Miracle-dz/UniFAR-FTUs huggingface dataset:
Pilot clinical and pharmacokinetic study of Δ9-Tetrahydrocannabinol (THC)/Cannabidiol (CBD) nanoparticle oro-buccal spray in patients with advanced cancer experiencing uncontrolled pain

This pilot study aimed to assess the safety, tolerability, pharmacokinetics and exploratory analgesic effect of a novel water-soluble oro-buccal nanoparticle spray of a cannabis-based medicine (MDCNS-01) in patients with advanced incurable malignancy with unrelieved pain from opioid analgesic. The study was a non-blinded single arm 2 stage study. Stage I was a single escalating dose (n = 5) [2.5 mg Δ9-THC and 2.5 mg CBD) versus a 3-fold escalated dose. Stage II was an up-titrated dose in patients with advanced cancers and intractable pain (n = 25). During Stage I with an increased cannabis-based medicine dose, maximum observed plasma concentrations of cannabinoids were dose dependant. The water-soluble formulation in the current study resulted in a higher median (min, max) systemic exposure of Δ9-THC than CBD (AUC from 2.5 mg each of Δ9-THC and CBD, was 1.71 ng mL.h−1 (1.1, 6.6) and 0.65 ng mL.h−1 (0.49, 4.1), respectively). During stage II a subgroup of patients diagnosed with breast and prostate cancers with bone metastases, had the highest mean pain score improvement from baseline of 40% (unadjusted) and 33% (adjusted for rescue medication use). For all patients the most reported adverse events were mild or moderate drowsiness affecting 11 (44%) and 4 (6%) patients, respectively, and nausea and vomiting that affected 18 (72%) patients. The water-soluble cannabis-based medicine provided acceptable bioavailability for Δ9-THC/CBD, appeared safe and tolerable in advanced incurable cancers with uncontrolled pain with preliminary evidence of analgesic efficacy.
Non-unitary Process and Quantum Communication

The no-communication theorem states that the observation of a subsystem of an entangled state does not affect another subsystem. Nevertheless, this theorem is based on the assumption that all quantum processes are unitary. We examine a feasible thought experiment and show that a non-unitary process included in this thought experiment enables the transmission of information by means of the quantum observation process.
Servicios de Razonamiento con Múltiples Criterios de Preferencia

Laboratorio de Investigación y Desarrollo en Inteligencia Artificial Departamento de Ciencias e Ingenieŕıa de la Computación, Universidad Nacional del Sur, Av. Alem 1253, (B8000CPB) Bah́ıa Blanca, Argentina Laboratorio de Investigación y Desarrollo en Inteligencia Artificial Concordia Facultad de Ciencias de la Administración, Universidad Nacional de Entre Ŕıos, Consejo Nacional de Investigaciones Cient́ıficas y Técnicas (CONICET) e-mail: {jct,sg,ajg,grs}@cs.uns. edu.ar
Effects of EZH2 on Invasion and Migration of Endometrial Stromal Cells in Endometriosis Patients by Regulating PCDH10 Gene H3K27 Methylation.

Context Endometriosis refers to the appearance of ectopic endometrioid tissue outside the uterus. Low PCDH10 expression has been associated with enhancer of zeste homolog 2 (EZH2), which catalyzes histone 3 (H3K27me3). H3K27me3 is an epigenetic marker associated with endometriosis. Objective The study intended to explore the influence of protocadherin 10 (PCDH10) on the invasion and migration of endometrial stromal cells in endometriosis as well as its mechanism. Design The research team designed a laboratory study using endometrial tissue. Setting The study took place in Department of Obstetrics and Gynecology at South University of Science and Technology Hospital in Shenzhen, Guangdong Province, China. Participants Participants were 10 patients with ovarian endometriosis (ovarian chocolate cysts) who were undergoing surgical treatment at the hospital between January and December 2019. The endometrial tissue of those participants became the endometriosis group. Other participants with normal endometrial tissue became the controls (n=10). Outcome Measures The research team collected tissues from participants and used immunofluorescence, real-time quantitative polymerase chain reaction (qPCR), and Western blot assay to determine the expression levels of PCDH10, enhancer of zeste homolog 2 (EZH2), and histone H3 (H3K27me3). The team cultured endometrial stromal cells from participants primarily to detect the effects of silencing EZH2 on PCDH10 and H3K27me3 expression. The team used a Transwell assay and scratch test to examine the influence of silencing EZH2 on invasion and migration of endometrial stromal cells and applied chromatin immunoprecipitation to determine H3K27me3 enrichment in the PCDH10 gene promoter region. Results PCDH10 in heterotopic endometrial tissues of endometriosis patients had low expression, while EZH2 and H3K27me3 were highly expressed. Silencing EZH2 inhibited EZH2 protein expression, increased PCDH10 expression, and inhibited invasion and migration of endometrial stromal cells by increasing PCDH10 expression. Silencing EZH2 also reduced H3K27me3 enrichment in PCDH10 promoter region. Conclusions Low PCDH10 expression may be associated with high EZH2 expression and H3K27me3 enrichment in endometriosis patients, which promotes the migration and invasion of endometrial stromal cells. This connection provides a theoretical basis for the treatment of endometriosis.
Lung carcinoid tumours: histology and Ki‐67, the eternal rivalry

WHO classification of Thoracic Tumours defines lung carcinoid tumours (LCTs) as well‐differentiated neuroendocrine neoplasms (NENs) classified in low grade typical (TC) and intermediate grade atypical carcinoids (AC). Limited data exist concerning protein expression and morphologic factors able to predict disease aggressiveness. Though Ki‐67 has proved to be a powerful diagnostic and prognostic factor for Gastro‐entero‐pancreatic NENs, its role in lung NENs is still debated. A retrospective series of 370 LCT from two oncology centers was centrally reviewed. Morphology and immunohistochemical markers (Ki‐67, TTF‐1, CD44, OTP, SSTR‐2A, Ascl1, and p53) were studied and correlated with Overall Survival (OS), Cancer‐specific survival (CSS) and Disease‐free survival (DFS). Carcinoid histology was confirmed in 355 patients: 297 (83.7%) TC and 58 (16.3%) AC. Ki‐67 at 3% was the best value in predicting DFS. Ki‐67 ≥ 3% tumours were significantly associated with AC histology, stage III‐IV, smoking, vascular invasion, tumour spread through air spaces OTP negativity, and TTF‐1, Ascl1 and p53 positivity. After adjustment for center and period of diagnosis, both Ki‐67 (≥3 versus <3) and histology (AC versus TC) alone significantly added prognostic information to OS and CSS multivariable model with age, stage and OTP; addition of both variables did not provide further prognostic information. Conversely, an improved significance of the DFS prediction model at multivariate analysis was seen by adding Ki‐67 (≥3 versus <3, P adj = 0.01) to TC and AC histological distinction, age, lymph node involvement, residual tumour and OTP. Ki‐67 ≥ 3% plays a potentially pivotal role in LCT prognosis, irrespective of histological grade.
Asia-Pacific International Center of Excellence in Malaria Research: Maximizing Impact on Malaria Control Policy and Public Health in Cambodia and Papua New Guinea

ABSTRACT. The Asia-Pacific International Center of Excellence in Malaria Research (ICEMR) was funded in 2016 to conduct a coordinated set of field and in-depth biological studies in Cambodia and Papua New Guinea (PNG), in sites that span the range of transmission intensities currently found in the Asia-Pacific regions. The overall objective is to gain an understanding of key parasite, human host, and vector factors involved in maintaining transmission in the face of intensified control and elimination programs, and to develop novel approaches to identify and target residual transmission foci. In this article, we will describe how the ICEMR program was designed to address key knowledge gaps and priority areas for the malaria control programs in each country. In PNG, partners have worked together on two consecutive ICEMR grants (2009–2016 and 2017–2024) and we present a case study of the partnership and engagement approach that has led to stronger coordination of research activities and integration with program, informing country-level strategic planning and prioritization of control activities. In both settings, the ICEMR program has generated insights into transmission foci, risk factors for ongoing transmission, highlighting the hidden burden of vivax malaria, and the need for additional complementary vector control tools. Finally, we will summarize the emerging research questions and priority areas—namely surveillance, vivax malaria, new vector control tools, and community/health systems-oriented approaches—where further tool development and implementation research have been identified as being needed to guide policy.
Prevalence and concentration of Campylobacter in faeces of dairy cows: A systematic review and meta-analysis

The consumption of raw milk from dairy cows has caused multiple food-borne outbreaks of campylobacteriosis in the European Union (EU) since 2011. Cross-contamination of raw milk through faeces is an important vehicle for transmission of Campylobacter to consumers. This systematic review and meta-analysis, aimed to summarize data on the prevalence and concentration of Campylobacter in faeces of dairy cows. Suitable scientific articles published up to July 2021 were identified through a systematic literature search and subjected to screening and quality assessment. Fifty-three out of 1338 identified studies were eligible for data extraction and 44 were further eligible for meta-analysis. The pooled prevalence was calculated in two different meta-analytic models: a simple model based on one average prevalence estimate per study and a multilevel meta-analytic model that included all prevalence outcomes reported in each study (including different subgroups of e.g. health status and age of dairy cows). The results of the two models were significantly different with a pooled prevalence estimate of 29%, 95% CI [23–36%] and 51%, 95% CI [44–57%], respectively. The effect of sub-groups on prevalence were analyzed with a multilevel mixed-effect model which showed a significant effect of the faecal collection methods and Campylobacter species on the prevalence. A meta-analysis on concentration data could not be performed due to the limited availability of data. This systematic review highlights important data gaps and limitations in current studies and variation of prevalence outcomes between available studies. The included studies used a variety of methods for sampling, data collection and analysis of Campylobacter that added uncertainty to the pooled prevalence estimates. Nevertheless, the performed meta-analysis improved our understanding of Campylobacter prevalence in faeces of dairy cows and is considered a valuable basis for the further development of quantitative microbiological risk assessment models for Campylobacter in (raw) milk and food products thereof.
Introduction to the papers

The global community has become increasingly concerned about the future of life on earth. Anthropologists have been among those who have seen the problems in remote places, but they have not been leading political actors among the many people and organizations that have worked to educate the public about the dangers to the environment. Following the United Nations conference in 1992 in Rio, Viacheslav Rudnev began his work to promote research papers on the contributions that the knowledge developed over generations among indigenous people has made, and could make, to sustainable development. He has worked to organize scholars in ethnology and in other disciplines who have done research that contributes to solving the problems of balancing the needs of humans, other living things, and nature so that we can develop sustainable ways to survive. He invited Dorothy Billings to join him as Co-Chair of the Commission on Indigenous Knowledge and Sustainable Development, a Commission which he successfully proposed to the International Union for Anthropological and Ethnological Sciences (IUAES) in 1998, and which has regularly organized panels for international congresses since then. Dr Rudnev reports the history of this work in his introductory article for this Special Issue. Researcherswho have presented theirwork at IUAESmeetingswere invited to give their papers at the 117thAmericanAnthropological AssociationAnnualMeeting inWashington, DC inDecember 2014. It is those papers, as well as some papers that had been given at recent meetings of the IUAES, that we have gathered together in this Special Issue of Global Bioethics. Anthropologists have been focused on the ethnography of indigenous peoples: their cultures, their values, and their knowledge. Our sojourn with “development” has been more recent; with “sustainable development” more recent still. After World War II, colonial governments began to leave their colonies, having prepared, more or less, the local people to take over their own governments. Neo-colonialism, largely of economic enterprises, began everywhere: developers moved in to remove resources needed by the industrialized world, and newly formed local governments needed the economic foundations they provided. The authors here have looked at what these outside “developers” have done that profoundly affects the lives of indigenous peoples and their ability to sustain and develop themselves. Ethel Vesper reports her research in Micronesia, islands that have been colonized by various European governments for centuries and have, since World War II, lost much of their land base to occupation by the US military. She focuses on Guam and the island of Bikini, which is no longer habitable.
ERS/ESTS statement on the management of pleural infection in adults

Pleural infection is a common condition encountered by respiratory physicians and thoracic surgeons alike. The European Respiratory Society (ERS) and European Society of Thoracic Surgeons (ESTS) established a multidisciplinary collaboration of clinicians with expertise in managing pleural infection with the aim of producing a comprehensive review of the scientific literature. Six areas of interest were identified: 1) epidemiology of pleural infection, 2) optimal antibiotic strategy, 3) diagnostic parameters for chest tube drainage, 4) status of intrapleural therapies, 5) role of surgery and 6) current place of outcome prediction in management. The literature revealed that recently updated epidemiological data continue to show an overall upwards trend in incidence, but there is an urgent need for a more comprehensive characterisation of the burden of pleural infection in specific populations such as immunocompromised hosts. There is a sparsity of regular analyses and documentation of microbiological patterns at a local level to inform geographical variation, and ongoing research efforts are needed to improve antibiotic stewardship. The evidence remains in favour of a small-bore chest tube optimally placed under image guidance as an appropriate initial intervention for most cases of pleural infection. With a growing body of data suggesting delays to treatment are key contributors to poor outcomes, this suggests that earlier consideration of combination intrapleural enzyme therapy (IET) with concurrent surgical consultation should remain a priority. Since publication of the MIST-2 study, there has been considerable data supporting safety and efficacy of IET, but further studies are needed to optimise dosing using individualised biomarkers of treatment failure. Pending further prospective evaluation, the MIST-2 regimen remains the most evidence based. Several studies have externally validated the RAPID score, but it requires incorporating into prospective intervention studies prior to adopting into clinical practice. Intrapleural fibrinolytic-based therapy has revolutionised pleural infection management, but surgical intervention remains vital in select patients. Studies into early and targeted escalation of treatment based on risk stratification are now required. https://bit.ly/3y6rZ8a
Regulation of programmed death ligand 1 (PD‐L1) expression by TNF‐related apoptosis‐inducing ligand (TRAIL) in triple‐negative breast cancer cells

Triple‐negative breast cancer (TNBC) is an aggressive form of breast cancer that lacks targeted therapies. Previous studies have shown that TNBC cells are highly sensitive to tumor necrosis factor (TNF)‐related apoptosis‐inducing ligand (TRAIL), making it a promising agent for treating TNBC. However, the development of TRAIL resistance limits its further clinical development, and the underlying mechanisms are not fully understood. In this study, we report the role of PD‐L1 in TRAIL resistance. Specifically, we found that TRAIL treatment increases PD‐L1 expression in TRAIL‐sensitive cells and that basal PD‐L1 expression is increased in acquired TRAIL‐resistant cells. Mechanistically, we found that increased PD‐L1 expression was accompanied by increased extracellular signal‐regulated kinase (ERK) activation. Using both genetic and pharmacological approaches, we showed that knockdown of ERK by siRNA or inhibition of ERK activation by the mitogen‐activated protein kinase kinase inhibitor U0126 decreased PD‐L1 expression and increased TRAIL‐induced cell death. Furthermore, we found that knockout or knockdown of PD‐L1 enhances TRAIL‐induced apoptosis, suggesting that PD‐L1‐mediated TRAIL resistance is independent of its ability to evade immune suppression. Therefore, this study identifies a noncanonical mechanism by which PD‐L1 promotes TRAIL resistance, which can be potentially exploited for immune checkpoint therapy.
Modified BaTiO3 Piezoelectric Ceramics with Bi2O3-Li2O Additive

Effects of Bi2O3-Li2O additive on the Mn-doped BaTiO3 piezoelectric ceramics were investigated. The additives were mixed by a liquid-mixing method. The results showed that coercive electric field E c was modified from 120 to 500 V/mm when Bi2O3-Li2O was 0.3 wt%, but dielectric constant (symbol)e_{33}/(symbol)eφ showed a large drop from 3500 to 1500. The electromechanical coupling factor k p kept approximately 36% for all the specimens, but piezoelectric constant d 33 decreased. The orthorhombic to tetragonal phase transition temperature changed to low temperature with increase of the additive.
A HIGHLY ECCENTRIC 3.9 MILLISECOND BINARY PULSAR IN THE GLOBULAR CLUSTER NGC 6652

We present the Robert C. Byrd Green Bank Telescope discovery of the highly eccentric binary millisecond pulsar PSR J1835-3259A in the Fermi Large Area Telescope-detected globular cluster NGC 6652. Timing over one orbit yields the pulse period 3.89 ms, orbital period 9.25 days, eccentricity ∼ 0.95, and an unusually high companion mass of 0.74 M ⊙ ? > assuming a 1.4 M ⊙ ? > pulsar. We caution that the lack of data near periastron prevents a precise measurement of the eccentricity, and that further timing is necessary to constrain this and the other orbital parameters. From tidal considerations, we find that the companion must be a compact object. This system likely formed through an exchange encounter in the dense cluster environment. Our initial timing results predict the measurements of at least two post-Keplerian parameters with long-term phase-connected timing: the rate of periastron advance &ohgr; ˙ ? > ∼ 0 &fdg; 1 ? > yr−1, requiring 1 year of phase connection; and the Einstein delay γ GR ? > ∼ 10 ms, requiring 2–3 years of timing. For an orbital inclination i > 50 ° ? > , a measurement of sin i ? > is also likely. PSR J1835-3259A thus provides an opportunity to measure the neutron star mass with high precision, to probe the cluster environment, and, depending on the nature of the companion, to investigate the limits of general relativity.
Competition of pairing symmetries and a mechanism for Berezinskii pairing in quasi-one-dimensional systems

We revisit the pairing symmetry competition in quasi-one-dimensional systems. We show that spin-triplet s-wave pairing, where the pair is formed by electrons with different times and has an odd-frequency symmetry, can be realized in systems with strong one-dimensionality when the strength of charge fluctuation dominates over spin fluctuation. The present study provides a novel microscopic mechanism for this exotic pairing originally proposed by Berezinskii in 1974.
The evolution of sex similarities in social signals: Climatic seasonality is associated with lower sexual dimorphism and greater elaboration of female and male signals in antbirds (Thamnophilidae)

Selection on signals that mediate social competition varies with resource availability. Climate regulates resource availability, which may affect the strength of competition and selection on signals. Traditionally, this meant that more seasonal, colder, or dryer—overall harsher—environments should favor the elaboration of male signals under stronger male‐male competition, increasing sexual dimorphism. However, females also use signals to compete; thus, harsher environments could strengthen competition and favor elaboration of signals in both sexes, decreasing sexual dimorphism. Alternatively, harsher environments could decrease sexual dimorphism due to scarcer resources to invest in signal elaboration in both sexes. We evaluated these contrasting hypotheses in antbirds, a family of Neotropical passerines that varies in female and male signals and occurs across diverse climatic regimes. We tested the association of sexual dimorphism of plumage coloration and songs with temperature, precipitation, and their seasonality. We found that greater seasonality is associated with lower sexual dimorphism in plumage coloration and greater elaboration of visual signals in both sexes, but not acoustic signals. Our results suggest that greater seasonality may be associated with convergent elaboration of female and male visual signals, highlighting the role of signals of both sexes in the evolution of sexual dimorphism.
Advances in Basic and Translational Research as Part of the Center for the Study of Complex Malaria in India

ABSTRACT. The Center for the Study of Complex Malaria in India (CSCMi) is one of 10 International Centers of Excellence in Malaria Research funded by the National Institutes of Health since 2010. The Center combines innovative research with capacity building and technology transfer to undertake studies with clinical and translational impact that will move malaria control in India toward the ultimate goal of malaria elimination/eradication. A key element of each research site in the four states of India (Tamil Nadu, Gujarat, Odisha, and Meghalaya) has been undertaking community- and clinic-based epidemiology projects to characterize the burden of malaria in the region. Demographic and clinical data and samples collected during these studies have been used in downstream projects on, for example, the widespread use of mosquito repellants, the population genomics of Plasmodium vivax, and the serological responses to P. vivax and Plasmodium falciparum antigens that reflect past or present exposure. A focus has been studying the pathogenesis of severe malaria caused by P. falciparum through magnetic resonance imaging of cerebral malaria patients. Here we provide a snapshot of some of the basic and applied research the CSCMi has undertaken over the past 12 years and indicate the further research and/or clinical and translational impact these studies have had.
Overcoming disparities to improve cancer care: The story of cervical cancer

Effective screening and vaccination programs can potentially eliminate cervical cancer in the future; however, to accomplish this goal, we have to be able to offer services to all girls and women. In particular, women who live in rural areas and women who have low socioeconomic status are at highest risk. Efforts are required to improve access to care at all levels for these women at risk.