Miracle-dz/UniFAR-FTUs huggingface dataset:
Mesenchymal stem cells release exosomes that transfer miRNAs to endothelial cells and promote angiogenesis

Mesenchymal stem cells (MSCs) have been found to benefit patients with a variety of ischemic diseases via promoting angiogenesis. It is also well established that exosomes secreted from MSCs deliver bioactive molecules, including microRNAs (miRs) to recipient cells. Therefore, we hypothesized that exosomes secreted from MSCs deliver miRs into endothelial cells and mediate angiogenesis. The pro-angiogenic stimulatory capacity of exosomes was investigated using tube-like structure formation and spheroid-based sprouting of human umbilical vein endothelial cells (HUVECs), and in vivo Matrigel plug assay. The secretion of pro-angiogenic miRs (pro-angiomiRs) from MSCs into culture medium and transfer of the miRs to HUVECs were confirmed using real-time quantitative PCR. Supplementation of the exosome secretion blocker GW4869 (10 μM) reduced the pro-angiomiRs in the MSC-derived conditioned medium (CdMMSC). Addition of exosomes isolated from CdMMSC could directly 1) promote HUVEC tube-like structure formation in vitro; 2) mobilize endothelial cells into Matrigel plug subcutaneously transplanted into mice; and 3) increase blood flow inside Matrigel plug. Fluorescence tracking showed that the exosomes were internalized rapidly by HUVECs causing an upregulated expression of pro-angiomiRs in HUVECs. Loss-and-gain function of the pro-angiomiRs (e.g., miR-30b) in MSCs significantly altered the pro-angiogenic properties of these MSC-derived exosomes, which could be associated with the regulation of their targets in HUVECs. These results suggest that exosomal transfer of pro-angiogenic miRs plays an important role in MSC mediated angiogenesis and stem cell-to-endothelial cell communication.
What's In It for the Volunteers?: An SROI Approach to Volunteers’ Return on Investment in the Good Food Markets

This article reports on a social return on investment (SROI) analysis of volunteers of the Good Food Market program, a food access initiative run by FoodShare Toronto, one of Canada's largest food-justice organizations. Unlike conventional SROI research, which typically focuses on the entire ecology of an organization or program, this article focuses solely on isolating the return volunteers receive on their investment of time, skills, energy, and the like—an SROI of volunteering. The article reviews the challenges of adapting the SROI methodology to the context of volunteer benefits and finds that ultimately SROI is a useful tool for articulating the value of volunteering.
In vivo administration of IL‐18 can induce IgE production through Th2 cytokine induction and up‐regulation of CD40 ligand (CD154) expression on CD4+ T cells

IL‐18 is considered to be a strong cofactor for CD4+ T helper 1 (Th1) cell induction. We have recently reported that IL‐18 can induce IL‐13 production in both NK cells and T cells in synergy with IL‐2 but not IL‐12, suggesting IL‐18 can induce Th1 and Th2 cytokines when accompanied by the appropriate first signals for T cells. We have now found that IL‐18 can act as a cofactor to induce IL‐4, IL‐10 and IL‐13 as well as IFN‐γ production in T cells in the presence of anti‐CD3 monoclonal antibodies (mAb). IL‐18 can rapidly induce CD40 ligand (CD154) mRNA and surface expression on CD4+ but not CD8+ T cells. The administration of IL‐18 alone in vivo significantly increased serum IgE levels in C57BL/6 (B6) and B6 IL‐4 knockout mice. Furthermore, the administration of IL‐18 plus IL‐2 induced approximately 70‐fold and 10‐fold higher serum levels of IgE and IgG1 than seen in control B6 mice, respectively. IgE and IgG1 induction in B6 mice by administration of IL‐18 plus IL‐2 was eliminated by the pretreatment of mice with anti‐CD4 or anti‐CD154, but not anti‐CD8 or anti‐NK1.1 mAb. These results suggest that IL‐18 can induce Th2 cytokines and CD154 expression, and can contribute to CD4+ T cell‐dependent, IL‐4‐independent IgE production.
The natural compound Jatrophone interferes with Wnt/β-catenin signaling and inhibits proliferation and EMT in human triple-negative breast cancer

Metastatic breast cancer is the leading cause of worldwide cancer-related deaths among women. Triple negative breast cancers (TNBC) are highly metastatic and are devoid of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) amplification. TNBCs are unresponsive to Herceptin and/or anti-estrogen therapies and too often become highly chemoresistant when exposed to standard chemotherapy. TNBCs frequently metastasize to the lung and brain. We have previously shown that TNBCs are active for oncogenic Wnt10b/β-catenin signaling and that WNT10B ligand and its downstream target HMGA2 are predictive of poorer outcomes and are strongly associated with chemoresistant TNBC metastatic disease. In search of new chemicals to target the oncogenic WNT10B/β-CATENIN/HMGA2 signaling axis, the anti-proliferative activity of the diterpene Jatrophone (JA), derived from the plant Jatropha isabelli, was tested on TNBC cells. JA interfered with the WNT TOPFLASH reporter at the level between receptor complex and β-catenin activation. JA efficacy was determined in various subtypes of TNBC conventional cell lines or in TNBC cell lines derived from TNBC PDX tumors. The differential IC50 (DCI50) responsiveness was compared among the TNBC models based on etiological-subtype and their cellular chemoresistance status. Elevated WNT10B expression also coincided with increased resistance to JA exposure in several metastatic cell lines. JA interfered with cell cycle progression, and induced loss of expression of the canonical Wnt-direct targets genes AXIN2, HMGA2, MYC, PCNA and CCND1. Mechanistically, JA reduced steady-state, non-phosphorylated (activated) β-catenin protein levels, but not total β-catenin levels. JA also caused the loss of expression of key EMT markers and significantly impaired wound healing in scratch assays, suggesting a direct role for JA inhibiting migration of TNBC cells. These results indicate that Jatrophone could be a powerful new chemotherapeutic agent against highly chemoresistant triple negative breast cancers by targeting the oncogenic Wnt10b/β-catenin signaling pathway.
Energy-Efficient Wireless Sensor Networks for Precision Agriculture: A Review

Wireless sensor networks (WSNs) can be used in agriculture to provide farmers with a large amount of information. Precision agriculture (PA) is a management strategy that employs information technology to improve quality and production. Utilizing wireless sensor technologies and management tools can lead to a highly effective, green agriculture. Based on PA management, the same routine to a crop regardless of site environments can be avoided. From several perspectives, field management can improve PA, including the provision of adequate nutrients for crops and the wastage of pesticides for the effective control of weeds, pests, and diseases. This review outlines the recent applications of WSNs in agriculture research as well as classifies and compares various wireless communication protocols, the taxonomy of energy-efficient and energy harvesting techniques for WSNs that can be used in agricultural monitoring systems, and comparison between early research works on agriculture-based WSNs. The challenges and limitations of WSNs in the agricultural domain are explored, and several power reduction and agricultural management techniques for long-term monitoring are highlighted. These approaches may also increase the number of opportunities for processing Internet of Things (IoT) data.
The Spirochete Brachyspira pilosicoli, Enteric Pathogen of Animals and Humans

SUMMARY Brachyspira pilosicoli is a slow-growing anaerobic spirochete that colonizes the large intestine. Colonization occurs commonly in pigs and adult chickens, causing colitis/typhlitis, diarrhea, poor growth rates, and reduced production. Colonization of humans also is common in some populations (individuals living in village and peri-urban settings in developing countries, recent immigrants from developing countries, homosexual males, and HIV-positive patients), but the spirochete rarely is investigated as a potential human enteric pathogen. In part this is due to its slow growth and specialized growth requirements, meaning that it is not detectable in human fecal samples using routine diagnostic methods. Nevertheless, it has been identified histologically attached to the colon and rectum in patients with conditions such as chronic diarrhea, rectal bleeding, and/or nonspecific abdominal discomfort, and one survey of Australian Aboriginal children showed that colonization was significantly associated with failure to thrive. B. pilosicoli has been detected in the bloodstream of elderly patients or individuals with chronic conditions such as alcoholism and malignancies. This review describes the spirochete and associated diseases. It aims to encourage clinicians and clinical microbiologists to consider B. pilosicoli in their differential diagnoses and to develop and use appropriate diagnostic protocols to identify the spirochete in clinical specimens.
Combined Intratympanic and Systemic Use of Steroids as a First-Line Treatment for Sudden Sensorineural Hearing Loss: A Meta-Analysis of Randomized, Controlled Trials.

OBJECTIVE To compare the efficacy of combination therapy (combined intratympanic and systemic use of steroids, CT) with systemic steroid therapy (SST) as a primary treatment for sudden sensorineural hearing loss (SSNHL). METHODS An electronic database search (PubMed, Embase, Cochrane Library, and CNKI databases) was performed. Review Manger 5.3 was used for data synthesis. Data were collected on the following outcomes of interest: the proportion of patients with hearing improvement, changes in pure tone averages (PTA), and speech discrimination score (SDS). RESULTS A total of 14 RCTs including 756 subjects allocated to CT and 638 to SST were selected. The proportion of patients with hearing improvement as outcome measure was observed in 13 studies, which resulted in an odds ratio (OR) of 2.50 (95% confidence interval [CI]: 1.95-2.1). The PTA changes (in dB) as outcome measure was observed in 12 studies, which resulted in mean difference (MD) 13 (95% CI: 9.24-16.77). SDS changes (in %) as outcome measure were reported in five studies, which resulted in MD 15.72 (95% CI: 5.11-26.33). CONCLUSION CT seems to confer a certain degree of benefit as a primary treatment of SSNHL as compared with SST. Further validation based on high quality studies is required.
Updated analysis of SWOG-directed intergroup study 0116: a phase III trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection.

PURPOSE Surgical resection of gastric cancer has produced suboptimal survival despite multiple randomized trials that used postoperative chemotherapy or more aggressive surgical procedures. We performed a randomized phase III trial of postoperative radiochemotherapy in those at moderate risk of locoregional failure (LRF) following surgery. We originally reported results with 4-year median follow-up. This update, with a more than 10-year median follow-up, presents data on failure patterns and second malignancies and explores selected subset analyses. PATIENTS AND METHODS In all, 559 patients with primaries ≥ T3 and/or node-positive gastric cancer were randomly assigned to observation versus radiochemotherapy after R0 resection. Fluorouracil and leucovorin were administered before, during, and after radiotherapy. Radiotherapy was given to all LRF sites to a dose of 45 Gy. RESULTS Overall survival (OS) and relapse-free survival (RFS) data demonstrate continued strong benefit from postoperative radiochemotherapy. The hazard ratio (HR) for OS is 1.32 (95% CI, 1.10 to 1.60; P = .0046). The HR for RFS is 1.51 (95% CI, 1.25 to 1.83; P < .001). Adjuvant radiochemotherapy produced substantial reduction in both overall relapse and locoregional relapse. Second malignancies were observed in 21 patients with radiotherapy versus eight with observation (P = .21). Subset analyses show robust treatment benefit in most subsets, with the exception of patients with diffuse histology who exhibited minimal nonsignificant treatment effect. CONCLUSION Intergroup 0116 (INT-0116) demonstrates strong persistent benefit from adjuvant radiochemotherapy. Toxicities, including second malignancies, appear acceptable, given the magnitude of RFS and OS improvement. LRF reduction may account for the majority of overall relapse reduction. Adjuvant radiochemotherapy remains a rational standard therapy for curatively resected gastric cancer with primaries T3 or greater and/or positive nodes.
Tests of Eustachian Tube Function: the Effect of Testing Technique on Tube Opening in Healthy Ears.

OBJECTIVE There is no agreement on the best clinical test for Eustachian tube (ET) dysfunction. Numerous tests have been developed to detect ET opening, and all require a patient to perform a Valsalva, Toynbee or sniff maneuver, or to swallow on demand. We aimed to characterize existing tests of ET function in healthy ears, and identify the optimal method and patient maneuver for each test. Our own normative data is presented alongside published comparisons. STUDY DESIGN Diagnostic test cohort study. SETTING Tertiary referral center. PATIENTS Seventy-five healthy ears from 42 volunteers. INTERVENTIONS Six tests of ET function, each performed using multiple different patient maneuvers. MAIN OUTCOME MEASURE Detected ET opening rate for each test-maneuver combination. RESULTS The highest detected opening rates were: Sonotubometry 94%; nine-step test inflation/deflation 93/94%; continuous impedance 88%, patient-reported opening 79%; observed tympanic membrane movement 78%; and Tubo-tympano-aerodynamic-graphy 76%. Valsalva maneuvers were most effective at opening the ET. Toynbee and swallow maneuvers were more effective when performed without water, when compared to with water. For Valsalva and sniff maneuvers, there was significant correlation between the peak nasopharyngeal pressure generated and the ET opening rate. CONCLUSION Based on ET opening detection rates, we recommend the use of dry swallows with sonotubometry and the nine-step test. When testing patient-reported opening and observed membrane movement, and when performing Tubo-tympano-aerodynamic-graphy and impedance tests, we recommend the use of Valsalva maneuvers. Further studies are required to explore the association between the test technique and results in ears with ET dysfunction.
Foxa2 Is Essential for Mouse Endometrial Gland Development and Fertility1

During embryonic development, Foxa2 is required for the formation of the node and notochord, and ablation of this gene results in defects in gastrulation, neural tube patterning, and gut morphogenesis. Foxa2 has been shown to be expressed specifically in the glandular epithelium of the murine uterus. To study the uterine function of Foxa2, this gene was conditionally ablated in the mouse uterus by crossing mice with floxed Foxa2 alleles, Foxa2loxP/loxP, with the Pgrcre mouse model. Pgrcre/+ Foxa2loxP/loxP mice showed significantly reduced fertility. Analysis of the uterus on Day 5.5 of pregnancy showed disrupted blastocyst implantation. Pgrcre/+ Foxa2loxP/loxP mice also showed a severe impairment of the uterus to respond to the artificial induction of the decidual response. Morphological examination of the uteri of these mice showed a severe reduction in the number of endometrial glands. The loss of endometrial glands resulted in the reduction of leukemia inhibitory factor (Lif) expression. The lack of a decidual response could be partially rescued by an intrauterine injection of LIF before the initiation of the decidual response. This analysis demonstrates that Foxa2 regulates endometrial gland development and that mice with a loss of endometrial glands cannot support implantation in part due to the loss of LIF, which is a requisite for fertility in the mouse.
Theory for Approved Social Work: the Use of the Compulsory Admissions Assessment Schedule

SUMMARY In his work on compulsory admissions under the Mental Health Act, 1983, Sheppard (1990) developed the Compulsory Admissions Assessment Schedule (CASH) in response to identified knowledge deficiencies and as a means for operationalizing a knowledge base distinctive to social work. While subject to detailed theoretical development it was not tested in practice. This article examines the use of CASH in practice, and the results have implications for compulsory admission assessments. This paper indicates that CASH is practical to use, that, although there are some grey areas, CASH on the whole distingu ishes clearly between possible sections and those not possible to section, that dangers, hazards and risks are clearly identified, that rating is consistent with the seriousness of dangers identified, that cumulative use of CASH may help develop accountability, and that social work evaluation of CASH is positive. This article concludes that there are considerable benefits from the use of CASH, that ASWs should be trained properly in its use, and, more widely, that these results, together with Sheppard's (1990) original research and theoretical development, indicates that, when conducted appropriately, social science can directly, and beneficially, be applied to practice.
Generation and characterization of an estrogen receptor alpha‐iCre knock‐in mouse

Two estrogen receptors, ESR1 and ESR2, are responsible for the classical actions of estrogens in mammalian species. They display different spatiotemporal expression patterns and nonoverlapping functions in various tissues and physiological conditions. In this study, a novel knock‐in mouse line that expresses codon‐improved Cre recombinase (iCre) under regulation of the natural Esr1 promoter (Esr1–iCre) was developed. Functional characterization of iCre expression by crossing them with reporter lines (ROSA26‐lacZ or Ai9‐RFP) showed that iCre is faithfully expressed in Esr1‐lineage cells. This novel transgenic mouse line will be a useful animal model for lineage‐tracing Esr1‐expressing cells, selective gene ablation in the Esr1‐lineage cells and for generating global Esr1 knockout mice.
Phospholipid Capped Mesoporous Nanoparticles for Targeted High Intensity Focused Ultrasound Ablation

The mechanical effects of cavitation can be effective for therapy but difficult to control, thus potentially leading to off‐target side effects in patients. While administration of ultrasound active agents such as fluorocarbon microbubbles and nanodroplets can locally enhance the effects of high intensity focused ultrasound (HIFU), it has been challenging to prepare ultrasound active agents that are small and stable enough to accumulate in tumors and internalize into cancer cells. Here, this paper reports the synthesis of 100 nm nanoparticle ultrasound agents based on phospholipid‐coated, mesoporous, hydrophobically functionalized silica nanoparticles that can internalize into cancer cells and remain acoustically active. The ultrasound agents produce bubbles when subjected to short HIFU pulses (≈6 µs) with peak negative pressure as low as ≈7 MPa and at particle concentrations down to 12.5 µg mL−1 (7 × 109 particles mL−1). Importantly, ultrasound agents are effectively uptaken by cancer cells without cytotoxic effects, but HIFU insonation causes destruction of the cells by the acoustically generated bubbles, as demonstrated by (2,3‐bis‐(2‐methoxy‐4‐nitro‐5‐sulfophenyl)‐2H‐tetrazolium‐5‐carboxanilide (XTT) and lactate dehydrogenase assays and flow cytometry. Finally, it is showed that the HIFU dose required to effectively eliminate cancer cells in the presence of ultrasound agents causes only a small temperature increase of ≈3.5 °C.
The best practices of human rights (Atham) programme in selected secondary schools in Malaysia

The World Programme for Human Rights Education (2005 – ongoing), set up by United Nations General Assembly and coordinated by the Office of the United Nations High Commissioner for Human Rights (OHCHR) in partnership with the United Nations Educational, Scientific and Cultural Organization (UNESCO) seeks to promote a common understanding of basic principles and methodologies of human rights education, to provide a realistic framework for action, and to strengthen partnerships and cooperation from international to grass-root levels. Aligned with the World Programme for Human Rights Education, the Human Rights Commission of Malaysia (SUHAKAM) in partnership with the Ministry of Education Malaysia implemented the first phase of the Best Practices of Human Rights programme, known as the ATHAM programme in five selected secondary schools in Malaysia. A research study using mixed method sequential exploratory design was conducted to examine the schools’ experiences with the ATHAM programme in terms of participation, implementation and challenges. The respondents consisted of school administrators, teachers and pupils; in total, 103 respondents were interviewed and 798 respondents answered the questionnaires. Drawing from these schools’ experiences, this article discusses the best practices of human rights or ATHAM programme in selected secondary schools in Malaysia.
Impact of fitting algorithms on errors of parameter estimates in dynamic contrast-enhanced MRI

Parameter estimation in dynamic contrast-enhanced MRI (DCE MRI) is usually performed by non-linear least square (NLLS) fitting of a pharmacokinetic model to a measured concentration-time curve. The two-compartment exchange model (2CXM) describes the compartments ‘plasma’ and ‘interstitial volume’ and their exchange in terms of plasma flow and capillary permeability. The model function can be defined by either a system of two coupled differential equations or a closed-form analytical solution. The aim of this study was to compare these two representations in terms of accuracy, robustness and computation speed, depending on parameter combination and temporal sampling. The impact on parameter estimation errors was investigated by fitting the 2CXM to simulated concentration-time curves. Parameter combinations representing five tissue types were used, together with two arterial input functions, a measured and a theoretical population based one, to generate 4D concentration images at three different temporal resolutions. Images were fitted by NLLS techniques, where the sum of squared residuals was calculated by either numeric integration with the Runge–Kutta method or convolution. Furthermore two example cases, a prostate carcinoma and a glioblastoma multiforme patient, were analyzed in order to investigate the validity of our findings in real patient data. The convolution approach yields improved results in precision and robustness of determined parameters. Precision and stability are limited in curves with low blood flow. The model parameter ve shows great instability and little reliability in all cases. Decreased temporal resolution results in significant errors for the differential equation approach in several curve types. The convolution excelled in computational speed by three orders of magnitude. Uncertainties in parameter estimation at low temporal resolution cannot be compensated by usage of the differential equations. Fitting with the convolution approach is superior in computational time, with better stability and accuracy at the same time.