Miracle-dz/UniFAR-FTUs huggingface dataset:
Docetaxel for the treatment of bladder cancer

Introduction: Docetaxel has had a significant impact on the management of urothelial carcinoma (UC). Multiple phase II trials have been conducted to evaluate the efficacy of docetaxel in the treatment of metastatic UC. Docetaxel is an accepted community standard for the therapy of platinum-treated patients with metastatic UC. Areas covered: This review focuses on the data supporting a role for docetaxel in the therapy of advanced UC. It also explores the future development of docetaxel and describes the ongoing clinical trials in the treatment of UC. Expert opinion: Docetaxel plays an important role as one of the standard agents used in the comparator arms of randomized trials evaluating new agents as salvage therapy for metastatic UC. Furthermore, biologic agents are being developed in chemo-biologic regimens using docetaxel as the platform. In the context of emerging novel agents such as T-cell checkpoint inhibitors, docetaxel may continue to play a role as a salvage therapy in select patients ineligible for immunotherapy or following checkpoint inhibitors.
Reversal of Stathmin-Mediated Resistance to Paclitaxel and Vinblastine in Human Breast Carcinoma Cells

Antimicrotubule agents are commonly used chemotherapy drugs for the treatment of breast and other cancers. However, these agents have variable activity partly because of microtubule regulatory proteins. Stathmin, an 18-kDa phosphoprotein that promotes microtubule depolymerization, was found to be frequently overexpressed in breast cancer. We previously identified stathmin-mediated mechanisms of resistance to antimicrotubule agents, including altered drug binding and delayed transit from G2 into M phase, where these agents are effective in disrupting microtubule dynamics. We hypothesized that by reversing stathmin-mediated depolymerization of microtubules or by promoting entry into mitosis, this could increase sensitivity to antimicrotubule agents in human breast cancer cells overexpressing stathmin. We found that targeting stathmin or wee-1 expression with RNA interference can induce microtubule polymerization and promote G2/M progression, respectively, and sensitize stathmin-overexpressing breast cancer cells to paclitaxel and vinblastine. Furthermore, targeting wee-1 led to the phosphorylation of stathmin, which is known to attenuate its activity. Therefore, these data suggest a novel approach to improving the efficacy of certain antimicrotubule agents against breast cancer by regulating the function of stathmin.
Lysophosphatidic acid‐induced membrane ruffling and brain‐derived neurotrophic factor gene expression are mediated by ATP release in primary microglia

We examined the effects of lysophosphatidic acid (LPA) on microglia, which may play an important role in the development and maintenance of neuropathic pain. LPA caused membrane ruffling as detected by scanning electron microscopy, and increased the expression of brain‐derived neurotrophic factor (BDNF) in a primary culture of rat microglia, which express LPA3, but not LPA1 or LPA2 receptors. These actions were inhibited by a Gαq/11‐antisense oligodeoxynucleotide (AS‐ODN), U73122, an inhibitor of phospholipase C (PLC), and apyrase, which specifically degrades ATP and ADP. When ATP release was measured using a luciferin‐luciferase bioluminescence assay, LPA was shown to increase it in an LPA3 and PLC inhibitor‐reversible manner. However, LPA‐induced ATP release was also blocked by the Gαq/11 AS‐ODN, but not by pertussis toxin. These results suggest that LPA induces the release of ATP from rat primary cultured microglia via the LPA3 receptor, Gαq/11 and PLC, and that the released ATP or ectopically converted ADP may in turn cause membrane ruffling via P2Y12 receptors and Gαi/o activation, and BDNF expression via activation of P2X4 receptors.
Hospital financial distress, recovery and closure: Managerial incentives and political costs

The purpose of this study is to examine the association of managerial incentives and political costs with hospital financial distress, recovery or closure. The Medicare Payment Advisory Commission has stated that hospital closures are important for evaluating the distribution of cost, quality and access to healthcare throughout the US. Using Logistic regression, we demonstrate that hospital closure is associated with low occupancy, return on investment, asset turnover, and lack of affiliation with a multihospital system. It is also significantly associated with urban location, teaching programs, high Medicare and Medicaid patient populations, and high debt. Essential access nonprofit hospitals are less likely to close, while this does not affect governmental and for-profit hospitals. Our research hypotheses are supported by these results.
Nusinersen for the treatment of spinal muscular atrophy

ABSTRACT Introduction: Spinal muscular atrophy (SMA) is an autosomal recessive degenerative neuromuscular disorder characterized by loss of spinal motor neurons leading to muscle weakness. This review article focuses on a novel antisense oligonucleotide treatment, first ever approved for SMA (nusinersen, SpinrazaTM) and describes the exciting journey from early ASO clinical trials to regulatory approval of the first ever known effective treatment for SMA. Areas covered: This article reviews the results of the published open label nusinersen studies in infants and children, and briefly covers the preliminary findings of the recently completed but as yet unpublished nusinersen–sham controlled trials, as well as the presymptomatic nusinersen trial known as Nurture. Clinical use of nusinersen is also reviewed. Expert commentary: Collectively, the studies show improvement in motor function across SMA of all types, including SMA type 3. Best motor response was observed with early treatment; presymptomatic treatment prevented disease manifestations. Nusinersen was found to be safe and well tolerated across all age groups studied. Nusinersen has irrevocably altered the natural history of SMA and allowed for the first time children to transition between SMA types. Nusinersen should be considered as standard of care for the treatment of SMA of all types.
Seasonality in Stock Returns: Evidence from Advanced Emerging Stock Markets

Despite an extensive number of studies documenting evidence of seasonal anomalies in developed markets, only a few studies have comprehensively examined these anomalies within emerging markets. Testing seasonal anomaly in emerging markets would first, help to examine the theoretical explanations that have been proposed and second, provide an out-of-sample result for seasonality anomaly. This study examines the efficiency of advanced emerging markets by testing five important seasonal anomalies: the month of the year, other January, day-of-the-week, holiday and week 44 effects. For each market, we use over two decades of stock return data denominated in both US dollars and the local currency to examine seasonal anomalies in returns and volatility. We find strong evidence of higher December returns in advanced emerging markets. The 44th week of the year consistently yields higher stock returns in eight out of nine advanced emerging markets. Our data also confirms the existence of the day of the week effect in six out of nine countries in the sample. In particular, Fridays tend to have higher while Mondays tend to have lower stock returns. We also find a strong holiday effect in seven countries in our sample. However, our data is unable to support the existence of the other January effect in advanced emerging markets, which may be due to the lack of institutional investors participating in these markets.
Activity Based Cost Management Making It Work A Managers Guide To Implementing And Sustaining An Effective Abc System

Thank you very much for downloading activity based cost management making it work a managers guide to implementing and sustaining an effective abc system. Maybe you have knowledge that, people have look hundreds times for their chosen readings like this activity based cost management making it work a managers guide to implementing and sustaining an effective abc system, but end up in malicious downloads. Rather than enjoying a good book with a cup of coffee in the afternoon, instead they are facing with some infectious bugs inside their laptop.
Development of vessel integrated power system

The Integrated Power System (IPS) is not only an important basis of the shipbased high-energy weapons but also a revolutionary way of the developing naval vessel power because it is characterized by lower noise, higher survivability, fewer prime movers, less fuel consumption, and greater convenience for general arrangement. This paper has described both the constitution and the latest developments of IPS, proposed the concept of two-generation IPSs, and presented their remarkable technical characteristics and typical architectures. The quantitative analyses of volume, weight, efficiency, power supply continuity, load flow adjustment and control capability, stability, protection and reconfiguration abilities demonstrate that the second-generation IPS has the advantage over the first-generation IPS. Finally, several key technologies concerning the second-generation IPS that need a breakthrough have been proposed according to the current technical level.
C1q/TNF-related protein 1: a novel link between visceral fat and athero-inflammation.

This editorial refers to ‘C1q/tumour necrosis factor-related protein 1: an adipokine marking and promoting atherosclerosis’, by L. Lu et al . , doi:10.1093/eurheartj/ehv649. Approximately 30% of the global population are overweight or obese, posing a major threat to healthcare in developed and developing countries. Obesity decreases life expectancy, mainly by increasing the risk of type 2 diabetes and cardiovascular disease. A mechanistic explanation for these intertwined metabolic and cardiovascular risks has been offered by adipokines, a large and diverse group of molecules secreted by adipose tissue that affect both glucose metabolism and cardiovascular function. Importantly, the perivascular depot of adipose tissue is situated around the majority of the arterial tree, and a large number of studies have shown that local adipokine expression controls vascular function and dysfunction.1 Well-known adipokines include cytokines such as interleukin-1β and tumour necrosis factor α (TNFα) (resulting in the term adipose tissue-derived cytokines), leptin, and fatty acids. Among the most intriguing adipokines are the 16-member family of C1q/TNF-related proteins (CTRPs) that includes the intensively studied adiponectin,2 also synthesized in arterial perivascular adipose tissue (PVAT). 3 The CTRPs share the globular adiponectin domain in their molecular structure, which binds and activates the adiponectin receptors AdipoR1 and AdipoR2, widely expressed in the cardiovascular system.4 CTRPs circulate as monomers but also as heterotrimers, enabling diverse biological effects.2 Figure 1 The adipokine CTRP1 (C1q/tumour necrosis factor-related protein 1) is produced in adipose tissue (yellow area) as well by oxidized LDL (OxLDL)- or interleukin-1β (IL-1β)-stimulated macrophages and endothelial cells in the atherosclerotic plaque (purple area). In the plaque, CTRP1 activates endothelial cells and macrophages themselves to produce leucocyte adhesion molecules and tumour necrosis factor α (TNFα), …
Long-term effect of brief intervention in at-risk alcohol drinkers: a 9-year follow-up study.

AIMS In 1986, 338 men and women attending a general population screening study were identified as at-risk alcohol drinkers and randomly assigned into three groups. Two groups received slightly different, brief interventions; a third group served as control. After 1 year there was a 50% reduction in alcohol intake in the intervention groups and a 20% increase in the control group. Controls then received advice to reduce their drinking. This study evaluates outcomes 9 years after these interventions. METHODS In a survey in the same city in 1995 (over 27 000 participants), 247 subjects (73.1%) from the 1986 study, were re-assessed. Serum gamma-glutamyltransferase (GGT) was examined and compared with values in 1986. A 'pseudo-control' group was established to compare 'treated' and 'untreated'. RESULTS After 9 years, the original study groups displayed significant mean reduction in GGT. The reductions achieved in the three groups did not significantly differ from each other. However, the reductions were significantly greater than that in the 'pseudo-control' group. CONCLUSION The impact of brief intervention appears to be long lasting. At 9 years follow-up, the at-risk drinkers displayed GGT values close to that of the background population.
The voluntary disclosure of intellectual capital by listed companies in Zimbabwe

This paper examines the cross-sectional effect of industry, listing status, company size, gearing, profitability and corporate governance mechanisms on the extent of voluntary disclosure of intellectual capital in 54 Zimbabwe Stock Exchange Companies for the year 2011/2012. The extent of voluntary disclosure is measured by a disclosure index based on intellectual capital attributes included in the narratives and illustrations of the annual reports. The paper predicts that agency costs may be minimised through voluntary disclosure and that the benefits of signalling may outweigh competitive costs that may be more prevalent in some industries. The results suggest that large companies operating in high-tech and innovative industries that are characterised by investment in employees and research and development processes have higher levels of hidden value. These companies, associated with reduced financial risk, the presence of financial expertise on their audit committees and higher levels of profitability, are characterised by higher levels of voluntary disclosure of intellectual capital. In contrast, multiple listing, proportion of non-executive directors and association with "big 5 auditors", are insignificant in explaining the variation in voluntary disclosure of intellectual capital in Zimbabwe.
CAPER, a novel regulator of human breast cancer progression

CAPER is an estrogen receptor (ER) co-activator that was recently shown to be involved in human breast cancer pathogenesis. Indeed, we reported increased expression of CAPER in human breast cancer specimens. We demonstrated that CAPER was undetectable or expressed at relatively low levels in normal breast tissue and assumed a cytoplasmic distribution. In contrast, CAPER was expressed at higher levels in ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) specimens, where it assumed a predominantly nuclear distribution. However, the functional role of CAPER in human breast cancer initiation and progression remained unknown. Here, we used a lentiviral-mediated gene silencing approach to reduce the expression of CAPER in the ER-positive human breast cancer cell line MCF-7. The proliferation and tumorigenicity of MCF-7 cells stably expressing control or human CAPER shRNAs was then determined via both in vitro and in vivo experiments. Knockdown of CAPER expression significantly reduced the proliferation of MCF-7 cells in vitro. Importantly, nude mice injected with MCF-7 cells harboring CAPER shRNAs developed smaller tumors than mice injected with MCF-7 cells harboring control shRNAs. Mechanistically, tumors derived from mice injected with MCF-7 cells harboring CAPER shRNAs displayed reduced expression of the cell cycle regulators PCNA, MCM7, and cyclin D1, and the protein synthesis marker 4EBP1. In conclusion, knockdown of CAPER expression markedly reduced human breast cancer cell proliferation in both in vitro and in vivo settings. Mechanistically, knockdown of CAPER abrogated the activity of proliferative and protein synthesis pathways.
Dopamine promotes striatal neuronal apoptotic death via ERK signaling cascades

Although the mechanisms underlying striatal neurodegeneration are poorly understood, we have shown that striatal pathogenesis may be initiated by high synaptic levels of extracellular dopamine (DA). Here we investigated in rat striatal primary neurons the mobilization of the mitogen‐activated protein kinase (MAPK) signaling pathways after treatment with DA. Instead of observing an elevation of the archetypical pro‐cytotoxic MAPKs, p‐JNK and p‐p38 MAPK, we found that DA, acting through D1 DA receptors, induced a sustained stimulation of the phosphorylated form of extracellular signal‐regulated kinase (p‐ERK) via a cAMP/protein kinase A (PKA)/Rap1/B‐Raf / MAPK/ERK kinase (MEK) pathway. Blockade of D2 DA receptors, β‐adrenergic receptors or N‐methyl‐d‐aspartate receptors with receptor‐specific antagonists had no significant effect on this process. Activation of D1 DA receptors and PKA by DA caused phosphorylation and inactivation of the striatal‐enriched tyrosine phosphatase, an important phosphatase for the dephosphorylation and subsequent inactivation of p‐ERK in the striatum. Interestingly, p‐ERK was primarily retained in the cytoplasm, with only low amounts translocated to the nucleus. The scaffold protein β‐arrestin2 interacted with both p‐ERK and D1 DA receptor, triggering the cytosolic retention of p‐ERK and inducing striatal neuronal apoptotic death. These data provide unique insight into a novel role of p‐ERK in striatal neurodegeneration.
Serum Folate and B12 Levels in Association With Cognitive Impairment Among Seniors

Objective: To summarize existing evidence on the effect of serum folate and vitamin B12 levels on cognitive impairment among elders via a meta-analysis, also including unpublished data from a cross-sectional study of seniors ( > 65 years) residing in Velestino, Greece. Method: Serum measurements and Mini-Mental State Examination (MMSE) assessments were available for 593 Velestinians. In addition, 12 studies availing data on folate blood levels (N = 9,747) and 9 on B12 (N = 8,122) were identified following a search algorithm; pooled effect estimates were derived. Results: Cognitive impairment (MMSE < 24) among Velestenians was associated with lower education level in both genders; decreased social activity, depressive symptoms and low folate levels in males; older age in females. Meta-analyses showed an adverse effect of low-folate levels on cognition (OR: 1.66, 95% CI: 1.40-1.96); B12 was nonsignificantly associated (OR: 1.11, 95% CI: 0.88-1.40). Discussion: Low folate levels are associated with cognitive impairment of seniors; underlying pathophysiological mechanisms should be further explored.
Electromyography of pongid shoulder muscles II. Deltoid, rhomboid and "rotator cuff".

Electromyographic (EMG) recordings were taken of action potentials in the deltoid, rhomboid, supraspinatus, infraspinatus, subscapularis, and teres minor muscles of pongid apes as they spontaneously elevated their arms and engaged in suspensory activity on a trapeze. During brachial elevation, activities of pongid deltoid, rhomboid, supra-spinatus, infraspinatus and subscapularis muscles basically resemble those of human subjects. The intermediate deltoid exhibited high potentials particularly near and at the zenith of brachial elevation. The anterior and, to a lesser extent, posterior deltoid were more variable than the intermediate deltoid during arm-raising. The three heads often acted discretely. Rhomboid potentials also increased steadily with the highest ones at 130–150°. The supraspinatus sometimes acted as an initiator and accelerator of arm-raising. Supraspinatus potentials commonly decreased markedly near the zenith of brachial elevation. When subjects reached overhead, it was impossible to discern whether the subscapularis acted fundamentally as an arm-raising muscle or merely as a medial rotator to position the hand. In the orangutan, the teres minor was inconsequentially active during arm-raising. This is strikingly different from the human activity pattern in which it is supposed to function in the inferior component of a glenohumeral force couple (Inman et al., '44). Remarkably little consequential EMG activity was recorded in the shoulder muscles of gorilla during hoisting activity. Per contra, in the orangutan some muscles were quite active as she hoisted herself on the trapeze. The teres minor seemed to be a prime retractor of the humerus in that context. In the chimpanzee, the rhomboid and especially the supraspinatus were significantly active during hoisting. All muscles tested in the three great apes were silent or inconsequentially active during pendent suspension from the trapeze. We conclude that at least during short-term pendent suspension, osseoligamentous mechanisms are probably chiefly responsible for maintaining integrity of pongid glenohumeral joints. The important role of the supraspinatus muscle as a brachial elevator should be emphasized in future studies of pongid scapular shape. In view of the variable, contextually dependent, actions of the pongid “rotator cuff” muscles we suggest that they be termed the deep scapulohumeral muscles.
The Prevalence of Transfusion Transmitted Infections in ABO Blood Groups and Rh Type System

Screening of blood and blood products is important to reduce the risk of transfusion transmitted infections (TTIs). The transfusion of unscreened or inadequately screened blood and blood products are the major source of TTIs. The aim of this paper is to find out the prevalence of TTIs in ABO blood groups and Rh type system. A total of 4128 blood donors were screened from January 2010 to April 2014. Serological tests were performed for hepatitis B surface antigen (HBsAg), anti hepatitis C virus (Anti-HCV), anti HIV-1 and 2, venereal disease research Laboratory test (VDRL) and malaria parasite (MP) antigen. In seroreactive donors, HBsAg, Anti-HCV, VDRL, MP antigen and anti HIV were positive in 40 cases, 26 cases, 19 cases, 6 cases and 2 cases, respectively. Highest percentage of HBsAg, Anti HCV, VDRL, MP antigen and anti HIV was observed in blood group A negative (2/50), O negative (1/66), B negative (1/91), AB positive (2/377) blood group respectively. In the present study, the total number of Rhnegative donors is lower when compared to Rh-positive blood donors, but Rh-negative blood donors show higher percentages of seroreactivity for TTIs. Larger scale studies at molecular level are required to improve the knowledge of this aspect.
An Analysis of the Role of Internal Audit in Implementing Risk Management - a S tudy of State Corporations in Kenya

The study analyzed the role of internal audit in Enterprise Risk Management (ERM) by providing empirical Evidence on the Kenyan public sector firms. The study examined the impact of Involvement in ERM by auditors and internal auditors’ willingness to report a breakdown in risk procedures and whether a strong relationship with the audit committee affects willingness to report. The study also investigated the use of ERM and the role of internal audit in ERM. The study was carried out as a cross-sectional survey where the study population was 99 respondents from nine state corporations operating under the State Corporations Act. From the findings, the study concluded that management of State Corporation needs to create an environment that will harness commitment and support to internal audit if it is to effectively perform its responsibility of giving assurance that organizational risks are managed effectively. This will only be possible if individuals within organizations are aware of the role and importance of internal audit function in implementation of enterprise risk management. The study made the following recommendations; the process regarding internal audit and regulatory compliance certification should be amended to ensure the corporations’ trust in them. This will have the desired effect of their wide-scale adoption that, in turn, leads to stronger internal controls and standardization of operations. The study suggested further research should be carried out to find out how the auditors themselves contribute to the effectiveness of internal audit function, for example factors such as competences, education status and others. Keyword: Internal Audit, Corporate governance, enterprise risk management