bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID-19 A Pure Gamble - An Engineering perspective
Authors: Ho Teck Tuak
Published: June 2020

COVID-19 A Pure Gamble - An Engineering perspective
Nature đăng bài tác giả Việt
Authors: Hoàng NGUYỄN Minh
Published: June 2020

Ngày 8-6 vừa qua, tạp chí Nature danh tiếng, 151 tuổi, một trong số rất ít ngọn hải đăng của khoa học nhân loại đã xuất bản bài của TS. Vương Quân Hoàng, Trung tâm ISR (trường Đạihọc Phenikaa, Hà Nội).
Fenomena Tuturan Emosi Verbal Bahasa Indonesia Suku Bajo Sampela
Authors: Susiati Susiati
Published: June 2020

AbstrakPenelitian ini bertujuan mendeskripsikanjenis emosi verbal Bahasa Indonesia suku Bajo Sampela (SBS) dan mengidentifikasi faktor munculnya emosi verbal Bahasa Indonesia Suku Bajo Sampea. Penelitian ini merupakan penelitian kualitatif. Data dikumpulkan menggunakan metode observasi. Sementara, teknik pengumpulan data menggunakan teknik observasi partisipasi yang moderat, rekam, dan catat. Data dianalisis secara deskriptif sesuai dengan teori penggolongan jenis emosi Goleman dan teori penggolongan faktor Hurlock.Hasil penelitian menunjukkan terdapat tujuh jenis emosi verbal bahasa Indonesia SBS, yakni (1) amarah; (2) kesedihan; (3) rasa takut; (4) kenikmatan; (5) cinta; (6) terkejut; dan (7) jengkel. Ketujuh jenis emosi tersebut didapat dari berbagai bentuk piranti linguistik, yakni kata, frasa, kalimat, dan gaya bahasa. Selanjutnya, ada dua faktor yang mempengaruhi munculnya emosi verbal bahasa Indonesia SBS, yaitu faktor internal dan faktor eksternal. Faktor internal dan faktor eksternal ditemukan dari tiap jenis emosi.
KONFIGURASI DAN INSTALASI NETWORK MONITORING SYSTEM UNTUK APLIKASI PELAPORAN TAHUNAN PADA SERVER MILIK PT. XYZ
Authors: Atmaja Shina Qolbunajati
Published: June 2020

Tujuan penelitian ini untuk mengimplementasikan network monitoring system untuk memantau pergerakan server pada server milik PT. XYZ. Software yang digunakan adalah Cacti, sebuah software opensource yang digunakan untuk network monitoring system. Cacti yang menyediakan fitur pemantauan kinerja jaringan yang meliputi trafik dan kepadatan serta sumber daya hardware seperti; sistem up/down, utilitas cpu dan memory, kapasitas storage dan manajemen port. Sehingga memudahkan pegawai PT. XYZ untuk mengetahui kinerja dari server tersebut.
Mapping outcome reporting bias in published non-pharmacological randomized trials: a protocol for a cross-sectional study
Authors: Helal Lucas , da Costa Gabriel Gonçalves , de Lucena Alves Charles Phillipe , Luizetti Barbara Okabaisse , Freccia Guilherme Weiss , Gonçalves Lívia Souza , Nascimento Dafne Port , Rice Danielle B , Mayo-Wilson Evan , Hoffmann Tammy
Published: June 2020

This pre-print refers to a protocol of a study which intends to explore outcome reporting bias in an extensive sample of the non-pharmacological literature and also to access the completeness of reporting of outcomes of such trials.
Factors associated with irrational drug use at a district hospital in Zambia patient record-based observations,
Authors: Muungo Lungwani
Published: June 2020

Background: The irrational use of drugs remains a keyhealth problem in many developing countries. Theprevalence of irrational drug use and factors associatedwith it were investigated at Kapiri Mposhi DistrictHospital in Zambia.Methods: The outpatient records (n = 680) of clinicalencounters from the hospital registry department for theyear 2010 were analysed. The selection process adapted arandom sampling method using the patient logbook inorder to get a representative sample. Standardised WorldHealth Organization (WHO) prescribing and facilityindicators were used to describe irrational drug use. Thecomposite measure of irrational drug use was used todetermine the prevalence of irrational drug use at thehospital. Logistic regression was used to assess factorsassociated with irrational drug use. In addition, a selfadministeredquestionnaire was administered to assessthe availability of key medical personnel at the hospital.
Evaluation of the quality of anti Tuberculosis drugs in Lusaka, Zambia
Authors: Muungo Lungwani
Published: June 2020

Background: Counterfeit and substandardmedicines are a threat to health and the risks theypose have been largely underestimated to date.Almost all areas of the world are affected by theavailability of substandard and counterfeitmedicines, but mounting evidence shows that theproblem is disproportionately severe in developingand emerging market countries, which also have ahigh burden of infectious diseases. In poorcountries, essential and life-saving drugs used totreat infectious diseases such as tuberculosis andmalaria are often the drugs under threat.
EBAG9 is a tumor‐promoting and prognostic factor for bladder cancer.
Authors: Muungo Lungwani
Published: June 2020

Upregulation of EBAG9 expression has been observed in severalmalignant tumors such as advanced breast and prostate cancers,indicating that EBAG9 may contribute to tumor proliferation. Inthe present study, we assess the role of EBAG9 in bladder cancer.We generated human bladder cancer EJ cells stably expressingFLAG-tagged EBAG9 (EJ-EBAG9) or empty vector (EJ-vector),and investigated whether EBAG9 overexpression modulates cellgrowth and migration in vitro as well as the in vivo tumor formationof EJ transfectants in xenograft models of BALB/c nude mice.EBAG9 overexpression promoted EJ cell migration, while theeffect of EBAG9 to cultured cell growth was rather minimal.Tumorigenic experiments in nude mice showed that the size of EJEBAG9-derived tumors was significantly larger than EJ-vectorderivedtumors. Loss-of-function study for EBAG9 using smallinterfering RNA (siRNA) in xenografts with parental EJ cellsshowed that the intra-tumoral injection of EBAG9 siRNA markedlyreduced the EJ tumor formation compared with controlsiRNA. Furthermore, immunohistochemical study for EBAG9expression was performed in 60 pathological bladder cancer specimens.Intense and diffuse cytoplasmic immunostaining wasobserved in 45% of the bladder cancer cases. Positive EBAG9immunoreactivity was closely correlated with poor prognosis ofthe patients (p 5 0.0001) and it was an independent prognosticpredictor for disease-specific survival in multivariate analysis(p 5 0.003). Our results indicate that EBAG9 would be a crucialregulator of tumor progression and a potential prognostic markerfor bladder cancer.
ARFGAP3 an androgen target gene promotes prostate cancer cell proliferation and migration.
Authors: Muungo Lungwani
Published: June 2020

ADP ribosylation factor GTPase-activating protein 3 (ARFGAP3) is a GTPase-activating protein that associates with the Golgiapparatus and regulates the vesicular trafficking pathway. In the present study, we examined the contribution of ARFGAP3 toprostate cancer cell biology. We showed that ARFGAP3 expression was induced by 100 nM of dihydrotestosterone (DHT) atboth the mRNA and protein levels in androgen-sensitive LNCaP cells. We generated stable transfectants of LNCaP cells withFLAG-tagged ARFGAP3 or a control empty vector and showed that ARFGAP3 overexpression promoted cell proliferation andmigration compared with control cells. We found that ARFGAP3 interacted with paxillin, a focal adhesion adaptor protein thatis important for cell mobility and migration. Small interfering RNA (siRNA)-mediated knockdown of ARFGAP3 showed thatARFGAP3 siRNA markedly reduced LNCaP cell growth. Androgen receptor (AR)-dependent transactivation activity on prostatespecificantigen (PSA) enhancer was synergistically promoted by exogenous ARFGAP3 and paxillin expression, as shown byluciferase assay in LNCaP cells. Thus, our results suggest that ARFGAP3 is a novel androgen-regulated gene that can promoteprostate cancer cell proliferation and migration in collaboration with paxillin.
Successful treatment of conversion chemotherapy for initially unresectable synchronous colorectal liver metastasis
Authors: Muungo Lungwani
Published: June 2020

A 72-year-old woman with a sigmoid colon cancer anda synchronous colorectal liver metastasis (CRLM), whichinvolved the right hepatic vein (RHV) and the inferiorvena cava (IVC), was referred to our hospital. Themetastatic lesion was diagnosed as initially unresectablebecause of its invasion into the confluence of theRHV and IVC. After she had undergone laparoscopicsigmoidectomy for the original tumor, she consequentlyhad 3 courses of modified 5-fluorouracil, leucovorin,and oxaliplatin (mFOLFOX6) plus cetuximab. Computedtomography revealed a partial response, and theconfluence of the RHV and IVC got free from cancerinvasion. After 3 additional courses of mFOLFOX6 pluscetuximab, preoperative percutaneous transhepaticportal vein embolization (PTPE) was performed tosecure the future remnant liver volume. Finally, a righthemihepatectomy was performed. The postoperativecourse was uneventful. The patient was dischargedfrom the hospital on postoperative day 13. She hadneither local recurrence nor distant metastasis 18 moafter the last surgical intervention. This multidisciplinarystrategy, consisting of conversion chemotherapy usingFOLFOX plus cetuximab and PTPE, could contributein facilitating curative hepatic resection for initiallyunresectable CRLM.Key words: Initially unresectable; Colorectal liver metastasis;Conversion chemotherapy; Cetuximab; Percutaneoustranshepatic portal vein embolization
Heterogeneity of the efficacy of the 23-valent pneumococcal polysaccharide vaccine caused by various underlying conditions of chronic pulmonary disease in older patients: prospective cohort study
Authors: Muungo Lungwani
Published: June 2020

Objective: To determine the ideal conditions for use ofthe 23-valent pneumococcal polysaccharide vaccine(PPV23) in older outpatients with chronic pulmonarydiseases.Design: Prospective cohort study.Participants: 1378 outpatients with chronicpulmonary diseases $60 years of age.Intervention: Participants were educated
SOME MOLECULAR ASPECTS OF PLANT PEROXIDASE BIOSYNTHETIC STUDIES
Authors: Muungo Lungwani
Published: June 2020

The early history of research on peroxidase is most capably reviewed bySaunders et al (67). The first color reaction of biological material withguaiacum as substrate was noted in 1809, but the term peroxidase was usedfor the first time nearly a century later for an enzyme isolated from horseradish.In fact, peroxidase is widely distributed in the plant kingdom and also occurs in the animal kingdom. Many of the spectral aspects of this hemoproteinand its reaction products have been described in the above-mentioned textand elsewhere (e.g. 23). Different types of peroxidases were recognized, andan ever-increasing number of functions were ascribed to them, particularly inplant physiology (31). Therefore, while the basic chemical reactions ofperoxidase (E. C . 1.1 1.1. 7) are well established, namely that of the peroxidaticcycle involving H202 and a large array of hydrogen donors (23), the questionsof how its many isozymes function (31) and how its action in differentiation iscontrolled (68) remain largely unanswered. I do not review all publications onthese topics here. A comprehensive tabulation has appeared recently (31).Instead, I offer a critical review of certain aspects of peroxidase in terms ofstructure and biosynthesis.
Association of single nucleotide polymorphisms in the promoter region of the pro-opiomelanocortin gene (POMC) with low bone mineral density in adult women.
Authors: Muungo Lungwani
Published: June 2020

Among multiple factors influencing osteoporosis,genetic variations involved in bone-mineralmetabolism can affect risks predisposing to the diseaseonset. Here, we studied single-nucleotide polymorphisms(SNPs) in the pro-opiomelanocortin (POMC)gene for possible association with bone mineral density(BMD) among 384 adult Japanese women and observedsignificant correlation between adjusted BMD and threeSNPs in the promoter region (r>0.14, p<0.01). Themost significant correlation was observed for ?2353G/A(r=?0.16, p=0.002); homozygous carriers of the major(G) allele had the highest BMD (0.405±0.054 g/cm2)while heterozygous carriers were intermediate(0.390±0.053 g/cm2) and homozygous A-allele carriershad the lowest BMDs (0.369±0.048 g/cm2). Althoughno association was detected between these SNPs andbody weight or body mass index (BMI), significantassociation was detected between the ?2313A/C genotypeand plasma total cholesterol level (r=?0.12,p=0.019). We propose that POMC is among the likelysusceptibility genes for osteoporosis and may also beinvolved in dyslipidemia.
Association of multiple nucleotide variations in the pituitary glutaminyl cyclase gene QPC with low radial BMD in adult women.
Authors: Muungo Lungwani
Published: June 2020

Correlation between 13 genetic variations of the glutaminyl-peptide cyclotransferase gene andadjusted aBMD was tested among 384 adult women. Among 13 variations with strong linkage disequilibrium,R54W showed a prominent association (p ? 0.0003), which was more striking when examined among 309 eldersubjects (>50 years; p ? 0.0001). Contribution for postmenopausal bone loss was suggested.Introduction: Alterations in homeostatic regulation of estrogen through the hypothalamus-pituitary-gonadal axis(HPG axis) importantly affect the pathogenesis of osteoporosis. Osteoporosis-susceptibility genes have beenproposed in this hormonal axis, such as estrogen receptor genes and the gonadotropin-releasing hormone gene(GnRH). Here we report another example of genes: glutaminyl-peptide cyclotransferase gene (QPCT), an essentialmodifier of pituitary peptide hormones, including GnRH.Materials and Methods: Analyses of association of 13 single nucleotide polymorphisms (SNPs) at the QPCT locuswith adjusted areal BMD (adj-aBMD) were carried out among 384 adult women. Linkage disequilibrium (LD) wasanalyzed by haplotype estimation and calculation of D? and r2. Multiple regression analysis was applied forevaluating the combined effects of the variations.Results and Conclusions: LD analysis indicated strong linkage disequilibrium within the entire 30-kb region of theQPCT gene. Significant correlations were observed between the genotypes of the six SNPs and the radial adj-aBMD,among which R54W (nt ? 160C?T) presented the most prominent association (p ? 0.0003). Striking associationwas observed for these SNPs among the 309 subjects ?50 years of age (R54W, p ? 0.0001; ?1095T?C, p ?0.0002; ?1844C?T, p ? 0.0002). Multiple regression analyses indicated that multiple SNPs in the gene might actin combination to determine the radial adj-aBMD. These results indicate that genetic variations in QPCT are theimportant factors affecting the BMD of adult women that contribute to susceptibility for osteoporosis. The datashould provide new insight into the etiology of the disease and may suggest a new target to be considered duringtreatment.J Bone Miner
Cellular Delivery of Doxorubicin via pH-Controlled Hydrazone Linkage Using Multifunctional Nano Vehicle Based on Poly(β-L-Malic Acid).
Authors: Muungo Lungwani
Published: June 2020

Doxorubicin (DOX) is currently used in cancer chemotherapy to treat manytumors and shows improved delivery, reduced toxicity and higher treatment efficacy whenbeing part of nanoscale delivery systems. However, a major drawback remains its toxicityto healthy tissue and the development of multi-drug resistance during prolonged treatment.This is why in our work we aimed to improve DOX delivery and reduce the toxicity bychemical conjugation with a new nanoplatform based on polymalic acid. For delivery intorecipient cancer cells, DOX was conjugated via pH-sensitive hydrazone linkage alongwith polyethylene glycol (PEG) to a biodegradable, non-toxic and non-immunogenicnanoconjugate platform: poly(β-L-malic acid) (PMLA). DOX-nanoconjugates were foundstable under physiological conditions and shown to successfully inhibit in vitro cancercell growth of several invasive breast carcinoma cell lines such as MDA-MB-231 andMDA-MB- 468 and of primary glioma cell lines such as U87MG and U251.
Clinical significance of amyloid precursor protein in patients with testicular germ cell tumor.
Authors: Muungo Lungwani
Published: June 2020

Testicular cancer is a relatively rare cancer that accountsfor approximately 1–1.5% of male cancers, and 90–95%of these cancers are testicular germ cell tumors (TGCTs)[1]. TGCTs can be classified into two major histologicalcategories, namely, seminomatous germ cell tumor (SGCT)and nonseminomatous germ cell tumor (NGCT). NGCTs,which include yolk sac tumors, embryonal cell carcinomas,teratomas, and choriocarcinomas, are different from SGCTswith regard to clinical characteristics and therapy required.Amyloid precursor protein (APP) is a type 1transmembrane protein that is considered to play a key rolein Alzheimer’s disease. It has multiple isoforms attributableto alternative splicing and is expressed in various types ofhuman cells. APP695 predominantly exists in the neuronswhereas other isoforms such as the APP751 and APP770are expressed in nonneuronal cells [2]. The biological roleof APP is not well understood. APP and its cleaved formshave been suggested to mediate various functions, includingcell adhesion [3], cell signaling [4], and cell growth [5–7].These functions are important in carcinogenesis, and APPexpression may be involved in the development of variouscancers [8–13].We have previously shown that APP is a primaryandrogen-responsive gene that promotes the growth of2 Advances in Urologyprostate cancer cells [14]. In the present study, we investigatedAPP immunoreactivity (IR) and APP mRNA expression inTGCTs and evaluated its clinical significance.
Prognostic phenotypic and genotypic factors associated with photodynamic therapy response in patients with age-related macular degeneration
Authors: Muungo Lungwani
Published: June 2020

Background: This study aimed to demonstrate the phenotypic and genotypic factors associated with photodynamic therapy (PDT) for age-related macular degeneration (AMD).Methods: The study included 149 patients with exudative AMD treated by PDT. Eight phenotypic factors and ten genotypic factors for three single nucleotide polymorphisms (SNPs; rs800292, rs1061170, rs1410996) in the complement factor H (CFH) gene, rs 11200638-SNP in the high temperature requirement A-1 (HTRA1) gene, two SNPs (rs699947, rs2010963) in the vascular endothelial growth factor (VEGF) gene, and four SNPs (rs12948385, rs12150053, rs9913583, rs1136287) in the pigment epithelium-derived factor (PEDF) gene were evaluated.Results: A significant association with best-corrected visual acuity change was demonstrated in the greatest linear dimension, presence or absence of pigment epithelial detachment, and HTRA1-rs11200638 genotype statistically (P=3.67×10-4, 1.95×10-2, 1.24×10-3, respectively). Best-corrected visual acuity in patients with AA genotype of HTRA1-rs11200638 significantly decreased compared with that in patients with GG genotype (P=1.33×10-3). Logistic regression analyses demonstrated HTRA1-rs11200638 genotype was most strongly associated with best-corrected visual acuity outcome from baseline at 12 months after photodynamic therapy (P=4.60×10-3; odds ratio 2.363; 95% confidence interval 1.303–4.285).Conclusion: The HTRA1-rs11200638 variant showed the most significant association. Therefore, this variant may be used as a prognostic factor to estimate the PDT response with significant predictive power.Keywords: age-related macular degeneration, photodynamic therapy, phenotypic and genotypic factors, high temperature requirement A-1, greatest linear dimension, pigment epithelial detachment
Differential regulation of CpG island methylation within divergent and unidirectional promoters in colorectal cancer
Authors: Muungo Lungwani
Published: June 2020

The silencing of tumor suppressor genes by promoter CpG island (CGI) methylation isan important cause of oncogenesis. Silencing of MLH1 and BRCA1, two examples ofoncogenic events, results from promoter CGI methylation. Interestingly, both MLH1and BRCA1 have a divergent promoter, from which another gene on the oppositestrand is also transcribed. Although studies have shown that divergent transcriptionis an important factor in transcriptional regulation, little is known about its implicationin aberrant promoter methylation in cancer. In this study, we analyzed the methylationstatus of CGI in divergent promoters using a recently enriched transcriptomedatabase. We measured the extent of CGI methylation in 119 colorectal cancer (CRC)clinical samples (65 microsatellite instability high [MSI-H]CRC with CGI methylatorphenotype, 28 MSI-HCRC without CGI methylator phenotype and 26 microsatellitestable CRC) and 21 normal colorectal tissues using Infinium MethylationEPICBeadChip. We found that CGI within divergent promoters are less frequently methylatedthan CGI within unidirectional promoters in normal cells. In the genome of CRCcells, CGI within unidirectional promoters are more vulnerable to aberrant methylationthan CGI within divergent promoters. In addition, we identified three DNA sequencemotifs that correlate with methylated CGI. We also showed that methylatedCGI are associated with genes whose expression is low in normal cells. Thus, we hereprovide fundamental observations regarding the methylation of divergent promotersthat are essential for the understanding of carcinogenesis and development of cancerprevention strategies.
Secondary prevention in the clinical management of patients with cardiovascular diseases. Core components, standards and outcome measures for referral and delivery
Authors: Muungo Lungwani
Published: June 2020

Despite major improvements in diagnostics and interventional therapies, cardiovascular diseases remain a major healthcare and socio-economic burden both in western and developing countries, in which this burden is increasing in closecorrelation to economic growth. Health authorities and the general population have started to recognize that the fightagainst these diseases can only be won if their burden is faced by increasing our investment on interventions in lifestylechanges and prevention. There is an overwhelming evidence of the efficacy of secondary prevention initiatives includingcardiac rehabilitation in terms of reduction in morbidity and mortality. However, secondary prevention is still too poorlyimplemented in clinical practice, often only on selected populations and over a limited period of time. The developmentof systematic and full comprehensive preventive programmes is warranted, integrated in the organization ofnational health systems. Furthermore, systematic monitoring of the process of delivery and outcomes is a necessity.
Androgen‐responsive tripartite motif 36 enhances tumor‐suppressive effect by regulating apoptosis‐related pathway in prostate cancer
Authors: Muungo Lungwani
Published: June 2020

Tripartite motif 36 (TRIM36) belongs to the TRIM family, most members of which areinvolved in ubiquitination and degradation of target proteins by functioning as E3ubiquitin ligases. The function of TRIM36 has not been well documented, therefore,we investigated the clinical significance and function of TRIM36 in human prostatecancer (PC). Multivariate logistic regression analysis showed that TRIM36 immunoreactivitywas an independent predictor of cancer-specificsurvival of PC patients.Gain-of-functionstudy revealed that overexpression of TRIM36 suppressed cell proliferationand migration of LNCaP, 22Rv1, and DU145 cells. Moreover, TRIM36knockdown using siRNA suppressed apoptosis and promoted cell proliferation andmigration in LNCaP and 22Rv1 cells. Furthermore, our microarray analysis revealedthat the apoptosis-relatedpathway was significantly upregulated by TRIM36 overexpression.The TUNEL assay showed that apoptosis promoted by docetaxel treatmentwas alleviated in siTRIM36-treatedLNCaP and 22Rv1 cells. Taken together, theseresults suggest that high expression of TRIM36 is associated with favorable prognosisand that TRIM36 plays a tumor-suppressiverole by inhibiting cell proliferation andmigration as well as promoting apoptosis in PC.
Estrogen responsive finger protein as a new potential biomarker for breast cancer
Authors: Muungo Lungwani
Published: June 2020

Purpose: Estrogen-responsive finger protein (Efp) is amember ofRINGfinger-B box-Coiled Coilfamily and is also a downstream target of estrogen receptor a. Previously, Efp was shown tomediate estrogen-induced cell growth, which suggests possible involvement in the developmentof human breast carcinomas. In this study, we examined expression of Efp in breast carcinomatissues and correlated these findings with various clinicopathologic variables.Experimental Design: Thirty frozen specimens of breast carcinomas were used for immunohistochemistryand laser capture microdissection/real-time PCR of Efp. Immunohistochemistryfor Efp was also done in 151breast carcinoma specimens fixed with formalin and embedded inparaffinwax.Results: Efp immunoreactivity was detected in breast carcinoma cells and was significantlyassociated with the mRNA level (n = 30). Efp immunoreactivity was positively associated withlymph node status or estrogen receptor a status and negatively correlated with histologic gradeor 14-3-3j immunoreactivity (n = 151). Moreover, Efp immunoreactivity was significantly correlatedwith poor prognosis of breast cancer patients, and multivariate analyses of disease-freesurvival and overall survival for151breast cancer patients showed that Efp immunoreactivity wasthe independentmarker.Conclusions: Our data suggest that Efp immunoreactivity is a significant prognostic factor inbreast cancer patients. These findings may account for an oncogenic role of Efp in the tumorprogression of breast carcinoma.
Building the future of financial healthcare technology practices
Authors: Inkster Becky , Stevenson Andrea , Mateen Bilal A. , Loo Peggy
Published: June 2020

Given the demands for services that intersect financial health and well-being, and that people are increasingly operationalizing their digital footprints, we argue for the co-evolution of healthcare practices and financial technology. Innovation bridged across finance, health and technology could inform new practice/operating models, whilst fostering environments that value and prioritize health, financial stability and individual privacy.
Advancing the global communication of scholarship and research for personalized healthcare The International Journal of Person Centered Medicine.
Authors: Muungo Lungwani
Published: June 2020

A simple Google search using the phrase ‘TheFoundational Philosophy of Medicine’ yields 1,510,000results. If one omits the word ‘Foundational’, then thesearch result yields 11,900,000 items. Certainly, muchmaterial of varying scholarship and complexity has beenwritten over the course of two millennia on this veryparticular subject, not all of which is immediatelyaccessible, not even through Google. Yet the fundamentalphilosophy of medicine can also be articulated very simplyand indeed has been and in the following few words: ‘tocure sometimes, to relieve often, to comfort always’.Originally attributed to Hippocrates, this striking maximhas become more closely associated in recent times withEdward Livingstone Trudeau, a nineteenth Centuryphysician who, retiring to Saranac Lake in the Adirondackmountains of New York in order to palliate histuberculosis, founded several important health facilitiesduring his remaining lifetime which continue in existencetoday.In our more modern times, the original maxim mustsurely be prefaced with ‘To prevent illness where possible’and may also come with time to be concluded with: ‘Toassist death when necessary’. If we accept the imperativefor the former as universally established (the latterremaining the subject of intensive ongoing ethical, legaland emotional debate), then are we able to say thatmodern medicine fulfils these four conceptually different,though highly interrelated missions? It would be difficult,in our view, to answer correctly and honestly in theaffirmative. Certainly, since Fleming’s discovery ofpenicillin in 1928 and the publication of the scienceunderlying the clinical use of radiation by Marie Curie forwhich she achieved the Nobel Prize in Physics in 1903 andfor Chemistry in 1911, there have been staggeringadvances in pharmacotherapeutics and medical technologythat have revolutionised the scope, possibility and power ofclinical practice. Yet despite such unprecedented andastonishing progress, it would be difficult to deny thatmodern medicine has not entered into crisis: a crisis ofcaring, a crisis of compassion and a crisis of costs. Indeed,the perception that major distortions have occurred in theunderstanding of the purpose of modern medicine [1], hasbeen accompanied by much soul searching, leading Miles,in an address to La Sapienza at Rome, to pose threedistinct and initially
Research, development and evaluation strategies for pharmaceutical education and the workforce a global report
Authors: Muungo Lungwani
Published: June 2020

The International Pharmaceutical Federation (FIP) hosted the first Global Conference on Pharmacy and Pharmaceutical SciencesEducation in Nanjing, China, on 7 & 8 November 2016. The global conference was an exceptional event that gathered pharmacyleaders from around the world to create a globally shared vision for transformative pharmacy and pharmaceutical scienceseducation.Following an extensive consensus-based consultation process, three critical documents that set the future milestones forworkforce development through education were adopted at the global conference: (1) a Global Vision for Education andWorkforce, (2) Pharmaceutical Workforce Development Goals, and (3) Statements on Pharmacy and Pharmaceutical SciencesEducation ("the Nanjing Statements").The global vision describes the future directions of our profession and how education can support the evolution of scienceand practice. A set of 13 Pharmaceutical Workforce Development Goals aim to facilitate the implementation of the global visionthrough a series of measurable, feasible and tangible goals. The Nanjing Statements are a set of 67 statements that describean envisioned future for education, to enable the enhancement of professional education standards worldwide.A full report of the global conference, “Transforming Pharmacy and Pharmaceutical Sciences Education in the Contextof Workforce Development”, was launched in May 2017. Through the report, FIP calls on leaders in pharmacy practice,pharmaceutical education and other key stakeholders to support and advocate the implementation of these key outcomes intheir countries.Under the aegis of FIP Education (FIPEd), FIP is committed to inform, guide and support the strategic planning andimplementation of the outcomes to facilitate the transformation of the global pharmaceutical workforce in line with overallhealth workforce strategies promoted by national and international agencies.Research, development and evaluation are key mechanisms for strategy implementation and this report widens the evidencebase for research, development and evaluation strategies for pharmaceutical education and the workforce. With evidence-basedexpert recommendations and comprehensive case studies from 21 countries around the world, the report provides guidanceon aligning national research, development and evaluation projects with the global vision and Pharmaceutical WorkforceDevelopment Goals.
Macrophage migration inhibitory factor (MIF) promotes cell survival and proliferation of neural stem/progenitor cells
Authors: Muungo Lungwani
Published: June 2020

In a previous study, we showed that murine dendritic cells (DCs) can increase the number of neural stem/progenitor cells (NSPCs) in vitroand in vivo. In the present study, we identified macrophage migration inhibitory factor (MIF) as a novel factor that can support theproliferation and/or survival of NSPCs in vitro. MIF is secreted by DCs and NSPCs, and its function in the normal brain remains largelyunknown. It was previously shown that in macrophages, MIF binds to a CD74–CD44 complex. In the present study, we observed theexpression of MIF receptors in mouse ganglionic-eminence-derived neurospheres using flow cytometry in vitro. We also found CD74expression in the ganglionic eminence of E14 mouse brains, suggesting that MIF plays a physiological role in vivo. MIF increased thenumber of primary and secondary neurospheres. By contrast, retrovirally expressed MIF shRNA and MIF inhibitor (ISO-1) suppressedprimary and secondary neurosphere formation, as well as cell proliferation. In the neurospheres, MIF knockdown by shRNA increasedcaspase 3/7 activity, and MIF increased the phosphorylation of Akt, Erk, AMPK and Stat3 (Ser727), as well as expression of Hes3 and Egfr,the products of which are known to support cell survival, proliferation and/or maintenance of NSPCs. MIF also acted as a chemoattractantfor NSPCs. These results show that MIF can induce NSPC proliferation and maintenance by multiple signaling pathways actingsynergistically, and it may be a potential therapeutic factor, capable of activating NSPC, for the treatment of degenerative brain disorders.
Health Practices and Vaginal Microbicide Acceptability among Urban Black Women
Authors: Muungo Lungwani
Published: June 2020

Background: Intravaginal topical microbicides are being investigated for prevention of HIV transmission. Useof vaginal microbicides will constitute a new type of practice, occurring in the context of other vaginal practicesrelated to contraception, hygiene, and self-care, which are affected by cultural norms and personal beliefs.Given the high rate of HIV infection among black women, research on practices and decision making relevantto microbicide acceptability is needed in this population.Methods: Twenty-three black women in New York City, aged 25–64, completed in-person semistructured interviewsand self-administered questionnaires. Quantitative analyses examined vaginal practices and willingnessto use microbicides. Qualitative analyses explored underlying decision-making processes involved inchoices regarding vaginal practices and general healthcare.Results: Willingness to use vaginal products for HIV prevention was high, especially among more educatedwomen. Safety was a major concern, and women were cautious about using vaginal products. Whereas someviewed synthetic products as having potentially harmful side effects, others perceived natural products as riskybecause of insufficient testing. Choices about vaginal practices were affected by assessments of risk and efficacy,prior experience, cultural background, and general approach to healthcare.Conclusions: The majority of women in the sample expressed willingness to use a vaginal product for HIV prevention.Decision-making processes regarding vaginal practices were complex and were affected by social, cultural,and personal factors. Although specific preferences may vary, attitudes toward using a vaginal productare likely to be positive when side effects are minimal and the product is considered safe.
A novel ACT-based video game to support mental health through embedded learning: A mixed-methods feasibility study protocol
Authors: Edwards Darren , Kemp Andrew Haddon
Published: June 2020

Introduction: In recent years, serious video games have been utilised to promote emotional regulation in individuals with mental health issues. Though these therapeutic strategies are innovative, they are limited in the scope of treatment, often focusing on specific cognitive skills, to help remediate a specific mental health disorder. Objective: Here, a protocol is proposed, which assesses the feasibility of a novel ACT-based video game for young adults. Methods and analysis: The MRC framework will be utilised for developing a complex intervention, to design and test the feasibility of an ACT-based video game intervention using a mixed-methods approach involving qualitative and quantitative data. The primary outcomes will include feasibility testing of recruitment processes and the acceptability of the intervention through qualitative interviews, attendance, and rates of attrition. Secondary outcomes will involve a series of quantitative questionnaires to obtain effect sizes for power analysis, allowing for the ideal sample size for a full randomized controlled trial to be determined. Ethics and Dissemination: This study has received approval from the College of Human and Health Sciences at Swansea University in the United Kingdom. Dissemination activities will involve publications in peer reviewed journals, presentations at local and national conferences, and promotion through social media.
The effects of Kigelia africana fruit extract on blood glucose in diabetes induced mices
Authors: Muungo Lungwani
Published: June 2020

Objective of this study was to determine the effect Kigelia africana fruit extract has on blood glucose levels ofdiabetes mice and its phytochemical profile. Mice were induced with diabetes using Alloxan monohydrate90mg/kg. Blood glucose was checked before induction and 72 hours after induction to confirm diabetes. Treatmentinvolved using oral administration of Kigelia fruit extract 1000mg/kg, Kigelia fruit extract 500mg/kg,Glibenclamide 0.25 mg/kg, Kigelia fruit extract 500mg/kg and Glibenclamide 0.25mg/kg and Normal Saline. Theresults showed a greater reduction in blood glucose of mice after treatment with Kigelia extract 1000mg/kgcompared to Kigelia 500mg/kg [(5.3 +/- 0.5mmol/l) vs (6.3+/- 0.6mmol/l), (p= 0.005)]. Further, Glibenclamide0.25mg/kg showed less reduction in blood glucose than Kigelia 1000mg/kg [(7.4+/-0.9mmol/l) vs (5.3 +/- 0.5), (p=0.00)]. The mean blood glucose levels were lower in mice that received Kigelia extract than those that receivedboth Kigelia extract and Glibenclamide [(5.3 +/- 0.5mmol/l) vs (7.8 +/- 0.6 mmol/l), (p=0.00)]. The fruit extracttested positive for Tannins, Saponins, Flavanoids, Alkaloids, Glycosides and Steroids. Findings of this studyindicate that Kigelia africana fruit extract causes reduction in blood glucose of diabetes induced mice and givesbetter results when used alone than in concomitant use with Glibenclamide. The study also indicates that the fruitextract has alkaloids, saponins, steroids, glycosides, tannins and flavonoids.
TET2 repression by androgen hormone regulates global hydroxymethylation status and prostate cancer progression
Authors: Muungo Lungwani
Published: June 2020

Modulation of epigenetic patterns has promising efficacy for treating cancer. 5-Hydroxymethylatedcytosine (5-hmC) is an epigenetic mark potentially important in cancer. Herewe report that 5-hmC is an epigenetic hallmark of prostate cancer (PCa) progression.A member of the ten–eleven translocation (TET) proteins, which catalyse the oxidation ofmethylated cytosine (5-mC) to 5-hmC, TET2, is repressed by androgens in PCa. Androgenreceptor (AR)-mediated induction of the miR-29 family, which targets TET2, are markedlyenhanced in hormone refractory PCa (HRPC) and its high expression predicts poor outcomeof PCa patients. Furthermore, decreased expression of miR-29b results in reduced tumourgrowth and increased TET2 expression in an animal model of HRPC. Interestingly, global5-hmC modification regulated by miR-29b represses FOXA1 activity. A reduction in 5-hmCactivates PCa-related key pathways such as mTOR and AR. Thus, DNA modification directlylinks the TET2-dependent epigenetic pathway regulated by AR to 5-hmC-mediated tumourprogression.
Increased expression of estrogen-related receptor a (ERRa) is a negative prognostic predictor in human prostate cancer
Authors: Muungo Lungwani
Published: June 2020

The nuclear receptor ERRa (estrogen-related receptor a) isknown to modulate the estrogen-signaling pathway, but the biologicalsignificance of ERRa in the prostate remains unclear. Weinvestigated the expression of ERRa in human prostate tissuesand cancer cell lines to evaluate the potential roles of the receptorin prostate cancer (PC). Western blot analysis of ERRa was performedin three cell lines of human PC (LNCaP, DU145 and PC-3). The expressions of ERRa in cancerous lesions (n 5 106) andbenign foci (n 5 99) of 106 surgically obtained prostate specimenswere evaluated by immunohistochemistry. The relationshipsbetween the ERRa expression and clinicopathological featureswere evaluated. Western blot analysis using the polyclonal anti-ERRa antibody detected a 52 kD band in all three PC cell lines.Positive immunostaining of ERRa in the nuclei was found in 73(69%) cancerous and 47 (47.5%) benign epithelium, whereas thestromal tissues were negative for ERRa. The mean immunoreactivityscore (IR score) of the cancerous lesions (3.5 6 2.6) was significantlyhigher than that of the benign foci (1.8 6 2.1) (p <0.0001). The IR score of the cancerous lesions significantly correlatedwith the Gleason score (p 5 0.0135). Univariate and multivariatehazard analyses revealed significant correlations betweenelevated ERRa expression and poor cancer-specific survival (p 50.0141 and 0.0367, respectively). The enhanced expression ofERRa might play a role in the development of human PC andserve as a significant prognostic factor for the disease.' 2007 Wiley-Liss, Inc.
Mutant IDH is sufficient to initiate enchondromatosis in mice
Authors: Muungo Lungwani
Published: June 2020

Enchondromas are benign cartilage tumors and precursors tomalignant chondrosarcomas. Somatic mutations in the isocitratedehydrogenase genes (IDH1 and IDH2) are present in the majorityof these tumor types. How these mutations cause enchondromasis unclear. Here, we identified the spectrum of IDH mutations inhuman enchondromas and chondrosarcomas and studied theireffects in mice. A broad range of mutations was identified, includingthe previously unreported IDH1-R132Q mutation. These mutationsharbored enzymatic activity to catalyze α-ketoglutarate toD-2-hydroxyglutarate (D-2HG). Mice expressing Idh1-R132Q in oneallele in cells expressing type 2 collagen showed a disorderedgrowth plate, with persistence of type X-expressing chondrocytes.Chondrocyte cell cultures from these animals or controls showedthat there was an increase in proliferation and expression of genescharacteristic of hypertrophic chondrocytes with expression ofIdh1-R132Q or 2HG treatment. Col2a1-Cre;Idh1-R132Q mutantknock-in mice (mutant allele expressed in chondrocytes) did notsurvive after the neonatal stage. Col2a1-Cre/ERT2;Idh1-R132 mutantconditional knock-in mice, in which Cre was induced by tamoxifenafter weaning, developed multiple enchondroma-like lesions.Taken together, these data show that mutant IDH or D-2HG causespersistence of chondrocytes, giving rise to rests of growth-platecells that persist in the bone as enchondromas.
Safety_and_Pharmacokinetics_of_Dapivirine_Delivery.7
Authors: Muungo Lungwani
Published: June 2020

Vaginal microbicides for the prevention of HIV transmission maybe an important option for protecting women from infection.Incorporation of dapivirine, a lead candidate nonnucleoside reversetranscriptase inhibitor, into intravaginal rings (IVRs) for sustainedmucosal delivery may increase microbicide product adherence andefficacy compared with conventional vaginal formulations. Twentyfourhealthy HIV-negative women 18–35 years of age were randomlyassigned (1:1:1) to dapivirine matrix IVR, dapivirine reservoir IVR,or placebo IVR. Dapivirine concentrations were measured in plasmaand vaginal fluid samples collected at sequential time points over the33-day study period (28 days of IVR use, 5 days of follow-up). Safetywas assessed by pelvic/colposcopic examinations, clinical laboratorytests, and adverse events. Both IVR types were safe and well toleratedwith similar adverse events observed in the placebo and dapivirinegroups. Dapivirine from both IVR types was successfully distributedthroughout the lower genital tract at concentrations over 4 logs greaterthan the EC50 against wild-type HIV-1 (LAI) in MT4 cells. Maximumconcentration (Cmax) and area under the concentration–time curve(AUC) values were significantly higher with the matrix than reservoirIVR. Mean plasma concentrations of dapivirine were ,2 ng/mL.These findings suggest that IVR delivery of microbicides is a viableoption meriting further study.Key Words: dapivirine, HIV, intravaginal ring, microbicide,pharmacokinetics, prevention
Association of bone mineral density with a dinucleotide repeat polymorphism at the calcitonin (CT ) locus
Authors: Muungo Lungwani
Published: June 2020

Calcitonin (CT), a calcium-regulating hormone,lowers the calcium level in serum by inhibiting bone resorption.Because CT may play a role in the pathogenesis ofosteoporosis, genetic variations in or adjacent to the CTgene may be associated with variations in bone mineraldensity (BMD). The present study examined the correlationbetween a dinucleotide (cytosine-adenine; CA) repeatpolymorphism at the CT locus and BMD in 311 Japanesepostmenopausal women (mean age, 64.1 years). Seven alleleswere present in this population; each allele contained 10,11, 16, 17, 18, 19, or 20 CA repeats. Thus, we designated therespective genotypes A10, A11, A16, A17, A18, A19, andA20. The A10 and A17 alleles were the predominant allelesin the population studied. Z scores (a parameter representingdeviation from the age-specific weight-adjusted averageBMD) were compared between individuals that possessedone or two alleles of each genotype and those that did notpossess the allele. Subjects who possessed one or two A10alleles had lower BMD Z scores than those who did not(lumbar 2–4 BMD Z score; 20.148 6 1.23 vs 0.182 6 1.54;P 5 0.04). No significant relationships were observedbetween allelic status and background data or biochemicalparameters. The significant association observed betweenBMD and genetic variations at the CT locus implies thatpolymorphism at this locus may be a useful marker for thegenetic study of osteoporosis.
The synergistic effect of bone mineral density and methylenetetrahydrofolate reductase (MTHFR) polymorphism (C677T) on fractures
Authors: Muungo Lungwani
Published: June 2020

A functional polymorphism in methylenetetrahydrofolatereductase (MTHFR) has been identifi ed at codon677 (C677T). The T-allele variant (valine type) has lowerenzyme activity than the wild type (C-allele or alaninetype), resulting in a slightly elevated homocysteine level,which has been recently recognized as a risk factor for fracture.However, whether subjects bearing the T allele havehigher susceptibility to fractures is still controversial. Wehave investigated the effects of MTHFR polymorphism onfracture susceptibility in Japanese postmenopausal women.A total of 502 postmenopausal ambulatory Japanese womenwere followed up for 5.1 ± 3.4 (mean ± SD) years, and atotal of 155 patients with incident fractures (121 patientswith vertebral fractures and 34 cases with fractures at othersites) were recorded. When compared with the patientswithout any fractures, the patients with incident fractureswere older, had more prevalent fractures, had higher urinarylevels of bone turnover markers as well as plasma homocysteinelevel, but were shorter in body height and had lowerbone mineral density. The prevalence of the TT genotypeof MTHFR was signifi cantly higher in the patients withincident fractures compared to the other genotypes. Thesubjects with the TT genotype had a higher incidence rateof fracture and higher plasma level of homocysteine thanthe subjects bearing the non-TT genotype. This relationshipwas observed in both osteoporotic and nonosteoporoticgroups. The hazard ratio for TT genotype without osteoporosis,non-TT genotype with osteoporosis, and TT genotypewith osteoporosis was 1.49 (0.91–2.45), 3.64 (2.50–5.29),and 7.21 (4.34–11.97), respectively, compared to the non-TTgenotype without osteoporosis. A higher hazard ratio forthe TT genotype with osteoporosis was still apparent afteradjustment for age, body size, and number of prevalentvertebral fractures. These results indicate that the TT genotypeof MTHFR may be a risk factor for future fracture inaddition to the traditional risk factors.