bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mammary hydroxylated oestrogen activates the NLRP3 inflammasome in tumor-associated macrophages to promote breast cancer progression and metastasis
Authors: Zhao Han , Xu Jiahao , Zhong Ya’nan , He Shiqing , Hao Zhixiang , Zhang Bei , Liu Zhao , Zhou Xueyan 
Published: September 2023

Abstract
Background: An imbalance of oestrogen homeostasis and an inflammatory tumor microenvironment (TME) are vital risk factors for the progression and metastasis of breast cancer.
Methods: The liquid chromatography-tandem mass spectrometry (LC-MS/MS) quantitative analysis method for oestrogen active substances was used to detect the levels of oestrogen and its metabolites of 238 clinical serum samples, 6 clinical malignant breast cancer tissues and their corresponding non-tumor adjacent tissues and MMTV-PyMT mice mammary tissues. In vitro and in vivo experiments were conducted to investigate the correlation between oestrogen and tumor-associated macrophages (TAMs) and the role and mechanism of the NLRP3 inflammasome activated by oestrogen in promoting breast cancer progression and metastasis.
Results: Results of the present study demonstrated that tumor-associated macrophages (TAMs) were the main population of immune cells present in the breast TME. Thus, TAM-dependent tumor metastasis may be triggered by hydroxylated oestrogen via NOD-like receptor thermal protein domain associated protein 3 (NLRP3), inflammasome activation and IL-1β production. Mechanistically, TAM-derived inflammatory cytokines induced the expression of matrix metalloproteinases in breast tumor cells, leading to breast tumor invasion and metastasis. Collectively, these results revealed a previously unknown role of hydroxylated oestrogen in the reprogramming of the TME via NLRP3 inflammasome activation in TAMs. These mechanisms may facilitate breast cancer cell proliferation, migration and invasion.
Conclusions: The disorder of oestrogen metabolism in the breast, especially the abnormal elevation of hydroxylated oestrogen, may be a risk factor for the metastasis of breast tumors. Hydroxylated oestrogens act on TAMs to induce the generation of an inflammatory microenvironment in breast tumors, thereby regulating the progression of breast cancer.
Home Garden Characteristics among Lao’s Vulnerable Upland Rural Farmers in Phoukhoud District, Lao PDR
Authors: Shrestha Suraj , Maraseni Porf. Tek , Apan Porf. Armando 
Published: September 2023

Abstract
The provincial and district agriculture and forestry offices of Lao PDR and local civil society groups are implementing several agricultural production initiatives and recognize the importance that home gardens contribute tohousehold livelihood. Despite of its importance, studies on home garden characteristics among rural vulnerable households are limited. Thus, this study assesses home garden characteristics among three types of vulnerable upland rural farmer households in Phoukhoud District, Lao PDR: People with Disability Households (PWDHH), Female-headed Households (FHHH), and Other Vulnerable Households(OVHH). The study applied mixed methods by integrating both quantitative and qualitative data analysis.
The study shows that approximately 84% of households used home garden crops for household consumption, with 21% PWDHH, 29% FHHH, and 34% OVHH also selling surplus. We found home gardens near and far from homes, with sizes varying from smaller to largerplots; FHHHs home gardens appear to be the largest, furthest from their home and they spent more time, whereas PWDHH's home gardens were the closest, smaller, less time spent and harvested the most compared to other HHs. On average, 37% of vulnerable households harvested crops year-round.
Despite the unpaid domestic work disparity, women felt it empowered them as managers and owners of their home gardens. Eighty-three different varieties of edible plant-based crops were found in the home gardens, with FHHHs producing the fewest varieties and OVHHs producing the most varieties. They primarily used their own traditional seeds, mostly using traditional methods to select and store them, and experienced seed loss.
This study discusses the constraints and opportunities and provides recommendations for optimizing home garden management. The study supports Lao PDR’s National Agriculture Policies and Strategies and the call for an urgent plan to reduce exposure and vulnerability for farmers and contributes to attaining Sustainable Development Goals (SDGs) 2, 3, 12, 13, and 15.
Эффективность режимов комбинированной лекарственной предтрансплантационной подготовки у пациентов с однократной трансплантацией аутологичных гемопоэтических стволовых клеток при множественной миеломе
Authors: Кострома Иван Иванович , Жук А. С. , Сидорова Ж. Ю. , Сабитова Р. Р. , Аксенова А. Ю. , Белопольская О. Б. , Бессмельцев С. С. , Сидоркевич С. В. , Грицаев С. В. 
Published: September 2023

Aim. To conduct an interim outcome analysis of conditioning regimens with carfilzomib or thiotepa compared to standard melphalan 200 mg/m2 regimen in multiple myeloma (MM) patients with single autologous hematopoietic stem cell transplantation (auto-HSCT).
Materials & Methods. The retrospective analysis focused on outcomes of 67 single auto-HSCTs performed from 2017 to 2021. Responses as well as progression-free (PFS) and overall survival (OS) rates were compared in MM patients per IWMG criteria in pre- and post-transplant periods. Three conditioning regimens were assigned: melphalan 200 mg/m2 (Mel200), melphalan/carfilzomib combination (Mel/Karfil), and melphalan/thiotepa combination (Mel/Thio). In an additional cohort of 12 MM patients, next-generation sequencing assay was used to detect inherited and somatic mutations associated with proteasome inhibitor efficacy. For this purpose, DNA of peripheral blood lymphocytes and bone marrow plasma cells were examined.
Results. PFS medians were comparable in MM patients treated with Mel200 (n = 40) and Mel/Karfil (n = 10) conditioning regimens, they were 32 and 23 months, respectively (p = 0.241). In these cohorts, OS median was not reached, and the curves showed no significant differences (p = 0.050). Out of 10 MM patients treated with Mel/Karfil, six received melphalan 140 mg/m2, the remaining 4 patients received 200 mg/m2. Complete response (CR) rate in the Mel200 and Mel/Karfil groups increased two-fold after auto-HSCT: from 35.5 % to 74.2 % and from 25.0 % to 50.0 %, respectively. The worst PFS and OS medians were in the Mel/Thio group, i.e., 12 and 17 months, respectively, and CR rate after auto-HSCT remained unchanged. The best PFS was associated with CR rather than very good partial or partial response after auto-HSCT, they were 48, 21, and 23 months, respectively (p = 0.001). Exome sequencing of DNA of peripheral blood lymphocytes and bone marrow plasma cells revealed polymorphic variants in the genes associated with chemotherapy response.
Conclusion. The outcomes of Mel/Karfil, the regimen containing the reduced dose of melphalan 140 mg/m2, and the statistical comparability with the Mel200 regimen suggest that this combination can be effective in the treatment of MM patients with impaired renal function, which still needs to be further confirmed. No advantage of the combined conditioning regimen over the standard one can be accounted for by the loss of plasma cell sensitivity to proteasome inhibitors. The obtained data provide ground for modifying the study protocol with a particular focus on evaluating the efficacy and safety of conditioning regimen Mel/Karfil with melphalan 200 mg/m2 depending on biologic phenotype of plasma cell.
KIR-генетические факторы и ответ на терапию ингибиторами тирозинкиназ при хроническом миелоидном лейкозе
Authors: Кузьмич Елена Витальевна , Павлова И. Е. , Бубнова Л. Н. , Бессмельцев С. С. 
Published: September 2023

The development of tyrosine kinase inhibitors (TKIs) and their introduction into clinical practice considerably improved the prognosis for chronic myeloid leukemia (CML) patients. About 50 % of patients with achieved deep molecular response are eligible for safe TKI discontinuation. Despite these advances, no reliable biomarkers are known to predict a response and sustaining treatment-free remission after TKI withdrawal. As TKIs do not destroy leukemic stem cells, which can be responsible for relapse, critical importance in CML is attached to natural killers (NK-cells) having antitumor activity. Functional activity of NK-cells is evaluated by expression level and repertoire of killer cell immunoglobulin-like receptors (KIR). Current studies demonstrate that a patient’s KIR genotype affects the probability of achieving early and deep molecular responses to first- and second-generation TKIs, progression-free and overall survivals, and sustaining treatment-free remission. On that ground, KIR-genetic factors can be regarded as promising predictors of response to TKI therapy in CML. Early clinical studies, which dealt with monoclonal antibodies blocking the inhibitory KIR in order to increase NK-cell activity, revealed an acceptable safety profile and efficacy in some hematological diseases (such as acute myeloid leukemia, multiple myeloma, Т-cell lymphoma) if used in combination with cytostatic drugs or antitumor monoclonal antibodies. KIR genotype determination can contribute to the development of effective therapies of this malignant hematological tumor.
Debunking the Falsehoods of Historical Interpretations: Arnold Spekke on George Kennan’s “Soviet-American Relations, 1917–1920. The Decision to Intervene”
Authors: Selga Marika 
Published: September 2023

In the spring of 1958, Arnold Spekke, Charge d’Affaires in Washington D.C., having read George Kennan’s book “Soviet-American Relations, 1917–1920. The Decision to Intervene” decided to write a comment on certain facts expressed in the book. He concentrated on the description of the execution of Czar Nicholas II and his family, as well as the fact that the book did not mention the Latvian units that fought under Allied leadership, namely, the Troitsk battalion as part of the 3rd Czechoslovak Division. Spekke also submitted a letter written in 1928 by Nikolai Sokolov’s assistant, Captain Pavel Bulygin, in which it was confirmed that there were no Latvians among the shooters. Kennan in his response assured that his goal had only been to emphasize the cruelty with which the murder was committed. The preparation of comments contributed to the efforts of Latvians in exile to focus on writing down memories and studying Latvian history.
20. gadsimta pirmās puses Latgales vēstures norises: aculiecinieka un dalībnieka Jāņa Rubuļa liecība
Authors: Jēkabsons Ēriks 
Published: September 2023

Latgales un Latgales latviešu vēsture līdz 20. gadsimtam attīstījās līdztekus, taču no pārējās latviešu tautas vēstures zināmā mērā atšķirīgos apstākļos, tādēļ Latgales latviešu nacionālā atmoda un apvienošanās ar pārējo tautu vienotā Latvijas valstī noritēja ar sarežģījumiem. Minētie procesi vēl līdz šim laikam nav pilnībā izpētīti, tādēļ jebkurš vēstures avots un tā analīze var būt nozīmīgs. Šajā gadījumā tas attiecas uz karavīru, sabiedrisku darbinieku, politiķi Jāni Rubuli, kurš no 1917. gada atradās sabiedriski politisko norišu epicentrā, aktīvi piedaloties Latgales kongresā, Latviešu strēlnieku pulku izpildkomitejas (Iskolastrela) Latgaliešu strēlnieku sekcijas darbā, Latvijas Neatkarības karā, Satversmes sapulces un Saeimas darbībā, valsts politiskajā un saimnieciskajā dzīvē kopumā, visbeidzot – trimdā Rietumos pēc Otrā pasaules kara.
1918. gada decembris Rīgā – Latvijas zemessardzes rotu dumpis
Authors: Buks Artis 
Published: September 2023

Rakstā aplūkota situācija Vācijas armijas okupētajā Vidzemē un Kurzemē 1918. gada rudenī – Latvijas Republikas proklamēšanas laikā –, kā arī sabiedrībā valdošo ideju un vēlmju pretrunu saspīlējums gada nogalē, kas izpaudās kā masveida nepakļaušanās pavēlei iestāties nupat izveidotajos Latvijas bruņotajos spēkos (zemessardzē). Proti, no latviešiem saformētās vienības atteicās doties uz fronti. Kara tiesa vairākiem dumpiniekiem piesprieda nāvessodu. Tālaika sabiedrībā notikušais izsauca visai plašu rezonansi, un daudz kas liek domāt, ka tas lielā mērā inspirēja arī masveida dezertēšanu no zemessardzes rindām 1919. gada janvāra pirmajās dienās. Šie notikumi historiogrāfijā praktiski nav aplūkoti, tāpēc rakstā mēģināts rekonstruēt notikumu gaitu, lai saprastu, kas īsti notika Rīgā 1918. gada pašās pēdējās dienās.
Use of intermediary contracts in maritime transportation
Authors: Naumova E. A. , Karaseva E. A. 
Published: September 2023

Shipping is an integral part of the supply chain for most industries, making it the backbone of global trade. This explains the relevance of the issues of legal regulation of maritime transport, the knowledge of which is necessary for the effective organization of international transport operations.The description of linear and tramp shipping is given. The concept of a bill of lading, the main shipping document in shipping, is considered, the advantages and possible difficulties with its use are given.Since the transportation of goods is characterized by the complexity of relations and the variety of contractual structures used, the authors consider the features of concluding contracts for maritime transportation, maritime agency and maritime mediation. The significance of intermediary agreements in the transport provision of foreign trade activities is substantiated.The main legislative and regulatory documents in the field of maritime transport are given. Systematized requirements for the organization of contractual relations in the implementation of maritime transportation.
Major cardiovascular events increase in long-term proprotein convertase subtilisin/kexin type 9 inhibitors therapy: the Tuscany cost-effective study
Authors: Sbrana Francesco , Dal Pino Beatrice , Bigazzi Federico , Ripoli Andrea , Corciulo Carmen , Lo Surdo Giuseppa , Biagini Stefania , Sampietro Tiziana 
Published: September 2023

Background
Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) represent a breakthrough in the treatment of hypercholesterolemia. The aim of this study was to perform a multicentre prospective analysis on the effects of PCSK9i since their distribution in Italy.

Methods
During the study period (July 2017 to February 2022) 246 patients (mean age 61 ± 11 years, male 73%) who were evolocumab (142/246) or alirocumab (104/246) new users were enrolled in the CERTI (Costo Efficacia Regione Toscana Inibitori PCSK9) study. Lipid value, adverse events (AEs), major cardiovascular events (MACEs) and intima-media thickness were analysed.

Results
PCSK9i therapy allowed a significant improvement in patients’ lipid profile [total cholesterol −35%, P < 0.001; triglycerides −9%, P < 0.05; low-density lipoprotein (LDL) cholesterol −51%, P < 0.001; Lp(a) levels −4%, P < 0.05], maintained during the follow-up. No significant variations in intima-media thickness were observed. In the subgroup of patients with more than 1 year of PCSK9i therapy (165/246 patients) we highlighted: a 66% reduction in MACEs compared with the year before recruitment; a progressive increase in MACEs during the follow-up (MACEs event/rate at first year 0.08 vs. MACEs event/rate at year 5: 0.47); a patients cluster with late MACEs older, with higher prevalence of hypertension, smoking habit and peripheral vascular disease. During the follow-up, we recorded AEs in 31% of patients, which mainly resulted in reduction/discontinuation of lipid-lowering therapy for 50 patients or in discontinuation/shift of PCSK9i (respectively 8 and 6 cases).

Conclusion
Our data agree with the large evidence on the effectiveness/tolerability of PCSK9i therapy; however, although PCSK9i represents a good cholesterol-lowering therapeutic option, our study shows a progressive increase in MACEs during the late follow-up that deserve further research.
Penetrance of missense mutation of OR2AT4 and OR9G1/9 gene polymorphism increases risk factor in azoospermic patients
Authors: Saxena Ajit Kumar , Tiwari Meenakshi , Agarwal Mukta , Shalini  
Published: September 2023

Objectives:
In human, olfactory receptor (ORs) gene polymorphism regulate testicular development and physiological functions during spermatogenesis. However, the etiopathology of OR gene in male infertility is still restricted that required further studies. Basic mechanism involves the identification of peripheral signals based on specific chemoreceptors site that are expressed on the surface of mature spermatozoa inside the female reproductive tract. These receptors belong to G-protein couple receptors (GPCR) of superfamily and the roles of ORs gene linked to sperm chemotaxis through chemokinesis. In the present study, we have studied the role of Olfactory receptor family 2 subfamilies AT member 4 (OR2AT4) and Olfactory receptor family 9 subfamily G member 1/9 (OR9G1/9) genes polymorphism in clinically diagnosed azoospermic patients.

Materials and Methods:
Systematically, GTG banded karyotypes were developed using short term lymphocyte cultures, fluorescence in situ hybridization using SRY probe and PCR based microdeletion of Y-chromosome was characterized using STS marker (SY255). Whole exome sequencing (WES) based analysis was performed in azoospermic patients to identify the involvement of de-novo mutation in OR2AT4 and OR9G1/OR9G9 genes mutation followed by bioinformatics tools used for the analysis to identify changes in respective amino acids.

Results:
OR2AT4 showing missense mutation after substitution of nucleotide (G→A) followed by lack of change in amino acid (Gln→Gln), but in OR9G1/G9 gene showing changes of substitution of nucleotide thymidine into adenine (T→A), whereas valine is replaced by glutamine (Val→ Glu), similarly thymidine is substituted by cysteine (T→C), after decode phenylalanine is replaced by leucine (Phe→Leu). Further, 3D protein helical structure was developed with the help of bioinformatics on the basis of amino acids coded protein and compare with mutated amino acid or truncated protein residues with the help of iTASSER server.

Conclusion:
Present study demonstrate the role of OR2AT4 and OR9G1/9 gene polymorphism elucidates the functional role of protamine in ectopic receptors followed by increasing “risk” of developing male infertility that leads the clinical condition defined as non-obstructive azoospermia.
The functioning of literary allusions and reminiscences in the novel "The Universal Storm" by Sleptsova-Kuorsunnakh
Authors: Burtsev A. A. , Burtseva M. A. 
Published: September 2023

The article analyses the artistic speciﬁcity in the novel "The Universal Storm" by Elena Sleptsova-Kuorsunnakh, dedicated to the tragic fate of the Sakha intelligentsia. By its genre nature, this is a synthetic work that combines the features of an epic novel with a document-based family chronicle. Although the narrative in the novel is built around the Orosin clan, its distinctive feature is the depiction of a complex polyphony of individual destinies and characters that do not merge into a single mass, but give rise to real diversity. The article features the images of such historical ﬁgures as Vasily Nikiforov, Anepodist Sofronov, Platon Oyunsky, and Vera Davydova. The depiction of the real vicissitudes of their private lives not only conﬁrms the novelistic character of the Kuorsunnakh's work, but also testiﬁes to the presence of the features of psychological "genre generalization". In this regard, as shown in the article, the use of literary allusions and reminiscences by the author among the ways of mastering the artistic material seems to be successful.
Boundaries of being: The images of inverted space in the prose of the Yakut writer Platon Oyunsky
Authors: Noeva (Karmanova) S. E. 
Published: September 2023

The article attempts to study the images of inverted space in the prose of Platon Oyunsky. Special attention is paid to the initial images of the artistic chronotope, forming a scheme of inversion: this is the underwater and lower worlds, the urban space in the writer's stories. The author of the article also highlights the image of the border, which forms a speciﬁc character of the Yakut world, also asserting the exceptional image of the initiating hero. The scholarly paradigm of this study also includes the issue of the body (clothing) as the main component of the image of the “I” of an urban person, deﬁning the boundaries of his/her social sphere.
Prospects of oil and gas potential of the Indigiro-Zyryansky trough based on direct geochemical data
Authors: Aleksandrov A. R. , Sivtsev A. I. 
Published: September 2023

Within Eastern Yakutia, certain prospects for oil and gas potential are associated with a number of negative structural elements of the Mesocainozoic age. Given the presence of a powerful sedimentary cover and a relatively calm tectonic situation, the Indigiro-Zyryansky trough is considered the most promising territory for oil and gas. According to the results of deep drilling conducted in the late 1980s and early 1990s, the presence of sufficiently powerful Cenozoic age strata was established. After joint processing of the drilling data with the seismic survey materials, the thickness of Cenozoic sediments in the trough is estimated at 2 – 2.5 km. The expediency of rethinking the materials of geochemical testing together with the data obtained during deep drilling is noted. According to the peculiarities of the composition of gases obtained during deep drilling and testing of wells in the section of the Indigiro-Zyryansky deflection, there are two types of natural gas. The first type is associated with Paleogene deposits and, judging by its composition, has a microbial genesis (wells No. 272-01 and 272-02). The second type of gas obtained from Upper Jurassic deposits appears to be catagenetic and heavier in composition (well No. 272-05). An analytical review of the results of direct geochemical testing is made, which also confirms the presence of at least two different types of gases. At the same time, the gas characterized as deep has clear features similar to the gases of collapsing oil accumulations. It is assumed that near-surface gases enriched with nitrogen and carbon dioxide may be associated with carbonaceous deposits of the Upper Jurassic and Lower Cretaceous. It is recommended to conduct areal geochemical testing using artificial sorbents for aromatic hydrocarbons.