bluuebunny/crossref_metadata_2025 huggingface dataset:
STRUCTURE AND FUNCTIONS OF ELEMENTS OF INNOVATION INFRASTRUCTURE OF DUAL-USE SCIENTIFIC AND INDUSTRIAL CLUSTER
Authors:   All-Russian Research Institute «Center» of the Ministry of Industry and Trade of Russia, Moscow, Russian Federation, BOBRYSHEV A.D. , CHEKADANOVA M.V. ,   JSC «Management Company of the Special Economic Zone "Istok"», Fryazino, Russian Federation, ARTYUKHOV V.V.
Published: November 2024

The purpose of the study is to develop a methodological apparatus for the formation of dual-use scientific and industrial clusters-a form recognized at the highest level of management of the military-industrial complex to help diversify defense enterprises and organizations. Based on the results of the work, the following main conclusions were obtained. The few dual-use scientific and industrial clusters created in recent years are still not much different from the well-known vary-ants of the organization of industrial and innovative clusters and it is not entirely clear how they will fulfill their main purpose-to facilitate the transfer of defense technologies to the civilian sector. First of all, this concerns the issues of removing the regime of secrecy from military technologies that can be used to produce civilian products. Experts call this problem the main obstacle to the transfer of such technologies. At the same time, starting in 2022, the list of dual-use goods and technologies that can be used in the creation of weapons and military equipment and for which export control is carried out is approved and updated. This list contains unambiguous exceptions allowing the use of dual-use goods and technologies for civilian purposes. The second problem-the choice of an anchor company for the cluster-is being addressed ambiguously today. The article shows that the most forest-like solution is the formation of a cluster around a reputable scientific and industrial company in the field of cluster specialization. Given the competitive nature of the activities of defense organizations in the civilian market, it is also necessary to provide options for organizing relations between its developers and manufacturers. The article describes organizational solutions of this plan, involving the creation of consortia, joint ventures, as well as the release of products within the framework of contract production and franchise.
TOPICAL ASPECTS OF THE ORGANIZATION OF INTER-BUDGETARY RELATIONS IN RUSSIA
Authors:   Financial University under the Government of the Russian Federation, Moscow, Russian Federation, MAKASHINA O.V. ,   Plekhanov Russian University of Economics
Published: November 2024

The purpose of the study. The article examines the problems of relations between public legal entities of the Russian Federation. The current aspects of the organization of inter-budgetary relations and the changes that have occurred over the past almost twenty years are analyzed. The purpose of the study is to identify the features of inter-budgetary relations at the present stage. This is necessary to determine the further development of inter-budgetary relations and their reorientation to new instruments. Conclusions. Because of the conducted research, the author concludes that inter-budgetary relations in the modern budgetary system of the country are undergoing significant changes. Some of these changes are positive and should be continued. Some of the changes raise doubts about their necessity. The budget system of the Russian Federation has a complex structure from the point of view of management. The differentiation of revenue receipts and expenditure powers between public legal entities is the basis of inter-budgetary relations. The provision of subsidies over a long period (since 1994) does not have a significant positive effect on the subjects receiving them. Despite efforts to reduce the number of targeted transfers, their fragmentation remains at a high level. Budget loans have fully become an instrument of inter-budgetary relations. In conclusion, the author defines the directions for improving the organization of inter-budgetary relations in the Russian Federation.
OBJECTIVE OF EXPANDING TAX RISK CRITERIA IN A PRELIMINARY ANALYSIS
Authors:   Financial University under the Government of the Russian Federation, Moscow, Russian Federation, SMIRNOVA E.E.
Published: November 2024

The article is considered current issues of pre-test analysis, which is an important stage in the control work of tax authorities and affects the increase in the effectiveness of tax control by improving the quality of the selection of taxpayers for inclusion in the plan of on-site tax audits. The criteria applied are considered, how tax risks are assessed. The article also analyzes the possibilities of expanding the list of publicly available criteria for different categories of audited entities. Purposes of writing a research paper: to identify the main issues, Pre-audit analysis of taxpayers, provide additional criteria for assessing tax risks. Conclusions, obtained in the course of the study: directions for improving the quality of pre-test analysis in order to improve the control work of tax authorities.
COLLECTIVE PORTRAIT AGAINST THE BACKGROUND OF THE HISTORICAL ERA: AUTHORS OF SCHOOL TEXTBOOKS IN THE HISTORY OF THE USSR (END 1950 - FIRST HALF 1960S)
Authors:   Ural Federal University named after the First President of Russia B. N. Yeltsin, Yekaterinburg, Russian Federation, OGONOVSKAYA I.S.
Published: November 2024

The author of the article continues the research devoted to historical education in the USSR, presented through the prism of school textbooks on the history of the USSR, published in the first half of the 1960s, and the fate of their authors. Particular attention is paid to the discussions of the late 1950s and early 1960s. about the structure of the history course at school and the textbook competition held in 1960. The editorial changes made to the textbooks of the “Stalin” era, and developed by the Institute of History of the USSR Academy of Sciences, and the content aspects of the new textbooks are considered. The difficulties of the authors in working on educational publications published under the ideological control of the CPSU Central Committee are shown.
¿CÓMO PROBAR UNA VACUNA?: EL USO DE LOS ENSAYOS CLÍNICOS
Authors: Vega Toro Angie Stephanie
Published: November 2024

Hoy por hoy, la COVID-19 es una enfermedad infecciosa causada por el coronavirus descubierto recientemente (WHO, 2020), el cual representa una pandemia que afecta a gran parte de los países en el mundo, enfrentándolos a la necesidad de generar medidas de confinamiento, como lo son las cuarentenas. Medidas de control de la infección que están alterando las condiciones sociales y económicas de la población mundial. Por tanto, la COVID-19 ha presentado al mundo la necesidad imperativa de generar una vacuna que mitigue sus efectos.
¿CÓMO PROBAR UNA VACUNA?: EL USO DE LOS ENSAYOS CLÍNICOS
Authors: MÉNDEZ CASTILLO JAIME ALBERTO
Published: November 2024

Hablar de relación docencia – investigación en educación superior no es sencillo, en la medida en que reta a las instituciones, facultades, programas y docentes a reflexionar frente a lo que implica la formación de profesionales de cara a profundas complejidades que actualmente demandan las sociedades contemporáneas, y que requieren de abordajes desde diferentes saberes y campos del conocimiento. En relación con esto, emergen necesidades en el proceso educativo de profesionales que superen los propósitos de estudio y las disciplinas, de forma que comprendan los profundos problemas de las sociedades y aporten desde el trabajo interdisciplinar, multidisciplinar y transdisciplinar en sus respuestas (Carmona and Hernández, 2017).
Predicting the impact of adding metakaolin on the flexural strength of concrete using ML classification techniques – a comparative study
Authors: Velastegui Luis , Velasco Nancy , Sanchez Quispe Hugo Rolando , Barahona Fredy , Onyelowe Kennedy C. , Hanandeh Shadi , Ebid Ahmed M. , John TrustGod A.
Published: November 2024

The structural design standards, particularly in concrete technology, heavily rely on the mechanical attributes of concrete. Utilizing dependable predictive models for these properties can minimize the need for extensive laboratory testing, evaluations, and experiments to acquire essential design data, thereby conserving time and resources. Metakaolin (MK) is frequently incorporated as an alternative to Portland cement in the production of sustainable concrete, owing to its technical advantages and positive environmental impact, aligning with the United Nations Sustainable Development Goals (UNSDGs) aimed at achieving net-zero objectives. However, this research presents a comparative study between eight (8) ML classification techniques namely, gradient boosting (GB), CN2, naïve bayes (NB), support vector machine (SVM), stochastic gradient descent (SGD), k-nearest neighbor (KNN), Tree and random forest (RF) to estimate the impact of adding metakaolin to concrete on its flexural strength considering mixture components contents and concrete age. The collected data entries for the prediction of the flexural strength (Ft) containing the following concrete components; contentof cement (C), content of metakaolin (MK), content of water (W), content of fine aggregates (FAg), content of coarse aggregates (CAg), content of super-plasticizer (P), and the concrete curing age at testing (Age) were partitioned into 80% and 20% for training and validation sets respectively. At the end of the model protocol, it was found that the GB, SVM, and KNN models which produced an average MSE value of zero (0) showed their decisive ability to predict the flexural strength of the metakaolin (MK) mixed concrete (Ft). This outcome agrees with the previous reports in the literatures; however the work of Shah et al. happens to be the closest in terms of concrete components used in the production of the mixes and the application of machine learning techniques. It was found that the present research work’s models outperformed those presented by Shah et al. Hence the decisive models reported in this research paper show potentials to be applied in the design and production of MK concrete with optimal flexural strength.
Epitope-based therapeutic targets in HCV genotype 1 non-structural proteins: a novel strategy to combat emerging drug resistance
Authors: Tudi Mireayi , Sawuti Adili , Abudurusuli Maimaitituerhong , Wu Chao , Chen Xiaoyu , Ailimu Gulimire , Wulayin Kuerbannisa , Tuerxun Maimaitiaili
Published: November 2024

Introduction

The hepatitis C virus (HCV) poses a major global health challenge, with its non-structural proteins being essential for viral replication and pathogenesis. Mutations in these proteins significantly contribute to drug resistance, necessitating innovative therapeutic strategies. This study aims to identify epitope-based therapeutic targets in the non-structural proteins of HCV genotype 1, employing in-depth in silico tools to counteract emerging drug resistance.

Methods

We retrieved approximately 250 sequences of each non-structural protein from the NCBI database, capturing a broad spectrum of variability and sequence alignments, variability analysis and physicochemical property analysis were conducted. We utilized the TEPITOOL server by IEDB to predict cytotoxic T lymphocyte (CTL) epitopes. Following this, we assessed the efficiency of TAP transport and proteasomal cleavage using IEDB’s combined predictor tool. The epitopes were selected based on conservancy analysis, immunogenicity, allergenicity, and presence in non-glycosylated regions, ensuring high predictive scores and suitability as vaccine candidates. Epitopes were docked with the HLA-A*02:01 allele and Toll-like receptor-3 using the ClusPro server. The immune response potential of the epitopes was evaluated through in-silico immune stimulation.

Results

The study identified 27 potential CTL epitopes from the non-structural proteins, including NS3, NS4a, NS4b, NS5a, and NS5b. Out of these, three lead epitopes demonstrated high conservation (>90%), strong binding affinities to HLA-A*02:01 and TLR-3, and robust immune response potential. These epitopes also showed favorable characteristics such as being non-allergenic and non-glycosylated.

Conclusion

This comprehensive in-silico analysis provides a promising foundation for developing an epitope-based vaccine targeting HCV non-structural proteins, offering a novel approach to overcoming drug resistance in HCV treatment.
Sex related disparities after complex percutaneous coronary interventions
Authors: Alperi Alberto , Almendárez Marcel , Pascual Isaac , Alvarez Rut , Betanzos Jose Luis , Hernández-Vaquero Daniel , Ptaszynski Raul , Ortiz Juan Francisco , Moris Cesar , Avanzas Pablo
Published: November 2024

Introduction

Complex Percutaneous coronary intervention (PCI) for the treatment of ischemic heart disease has increased significantly. We aimed to evaluate sex-related differences in patients undergoing complex PCI.

Methods

single-center prospective observational study including patients undergoing complex PCI between 2017 and 2023. Baseline and procedural features, and mid-term outcomes were compared according to the gender distribution. The combined primary endpoint included stroke, myocardial infarction, need for a new coronary revascularization, and all-cause mortality. Propensity score (PS) matching with an inverse probability of treatment weight (IPW) approach was used to adjust for differences in baseline characteristics.

Results

1,283 patients were included, 983 (76.6%) male and 300 (23.4%) female. Median follow-up was 2.4 (IQR: 1–3.8) years. There was a higher rate of no-reflow phenomenon (4% vs. 1.8%, p = 0.03) among female patients. In the overall cohort, female patients had a greater risk for the combined primary endpoint (HR 1.28, 95% CI: 1.02–1.59). In the matched cohort, female patients exhibited a higher risk for the combined primary endpoint (HR 1.23, 95% CI: 1.06–1.42), as well as for myocardial infarction (HR 1.34, 95% CI 1.03–1.75), and all-cause mortality (HR 1.21, 95% CI 1.02–1.45), and a trend towards a higher risk for the need of a new coronary revascularization (HR 1.22, 95% CI 0.92–1.61).

Conclusions

in a contemporary cohort of patients undergoing complex PCI procedures, female patients are associated with a higher risk of early complications.
Effect of bariatric surgery on HDL-mediated cholesterol efflux capacity
Authors: Castañer O. , Pérez-Vega K. A. , Álvarez S. , Vázquez S. , Casajoana A. , Blanchart G. , Gaixas S. , Schröder H. , Zomeño M. D. , Subirana I. , Muñoz-Aguayo D. , Fitó M. , Benaiges D. , Goday A. , Oliveras A.
Published: November 2024

Background

Bariatric surgery (BS) is the most effective intervention for severe obesity, leading to sustained weight loss, reduced obesity-related comorbidities, and cardiovascular mortality.

Aim

To assess changes in high-density lipoprotein (HDL) functions [cholesterol efflux capacity (CEC) and anti-inflammatory capacity] at different follow-up times in patients with severe obesity undergoing BS.

Methods

A prospective observational study within a cohort of consecutively enrolled patients with severe obesity scheduled to undergo BS. In total, 62 participants (77% women), with a mean age of 42.1 years (SD 9.33 years) underwent BS. Regarding the surgical procedure, 27 (43.5%) underwent sleeve gastrectomy and 35 (56.5%) Roux-en-Y gastric bypass. All patients were evaluated preoperatively and at 1, 3, 6, and 12 months after surgery.

Results

A decrease in body mass index and an improvement in the systemic lipid profile, indicated by reductions in total cholesterol, low-density lipoprotein cholesterol (LDLc), and remnant cholesterol, and an increase in HDL cholesterol (HDLc) was observed (all p trend < 0.001). Time-series comparisons vs. baseline showed that, in general, anthropometric measures, glycemia, total cholesterol, LDLc, and remnant cholesterol decreased at all follow-ups, whereas HDLc and triglyceride concentrations significantly improved vs. baseline from 6 months, reaching at 12 months the highest HDLc levels (29.6%, p < 0.001) and the lowest circulating triglycerides (−30%, p < 0.001). Although HDL's anti-inflammatory ability worsens after surgery, the HDL-mediated CEC linearly increased after surgery (for both p trend < 0.013).

Conclusion

BS improves the lipid profile both quantitatively and qualitatively after 1 year, specifically enhancing HDL-mediated cholesterol efflux capacity, which may contribute to a reduced cardiovascular risk in individuals with severe obesity.
Visualization analysis of ambient seismic noise research
Authors: Wu Lihui , Li Jinling , Bao Sarina , Gong Qianbin
Published: November 2024

In recent years, ambient seismic noise has gained considerable attention in seismology due to its potential to advance understanding of Earth’s subsurface dynamics and monitor anthropogenic activities. This study presents a comprehensive review of ambient seismic noise research (ASNR), by exploring its current status, key research hotspots, and emerging trends through a bibliometric and visual analysis of 3,028 articles indexed in the Web of Science database (1984–2023). Using CiteSpace, the study systematically examines key authors, institutions, and countries, as well as thematic keywords and foundational references. Techniques such as cluster analysis, co-citation network analysis, and burst detection are employed to map the evolution of research fields and identify significant collaboration patterns. The analysis reveals a dramatic increase in research output, particularly since 2004, underscoring the expanding role of ASNR in geophysics, geochemistry, and engineering applications. Additionally, the rising interest in detecting human activities through seismic noise, especially in response to events like the COVID-19 pandemic, highlights the broadening scope of ASNR. Notably, the findings emphasize the pivotal importance of ambient noise tomography, a method that has transformed subsurface imaging techniques. This review not only synthesizes the current research landscape but also highlights critical gaps and emerging opportunities, providing a roadmap for future studies. In particular, it emphasizes advancements in seismic risk mitigation, geotechnical investigations, and the monitoring of human activities, offering a timely review and valuable insights that aligns with the interests of researchers in these fields.
Glycemic profile variability as an independent predictor of diabetic retinopathy in patients with type 2 diabetes: a prospective cohort study
Authors: Dehghani Firouzabadi Fatemeh , Poopak Amirhossein , Samimi Sahar , Deravi Niloofar , Nakhaei Pooria , Sheikhy Ali , Moosaie Fatemeh , Rabizadeh Soghra , Meysamie Alipasha , Nakhjavani Manouchehr , Esteghamati Alireza
Published: November 2024

Background

Glycemic variability is a novel predictor for diabetic complications. Different studies have demonstrated contradictory results for the association between HbA1c variability and diabetic retinopathy. We aimed to assess the relationship between visit-to-visit variability in glycemic profile (HbA1c, 2hPP, and FBS) and diabetic retinopathy.

Methods

Patients with type 2 diabetes were monitored for the development of retinopathy for 10 years. The association between the incidence of retinopathy and glycemic variability was assessed via Cox regression analysis, and coefficient of variation for glycemic indices was compared using independent sample t-test.

Results

Patients with diabetic retinopathy had significantly higher glycemic profile variability. The incidence of retinopathy was positively correlated with cv-FBS10% (10% of coefficient of variance), cv-FBS20%, cv-2hpp10%, and cv-HbA1c5%. Our analysis revealed that the higher variability of FBS increased the incidence and progression of retinopathy (HR: 12.29, p-value = 0.003).

Conclusion

Our findings demonstrated glycemic profile variability as an independent risk factor for diabetic retinopathy in patients with type 2 diabetes and support glycemic profile variability measurement in addition to common glycemic parameters to improve risk stratification in patients with type 2 diabetes. Further investigation is required to demonstrate the long-term effects of alleviating glycemic variability on the prognosis of patients with type 2 diabetes.
Association of weight-adjusted waist index with all-cause and cause-specific mortality among cancer survivors: a cohort study of the NHANES 1999-2018
Authors: Li Shi , Jin Jing , Zhang Wenshun , Cao Ying , Qin Haiyun , Wang Jianguang , Yu Jiaxiang , Wang Wenping
Published: November 2024

Background

Obesity is becoming more widely acknowledged as a chronic illness that raises the risk of oncogenesis. This inquiry aimed to look into the correlation between cancer patient mortality and obesity, as measured by the weight-adjusted waist index (WWI).

Methods

We used continuous data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018 as the benchmark, with a follow-up validity period of December 31, 2019. First, we assessed the correlation between WWI and the all-cause and cause-specific execution of cancer sufferers using multivariable Cox proportional hazards models. Second, a smoothed curve fit was utilized to examine the relationship between WWI and both cause-specific and all-cause mortality in cancer patients. Lastly, we analyzed the relationship between WWI and both cause-specific and all-cause mortality in cancer patients, to find out if this link held across the population subgroup evaluation and impact analyses were used as well during the last step.

Results

With a median follow-up of 87.8 months, 1,547 (34.7%) of the 4,463 cancer patients had deceased. Among them, 508 (11.4%) succumbed to cancer, while 322 (7.2%) passed away due to cardiovascular disease. Multivariate Cox proportional hazards model of mortality among cancer patients revealed an all-cause mortality hazard ratio [HR=1.13; 95% CI (1.04, 1.23)] and cardiovascular mortality [HR=1.39; 95% CI (1.16, 1.67)]. Furthermore, for each unit increase in WWI, all-cause mortality was significantly higher in male cancer survivors than in female cancer survivors.

Conclusions

Our study reveals substantial correlations between WWI and all-cause and cardiovascular mortality in US cancer survivors, helping to identify cancer survivors at higher risk of death and thus potentially guiding targeted interventions.
Analysis of factors influencing prevalence and malignancy of thyroid nodules in various iodine uptake areas
Authors: Xie HongLei , Pan HaoWen , Qian TingTing , Hou Xin , Zhao Meng , Che WenJing , Li WeiDong , Xu Xian , Su Yue , Li Jia , Yue ZongYu , Zhang ZeXu , Liu Peng
Published: November 2024

Background

The prevalence of thyroid nodules (TNs) has been increasing rapidly. However, little is known about the drivers of its high prevalence and tendency of malignancy. This study aimed to analyze the factors influencing the prevalence and malignancy of TNs in the adult population.

Methods

A multi-stage stratified cluster random sampling was used to conduct a cross-sectional survey of the population in different iodine uptake areas in Anhui Province. The areas with deficient, adequate, and excess iodine intake were grouped according to population's urine iodine. A questionnaire, laboratory examination and ultrasound diagnosis were conducted on the participants. Nodules were diagnosed and distinguished using ultrasonography. Spearman rank correlation, random forest importance ranking, ROC curve, and unconditional binary logistic regression analyses were used to screen for risk factors.

Results

A total of 1,697 participants (539 males and 1,158 females) aged 18–60 years were included, 355 of whom were diagnosed with TN. The prevalence of TNs was 20.9% and varied in different areas, with 21.9%, 25.8%, and 18.0% in the iodine deficient, adequate, and iodine excess areas, respectively. The prevalence of TNs in females was significantly higher than that in males (24.5% vs. 13.2%) and it increased with age. Female sex (OR, 1.67 [1.21–2.30]), old age (>41 years, OR, 2.00 [1.14, 3.50]) and smoking were risk factors for the development and deterioration of TNs.

Conclusions

Patients with TNs should exercise caution when consuming goitrogens and adhere to a scientifically balanced diet. Given the high incidence of TNs in field setting, it is necessary to raise public health awareness among residents and perform regular thyroid ultrasound screening to facilitate early detection and treatment.
Unveiling the hidden risks: albumin-corrected anion gap as a superior marker for cardiovascular mortality in type 2 diabetes: insights from a nationally prospective cohort study
Authors: Wang Mingsi , Yang Shu , Deng Jingwen , Wu Dehai , He Changzhi , Li Guanghua , Dong Ying , Zhang Yongxiang , Li Yilan
Published: November 2024

Aims

Hypoalbuminemia can lead to underestimations of the true anion gap levels. There are few data on albumin-corrected serum anion gap (ACAG) status and mortality in the diabetes. The study aimed to examine the association between ACAG and all-cause, cardiovascular, and cancer mortality in type 2 diabetes (T2D) patients.

Methods

Herein, 8,161 diabetic adults were included in the National Health and Nutrition Examination Survey (NHANES) 1999-2018. National Mortality Index (NDI) data were used for determining mortality outcomes through 31 December 2019. Cox proportional hazards models were used to estimate the risk of all-cause, cardiovascular, and cancer mortality. We conducted a mediation analysis using the counterfactual framework method to estimate how ACAG may be indirectly associated with increased mortality risk through mediators.

Results

A total of 2,309 deaths were documented over 8,161 person-years of follow up, including 659 cardiovascular and 399 cancer deaths. In multivariate analyses, higher ACAG levels had a significant correlation with an increase in all-cause (HR, 1.58; 95% CI, 1.38-1.81; P=0.001), cardiovascular (HR, 1.34; 95% CI, 1.05-1.72; P=0.019), and cancer (HR, 1.41; 95% CI, 1.02-1.96; P=0.018) mortality rates than the controls. Results of the mediation analysis showed that altered levels of C-reactive protein and estimated glomerular filtration rate (eGFR) explained 7.867% and 7.669% of the relation between serum ACAG and all-cause mortality, respectively (all P<0.05). Total cholesterol and HbA1c mediated 15.402% and 14.303% of the associations with cardiovascular mortality, respectively (all P<0.05).

Conclusions

Higher ACAG levels were significantly associated with increased all-cause, cardiovascular, and cancer mortality. Researchers suggest that patients with T2D who control ACAG in a normal state may be at a lower risk of mortality.
Bone metastasis in differentiated thyroid cancer: Spanish multicenter study of clinical characteristics, survival and prognostic factors
Authors: Dueñas-Disotuar Suset , Piñar-Gutiérrez Ana , de Lara-Rodríguez Irene , Sastre-Marcos Julia , Anda-Apiñániz Emma , Oleaga-Alday Amelia , Galofré JC , Orois Aida , Alcázar-Lázaro Victoria , Martínez-Guasch Laia , Sánchez-Ragnarsson Cecilia , Gálvez-Moreno María Ángeles , Familiar-Casado Cristina , Martín-Hernández Tomás , Romero-Lluch Ana R.
Published: November 2024

Objective

This study describes the characteristics, survival and prognostic factors in a cohort of patients with bone metastases (BM) from differentiated thyroid carcinoma (DTC).

Methods

This was a multicenter retrospective observational study conducted in Spain, including patients diagnosed with DTC and BM between 1980 and 2022. A Cox regression analysis was performed to examine prognostic factors for survival. Kaplan-Meier and log-rank tests were performed for survival analysis and comparison between groups.

Results

A total of 133 patients were included with a median follow-up of 40 (17-70) months. Seventy patients (52.6%) had BM at the initial diagnosis. Fifty-two (39.1%) had follicular carcinoma. Sixty-six (49.6%) presented multiple BM. The most frequent location was the spine (63.2%). Other metastases were present at diagnosis in 88 (66.2%), mainly lung (60.9%). BM were treated with I131 in 91 (68.4%) patients, with BM uptake in 63 (47.4%). Fifty-six (42.1%) received treatment with multikinase inhibitors. Fifty-three (3.9%) had skeletal-related events. Seventy-two (54.1%) died. The 3-, 5- and 10-year survival was 53.5, 39.5% and 28.5%, respectively. Significant prognostic factors in the multivariate analysis were the presence of lymph node metastases (N1) HR 1.71 (95% CI 1.005-2.098; p=0.048), BM treatment with I131 HR 0.532 (95% CI 0.304-0.931; p=0.027) and age ≥67 years at BM diagnosis HR 1.991 (95% CI 1.142-3.47; p=0.015).

Conclusions

Survival of DTC patients with BM treated in a Spanish cohort was 39.5% at 5 years and 28.5% at 10 years. Patients with BM treated with I131 appear to have a better outcome in terms of mortality and the presence of lymph node involvement and age over 67 years were associated with higher mortality.
Energy performance of self-powered green IoT nodes
Authors: Kuaban Godlove Suila , Czachórski Tadeusz , Gelenbe Erol , Pecka Piotr , Sharma Sapana , Singh Pradeep , Nkemeni Valery , Czekalski Piotr
Published: November 2024

The widespread adoption of the Internet of Things (IoT) partly depends on the successful design and deployment of IoT nodes that can operate for several years without any service outage and the need to replace their energy storage systems (ESSs) (e.g., battery, capacitor, or supercapacitor) when all the stored energy is depleted or when the cycle life of the ESSs is reached. Replacing batteries in the case of large-scale IoT networks and nodes located in places that are hard to reach is very challenging and costly, requiring the design of IoT nodes that can operate for several years without the need for human intervention. One such example is the deployment of IoT nodes in large agricultural fields (for soil or crop monitoring) or a long-distance pipeline (for pipeline monitoring). In this paper, we investigated the practical implications of imposing energy-saving thresholds on the energy performance metrics of green IoT nodes. We propose an energy packet-based model for the evaluation of the energy performance of a green IoT node with the possibility of switching the node to energy-saving regimes on the fly when the energy content of the ESS reaches defined thresholds. Configuring single or multiple thresholds improves the energy performance of the node significantly (e.g., increases the lifetime of the node and reduces the probability of service outage and energy wastage), and the value of the threshold(s) should be carefully chosen. The energy performance of the IoT node can also be improved by dimensioning the energy harvesting system to ensure that the node operates for several years without running out of energy (e.g., maximizing the lifetime of the nodes and minimizing the probability of service outage and energy wastage).
Which microbiome are we talking about? Contrasted diversity patterns and eco-evolutionary processes between gill and intestinal microbiomes of Antarctic fairy shrimps
Authors: Schwob Guillaume , Cabrol Léa , Vidal Paula M. , Tapia Yasna C. , Moya Fernando , Contador Tamara , Orlando Julieta , Maturana Claudia S.
Published: November 2024

Metazoans comprise multiple physical niches (“microenvironments”), each colonized by unique microbiomes that contribute to their hosts’ evolutionary dynamics, influencing their health, physiology, and adaptation to changing environments. Most wildlife microbiome studies focus on higher metazoans and multiple host microenvironments, while studies of lower species often concentrate on a single microenvironment, sometimes pooling whole bodies or specimens. This is particularly evident in small-sized animals, such as freshwater meiofaunal invertebrates, thus impeding a holistic understanding of microbiome assembly across host microenvironments and its relation with host population genetics. Leveraging the anostracan fairy shrimp Branchinecta, which has easily discernible organs and expected high levels of intraspecific genetic divergence, we aimed to investigate the microbiome assembly processes and test the phylosymbiosis signal in two microenvironments (gill and intestine) across four host populations of Branchinecta gaini within Maritime Antarctica, using 16S rRNA metabarcoding. Our results showed that the gill and intestine harbor strikingly different microbiomes resulting from the B. gaini ecological filtering of the surrounding environment microbial community. Both microenvironments exhibit their respective core microbiomes, yet the gill’s core microbiome is narrower and constitutes a smaller proportion of the overall bacterial community compared to that of the intestine. Within each host population (i.e. each sampling site), the microbiome assembles through distinct eco-evolutionary processes in both microenvironments, mostly stochastically (ecological drift) in the gill and deterministically (variable selection) in the intestine. Across different B. gaini populations, variable selection dominates in driving compositional divergence of both microenvironment microbiomes, although to a lesser extent in the gill. Lastly, our study reveals robust correlation between host intraspecific genetic structure and intestine microbiome composition, providing evidence of phylosymbiosis in anostracans. Contrastingly, phylosymbiosis was less pronounced in the gill microbiome. We discuss the potential differences in ecological filtering between each host microenvironment that may underlie the difference in the strength of phylosymbiosis. Our study highlights the relevance of considering host microenvironment and intraspecific levels in testing the phylosymbiosis hypothesis to better understand the intricate eco-evolutionary relationships between hosts and their microbiomes.
A particular focus on the prevalence of α-thalassemia and β-thalassemia among pregnant women in Changsha County, Hunan Province
Authors: Xia Yu , Huang Cailian , Yang Mudan , Zhang Meng , Lu Yang
Published: November 2024

Background

Thalassemia is a inherited monogenic blood disorder and more prevalent in southern China. In this study, Our aim was to elucidate the molecular spectrum and phenotypic features of thalassemia in pregnant women in Changsha County.

Methods

Next-generation sequencing (NGS) was conducted for 38,810 pregnant women to diagnose thalassemia in Changsha County. Further analysis of hematological parameters was conducted on subjects who had not previously undergone thalassemia screening in other hospitals.

Results

In this study, 2,208 (5.69%) pregnant women were diagnosed as carriers of thalassemia using NGS analysis. Among 1,594 cases of α-thalassemia, 23 genotypes were identified, and among 578 cases of β-thalassemia, 22 genotypes were detected. Additionally, 18 genotypes were detected among 36 cases of composite α- and β-thalassemia. Among all carriers of thalassemia, 8 rare α-mutations and 11 rare β-mutations were found in the study population. Notably, pregnant women diagnosed as carriers of thalassemia tended to have lower hemoglobin levels. Furthermore, multivariable logistic regression analysis indicates that the values of MCV and MCH have the greatest impact on genetic diagnosis.

Conclusion

Our study has provided detailed genotypes and hematological parameters of thalassemia in pregnant women in Changsha county and reveal that certain abnormal blood parameters have a remarkably impact on genetic diagnosis results. Furthermore, our data suggest that combining hemoglobin electrophoresis and NGS provides a powerful tool for prenatal diagnosis, which will increase the accuracy of clinical diagnosis of thalassemia.
s-CAPE trauma recovery program: the need for a holistic, trauma- and violence-informed domestic violence framework
Authors: Williams Karen , Harb Merrylord , Satyen Lata , Davies Mia
Published: November 2024

Introduction

Domestic violence is a worldwide issue of significant concern due to its high global prevalence rates, societal costs, and the pervasive individual-level effects on physical, mental, economic, and social health and functioning. There is therefore an urgent need to deliver effective and consistent recovery services in order to mitigate the harmful societal and individual-level impacts of experiencing domestic violence and to promote victim-survivor recovery and wellbeing. This paper reviews the literature around practice models and frameworks for recovery after domestic violence and proposes the need for a holistic, trauma- and violence-informed approach to facilitate recovery and healing.

Findings

Research indicates that formal supports improve recovery and wellbeing outcomes for victim-survivors, despite some literature gaps. Trauma-and-violence-informed approaches to care and holistic support are proposed as a means of improving recovery services and minimising harm to victim-survivors while maximising wellbeing. However, the literature reveals existing service gaps, including a lack of trauma-informed services and service providers engaging in practices that are retraumatising for victim-survivors.

Discussion

The review findings indicate the lack of a clear and consistent evidence-based recovery framework to provide holistic, trauma-and-violence-informed care that is tailored to the needs of victim-survivors of domestic violence.

Conclusion

We present the development of the s-CAPE trauma and recovery program, an integrated, holistic, trauma-and-violence-informed framework for recovery after domestic violence. s-CAPE was developed in Australia's first holistic, women's-only trauma treatment facility and is evidence-based and designed to address current service gaps, promoting positive recovery outcomes for victim-survivors.
Human CD34+-derived plasmacytoid dendritic cells as surrogates for primary pDCs and potential cancer immunotherapy
Authors: Fiore Giovanna , Weckwarth Wolfgang , Paetzold Kerstin , Albertí Servera Llucia , Gies Manuela , Rosenhauer Jakob , Antoniolli Martina , Nassiri Sina , Schmeing Stephan , Dettling Steffen , Soni Bhavesh , Majety Meher , Krug Anne B. , Hoves Sabine , Wolf Monika Julia
Published: November 2024

Introduction

Plasmacytoid dendritic cells (pDCs) are capable of triggering broad immune responses, yet, their scarcity in blood coupled to their reduced functionality in cancer, makes their therapeutic use for in situ activation or vaccination challenging.

Methods

We designed an in vitro differentiation protocol tailored for human pDCs from cord blood (CB) hematopoietic stem cells (HSCs) with StemRegenin 1 (SR-1) and GM-CSF supplementation. Next, we evaluated the identity and function of CB-pDCs compared to human primary pDCs. Furthermore, we tested the potential of CB-pDCs to support anti-tumor immune responses in co-culture with tumor explants from CRC patients.

Results

Here, we report an in vitro differentiation protocol enabling the generation of 200 pDCs per HSC and highlight the role of GM-CSF and SR-1 in CB-pDC differentiation and function. CB-pDCs exhibited a robust resemblance to primary pDCs phenotypically and functionally. Transcriptomic analysis confirmed strong homology at both, baseline and upon TLR9 or TLR7 stimulation. Further, we could confirm the potential of CB-pDCs to promote inflammation in the tumor microenvironment by eliciting cytokines associated with NK and T cell recruitment and function upon TLR7 stimulation ex vivo in patient tumor explants.

Discussion

This study highlights CB-pDCs as surrogates for primary pDCs to investigate their biology and for their potential use as cell therapy in cancer.
Causal association between plasma metabolites and diverse autoimmune diseases: a two-sample bidirectional mendelian randomization study
Authors: Yuan Xiwen , Yang Peiyan , Hu Jiapeng , Cai Dixin , Hu Baoshan , Rui Gang , Lin Zhiming
Published: November 2024

Background

Autoimmune diseases (ADs) are a category of conditions characterized by misrecognition of autologous tissues and organs by the immune system, leading to severe impairment of patients’ health and quality of life. Increasing evidence suggests a connection between fluctuations in plasma metabolites and ADs. However, the existence of a causal relationship behind these associations remains uncertain.

Methods

Applying the two-sample mendelian randomization (MR) method, the reciprocal causality between plasma metabolites and ADs was analyzed. We took the intersection of two metabolite genome-wide association study (GWAS) datasets for GWAS-meta and obtained 1,009 metabolites’ GWAS data using METAL software. We accessed GWAS summary statistics for 5 common ADs, inflammatory bowel disease (IBD), multiple sclerosis (MS), type 1 diabetes (T1D), systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) from published GWAS data. MR analyses were performed in discovery and replication stage simultaneously. Meanwhile, the reverse MR analysis was conducted to investigate the possibility of reverse causal association. Furthermore, a series of sensitivity analyses were conducted to validate the robustness of the results. These statistical analyses were conducted using R software. Finally, the web version of MetaboAnalyst 5.0. was applied to analyze metabolic pathways. Ultimately, we conducted ELISA assays on plasma samples from patients to validate the results.

Results

4 metabolites were identified to have causal relationships with IBD, 2 metabolites with MS, 13 metabolites with RA, and 4 metabolites with T1D. In the reverse MR analysis, we recognized causality between SLE and 22 metabolites, IBD and 4 metabolites, RA and 22 metabolites, and T1D and 37 metabolites. Additionally, 4 significant metabolic pathways were identified in RA by metabolic pathway analysis in the forward MR analysis. Correspondingly, in the reverse, 11 significant metabolic pathways in RA, 8 in SLE, and 4 in T1D were obtained using identical approaches. Furthermore, the protective role of glutamate was confirmed through ELISA assays.

Conclusions

Our research established a reciprocal causality between plasma metabolites and ADs. Furthermore, diverse metabolic pathways correlated with ADs were uncovered. Novel insights into the prediction and diagnosis were provided, as well as new targets for precise treatment of these conditions were discovered.
IFNγ-secreting T cells that highly express IL-2 potently inhibit the growth of intracellular M. tuberculosis in macrophages
Authors: Zhu Liying , Wang Bo , Gu Jin , Zhou Jiayu , Wu Yuan , Xu Wei , Yang Min , Cai Xia , Shen Hongbo , Lu Lu , Wang Feifei
Published: November 2024

Cytokine of interferon-gamma (IFNγ) plays a vital role in the immune response against Mycobacteria tuberculosis (Mtb) infection, yet the specific function of T cells producing IFNγ in this process remains unclear. In this study, we first isolated IFNγ+CD3+ T cells induced by Mtb antigens using surface staining assays. which showed a strong ability to inhibit the growth of intracellular mycobacteria in macrophages. Peripheral blood mononuclear cells (PBMCs) from healthy individuals were then challenged with Bacillus Calmette–Guérin (BCG) or Mtb, respectively, to sort IFNγ-secreting T cells for mRNA sequencing to analyze the gene expression patterns. The results of the integrated data analysis revealed distinct patterns of gene expression between IFNγ+CD3+ T cells induced by the BCG vaccine and those induced by Mtb pathogens. Further, unlike Mtb-induced cells, BCG-induced IFNγ+CD3+ T cells expressed high levels of interleukin-2 (IL-2), which increased the frequencies of these cells and the production of effector cytokines IFNγ and IL-2. Our findings suggested that IFNγ+CD3+ T cells with high IL-2 expression presented potent effector functions to inhibit intracellular Mtb growth, while Mtb infection impaired IL-2 expression in IFNγ+CD3+ T cells.
Depicting the cellular complexity of pancreatic adenocarcinoma by Imaging Mass Cytometry: focus on cancer-associated fibroblasts
Authors: Erreni Marco , Fumagalli Maria Rita , D’Anna Raffaella , Sollai Mauro , Bozzarelli Silvia , Nappo Gennaro , Zanini Damiano , Parente Raffaella , Garlanda Cecilia , Rimassa Lorenza , Terracciano Luigi Maria , Biswas Subhra K. , Zerbi Alessandro , Mantovani Alberto , Doni Andrea
Published: November 2024

Introduction

Pancreatic ductal adenocarcinoma (PDAC) represents the complexity of interaction between cancer and cells of the tumor microenvironment (TME). Immune cells affect tumor cell behavior, thus driving cancer progression. Cancer-associated fibroblasts (CAFs) are responsible of the desmoplastic and fibrotic reaction by regulating deposition and remodeling of extracellular matrix (ECM). As tumor-promoting cells abundant in PDAC ECM, CAFs represent promising targets for novel anticancer interventions. However, relevant clinical trials are hampered by the lack of specific markers and elusive differences among CAF subtypes. Indeed, while single-cell transcriptomic analyses have provided important information on the cellular constituents of PDACs and related molecular pathways, studies based on the identification of protein markers in tissues aimed at identifying CAF subtypes and new molecular targets result incomplete.

Methods

Herein, we applied multiplexed Imaging Mass Cytometry (IMC) at single-cell resolution on 8 human PDAC tissues to depict the PDAC composing cells, and profiling immune cells, endothelial cells (ECs), as well as endocrine cells and tumor cells.

Results

We focused on CAFs by characterizing up to 19 clusters distinguished by phenotype, spatiality, and interaction with immune and tumor cells. We report evidence that specific subtypes of CAFs (CAFs 10 and 11) predominantly are enriched at the tumor-stroma interface and closely associated with tumor cells. CAFs expressing different combinations of FAP, podoplanin and cadherin-11, were associated with a higher level of CA19-9. Moreover, we identified specific subsets of FAP+ and podoplanin+/cadherin-11+ CAFs enriched in patients with negative prognosis.

Discussion

The present study provides new general insights into the complexity of the PDAC microenvironment by defining phenotypic heterogeneities and spatial distributions of CAFs, thus suggesting different functions of their subtypes in the PDAC microenvironment.
Identifying optimal tumor-associated antigen combinations with single-cell genomics to enable multi-targeting therapies
Authors: Nix Matthew A. , Lareau Caleb A. , Verboon Jeffrey , Kugler David G.
Published: November 2024

Targeted antibody-based therapy for oncology represents a highly efficacious approach that has demonstrated robust responses against single tumor-associated antigen (TAA) targets. However, tumor heterogeneity presents a major obstacle for targeting most solid tumors due to a lack of single targets that possess the right on-tumor/off-tumor expression profile required for adequate therapeutic index. Multi-targeting antibodies that engage two TAAs simultaneously may address this challenge through Boolean logic-gating function by improving both therapeutic specificity and efficacy. In addition to the complex engineering of multi-targeting antibodies for ideal logic-gate function, selecting optimal TAA combinations ab initio is the critical step to initiate preclinical development but remains largely unexplored with modern data-generation platforms. Here, we propose that single-cell atlases of both primary tumor and normal tissues are uniquely positioned to unveil optimal target combinations for multi-targeting antibody therapeutics. We review the most recent progress in multi-targeting antibody clinical development, as well as the designs of current TAA combinations currently exploited. Ultimately, we describe how multi-targeting antibodies tuned to target pairs nominated through a data-driven process are poised to revolutionize therapeutic safety and efficacy, particularly for difficult-to-treat solid tumors.