Miracle-dz/UniFAR-FTUs huggingface dataset:
Safety Assessment of Neoadjuvant Pertuzumab Combined with Trastuzumab in Nonmetastatic HER2-Positive Breast Cancer in Postmenopausal Elderly Women of South Asia

Aim To evaluate the safety issues and adverse effects of using TCHP regimen (docetaxel, carboplatin, trastuzumab, and pertuzumab) versus TCP regimen (docetaxel, carboplatin, and trastuzumab) in older postmenopausal women with nonmetastatic HER2-positive breast cancer. HER2 overexpressed in 20–25% of breast cancer signals an aggressive form of breast cancer and is treated with trastuzumab and pertuzumab. Methods The patient record database was accessed to identify all postmenopausal women in the Punjab Care hospital who were above 65 years old, with stages 1–3 HER2-positive breast cancer and treated with neoadjuvant TCHP and neoadjuvant TCP from 2013 till 2016. Results In TCH-P group and TCH group, mild fatigue (34% versus 36%) and diarrhea (48% versus 49%) were most common toxicities. Fever in TCH-P group and TCH group (12% versus 13%) was common. Anorexia affected 21% and 16% of patients receiving TCH and TCHP regimen, respectively. Febrile neutropenia was higher in TCH-P group 13% (3/23) versus 4.5% (1/22) in TCH group. Also 27.2% (6/22) of TCH-P group was hospitalized for treatment related toxicities versus 21.7% (5/23) of TCH group. Conclusion Comparing neoadjuvant TCP and neoadjuvant TCH-P showed TCH-P regimen had an acceptable toxicity profile. Severe cardiac dysfunction was not observed. Using TCH-P regimen can be considered as relatively safe therapeutic option for elderly postmenopausal women with nonmetastatic HER2-positive breast cancer.
Based Clustering : A Foundational Perspective

In the first part of this chapter we detail center based clustering methods, namely methods based on finding a “best” set of center points and then assigning data points to their nearest center. In particular, we focus on k-means and k-median clustering which are two of the most widely used clustering objectives. We describe popular heuristics for these methods and theoretical guarantees associated with them. We also describe how to design worst case approximately optimal algorithms for these problems. In the second part of the chapter we describe recent work on how to improve on these worst case algorithms even further by using insights from the nature of real world clustering problems and data sets. Finally, we also summarize theoretical work on clustering data generated from mixture models such as a mixture of Gaussians. 1 Approximation algorithms for k-means and k-median One of the most popular approaches to clustering is to define an objective function over the data points and find a partitioning which achieves the optimal solution, or an approximately optimal solution to the given objective function. Common objective functions include center based objective functions such as k-median and k-means where one selects k center points and the clustering is obtained by assigning each data point to its closest center point. Here closeness is measured in terms of a pairwise distance function d(), which the clustering algorithm has access to, encoding how dissimilar two data points are. For instance, the data could be points in Euclidean space with d() measuring Euclidean distance, or it could be strings with d() representing an edit distance, or some other dissimilarity score. For mathematical convenience it is also assumed that the distance function d() is a metric. In k-median clustering the objective is to find center points c1, c2, · · · ck, and a partitioning of the data so as to minimize Φk−median = ∑ x mini d(x, ci). This objective is historically very useful and well studied for facility location problems [16, 43]. Similarly the objective in k-means is to minimize Φk−means = ∑ x mini d(x, ci) . Optimizing this objective is closely related to fitting the maximum likelihood mixture model for a given dataset. For a given set of centers, the optimal clustering for that set is obtained by assigning each data point to its closest center point. This is known as the Voronoi partitioning of the data. Unfortunately, exactly optimizing the k-median and the k-means objectives is a notoriously hard problem. Intuitively this is expected since the objective function is a non-convex function of the variables involved. This apparent hardness can also be formally justified by appealing to the
Dual-band microstrip antenna for the fifth generation indoor/outdoor wireless applications

In this paper a dual band monopole antenna with omnidirectional radiation pattern suitable for indoor and outdoor fifth generation (5G) applications at 28 GHz and 60 GHz systems is developed. The proposed monopole antenna is built up using a microstrip of two rectangular patches and a T-shaped folded patch. The analysis and optimization processes throughout this paper are carried out using a High Frequency Surface Structure (HFSS) that uses the Finite Element Method (FEM) numerical method, and CST Microwave Studio that uses the Finite Integral Technique (FIT) numerical method. Good agreement between the two methods is obtained. The bandwidth of the lower and upper bands is about 1.44 GHz (5.1%) and 39.24 GHz (60.6%), respectively. The antenna directivity is about 2.28 dBi at 28 GHz with a total efficiency of 93% and about 3.414 dBi with a total efficiency of 97.5% at 60 GHz.
Cardiovascular risk factors and frailty in a cross-sectional study of older people: implications for prevention

Abstract Objective to examine the associations of cardiovascular disease (CVD) and cardiovascular risk factors with frailty. Design a cross-sectional study. Setting the Irish Longitudinal Study on Ageing (TILDA). Participants frailty measures were obtained on 5,618 participants and a subset of 4,330 participants with no prior history of CVD. Exposures for observational study cardiovascular risk factors were combined in three composite CVD risk scores (Systematic Coronary Risk Evaluation [SCORE], Ideal Cardiovascular Health [ICH] and Cardiovascular Health Metrics [CHM]). Main outcome measures a frailty index (40-items) was used to screen for frailty. Methods the associations of CVD risk factors with frailty were examined using logistic regression. Results overall, 16.4% of participants had frailty (7.6% at 50–59 years to 42.5% at 80+ years), and the prevalence was higher in those with versus those without prior CVD (43.0% vs. 10.7%). Among those without prior CVD, mean levels of CVD risk factors were closely correlated with higher frailty index scores. Combined CVD risk factors, assessed using SCORE, were linearly and positively associated with frailty. Compared to low-to-moderate SCOREs, the odds ratio (OR) (95% confidence interval, CI) of frailty for those with very high risk was 3.18 (2.38–4.25). Conversely, ICH was linearly and inversely associated with frailty, with an OR for optimal health of 0.29 (0.21–0.40) compared with inadequate health. Conclusions the concordant positive associations of SCORE and inverse associations of ICH and CHM with frailty highlight the potential importance of optimum levels of CVD risk factors for prevention of disability in frail older people.
Protective effect of betulin and betulinic acid on acetaminophen and ethanol-induced cytotoxicity and reactive oxygen species production in HepG2 cells

Natural triterpenoids such as ursolic and oleanolic acids have been detected to suppress enzymes which play a role in liver damage, e.g. cytochrome P450, cytochrome b5, CYP1A and CYP2A, and to increase the antioxidant substances glutathione, metallothioneins, and glutathione-S-transferase, with simultaneous protective effects on liver mitochondria. To test the hypothesis that plant triterpenes may also induce mechanisms leading to reduced production of reactive oxygen species after induction with ethanol and acetaminophen, the cytoprotective effect of two plant triterpenes, betulin and its oxidized form, betulinic acid, was compared. Acetaminophen alone at concentrations between 25-250 µg/ml exhibited dose-dependent cytotoxicity for HepG2 cells. When a mixture of 25 µg/ml of acetaminophen was mixed with different concentrations of 5-50 mM of ethanol, an additional increase in the toxicity was observed, depending on the ethanol concentration used. Acetaminophen alone was detected as a strong inducer of superoxide anion in HepG2 cells. Moreover, the mixture of acetaminophen with ethanol induced significantly more superoxide anion than acetaminophen and ethanol alone. When betulin or betulinic acid were preincubated with HepG2 cells the level of superoxide anion and hydrogen peroxide was significantly lower than in respective controls. Betulin, in comparison to betulinic acid, was a stronger inhibitor of oxidative burst.
Endorse or Not to Endorse: Understanding the Determinants of Newspapers' Likelihood of Making Political Recommendations

This paper investigates the determinants of newspapers' provision for political endorsements. I empirically examine the role of newspapers' political preferences and market competition on newspapers' decision. Regression results suggest that market competition inhibits newspapers from making endorsements. Results from a simple model show that newspapers' ideology determine their endorsements, turning partisan papers more likely to make political recommendations and more likely to endorse challengers than non-partisan newspapers.
Deep learning based gastric cancer identification

Gastric cancer is one of the most common cancers, which causes the second largest deaths worldwide. Manual pathological inspection of gastric slice is time-consuming and usually suffers from inter-observer variations. In this paper, we proposed a deep learning based framework, namely GastricNet, for automatic gastric cancer identification. The proposed network adopts different architectures for shallow and deep layers for better feature extraction. We evaluate the proposed framework on publicly available BOT gastric slice dataset. The experimental results show that our deep learning framework performs better than state-of-the-art networks like DenseNet, ResNet, and achieved an accuracy of 100% for slice-based classification.
The Open-Closed Principle of Modern Machine Learning Frameworks

Recent advances in computing technologies and the availability of huge volumes of data have sparked a new machine learning (ML) revolution, where almost every day a new headline touts the demise of human experts by ML models on some task. Open source software development is rumoured to play a significant role in this revolution, with both academics and large corporations such as Google and Microsoft releasing their ML frameworks under an open source license. This paper takes a step back to examine and understand the role of open source development in modern ML, by examining the growth of the open source ML ecosystem on GitHub, its actors, and the adoption of frameworks over time. By mining LinkedIn and Google Scholar profiles, we also examine driving factors behind this growth (paid vs. voluntary contributors), as well as the major players who promote its democratization (companies vs. communities), and the composition of ML development teams (engineers vs. scientists). According to the technology adoption lifecycle, we find that ML is in between the stages of early adoption and early majority. Furthermore, companies are the main drivers behind open source ML, while the majority of development teams are hybrid teams comprising both engineers and professional scientists. The latter correspond to scientists employed by a company, and by far represent the most active profiles in the development of ML applications, which reflects the importance of a scientific background for the development of ML frameworks to complement coding skills. The large influence of cloud computing companies on the development of open source ML frameworks raises the risk of vendor lock-in. These frameworks, while open source, could be optimized for specific commercial cloud offerings.
Restrictive Breathing Mask Reduces Repetitions to Failure During a Session of Lower-Body Resistance Exercise

Abstract Andre, TL, Gann, JJ, Hwang, PS, Ziperman, E, Magnussen, MJ, and Willoughby, DS. Restrictive breathing mask reduces repetitions to failure during a session of lower-body resistance exercise. J Strength Cond Res 32(8): 2103–2108, 2018—The purpose of this study was to determine the effect of restrictive breathing mask (RBM) on muscle performance, hemodynamic, and perceived stress variables during a session of lower-body resistance exercise. In a crossover design, 10 participants performed 2 separate testing sessions, RBM and no mask, consisting of squat, leg press, and leg extension. The paired-samples t-test was used for session rating of perceived exertion (S-RPE), perceived stress before and after, heart rate (HR), pulse oximetry, and a 2 × 4 (session [mask, no mask] × time [squat exercise, leg press exercise, leg extension exercise, total resistance exercise session]) factorial analysis of variance with repeated measures (p ⩽ 0.05). A significant decrease was found in total repetitions during the RBM condition (p < 0.01). A majority of the decrease in repetitions to failure occurred in the squat (p < 0.05) and in the leg press (p < 0.01), whereas no difference was observed in leg extension (p = 0.214). A significant increase was observed in S-RPE during the RBM session (p < 0.01). A significant increase was found in prestress (p < 0.01) and poststress (p = 0.01) in the RBM session. No significant difference existed for HR between exercise sessions (p = 0.08). A significant decrease existed in pulse oximetry during the RBM session (p < 0.01). The use of an RBM had a negative effect on the number of repetitions completed during an acute session of lower-body resistance training.
Difference in Serum Endostatin Levels in Diabetic Patients with Critical Limb Ischemia Treated by Autologous Cell Therapy or Percutaneous Transluminal Angioplasty

The aim of this study was to compare the serum levels of the anti-angiogenic factor endostatin (S-endostatin) as a potential marker of vasculogenesis after autologous cell therapy (ACT) versus percutaneous transluminal angioplasty (PTA) in diabetic patients with critical limb ischemia (CLI). A total of 25 diabetic patients with CLI treated in our foot clinic during the period 2008–2014 with ACT generating potential vasculogenesis were consecutively included in the study; 14 diabetic patients with CLI who underwent PTA during the same period were included in a control group in which no vasculogenesis had occurred. S-endostatin was measured before revascularization and at 1, 3, and 6 months after the procedure. The effect of ACT and PTA on tissue ischemia was confirmed by transcutaneous oxygen pressure (TcPO2) measurement at the same intervals. While S-endostatin levels increased significantly at 1 and 3 months after ACT (both P < 0.001), no significant change of S-endostatin after PTA was observed. Elevation of S-endostatin levels significantly correlated with an increase in TcPO2 at 1 month after ACT (r = 0.557; P < 0.001). Our study showed that endostatin might be a potential marker of vasculogenesis because of its significant increase after ACT in diabetic patients with CLI in contrast to those undergoing PTA. This increase may be a sign of a protective feedback mechanism of this anti-angiogenic factor.
Targeting PIM kinase as a therapeutic strategy in human hepatoblastoma

Increasing incidence coupled with poor prognosis and treatments that are virtually unchanged over the past 20 years have made the need for the development of novel therapeutics for hepatoblastoma imperative. PIM kinases have been implicated as drivers of tumorigenesis in multiple cancers, including hepatocellular carcinoma. We hypothesized that PIM kinases, specifically PIM3, would play a role in hepatoblastoma tumorigenesis and that PIM kinase inhibition would affect hepatoblastoma in vitro and in vivo. Parameters including cell survival, proliferation, motility, and apoptosis were assessed in human hepatoblastoma cells following PIM3 knockdown with siRNA or treatment with the PIM inhibitor AZD1208. An in vivo model of human hepatoblastoma was utilized to study the effects of PIM inhibition alone and in combination with cisplatin. PIM kinases were found to be present in the human hepatoblastoma cell line, HuH6, and in a human hepatoblastoma patient-derived xenograft, COA67. PIM3 knockdown or inhibition with AZD1208 decreased cell survival, attachment independent growth, and motility. Additionally, inhibition of tumor growth was observed in a hepatoblastoma xenograft model in mice treated with AZD1208. Combination therapy with AZD1208 and cisplatin resulted in a significant increase in animal survival when compared to either treatment alone. The current studies showed that PIM kinase inhibition decreased human hepatoblastoma tumorigenicity both in vitro and in vivo, implying that PIM inhibitors may be useful as a novel therapeutic for children with hepatoblastoma.
Calcium Signaling in the Ventricular Myocardium of the Goto-Kakizaki Type 2 Diabetic Rat

The association between diabetes mellitus (DM) and high mortality linked to cardiovascular disease (CVD) is a major concern worldwide. Clinical and preclinical studies have demonstrated a variety of diastolic and systolic dysfunctions in patients with type 2 diabetes mellitus (T2DM) with the severity of abnormalities depending on the patients' age and duration of diabetes. The cellular basis of hemodynamic dysfunction in a type 2 diabetic heart is still not well understood. The aim of this review is to evaluate our current understanding of contractile dysfunction and disturbances of Ca2+ transport in the Goto-Kakizaki (GK) diabetic rat heart. The GK rat is a widely used nonobese, nonhypertensive genetic model of T2DM which is characterized by insulin resistance, elevated blood glucose, alterations in blood lipid profile, and cardiac dysfunction.
Adaptive Regulation of Osteopontin Production by Dendritic Cells Through the Bidirectional Interaction With Mesenchymal Stromal Cells

Mesenchymal stromal cells (MSCs) exert immunosuppressive effects on immune cells including dendritic cells (DCs). However, many details of the bidirectional interaction of MSCs with DCs are still unsolved and information on key molecules by which DCs can modulate MSC functions is limited. Here, we report that osteopontin (OPN), a cytokine involved in homeostatic and pathophysiologic responses, is constitutively expressed by DCs and regulated in the DC/MSC cocultures depending on the activation state of MSCs. Resting MSCs promoted OPN production, whereas the production of OPN was suppressed when MSCs were activated by proinflammatory cytokines (i.e., TNF-α, IL-6, and IL-1β). OPN induction required cell-to-cell contact, mediated at least in part, by β1 integrin (CD29). Conversely, activated MSCs inhibited the release of OPN via the production of soluble factors with a major role played by Prostaglandin E2 (PGE2). Accordingly, pretreatment with indomethacin significantly abrogated the MSC-mediated suppression of OPN while the direct addition of exogenous PGE2 inhibited OPN production by DCs. Furthermore, DC-conditioned medium promoted osteogenic differentiation of MSCs with a concomitant inhibition of adipogenesis. These effects were paralleled by the repression of the adipogenic markers PPARγ, adiponectin, and FABP4, and induction of the osteogenic markers alkaline phosphatase, RUNX2, and of the bone-anabolic chemokine CCL5. Notably, blocking OPN activity with RGD peptides or with an antibody against CD29, one of the OPN receptors, prevented the effects of DC-conditioned medium on MSC differentiation and CCL5 induction. Because MSCs have a key role in maintenance of bone marrow (BM) hematopoietic stem cell niche through reciprocal regulation with immune cells, we investigated the possible MSC/DC interaction in human BM by immunohistochemistry. Although DCs (CD1c+) are a small percentage of BM cells, we demonstrated colocalization of CD271+ MSCs with CD1c+ DCs in normal and myelodysplastic BM. OPN reactivity was observed in occasional CD1c+ cells in the proximity of CD271+ MSCs. Altogether, these results candidate OPN as a signal modulated by MSCs according to their activation status and involved in DC regulation of MSC differentiation.
Pinot: Realtime OLAP for 530 Million Users

Modern users demand analytical features on fresh, real time data. Offering these analytical features to hundreds of millions of users is a relevant problem encountered by many large scale web companies. Relational databases and key-value stores can be scaled to provide point lookups for a large number of users but fall apart at the combination of high ingest rates, high query rates at low latency for analytical queries. Online analytical databases typically rely on bulk data loads and are not typically built to handle nonstop operation in demanding web environments. Offline analytical systems have high throughput but do not offer low query latencies nor can scale to serving tens of thousands of queries per second. We present Pinot, a single system used in production at Linkedin that can serve tens of thousands of analytical queries per second, offers near-realtime data ingestion from streaming data sources, and handles the operational requirements of large web properties. We also provide a performance comparison with Druid, a system similar to Pinot.
An epoxysterol and other constituents of Tanzania soft corals

Three biologically active Lobophytum species, L. crassum von Marenzeller (1886), L. rotundum Tixier- Durivault (1957) and L. venustum Tixier-Durivault (1957) and one Sinularia species were phytochemically investigated. Lobophytum rotundum afforded an epoxysterol (1), cembraolide (2), and fatty acid ester (4), and ether glycerols (6 and 7). Compound 2 was also isolated in L. crassum together with another fatty acid ester (5). Lobophytum venustum produced epoxycembrene 3 and compound 4. Two ether glycerols (6 and 8) were isolated from the Sinularia species. This paper reports the isolation and structure elucidation of compounds 1, and 4-8. Keywords : Marine sterols, Cnidaria, soft corals.
The use of drawings to facilitate interviews with orphaned children in Mpumalanga province, South Africa

HIV/AIDS and being orphaned impact greatly on children’s lives. This article explores the life experiences of orphaned children in Mpumalanga province, South Africa. In this qualitative case study, draw-write techniques and face-to-face interviews were used to generate data related to the experiences of the children. Results suggest that although the interviewed children yearn for their parents and experience unmet emotional and material needs, they use promotive factors, such as personal agency and environmental relationships, as resilience in fulfilling their needs. Furthermore, the results suggest relationships based on values, such as caring, respect and mutual understanding, as protective factors that may contribute to the fulfilment of social needs as well as enabling their emotional well-being.