and chloritizatiom, which lead to the mobilization of these elements and forming of specific mineral association in the least altered granites such as autonite, tripiolite, columbite, Zircon and galena. On the second stage, granites were subjected to intense alteration processes by mineralizing fluids, causing wholly muscovitization of biotite and feldspar, albitization of plagioclase, carbonitization and apatitization. Many elements were mobilized from these altered minerals, including Ti, Al, Mn, Mg, Ca, Na, K, Mo, Cu, Pb, Zn, Ag, Co, Sr, V, Cr, Sn, Rb, Ta, Li, Sc, W, S, In, and Tl, leading to definite mineralization as kaslite, monazite, xenotime, polycrase and apatite. The mineralizing fluids in the least and highly episyenitized granites are incorporated in some ore minerals like uranophane, fergusonite, bazzite and garnet. Notably, the presence of elements such as U, Th, and other heavy metals in Kab Amiri granites highlights the potential for these rocks in radiation shielding applications. The unique combination of elements and minerals resulting from the alteration processes can be leveraged for developing new materials or enhancing existing materials used in radiation shielding.
The short- and long-term readmission of four major categories of digestive system cancers: does obesity or metabolic disorder matter?
Authors: Li Yan , Wu Xiaoqin , Song Yongfeng , Wang Peipei , Zhang Bofei , Guo Bingzhou , Liu Ziwei , Wu Yafei , Shao Shanshan , Cheng Yiping , Guo Honglin , Fan Xiude , Zhao Jiajun
Published: October 2023

Purpose

Patients with digestive system cancers (DSCs) are at a high risk for hospitalizations; however, the risk factors for readmission remain unknown. Here, we established a retrospective cohort study to assess the association between metabolic obesity phenotypes and readmission risks of DSC.

Experimental design

A total of 142,753 and 74,566 patients at index hospitalization were ultimately selected from the Nationwide Readmissions Database (NRD) 2018 to establish the 30-day and 180-day readmission cohorts, respectively. The study population was classified into four groups: metabolically healthy non-obese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy non-obese (MUNO), and metabolically unhealthy obese (MUO). Multivariate Cox regression analysis was used to estimate the effect of metabolic obesity phenotypes on DSC readmission.

Results

The MUNO phenotype had 1.147-fold (95% CI: 1.066, 1.235; p < 0.001) increased 180-day readmission risks in patients with neoplasm of the upper digestive tract. The MUNO phenotype had 1.073-fold (95% CI: 1.027, 1.121; p = 0.002) increased 30-day readmission risks and 1.067-fold (95% CI: 1.021, 1.115; p = 0.004) increased 180-day readmission risks in patients with neoplasm of the lower digestive tract. The MUNO and MUO phenotypes were independent risk factors of readmission in patients with liver or pancreatic neoplasm. Metabolic obesity status was independently associated with a high risk of severe and unplanned hospitalization within 30 days or 180 days.

Conclusion

Both obesity and metabolic abnormalities are associated with a high risk for the poor prognosis of DSC patients. The effect of metabolic categories on the short- or long-term readmission of liver or pancreas cancers may be stronger than that of obesity.
Enteroviral infections are not associated with type 2 diabetes
Authors: Liu Huan , Geravandi Shirin , Grasso Ausilia Maria , Sikdar Saheri , Pugliese Alberto , Maedler Kathrin
Published: October 2023

Introduction

For more than a century, enteroviral infections have been associated with autoimmunity and type 1 diabetes (T1D). Uncontrolled viral response pathways repeatedly presented during childhood highly correlate with autoimmunity and T1D. Virus responses evoke chemokines and cytokines, the “cytokine storm” circulating through the body and attack cells especially vulnerable to inflammatory destruction. Intra-islet inflammation is a major trigger of β-cell failure in both T1D and T2D. The genetic contribution of islet inflammation pathways is apparent in T1D, with several mutations in the interferon system. In contrast, in T2D, gene mutations are related to glucose homeostasis in β cells and insulin-target tissue and rarely within viral response pathways. Therefore, the current study evaluated whether enteroviral RNA can be found in the pancreas from organ donors with T2D and its association with disease progression.

Methods

Pancreases from well-characterized 29 organ donors with T2D and 15 age- and BMI-matched controls were obtained from the network for pancreatic organ donors with diabetes and were analyzed in duplicates. Single-molecule fluorescence in-situ hybridization analyses were performed using three probe sets to detect positive-strand enteroviral RNA; pancreas sections were co-stained by classical immunostaining for insulin and CD45.

Results

There was no difference in the presence or localization of enteroviral RNA in control nondiabetic and T2D pancreases; viral infiltration showed large heterogeneity in both groups ranging from 0 to 94 virus+ cells scattered throughout the pancreas, most of them in the exocrine pancreas. Very rarely, a single virus+ cell was found within islets or co-stained with CD45+ immune cells. Only one single T2D donor presented an exceptionally high number of viruses, similarly as seen previously in T1D, which correlated with a highly reduced number of β cells.

Discussion

No association of enteroviral infection in the pancreas and T2D diabetes could be found. Despite great similarities in inflammatory markers in islets in T1D and T2D, long-term enteroviral infiltration is a distinct pathological feature of T1D-associated autoimmunity and in T1D pancreases.
Long-term changes in coarse woody debris abundance in three Appalachian headwater streams with differing best management practices
Authors: Sena Kenton L. , Flynn Jerrica K. , Leuenberger Wendy , Kolka Randall , Barton Christopher D.
Published: October 2023

Introduction

Timber harvests influence coarse woody debris (CWD) dynamics both initially and long-term—contributing a significant amount of CWD as slash immediately after harvest, but also removing some or all of the mature trees necessary to produce CWD over time. Whereas shelterwood and other similar timber harvest systems retain varying amounts of the overstory, preserving CWD production after harvest, commercial clearcutting essentially eliminates sources of fresh CWD until regenerating trees are large enough to contribute CWD through fallen limbs or trunks, often decades after harvest. Forestry best management practices (BMPs) are critical for reducing the water quality impacts of timber harvest, but their effects on riparian and stream CWD are not well understood.

Methods

The current project explores CWD dynamics (surveyed in 2001, 2004, 2009, and 2020) in three eastern Kentucky watersheds receiving differing timber harvest treatments in 1983: unharvested control, BMPs (clearcut with a protected streamside management zone), and no BMPs (clearcut).

Results

Analysis of hydrology data over the period of record demonstrated significant flooding in 2004 that likely “reset” CWD in the study watersheds. Coarse woody debris volume was higher in control (3.33 m3/ha) than no BMP (1.03 m3/ha) in 2020, with CWD accumulation rates ranging from 0.039 m3/ha in the no BMP watershed to 0.19 m3/ha in the control.

Discussion

While not significantly different, CWD volume was nominally higher in the BMP watershed than the No BMP watershed, suggesting that, in addition to their many other benefits, streamside management zones help facilitate CWD provisioning during stand initiation after a commercial clearcut harvest. Furthermore, this study suggests that provisioning of CWD may not recover after clearcut harvesting for 100 years or more.
Novel mediator in anaphylaxis: decreased levels of miR-375-3p in serum and within extracellular vesicles of patients
Authors: Nuñez-Borque Emilio , Fernandez-Bravo Sergio , Rodríguez Del Rio Pablo , Palacio-García Lucia , Di Giannatale Angela , Di Paolo Virginia , Galardi Angela , Colletti Marta , Pascucci Luisa , Tome-Amat Jaime , Cuesta-Herranz Javier , Ibañez-Sandin María Dolores , Laguna José Julio , Benito-Martin Alberto , Esteban Vanesa
Published: October 2023

Introduction

Anaphylaxis is among the most severe manifestations of allergic disorders, but its molecular basis remains largely unknown and reliable diagnostic markers are not currently available. MicroRNAs (miRNAs) regulate several pathophysiological processes and have been proposed as non-invasive biomarkers. Therefore, this study aims to evaluate their involvement in anaphylactic reaction and their value as biomarkers.

Methods

Acute (anaphylaxis) and baseline (control) serum samples from 67 patients with anaphylaxis were studied. Among them, 35 were adults with drug-induced anaphylaxis, 13 adults with food-induced anaphylaxis and 19 children with food-induced anaphylaxis. The circulating serum miRNAs profile was characterized by next-generation sequencing (NGS). For this purpose, acute and baseline samples from 5 adults with drug-induced anaphylaxis were used. RNA was extracted, retrotranscribed, sequenced and the readings obtained were mapped to the human database miRBase_20. In addition, a system biology analysis (SBA) was performed with its target genes and revealed pathways related to anaphylactic mediators signaling. Moreover, functional and molecular endothelial permeability assays were conducted with miR-375-3p-transfected cells in response to cAMP.

Results

A total of 334 miRNAs were identified, of which 21 were significant differentially expressed between both phases. Extracellular vesicles (EVs) were characterized by Western blot, electron microscopy and NanoSight. A decrease of miR-375-3p levels was determined by qPCR in both serum and EVs of patients with anaphylaxis (****p<.0001). Precisely, the decrease of miR-375-3p correlated with the increase of two inflammatory cytokines: monocyte chemoattractant protein-1 (MCP-1) and granulocyte macrophage colony-stimulating factor (GM-CSF). On the other hand, functional and molecular data obtained showed that miR-375-3p partially blocked the endothelial barrier maintenance and stabilization by disassembly of cell-cell junctions exhibiting low Rac1-Cdc42 levels.

Discussion

These findings demonstrate a differential serum profile of circulating miRNAs in patients with anaphylaxis and exhibit the miR-375-3p modulation in serum and EVs during drug- and food-mediated anaphylactic reactions. Furthermore, the in silico and in vitro studies show a negative role for miR-375-3p/Rac1-Cdc42 in the endothelial barrier stability.
Immunological characterization of stroke-heart syndrome and identification of inflammatory therapeutic targets
Authors: Zheng Junyi , Ma Yilin , Guo Xukun , Wu Jialing
Published: October 2023

Acute cardiac dysfunction caused by stroke-heart syndrome (SHS) is the second leading cause of stroke-related death. The inflammatory response plays a significant role in the pathophysiological process of cardiac damage. However, the mechanisms underlying the brain–heart interaction are poorly understood. Therefore, we aimed to analysis the immunological characterization and identify inflammation therapeutic targets of SHS. We analyzed gene expression data of heart tissue 24 hours after induction of ischemia stoke by MCAO or sham surgery in a publicly available dataset (GSE102558) from Gene Expression Omnibus (GEO). Bioinformatics analysis revealed 138 differentially expressed genes (DEGs) in myocardium of MCAO-treated compared with sham-treated mice, among which, immune and inflammatory pathways were enriched. Analysis of the immune cells infiltration showed that the natural killer cell populations were significantly different between the two groups. We identified five DIREGs, Aplnr, Ccrl2, Cdkn1a, Irak2, and Serpine1 and found that their expression correlated with specific populations of infiltrating immune cells in the cardiac tissue. RT–qPCR and Western blot methods confirmed significant changes in the expression levels of Aplnr, Cdkn1a, Irak2, and Serpine1 after MCAO, which may serve as therapeutic targets to prevent cardiovascular complications after stroke.
Real world experience on the effectiveness and safety of pirfenidone in patients with idiopathic pulmonary fibrosis in Taiwan
Authors: Chang Cheng-Yu , Wei Yu-Feng , Chen Chung-Yu , Lai Yi-Chun , Hu Po-Wei , Hung Jui-Chi , Chu Chi-Hsiang , Chuang Hsin-Tzu , Chang Shih-Chieh
Published: October 2023

Introduction

Randomized controlled trials have demonstrated a reduction in the decline of lung function and a reduced risk of acute exacerbation in patients with idiopathic pulmonary fibrosis treated with the antifibrotic prifenidone. The present study aimed to investigate the real-world effectiveness and safety profile of pirfenidone treatment for patients with IPF in Taiwan.

Methods

Between January 1, 2019 and December 31, 2020, we enrolled 50 patients who were newly diagnosed with IPF and had at least 12 months follow-up period after pirfenidone administration.

Result

The primary outcome of pharmacologic effect showed that the mean differences in the absolute values of forced vital capacity from baseline were 0.2 liter (n = 36), 0.13 liter (n = 32), 0.04 liter (n = 26), and − 0.004 liter (n = 26) after 3, 6, 9, and 12 months of administration, respectively. A slight improvement in quality of life, including scores of chronic obstructive pulmonary disease assessment test and St. George’s respiratory questionnaire scores. The most common adverse effects were gastrointestinal upset and dermatological problems. No new safety concerns were observed in the present study.

Conclusion

Our real-world study describe for the first time in Taiwan, the use of pirfenidone over a 12 months period. This drug preserves the lung function and improves quality of life with tolerable side effects.
DNA supercoiling in bacteria: state of play and challenges from a viewpoint of physics based modeling
Authors: Junier Ivan , Ghobadpour Elham , Espeli Olivier , Everaers Ralf
Published: October 2023

DNA supercoiling is central to many fundamental processes of living organisms. Its average level along the chromosome and over time reflects the dynamic equilibrium of opposite activities of topoisomerases, which are required to relax mechanical stresses that are inevitably produced during DNA replication and gene transcription. Supercoiling affects all scales of the spatio-temporal organization of bacterial DNA, from the base pair to the large scale chromosome conformation. Highlightedin vitroandin vivoin the 1960s and 1970s, respectively, the first physical models were proposed concomitantly in order to predict the deformation properties of the double helix. About fifteen years later, polymer physics models demonstrated on larger scales the plectonemic nature and the tree-like organization of supercoiled DNA. Since then, many works have tried to establish a better understanding of the multiple structuring and physiological properties of bacterial DNA in thermodynamic equilibrium and far from equilibrium. The purpose of this essay is to address upcoming challenges by thoroughly exploring the relevance, predictive capacity, and limitations of current physical models, with a specific focus on structural properties beyond the scale of the double helix. We discuss more particularly the problem of DNA conformations, the interplay between DNA supercoiling with gene transcription and DNA replication, its role on nucleoid formation and, finally, the problem of scaling up models. Our primary objective is to foster increased collaboration between physicists and biologists. To achieve this, we have reduced the respective jargon to a minimum and we provide some explanatory background material for the two communities.
Potential modulating effects of Allium mongolicum regel ethanol extract on rumen fermentation and biohydrogenation bacteria of dairy cows in vitro
Authors: Wang XiaoYuan , Bai Chen , Khas Erdene  , Umair Ashraf Muhammad , Cao QiNa , Ao ChangJin , Jiang LinShu
Published: October 2023

The objective of this study was to evaluate the potential modulating effects of Allium mongolicum regel ethanol extract (AME) on rumen fermentation and biohydrogenation (BH) bacteria in vitro. Four Holstein cows were used as donors for the rumen fluid used in this study. In experiment 1, five treatments (supplemented with 0 mg/g, 1 mg/g, 2 mg/g, 3 mg/g, and 4 mg/g of AME based on fermentation substrate, respectively) were conducted to evaluate the effects of different levels of AME on fermentation status in vitro. The results showed that after 24 h of fermentation, MCP was reduced with AME supplementation (p < 0.05), and the multiple combinations of different combinations index (MFAEI) value was the highest with 3 mg/g of AME. In experiment 2, six treatments were constructed which contained: control group (A1); the unsaturated fatty acid (UFA) mixture at 3% concentration (A2); the mixture of A2 and 3 mg/g of AME (A3); 3 mg/g of AME (A4); the UFA mixture at 1.5% concentration (A5); the mixture of A5 and 3 mg/g of AME (A6). The abundance of bacterial species involved in BH was measured to evaluate the potential modulating effect of AME on rumen BH in vitro. Compared with the A1 group, the A3, A4, and A6 groups both showed significant decreases in the abundance of rumen BH microbial flora including Butyrivibrio proteoclasticus, Butyrivibrio fibrisolvens, Ruminococcus albus and Clostridium aminophilum (p < 0.01). The A3 group was less inhibitory than A4 in the abundance of B. proteoclasticus, B. fibrisolvens, and R. albus, and the inhibitory effect of the A6 group was higher than that of A4. In conclusion, the supplementation with 3 mg/g of AME could modulate the rumen fermentation and affect BH key bacteria, which suggests that AME may have the potential to inhibit the rumen BH of dairy cows.
Antibacterial and antibiofilm activity of Abroma augusta stabilized silver (Ag) nanoparticles against drug-resistant clinical pathogens
Authors: Kumar Sachin , Khan Haris M. , Husain Fohad Mabood , Ahmad Rafiq , Qais Faizan Abul , Khan Mo Ahamad , Jalal Mohammad , Tayyaba Uzma , Ali Syed Ghazanfar , Singh Amardeep , Shahid Mohammad , Lee Byeong-Il
Published: October 2023

Infectious diseases remain among the most pressing concerns for human health. This issue has grown even more complex with the emergence of multidrug-resistant (MDR) bacteria. To address bacterial infections, nanoparticles have emerged as a promising avenue, offering the potential to target bacteria at multiple levels and effectively eliminate them. In this study, silver nanoparticles (AA-AgNPs) were synthesized using the leaf extract of a medicinal plant, Abroma augusta. The synthesis method is straightforward, safe, cost-effective, and environment friendly, utilizing the leaf extract of this Ayurvedic herb. The UV-vis absorbance peak at 424 nm indicated the formation of AA-AgNPs, with the involvement of numerous functional groups in the synthesis and stabilization of the particles. AA-AgNPs exhibited robust antibacterial and antibiofilm activities against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE). The MIC values of AA-AgNPs ranged from 8 to 32 μg/mL. Electron microscopic examination of the interaction of AA-AgNPs with the test bacterial pathogens showed a deleterious impact on bacterial morphology, resulting from membrane rupture and leakage of intracellular components. AA-AgNPs also demonstrated a dose-dependent effect in curtailing biofilm formation below inhibitory doses. Overall, this study highlights the potential of AA-AgNPs in the successful inhibition of both the growth and biofilms of MRSA and VRE bacteria. Following studies on toxicity and dose optimization, such AgNPs could be developed into effective medical remedies against infections.
Proteomic analysis of peripheral nerve myelin during murine aging
Authors: Helbing Dario Lucas , Kirkpatrick Joanna M. , Reuter Michael , Bischoff Julia , Stockdale Amy , Carlstedt Annemarie , Cirri Emilio , Bauer Reinhard , Morrison Helen
Published: October 2023

Aging of the peripheral nervous system (PNS) is associated with structural and functional changes that lead to a reduction in regenerative capacity and the development of age-related peripheral neuropathy. Myelin is central to maintaining physiological peripheral nerve function and differences in myelin maintenance, degradation, formation and clearance have been suggested to contribute to age-related PNS changes. Recent proteomic studies have elucidated the complex composition of the total myelin proteome in health and its changes in neuropathy models. However, changes in the myelin proteome of peripheral nerves during aging have not been investigated. Here we show that the proteomes of myelin fractions isolated from young and old nerves show only subtle changes. In particular, we found that the three most abundant peripheral myelin proteins (MPZ, MBP, and PRX) do not change in old myelin fractions. We also show a tendency for high-abundance myelin proteins other than these three to be downregulated, with only a small number of ribosome-related proteins significantly downregulated and extracellular matrix proteins such as collagens upregulated. In addition, we illustrate that the peripheral nerve myelin proteome reported in this study is suitable for assessing myelin degradation and renewal during peripheral nerve degeneration and regeneration. Our results suggest that the peripheral nerve myelin proteome is relatively stable and undergoes only subtle changes in composition during mouse aging. We proffer the resultant dataset as a resource and starting point for future studies aimed at investigating peripheral nerve myelin during aging. Said datasets are available in the PRIDE archive under the identifier PXD040719 (aging myelin proteome) and PXD041026 (sciatic nerve injury proteome).
Effect of recombinant human nerve growth factor treatment on corneal nerve regeneration in patients with neurotrophic keratopathy
Authors: Balbuena-Pareja Ana , Bogen Chloe S. , Cox Stephanie M. , Hamrah Pedram
Published: October 2023

Introduction

Neurotrophic Keratopathy (NK) is a neurodegenerative corneal disease that results in diminished corneal sensation. Previous studies have found that Cenegermin 0.002%, a recombinant human nerve growth factor (rhNGF), improves corneal epithelial healing in stage 2 and 3 NK patients. However, rhNGF effect on corneal sensation and nerve regeneration has not been well established. Thus, this study aims to analyze the effect of rhNGF on corneal nerve regeneration using in vivo confocal microscopy (IVCM) and on corneal sensitivity in NK patients.

Methods

This is a retrospective, longitudinal, case–control study that included patients with NK, treated with rhNGF for at least 4 weeks, with pre- and post-treatment IVCM images available for analysis. Chart reviews were conducted documenting prior medical and surgical history, clinical signs and symptoms, and corneal sensation using Cochet-Bonnet esthesiometry. Corneal nerve parameters were assessed by IVCM. Sex- and age-matched reference controls were selected from a database of healthy subjects for comparison.

Results

The study included 25 patients, with 22 (88%) stage 1, two (8%) stage 2, and 1 (4%) stage 3 NK patients, with a median age of 64 years (range: 30–93 years). Total, main, and branch nerve densities [median (range) in mm/mm2] were lower in the NK group pre-treatment [2.3 (0.0–21.1); 1.7 (0.0–13.0); 0.5 (0.0–10.2); respectively] vs. controls [22.3 (14.9–29.0); 10.1 (3.2–15.4); and 12.1 (6.2–18.4), (p < 0.0001 for all), respectively]. Post-treatment nerve densities increased compared to pre-treatment to 5.3 (0.0–19.4, p = 0.0083) for total, 3.5 (0.0–13.2, p = 0.0059) for main, and 2.0 (0.0–10.4, p = 0.0251) for branch nerves, but remained lower than controls (p < 0.0001 for all). Corneal sensation increased from 2.3 ± 1.1 cm pre-treatment to 4.1 ± 1.4 cm post-treatment (p = 0.001). Median best corrected visual acuity significantly increased following rhNGF treatment from 0.4 (0.0–1.6) to 0.12 (−0.1 to 1.6) (p = 0.007).

Conclusion

Patients with NK treated with at least 4 weeks of rhNGF, showed a significant increase in corneal nerve densities after treatment. A significant increase in corneal sensation, as well as best corrected visual acuity, was observed following treatment.
Maximum intensity projection based on high frame rate contrast-enhanced ultrasound for the differentiation of breast tumors
Authors: Li Jia , Wei Cong , Ma Xinxin , Ying Tao , Sun Di , Zheng Yuanyi
Published: October 2023

Objective

We explored the role of maximum intensity projection (MIP) based on high frame rate contrast-enhanced ultrasound (H-CEUS) for the differentiation of breast tumors.

Methods

MIP imaging was performed in patients with breast tumors who underwent H-CEUS examinations. The microvasculature morphology of breast tumors was assessed. The receiver operating characteristic curve was plotted to evaluate the diagnostic performance of MIP.

Results

Forty-three breast tumors were finally analyzed, consisting of 19 benign and 24 malignant tumors. For the ≤30-s and >30-s phases, dot-, line-, or branch-like patterns were significantly more common in benign tumors. A tree-like pattern was only present in the benign tumors. A crab claw-like pattern was significantly more common in the malignant tumors. Among the tumors with crab claw-like patterns, three cases of malignant tumors had multiple parallel small spiculated vessels. There were significant differences in the microvasculature morphology for the ≤30-s and >30-s phases between the benign and malignant tumors (all p < 0.001). The area under the curve, sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the ≤30-s phase were all higher than those of the >30-s phase for the classification of breast tumors.

Conclusion

MIP based on H-CEUS can be used for the differentiation of breast tumors, and the ≤30-s phase had a better diagnostic value. Multiple parallel small spiculated vessels were a new finding, which could provide new insight for the subsequent study of breast tumors.
Pyroptosis: the dawn of a new era in endometrial cancer treatment
Authors: Peng Tian , Zhang Chi , Chen Wen-Jun , Zhao Xue-Fei , Wu Wei-Bo , Yang Wei-Ji , Liang Ruo-Jia
Published: October 2023

Endometrial cancer (EC) is a malignancy of the inner epithelial lining of the uterus. While early-stage EC is often curable through surgery, the management of advanced, recurrent and metastatic EC poses significant challenges and is associated with a poor prognosis. Pyroptosis, an emerging form of programmed cell death, is characterized by the cleavage of gasdermin proteins, inducing the formation of extensive gasdermin pores in the cell membrane and the leakage of interleukin-1β (IL-1β) and interleukin-18 (IL-18), consequently causing cell swelling, lysis and death. It has been found to be implicated in the occurrence and progression of almost all tumors. Recent studies have demonstrated that regulating tumor cells pyroptosis can exploit synergies function with traditional tumor treatments. This paper provides an overview of the research progress made in molecular mechanisms of pyroptosis. It then discusses the role of pyroptosis and its components in initiation and progression of endometrial cancer, emphasizing recent insights into the underlying mechanisms and highlighting unresolved questions. Furthermore, it explores the potential value of pyroptosis in the treatment of endometrial cancer, considering its current application in tumor radiotherapy, chemotherapy, targeted therapy and immunotherapy.
Pediatric precision oncology: “better three hours too soon than a minute too late”
Authors: Marshall Mark , Ivanovich Jennifer , Schmitt Morgan , Helvie Amy , Langsford Lisa , Casterline Jennifer , Ferguson Michael
Published: October 2023

Precision oncology is defined as the selection of an effective treatment for a cancer patient based upon genomic profiling of the patient’s tumor to identify targetable alterations. The application of precision oncology toward pediatric cancer patients has moved forward more slowly than with adults but is gaining momentum. Clinical and pharmaceutical advances developed over the past decade for adult cancer indications have begun to move into pediatric oncology, expanding treatment options for young high-risk and refractory patients. As a result, the FDA has approved 23 targeted drugs for pediatric cancer indications, moving targeted drugs into the standard of care. Our precision oncology program is in a medium sized children’s hospital, lacking internal sequencing capabilities and bioinformatics. We have developed methods, medical and business partnerships to provide state-of-the-art tumor characterization and targeted treatment options for our patients. We present here a streamlined and practical protocol designed to enable any oncologist to implement precision oncology options for their patients.
Do disease-modifying antirheumatic drugs and non-steroidal anti-inflammatory drugs increase the burden on ankylosing spondylitis patients with mild-moderate COVID-19? evidence from a retrospective cohort study
Authors: Li Yan , Hu Zhengyuan , Guo Yufei , Zhao Zheng , Li Kunpeng , Wang Xiuru , Zhang Jie , Liang Dongfeng , Zhang Jianglin , Hu Xiaoyue , Zhu Jian , Huang Feng
Published: October 2023

Objectives: The impact of non-steroidal anti-inflammatory drugs (NSAIDs), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and tumor necrosis factor inhibitors (TNFi) on the outcomes of mild-moderate COVID-19 in patients with ankylosing spondylitis (AS) remains unclear. This study aimed to evaluate the effects of NSAIDs, csDMARDs, and TNFi on AS patients with mild-moderate COVID-19.

Methods: This cohort study utilized patient-reported PCR/antigen tests to determine the occurrence of COVID-19 and assessed clinical manifestations to determine its severity. The study focused on two primary outcomes: an increased number of COVID-19 symptoms and a prolonged disease course (longer than 10 or 28 days). Modified Poisson regression was performed to analyze the association between exposures and outcomes.

Results: A total of 521 patients were included in the analysis. The median age was 34.8 (inter-quartile range: 27.2–46.7), with 420 (80.6%) being men. Among the patients, 52 (10.0%) had comorbidities and 443 (85%) had been vaccinated. After adjusting for confounding factors, there was no significant association between csDMARDs or TNFi and the presence of more than 5 symptoms in mild-moderate COVID-19 (adjusted relative risk (RRa) 1.08, 95% CI: 0.84–1.40 or 1.09, 0.92–1.29 for csDMARDs or TNFi, respectively), whereas the prevalence of experiencing more than 5 symptoms increased in patients with NSAID monotherapy (RRa 1.22, 95% CI: 1.01–1.46). Similarly, there was no significant association with having more than 10 symptoms (RRa 0.65, 95% CI: 0.26–1.64; 0.95, 0.36–2.54; and 1.01, 0.53–1.91 for NSAIDs, csDMARDs, and TNFi, respectively). Patients who had pre-existing use of NSAIDs, csDMARDs and TNFi had similar odds of experiencing a disease course longer than 10 days (RRa 1.17, 95% CI: 0.82–1.66; 1.18, 0.78–1.77; and 1.22, 0.92–1.63 for NSAIDs, csDMARDs, and TNFi, respectively) and longer than 28 days (RRa 0.94, 95% CI: 0.31–2.81; 0.97, 0.25–3.74 and 1.05, 0.44–2.49, respectively) compared to those not using medication.

Conclusion: AS patients treated with csDMARDs or TNFi did not show inferior outcomes in terms of symptom burden or recovery compared to those not using medication in mild-moderate COVID-19. The observed inverse association between pre-existing NSAIDs use and COVID-19 symptom burden in AS deserves further investigation.
From seeds to survival rates: investigating Linum usitatissimum’s potential against ovarian cancer through network pharmacology
Authors: Islam Mohammed Monirul , Sreeharsha Nagaraja , Alshabrmi Fahad M. , Asif Afzal Haq , Aldhubiab Bandar , Anwer Md Khalid , Krishnasamy Rajendiran , Rehman Abdur
Published: October 2023

Ovarian cancer is a malignant tumor that primarily forms in the ovaries. It often goes undetected until it has spread to the pelvis and abdomen, making it more challenging to treat and often fatal. Historically, natural products and their structural analogues have played a pivotal role in pharmacotherapy, especially for cancer. Numerous studies have demonstrated the therapeutic potential of Linum usitatissimum against ovarian cancer, but the specific molecular mechanisms remain elusive. This study combines data mining, network pharmacology, and molecular docking analysis to pioneer an innovative approach for ovarian cancer treatment by identifying potent phytochemicals. Findings of current study revealed that Apigenin, Vitamin E, Palmitic acid, Riboflavin, Isolariciresinol, 5-Dehydro-avenasterol, Cholesterol, Pantothenic acid, Nicotinic acid, Campesterol, Beta-Sitosterol, Stigmasterol, Daucosterol, and Vitexin suppress tumor growth by influencing AKT1, JUN, EGFR, and VEGFA. Kaplan–Meier survival analysis spotlighted AKT1, JUN, EGFR, and VEGFA as potential diagnostic and prognostic biomarkers for ovarian cancer. However, it is imperative to conduct in vivo and in vitro examinations to ascertain the pharmacokinetics and biosafety profiles, bolstering the candidacy of L. usitatissimum in ovarian cancer therapeutics.
Epigenetic control of plant senescence and cell death and its application in crop improvement
Authors: Zhang Yu , Huang Dongmei , Miao Ying
Published: October 2023

Plant senescence is the last stage of plant development and a type of programmed cell death, occurring at a predictable time and cell. It involves the functional conversion from nutrient assimilation to nutrient remobilization, which substantially impacts plant architecture and plant biomass, crop quality, and horticultural ornamental traits. In past two decades, DNA damage was believed to be a main reason for cell senescence. Increasing evidence suggests that the alteration of epigenetic information is a contributing factor to cell senescence in organisms. In this review, we summarize the current research progresses of epigenetic and epitranscriptional mechanism involved in cell senescence of plant, at the regulatory level of DNA methylation, histone methylation and acetylation, chromatin remodeling, non-coding RNAs and RNA methylation. Furthermore, we discuss their molecular genetic manipulation and potential application in agriculture for crop improvement. Finally we point out the prospects of future research topics.