bluuebunny/crossref_metadata_2025_split huggingface dataset:
Medicinal plants show remarkable antiproliferative potential in human cancer cell lines
Authors: Nawaz Aisha , Arif Amina , Jamal Adil , Shahid Muhammad Naveed , Nomani Ibtesam , Bahwerth Fayez Saeed 
Published: January 2022

ABSTRACT
Molecules isolated and identified from plant origin are used to manufacture most chemotherapeutic drugs for cancer treatment. We assumed that these plant extracts contain prolific bioactive compounds with potent antiproliferative activities and could be effective against different human cancer cells. Ethanolic extracts were prepared from Chelidonium majus, Myrica cerifera, Fumaria indica, Nigella sativa, and Silybum marianum, and the antiproliferative assay was performed in HepG2 and HeLa human cancer cell lines. All plants extract exhibited antiproliferative potential against studied cancer cell lines in the dose and time-dependent manner. Chelidonium majus and Silybum marianum have shown promising results against HepG2 and HeLa cells, respectively, followed by Myrica cerifera, Fumaria indica, and Nigella sativa. Results indicated that utilization of whole plant extract as anticancer compounds could be of great value in generating novel chemotherapeutic drugs.
Anc2vec: embedding gene ontology terms by preserving ancestors relationships
Authors: Edera Alejandro A , Milone Diego H , Stegmayer Georgina 
Published: January 2022

Abstract
The gene ontology (GO) provides a hierarchical structure with a controlled vocabulary composed of terms describing functions and localization of gene products. Recent works propose vector representations, also known as embeddings, of GO terms that capture meaningful information about them. Significant performance improvements have been observed when these representations are used on diverse downstream tasks, such as the measurement of semantic similarity between GO terms and functional similarity between proteins. Despite the success shown by these approaches, existing embeddings of GO terms still fail to capture crucial structural features of the GO. Here, we present anc2vec, a novel protocol based on neural networks for constructing vector representations of GO terms by preserving three important ontological features: its ontological uniqueness, ancestors hierarchy and sub-ontology membership. The advantages of using anc2vec are demonstrated by systematic experiments on diverse tasks: visualization, sub-ontology prediction, inference of structurally related terms, retrieval of terms from aggregated embeddings, and prediction of protein–protein interactions. In these tasks, experimental results show that the performance of anc2vec representations is better than those of recent approaches. This demonstrates that higher performances on diverse tasks can be achieved by embeddings when the structure of the GO is better represented. Full source code and data are available at https://github.com/sinc-lab/anc2vec.
Kiss1 expression in the hypothalamic arcuate nucleus is lower in dairy cows of reduced fertility
Authors: Clarke Iain J , Reed Charlotte B , Burke Chris R , Li Qun , Meier Susanne 
Published: January 2022

Abstract
We tested the hypothesis that divergent genetic merit for fertility of dairy cows is due to aberrant reproductive neuroendocrine function. The kisspeptin status of non-pregnant cows of either positive (POS) or negative (NEG) breeding values (BVs) for fertility was studied in three groups (n = 8), based on their previous post-partum period: POS cows, which had spontaneous ovarian cycles (POS-CYC) and NEG cows, which either cycled (NEG-CYC) or did not cycle (NEG-NONCYC). Ovarian cycles were synchronized, blood samples were taken to define endocrine status, and the animals were slaughtered in an artificial follicular phase. The brains and the pituitary glands were collected for quantitative polymerase chain reaction (qPCR) and in situ hybridization of hypothalamic GNRH1, Kiss1, TAC3, and PDYN and pituitary expression of LHB and FSHB. Gonadotropin releasing hormone (GnRH) and kisspeptin levels were quantified in snap frozen median eminence (ME). GNRH1 expression and GnRH levels in the ME were similar across groups. Kiss1 expression in the preoptic area of the hypothalamus was also similar across groups, but Kiss1 in the arcuate nucleus was almost 2-fold higher in POS-CYC cows than in NEG groups. TAC3 expression was higher in POS-CYC cows. The number of pituitary gonadotropes and the level of expression of LHB and FSHB were similar across groups. We conclude that the lower levels of Kiss1 and TAC3 in NEG cows with low fertility status and may lead to deficient GnRH and gonadotropin secretion.
Age-associated changes in cumulus cells and follicular fluid: the local oocyte microenvironment as a determinant of gamete quality
Authors: Babayev Elnur , Duncan Francesca E 
Published: January 2022

AbstractThe ovary is the first organ to age in humans with functional decline evident already in women in their early 30s. Reproductive aging is characterized by a decrease in oocyte quantity and quality, which is associated with an increase in infertility, spontaneous abortions, and birth defects. Reproductive aging also has implications for overall health due to decreased endocrinological output. Understanding the mechanisms underlying reproductive aging has significant societal implications as women globally are delaying childbearing and medical interventions have greatly increased the interval between menopause and total lifespan. Age-related changes inherent to the female gamete are well-characterized and include defects in chromosome and mitochondria structure, function, and regulation. More recently, it has been appreciated that the extra-follicular ovarian environment may have important direct or indirect impacts on the developing gamete, and age-dependent changes include increased fibrosis, inflammation, stiffness, and oxidative damage. The cumulus cells and follicular fluid that directly surround the oocyte during its final growth phase within the antral follicle represent additional critical local microenvironments. Here we systematically review the literature and evaluate the studies that investigated the age-related changes in cumulus cells and follicular fluid. Our findings demonstrate unique genetic, epigenetic, transcriptomic, and proteomic changes with associated metabolomic alterations, redox status imbalance, and increased apoptosis in the local oocyte microenvironment. We propose a model of how these changes interact, which may explain the rapid decline in gamete quality with age. We also review the limitations of published studies and highlight future research frontiers.
Extracellular vesicle research in reproductive science: Paving the way for clinical achievements
Authors: Aleksejeva Elina , Zarovni Natasa , Dissanayake Keerthie , Godakumara Kasun , Vigano Paola , Fazeli Alireza , Jaakma Ülle , Salumets Andres 
Published: January 2022

Abstract
Mammalian conception involves a multitude of reciprocal interactions via a molecular dialogue between mother and conceptus. Extracellular vesicles (EVs) are secreted membrane-encapsulated particles that mediate cell-to-cell communication in various contexts. EVs, which are present in seminal, follicular, oviductal, and endometrial fluids, as well as in embryo secretions, carry molecular constituents that impact gamete maturation, fertilization, early embryo development, and embryo–maternal communication. The distribution, concentration, and molecular cargo of EVs are regulated by steroid hormones and the health status of the tissue of origin, and thus are influenced by menstrual phase, stage of conception, and the presence of infertility-associated diseases. EVs have been recognized as a novel source of biomarkers and potential reproductive medicine therapeutics, particularly for assisted reproductive technology (ART). There are still many technological and scientific hindrances to be overcome before EVs can be used in clinical diagnostic and therapeutic ART applications. Issues to be resolved include the lack of standardized measurement protocols and an absence of absolute EV quantification technologies. Additionally, clinically suitable and robust EV isolation methods have yet to be developed. In this review, we provide an overview of EV-mediated interactions during the early stages of reproduction from gamete maturation to embryo implantation and then outline the technological progress that must be made for EV applications to be translated to clinical settings.
Curcumin-incorporated 3D bioprinting gelatin methacryloyl hydrogel reduces reactive oxygen species-induced adipose-derived stem cell apoptosis and improves implanting survival in diabetic wounds
Authors: Xia Sizhan , Weng Tingting , Jin Ronghua , Yang Min , Yu Meirong , Zhang Wei , Wang Xingang , Han Chunmao 
Published: January 2022

Abstract

Background
Gelatin methacryloyl (GelMA) hydrogels loaded with stem cells have proved to be an effective clinical treatment for wound healing. Advanced glycation end product (AGE), interacting with its particular receptor (AGER), gives rise to reactive oxygen species (ROS) and apoptosis. Curcumin (Cur) has excellent antioxidant activity and regulates intracellular ROS production and apoptosis. In this study, we developed a Cur-incorporated 3D-printed GelMA to insert into adipose-derived stem cells (ADSCs) and applied it to diabetic wounds.

Methods
GelMA hydrogels with Cur were fabricated and their in vitro effects on ADSCs were investigated. We used structural characterization, western blot, ROS and apoptosis assay to evaluate the antioxidant and anti-apoptotic activity, and assessed the wound healing effects to investigate the mechanism underlying regulation of apoptosis by Cur via the AGE/AGER/nuclear factor-κB (NF-κB) p65 pathway.

Results
A 10% GelMA scaffold exhibited appropriate mechanical properties and biocompatibility for ADSCs. The circular mesh structure demonstrated printability of 10% GelMA and Cur-GelMA bioinks. The incorporation of Cur into the 10% GelMA hydrogel showed an inhibitory effect on AGEs/AGER/NF-κB p65-induced ROS generation and ADSC apoptosis. Furthermore, Cur-GelMA scaffold promoted cell survival and expedited in vivo diabetic wound healing.

Conclusions
The incorporation of Cur improved the antioxidant activity of 3D-printed GelMA hydrogel and mitigated AGE/AGER/p65 axis-induced ROS and apoptosis in ADSCs. The effects of scaffolds on wound healing suggested that Cur/GelMA-ADSC hydrogel could be an effective biological material for accelerating wound healing.
Cystathionine-β-synthase (CBS)/H2S system promotes lymph node metastasis of esophageal squamous cell carcinoma (ESCC) by activating SIRT1
Authors: Liu Ya , Pan Limin , Li Yuxi , Deng Yuying , Han Xue , Fu Han , Wang Tianxiao 
Published: January 2022

Abstract
Lymph node metastasis is a key factor of death and prognosis in patients with esophageal squamous cell carcinoma (ESCC). Previous studies have demonstrated that Cystathionine-β-synthase (CBS)/H2S system plays important roles in progression of various cancer. However, the function and mechanism of CBS/H2S system in lymph node metastasis of ESCC remains unclear. Here, we found that CBS was highly expressed in human ESCC tissues and closely associated with lymph node metastasis in ESCC patients. Functional studies demonstrated that CBS could significantly promote lymph node metastasis of ESCC tumor cells. In vitro, CBS knockdown inhibited tumor cell proliferation, migration and invasion, whereas CBS overexpression produced the opposite results. In vivo, downregulation of CBS distinctly inhibited ESCC tumor growth and lymphatic metastasis, as evidenced by the decreased size and weight of tumor and popliteal lymph node. Meanwhile, we also found high expression of CBS-induced ESCC angiogenesis and lymphangiogenesis in vitro and in vivo by upregulating VEGF, VEGF-C, and VEGF-D. Mechanistically, CBS up-regulated the expression of SIRT1 and thus interrupted the Notch1/Hes1 axis, which plays a crucial role in lymph node metastasis of ESCC. Moreover, it was demonstrated that H2S derived from CBS-activated SIRT1 via increasing the NAD+/NADH ratio and promoting the phosphorylation of SIRT1. In addition, H2S derived from CBS also enhanced SIRT1 protein stability. Taken together, these data show that the high expression of CBS/H2S system promotes ESCC lymph node metastasis via activating SIRT1 signaling pathway and CBS could serve as a potential therapeutic target for clinical intervention in ESCC.
Whole Genome Sequencing Assessing Impact of Diabetes Mellitus on Tuberculosis Mutations and Type of Recurrence in India
Authors: Mave Vidya , Chen Liang , Ranganathan Uma Devi , Kadam Dileep , Vishwanathan Vijay , Lokhande Rahul , S Siva Kumar , Kagal Anju , Pradhan Neeta N , Shivakumar Shri Vijay Bala Yogendra , Paradkar Mandar S , Deshmukh Sona , Tornheim Jeffrey A , Kornfeld Hardy , Farhat Maha , Gupta Amita , Padmapriyadarsini Chandrasekaran , Gupte Nikhil , Golub Jonathan E , Mathema Barun , Kreiswirth Barry N 
Published: January 2022

Abstract

Background
Evidence describing the impact of diabetes mellitus (DM) on the recurrence and mutation rate of Mycobacterium tuberculosis (Mtb) is limited.

Methods
This study was nested in 3 cohort studies of tuberculosis (TB) patients with and without DM in India. Paired Mtb isolates recovered at baseline and treatment failure/recurrence underwent whole genome sequencing. We compared acquisition of single-nucleotide polymorphisms (SNPs), TB drug resistance mutations, and type of recurrence (endogenous reactivation [&lt;8 SNPs] or exogenous reinfection [≥8 SNPs]) by DM status.

Results
Of 1633 enrolled in the 3 parent cohorts, 236 (14.5%) had microbiologically confirmed TB treatment failure/recurrence; 76 Mtb isolate pairs were available for sequencing (22 in TB-DM and 54 in TB-only). The SNP acquisition rate was overall was 0.43 (95% confidence interval [CI], .25–.64) per 1 person-year (PY); 0.77 (95% CI, .40–1.35) per 1 PY, and 0.44 (95% CI, .19–.86) per 1 PY at treatment failure and recurrence, respectively. Significant difference in SNP rates by DM status was seen at recurrence (0.21 [95% CI, .04–.61]) per 1 PY for TB-only vs 1.28 (95% CI, .41–2.98) per 1 PY for TB-DM; P = .02). No significant difference in SNP rates by DM status was observed at treatment failure. Acquired TB drug resistance was seen in 4 of 18 (22%) in TB-DM vs 4 of 45 (9%) in TB-only (P = .21). Thirteen (17%) participants had exogenous reinfection; the reinfection rate at recurrence was 25% (3/12) for TB-DM vs 17% (4/24) in TB-only (P = .66).

Conclusions
Considerable intrahost Mtb mutation rates were present at recurrence among patients with DM in India. One-fourth of patients with DM had exogenous reinfection at recurrence.
Attributable Mortality of Candida Bloodstream Infections in the Modern Era: A Propensity Score Analysis
Authors: Mazi Patrick B , Olsen Margaret A , Stwalley Dustin , Rauseo Adriana M , Ayres Chapelle , Powderly William G , Spec Andrej 
Published: January 2022

Abstract

Background
This study quantifies the mortality attributable to Candida bloodstream infections (BSI) in the modern era of echinocandins.

Methods
We conducted a retrospective cohort study of adult patients admitted to Barnes Jewish Hospital, a 1368-bed tertiary care academic hospital, in Saint Louis, Missouri, from 1 February 2012 to 30 April 2019. We identified 626 adult patients with Candida BSI that were frequency-matched with 6269 control patients that had similar Candida BSI risk-factors. The 90-day all-cause mortality attributable to Candida BSI was calculated using three methods—propensity score matching, matching by inverse weighting of propensity score, and stratified analysis by quintile.

Results
The 90-day crude mortality was 42.4% (269 patients) for Candida BSI cases and 17.1% (1083 patients) for frequency-matched controls. Following propensity score-matching, the attributable risk difference for 90-day mortality was 28.4% with hazard ratio (HR) of 2.12 (95% confidence interval [CI], 1.98–2.25, P &lt; .001). In the stratified analysis, the risk for mortality at 90 days was highest in patients in the lowest risk quintile to develop Candida BSI (hazard ratio [HR] 3.13 (95% CI, 2.33–4.19). Patients in this lowest risk quintile accounted for 81(61%) of the 130 untreated patients with Candida BSI. Sixty-nine percent of untreated patients (57/83) died versus 35% of (49/127) of treated patients (P &lt; .001).

Conclusions
Patients with Candida BSI continue to experience high mortality. Mortality attributable to Candida BSI was more pronounced in patients at lowest risk to develop Candida BSI. A higher proportion of these low-risk patients went untreated, experienced higher mortality, and should be the target of aggressive interventions to ensure timely, effective treatment.
Incidence and Predictors of Community-Acquired Pneumonia in Patients With Hematological Cancers Between 2016 and 2019
Authors: Certan Maria , Garcia Garrido Hannah M , Wong Gino , Heijmans Jarom , Grobusch Martin P , Goorhuis Abraham 
Published: January 2022

Abstract

Background
Patients with hematological cancers (HC) are at high risk of infections, in particular community-acquired pneumonia (CAP). Recent data on incidence and predictors of CAP among patients with HC are scarce.

Methods
We performed a cohort study (2016–2019) in 2 hospitals in the Netherlands among adults with HC to calculate incidence rates (IRs) of CAP. In addition, we performed a nested case-control study to identify predictors of CAP.

Results
We identified 275 CAP cases during 6264 patient-years of follow-up. The IR of CAP was 4390/100 000 patient-years of follow-up. Compared with the general population, IR ratios ranged from 5.4 to 55.3 for the different HCs. The case fatality and intensive care unit (ICU) admission rates were 5.5% and 9.8%, respectively. Predictors for CAP in patients with HC were male sex, anemia, lymphocytopenia, chronic kidney disease, cardiovascular disease, autologous and allogeneic stem cell transplantation, treatment with immunosuppressive medication for graft-vs-host disease, treatment with rituximab in the past year, and treatment with immunomodulators (lenalidomide, thalidomide, pomalidomide and/or methotrexate) in the past month. Independent predictors of a severe disease course (death or ICU admission) included neutropenia (odds ratio, 4.14 [95% confidence interval, 1.63–10.2]), pneumococcal pneumonia (10.24 [3.48–30.1]), chronic obstructive pulmonary disease (6.90 [2.07–23.0]), and the use of antibacterial prophylaxis (2.53 [1.05–6.08]).

Conclusions
The burden of CAP in patients with HC is high, with significant morbidity and mortality rates. Therefore, vaccination against respiratory pathogens early in the disease course is recommended, in particular before starting certain immunosuppressive therapies.
Effect of Influenza Vaccination on Risk of Coronavirus Disease 2019: A Prospective Cohort Study of 46 000 Healthcare Workers
Authors: Kristensen Jonas Henrik , Bo Hasselbalch Rasmus , Pries-Heje Mia , Nielsen Pernille Brok , Dehlbæk Knudsen Andreas , Fogh Kamille , Boesgaard Norsk Jakob , Eiken Aleksander , Andersen Ove , Fischer Thea Kølsen , Juul Jensen Claus Antonio , Torp-Pedersen Christian , Rungby Jørgen , Ditlev Sisse Bolm , Hageman Ida , Møgelvang Rasmus , Gybel-Brask Mikkel , Dessau Ram Benny , Sørensen Erik , Harritshøj Lene , Folke Fredrik , Engel Møller Maria Elizabeth , Benfield Thomas , Ullum Henrik , Sværke Jørgensen Charlotte , Rye Ostrowski Sisse , Dam Nielsen Susanne , Bundgaard Henning , Iversen Kasper 
Published: January 2022

Abstract

Background
The purpose of this study was to assess whether influenza vaccination has an impact on the risk of coronavirus disease 2019 (COVID-19).

Methods
A cohort of 46 112 healthcare workers were tested for antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and filled in a survey on COVID-19 symptoms, hospitalization, and influenza vaccination.

Results
The risk ratio of hospitalization due to SARS-CoV-2 for influenza vaccinated compared with unvaccinated participants was 1.00 for the seasonal vaccination in 2019/2020 (confidence interval, .56–1.78, P = 1.00). Likewise, no clinical effect of influenza vaccination on development of antibodies against SARS-CoV-2 was found.

Conclusions
The present findings indicate that influenza vaccination does not affect the risk of SARS-CoV-2 infection or COVID-19.
Modelling dynamic behaviour of agents in a multiagent world: Logical analysis of Wh-questions and answers
Authors: Číhalová Martina , Duží Marie 
Published: January 2022

AbstractIn a multiagent and multi-cultural world, the fine-grained analysis of agents’ dynamic behaviour, i.e. of their activities, is essential. Dynamic activities are actions that are characterized by an agent who executes the action and by other participants of the action. Wh-questions on the participants of the actions pose a difficult particular challenge because the variability of the types of possible answers to such questions is huge. To deal with the problem, we propose the analysis and classification of Wh-questions apt for agents’ communication in a multiagent system (MAS). Our proposal of such a system consists of agents who communicate with their fellow agents by messaging so that each autonomous agent, though resource-bounded, can make less or more rational decisions to meet its own and collective goals. In addition, by communicating with other fellow agents and their environment, agents can learn new concepts and enrich their ontology so that their behaviour is dynamic. We aim to make a general proposal of the system so that the ‘envelope’ of agents’ messages can be formalized in any MAS standard, be it The Foundation for Intelligent Physical Agents - Agent Communication Language (FIPA-ACL) or Knowledge Query and Manipulation Language (KQML). Yet, the content of messages is encoded in a formalized natural language. To this end, we apply Transparent Intensional Logic (TIL) with its procedural semantics which is particularly apt for a fine-grained analysis in which all the semantically salient features of natural language can be plausibly formalized. In this paper, we concentrate on analysing the content of query messages, particularly the content of those that encode Wh-questions and the answers to them. We also summarize TIL deduction system that makes it possible to answer such questions in an intelligent way. Linguists distinguish several subtypes of Wh-questions. Though the linguistic classification is helpful, it is not always suitable for agents’ communication and reasoning. We need the classification based on a logical analysis of Wh-questions so that the agents can infer possible answers to such questions rather than only looking for them by keywords. This paper aims to apply an appropriate classification of the logical types of Wh-questions and the analysis of such questions; we concentrate in particular on questions concerning the participants of activities. The application of these results to the analysis of processes and events based on verb valency frames is another novelty of the paper.