bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application of the CDK9 inhibitor FIT-039 for the treatment of KSHV-associated malignancy
Authors: Sakamoto Tetsunori , Ajiro Masahiko , Watanabe Akira , Matsushima Shingo , Ueda Keiji , Hagiwara Masatoshi 
Published: January 2023

AbstractChronic infection with Kaposi’s sarcoma-associated herpes virus (KSHV) in B lymphocytes causes primary effusion lymphoma (PEL), the most aggressive form of KSHV-related cancer, which is resistant to conventional chemotherapy. In this study, we report that the BCBL-1 KSHV+ PEL cell line does not harbor oncogenic mutations responsible for its aggressive malignancy. Assuming that KSHV viral oncogenes play crucial roles in PEL proliferation, we examined the effect of cyclin-dependent kinase 9 (CDK9) inhibitor FIT-039 on KSHV viral gene expression and KSHV+ PEL proliferation. We found that FIT-039 treatment impaired the proliferation of KSHV+ PEL cells and the expression of KSHV viral genes in vitro. The effects of FIT-039 treatment on PEL cells were further evaluated in the PEL xenograft model that retains a more physiological environment for the growth of PEL growth and KSHV propagation, and we confirmed that FIT-039 administration drastically inhibited PEL growth in vivo. Our current study indicates that FIT-039 is a potential new anticancer drug targeting KSHV for PEL patients.
Exploring the relationship between breastfeeding and the incidence of infant illnesses in Ireland: evidence from a nationally representative prospective cohort study
Authors: Murphy Sarah , Carter Laura , Al Shizawi Tasneem , Queally Michelle , Brennan Sarah , O’Neill Stephen 
Published: January 2023

Abstract
Background
Ireland has one of the lowest BF rates in the world. This study investigates the association between breastfeeding and infant health in Ireland.

Methods
A cross-sectional, secondary analysis of data collected from Growing Up in Ireland (GUI): the National Longitudinal Study of Children was conducted. The average morbidity for 2212.
infants exclusively breastfed for at least 90 days (EBF90days) was compared to data for 3987 infants in the non-breastfed (Non-BF) group. Data were weighted using entropy balancing to ensure the comparability of groups. Sensitivity analyses considered alternative definitions of the breastfeeding group.

Results
Infants who were EBF90days were significantly less likely to be admitted to hospital (CI: − 0.06 to − 0.03), spent less nights in hospital (CI: − 0.37 to − 0.11), and were less likely to develop respiratory diseases including asthma (CI: − 0.03 to − 0.01), chest infections (CI: − 0.12 to − 0.08), snuffles/common colds (CI: − 0.07 to − 0.02), ear infections (CI: − 0.08 to − 0.04), eczema (CI: − 0.08 to − 0.04), skin problems (CI: − 0.04 to − 0.00), wheezing or asthma (CI: − 0.06 to − 0.03), vomiting (CI: − 0.03 to − 0.00), and colic (CI: − 0.04 to − 0.01). Further outcomes such as current health of the infant at time of interview (CI: − 0.04 to − 0.00), feeding problems (CI: − 0.04 to − 0.02) and sleeping problems (CI: − 0.02 to − 0.00) indicated a protective effect of EBF90days versus Non-BF. However, these infants were also more likely to fail to gain weight (CI: 0.01 to 0.02) and were at a slightly higher risk of developing nappy rash (CI: 0.00 to 0.02).

Conclusion
Exclusive breastfeeding for 90+ days is associated with protection against childhood morbidity. Given the protective effect of breastfeeding on adverse health effects in infants, policy makers should prioritise policies that support, promote and protect exclusive breastfeeding.
Endometriosis, infertility and occupational life: women's plea for recognition
Authors: Gremillet Letizia , Netter Antoine , Sari-Minodier Irène , Miquel Laura , Lacan Arnaud , Courbiere Blandine 
Published: January 2023

AbstractThe objective of this study was to explore and describe the specificities of the occupational life of infertile endometriotic women treated by in vitro fertilization. We conducted a qualitative monocentric study between December 2020 and June 2021. Twelve semi-structured in-depth interviews using a theme-based interview guide with open questions were undertaken with infertile women with deep infiltrating endometriosis. Data analysis was conducted using an inductive approach according to the grounded theory method. Three main themes emerged from the interviews: (i) barriers to reconciling illness and work life, (ii) facilitating factors for well-being at work, and (iii) consequences and outlooks. It appeared that the time of infertility treatment represents a particular period of change in the working lives of women with endometriosis. For most women, these changes are experienced negatively, often with a renunciation of goals. For others, this is the time to communicate the difficulties linked to their illness to their professional entourage. There is a long path ahead to finally achieving recognition of endometriosis in the context of professional life.
A qualitative description of barriers to visual rehabilitation experienced by stroke survivors with visual impairment in Alberta, Canada
Authors: Manhas Kiran Pohar , Brehon Katelyn , Jiang Jennis , Damji Karim F. , Costello Fiona 
Published: January 2023

Abstract
Background
Post-stroke visual impairment (VI) is a common but under-recognized care challenge. Common manifestations of post-stroke VI include: diplopia, homonymous hemianopia, oscillopsia secondary to nystagmus, and visual inattention or neglect. In acute care settings, post-stroke VI recognition and treatment are often sub-optimal as emphasis is placed on survival. Stroke survivors with VI often face inconsistencies when accessing care out of hospital because variable availability and subsidization of visual rehabilitation. We sought to identify gaps in care experienced by stroke survivors with VI from stroke survivors’ and care providers’ perspectives.

Methods
We conducted a qualitative description study across 12 care sites in Alberta, Canada, using semi-structured interviews. Survivor interviews focused on the health system experience. Provider interviews discussed approaches to care, perceived gaps, and current resources. Interviews were audio-recorded and transcribed. Iterative content analysis was completed using NVivo 12. We promoted rigour through an audit trail, open-ended questions, thick description, and collaborative coding.

Results
We completed 50 interviews: 19 survivor interviews and 31 provider interviews. The majority of survivors were male (n = 14) and recruited from community settings (n = 16). Providers varied in profession and location within the care continuum. Two key themes emerged from the provider and survivor interviews pertaining to (a) facets of visual rehabilitation (sub-themes: access, resources, and multidisciplinary professional interaction); and (b) functioning with post-stroke VI (sub-themes: early experiences post-stroke and living with VI in the real world).

Conclusions
The visual rehabilitation model needs to be optimized to ensure transparent inter-disciplinary communication and efficient referral pathways. Future research will focus on evaluating the effectiveness of post-stroke care from multiple perspectives in Alberta.
Good practice in medicine and biology: scientific integrity needs global bioethics
Authors: Stoeklé Henri-Corto , Ivasilevitch Achille , Hervé Christian 
Published: January 2023

AbstractWe consider scientific integrity to constitute a new theory of morality of science, in a very specific deontological sense. Indeed, at least in practice, scientific integrity extends beyond scientific concerns, seeking to develop specific moral duties and/or procedures based on general moral values and/or standards, leading to common moral frameworks for usual scientific practices. This is, of course, necessary. Contemporary history has shown us only too well that usual scientific practices need common moral frameworks, especially in medicine and biology. However, like scientific practices, and medical and biological practices in particular, the persistence of certain moral values and/or standards and the priority attributed to them, can change significantly, due to changes in society, people, the times and/or environments, and they may be under strong tension. We therefore believe that a new theory of ethics of science, in a very specific teleological sense, may be required in this case, particularly in medicine and biology, in addition to scientific integrity. This ethical theory, through research, professionals and structures in ethics of science— also called medical ethics, research ethics or bioethics in the fields of medicine and biology—, should seek to identify and find specific ethical solutions to these tensions, applicable at a particular place and time, based on common ethical purposes and/or consequences. As a result, these specific ethical solutions may, or may not, lead to an evolution of common moral frameworks, which may, or may not, be developed on the basis of scientific integrity. In the fields of medicine and biology, this ethical theory is closely related to another theory, global bioethics, but with a number of new conceptual and methodological developments.
Requirement for hippocampal CA3 NMDA receptors in artificial association of memory events stored in CA3 cell ensembles
Authors: Nomoto Masanori , Ohkawa Noriaki , Inokuchi Kaoru , Oishi Naoya 
Published: January 2023

AbstractThe N-methyl-d-aspartate receptors (NRs) in hippocampal CA3 are crucial for the synaptic transmission and plasticity within the CA3 recurrent circuit, which supports the hippocampal functions, such as pattern completion, and reverberatory association of sensory inputs. Previous study showed that synchronous activation of distinct cell populations in CA3, which correspond to distinct events, associated independent events, suggesting that the recurrent circuit expressing NRs in CA3 mediates the artificial association of memory events stored in CA3 ensembles. However, it is still unclear whether CA3 NRs are crucial for the artificial association of memory events stored in the CA3 ensembles. Here we report that the triple transgenic mice (cfos-tTA/KA1-Cre/NR1 flox/flox), which specifically lack NRs in the CA3 cell ensembles, showed impairment in artificial association between two events, which in control mice triggered artificial association. This result indicates that NRs in the hippocampal CA3 are required for the artificial association of memory events stored in the CA3 cell ensembles.
The safety and efficacy of mesenchymal stromal cells in ARDS: a meta-analysis of randomized controlled trials
Authors: Wang Fengyun , Li Yiming , Wang Bingqing , Li Jianguo , Peng Zhiyong 
Published: January 2023

AbstractMesenchymal stromal cells (MSC) have shown potential efficacy in both animal and human trials of acute respiratory distress syndrome (ARDS). Especially during the COVID-19 pandemic, MSC was intensely studied for treating COVID-19-induced ARDS. The purpose of this study is to evaluate the safety and efficacy of MSC in ARDS via a meta-analysis of randomized controlled trials (RCTs). Therefore, a meta-analysis of RCTs of MSC as a therapy for ARDS was conducted. The protocol of this review was registered on Open Science Framework. With no language restriction and according to the “PICOs” principle, searches were conducted on Pubmed and Embase to retrieve any clinical literature on MSC for ARDS. Any RCT, which compared MSC to controls for ARDS, where MSC and controls were intravenously infused, of any dosage, was eligible for inclusion. A total of 13 RCTs, which evaluated MSC versus control for treating ARDS, enrolling a total of 655 cases, met the inclusion criteria and appeared in this meta-analysis. A heterogeneity assessment was carried out using the χ2 test, where a P value less than 0.05 was considered significant. The choice of a fixed-effect or a random-effect model was decided by the I2 value in each of the analyses. This meta-analysis indicated that there was no significant difference in terms of adverse events between MSC and control for ARDS (OR = 0.64, 95% CI [0.34, 1.20], P = 0.17, and I2 = 0%). In comparison with control, MSC could reduce the mortality of ARDS (OR = 0.66, 95% CI [0.46, 0.96], P = 0.03, and I2 = 10%). Based on the results of our meta-analysis, the safety of MSC was demonstrated to be non-inferior to that of standard treatment, and MSC may reduce the mortality rate of ARDS. Though the heterogeneity in the main results was low (I2 < 25%), more high-quality and large-scale clinical trials are needed to further confirm our findings.
Respiratory viruses and postoperative hemodynamics in patients with unrestrictive congenital cardiac communications: a prospective cohort study
Authors: Abud Kelly C. O. , Machado Clarisse M. , Vilas Boas Lucy S. , Maeda Nair Y. , Carvalho Eloisa S. , Souza Maria Francilene S. , Gaiolla Paula V. , Castro Claudia R. P. , Pereira Juliana , Rabinovitch Marlene , Lopes Antonio Augusto 
Published: January 2023

Abstract
Background
Pulmonary vascular abnormalities pose a risk for severe life-threatening hemodynamic disturbances following surgical repair of congenital cardiac communications (CCCs). In the distal lung, small airways and vessels share a common microenvironment, where biological crosstalks take place. Because respiratory cells infected by viruses express a number of molecules with potential impact on airway and vascular remodeling, we decided to test the hypothesis that CCC patients carrying viral genomes in the airways might be at a higher risk for pulmonary (and systemic) hemodynamic disturbances postoperatively.

Methods
Sixty patients were prospectively enrolled (age 11 [7–16] months, median with interquartile range). Preoperative pulmonary/systemic mean arterial pressure ratio (PAP/SAP) was 0.78 (0.63–0.88). The presence or absence of genetic material for respiratory viruses in nasopharyngeal and tracheal aspirates was investigated preoperatively in the absence of respiratory symptoms using real-time polymerase chain reaction (kit for detection of 19 pathogens). Post-cardiopulmonary bypass (CPB) inflammatory reaction was analyzed by measuring serum levels of 36 inflammatory proteins (immunoblotting) 4 h after its termination. Postoperative hemodynamics was assessed using continuous recording of PAP and SAP with calculation of PAP/SAP ratio.

Results
Viral genomes were detected in nasopharynx and the trachea in 64% and 38% of patients, respectively. Rhinovirus was the most prevalent agent. The presence of viral genomes in the trachea was associated with an upward shift of postoperative PAP curve (p = 0.011) with a PAP/SAP of 0.44 (0.36–0.50) in patients who were positive versus 0.34 (0.30–0.45) in those who were negative (p = 0.008). The presence or absence of viral genomes in nasopharynx did not help predict postoperative hemodynamics. Postoperative PAP/SAP was positively correlated with post-CPB levels of interleukin-1 receptor antagonist (p = 0.026), macrophage migration inhibitory factor (p = 0.019) and monocyte chemoattractant protein-1 (p = 0.031), particularly in patients with virus-positive tracheal aspirates.

Conclusions
Patients with CCCs carrying respiratory viral genomes in lower airways are at a higher risk for postoperative pulmonary hypertension, thus deserving special attention and care. Preoperative exposure to respiratory viruses and post-CPB inflammatory reaction seem to play a combined role in determining the postoperative behavior of the pulmonary circulation.
Physical home-learning environments of traditional and non-traditional students during the COVID pandemic: exploring the impact of learning space on students’ motivation, stress and well-being
Authors: Brachtl Sonja , Ipser Christina , Keser Aschenberger Filiz , Oppl Sabrina , Oppl Stefan , Pakoy Emre Kevin , Radinger Gregor 
Published: January 2023

AbstractWhen the COVID-19 pandemic forced higher education institutions to implement their programs in an online setting, different groups of students were influenced to different extents. In many cases, the main locus of learning moved to students' homes, and their learning experiences were suddenly contextualized in their residential situation and immediate physical learning environment. The present study consequently examines the role of physical learning environments on different factors influencing students’ learning when pursuing their study from at home. It contrasts the situation of traditional students in a higher education institution and non-traditional students in an academic continuing education institution, which address target groups with different living conditions and needs in learning support. Data were collected via an online survey sent to students enrolled in these two institutions, with a total of 353 students participating during a timeframe impacted by COVID-related lockdowns. We found that stress and well-being is strongly linked to the quality of the surrounding environment of the learning place, whereas perceived motivation is more strongly related to the quality of the learning place itself. How strongly students are affected by these factors is moderated by their overall socio-spatial context. Academic continuing education students are more resilient to sub-optimal physical learning environment than traditional students. Altering the design of the immediate learning environment consequently can help to mitigate factors that negatively impact students’ well-being and learning motivation, which is particularly important for traditional students, who primarily dedicate their time to pursuing their studies.
Design and piloting of a proposal for intervention with educational robotics for the development of lexical relationships in early childhood education
Authors: Campos Verónica Moreno , Muñoz Francisco José Rodríguez 
Published: January 2023

AbstractAn applied research proposal for integrated learning based on the use of educational robotics has been proposed. The design has been implemented with a sample of 21 four-year-old students applying twenty-first-century competencies (collaboration, creativity, critical thinking, and communication) to learn the curricula related to the development of lexical relations. This research aims to apply data directly derived from the application of educational robotics in the classroom. The research aims focus on two fundamental questions: on the one hand, to verify whether the use of educational robotics in teaching practice is related to greater conceptual achievement and, on the other hand, to validate whether students apply transversal competencies through educational robotics. The results allow us to affirm that the didactic application of robotics activities achieves a high degree of conceptual integration when establishing lexical relationships and allows students to put into practice key transversal problem-solving and critical thinking competencies.
Association of Thyroid-Stimulating Hormone With All-Cause Mortality: A 2-Sample Mendelian Randomization Study
Authors: Gu Yeqing , Song Zimin , Li Qingkui , Wang Jinhan , Song Yanqi , Meng Ge , Wu Hongmei , Zhang Shunming , Wang Xuena , Zhang Juanjuan , Lu Xinran , Liu Qiang , Huang Tao , Yang Jian , Niu Kaijun 
Published: January 2023

Abstract

Context
Thyroid-stimulating hormone (TSH), as the most sensitive and specific marker of thyroid status, is associated with multiple health outcomes, including mortality. However, whether TSH levels are causally associated with the risk of mortality remains unclear.

Objective
This study aims to investigate the causal association between TSH levels and all-cause mortality using Mendelian randomization (MR) analyses.

Methods
MR analyses using single-nucleotide polymorphisms (SNPs) associated with TSH levels (P &lt; 5 × 10−8) as instruments. Mortality data were obtained from the UK Biobank, including 384 344 participants who were recruited from 22 assessment centers across the UK taken between 2006 and 2010. Cox proportional hazards regression was used to estimate the association of the TSH genetic risk score (GRS) with all-cause and cause-specific mortality.

Results
15 557 individuals died during a median of 9.00 years of follow-up in the UK Biobank. A total of 70 SNPs were included in the MR analysis. The main MR analyses showed that 1 SD increase in TSH was associated with a decreased risk of all-cause mortality (OR 0.972, 95% CI 0.948-0.996), which may be largely attributed to respiratory disease mortality (OR 0.881, 95% CI 0.805-0.963). The multivariable hazard ratios (HRs) (95% CI) of all-cause mortality across 3 TSH GRS categories were 1.00 (reference), 0.976 (0.940-1.014), and 0.947 (0.911-0.985), respectively (P for trend &lt; .01). Moreover, except digestive diseases mortality, genetically predicted TSH levels were negatively associated with mortality from CVD, cancer, noncancer diseases causes, and dementia, although not statistically significant.

Conclusion
Higher TSH levels were causally associated with lower risk of all-cause mortality, which may be largely attributed to respiratory disease mortality.
The Impact of Acute Nutritional Interventions on the Plasma Proteome
Authors: Vernardis Spyros I , Demichev Vadim , Lemke Oliver , Grüning Nana-Maria , Messner Christoph , White Matt , Pietzner Maik , Peluso Alina , Collet Tinh-Hai , Henning Elana , Gille Christoph , Campbell Archie , Hayward Caroline , Porteous David J , Marioni Riccardo E , Mülleder Michael , Zelezniak Aleksej , Wareham Nicholas J , Langenberg Claudia , Farooqi I Sadaf , Ralser Markus 
Published: January 2023

Abstract

Context
Humans respond profoundly to changes in diet, while nutrition and environment have a great impact on population health. It is therefore important to deeply characterize the human nutritional responses.

Objective
Endocrine parameters and the metabolome of human plasma are rapidly responding to acute nutritional interventions such as caloric restriction or a glucose challenge. It is less well understood whether the plasma proteome would be equally dynamic, and whether it could be a source of corresponding biomarkers.

Methods
We used high-throughput mass spectrometry to determine changes in the plasma proteome of i) 10 healthy, young, male individuals in response to 2 days of acute caloric restriction followed by refeeding; ii) 200 individuals of the Ely epidemiological study before and after a glucose tolerance test at 4 time points (0, 30, 60, 120 minutes); and iii) 200 random individuals from the Generation Scotland study. We compared the proteomic changes detected with metabolome data and endocrine parameters.

Results
Both caloric restriction and the glucose challenge substantially impacted the plasma proteome. Proteins responded across individuals or in an individual-specific manner. We identified nutrient-responsive plasma proteins that correlate with changes in the metabolome, as well as with endocrine parameters. In particular, our study highlights the role of apolipoprotein C1 (APOC1), a small, understudied apolipoprotein that was affected by caloric restriction and dominated the response to glucose consumption and differed in abundance between individuals with and without type 2 diabetes.

Conclusion
Our study identifies APOC1 as a dominant nutritional responder in humans and highlights the interdependency of acute nutritional response proteins and the endocrine system.