bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic Venous Disease and Its Intersections With Diabetes Mellitus
Authors: Jarošíková R , Roztočil K , Husáková J , Dubský M , Bém R , Wosková V , Fejfarová V
Published: July 2023

Chronic venous disease (CVD) is a vascular disorder in which blood return is severely compromised and CVD is usually characterized by venous hypertension. Along with obesity and diabetes mellitus, CVD is one of the most common civilization diseases. In general, the estimated prevalence of CVD ranges from 60-80 %. Early diagnosis and adequate treatment are important for preventing progression to more severe stages of the disease like venous leg ulcers. Clinical manifestations of CVD in initial stages of the disease are often asymptomatic. However, as CVD progresses, symptoms begin to develop. Treatment of CVD could be divided into conservative and surgical. Conservative therapy consists of compression, pharmacological treatment and lifestyle change. In cases where conservative therapy is ineffective, surgical or endovascular treatment may be required. The intersections between diabetes mellitus (DM) and CVD are not to be underestimated. CVD and DM have often the same risk factors. Symptoms of CVD can be modified by late complications of DM, but the incidence of different CVD degrees seems to be the same as in diabetics as in non-diabetics population. We are particularly concerned in diabetics about worse compliance with treatment due to their often-poorer adherence to treatment of DM and lifestyle changes. Moreover, there exist a higher risk of CVD and peripheral arterial disease in diabetics patients. Patients with CVD should always be inspected for the presence of DM, considering its presence can have a bearing on CVD symptoms, diagnostic procedures, and therapeutic strategies.
NewStudy of the Pan-European Phenomenon in Ukrainian Art
Authors:   Kharkiv State Academy of Design and Fine Arts, Sokolyuk Lyudmyla
Published: July 2023

Holubets, O. (2020). Magia tretjogo vymiru. Skuljpturna plastyka kintsia ХІХ — pochakku ХХІ stolittia [Magic of third dimensions. Sculpture at the end of ХІХ — beginning of ХХІ centuries] [Monograph]. Lviv: Color PRO. [In Ukrainian].
Control del Dengue
Authors: Cabezas César
Published: July 2023

El dengue es una enfermedad causada por el virus del dengue que tiene cuatro serotipos distintos, pero estrechamenterelacionados (DENV-1-4) que son transmitidos principalmente por un vector muy efectivo. Es la enfermedad arboviral máscomún en todo el mundo, con la mayor carga en regiones tropicales y subtropicales, por lo que, en ausencia de unaprevención y medidas de control, se prevé que aumente tanto en la carga de la enfermedad como rango geográfico, como viene ocurriendo en el Perú, en las Américas y en el mundo.
Peningkatan Keterampilan Kader Posyandu dalam Pengukuran Antropometri di Desa Meteseh, Boja, Kendal
Authors: Puji Lestari  , Wenny Dwi Kurniati  , Anisa Herdin Hidayati
Published: July 2023

Meteseh Village is a village with 8 Posyandu. Various posyandu activities have been carried out, one of the routine activities carried out is anthropometric measurements, but there are still cadres who take measurements in an inappropriate way. This can produce erroneous measurement results, resulting in inaccurate interpretation. The accuracy of anthropometric measurements depends on the ability of cadres to make measurements, so training and assistance is needed in anthropometric measurements with the aim of increasing the knowledge and abilities of cadres in taking anthropometric measurements. The methods used in training and mentoring anthropometric measurements are lecture, discussion, simulation and demonstration methods using Ms. Power Point and various anthropometric measurement tools. Assistance is carried out within two months. Measurement of knowledge is done by giving pre-test and post-test. The activity was carried out with 50 Meteseh Village cadres, Boja, Kendal from June to September 2022. Based on the results of the pre-test and post-test, 60% of the cadres experienced an increase in knowledge. The results of the observations during the mentoring and evaluation of the participants also showed good results in the training and mentoring activities. suggestions that training and mentoring can be carried out on an ongoing basis to refresh the knowledge and consistency of cadres in making anthropometric measurements.
Stable and low-threshold photon upconversion in nondegassed water by organic crystals
Authors: Murakami Yoichi , Enomoto Riku
Published: July 2023

Photon upconversion (UC) is a technology that converts lower-energy photons (longer wavelength light) into higher-energy photons (shorter wavelength light), the opposite of fluorescence. Thus, UC is expected to open a vast domain of photonic applications that are not otherwise possible. Recently, UC by triplet−triplet annihilation (TTA) between organic molecules has been studied because of its applicability to low-intensity light, although the majority of such studies have focused on liquid samples in the form of organic solvent solutions. To broaden the range of applications, solid-state UC materials have been an active area of research. We recently developed air-stable, high-performance molecular UC crystals that utilize a stable solid-solution phase of bicomponent organic crystals. This article begins with a brief overview of previous challenges in developing and improving solid-state TTA–UC materials. Then, we briefly review and explain the concept as well as advantages of our molecular solid-solution UC crystals. We applied these organic crystals for the first time to a water environment. We observed blue UC emission upon photoexcitation at 542 nm (green–yellow light) and then measured the excitation intensity dependence as well as the temporal stability of the UC emission in air-saturated water. In nondegassed water, these organic crystals were stable, functioned with a low excitation threshold intensity of a few milliwatts per square centimeter, and exhibited high photo-irradiation durability at least over 40 h; indicating that the developed organic crystals are also viable for aqueous conditions. Therefore, the organic crystals presented in this report are expected to extend the domain of UC-based photonic applications in practical water systems including in vivo diagnostic, clinical, and therapeutic applications.
Development of culture methods capable of culturing a wide range of predominant species of intestinal bacteria
Authors: Hirano Rika , Nishita Izumi , Nakai Riho , Bito Ayaka , Sasabe Ryunosuke , Kurihara Shin
Published: July 2023

In recent years, with the development of non-cultivation approaches, it has become evident that intestinal bacteria have a significant impact on human health. However, because one-third of the genes cannot be annotated, it is difficult to elucidate the function of all intestinal bacteria by in silico analysis, and it is necessary to study the intestinal bacteria by culturing them. In addition, various media recommended for each individual bacterium have been used for culturing intestinal bacteria; however, the preparation of each medium is complex. To simultaneously culture many bacteria and compare bacterial phenotypes under the same conditions, a medium capable of culturing a wide range of bacteria is needed. In this study, we developed GAM + blood medium (GB medium), which consists of Gifu anaerobic medium containing 5% (v/v) horse blood; it is easy to prepare and it allowed the successful cultivation of 85% of the available predominant species in the human intestinal microbiota.
Chlamydia trachomatis TmeB antagonizes actin polymerization via direct interference with Arp2/3 activity
Authors: Scanlon Kaylyn R. , Keb Gabrielle , Wolf Katerina , Jewett Travis J. , Fields Kenneth A.
Published: July 2023

Chlamydia trachomatis is an obligate intracellular pathogen that actively promotes invasion of epithelial cells. A virulence-associated type III secretion system contributes to chlamydial entry and at least four effectors have been described that are deployed during this time. Two of these invasion-related effectors, the translocated membrane-associated effectors A and B (TmeA and TmeB), are encoded in a bi-cistronic operon. TmeA directly activates host N-WASP to stimulate Arp2/3-dependent actin polymerization. According to current working models, TmeA-mediated N-WASP activation contributes to invasion. TmeB has not been functionally characterized. Unlike a tmeA null strain, loss of tmeB does not impact invasion efficiency of C. trachomatis. Using strains deficient for multiple genes, we provide evidence that TmeA is dispensable for invasion in the absence of TmeB. Our data indicate that overabundance of TmeB interferes with invasion and that this activity requires active Arp2/3 complex. We further show that TmeB is capable of interfering with Arp2/3-mediated actin polymerization. In aggregate, these data point to opposing functions for TmeA and TmeB that manifest during the invasion process. These studies raise intriguing questions regarding the dynamic interplay between TmeA, TmeB, and branched actin polymerization during chlamydial entry.
Safety and performance of the Vienna self-expandable transcatheter aortic valve system: 6-month results of the VIVA first-in-human feasibility study
Authors: Briedis Kasparas , Mizariene Vaida , Rumbinaite Egle , Jurenas Martynas , Aldujeli Ali , Briede Kamilija , Jakuska Povilas , Jankauskas Antanas , Ceponiene Indre , Lenkutis Tadas , Zaliunas Remigijus , Benetis Rimantas
Published: July 2023

Background

The novel Vienna TAVI system is repositionable and retrievable, already pre-mounted on the delivery system, eliminating the need for assembly and crimping of the device prior to valve implantation.

Aims

The purpose of this first-in-human feasibility study was to determine the safety, feasibility, clinical and hemodynamic performance of the Vienna TAVI system at 6-month follow-up. (ClinicalTrials.gov identifier NCT04861805).

Methods

This is a prospective, non-randomized, single-arm, single-center, first-stage FIH feasibility study, which is followed by a second-stage pivotal, multicenter, multinational study in symptomatic patients with severe aortic stenosis (SAS). The first-stage FIH study evaluated the safety and feasibility, clinical and hemodynamic performance of the device in 10 patients with SAS based on recommendations by the VARC-2.

Results

All patients were alive at 3-month follow-up. 1 non-cardiovascular mortality was reported 5 months after implantation. There were no new cerebrovascular events, life-threatening bleeding or conduction disturbances observed at 6-month follow-up. The mean AV gradient significantly decreased from 48.7 ± 10.8 to 7.32 ± 2.0 mmHg and mean AVA increased from 0.75 ± 0.18 to 2.16 ± 0.42 cm2 (p < 0.00001). There was no incidence of moderate or severe total AR observed. In the QoL questionnaires, the patients reported a significant improvement from the baseline 12-KCCQ mean score 58 ± 15 to 76 ± 20. NYHA functional class improved in two patients, remained unchanged in one patient. There was an increase in mean 6-min-walk distance from baseline 285 ± 97 to 347 ± 57 m.

Conclusions

This study demonstrates that using Vienna TAVI system has favourable and sustained 6-month safety and performance outcomes in patients with symptomatic severe aortic stenosis.
Case report: New is not always better: treatment of non-bacterial thrombotic endocarditis
Authors: Akiki Elias , Ahmad Ali , El-Am Edward A. , Casanegra Ana I. , Klarich Kyle W. , Kurmann Reto
Published: July 2023

An elderly female with metastatic adenocarcinoma of the lung and atrial fibrillation presented with multiple embolic strokes while on anticoagulation with Apixaban. After further investigation, a TEE showed lesions of non-bacterial thrombotic endocarditis on the mitral valve. A decision to switch the patient to LMWH for anticoagulation was then made and a follow-up TEE showed resolution of the NBTE. In this abstract, we show that heparin should remain as the anticoagulation agent of choice in the setting of NBTE associated with malignancy.
A general forward solver for 3D CSEMs with multitype sources and operating environments
Authors: Li Dajun , Wang Zhiqiang , Li Yabin , Jin Liubiao
Published: July 2023

To determine the electromagnetic (EM) fields of different three-dimensional (3D) controlled-source electromagnetic methods (CSEMs) using the same parameters of the forward solution, by explicitly considering the commonalities, we present a general 3D forward modeling solver for CSEMs with multitype sources and operating environments. The commonality of the solver is reflected in two aspects. First, the solver is based on a frequency-domain (FD) vector Helmholtz equation for determining the scattered electric field. The different types of sources are imposed on the right-hand term of the equation, expressed as background Green’s function. Second, sources of any CSEM can be composed of electric dipole (ED) or magnetic dipole (MD) superposition. Thus, the focus of the 3D forward modeling of CSEMs is reduced to determining the EM fields of ED or MD sources for the background medium. The quasi-minimal residual (QMR) method is used to solve the large sparse complex linear system. Once the FD EM fields have been calculated, the time-domain (TD) response can be obtained using the cosine/sine transformation. The numerical results show that the relative error is less than 5% between the 3D numerical and analytical solutions, which verifies the accuracy of the solver. We further study the difference between the real (bent) and theoretical (straight) wires. We suggest that the shape of the source must be considered for TD and FD CSEMs with a wire source during data processing and inversion. The last example investigated the characteristics of FD EM fields from a finite-length wire and TD EM fields from a rectangular fixed loop on the same conductive tilted disk model buried in resistive sediments. According to the numerical results, we recommend FD CSEMs with a wire source for detecting deep anomalies.
Dynamic response of large-section inclined shallow-buried pipe tunnel under train loads
Authors: Cui Guo-Jing , Xie Jiang-Sheng , Sun Yin-hao , Tian Xiao-xu , Meng Chen
Published: July 2023

To ensure the normal passage of an ascending road during the construction of a pipe-jacking tunnel, trains generally run at low speeds during the construction phase and adopt normal speeds later. Using Jingjiu Road, Xi’an, China, as an engineering case, this study evaluated and predicted the dynamic response of a tunnel structure and soil mass when trains run at low to normal speeds. When the train speed was controlled in the range of 30–60 km/h, the soil deformation change rate around the shallow-buried pipe-jacking tunnel was 0.41%. The maximum tensile stress growth rate of the pipe-jacking tunnel structure was 0.037%, the maximum compressive stress growth rate was 0.128%, and the maximum increase in the stress of the pipe-jacking structure was 1.82%. Thus, the soil and structure of the pipe-jacking tunnel were in a safe-stress state. The results show that the influence of train speed on soil and structural stress is small and can be ignored.
Exploring the relationship between students’ note-taking and interpreting quality: a case study in the Chinese context
Authors: Liu Yuqiao , Luo Weihua , Wang Xiaochen
Published: July 2023

This paper aims to explore the relationship between note-taking and interpreting quality in consecutive interpreting. Research questions focus on three perspectives: language choice, the use of symbols and their influence on interpreting quality, and the problems in note-taking. The research design is divided into three steps: pre-interpretation preparation, consecutive interpretation, and retrospective interview. Through the empirical study, a mixed research method is adopted with the analysis of the notes and retrospective interviews with six participants whose major is translation and interpreting at a university in Northeast China. Specifically, both descriptive data analysis and correlation analysis are used for quantitative data, and thematic analysis aims to better describe qualitative data. Findings are as follows: first, students prefer to use English to take notes in English-to-Chinese consecutive interpreting, while Chinese is used more in Chinese-to-English consecutive interpreting; second, the number of symbols used is not related to the quality of interpreting; third, the following five problems are identified from the interview with student participants in students’ notes: missing key information, inconsistent abbreviations, unclear logics, incomplete records of figures and the meaning of figures, and inadequate records of high-density information. The identification of language choice and problems of note-taking in interpreting practice might help teachers and students understand the problems of students’ note-taking and shed light on teaching and learning consecutive interpreting.
A new mutation in the CAVIN1/PTRF gene in two siblings with congenital generalized lipodystrophy type 4: case reports and review of the literature
Authors: Mancioppi Valentina , Daffara Tommaso , Romanisio Martina , Ceccarini Giovanni , Pelosini Caterina , Santini Ferruccio , Bellone Simonetta , Mellone Simona , Baricich Alessio , Rabbone Ivana , Aimaretti Gianluca , Akinci Baris , Giordano Mara , Prodam Flavia
Published: July 2023

Lipodystrophy syndromes are characterized by a progressive metabolic impairment secondary to adipose tissue dysfunction and may have a genetic background. Congenital generalized lipodystrophy type 4 (CGL4) is an extremely rare subtype, caused by mutations in the polymerase I and transcript release factor (PTRF) gene. It encodes for a cytoplasmatic protein called caveolae-associated protein 1 (Cavin-1), which, together with caveolin 1, is responsible for the biogenesis of caveolae, being a master regulator of adipose tissue expandability. Cavin-1 is expressed in several tissues, including muscles, thus resulting, when dysfunctional, in a clinical phenotype characterized by the absence of adipose tissue and muscular dystrophy. We herein describe the clinical phenotypes of two siblings in their early childhood, with a phenotype characterized by a generalized reduction of subcutaneous fat, muscular hypertrophy, distinct facial features, myopathy, and atlantoaxial instability. One of the siblings developed paroxysmal supraventricular tachycardia leading to cardiac arrest at 3 months of age. Height and BMI were normal. Blood tests showed elevated CK, a mild increase in liver enzymes and triglycerides levels, and undetectable leptin and adiponectin concentrations. Fasting glucose and HbA1c were normal, while Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was mildly elevated. Both patients were hyperphagic and had cravings for foods rich in fats and sugars. Genetic testing revealed a novel pathogenic mutation of the CAVIN1/PTRF gene (NM_012232 exon1:c T21A:p.Y7X) at the homozygous state. The diagnosis of lipodystrophy can be challenging, often requiring a multidisciplinary approach, given the pleiotropic effect, involving several tissues. The coexistence of generalized lack of fat, myopathy with elevated CK levels, arrhythmias, gastrointestinal dysmotility, and skeletal abnormalities should prompt the suspicion for the diagnosis of CGL4, although phenotypic variability may occur.
First insights into herbivore–plant interaction of the spurge hawkmoth and Euphorbia cyparissias
Authors: Fiedler Stephanie , Langner Mathias , Oertel Reinhard , Vassão Daniel G. , Nitschke Julia , Gershenzon Jonathan , Hundsdoerfer Anna K.
Published: July 2023

The spurge hawkmoth Hyles euphorbiae (Lepidoptera, Sphingidae) is an insect herbivore feeding exclusively on spurges (Euphorbia). These are toxic due to their secondary metabolites including diterpene esters with numerous harmful biological activities, preventing their use by most herbivores. Extracts of frass from H. euphorbiae and of its main larval food plant in Central Europe, the cypress spurge (Euphorbia cyparissias L.), were analyzed via liquid chromatography using a triple-quadrupole (MS/MS) and a high-resolution–quadrupole time-of-flight mass spectrometer (QTOF-MS). We report for the first time the finding of the tigliane (phorbol ester) phorbol-13-acetate and two 12-O-tetradecanoylphorbol-13-acetate (TPA) isomers of unknown structure (compounds 2 and 3) in E. cyparissias. Our data support the assignment of these two compounds as tiglianes and are therefore referred to by us as “putative tiglianes”. Additionally, the distribution of the three reported compounds within the plant parts (leaves, stem and root) was analyzed to gain first insights into the metabolite conditions H. euphorbiae copes with in nature. Phorbol-13-acetate was detected in the plant’s root only, while the other compounds were observed in all three plant parts, although in different distributions. Moreover, our results indicate that the occurrence of compound 3 rises upon larval feeding. Finally, the presence of the plant-derived putative tiglianes in frass from E. cyparissias leaves feeding larvae is confirmed, corroborating the close plant–herbivore interaction.
Clinical and mutational spectrum of paediatric Charcot-Marie-Tooth disease in a large cohort of Chinese patients
Authors: Ma Yan , Duan Xiaohui , Liu Xiaoxuan , Fan Dongsheng
Published: July 2023

Background: Charcot-Marie-Tooth disease (CMT) is the most common inherited neurological disorder suffered in childhood. To date, the disease features have not been extensively characterized in the Chinese paediatric population. In this study, we aimed to analyse the clinical profiles and genetic distributions of a paediatric CMT cohort in China.

Methods: A total of 181 paediatric CMT patients were enrolled. After preexcluding PMP22 duplication/deletion by multiplex ligation-dependent probe amplification (MLPA), Sanger sequencing, targeted next-generation sequencing (NGS) or whole-exome sequencing (WES) was performed to obtain a genetic diagnosis. Detailed information was collected to explore the spectrum of subtypes and genotype-phenotype correlations.

Results: Pathogenic mutations were identified in 68% of patients in this study; with PMP22 duplication, MFN2 and GJB1 were the most frequent disease-causing genes. Of note, respect to the higher prevalence worldwide, CMT1A (18.2%) was relatively lower in our cohort. Besides, the mean age at onset (8.3 ± 5.7 years) was significantly older in our series. In genotype-phenotype analyse, PMP22 point mutations were considered the most severe genotypes and were mostly de novo. In addition, the de novo mutations were identified in up to 12.7% of all patients, which was higher than that in other studies.

Conclusion: We identified a relatively lower detection rate of PMP22 duplication and a higher frequency of de novo variants among paediatric patients in China. We also identified the genetic and phenotypic heterogeneity of this cohort, which may provide clues for clinicians in directing genetic testing strategies for Chinese patients with early-onset CMT.
Oxidative stress genes define two subtypes of triple-negative breast cancer with prognostic and therapeutic implications
Authors: Liu Shenting , Xu He , Feng Ying , Kahlert Ulf D. , Du Renfei , Torres-de la Roche Luz Angela , Xu Kai , Shi Wenjie , Meng Fanshuai
Published: July 2023

Introduction: Oxidative stress (OS)-related genes have been confirmed to be closely related to the prognosis of triple-negative breast cancer (TNBC) patients; despite this fact, there is still a lack of TNBC subtype strategies based on this gene guidance. Here, we aimed to explore OS-related subtypes and their prognostic value in TNBC.

Methods: Data from The Cancer Genome Atlas (TCGA)-TNBC and Sequence Read Archive (SRA) (SRR8518252) databases were collected, removing batch effects using a combat method before analysis. Consensus clustering analysis identified two OS subtypes (clusters A and B), with cluster A showing a better prognosis. Immune infiltration characteristics were analyzed using ESTIMATE and single-sample gene set enrichment analysis (ssGSEA) algorithms, revealing higher ImmuneScore and ESTIMATEscore in cluster A. Tumor-suppressive immune cells, human leukocyte antigen (HLA) genes, and three immune inhibitors were more prevalent in cluster A.

Results: An eight-gene signature, derived from differentially expressed genes, was developed and validated as an independent risk factor for TNBC. A nomogram combining the risk score and clinical variables accurately predicted patient outcomes. Finally, we also validated the classification effect of subtypes using hub markers of each subtype in the test dataset.

Conclusion: Our study reveals distinct molecular clusters based on OS-related genes to better clarify the reactive oxygen species (ROS)-mediated progression and the crosstalk between the ROS and tumor microenvironment (TME) in this heterogenetic disease, and construct a risk prognostic model which could provide more support for clinical treatment decisions.
Immunologic and nonimmunologic sclerodermal skin conditions - review
Authors: Bobeica Carmen , Niculet Elena , Craescu Mihaela , Parapiru Elena-Laura , Corduneanu-Luca Andreea Mioara , Debita Mihaela , Pelin Ana Maria , Tiutiuca Carmen , Vasile Claudiu Ionut , Nicolescu Alin Codrut , Miulescu Magdalena , Balan Gabriela , Tatu Alin Laurentiu
Published: July 2023

Scleroderma-like cutaneous lesions have been found in many pathological conditions and they have the clinical appearance of sclerotic or scleroatrophic lesions. Affected skin biopsies described histopathological changes similar to those of scleroderma located strictly on the skin or those of systemic sclerosis. These skin lesions can be found in inflammatory diseases with autoimmune substrate (generalized morphea, chronic graft versus host disease, eosinophilic fasciitis), tissue storage diseases (scleredema, scleromyxedema, nephrogenyc systemic fibrosis, systemic amyloidosis), metabolic diseases (porphyrya cutanea tarda, phenylketonuria, hypothyroidism, scleredema diabeticorum), progeroid syndromes. Given the multiple etiologies of sclerodermal lesions, a correct differential diagnosis is necessary to establish the appropriate treatment.
Case Report: Genetic and immune microenvironmental characteristics of a rectal cancer patient with MSS/PD-L1-negative recurrent hepatopulmonary metastasis who achieved complete remission after treatment with PD-1 inhibitor
Authors: Song Yang , Long Juan , Su Xiaona , Chen Zhuo , He Yue , Shao Weikang , Wang Bin , Chen Chuan
Published: July 2023

Currently, microsatellite high instability (MSI-H)/mismatch repair protein deletion (dMMR) has become a crucial biomarker for utilizing immune checkpoint inhibitors in patients with advanced colorectal cancer (mCRC). However, the proportion of MSI-H/dMMR in advanced patients is only about 5% and mCRC patients with microsatellite stability (MSS)/proficient mismatch repair (pMMR) exhibit poor responses to immunotherapy. Although diverse immune combination therapy regimens have been examined in patients with advanced colorectal cancer who demonstrate MSS/pMMR, these approaches have not yielded favorable efficacy and only a limited proportion of patients have benefited, especially for advanced colorectal cancer patients with liver metastases. Therefore, the mechanism of benefit and potential biomarkers of immunotherapy in patients with MSS/pMMR mCRC deserve more in-depth exploration. Here, we present a case study of a rectal cancer patient with MSS and PD-L1-negative recurrent hepatopulmonary metastases who attained complete remission (CR) and sustained benefits with immunotherapy after systemic therapy had failed. The analysis of the patient’s genetic and immune microenvironmental characteristics revealed that mutations in DNA damage repair (DDR) pathway genes and the existence of abundant tumor-infiltrating lymphocytes could contribute to his potential benefit.
In vitro differentiated human CD4+ T cells produce hepatocyte growth factor
Authors: Ford Shayne Lavondua , Buus Terkild Brink , Nastasi Claudia , Geisler Carsten , Bonefeld Charlotte Menné , Ødum Niels , Woetmann Anders
Published: July 2023

Differentiation of naive CD4+ T cells into effector T cells is a dynamic process in which the cells are polarized into T helper (Th) subsets. The subsets largely consist of four fundamental categories: Th1, Th2, Th17, and regulatory T cells. We show that human memory CD4+ T cells can produce hepatocyte growth factor (HGF), a pleiotropic cytokine which can affect several tissue types through signaling by its receptor, c-Met. In vitro differentiation of T cells into Th-like subsets revealed that HGF producing T cells increase under Th1 conditions. Enrichment of HGF producing cells was possible by targeting cells with surface CD30 expression, a marker discovered through single-cell RNA-sequencing. Furthermore, pharmacological inhibition of PI3K or mTOR was found to inhibit HGF mRNA and protein, while an Akt inhibitor was found to increase these levels. The findings suggest that HGF producing T cells could play a role in disease where Th1 are present.
Nanocrystal formation during thermal treatment of phosphoric-acid-swollen polybenzimidazole membranes
Authors: Ivanova O. , Lüke W. , Nemkovski K. , Appavou M.-S. , Szekely N. K. , Pipich V. , Frielinghaus H. , Monkenbusch M. , Zorn R. , Lehnert W. , Holderer O.
Published: July 2023

The design of suitable and efficient membranes for fuel and electrolyzer cells has been a long standing problem that still seeks for technical improvements. The structural properties of proton conducting poly [2,2-(m-phenylene)-5,5-bibenzimidazole] (PBI) membranes doped with phosphoric acid as electrolyte have been investigated prior and after thermal treatment by small angle neutron scattering (SANS), neutron diffraction with polarization analysis and transmission electron microscopy (TEM). Our observations indicate that during the first heating attempt stable crystalline domains in the PBI are formed and they persist in all further thermal cycles typical for electrolyte membrane operation. The combination of real space TEM picture under cryogenic conditions and reciprocal space scattering pattern with enhanced contrast by partial deuteration allows obtaining unique insight into the structure of proton conducting membranes, i.e., characteristic distances associated with irreversible changes as well as volume fraction of the different phases of the sample.
Efficacy and safety of Nirmatrelvir/Ritonavir for treating the Omicron variant of COVID-19
Authors: Qiu Chaochao , Wu Zhengxing , Liu Xiaojing , Zhang Qiang , Wu Lianpeng , Ye Xinchun , Zhou Jiajun , Shi Jichan , Jiang Xiangao
Published: July 2023

Objective

To evaluate the efficacy and safety of Nirmatrelvir/Ritonavir in the treatment of the Omicron variant of coronavirus disease 2019 (COVID-19).

Methods

Data from 58 patients who were infected with the Omicron variant of COVID-19 were retrospectively collected. The patients were divided into two groups according to the treatment regimen they received. Patients in both groups were given Lianhua Qingwen capsules orally, three times/day, 6 g/time. The study group was given Nirmatrelvir 300 mg/Ritonavir 100 mg orally, q12h, for 5 days, and the control group was not given any antiviral drugs. The two groups were compared in terms of the change in computed tomography (CT) values of COVID-19 nucleic acid, the negative conversion time of COVID-19 RNA, hospitalization time, adverse drug reactions and COVID-19 nucleic acid re-positive tests.

Results

The time to increase the CT values in the study group was faster than that in the control group, and the CT values in the study group were significantly larger than in the control group on days four and seven (p < 0.05); The negative conversion time in the study group was shorter than the control group (Z = –2.424, p = 0.015), and the hospitalization time was also shorter (Z = –2.603, p = 0.009). There were no statistically significant adverse drug reactions during hospitalization in both groups (χ2 = 2.747, p = 0.097). None of the study group tested re-positive for SARS-CoV-2 nucleic acid after discharge.

Conclusion

The efficacy of Nirmatrelvir/Ritonavir in the treatment of the Omicron variant of COVID-19 was positive and had good tolerance in patients.
Mendelian randomization study reveals the effect of idiopathic pulmonary fibrosis on the risk of erectile dysfunction
Authors: Zhang Kun , Zhou Jiejun , Li Anqi , Chen Mingwei
Published: July 2023

Background

Several studies have found that erectile dysfunction (ED) is associated with interstitial lung disease. However, the causal relationship between idiopathic pulmonary fibrosis (IPF) and ED risk remains unclear. The present two-sample Mendelian randomization (MR) study aimed to reveal the causal effect of IPF on ED risk.

Methods

This study included two GWAS summary statistics of IPF (1,028 cases and 196,986 controls) and ED (6,175 cases and 217,630 controls) of European ancestry. The inverse-variance weighted (IVW) was applied as the primary method, and MR-Egger, weighted median, weighted mode, and simple mode were applied as complementary methods to estimate the causal impact of IPF on ED risk. The MR-PRESSO global test and MR-Egger regression were applied to evaluate the pleiotropy. The Cochran’s Q test was applied to examine heterogeneity. The leave-one-out analysis ensured the robustness and reliability of the results.

Results

Twenty-one genetic variants were obtained as IPF instrumental variables without pleiotropy and heterogeneity. MR analysis using the IVW showed a potential causal relationship between IPF and increased ED risk (ORIVW = 1.046, 95% CI: 1.020–1.073, p = 0.001), and consistent results were obtained with MR-Egger, weighted median, and weighted mode. The leave-one-out analysis showed that no instrumental variables unduly influenced the results.

Conclusion

This study suggested that IPF may increase the ED risk of the European population.
Targeted metagenomics using bait-capture to detect antibiotic resistance genes in retail meat and seafood
Authors: Flint Annika , Cooper Ashley , Rao Mary , Weedmark Kelly , Carrillo Catherine , Tamber Sandeep
Published: July 2023

Metagenomics analysis of foods has the potential to provide comprehensive data on the presence and prevalence of antimicrobial resistance (AMR) genes in the microbiome of foods. However, AMR genes are generally present in low abundance compared to other bacterial genes in the food microbiome and consequently require multiple rounds of in-depth sequencing for detection. Here, a metagenomics approach, using bait-capture probes targeting antimicrobial resistance and plasmid genes, is used to characterize the resistome and plasmidome of retail beef, chicken, oyster, shrimp, and veal enrichment cultures (n = 15). Compared to total shotgun metagenomics, bait-capture required approximately 40-fold fewer sequence reads to detect twice the number of AMR gene classes, AMR gene families, and plasmid genes across all sample types. For the detection of critically important extended spectrum beta-lactamase (ESBL) genes the bait capture method had a higher overall positivity rate (44%) compared to shotgun metagenomics (26%), and a culture-based method (29%). Overall, the results support the use of bait-capture for the identification of low abundance genes such as AMR genes from food samples.
ACE2 receptor polymorphism in humans and animals increases the risk of the emergence of SARS-CoV-2 variants during repeated intra- and inter-species host-switching of the virus
Authors: Devaux Christian A. , Fantini Jacques
Published: July 2023

Like other coronaviruses, SARS-CoV-2 has ability to spread through human-to-human transmission and to circulate from humans to animals and from animals to humans. A high frequency of SARS-CoV-2 mutations has been observed in the viruses isolated from both humans and animals, suggesting a genetic fitness under positive selection in both ecological niches. The most documented positive selection force driving SARS-CoV-2 mutations is the host-specific immune response. However, after electrostatic interactions with lipid rafts, the first contact between the virus and host proteins is the viral spike-cellular receptor binding. Therefore, it is likely that the first level of selection pressure impacting viral fitness relates to the virus’s affinity for its receptor, the angiotensin I converting enzyme 2 (ACE2). Although sufficiently conserved in a huge number of species to support binding of the viral spike with enough affinity to initiate fusion, ACE2 is highly polymorphic both among species and within a species. Here, we provide evidence suggesting that when the viral spike-ACE2 receptor interaction is not optimal, due to host-switching, mutations can be selected to improve the affinity of the spike for the ACE2 expressed by the new host. Notably, SARS-CoV-2 is mutation-prone in the spike receptor binding domain (RBD), allowing a better fit for ACE2 orthologs in animals. It is possibly that this may also be true for rare human alleles of ACE2 when the virus is spreading to billions of people. In this study, we present evidence that human subjects expressing the rare E329G allele of ACE2 with higher allele frequencies in European populations exhibit a improved affinity for the SARS-CoV-2 spike N501Y variant of the virus. This may suggest that this viral N501Y variant emerged in the human population after SARS-CoV-2 had infected a human carrying the rare E329G allele of ACE2. In addition, this viral evolution could impact viral replication as well as the ability of the adaptive humoral response to control infection with RBD-specific neutralizing antibodies. In a shifting landscape, this ACE2-driven genetic drift of SARS-CoV-2 which we have named the ‘boomerang effect’, could complicate the challenge of preventing COVID with a SARS-CoV-2 spike-derived vaccine.
Nitenpyram biodegradation by a novel nitenpyram-degrading bacterium, Ochrobactrum sp. strain DF-1, and its novel degradation pathway
Authors: Wang Guangli , Chen Mengqing , Jiang Li , Zhang Yunfang
Published: July 2023

Nitenpyram is a neonicotinoid insecticide that is commonly found in the environment. However, its biodegradation by pure cultures of bacteria has not been widely investigated and the catabolic pathway (s) for nitenpyram metabolism remain elusive. In this study, the aerobic strain DF-1, isolated from a wastewater-treatment pool contaminated with nitenpyram. The strain was designated an Ochrobactrum sp. utilizing a combination of traditional methods and molecular ones. Strain DF-1 can use nitenpyram as a sole carbon or nitrogen source for growth. In liquid medium, 100 mg·L−1 nitenpyram was metabolized to undetectable levels within 10 days. Four metabolites were found by gas chromatography–mass spectrometry (GC–MS) analyses during nitenpyram degradation. According to the aforementioned data, a partial metabolic pathway of nitenpyram was proposed of strain DF-1. Inoculation of strain DF-1 promoted nitenpyram (10 mg·kg−1) degradation in either sterile or non-sterile soil. To our knowledge, this is the first characterization of nitenpyram degradation by a specific bacterium and likely to be exploited for the remediation of nitenpyram-contaminated sites.
Comparative analysis of nine Tilletia indica genomes for the development of novel microsatellite markers for genetic diversity and population structure analysis
Authors: Kashyap Prem Lal , Kumar Sudheer , Kumar Ravi Shekhar , Sharma Anju , Khanna Annie , Kajal  , Raj Shubham , Jasrotia Poonam , Singh Gyanendra
Published: July 2023

Karnal bunt (KB; Tilletia indica) is the prime quarantine concern for quality wheat production throughout the world. The most effective approach to dealing with this biotic stress is to breed KB-resistant wheat varieties, which warrants a better understanding of T. indica genome architecture. In India, the North Western Plain Zone is the prime hot spot for KB disease, but only limited efforts have been made to decipher T. indica diversity at the genomic level. Microsatellites offer a powerful and robust typing system for the characterization and genetic diversity assessment of plant pathogens. At present, inadequate information is available with respect to the development of genome-derived markers for revealing genetic variability in T. indica populations. In current research, nine complete genome sequences of T. indica (PSWKBGH_1, PSWKBGH_2, PSWKBGD_1_3, RAKB_UP_1, TiK_1, Tik, DAOMC236408, DAOMC236414, and DAOMC236416) that exist in the public domain were explored to know the dynamic distribution of microsatellites. Comparative genome analysis revealed a high level of relative abundance and relative density of microsatellites in the PSWKBGH_1 genome in contrast to other genomes. No significant correlation between microsatellite distribution for GC content and genome size was established. All the genomes showed the dominance of tri-nucleotide motifs, followed by mono-, di-, tetra-, hexa-, and penta-nucleotide motifs. Out of 50 tested markers, 36 showed successful amplification in T. indica isolates and produced 52 different alleles. A PCR assay along with analysis of the polymorphic information content (PIC) revealed 10 markers as neutral and polymorphic loci (PIC 0.37). The identified polymorphic SSR loci grouped a geographically distinct T. indica population of 50 isolates representing seven Indian regions (Jammu, Himachal Pradesh, Punjab, Haryana, Uttarakhand, Uttar Pradesh, and Rajasthan) into four distinct clusters. The results of the analysis of molecular variance identified 94% genetic variation within the population and 6% among the population. Structure analysis also confirmed the existence of four genetically diverse groups containing admixtures of T. indica isolates across populations. In nutshell, the current study was successful in identifying novel, neutral and polymorphic microsatellite markers that will be valuable in offering deep insight into the evolutionary relationship and dynamics of the T. indica population for devising effective KB management strategies in wheat.
The lipid composition of extracellular vesicles: applications in diagnostics and therapeutic delivery
Authors: Ghadami Samaneh , Dellinger Kristen
Published: July 2023

Extracellular vesicles (EVs), including exosomes, with nanoscale sizes, biological origins, various functions, and unique lipid and protein compositions have been introduced as versatile tools for diagnostic and therapeutic medical applications. Numerous studies have reported the importance of the lipid composition of EVs and its influence on their mechanism of action. For example, changes in the lipidomic profile of EVs have been shown to influence the progression of various diseases, including ovarian malignancies and prostate cancer. In this review, we endeavored to examine differences in the lipid content of EV membranes derived from different cell types to characterize their capabilities as diagnostic tools and treatments for diseases like cancer and Alzheimer’s disease. We additionally discuss designing functionalized vesicles, whether synthetically by hybrid methods or by changing the lipid composition of natural EVs. Lastly, we provide an overview of current and potential biomedical applications and perspectives on the future of this growing field.
Differences in the lipid metabolism profile and clinical characteristics between eosinophilic and non-eosinophilic acute exacerbation of chronic obstructive pulmonary disease
Authors: Wang Yating , Chang Chun , Tian Sifan , Wang Juan , Gai Xiaoyan , Zhou Qiqiang , Chen Yahong , Gao Xu , Sun Yongchang , Liang Ying
Published: July 2023

Objective: In this study, we aimed to investigate the differences in serum lipid metabolite profiles and their relationship with clinical characteristics between patients with eosinophilic and non-eosinophilic AECOPD.

Methods: A total of 71 AECOPD patients were enrolled. Eosinophilic AECOPD was defined as blood EOS% ≥ 2% (n = 23), while non-eosinophilic AECOPD, as blood EOS< 2% (n = 48). Clinical data were collected, and serum lipid metabolism profiles were detected by liquid chromatography–mass spectrometry (LC-MS). The XCMS software package was used to pre-process the raw data, and then, lipid metabolite identification was achieved through a spectral match using LipidBlast library. Differences in lipid profiles and clinical features between eosinophilic and non-eosinophilic groups were analyzed by generalized linear regression. The least absolute shrinkage and selection operator (LASSO) was applied to screen the most characteristic lipid markers for the eosinophilic phenotype.

Results: Eosinophilic AECOPD patients had less hypercapnic respiratory failures, less ICU admissions, a shorter length of stay in the hospital, and a lower fibrinogen level. In the lipid metabolism profiles, 32 significantly different lipid metabolites were screened through a t-test adjusted by using FDR (FDR-adjusted p < 0.05 and VIP> 1). Nine differential lipid metabolites were found to be associated with the three clinical features, namely, hypercapnia respiratory failure, ICU admission, and fibrinogen in further integration analysis. The species of triacylglycerol (TAG), phosphatidylcholine (PC), lysophosphatidylcholine (LPC), and diacylglyceryl trimethylhomoserine (DGTS) were high in these eosinophilic AECOPD. The LASSO was applied, and three lipid metabolites were retained, namely, LPC (16:0), TAG (17:0/17:2/17:2), and LPC (20:2). The logistic regression model was fitted using these three markers, and the area under the ROC curve of the model was 0.834 (95% CI: 0.740–0.929).

Conclusion: Patients with eosinophilic AECOPD had a unique lipid metabolism status. Species of TAGs and LPCs were significantly increased in this phenotype and were associated with better clinical outcomes.
Social-coalitional trait is related to coping capacity with mortality threat: association with leadership and a reduced parietal response to mortality salience
Authors: Hirano Kanan , Oba Kentaro , Saito Toshiki , Kawashima Ryuta , Sugiura Motoaki
Published: July 2023

Introduction

Coping with mortality threat, a psychological threat unique to humans and distinct from general emotional distress, is traditionally characterized by immediate suppression and prolonged worldview defense within the framework of the influential terror management theory (TMT). Views regarding the personality-trait concepts for this coping capacity diverge: some favor a broad definition based on general psychological attitudes (e.g., hardiness), while others prefer a narrow definition linked to interpersonal attitudes related to social coalition (e.g., attachment style and self-transcendence).

Methods

Using functional MRI, we presented healthy older participants with death-related words and explored correlations between the neural responses to mortality threat and the factor scores of the Power to Live questionnaire, which measures eight resilience-related psychobehavioral traits.

Results

We observed a significant association between the factor score and a neural response only for leadership; individuals with a high leadership score exhibited reduced neural response to mortality salience in the right inferior parietal lobule.

Discussion

Within the TMT framework, our findings align with the concept of the immediate suppression of death-thought accessibility associated with a secure attachment style, a trait conceptually linked to leadership. These findings highlight the unique role for the narrowly defined social-coalitional trait during the immediate stage of the coping process with mortality salience, in contrast to the broadly defined resilience-related personality traits associated with a prolonged worldview defense process. The deterioration of this coping process could constitute a distinct aspect of psychopathology, separate from dysfunction in general emotion regulation.