Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of angiopoietin-2 in the cardioprotective effect of fibroblast growth factor 21 on ischemia/reperfusion-induced injury in H9c2 cardiomyocytes

Fibroblast growth factor 21 (FGF21) exerts a protective effect in ischemia/reperfusion (I/R)-induced cardiac injury. However, the exact molecular mechanism underlying the FGF21 action remains unclear. The present study aimed to evaluate the role of angiopoietin-2 (Angpt2) in the cardioprotective effect of FGF21. For this purpose, the H9C2 cell line was subjected to simulated I/R or aerobic conditions with or without FGF21 administration. Certain groups were also transfected with Angpt2 small interfering RNA (siRNA). Cell viability, apoptosis rate and cell migration were examined, and the expression levels of Angpt2, glucose transporter 1 (GLUT1) and caspase-3 were measured by quantitative polymerase chain reaction (qPCR) and western blot analyses. The results demonstrated that FGF21 administration suppressed apoptosis and increased the cell migration ability following I/R-induced injury. qPCR and western blot data showed a decreased level of GLUT1 after I/R-induced injury, which was reversed by FGF21 administration. Furthermore, inhibition of Angpt2 expression using siRNA enhanced the cardioprotective effect of FGF21 by upregulation of GLUT1. In conclusion, FGF21 administration protected against I/R-induced injury in cardiomyocytes, and further inhibition of Angpt2 with FGF21 administration induced the expression of GLUT1, which may promote the energy metabolism in cardiomyocytes, consequently resulting in a more efficient cardioprotective effect. These results suggested that FGF21 administration and inhibition of Angpt2 could be a novel therapeutic approach for I/R-induced cardiac injury.
CHK2–BRCA1 tumor-suppressor axis restrains oncogenic Aurora-A kinase to ensure proper mitotic microtubule assembly

Significance Inactivation of the tumor-suppressor gene breast cancer susceptibility type 1 (BRCA1) triggers abnormal microtubule assembly during mitosis, causing chromosome missegregation and aneuploidy. Unraveling how BRCA1 is regulated during mitosis and how it contributes to microtubule assembly is pivotal to understand its tumor-suppressor function. We showed that BRCA1 is positively regulated during mitosis by the tumor-suppressor kinase checkpoint kinase 2 (Chk2). This regulation is required for the recruitment of a protein phosphatase, which restrains oncogenic Aurora-A kinase activity bound to BRCA1. Unleashed Aurora-A, in turn, can negatively regulate the mitotic function of BRCA1. Thus we define a network in which the Chk2–BRCA1 tumor-suppressor axis restrains oncogenic Aurora-A to ensure proper function of BRCA1 in mitosis essential for normal regulation of microtubule dynamics and chromosome segregation. BRCA1 (breast cancer type 1 susceptibility protein) is a multifunctional tumor suppressor involved in DNA damage response, DNA repair, chromatin regulation, and mitotic chromosome segregation. Although the nuclear functions of BRCA1 have been investigated in detail, its role during mitosis is little understood. It is clear, however, that loss of BRCA1 in human cancer cells leads to chromosomal instability (CIN), which is defined as a perpetual gain or loss of whole chromosomes during mitosis. Moreover, our recent work has revealed that the mitotic function of BRCA1 depends on its phosphorylation by the tumor-suppressor kinase Chk2 (checkpoint kinase 2) and that this regulation is required to ensure normal microtubule plus end assembly rates within mitotic spindles. Intriguingly, loss of the positive regulation of BRCA1 leads to increased oncogenic Aurora-A activity, which acts as a mediator for abnormal mitotic microtubule assembly resulting in chromosome missegregation and CIN. However, how the CHK2–BRCA1 tumor suppressor axis restrains oncogenic Aurora-A during mitosis to ensure karyotype stability remained an open question. Here we uncover a dual molecular mechanism by which the CHK2–BRCA1 axis restrains oncogenic Aurora-A activity during mitosis and identify BRCA1 itself as a target for Aurora-A relevant for CIN. In fact, Chk2-mediated phosphorylation of BRCA1 is required to recruit the PP6C–SAPS3 phosphatase, which acts as a T-loop phosphatase inhibiting Aurora-A bound to BRCA1. Consequently, loss of CHK2 or PP6C-SAPS3 promotes Aurora-A activity associated with BRCA1 in mitosis. Aurora-A, in turn, then phosphorylates BRCA1 itself, thereby inhibiting the mitotic function of BRCA1 and promoting mitotic microtubule assembly, chromosome missegregation, and CIN.
Accelerating reproductive and child health programme impact with community-based services: the Navrongo experiment in Ghana.

OBJECTIVE To determine the demographic and health impact of deploying health service nurses and volunteers to village locations with a view to scaling up results. METHODS A four-celled plausibility trial was used for testing the impact of aligning community health services with the traditional social institutions that organize village life. Data from the Navrongo Demographic Surveillance System that tracks fertility and mortality events over time were used to estimate impact on fertility and mortality. RESULTS Assigning nurses to community locations reduced childhood mortality rates by over half in 3 years and accelerated the time taken for attainment of the child survival Millennium Development Goal (MDG) in the study areas to 8 years. Fertility was also reduced by 15%, representing a decline of one birth in the total fertility rate. Programme costs added 1.92 US Dollar per capita to the 6.80 US Dollar per capita primary health care budget. CONCLUSION Assigning nurses to community locations where they provide basic curative and preventive care substantially reduces childhood mortality and accelerates progress towards attainment of the child survival MDG. Approaches using community volunteers, however, have no impact on mortality. The results also demonstrate that increasing access to contraceptive supplies alone fails to address the social costs of fertility regulation. Effective deployment of volunteers and community mobilization strategies offsets the social constraints on the adoption of contraception. The research in Navrongo thus demonstrates that affordable and sustainable means of combining nurse services with volunteer action can accelerate attainment of both the International Conference on Population and Development agenda and the MDGs.
AVANT: Results from a randomized, three-arm multinational phase III study to investigate bevacizumab with either XELOX or FOLFOX4 versus FOLFOX4 alone as adjuvant treatment for colon cancer.

362 Background: Bevacizumab (BEV), a humanized anti-VEGF monoclonal antibody, has demonstrated clinical efficacy in combination with 5-FU-based regimens in patients with metastatic colorectal cancer. The therapeutic impact of concurrent BEV with either FOLFOX4 or XELOX chemotherapy in the adjuvant setting was evaluated in this international, controlled phase III trial. METHODS Eligible patients had high-risk stage II or stage III colon cancer and had undergone surgical resection. Patients were randomly assigned to one of three treatment groups and stratified by geographic region and tumor stage: Arm A: FOLFOX4 on weeks 1-24; Arm B: FOLFOX4 + BEV on weeks 1-24, then BEV alone on weeks 25-48; Arm C: XELOX + BEV on weeks 1-24, then BEV alone on weeks 25-48. The primary endpoint was disease-free survival (DFS) for patients with stage III colon cancer; secondary endpoints included overall survival (OS), and safety. DFS/OS follow-up assessments were performed every 6 months after randomization for 4 years, then annually until recurrence or death. RESULTS 3,451 (2,867 stage III) patients were enrolled between December 2004 and June 2007; median age was 58-59 years. Median duration of follow-up was 48 months (range 0-66 months). BEV did not prolong DFS or OS when added to either FOLFOX4 or XELOX in patients with stage III colon cancer based on the final efficacy analysis conducted in September 2010. Efficacy results favored the chemotherapy-alone control arm. Numerically more relapses and deaths occurred in both the BEV arms compared to control. The observed adverse events were consistent with those previously reported in pivotal trials of BEV across tumor types for approved indications. CONCLUSIONS The primary endpoint of the AVANT study was not met. BEV does not prolong DFS when added to either FOLFOX4 or XELOX in patients with stage III colon cancer. The safety profile of BEV was consistent with prior study results. [Table: see text].
A low-voltage high-efficiency voltage doubler for thermoelectric energy harvesting

This paper presents a low-voltage high-efficiency voltage doubler for thermoelectric energy harvesting. A negative charge pump is used to reduce on-resistance of PMOSFET load switches. Additional circuitry for achieving high efficiency just requires small chip-area and low-cost. The voltage doubler is implemented in 0.13-μm 1.2V CMOS process. The proposed doubler improves the low-voltage power efficiency by 17%, compared to conventional voltage doublers. Moreover, the proposed doubler can support wider load range. The maximum power efficiency reaches 52% at the input voltage of 0.2V.
Bortezomib plus melphalan and prednisone compared with melphalan and prednisone in previously untreated multiple myeloma: updated follow-up and impact of subsequent therapy in the phase III VISTA trial.

PURPOSE The purpose of this study was to confirm overall survival (OS) and other clinical benefits with bortezomib, melphalan, and prednisone (VMP) versus melphalan and prednisone (MP) in the phase III VISTA (Velcade as Initial Standard Therapy in Multiple Myeloma) trial after prolonged follow-up, and evaluate the impact of subsequent therapies. PATIENTS AND METHODS Previously untreated symptomatic patients with myeloma ineligible for high-dose therapy received up to nine 6-week cycles of VMP (n = 344) or MP (n = 338). RESULTS With a median follow-up of 36.7 months, there was a 35% reduced risk of death with VMP versus MP (hazard ratio, 0.653; P < .001); median OS was not reached with VMP versus 43 months with MP; 3-year OS rates were 68.5% versus 54.0%. Response rates to subsequent thalidomide- (41% v 53%) and lenalidomide-based therapies (59% v 52%) appeared similar after VMP or MP; response rates to subsequent bortezomib-based therapy were 47% versus 59%. Among patients treated with VMP (n = 178) and MP (n = 233), median survival from start of subsequent therapy was 30.2 and 21.9 months, respectively, and there was no difference in survival from salvage among patients who received subsequent bortezomib, thalidomide, or lenalidomide. Rates of adverse events were higher with VMP versus MP during cycles 1 to 4, but similar during cycles 5 to 9. With VMP, 79% of peripheral neuropathy events improved within a median of 1.9 months; 60% completely resolved within a median of 5.7 months. CONCLUSION VMP significantly prolongs OS versus MP after lengthy follow-up and extensive subsequent antimyeloma therapy. First-line bortezomib use does not induce more resistant relapse. VMP used upfront appears more beneficial than first treating with conventional agents and saving bortezomib- and other novel agent-based treatment until relapse.
Sonographic evaluation of the immediate effects of eccentric heel drop exercise on Achilles tendon and gastrocnemius muscle stiffness using shear wave elastography

Background Mechanical loading is crucial for muscle and tendon tissue remodeling. Eccentric heel drop exercise has been proven to be effective in the management of Achilles tendinopathy, yet its induced change in the mechanical property (i.e., stiffness) of the Achilles tendon (AT), medial and lateral gastrocnemius muscles (MG and LG) was unknown. Given that shear wave elastography has emerged as a powerful tool in assessing soft tissue stiffness with promising intra- and inter-operator reliability, the objective of this study was hence to characterize the stiffness of the AT, MG and LG in response to an acute bout of eccentric heel drop exercise. Methods Forty-five healthy young adults (36 males and nine females) performed 10 sets of 15-repetition heel drop exercise on their dominant leg with fully-extended knee, during which the AT and gastrocnemius muscles, but not soleus, were highly stretched. Before and immediately after the heel drop exercise, elastic moduli of the AT, MG and LG were measured by shear wave elastography. Results After the heel drop exercise, the stiffness of AT increased significantly by 41.8 + 33.5% (P < 0.001), whereas the increases in the MG and LG stiffness were found to be more drastic by 75 + 47.7% (P < 0.001) and 71.7 + 51.8% (P < 0.001), respectively. Regarding the AT, MG and LG stiffness measurements, the inter-operator reliability was 0.940, 0.987 and 0.986, and the intra-operator reliability was 0.916 to 0.978, 0.801 to 0.961 and 0.889 to 0.985, respectively. Discussion The gastrocnemius muscles were shown to bear larger mechanical loads than the AT during an acute bout of eccentric heel drop exercise. The findings from this pilot study shed some light on how and to what extent the AT and gastrocnemius muscles mechanically responds to an isolated set of heel drop exercise. Taken together, appropriate eccentric load might potentially benefit mechanical adaptations of the AT and gastrocnemius muscles in the rehabilitation of patients with Achilles tendinopathy.
Direct Medical Costs of Acute Pancreatitis Hospitalizations in the United States

Objectives: To determine the direct medical costs of hospitalizations for acute pancreatitis in the United States and analyze the demographic characteristics of hospitalized patients. Methods: We searched the 2003 Healthcare Cost and Utilization Project-National Inpatient Sample for hospitalizations with a primary discharge diagnosis of acute pancreatitis. These were analyzed with respect to patient demographics, hospitalization rates, and total hospital charges and costs. Results: The estimated total cost for acute pancreatitis admissions was $2.2 billion (95% confidence interval [CI], 2.0 billion-2.3 billion) at a mean cost per hospitalization of $9870 (95% CI, 9300-10,400), and a mean cost per hospital day of $1670 (95% CI, 1620-1720). Costs per hospitalization were higher in urban hospitals, teaching hospitals, and for patients older than 65 years, based on a longer length of stay (LOS). The hospitalization rate was 0.52 per 1000 US population (95% CI, 0.48-0.56) for whites versus 0.76 per 1000 (95% CI, 0.65-0.87) for blacks. Conclusions: Acute pancreatitis hospitalizations cost more than $2 billion annually, and certain population groups (blacks and older patients) have disproportionately high hospitalization rates. This study highlights the need for prevention efforts, particularly targeting high-risk groups, and for further studies to identify cost effective treatment strategies for acute pancreatitis.
Radiation dose and risk from fluoroscopically guided percutaneous transhepatic biliary procedures.

PURPOSE To estimate radiation dose and associated risks after fluoroscopically guided percutaneous transhepatic biliary (PTB) drainage and stent implantation procedures. MATERIALS AND METHODS Organ and effective doses, normalized to dose-area product (DAP), were estimated for PTB procedures with use of a Monte Carlo transport code and an adult mathematical phantom. Exposure parameters from 51 consecutive patients were used to determine average examination parameters for biliary drainage and stent implantation procedures. Thermoluminescent dosimeters were used in an anthropomorphic phantom to verify Monte Carlo calculations. Radiation-induced cancer and genetic risks were estimated. RESULTS The results consist of doses normalized to DAP so patient dose from any technique and x-ray unit can be easily calculated for left and right biliary access and for separate or combined biliary and metallic stent implantation sessions. A good agreement was found between Monte Carlo-calculated data and data derived from thermoluminescent dosimetry. The average effective dose varied from 1.8 to 5.4 mSv depending on procedure approach (left vs right access) and procedure scheme. A maximum effective dose of 13 mSv was estimated for 30 minutes of fluoroscopy. CONCLUSIONS Doses delivered to patients undergoing PTB procedures are comparable to those that arise from computed tomography protocols. Radiation-induced cancer risk may be considerable for young patients undergoing PTB drainage and stent implantation procedures.
Acute respiratory distress syndrome: a life threatening associated complication of SARS-CoV-2 infection inducing COVID-19

Abstract Acute Respiratory Distress Syndrome (ARDS) is a form of respiratory failure in human. The number of deaths caused by SARS-CoV-2 infection inducing this severe pneumonia (ARDS) is relatively high. In fact, COVID-19 might get worsen in ARDS and provoke respiratory failure. A better understood of ARDS key features and the pathophysiological injuries of the pulmonary parenchyma are linked to lessons learned from previous severe diseases associated previous coronaviruses outbreaks (especially SARS-CoV and MERS-CoV) and more the ongoing SARS-CoV-2. The ARDS mechanism includes a diffuse alveolar damage associated disruption of alveolar capillary membrane, pulmonary edema, damaged endothelium and increased permeability. A diffuse inflammation, with acute onset, on the lung tissue accompanied by release of biochemical signal and inflammatory mediators (TNFα, IL-1 and IL-6) leading to hypoxemia, low PaO2/FiO2 ratio and the chest radiological expression of bilateral infiltrates in ARDS. The ongoing outbreak could lead to a better understood of ARDS pathophysiology and prognostic. An overview is also highlighted about the seven coronaviruses proved to infect human especially those having ability to cause severe disease SARS-CoV, MERS-CoV and SARS-CoV-2. In this review, we focused on the major pathological mechanisms leading to the ARDS development as a result of viral infection, severe COVID-19 worsening. Communicated by Ramaswamy H. Sarma
Inhibition of IL-10 Receptor Function in Alveolar Macrophages by Toll-Like Receptor Agonists1

Despite an immunosuppressive lung environment, alveolar macrophages (AM) retain the capacity to respond to microorganisms. This report demonstrates that IL-10, constitutively produced by normal alveolar epithelium, stimulates signal transduction through the IL-10R on AM and that IL-10R function can be inhibited by stimulation of Toll-like receptor (TLR) on AM. IL-10 mRNA and protein were constitutively expressed in normal alveolar epithelium of mice, and IL-10R were constitutively expressed on normal murine AM. Stimulation of AM through TLR2, TLR4, or TLR9 was sufficient to inhibit IL-10R signal transduction, including phosphorylation and nuclear translocation of STAT3 transcription factor. Inhibition of IL-10R function by TLRs was not associated with a decrease in IL-10R expression, but did require expression of the myeloid differentiation factor 88 adaptor protein. Continuous exposure of macrophages to IL-10 caused sustained expression of the chemokine receptors CCR1 and CCR5. However, the addition of TLR ligands inhibited IL-10-induced expression of CCR1 and CCR5. Finally, exposure of macrophages to TLR ligands blocked the ability of IL-10 to inhibit the induction of TNF-α by C2-ceramide. These findings demonstrate a novel regulatory mechanism that may allow AM to overcome inhibitory effects of constitutive IL-10 in the lungs that may permit a more effective response to pulmonary infections.
Chunk-based Decoder for Neural Machine Translation

Chunks (or phrases) once played a pivotal role in machine translation. By using a chunk rather than a word as the basic translation unit, local (intra-chunk) and global (inter-chunk) word orders and dependencies can be easily modeled. The chunk structure, despite its importance, has not been considered in the decoders used for neural machine translation (NMT). In this paper, we propose chunk-based decoders for (NMT), each of which consists of a chunk-level decoder and a word-level decoder. The chunk-level decoder models global dependencies while the word-level decoder decides the local word order in a chunk. To output a target sentence, the chunk-level decoder generates a chunk representation containing global information, which the word-level decoder then uses as a basis to predict the words inside the chunk. Experimental results show that our proposed decoders can significantly improve translation performance in a WAT ‘16 English-to-Japanese translation task.
Detection for cross-reactive proteins in filarial worm Setaria equina, MCF-7 human breast cancer, and Huh-7 hepatoma cells

ABSTRACT This study aimed to detect the cross-reactive proteins in filarial parasite adult worm Setaria equina and two different tumor cell lines (MCF-7 human breast cancer and Huh-7 hepatoma cells). This was performed using rabbit anti-S. equina extract (SeqE) or DEC (Diethylcarbamazine citrate) polyclonal IgG antibodies by indirect ELISA and western blotting. The results indicated cross-reactive bands at 70 and 75 kDa in all extracts by anti-DEC and SeqE antibodies, respectively. In addition, the expression of 70 kDa protein was only reduced in filarial worms and Huh-7 after in vitro DEC treatment compared to the control.
Quantitative characterization, classification and reconstruction of oocyst shapes of Eimeria species from cattle

This study reports on morphological variability of Eimeria species, which may be given either by drawings or as quantitative data. The drawings may be used to facilitate identification by eye of ‘unknown’ Eimeria specimens, whereas quantitative data may serve as a reference set for identification by multivariate statistical techniques. The morphology of 810 Eimeria specimens was defined in binary (b/w) digital images by pixels of their oocyst outline. A Fourier transform of pixel positions yielded size and shape features. To classify coccidia, the quantitative data were employed in an agglomerative clustering by average linkage algorithm with equal weight assigned to size and shape. An inverse Fourier transform served to reconstruct oocyst outlines, i.e. outlines of average shape and size, from mean values of features in resulting clusters. Clusters were subsequently identified based on their average morphology by comparison with drawings of species in an earlier taxonomical work. Five hundred oocyst outlines were simulated for each cluster representing a species, and shape/size variability was presented in contour diagrams. Differences in species shapes, and correspondence in length and width, were seen after reconstruction by inverse Fourier transform and comparison with earlier studies.
DEVELOPMENT OF A CLINICAL ASSESSMENT OF QUALITY OF MOVEMENT FOR UNILATERAL UPPER‐LIMB FUNCTION

Eleven subjects with cerebral palsy were assessed both with the Melbourne Assessment and by four clinical experts. Comparison of their assessment ratings revealed that the Melbourne Assessment was strongly related to the clinical judgement of the experts. A further 20 subjects were administered the Melbourne Assessment and two occupational therapists scored each subject's performance from videotaped assessments with substantial inter‐rater reliability (0–68); intra‐rater agreement after two weeks was 0–80. The Melbourne Assessment may provide a satisfactory objective measure of the quality of upper‐limb function.