bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma Glycoproteins and Biotherapeutics from a Proteoform Perspective
Authors:   , Cramer Dario Alexander Taco
Published: September 2024

For an analytical chemist interested in plasma proteins, a key question is: how do we best analyze (glyco)proteins and their glycans in all their beauty? This thesis describes an approach to these questions using peptide-centric and native mass spectrometry. A thorough introduction of protein characteristics on a biomolecular level, mass spectrometry techniques and glycosylation is followed by a review of current cell expression systems for recombinant glycoproteins. Using a combination of ion-exchange chromatography and native mass spectrometry, blood serum proteins are investigated in depth, revealing a wealth of proteoforms of serum glycoproteins, including new annotations such as phosphorylation and specific glycoforms, spanning a large range of masses. The metalloprotein cerulopasmin was also characterized including its copper metal masses by combining several analytical techniques. Additionally, two serum glycoproteins are studied in detail – alpha-1-antitrypsin and plasminogen. In the first, common mutations were resolved by native mass spectrometry with such detail that it was possible to quantify the different allelic expressions, revealing a discrepancy in abundance between common allelic mutations. In the latter, a new intermediate step in the activation of plasminogen to plasmin was found, as well as its elusive phosphorylation site by combining peptide-centric and native mass spectrometry. Knowledge gained on the analysis of these serum glycoproteins was also applied to complex, high molecular weight antibodies and their many by-products, making it possible to characterize potentially unwanted by-products on the molecular level. Here, the use of size-exclusion chromatography combined with mass photometry under various conditions permitted to draw conclusions on the effect of different by-products and their stability.
Evaluasi Usability Pada Aplikasi Teman Bus Menggunakan Metode System Usability Scale dan Heuristic Evaluation
Authors: Yuniati Trihastuti , Christiawan Dhamara Alan
Published: September 2024

Abstract : Teman Bus application is one form of digital development utilized to support Teman Bus transportation services. Based on comments found on the Google Play Store, users have encountered difficulties when using the application. Additionally, observations of the application have revealed several interface-related shortcomings, indicating the need for usability evaluation. The System Usability Scale (SUS) method was employed to evaluate the user perspective, while the Heuristic Evaluation (HE) method was used to evaluate from the expert perspective. The evaluation results showed an SUS score of 60.225 for the Teman Bus application, which falls into the "D" grade with an adjective rating of "OK" and a marginal level of acceptance. According to the Net Promoter Score (NPS), the obtained SUS score of 60.225 falls into the "Detractor" category. The HE evaluation identified three aspects with the highest severity ratings: "flexibility and efficiency of use," "recognition rather than recall," and "aesthetic & minimalist design."
Abstrak : Aplikasi Teman Bus merupakan salah satu bentuk perkembangan digital yang dimanfaatkan untuk mendukung layanan transportasi Teman Bus. Berdasarkan komentar yang ada pada Google Play Store, ditemukan kesulitan yang dialami oleh pengguna ketika menggunakan aplikasi tersebut, dan berdasarkan pengamatan pada aplikasi masih terdapat beberapa kekurangan pada aplikasi yang berkaitan dengan antarmuka sehingga perlu dilaksanakan evaluasi usability. Metode system usability scale digunakan untuk melakukan evaluasi dari perspektif pengguna, dan metode heuristic evaluation digunakan untuk melakukan evaluasi dari perspektif ahli. Hasil yang diperoleh pada evaluasi yaitu skor SUS pada aplikasi Teman Bus sebesar 60,225 masuk ke dalam grade �D� dengan tingkat adjective kategori �OK� dan tingkat penerimaannya kategori �Marginal�. Berdasarkan net promoter score (NPS) didapatkan bahwa skor SUS yang diperoleh sebesar 60,225 berada pada kategori �Detractor�. Evaluasi menggunakan metode HE diperoleh 3 aspek yang mendapatkan severity rating tertinggi yaitu �flexibility and efficiency of use�, �recognition rather than recall�, dan �aesthetic & minimalist design�.
Diatoms and geochemical features of bottom sediments of the Eastern Siberia seas and their implication for paleoreconstructions
Authors: Obrezkova Maria S. , Tsoy Ira B. , Astakhov Anatolii S.
Published: September 2024

The study of diatoms in the surface sediments of the seas of Eastern Siberia (SES) has shown that since the end of the last century there have been significant changes in the composition of species and their number in the diatom assemblages of this region. A promising direction in the in the reconstruction of changes in the natural environment in the Holocene is the study of diatoms and geochemical parameters of the host sediments, which allows us to obtain more meaningful and objective information about the paleoconditions and processes of sedimentation in the SES and other regions.
Diatoms in deposits of termocarstic lakes in Yamalo-Nenets Autonomous Okrug, West Siberian Arctic, Russia
Authors: Palagushkina Olga V. , Frolova Larisa A.
Published: September 2024

114 species of diatoms of two classes of thirty-three genera were identified from bottom sediments of three thermokarst lakes on the watershed of the river Pur (Yamalo-Nenets Autonomous Okrug - YNAO, West Siberian Arctic, Russian Federation). The species composition was dominated by penate cosmopolitan benthic oligohalobic species preferring alkaline environmental conditions.
Holocene diatom record of Gryazevoe Lake evolution
(Magadan region)
Authors: Cherepanova Marina V. , Romanova Alexandra V. , Minyuk Pavel S.
Published: September 2024

Diatoms from core Gz-1 (Lake Gryazevoe, Magadan region) belonging to 189 species and intraspecific taxa were studied. Three local zones (LzGz) were identified based on changes in the taxonomic composition and ecological structure of fossil diatom assemblages. They correspond to different stages of the lake ecosystem evolution during the Late Pleistocene-Holocene. A sensitive reaction of diatoms to hydrological and hydrochemical changes of the lake regimes associated with paleoclimatic fluctuations has been established.
Soil diatoms of oilfield areas
Authors: Dorokhova Marina F.
Published: September 2024

The results of the study of soil diatoms in oil production areas of Russia are presented. The contribution of the Kirov school of algologists to the development of ideas about the diversity of soil diatoms in oil-producing areas and the possibility of their use for bioindication of the state of technogenically transformed soils is shown.
Diatoms of the Novosibirsk reservoir as indicators of the quality of its waters
Authors: Mikhailov Vyacheslav V.
Published: September 2024

According to the saprobity of diatoms, the water quality in 2016–2017 in the upper zone of the Novosibirsk reservoir met the category of “satisfactory cleanliness”. In the middle and lower parts in 2017 – “satisfactory cleanliness”, except for 2016, where it was “polluted”. In Berdsky Bay, water in 2016 was classified as “satisfactory purity”, and in 2017 it was «polluted».
The role of diatoms algae in phytoplankton of dystrophic lakes
Authors: Petrov Vladimir N. , Karpaeva Anastasija J.
Published: September 2024

The paper presents seasonal indicators of the abundance and biomass of the dominant groups of algae in the phytoplankton of lakes Kurganistoye and Yazhginya. In both lakes the largest values of summer abundance and biomass are formed by cryptophyte algae. A group of diatoms formed the peaks of only the May values of the abundance and biomass of phytoplankton in Lake Yazhginya.
A new algorithm for integral sedimentation zones identification on the example of the Ivankovo and Rybinsk reservoirs
Authors: Razumovskij Lev V. , Razumovskij Vikentii L. , Kushnareva Tatiana N. , Gubernatorova Tatiana N. , Anisimova Alexandra V.
Published: September 2024

The work is devoted to the new concept of integrated monitoring practical application and evaluation it’s results. The theoretical novelty of the concept consists in the joint analysis of diatom complexes from bottom sediments columns and modern phytoplankton complexes. The Ivankovo and Rybinsk reservoirs were chosen as the objects of research. This decision was made due to their advanced age, the power of accumulated deposits and the degree of study. The bottom sediment columns sampling points optimal locations in the Rybinsk and Ivankovo reservoirs was established as a result of the conducted research. During the creation of reservoirs, the lakes on their territory were flooded. The resulting morphometric bottom relief determined those relict lakes locations as zones of stable sedimentation. According to the comprehensive studies results, long-term negative processes caused by anthropogenic load have been confirmed in the investigated reservoirs.
Perubahan Peran Suami dan Isteri dalam Keluarga di Desa Molinese Kecamatan Lainea Kabupaten Konawe Selatan
Authors: Al Kausar Muhamad , Desrianti Desrianti
Published: September 2024

The purpose of this research is to find out how the roles of husbands and wives in the family and what the implications of changes in the roles of husbands and wives are for the family. The selection of informants in this study used the purposive sampling technique . This research uses the Theory of Social Change by William F. Ogburn. The data collection technique used in this research is field work using two methods, namely observation and in-depth interviews. This research is qualitative research using ethnographic research methods. The results of this study show that, role change in Molinese Village has slowly occurred in the 2000s and above and there are several families who experience it because of the lack of income in the family so that it affects the economy. However, with the entry of the oil palm company in this village in 2007, immediately the wives flocked to work as employees of the oil palm plantation as well as the husbands, but over time many husbands stopped working because of the wage system that was considered uneven and they chose to do gardening and some did not have a permanent job. Meanwhile, the wives are still working as employees of the oil palm plantation or PT MERBAU, until now. Some of the implications of changes in the role of husbands and wives on the family are the lack of harmony in the household, not having a tire, and the lack of a permanent job.
Nilai-Nilai Luhur bagi Orang Bajo di Desa Tapi-Tapi Kecamatan Marobo Kabupaten Muna
Authors: Feni Feni , Suraya Rahmat Sewa , Almarsaban Almarsaban
Published: September 2024

This study aims to determine and describe the Bajo people's views on noble values, and how the implementation of noble values for Bajo people in Tapi-Tapi Village, Marobo District, Muna Regency. The method used in the research is ethnographic method, researchers try to describe, describe and explain how the Bajo people view noble values-using in-depth observation and interview techniques. The data collected was then analyzed using Koentjaraningrat's theory of cultural values (1984). The Bajo people who live in Tapi-Tapi Village, Marobo District, Muna Regency are a fishing community that upholds noble values that have been passed down from generation to generation in the value of responsibility, namely: (a) Sipakkulong (supporting each other), (b) Mapulus jamaah itu dolo modi bunang (completing the work given), in the value of social care, namely: (a) Nggai kole sikalasa kadadarua (there should be no misunderstanding of others), (b) Sitabangang (helping each other in work), (c) Nggai kole mangasora'dialo (should not damage the sea), in the value of honesty, namely: (a) Nggai kole malaponggang aha sadiri (do not like to lie), in the value of independence, namely: (a) Ngajama diriang (work independently). The implementation of noble values for Bajo people is realized in several values, namely: (a) Si tuluh (helping), (b) Dianggo (mutual respect), (c) Sitabangang (cooperation) d Bapongka (group fishing activities).
Elevated remnant cholesterol as a potential predictor for cardiovascular events in rheumatoid arthritis patients
Authors: Chang Ching-Kun , Li Yi-Chen , Chen Po-Ku , Chang Shih-Hsin , Chen Der-Yuan
Published: September 2024

Objective

The risk of cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA) remains inadequately defined. Consequently, this study aims to evaluate the predictive value of remnant cholesterol (RC) for assessing CVD risk in RA patients.

Methods

Plasma RC levels were measured in 114 RA patients and 41 healthy controls, calculated as total cholesterol minus HDL-C and LDL-C. These levels were further analyzed using 1H-NMR lipid/metabolomics. Meanwhile, the 28-joint Disease Activity Score (DAS28) assessed RA activity.

Results

RC levels were significantly elevated in RA patients (19.0 mg/dl, p < 0.001) compared to healthy controls (14.5 mg/dl). Furthermore, RC levels were significantly elevated at 37.4 mg/dl in patients who experienced cardiovascular event (CVE) compared to 17.4 mg/dl in those without CVE (p < 0.001). To enhance the precision and reliability of RC measurements, RC concentrations were further validated using 1H-NMR spectroscopy. Additionally, a positive correlation was observed between RC levels and DAS28. Multivariate analysis identified RC as a significant predictor of CVE (odds ratio = 1.82, p = 0.013). ROC curve analysis revealed superior predictive capability of RC for CVE (AUC = 0.919, p < 0.001) compared to LDL-C (AUC = 0.669, p = 0.018), with a high sensitivity of 94.7% and a specificity of 82.1%.

Conclusion

Elevated RC levels demonstrate greater accuracy in predicting CVE occurrence in RA patients compared to traditional measures such as LDL-C. These findings suggest that elevated RC levels may serve as a novel predictor for occurrence of CVE in RA patients, facilitating early intervention strategies based on the risk stratification.
Correction of osteopetrosis in the neonate oc/oc murine model after lentiviral vector gene therapy and non-genotoxic conditioning
Authors: Penna Sara , Zecchillo Alessandra , Di Verniere Martina , Fontana Elena , Iannello Valeria , Palagano Eleonora , Mantero Stefano , Cappelleri Andrea , Rizzoli Elena , Santi Ludovica , Crisafulli Laura , Filibian Marta , Forlino Antonella , Basso-Ricci Luca , Scala Serena , Scanziani Eugenio , Schinke Thorsten , Ficara Francesca , Sobacchi Cristina , Villa Anna , Capo Valentina
Published: September 2024

Introduction

Autosomal recessive osteopetrosis (ARO) is a rare genetic disease, characterized by increased bone density due to defective osteoclast function. Most of the cases are due to TCIRG1 gene mutation, leading to severe bone phenotype and death in the first years of life. The standard therapy is the hematopoietic stem cell transplantation (HSCT), but its success is limited by several constraints. Conversely, gene therapy (GT) could minimize the immune-mediated complications of allogeneic HSCT and offer a prompt treatment to these patients.

Methods

The Tcirg1-defective oc/oc mouse model displays a short lifespan and high bone density, closely mirroring the human condition. In this work, we exploited the oc/oc neonate mice to optimize the critical steps for a successful therapy.

Results

First, we showed that lentiviral vector GT can revert the osteopetrotic bone phenotype, allowing long-term survival and reducing extramedullary haematopoiesis. Then, we demonstrated that plerixafor-induced mobilization can further increase the high number of HSPCs circulating in peripheral blood, facilitating the collection of adequate numbers of cells for therapeutic purposes. Finally, pre-transplant non-genotoxic conditioning allowed the stable engraftment of HSPCs, albeit at lower level than conventional total body irradiation, and led to long-term survival and correction of bone phenotype, in the absence of acute toxicity.

Conclusion

These results will pave the way to the implementation of an effective GT protocol, reducing the transplant-related complication risks in the very young and severely affected ARO patients.
Year-round monitoring of antibiotic-resistant bacteria in pristine uppermost stream and estimation of pollution sources
Authors: Nishimura Emi , Xie Hui , Tamai Soichiro , Nishiyama Masateru , Nukazawa Kei , Hoshiko Yuki , Ogura Yoshitoshi , Suzuki Yoshihiro
Published: September 2024

Studies on the conditions and pollution routes of antibiotic-resistant bacteria (ARB) in rivers can help provide countermeasures against the spread of ARB. This study focused on the pristine uppermost stream of a river, where Escherichia coli (E. coli) and enterococci were detected, although the stream flows through a pristine forest catchment. Antibiotic resistance of E. coli and enterococci isolated from the river water, riverbed sediment, and feces of waterside animals, such as birds and Mustelidae, were investigated throughout the year in the pristine uppermost sites. Antibiotic resistance was present in 1.4% (7/494) of the E. coli strains and 3.0% (24/812) of the enterococcal strains, and was low throughout the year. Although antibiotic resistance of bacteria isolated from feces was not detected in this watershed, the prevalence of multidrug-resistant E. coli was 0.4% (1/246) and 0.6% (1/172) in river water and riverbed sediment samples, respectively were observed. The presence of extended-spectrum β-lactamase (ESBL)-producing E. coli was confirmed in river water samples, and genomic analysis revealed that the samples possessed the CTX-M-15 group. Multidrug-resistant strains and ESBL-producing strains were classified as phylogroups B1 and A, respectively, which are E. coli phenotypes isolated from wild animals. Pulsed-field gel electrophoresis revealed analysis targeting enterococci that strains isolated from river water and bird feces were in the same cluster with 100% similarity. Therefore, bird feces are a source of enterococci in the uppermost stream of the river. Because multidrug-resistant bacteria and ESBL-producing bacteria were present in the pristine uppermost stream of the pristine river, urgent elucidation of the spreading routes of ARB is important.
De novo and inherited micro-CNV at 16p13.11 in 21 Chinese patients with defective cardiac left-right patterning
Authors: Yu Kun , Chen Weicheng , Chen Yan , Shen Libing , Wu Boxuan , Zhang Yuan , Zhou Xiangyu
Published: September 2024

Objective

Copy number changes at Chromosomal 16p13.11 have been implicated in a variety of human diseases including congenital cardiac abnormalities. The clinical correlation of copy number variants (CNVs) in this region with developmental abnormalities remains controversial as most of the patients inherit the duplication from an unaffected parent.

Methods

We performed CNV analysis on 164 patients with defective left-right (LR) patterning based on whole genome-exome sequencing (WG-ES) followed by multiplex ligation-dependent probe amplification (MLPA) validation. Most cases were accompanied with complex congenital heart disease (CHD).

Results

CNVs at 16p13.11 were identified in a total of 21 cases, accounting for 12.80% (21/164) evaluated cases. We observed a marked overrepresentation of chromosome 16p13.11 duplications in cases when compared with healthy controls according to literature reports (15/164, 9.14% versus 0.09% in controls). Notably, in two independent family trios, de novo 16p13.11 micro-duplications were identified in two patients with laterality defects and CHD. Moreover, 16p13.11 micro-duplication was segregated with the disease in a family trio containing 2 affected individuals. Notably, five coding genes, NOMO1, PKD1P3, NPIPA1, PDXDC1, and NTAN1, were potentially affected by micro-CNV at 16p13.11 in these patients.

Conclusion

Our study provides new family-trio based evidences to support 16p13.11 micro-duplications predispose individuals to defective cardiac left-right patterning and laterality disorder.
Cost-effectiveness of first-line enfortumab vedotin in addition to pembrolizumab for metastatic urothelial carcinoma in the United States
Authors: Li Andong , Wu Meiyu , Xie Ouyang , Xiang Heng , Meng Kehui , Tan Chongqing , Wang Long , Wan Xiaomin
Published: September 2024

Background and objective

The EV-302 trial found that the combination of enfortumab vedotin (EV) with pembrolizumab significantly improved survival for patients with metastatic urothelial carcinoma (mUC). However, given the high cost of the drugs, there is a need to assess its value by considering both efficacy and cost. This study assessed the cost-effectiveness of EV plus pembrolizumab as a first-line treatment for patients with mUC from the perspective of U.S. payers.

Methods

A Markov model was developed to compare the lifetime costs and effectiveness of EV in combination with pembrolizumab with chemotherapy in the treatment of mUC patients from U.S. payer perspective. Life-years (LYs), quality-adjusted LYs (QALYs), and lifetime costs were estimated. One-way, two-way and probabilistic sensitivity analyses were conducted to evaluate model uncertainty. Additionally, subgroup analyses were performed.

Results

Compared to chemotherapy, the combination of EV and pembrolizumab provided an additional 2.10 LYs and 1.72 QALYs, at an incremental cost of $962,240.8 per patient. The incremental cost-effectiveness ratio (ICER) is $558,973 per QALY. Subgroup analysis indicated that patients ineligible for cisplatin treatment had a lower ICER compared to those who were eligible for cisplatin.

Conclusions

From the perspective of US payers, at a willingness-to-pay threshold of $150,000 per QALY, the combination of EV and pembrolizumab is estimated to not be cost-effective compared to traditional chemotherapy in the first-line treatment of mUC patients.
Case reports: Intraoperative migratory retinal venous thrombus in proliferative diabetic retinopathy
Authors: Lyu Danni , Liu Huan , Fang Yijiong , Wang Yao
Published: September 2024

Purpose

This study aimed to study the characteristics, possible causes, and clinical implications of intraoperative migratory retinal venous thrombus in proliferative diabetic retinopathy (PDR).

Cases

Two middle-aged Chinese patients with diabetes mellitus presented with blurred vision and were diagnosed with PDR and tractional retinal detachment (TRD). An interesting phenomenon was observed during pars plana vitrectomy in both patients. Movement of tiny white thrombi and interruption of blood flow were observed in a branch of the central retinal vein when the vein was pulled at the time of fibrovascular membrane delamination and disappeared with the elimination of retinal traction after finishing the process of delamination. Laboratory studies revealed abnormal erythrocyte sedimentation rate, fibrinogen, D-dimer, international normalized ratio, and IgA anti-β2-glycoprotein I in one patient and elevated fibrinogen and IgA anticardiolipin in the other. Follow-up examinations at 1 week, 1, 3, and 6 months postoperatively showed good prognosis. Fluorescein fundus angiography at 1 month postoperatively showed neither embolus sign nor prolonged venous filling time in both patients.

Discussion

Local blood stasis of the retinal vein persistently dragged by the fibrovascular membrane may result in thrombogenesis, and traction of the retina during the delamination process may lead to the movement of thrombi. On the other hand, endothelial injury and disordered local blood stasis during delamination may also activate the biological coagulation process and instant thrombus formation. As well, antiphospholipid antibodies may also be a risk factor of ocular thrombogenesis.

Conclusion

This study provides the first videos recording migratory thrombus in terminal vessels, which indicates that fibrovascular membrane in PDR can lead to thrombogenesis due to dragging and hemostasis of the involved retinal vein. PDR patients with fibrovascular membranes may benefit from early relief of vascular traction through fibrovascular membrane delamination.
Perspective: on the future of fecal microbiota transplantation
Authors: Larsen Olaf F. A. , Brummer Robert J. M.
Published: September 2024

Fecal Microbiota Transplantation (FMT) has shown to possess impressive potential benefit for a wide range of clinical indications. Due to its inherent safety issues and efficacy constraints, the use of personalized FMT analogs could be a promising avenue. The development of such analogs will require a detailed understanding of their functionality, encompassing not only microbe-host interactions of the microbial taxa that are involved, but also of the ecological dimensions of the analogs and an overview of the gastrointestinal sites where these relevant microbial interactions take place. Moreover, characterization of taxa that have been lost due to diminished exposure to beneficial microbes, as a consequence of Western lifestyle, may lead to creation of future FMT analogs with the capacity to restore functionalities that we have lost.
Exploring metabolic anomalies in COVID-19 and post-COVID-19: a machine learning approach with explainable artificial intelligence
Authors: Oropeza-Valdez Juan José , Padron-Manrique Cristian , Vázquez-Jiménez Aarón , Soberon Xavier , Resendis-Antonio Osbaldo
Published: September 2024

The COVID-19 pandemic, caused by SARS-CoV-2, has led to significant challenges worldwide, including diverse clinical outcomes and prolonged post-recovery symptoms known as Long COVID or Post-COVID-19 syndrome. Emerging evidence suggests a crucial role of metabolic reprogramming in the infection’s long-term consequences. This study employs a novel approach utilizing machine learning (ML) and explainable artificial intelligence (XAI) to analyze metabolic alterations in COVID-19 and Post-COVID-19 patients. Samples were taken from a cohort of 142 COVID-19, 48 Post-COVID-19, and 38 control patients, comprising 111 identified metabolites. Traditional analysis methods, like PCA and PLS-DA, were compared with ML techniques, particularly eXtreme Gradient Boosting (XGBoost) enhanced by SHAP (SHapley Additive exPlanations) values for explainability. XGBoost, combined with SHAP, outperformed traditional methods, demonstrating superior predictive performance and providing new insights into the metabolic basis of the disease’s progression and aftermath. The analysis revealed metabolomic subgroups within the COVID-19 and Post-COVID-19 conditions, suggesting heterogeneous metabolic responses to the infection and its long-term impacts. Key metabolic signatures in Post-COVID-19 include taurine, glutamine, alpha-Ketoglutaric acid, and LysoPC a C16:0. This study highlights the potential of integrating ML and XAI for a fine-grained description in metabolomics research, offering a more detailed understanding of metabolic anomalies in COVID-19 and Post-COVID-19 conditions.
Case report: Development of clonal hematologic disorders from inherited bone marrow failure
Authors: Cermak Jaroslav
Published: September 2024

Introduction

Inherited bone marrow failure (IBMF) syndromes are caused by mutations forming pathologic germline variants resulting in the production of defective hematopoietic stem cells (HSC) and in congenital failure in the production of one or more blood lineages. An acquisition of subsequent somatic mutations is determining further course of the disease. Nevertheless, a certain number of patients with IBMF may escape correct diagnosis in childhood, especially those with mild cytopenia and minimal clinical features without non-hematologic symptoms. These patients usually present in the third decade of life with unexplained cytopenia or myelodysplastic syndrome (MDS).

Methods and results

We report 2 patients with IBMF who were correctly diagnosed between 20 and 40 years of age when they were referred with progressive MDS with adverse prognostic factors that affected their outcome.

Discussion

IBMF syndromes should be excluded in all patients below 40 years of age with unexplained cytopenia. Early hematopoietic stem cell transplantation (HSCT) is the treatment of choice in these patients.
Tumor lysis syndrome signal with the combination of encorafenib and binimetinib for malignant melanoma: a pharmacovigilance study using data from the FAERS database
Authors: Xia Shuang , Xu Jing-Wen , Yan Kang-Xin , Noguchi Yoshihiro , Sarangdhar Mayur , Yan Miao
Published: September 2024

Objective

To investigate the potential association between tumor lysis syndrome (TLS) and drugs for the treatment of malignant melanoma (MM).

Methods

Reports of TLS recorded in the FDA Adverse Event Reporting System (FAERS) (January 2004–2023q3) were identified. Demographic and clinical characteristics were described, and disproportionality signals were assessed through the Reporting Odds Ratio (ROR) and Information Component (IC). The latency of TLS with anticancer drugs was described based on parametric models. Subgroup analysis was conducted to explore the differences of TLS signals in different age and sex.

Results

We found 5 (1.49%), 59 (17.61%), 79 (23.58%), 19 (5.67%), 13 (3.88%), 13 (3.88%), 33 (9.85%), 49 (14.63%), 16 (4.78%) TLS reports with pembrolizumab, nivolumab, ipilimumab, dabrafenib, vemurafenib, dacarbazine, “encorafenib and binimetinib”, “nivolumab and ipilimumab”, “dabrafenib and trametinib”, respectively. The combination of encorafenib and binimetinib showed the strongest signal of TLS (IC025 = 3.98). The median days of latency of TLS with combination of encorafenib and binimetinib is 2 days, which was much shorter than nivolumab (22.0 days) and ipilimumab (21.5 days). TLS cases associated with drugs for MM were predominantly recorded in females and aged 25–65 years. After excluding confounding factors such as pre-existing diseases and co-treated drugs, the disproportionate signal of TLS with “encorafenib and binimetinib” remained strong.

Conclusions

Stronger disproportionate signal of TLS was detected in MM patients using the combination of encorafenib and binimetinib than other drugs. Further research is needed to investigate the underlying mechanisms and identify patient-related predisposing factors to support safe prescribing of the combination of encorafenib and binimetinib.
A novel image encryption method based on improved two-dimensional logistic mapping and DNA computing
Authors: Chen Yuanlin , Lu Tianxiu , Chen Caiwen , Xiang Yi
Published: September 2024

In the digital era, the significance of cryptographic algorithms has grown significantly within the realm of cybersecurity. This research presents an innovative approach to image encryption that eliminates the security limitations of the conventional one-dimensional logistic mapping. This approach relies on an enhanced two-dimensional logistic-fraction hybrid chaotic mapping (2D-LFHCM) and deoxyribonucleic acid (DNA) computing. Initially, the improved 2D-LFHCM is utilized to effectively scramble the image by incorporating chaotic sequences. Then, two novel algebraic DNA computing rules are introduced to enhance diffusion encryption. Experimental findings show that this approach offers superior security performance, even with renowned attacks.
Limited genetic diversity found among genotypes of the Entada landrace (Ensete ventricosum, (Welw.) Chessman) from Ethiopia
Authors: Haile Alye Tefera , Kovi Mallikarjuna Rao , Johnsen Sylvia Sagen , Hvoslef-Eide Trine , Tesfaye Bizuayehu , Rognli Odd Arne
Published: September 2024

The Entada landrace of enset (Ensete ventricosum (Welw.) Chessman) is probably the most unique indigenous crop in Ethiopia, being maintained and utilized by the Ari people in the South of Ethiopia. Here we describe genetic diversity, selection signatures and relationship of Entada with cultivated and wild enset using 117 Entada genotypes collected from three Entada growing regions in Ethiopia (Sidama, South and North Ari). A total number of 1,617 high-quality SNP markers, obtained from ddRAD-sequences, were used for the diversity studies. Phylogenetic analysis detected a clear distinction between cultivated enset, Entada and wild enset with Entada forming a completely separated clade. However, extremely short branch lengths among the Entada genotypes indicate very little molecular evolution in the Entada lineages. Observed and expected heterozygosities were high, 0.73 and 0.50, respectively. Overall, our results strongly indicate that the Entada genotypes we have studied originated from one or a few clonal lineages that have been propagated and spread among farmers as clones. Prolonged clonal propagation of heterozygous genotypes from a single or few founding lineages has led to populations with very little or no diversity between genotypes, and high heterozygosity within genotypes. Signatures of directional selection were identified at eight loci based on an FST outlier analysis. Four candidate genes detected are involved in axillary shoot growth and might be involved in controlling natural sucker formation in Entada.
Multi-trait modeling and machine learning discover new markers associated with stem traits in alfalfa
Authors: Medina Cesar A. , Heuschele Deborah J. , Zhao Dongyan , Lin Meng , Beil Craig T. , Sheehan Moira J. , Xu Zhanyou
Published: September 2024

Alfalfa biomass can be fractionated into leaf and stem components. Leaves comprise a protein-rich and highly digestible portion of biomass for ruminant animals, while stems constitute a high fiber and less digestible fraction, representing 50 to 70% of the biomass. However, little attention has focused on stem-related traits, which are a key aspect in improving the nutritional value and intake potential of alfalfa. This study aimed to identify molecular markers associated with four morphological traits in a panel of five populations of alfalfa generated over two cycles of divergent selection based on 16-h and 96-h in vitro neutral detergent fiber digestibility in stems. Phenotypic traits of stem color, presence of stem pith cells, winter standability, and winter injury were modeled using univariate and multivariate spatial mixed linear models (MLM), and the predicted values were used as response variables in genome-wide association studies (GWAS). The alfalfa panel was genotyped using a 3K DArTag SNP markers for the evaluation of the genetic structure and GWAS. Principal component and population structure analyses revealed differentiations between populations selected for high- and low-digestibility. Thirteen molecular markers were significantly associated with stem traits using either univariate or multivariate MLM. Additionally, support vector machine (SVM) and random forest (RF) algorithms were implemented to determine marker importance scores for stem traits and validate the GWAS results. The top-ranked markers from SVM and RF aligned with GWAS findings for solid stem pith, winter standability, and winter injury. Additionally, SVM identified additional markers with high variable importance for solid stem pith and winter injury. Most molecular markers were located in coding regions. These markers can facilitate marker-assisted selection to expedite breeding programs to increase winter hardiness or stem palatability.
Morphological, physiological, and biochemical responses of three different soybean (Glycine max L.) varieties under salinity stress conditions
Authors: Kokebie Desilal , Enyew Abiyu , Masresha Getinet , Fentie Tarekegn , Mulat Emebet
Published: September 2024

Salinity is one of the most detrimental factors for the growth performance and productivity of crops worldwide. Therefore, understanding crop responses or growth potentials and their effectiveness in salinity mitigation is highly important for the selection of salinity-tolerant plant varieties. In this study, the effects of salinity at various stress levels (0 mM, 50 mM, 100 mM, and 150 mM NaCl) on the morphological, physiological, and biochemical parameters of three soybean varieties (‘Afigat’, ‘Gishama’, and ‘Pawi-2’) were investigated. The results showed that salinity significantly reduced morphological traits including plant height, number of leaves per plant, stem thickness, shoot and root length, and fresh and dry weight. This reduction was more prominent in the ‘Afigat’ variety for all of these traits except shoot and root length. The concentrations of chlorophyll a and b decreased with increasing salinity. In addition, salinity significantly increased leaf electrolyte leakage (EL), lipid peroxidation, proline accumulation, and phenol and flavonoid content. The ‘Pawi-2’ variety was more tolerant than the other studied varieties in terms of membrane stability (less EL and a low malondialdehyde content) and proline, phenol, and flavonoid accumulation. Therefore, ‘Pawi-2’ may be considered as the most salt-tolerant variety in comparison with the other studied soybean varieties. Further complementary studies in field conditions including anatomical parameters are needed to confirm these findings.
Genomic prediction of yield-related traits and genome-based establishment of heterotic pattern in maize hybrid breeding of Southwest China
Authors: Xiang Yong , Xia Chao , Li Lujiang , Wei Rujun , Rong Tingzhao , Liu Hailan , Lan Hai
Published: September 2024

When genomic prediction is implemented in breeding maize (Zea mays L.), it can accelerate the breeding process and reduce cost to a large extent. In this study, 11 yield-related traits of maize were used to evaluate four genomic prediction methods including rrBLUP, HEBLP|A, RF, and LightGBM. In all the 11 traits, rrBLUP had similar predictive accuracy to HEBLP|A, and so did RF to LightGBM, but rrBLUP and HEBLP|A outperformed RF and LightGBM in 8 traits. Furthermore, genomic prediction-based heterotic pattern of yield was established based on 64620 crosses of maize in Southwest China, and the result showed that one of the parent lines of the top 5% crosses came from temp-tropic or tropic germplasm, which is highly consistent with the actual situation in breeding, and that heterotic pattern (Reid+ × Suwan+) will be a major heterotic pattern of Southwest China in the future.
Improving transient expression in N. benthamiana by suppression of the Nb-SABP2 and Nb-COI1 plant defence response related genes
Authors: Kopertekh Lilya
Published: September 2024

Currently transient expression is one of the preferred plant-based technologies for recombinant protein manufacturing, particularly in respect to pharmaceutically relevant products. Modern hybrid transient expression systems combine the features of Agrobacterium tumefaciens and viral vectors. However, host plant reaction to Agrobacterium-mediated delivery of gene of interest can negatively affect foreign protein accumulation. In this study, we investigated whether the modulation of plant immune response through knockdown of the Nb-SABP2 and Nb-COI1 N. benthamiana genes could improve recombinant protein yield. In plants, the SABP2 and COI1 proteins are involved in the salicylic acid and jasmonic acid metabolism, respectively. We exemplified the utility of this approach with the green fluorescence (GFP) and β nerve growth factor (βNGF) proteins: compared to the tobacco mosaic virus (TMV)-based vector the Nb-SABP2 and Nb-COI1-suppressed plants provided an increased recombinant protein accumulation. We also show that this strategy is extendable to the expression systems utilizing potato virus X (PVX) as the vector backbone: the enhanced amounts of βNGF were detected in the Nb-SABP2 and Nb-COI1-depleted leaves co-infiltrated with the PVX-βNGF. These findings suggest that modulating host plant reaction to agrodelivery of expression vectors could be useful for improving transient foreign protein production in N. benthamiana.
Shift in intelligence issue ownership: conceptualizing CITINT—intelligence conducted by citizens
Authors: Pietilä Iikka , Kortesuo Katleena , Pohjanen Ulla , Tuominen Mikko
Published: September 2024

This article elaborates on the conceptualization of CITINT, i.e., the intelligence activities conducted by citizens and NGOs. This article is a preliminary attempt to establish foundation and perspectives for future research and to provide for initial conceptualization of CITINT. Moreover, this article elucidates CITINT’s implications from legislative perspective within the Finnish context. A semi-systematic, limited literature review incorporating academic literature, governmental outlets, and news was executed to explore the contexts and definitions regarding CITINT. Interviews with a journalist, an active CITINT individual, and a detective superintendent of the Finnish National Bureau of Investigation were conducted to clarify and provide backrest for conceptualization. The key contributions of this article are further elucidation of CITINT as a concept and its implications. Moreover, this article discusses the shift in power relations from centralized issue ownership of intelligence activities toward a more fragmented scene in which individuals and non-governmental organizations (NGOs) have more relevance, possibilities, and weight. Within CITINT, this article points out the differentiation between governmentally facilitated CITINT and the bottom-up CITINT conducted by individuals and NGOs on their own terms and tools. One key contribution of this article is connecting CITINT to societal participation through the CCSCM framework. Although the interviews comprise an empirical component, support contextualization, and provide tangible examples, this article’s focus is on the theoretical and conceptual aspects of CITINT. The article concludes with a discussion on the outlook, possibilities, and challenges of CITINT and provokes questions for further discussion on the matter.
Chinese EFL learners’ processing of English binomials: the role of interlexical and intralexical factors
Authors: Chen Zhuo , Fang Nan
Published: September 2024

Binomials have been relatively understudied compared to other types of multiword expressions (MWEs) in second language research, such as collocations and idioms. This study investigated English as a Foreign Language (EFL) learners’ processing of English binomials and how it is influenced by interlexical factors (L1-L2 congruency and L1-lexicalization) and intralexical factors (word and binomial frequency, binomial reversibility, and binomial predictability). Forty Chinese EFL learners participated in a phrase acceptability judgment task of 64 target binomials (16 congruent L1-lexicalized, 16 congruent L1-nonlexicalized, and 32 incongruent) and 64 non-binomial controls. Results revealed that learners experienced difficulty judging the formulaicity of binomials. They processed binomial stimuli significantly faster than non-binomial baselines, demonstrating a binomial phrase effect. They also processed L1-L2 congruent items faster and more accurately than incongruent items, showing a robust congruency effect. The congruent items which are lexicalized in the L1 showed further processing advantage than the non-lexicalized items, indicating a graded congruency effect. Moreover, binomial reversibility and binomial predictability (measured with cloze probability) also showed significant effects. These findings highlight the need to distinguish and investigate different types of congruency, explore appropriate measures for MWE predictability, and to examine binomials focusing on their unique features.
Slovenian validation of the Capacity to Love Inventory: associations with clinical measures and mindfulness
Authors: Glavač Timotej , Poštuvan Vita , Schmeckenbecher Jim , Kapusta Nestor D.
Published: September 2024

Aim

The main purpose of the present study was to validate the Slovenian version of the 41- item Capacity to Love Inventory (CTL-I). Based on psychoanalytic theory, limitations to capacity to love are expected to be associated with personality dysfunction and disintegration as well as fundamental mental capacities such as self-reflection and self-awareness.

Method

To examine these assumptions, a sample of 552 Slovenian non-clinical individuals were recruited through academic networks. The construct validity of the CTL-I was assessed using a confirmatory factor analysis and convergent validity of the CTL-I and its subscales was established against IPO-16, PID-5 BF, MAAS.

Results

Our findings show that the Slovenian version of the CTL-I replicated the six-factor structure, exhibiting good model fit as well as satisfactory internal consistency of all subscales. In line with expectations, capacity to love was found to be inversely associated with dysfunctional personality traits and structural personality disturbances. Accordingly, higher dispositional mindfulness was coherently associated with all domains of CTL-I.

Conclusion

The results add to the growing evidence for the cross-cultural validity and sound psychometric properties of CTL-I, presented here in the Slovenian version. Our findings also point to the significance of dispositional mindfulness both in relation to capacity to love as well as mental health.
Internal blood lead exposure levels in permanent residents of Jiangxi Province and its effects on routine hematological and biochemical indices
Authors: He Wenxin , Fu Junjie , Fu Ruiyi , Song Xiaoguang , Huang Siyue , Wang Yujue , Lu Keke , Wu Hao
Published: September 2024

Background

Lead exposure levels are closely linked to human health and can cause damage to multiple organ systems, including the blood system and liver. However, due to insufficient evidence, the effects of lead exposure on hematological and biochemical indices have not been fully established.

Objective

This study aims to explore the blood lead levels of permanent residents in Jiangxi Province and analyze the factors affecting blood lead levels and the impact of blood lead levels on hematological and biochemical indices.

Methods

We conducted a cross-sectional study including questionnaires, health examinations, and blood sample examinations on 720 randomly selected permanent residents (3–79 years) in Jiangxi Province in 2018. The blood lead levels were measured using inductively coupled plasma mass spectrometry. Routine hematological and biochemical tests were determined by qualified medical institutions using automated hematology analyzers and biochemistry analyzers.

Results

The geometric mean of blood lead concentration in permanent residents of Jiangxi Province was 20.45 μg/L. Gender, age, annual household income, smoking, and hypertension were the influencing factors for blood lead levels. For each 1 μg/L increase in blood lead, the risks of elevated red blood cell count (from low to high), platelet volume distribution width, alkaline phosphatase (from low to high), and cholesterol increased by 2.4, 1.6, 3.6, and 2.3%, respectively, whereas the risks of elevation of direct bilirubin and total bilirubin both decreased by 1.7%.

Conclusion

The blood lead level in permanent residents of Jiangxi Province is higher than the national average. Higher blood lead levels were found in men than in women; blood lead levels were positively correlated with age but negatively correlated with annual household income; smoking and hypertension are risk factors for elevated blood lead; and blood lead levels affect routine hematological and biochemical markers such as red blood cell count, platelet volume distribution width, direct bilirubin, total bilirubin, alkaline phosphatase, and cholesterol.