bluuebunny/crossref_metadata_2025 huggingface dataset:
Opinions of Resident Foreign Parents Living in Antalya on The Turkish Learning Process
Authors: ÇALIŞKAN Emre
Published: August 2023

The aim of this study is to examine the views of parents on foreign children's language, school adjustment and social skills by considering the level of certain different skills in the educational environment of foreign children included in the education system. In the research, the qualitative research method depending on the situation pattern was used and the opinions of the parents of 20 foreign children were taken. Interviews were conducted through a semi-structured interview form, and direct quotations were included in the study. Expert opinions on the relevant measurement tool were received and five questions were asked within the scope of the research. The parents of 20 students studying at primary and secondary schools in the city of Antalya were determined according to the criterion sampling method. Content analysis method was used in the analysis of the data. Content analysis; coding of the data, finding the themes, arranging the codes and themes, defining and interpreting the findings took place in four stages. According to the results of the research, the parents stated that the most important factor that negatively affects the language, school adaptation and social skills of foreign students is not knowing Turkish. For this reason, it has been stated that in order to improve the social skills of foreign students, it is necessary to teach Turkish to all foreign students first, and then move on to other skills training.
Global Goals for Sustainability Integration?
Authors:   , Montesano Francesco Saverio
Published: August 2023

In the Anthropocene, the interplay between human and natural systems has become deeper and more complex than ever. This has increased the normative urgency of sustainability integration, exposing two main gaps. First, a knowledge gap between the new context and the conceptual frameworks available to understand its impact on how we perceive and deal with sustainability integration as a response to those changes. Second, an institutional gap between the structure and aims of current institutions – which include the Sustainable Development Goals - and the demands and challenges of the new Anthropocenic context. This thesis begins by developing a conceptual framework to investigate whether and how change towards sustainability integration is happening at the ideational, normative, and institutional level. It then puts the framework to the test and addresses three main research questions. First, how can we study and explain which models of sustainability integration are prevalent in the Anthropocene? Second, which models of sustainability integration are prevalent and why? Third, how do institutions such as the SDGs influence the prevalence of different models of sustainability integration? The results show a generalised prevalence of the balanced model of integration over the ecocentric model. The ambiguous relationship observed between the SDGs and different models of integration is also likely to affect their ability to fulfil their ambitious claims.
STUDY OF PREVALENCE AND CAUSES OF SUB-CLINICAL MASTITIS IN GOATS OF GANDAKI PROVINCE, NEPAL
Authors: Poudel B. , Poudel N , Bhattarai N , Kandel R , Dahal M , Shrestha A , Malla S , Ghimire SH , Bhattarai P.S ,   Agriculture and Forestry University,   Goat Research Station, NARC, Bandipur, Nepa,   Ministry of Land Management, Agriculture and Cooperatives, Gandaki Province, Kaski, Nepal
Published: August 2023

A study was conducted to determine the prevalence and causes of subclinical mastitis in goats at Goat Research Station (GRS), Bandipur, and National Livestock Breeding Office (NLBO) farm Lampatan, Pokhara. Altogether 61 samples including 43 from GRS and 18 from NLBO were screened for subclinical mastitis using the California Mastitis Test (CMT) reagent, of which positive samples were then aseptically collected in a sterile 10 ml plastic tube and cultured in nutrient agar. Culturepositive samples were Gram-stained to determine their type (gram-positive or gram-negative). In the case of mixed colonies, the culture was sub-cultured. The data were entered and tabular and graphical representation was done in MS-Excel 2010. Results revealed that 26.23% of samples were positive for CMT and of 122 active teats tested, 19 (15.57%) were positive for CMT. Similarly, 23.3% of samples from goats of GRS, and Bandipur were CMT positive whereas 33.3% of samples from goats of NLBO, and Pokhara were positive. On the other hand, the prevalence of subclinical mastitis was 27.27%, 31.03%, and 19.04% for Saanen, Boer, and cross-bred goats, respectively. Considering the samples collected from GRS, 75% were culture-positive of total cultured samples while those from NLBO showed 57.14 % culture positive. In the meantime, overall samples showed 68.42% of total cultured samples to be culture positive. Out of 12 culturepositive samples, 92.30 %( 11/12) were gram-positive and only 7.69 %( 1/12) were gram-negative.
PNEUMATIC BENCH VICE
Authors: Shafi S Mohamed , O H Purushothaman ,   Mohamed Sathak AJ College of Engineering
Published: August 2023

The goal of this project is to create a model of bench vice which is pneumatically operated. Using air pressure to create mechanical motion in the spindle of the vice provides a safe &efficient way to reduce human effort. The mechanical motion in the spindle is created with the help of a double actuating cylinder which is operated by a 5/2 pilot valve & two 3/2 push buttons with the help of the air hoses. A vice is a mechanical screw apparatus used for holding or clamping a work piece to allow work to be performed on it with tools such as saws, planes, drills, mills, screwdrivers, sandpaper, etc. Vices usually have one fixed jaw and another parallel jaw which is moved towards or away from the fixed jaw by the screw. Vice is used to drill a wood, metal, etc. by holding your work piece tightly, it gives you all stability you need so you can make precise cuts. Even it is used for sawing a job with constant force applied by hand, or automatically, in order to cut desired shapes. A pneumatic system is controlled through manual or automatic process. In this Automatic pneumatic vice project for metal working is provided with widely and quick movable clamping jaw and fixed jaw where the vertical clamping surface of the fixed jaw and the horizontal surface of the fastening plane for the working piece confirm an accurate and unchangeable. Using automatically operated pneumatic vice will help you to get the work down easily and save energy.
EXPLORATORY ANALYSIS OF GEOLOCATIONAL DATA
Authors: D Likhitha , K Pooja , . Ashwini , Shankar Bhagyashree , Rapate Gauri Sameer ,   PES UNIVERSITY
Published: August 2023

This paper is about development of a website to find best accommodation for people or wishing to relocate based on the budget and proximity to the desired location. The user canlog in and search for the houses based on the desired location and budget and user can also contact owner and can view the place with 360-degree view of image. For this we use K-means Clustering algorithm to refine the search.. Grocery shopping is the second objective of the proposed work.
FIRE FIGHTING ROBOT
Authors: Iyer Dr.Rajiv , Kamble Vinayak , Bhagat Mayur , Upadhyay Chandradhar , Therattil Dhaval ,   K.C. College of Engineering
Published: August 2023

— The Project is designed to develop a Low-Cost firefighting Robot using Bluetooth technology for remote operation. Bluetooth HC-05 module is used for this purpose. The robotic vehicle is loaded with water tanker and a pump which is controlled over wireless communication to sprinkle water. At the transmitting end using push Bluetooth app, commands are sent to the receiver to control the movement of the robot either to move forward, backward and left or right etc. At the receiving end four motors are interfaced to the micro controller where two of them are used for the movement of the vehicle. A water tank along with water pump is mounted on the robot body. The whole operation is controlled by an ATMEGA328 series micro-controller. A motor driver IC, L293D is interfaced to the microcontroller through which the controller drives the motors. We are using ESP32 MCU and camera module to process the real time video transmission. The transmitted video can we streaming on IP network.
THE PROSE OF IHOR KOSTETSKYI
Authors: Vasylenko Vadym
Published: August 2023

The paper examines the literary technique of Ihor Kostetskyi and the innovative forms and content of his prose from the late 1940s. It focuses on the author’s attempts to update the genre nature of a short story. The analysis covers the principles of creating a figurative system, the structure of a prose narrative, the use of cinematic constructions, the ‘stream of consciousness’ technique, the situation of a lacuna, ‘text within a text’, etc.

The research involved the works included in the collection “Stories about the Winners”, as well as the short stories “You Own the Whole World”, “Before the Upcoming Day”, “Divine Lies”, and samples of their critical reception (in particular, the studies by Victor Petrov, Volodymyr Derzhavyn, Yurii Sherekh, and others).

Kostetskyi’s collection of short prose “The Story of the Winners” is regarded as a kind of laboratory in which the writer explored the possibilities of language and literary techniques, experimenting with the concepts of genre and image. It is argued that the writer sought to create a technical picture of the world that has nothing to do with the physical world, and the images he created are signs and symbols that need to be deciphered. In the short story “You Own the Whole World”, which is perceived as a “telegraphic mini-version of a psychological novel” or a “mini-novel with a mini-prologue”, one can find the ‘stream of consciousness’ technique and the situation of a gap, that is, a gap between the story of traumatic event and reality when the reader does not receive an unambiguous answer to the question of where the event occurs and whether it occurs at all. The compositional technique of ‘text within a text’, tested by Kostetskyi in the short story “Before the Upcoming Day”, performs the function of a hidden ‘message’ and allows inserting ‘internal’ actions and dialogues into ‘external’ ones.

In general, Kostetskyi’s works appeal to the subconscious, enhanced associativity and imagination, and the play factor is important in them as one of the elements of the author’s poetics.
Plant Diseases Classification based Leaves Image using Convolutional Neural Network
Authors: Imanulloh Satrio Bagus , Muslikh Ahmad Rofiqul , Setiadi De Rosal Ignatius Moses
Published: August 2023

Plant disease is one of the problems in the world of agriculture. Early identification of plant diseases can reduce the risk of loss, so automation is needed to speed up identification. This study proposes a custom-designed convolutional neural network (CNN) model for plant disease recognition. The proposed CNN model is not complex and lightweight, so it can be implemented in model applications. The proposed CNN model consists of 12 CNN layers, which consist of eight layers for feature extraction and four layers as classifiers. Based on the experimental results of a plant disease dataset consisting of 38 classes with a total of 87,867 image records. The proposed model can get high performance and not overfitting, with 97%, 98%, 97% and 97%, respectively, for accuracy, precision, recall and f1-score. The performance of the proposed model is also better than some popular pre-trained models, such as InceptionV3 and MobileNetV2. The proposed model can also work well when implemented in mobile applications.
Deskripsi kemampuan penalaran matematis siswa SMP pada kompetensi barisan dan deret
Authors: Fitria Mia , Ferita Rolina Amriyanti , Roniannor M. , Yanti Williza , Hidayat Farid
Published: August 2023

Penelitian deskriptif kualitatif ini bertujuan untuk mendeskripsikan kemampuan penalaran matematis siswa SMP pada kompetensi barisan dan deret, khususnya aritmetika. Indikator yang digunakan terdiri dari empat yaitu kemampuan mengajukan dugaan, menyajikan pernyataan matematika melalui lisan atau tulisan, melakukan manipulasi matematika, dan menarik kesimpulan atau melakukan generalisasi. Penelitian dilaksanakan di SMP Negeri 1 Gambut, dengan subjek siswa kelas VIIIG. Dari 29 siswa yang ada, dipilih secara purposive sampling masing-masing 3 siswa dengan kategori kelompok skor tinggi, sedang, dan rendah. Teknik pengumpulan data yang digunakan adalah tes tertulis dan wawancara. Untuk menjamin keabsahan data dilakukan triangulasi teknik (tes dan wawancara) serta triangulasi sumber (siswa dan guru). Hasil penelitian menunjukkan bahwa indikator yang paling banyak muncul adalah kemampuan melakukan manipulasi matematika, sedangkan yang paling sedikit muncul adalah kemampuan menyajikan pernyataan matematika melalui lisan atau tulisan. Disarankan agar siswa tidak hanya fokus pada kemampuan perhitungan teknis tetapi harus mampu mengubah soal cerita ke dalam pernyataan matematika yang sesuai.
Nanoparticles and cytokine response
Authors: Nasrullah Mohammad , Meenakshi Sundaram Daniel Nisakar , Claerhout Jillian , Ha Khanh , Demirkaya Erkan , Uludag Hasan
Published: August 2023

Synthetic nanoparticles (NPs) are non-viral equivalents of viral gene delivery systems that are actively explored to deliver a spectrum of nucleic acids for diverse range of therapies. The success of the nanoparticulate delivery systems, in the form of efficacy and safety, depends on various factors related to the physicochemical features of the NPs, as well as their ability to remain “stealth” in the host environment. The initial cytokine response upon exposure to nucleic acid bearing NPs is a critical component of the host response and, unless desired, should be minimized to prevent the unintended consequences of NP administration. In this review article, we will summarize the most recent literature on cytokine responses to nanoparticulate delivery systems and identify the main factors affecting this response. The NP features responsible for eliciting the cytokine response are articulated along with other factors related to the mode of therapeutic administration. For diseases arising from altered cytokine pathophysiology, attempts to silence the individual components of cytokine response are summarized in the context of different diseases, and the roles of NP features on this respect are presented. We finish with the authors’ perspective on the possibility of engineering NP systems with controlled cytokine responses. This review is intended to sensitize the reader with important issues related to cytokine elicitation of non-viral NPs and the means of controlling them to design improved interventions in the clinical setting.
Decreasing hydrophobicity or shielding hydrophobic areas of CH2 attenuates low pH-induced IgG4 aggregation
Authors: Wu Qiang , Cao Chunlai , Wei Suzhen , He Hua , Chen Kangyue , Su Lijuan , Liu Qiulian , Li Shuang , Lai Yongjie , Li Jing
Published: August 2023

Protein aggregation is a major challenge in the development of therapeutic monoclonal antibodies (mAbs). Several stressors can cause protein aggregation, including temperature shifts, mechanical forces, freezing-thawing cycles, oxidants, reductants, and extreme pH. When antibodies are exposed to low pH conditions, aggregation increases dramatically. However, low pH treatment is widely used in protein A affinity chromatography and low pH viral inactivation procedures. In the development of an IgG4 subclass antibody, mAb1-IgG4 showed a strong tendency to aggregate when temporarily exposed to low pH conditions. Our findings showed that the aggregation of mAb1-IgG4 under low pH conditions is determined by the stability of the Fc. The CH2 domain is the least stable domain in mAb1-IgG4. The L309E, Q311D, and Q311E mutations in the CH2 domain significantly reduced the aggregation propensity, which could be attributed to a reduction in the hydrophobicity of the CH2 domain. Protein stabilizers, such as sucrose and mannose, could also attenuate low pH-induced mAb1-IgG4 aggregation by shielding hydrophobic areas and increasing protein stability. Our findings provide valuable strategies for managing the aggregation of protein therapeutics with a human IgG4 backbone.
Erythrocyte parameters, anemia conditions, and sex differences are associated with the incidence of contrast-associated acute kidney injury after coronary angiography
Authors: Li Xihong , Chen Qingqing , Yang Xinrui , Li Duanbin , Du Changqing , Zhang Jun , Zhang Wenbin
Published: August 2023

Objective

Contrast-associated acute kidney injury (CA-AKI) is a critical complication when applying contrast medium, and the risk factors of CA-AKI have not been fully clarified. This study aimed to explore the relationships of CA-AKI with erythrocyte parameters, anemia conditions, and sex differences in patients after coronary angiography (CAG).

Methods

In this retrospective study, 4,269 patients who underwent CAG were enrolled. CA-AKI was defined as an increase in plasma creatinine of at least 0.5 mg/dl (44 μmol/L) or 25% within 72 h after exposure to the contrast medium. Three erythrocyte parameters, including hemoglobin, hematocrit, and red blood cell (RBC) count, were collected on admission. Logistic regression analyses were used to examine the associations of sex differences and erythrocyte parameters with CA-AKI in the overall population, restricted cubic splines to visualize these associations flexibly. Moreover, stratified and sensitivity analyses were conducted to assess the robustness of the findings.

Results

Overall, the mean (± standard deviations) age of patients was 67.05 ± 10.77 years, and 759 subjects (17.8%) developed CA-AKI. The results showed L-shaped relationships between erythrocyte parameters and CA-AKI incidence in each model (all P < 0.001). The incidence of CA-AKI was positively associated with the severity of anemia, while it showed no significant differences among the types of anemia. Moreover, female patients undergoing CAG had a higher risk of CA-AKI than male patients. Mediation analysis verified that erythrocyte parameters exerted an indirect effect on the sex differences of CA-AKI incidences.

Conclusion

In conclusion, females, perioperative anemia conditions, and lower erythrocyte parameters (hemoglobin, hematocrit, and RBC count) were verified as risk factors of CA-AKI in patients undergoing CAG. Furthermore, lower erythrocyte parameters among females exerted indirect effects on the sex differences in CA-AKI incidence.
Platinum-group elements (PGE) in the New Afton alkalic Cu-Au porphyry deposit, Canadian Cordillera, II: PGE distribution and models for the hydrothermal coprecipitation of Co-Ni-Pd-Pt in pyrite
Authors: Robb Samuel J. , Boucher Brandon M. , Mungall James E. , Hanley Jacob J.
Published: August 2023

The first part of this article can be found here: 10.3389/feart.2023.819129 (DOI). Occurrences of significant concentrations of platinum-group elements (PGE) in porphyry deposits have seen limited attention and the geochemical controls on their deposition are poorly understood. New Afton is a late Triassic alkalic Cu-Au porphyry deposit situated 10 km west of Kamloops, British Columbia with Pt and Pd enrichments locally exceeding 30 ppm. Primary PGE deposition accompanied hypogene Cu-Au mineralization linked to potassic alteration, with Pt and Pd deportment dominated by their inclusion in early Ni- and Co-rich pyrite with secondary amounts of platinum-group minerals (PGM) mertieite-II, isomertieite > temagamite, and kotulskite. Secondary hydrothermal alteration of hypogene PGE-rich pyrite promoted remobilization of PGE, creating vein-controlled PGE enrichment where essentially all Pt and Pd are hosted by PGM dominated by temagamite > mertieite-II, and sperrylite, leaving behind complementary PGE-depleted domains. Thermodynamic modelling shows that primary co-precipitation of Pt with Co and Pd with Ni can be explained solely through the cooling of a hydrothermal system, regardless of whether the mineralizing fluid was a brine or a low-density vapour. Pd and Pt were transported from an underlying magma reservoir into the porphyry system by a magmatic-hydrothermal fluid as Cl− complexes. Pt-rich cobaltian pyrite formed at the highest temperatures, whereas Pd-rich nickeliferous pyrite formed at somewhat lower temperatures. Zonation of metals in pyrite suggests that PGE were incorporated in pyrite under conditions of fluctuating fluid temperatures during transport and cooling of orthomagmatic fluids during the main Cu-Au mineralization stage. There exists a hitherto overlooked potential for significant Pt and Pd mineralization in early hypogene pyrite that may be spatially separated from visible Cu mineralization, especially in potassic or ultrapotassic systems.
Obesity and risk for respiratory diseases: a Mendelian randomization study
Authors: Yang Wenwen , Yang Yanjiang , Guo Yan , Guo Jinde , Ma Minjie , Han Biao
Published: August 2023

Background

No existing comprehensive Mendelian randomization studies have focused on how obesity affects respiratory diseases.

Methods

BMI and waist circumference, mainly from the UK Biobank, and 35 respiratory diseases from the FinnGen Biobank were subjected to Mendelian randomization analyses. In this study, the inverse variance weighting method was used as the predominant analysis method and was complemented by MR-Egger and weighted median methods. Horizontal pleiotropy and potential outliers were detected by employing the MR-PRESSO method.

Results:

This study indicated that obesity rises the possibility of acute upper respiratory infections (BMI: OR=1.131, p<0.0001; WC: OR=1.097, p=0.00406), acute sinusitis (BMI: OR=1.161, p=0.000262; WC: OR=1.209, p=0.000263), acute pharyngitis (WC: OR=1.238, p=0.0258), acute laryngitis and tracheitis (BMI: OR=1.202, p=0.0288; WC: OR=1.381, p=0.00192), all influenza (BMI: OR=1.243, p=0.000235; WC: OR=1.206, p=0.0119), viral pneumonia (WC: OR=1.446, p=0.000870), all pneumoniae (BMI: OR=1.174, p <0.0001; WC: OR=1.272, p <0.0001), bacterial pneumoniae (BMI: OR=1.183, p=0.000290; WC: OR=1.274, p<0.0001), acute bronchitis (BMI: OR=1.252, p <0.0001; WC: OR=1.237, p=0.000268), acute unspecified lower respiratory infection (BMI: OR=1.303, p=0.000403), chronic tonsils and adenoids diseases (BMI: OR=1.236, p <0.0001; WC: OR=1.178, p=0.000157), chronic laryngotracheitis and laryngitis (WC: OR=1.300, p=0.00785), COPD (BMI: OR=1.429, p <0.0001; WC: OR=1.591, p <0.0001), asthma (BMI: OR=1.358, p <0.0001; WC: OR=1.515, p <0.0001), necrotic and suppurative conditions of lower respiratory tract (WC: OR=1.405, p=0.0427), pleural effusion (BMI: OR=1.277, p=0.00225; WC: OR=1.561, p<0.0001), pleural plaque (BMI: OR=1.245, p=0.0312), other diseases of the respiratory system (BMI: OR=1.448, p <0.0001; WC: OR=1.590, p <0.0001), and non-small cell lung cancer (BMI: OR=1.262, p=0.00576; WC: OR=1.398, p=0.00181). This study also indicated that obesity decreases the possibility of bronchiectasis (BMI: OR=0.705; p=0.00200).

Conclusion:

This study revealed that obesity increases the risk of the majority of respiratory diseases (including 20 of all 35 respiratory diseases) and that obesity decreases the risk of bronchiectasis.
Incorporating phylogenetic conservatism and trait collinearity into machine learning frameworks can better predict macroinvertebrate traits
Authors: Li Shuyin , Luo Qingyi , Li Ruiwen , Li Bin
Published: August 2023

In the face of rapid environmental changes, understanding and monitoring biological traits and functional diversity are crucial for effective biomonitoring. However, when it comes to freshwater macroinvertebrates, a significant dearth of biological trait data poses a major challenge. In this opinion article, we put forward a machine-learning framework that incorporates phylogenetic conservatism and trait collinearity, aiming to provide a better vision for predicting macroinvertebrate traits in freshwater ecosystems. By adopting this proposed framework, we can advance biomonitoring efforts in freshwater ecosystems. Accurate predictions of macroinvertebrate traits enable us to assess functional diversity, identify environmental stressors, and monitor ecosystem health more effectively. This information is vital for making informed decisions regarding conservation and management strategies, especially in the context of rapidly changing environments.
A novel homozygous variant in PADI6 is associate with human cleavage-stage embryonic arrest
Authors: Cao Guangyi , Zhu Xiangyu , Lin Yuling , Fang Junshun , Shen Xiaoyue , Wang Shanshan , Kong Na
Published: August 2023

Repeated absence of useable embryos is a difficult problem for infertility patients. Among them, embryonic developmental arrest is more common, but the genetic cause is not known. The embryos of a patient who came to our hospital three times could not develop beyond the four-cell stage. In addition to recording the developmental details of the embryos by daily photo-taking, the PADI6R132C homozygous variants was further confirmed by whole-exome sequencing. Subsequently, PADI6R132C was analyzed by bioinformatics methods for conservativeness across species. In addition, the possible impact of the pathogenic mutation on the structure of the protein PADI6 were also assessed. Generally, we identified a homozygous variants [NM_207421.4, c.394C>T(p.R132C] in the middle protein-arginine deiminase domain in PADI6 gene. The homozygous variant is highly conserved across species. Homozygous variant in PADI6R132C could cause a human cleavage-stage embryonic arrest in female patients. These findings provide further evidence for the important roles of the homozygous PADI6R132C variant in embryonic development. Our findings contribute to a deeper understanding of the molecular genetic basis of female infertility.
Neutrophil extracellular traps and neutrophil-related mediators in human thyroid cancer
Authors: Modestino Luca , Cristinziano Leonardo , Poto Remo , Ventrici Annagioia , Trocchia Marialuisa , Ferrari Silvia Martina , Fallahi Poupak , Paparo Sabrina Rosaria , Marone Gianni , Antonelli Alessandro , Varricchi Gilda , Galdiero Maria Rosaria
Published: August 2023

Background

Polymorphonuclear neutrophils (PMNs) are the main effector cells in inflammatory responses and play multiple roles in thyroid cancer (TC). PMNs contain and release a plethora of mediators, including granular enzymes [e.g., myeloperoxidase (MPO), pentraxin-3 (PTX3) and matrix metalloproteinase-9 (MMP-9)], and neutrophil extracellular traps (NETs). The aim of this study was to evaluate NETs and neutrophil-derived mediators as possible biomarkers in TC patients.

Methods

20 patients with differentiated thyroid cancer (DTC), 26 patients with dedifferentiated thyroid cancer (De-DTC), 26 patients with multinodular goiter (MNG) and 22 healthy controls (HCs) were recruited. Serum concentrations of free DNA (dsDNA), nucleosomes, citrullinated histone H3 (CitH3) and MPO-DNA complexes were evaluated as NET biomarkers. Neutrophil-related mediators such as MPO, PTX3, MMP-9, CXCL8, and granulocyte-monocyte colony-stimulating factor (GM-CSF) were measured by ELISA.

Results

Serum levels of all four NET biomarkers were increased in DeDTC patients compared to HCs. CitH3 serum levels were selectively increased in both DeDTC and DTC patients compared to HCs and MNG patients. MPO-DNA complexes and nucleosomes were selectively increased only in DeDTC patients compared to HCs and MNG patients. Moreover, MPO-DNA complexes were selectively increased in DeDTC patients compared to DTC patients also. MPO circulating levels were selectively increased in the DeDTC patient subgroup compared to HCs. Circulating levels of PTX3, MMP-9 and GM-CSF were increased in DTC and DeDTC patients compared to HCs. Nucleosomes positively correlated with dsDNA, CitH3, MPO and CXCL8. MPO-DNA complexes positively correlated with dsDNA, CitH3, CXCL8, MPO and nucleosome levels. Moreover, three out of the four NET biomarkers (i.e., dsDNA, nucleosomes and MPO-DNA complexes) were increased in elderly patients compared to young patients and in patients with metastatic disease at diagnosis compared to non metastatic patients. Nucleosomes were higher in males compared to females.

Conclusion

MPO-DNA complexes, nucleosomes and, to some extent, CitH3 levels seem to correlate with malignancy and severity of progressive TC. Moreover, serum concentrations of PMN-related mediators (MPO, PTX3, GM-CSF) were increased in TCs compared to MNG and HCs.
Peripheral blood CD3+HLADR+ cells and associated gut microbiome species predict response and overall survival to immune checkpoint blockade
Authors: Gorgulho Joao , Roderburg Christoph , Beier Fabian , Bokemeyer Carsten , Brümmendorf Tim H. , Luedde Tom , Loosen Sven H.
Published: August 2023

Background

The search for biomarkers to identify ideal candidates for immune checkpoint inhibitor (ICI) therapy is fundamental. In this study, we analyze peripheral blood CD3+HLADR+ cells (activated T-cells) as a novel biomarker for ICI therapy and how its association to certain gut microbiome species can indicate individual treatment outcomes.

Methods

Flow cytometry analysis of peripheral mononuclear blood cells (PBMCs) was performed on n=70 patients undergoing ICI therapy for solid malignancies to quantify HLA-DR on circulating CD3+ cells. 16s-rRNA sequencing of stool samples was performed on n=37 patients to assess relative abundance of gut microbiota.

Results

Patients with a higher frequency of CD3+HLADR+ cells before treatment initiation showed a significantly reduced tumor response and overall survival (OS), a worst response and experienced less toxicities to ICI therapy. As such, patients with a frequency of CD3+HLADR+ cells above an ideal cut-off value of 18.55% had a median OS of only 132 days compared to 569 days for patients below. Patients with increasing CD3+HLADR+ cell counts during therapy had a significantly improved OS. An immune signature score comprising CD3+HLADR+ cells and the neutrophil-lymphocyte ratio (NLR) was highly significant for predicting OS before and during therapy. When allied to the relative abundance of microbiota from the Burkholderiales order and the species Bacteroides vulgatus, two immune-microbial scores revealed a promising predictive and prognostic power.

Conclusion

We identify the frequencies and dynamics of CD3+HLADR+ cells as an easily accessible prognostic marker to predict outcome to ICIs, and how these could be associated with immune modulating microbiome species. Two unprecedented immune-microbial scores comprising CD3+HLADR+, NLR and relative abundance of gut bacteria from the Burkhorderiales order or Bacteroides vulgatus species could accurately predict OS to immune checkpoint blockade.
The role of ion channels in T cell function and disease
Authors: Manolios Nicholas , Papaemmanouil John , Adams David J.
Published: August 2023

T lymphocytes (T cells) are an important sub-group of cells in our immune system responsible for cell-mediated adaptive responses and maintaining immune homeostasis. Abnormalities in T cell function, lead the way to the persistence of infection, impaired immunosurveillance, lack of suppression of cancer growth, and autoimmune diseases. Ion channels play a critical role in the regulation of T cell signaling and cellular function and are often overlooked and understudied. Little is known about the ion “channelome” and the interaction of ion channels in immune cells. This review aims to summarize the published data on the impact of ion channels on T cell function and disease. The importance of ion channels in health and disease plus the fact they are easily accessible by virtue of being expressed on the surface of plasma membranes makes them excellent drug targets.
Comparison of live and fixed cell-based assay performance: implications for the diagnosis of MOGAD in a low-middle income country
Authors: Pandit Lekha , D’Cunha Anitha , Malli Chaithra , Sudhir Akshatha
Published: August 2023

Background

Though considered optimal, live cell-based assay (LCBA) is often unavailable for the diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD) in resource-poor regions. This study was undertaken to determine the agreement between LCBA and the widely available fixed cell-based assay (FCBA), for recommending testing guidelines within our region.

Method

All consecutive patients in our registry with a MOGAD phenotype were tested. The results from a commercially available FCBA (Euroimmun, Germany) were compared with a validated “in-house” LCBA. Clinical and MRI data were available for correlation.

Results

Among the 257 patient samples tested, 118 (45.9%) were positive by FCBA titre ≥1: 10 and or LCBA titres ≥1: 160 titre and 139 samples were negative. There was robust agreement between the two assays (agreement 98.8%, Cohen’s kappa 0.98 [95% CI- 0.95-1.00], Spearman correlation 0.97 (p < 0.0001). Among five discordant samples, four had clinical and or MRI data which supported an alternate diagnosis. There was a modest correlation between assay titres, particularly for samples with titres ≥ 1:100 in FCBA (Spearman’s Rho 0.26, p 0.005). Thirty samples were positive by FCBA at < 1:100 titre and included 1:80 (20),1:40(7) and 1:10 (3) titres. Among them, 80% had clear positive titres when tested by LCBA.

Conclusion

The FCBA tested with serum dilutions of 1:10 was highly predictive of MOGAD in our study and compared well with our “in-house” LCBA. The current recommendations for testing at higher dilutions need to be re-examined in light of our findings. The results of our study should ideally be replicated in a larger dataset but at the same time provide some guidance for the accurate diagnosis of MOGAD in resource-poor settings.
Multi-year variability of summer phytoplankton biomass and size structure in the northern Chukchi and East Siberian Seas, Arctic Ocean: role of light and nutrient availability
Authors: Lee Youngju , Cho Kyoung-Ho , Jung Jinyoung , Moon Jong Kuk , Yang Eun Jin , Kang Sung-Ho
Published: August 2023

In the Arctic Ocean, the northern Chukchi and East Siberian Seas (NCESS) are vulnerable to climate change due to warming, sea ice melting, and surface freshening. To investigate how local physical forcing affects phytoplankton biomass and communities in this area, the multi-year (2015-2020) distributions of summer (August) chlorophyll-a concentrations and size structures using data collected by the Korea-Arctic Ocean Observing System (K-AOOS) program were investigated. The environmental characteristics and phytoplankton communities in the study area showed east-west regional differences. It is characterized by warm fresh waters and strong stratification to the east and cold saline waters and relatively high nutrient and sea ice concentrations to the west. Despite the differences between the east and west regions, patterns of the inter-annual variation in phytoplankton biomass and communities were similar across the entire study area, implying environmental controllers regulating phytoplankton in the NCESS. Inter-annually, higher sea surface salinity and weaker water column stratification were observed in 2017-2019 than in 2015 and 2020, implying the possibility of a potential modulation by the Arctic Oscillation. The shallower nitracline depth and higher surface nutrient concentrations since 2017 compared to the period from 2015-2016, indicate improved nutrient availability due to Atlantic water intrusion. However, average insolation has been relatively low since 2017, with the exception of August 2018. August mean phytoplankton biomass was highest in 2018 in the study area (average 83.7 mgm-2) and was dominated by large-sized phytoplankton. The low phytoplankton biomass in 2017 (23.9 mgm-2) and 2019 (62.4 mgm-2), despite similar characteristics of nutrient concentration to 2018, is likely due to lower average daily insolation in both years (206 μEm-2d-1 and 184 μEm-2d-1 in 2017 and 2019, respectively) compared to the 2018 average (271 μEm-2d-1). These results suggest that increased intrusion through upwelling of Atlantic water, along with nutrient loading, could be a pivotal driving factor contributing to this enhanced production in the NCESS, particularly under conditions where light levels are sufficient for phytoplankton growth and bloom development.
Case report: Allogeneic stem cell transplantation for type B insulin resistance
Authors: Ebert Thomas , Behre Gerhard , Weidhase Lorenz , Vucinic Vladan , Gewert Cornelia , Semple Robert K. , Stumvoll Michael , Tönjes Anke
Published: August 2023

Type B insulin resistance (TBIR) is a rare, often fulminant form of insulin resistance caused by autoantibodies against the insulin receptor. If left untreated, its mortality is high. Various immunosuppressive regimens have shown efficacy, but treatment effects are variable and time-delayed, and drug-induced complications may arise. We report a patient with TBIR arising as a complication of Wiskott–Aldrich syndrome. Stable remission of TBIR was achieved through allogeneic peripheral blood stem cell transplantation (PBSCT) over a follow-up period of more than 1.5 years. We thus demonstrate that PBSCT can be considered a treatment option in TBIR where conventional immunosuppressive therapy is ineffective or contraindicated.
Colonization potential of endophytes from halophytic plants growing in the “Runn of Kutch” salt marshes and their contribution to mitigating salt stress in tomato cultivation
Authors: Sahu Pramod K. , Shafi Zaryab , Singh Shailendra , Ojha Khushboo , Jayalakshmi K. , Tilgam Jyotsana , Manzar Nazia , Sharma Pawan K. , Srivastava Alok K.
Published: August 2023

Increasing soil salinity depreciates the quantity of the crop produce. Looking at the tremendous potential of plant-associated microorganisms in salinity stress mitigation, it would be very useful in exploring and deciphering salt-tolerant microorganisms from halophytic plants and their utilization in cultivated plants. With this aim, in the present study, four halophytic plants were taken from Rann of Kutch, and bacterial endophytes were isolated from different plant organs. These endophytes were characterized by plant growth and health promotion features. The molecular identification was done based on 16 s rRNA sequence similarity. It was found that the endophytic bacteria isolated from 4 different halophytes found sharing phylogenetic relatedness. Four potential endophytes Alkalihalobacillus gibsonii 2H2, Achromobacter insuavis 2H18, Terribacillus halophilus 2H20, and Bacillus siamensis 4H1 were tested in tomato for salinity stress alleviation. Changes in the levels of antioxidants were analyzed. Total chlorophyll, total phenolics, malondialdehyde, and proline content indicated reduced damage in the plant system due to salinity by the application of endophytes. All the treatments exhibited low levels of electrolyte leakage. The accumulation of enzymatic reactive oxygen species scavengers was assessed from the levels of peroxidase, catalase, superoxide dismutase, phenylalanine ammonia-lyase, ascorbate peroxidase, and guiacol peroxidase. The NBT and DAB staining confirmed the findings. The reduction in the accumulation of Na+ ions in tomato leaves was visualized using Sodium Green probes under CSLM and found to be lowest in Terribacillus halophilus 2H20 and Bacillus siamensis 4H1 inoculated plants. The endophyte Terribacillus halophilus 2H20 was the most promising isolate. The colonization in tomato roots was confirmed using a cell tracker system. Results showed that the endophytes were found to have salinity stress mitigation traits. The efficiency could be further improved with the combination of other endophytes tested earlier.
Needs and supporting tools for primary care physicians to improve care of patients with vertigo and dizziness: a national survey
Authors: Mantokoudis Georgios , Zwergal Andreas , Heg Dierik , Kerkeni Hassen , Diener Suzie , Kalla Roger , Korda Athanasia , Candreia Claudia , Welge-Lüssen Antje , Tarnutzer Alexander Andrea
Published: August 2023

Background

The diagnostic workup and treatment decisions for vertigo or dizziness in primary care can be challenging due to the broad range of possible causes and limited time and expertise of physicians. This can lead to delays in treatment and unnecessary tests. We aimed to identify the unmet needs of primary care physicians (PCPs) and strategies to improve care for dizzy patients.

Materials and methods

An online survey was conducted among board-certified PCPs in Switzerland to explore needs in caring for dizzy patients and potential educational approaches.

Results

Based on responses from 152 participating PCPs, satisfaction and confidence were higher in diagnosing (82%) and treating (76%) acute dizziness compared to episodic/chronic cases (63 and 59%, respectively). Younger PCPs had lower diagnostic yield and confidence. Areas for improvement in specialist interactions included communication between physicians (23%/36%; always/often true), shorter waiting times for consultations (19%/40%), more detailed feedback (36%/35%), and consistent patient back referrals (31%/30%). PCPs expressed interest in hands-on courses, workshops, practical guidelines, web-based algorithms, and digital tools such as printed dizzy diaries and apps for follow-up.

Conclusion

Enhanced dialog between PCPs and specialists is crucial to address the most common unmet needs. Reducing waiting times for referrals and providing clear instructions to specialists for triage are essential. The findings from this survey will guide the development of tools to improve the diagnosis and treatment of dizzy patients. Younger PCPs, who face higher diagnostic uncertainty, should be prioritized for educational approaches such as hands-on courses, workshops, and practical recommendations.
CT radiomics model for predicting the Ki-67 proliferation index of pure-solid non-small cell lung cancer: a multicenter study
Authors: Liu Fen , Li Qingcheng , Xiang Zhiqiang , Li Xiaofang , Li Fangting , Huang Yingqiong , Zeng Ye , Lin Huashan , Fang Xiangjun , Yang Qinglai
Published: August 2023

Purpose

This study aimed to explore the efficacy of the computed tomography (CT) radiomics model for predicting the Ki-67 proliferation index (PI) of pure-solid non-small cell lung cancer (NSCLC).

Materials and methods

This retrospective study included pure-solid NSCLC patients from five centers. The radiomics features were extracted from thin-slice, non-enhanced CT images of the chest. The minimum redundancy maximum relevance (mRMR) and least absolute shrinkage and selection operator (LASSO) were used to reduce and select radiomics features. Logistic regression analysis was employed to build predictive models to determine Ki-67-high and Ki-67-low expression levels. Three prediction models were established: the clinical model, the radiomics model, and the nomogram model combining the radiomics signature and clinical features. The prediction efficiency of different models was evaluated using the area under the curve (AUC).

Results

A total of 211 NSCLC patients with pure-solid nodules or masses were included in the study (N=117 for the training cohort, N=49 for the internal validation cohort, and N=45 for the external validation cohort). The AUC values for the clinical models in the training, internal validation, and external validation cohorts were 0.73 (95% CI: 0.64–0.82), 0.75 (95% CI:0.62–0.89), and 0.72 (95% CI: 0.57–0.86), respectively. The radiomics models showed good predictive ability in diagnosing Ki-67 expression levels in the training cohort (AUC, 0.81 [95% CI: 0.73-0.89]), internal validation cohort (AUC, 0.81 [95% CI: 0.69-0.93]) and external validation cohort (AUC, 0.78 [95% CI: 0.64-0.91]). Compared to the clinical and radiomics models, the nomogram combining both radiomics signatures and clinical features had relatively better diagnostic performance in all three cohorts, with the AUC of 0.83 (95% CI: 0.76–0.90), 0.83 (95% CI: 0.71–0.94), and 0.81 (95% CI: 0.68–0.93), respectively.

Conclusion

The nomogram combining the radiomics signature and clinical features may be a potential non-invasive method for predicting Ki-67 expression levels in patients with pure-solid NSCLC.
Predictive analysis of catecholamines and electrolytes for recurrence of orthostatic intolerance in children
Authors: Chang Lujie , Peng Lu , Liu Jianglin , Wang Minmin , Li Meng , Kong Qingyu , Zhao Haizhao , Zhao Cuifen
Published: August 2023

Background

Orthostatic intolerance (OI) is usually mediated by the autonomic nerve and most often happens in the upright position. However, it can also occur in other positions and can be relieved by lying down while likely to have another attack after relief. In the current study, we aim to evaluate the predictive effect of catecholamines and electrolytes on the recurrence of OI in children.

Materials and methods

Children who were diagnosed with vasovagal syncope (VVS), postural tachycardia syndrome (POTS), and VVS combined with POTS were enrolled in this retrospective study and were followed up after 1-year physical treatment. Catecholamines in urine collected within 24 h, renin, angiotensin II, aldosterone in plasma, and electrolytes in both blood and urine collected in the morning were tested. A multivariate analysis and a receiver operating characteristic curve were used to validate the prediction effect.

Results

In the VVS cohort, the 24 h urine adrenaline (AD) and norepinephrine (NE) levels of the non-recurrence group were lower than the 24 h urine AD and NE levels of the recurrence group, with a significant difference of P < 0.05. A different content can also be witnessed in the POTS cohort that the urine of the non-recurrence group contained lower sodium and chlorine. As for the VVS + POTS cohort, the non-recurrence group has lower AD and NE levels and higher potassium and phosphorus levels in urine, the difference of which proved prominent as well.

Conclusion

The study provides further evidence that AD, NE, and electrolytes in urine are promising factors that are closely related to the recurrence of OI in children. The integrated evaluation system merging AD and NE may have better predictive ability.