Miracle-dz/UniFAR-FTUs huggingface dataset:
Personalized medicine and genome-based treatments: Why personalized medicine ≠ individualized treatments

The sequencing of the human genome and decreasing costs of sequencing technology have led to the notion of ‘personalized medicine’. This has been taken by some authors to indicate that personalized medicine will provide individualized treatments solely based on one’s DNA sequence. We argue this is overly optimistic and misconstrues the notion of personalization. Such interpretations fail to account for economic, policy and structural constraints on the delivery of healthcare. Furthermore, notions of individualization based on genomic data potentially take us down the road of genetic reductionism obscuring the role of environmental factors in disease and ill health. We propose that one should see personalized medicine as a way of using personal genomic information to stratify individuals into subpopulations and suggest that personalized medicine be seen within a broader idea of personalized healthcare, reflecting healthcare that integrates personal genomic data into cultural, environmental and personal contexts.
Clinical and Translational Research and Community Engagement: Implications for Researcher Capacity Building

This research sought to better understand how clinical and translational research is defined and perceived by community service providers. In addition, the research sought to elicit how the perspectives of service providers may hinder or facilitate collaborative research efforts. The study employed a qualitative methodology, focus groups. A nonprobability sampling strategy was used to recruit participants from three neighborhoods in the Tufts University’s catchment area. Focus group findings add to the nascent body of literature on how community partners view clinical and translational research and researchers. Findings indicate that cultural disconnects, between researchers and community partners exist, as does mistrust, all of which serve as potential barriers to community research partnerships. This paper suggests rethinking the business of community engagement in researcher, particularly as it relates to building research capacity to approach, engage, and partner with communities. Clin Trans Sci 2012; Volume 5: 329–332
Combining anaerobic bacterial oncolysis with vaccination that blocks interleukin-10 signaling may achieve better outcomes for late stage cancer management

ABSTRACT Late stage solid tumors cause significant cancer mortality rates worldwide and effective therapy remains a big challenge. Cancer therapeutic vaccines elicit tumor specific T cells that kill tumor cells yet often fail to result in tumor destruction because of the limited T cell response and the local immune-suppressive environment. Blocking interleukin 10 (IL-10) signaling at the time of therapeutic vaccination elicits much stronger T cell responses than vaccination without IL-10 blocking. Anaerobic oncolytic bacteria target hypoxic regions of the late stage tumor tissues which not only stops tumor growth but also provides a pro-inflammatory environment that may increase the effectiveness of a therapeutic vaccine by recruiting more effector T cells to tumor site. In this review, we argue that combining both bacterial and vaccine therapies may improve the efficiency of late stage cancer management.
Prospective, Randomized, Double-Blind Trial of Local Anesthetic Infusion and Intravenous Narcotic Patient-Controlled Anesthesia Pump for Pain Management after Free TRAM Flap Breast Reconstruction

Background: This study assessed the efficacy of a continuous infusion pump system for postoperative pain control at muscle-sparing transverse rectus abdominis musculocutaneous (TRAM) flap donor sites. Methods: In this prospective, randomized, double-blind trial, a dual-catheter continuous infusion pump system was placed in the muscle-sparing TRAM flap donor-site area in all patients. Bupivacaine (0.375%; continuous infusion pump group) or isotonic saline (control group) was infused at 4 ml/hour. All patients also had a patient-controlled anesthesia system delivering intravenous narcotics on demand. Pain scores, patient satisfaction, narcotic use, milestones of surgical recovery, and side effects of narcotics were compared between the two groups. Results: Forty-eight patients were included in the study (23 continuous infusion pump patients and 25 control patients). The continuous infusion patients used less mean patient-controlled anesthesia narcotic during the first 2 postoperative days (78.0 mg versus 42.7 mg; p = 0.019) and transitioned earlier to oral narcotics than did control patients. Patients’ overall pain satisfaction scores were significantly better in the continuous infusion group than in the control group. There were no significant differences between groups with regard to overall abdominal pain intensity scores, total narcotic use, length of hospitalization, incidence of narcotic side effects, or milestones of surgical recovery. Conclusions: The continuous infusion pump system appears to be a safe and effective method for postoperative donor-site pain management in TRAM flap breast reconstruction patients and should be considered for postoperative donor-site pain management. However, continuous infusion pump local anesthetic delivery to the muscle-sparing TRAM flap donor site did not eliminate narcotic use for pain control.
Vaccine criticism on the Internet: Propositions for future research

ABSTRACT Research on vaccine criticism on the Internet is now at a crossroads, with an already important body of knowledge published on the subject but also a continuous and even growing interest in the scientific community. In this commentary, we reflect on the published literature from the standpoint of sociologists interested in social movements and their activists and the influence they can have on vaccination behaviors. We suggest several avenues of research for future studies of vaccine criticism on the Internet: 1) paying more attention to the actors who publish vaccine critical contents and to their use of the Internet in relationship to the other means through which they try to mobilize the population - the production of vaccine critical information on the Internet, and not only its nature and its reception, should therefore become one of the main objects of this strand of research -; 2) paying closer attention to what distinguishes the different strands of vaccine criticism regarding both what they dislike about vaccines (or about a given vaccine) and how this fight is integrated in a more general political or cultural struggle; 3) investigating further how the new forms of social interactions allowed by the Internet affect the transmission of vaccine related information and the capacity of vaccine critical actors to enroll members of the public in their political or cultural struggle.
Dose‐related Induction of Digital Malformations in Rats by 5‐Azacytidine: Description of the Defects

Abstract Dose‐related changes of 5‐azacytidine (5‐AC) induced digital malformations are reported. Dosages of 0.4, 0.5, 0.6, 0.7, and 1.0 mg/kg of 5‐AC were injected intraperitoneally into pregnant rats on day 13 of gestation. The susceptibility order of each digit was the second > third > first > fourth > fifth in the forepaw and the second > first > third ė fourth > fifth in the hindpaw. In the forepaw, the percentages of cutaneous syndactyly with closely apposed metacarpals or osseous syndactyly between the first and second digits (type FA defect) and brachydactyly of the third digit (type FB defect) were increased in a clear dose‐related trend. In the hindlimb, the percentages of osseous or cutaneous syndactyly between the first and second digits (type HA defect), brachydactyly or ametatarsia of the second digit (type HB defect), and osseous or cutaneous syndactyly, closely apposed metacarpals, lateral metacarpal fusion, or osseous or cutaneous syndactyly with lateral metacarpal fusion or closely apposed metacarpals between the third and fourth digits (type HC defect) reached a maximum at 0.7 mg/kg of 5‐AC and then decreased. However, the percentages of ectrodactyly, 1 missing digit (type M1 defect) or 2 missing digits (type M2 defect), were increased from 0.6 mg/kg or 0.7 mg/kg, respectively. Ectrodactyly, missing 3 digits (type M3 defect), was rarely observed in the dose range used.
Prevalence of Elder Mistreatment as Reported by Social Workers in a Probability Sample of Adult Day Health Care Clients

ABSTRACT There are growing numbers of Adult Day Health Care (ADHC) programs providing needed health services to community-dwelling elderly. Therefore, ADHC staff are in an opportune position to identify and to intervene in suspected elder mistreatment (EM) cases. In this paper, prevalence estimates of EM are reported for a probability sample of ADHC clients in New York State, using data provided during a social worker informant interview. The abuse “signs and symptoms” items in the social worker informant interview schedule were divided into two categories: (1) physical indicators and (2) client's behavioral indicators. Physical indicators included unexplained bruises and welts, unexplained burns, unexplained lacerations or abrasions, human bite marks, and frequent injuries that are “accidental” or “unexplained. ” Client's behavioral indicators included apprehension, being frightened, and afraid to go home. EM prevalence for all 8 items was 12.3 percent. When “apprehensive” was excluded, the EM prevalence was 3.6 percent in this sample. These findings suggest that ADHC provides a point of contact for the assessment and intervention of EM that might otherwise be overlooked among elders who are often isolated or homebound.
Medicine counseling services at Tertiary care Hospital in Nepal

Background and Objectives : Patient needs specific guidelines from their pharmacist in support of better compliance of their medicine used. Counseling of the patient and patient representative is important for improving the therapeutic out comes. Counseling patients can improve their understanding regarding medication, disease and life style modifications which in turn improves compliance. Material and Methods: Patients and/or patient party were counseled as per the Omnibus Budget Reconciliation Act-1990 guidelines. The data was collected as per OBRA-90 during the period of eighteen month and was analyzed using statistical software SPSS version 17. Results: Three hundred and fifty patients were counseled during the study period. Majority of the counseled patients were females [75.9%]. Mean counseling time taken by the pharmacist was 7.43 minute. Minimum time taken to counsel the patient was 6-10 minutes in 58.41% of the counseled, followed by less than 5 minutes in 19.68% and 11-15 minutes in 8.89%. About 10.47% were counseled for more than 15 minutes by the pharmacist. Greater numbers of the patients referred to the Medicine Counseling Center (MCC) were from Obstetrics and Gynecology departments and most of them were directed by doctors [50.47%]. Conclusion: This study highlights that role of doctor is important to encourage patient to attend counseling services. Counseling is the integral part that not only help patient to understand the use of their medicine but also to improve their therapeutic out comes. The effect of counseling on compliance should be studied in future. DOI: http://dx.doi. org/10.3126/jmcjms.v1i1. 7881 Janaki Medical College Journal of Medical Sciences (2013) Vol. 1 (1):14-20
A safe and efficient BCG vectored vaccine to prevent the disease caused by the human Respiratory Syncytial Virus

Abstract The human Respiratory Syncytial Virus (hRSV) causes lower respiratory tract infections including pneumonia and bronchiolitis. Such infections also cause a large number of hospitalizations and affects mainly newborns, young children and the elderly worldwide. Symptoms associated with hRSV infection are due to an exacerbated immune response characterized by low levels of IFN-γ, recruitment of neutrophils and eosinophils to the site of infection and lung damage. Although hRSV is a major health problem, no vaccines are currently available. Different immunization approaches have been developed to achieve a vaccine that activates the immune system, without triggering an unbalanced inflammation. These approaches include live attenuated vaccine, DNA or proteins technologies, and the use of vectors to express proteins of the virus. In this review, we discuss the host immune response to hRSV and the immunological mechanisms underlying an effective and safe BCG vectored vaccine against hRSV.
Type III hypersensitivity reactions to a B cell epitope antigen are abrogated using a depot forming vaccine platform

ABSTRACT Peptide antigens are combined with an adjuvant in order to increase immunogenicity in vivo. The immunogenicity and safety of a RSV vaccine formulated in a novel oil-based platform, DepoVax™ (DPX), was compared to an alum formulation. A peptide B cell epitope derived from RSV small hydrophobic ectodomain (SHe) served as the antigen. Both vaccines induced SHe-specific antibodies after immunization of mice. A single dose of the DPX-based formulation resulted in anti-SHe titres for up to 20 weeks. Boosting with Alum-SHe, but not with DPX-SHe, led to unexpected clinical signs such as decreased activity, cyanosis and drop in body temperature in mice but not in rabbits. The severity of adverse reactions correlated with magnitude of SHe-specific IgG immune responses and decreased complement component 3 plasma levels, indicating a type III hypersensitivity reaction. By RP-HPLC analysis, we found that only 8–20% of the antigen was found to be adsorbed to alum in vitro, indicating that this antigen is likely released systemically upon injection in vivo. Clinical signs were not observed in rabbits, indicating the response correlates with peptide dose relative to size of animal. These results suggest that peptide antigens targeted to produce B cell mediated response may result in increased incidence of type III hypersensitivity reactions when delivered in non-depot forming vaccines. The DPX formulation induced strong antibody titres to the antigen without causing adverse events, likely due to the strength of the depot in vivo, and demonstrates the potential safety and immunogenicity of this platform for B cell peptide antigens.
The knowledge level reinterpreted: Modeling socio‐technical systems

Knowledge acquisition is a process of developing qualitative models of systems in the world—physical, social, technological—often for the first time, not extracting facts and rules that are already written down and filed away in an expert's mind. Models of reasoning describe how people behave—how they interactively gather evidence by looking and asking questions, represent a situation by saying and writing things, and plan to act in some environment. But such models are inherently brittle mechanisms: Human reinterpretation of rules and procedures is metaphorical, based on prelinguistic perceptual categorization and nondeliberated sensory‐motor coordination. This view of people, relative to computer models, yields an alternative view of what tools can by and the tool design process. Knowledge engineers are called to participate with social scientists and workers in the codesign of the workplace and tools for enhancing worker creativity and response to unanticipated situations. the emphasis is on augmenting human capabilities as they interact with each other to construct new conceptualizations—facilitating conversations, not just automating routine behavior. Software development in the context of use maintains connection to nontechnical, social factors such as ownership of ideas and authority to participate. the role of knowledge engineering is not merely “capturing knowledge” in a program delivered by technicians to users. Rather, we seek to develop tools that help people in a community in their everyday practice of creating new understandings and capabilities, new forms of knowledge. © 1993 John Wiley & Sons, Inc.
Progress toward a group B streptococcal vaccine

Abstract Streptococcus agalactiae (group B Streptococcus, GBS) is a leading cause of severe invasive disease in neonate, elderly, and immunocompromised patients worldwide. Despite recent advances in the diagnosis and intrapartum antibiotic prophylaxis (IAP) of GBS infections, it remains one of the most common causes of neonatal morbidity and mortality, causing serious infections. Furthermore, recent studies reported an increasing number of GBS infections in pregnant women and elderly. Although IAP is effective, it has several limitations, including increasing antimicrobial resistance and late GBS infection after negative antenatal screening. Maternal immunization is the most promising and effective countermeasure against GBS infection in neonates. However, no vaccine is available to date, but two types of vaccines, protein subunit and capsular polysaccharide conjugate vaccines, were investigated in clinical trials. Here, we provide an overview of the GBS vaccine development status and recent advances in the development of immunoassays to evaluate the GBS vaccine clinical efficacy.
A centre for provision of assistive technology services in Singapore

Abstract Traditionally, persons with acquired disabilities in Singapore receive rehabilitation services at Rehabilitation Centres or Community Hospitals. They would be prescribed activities of daily living aids and mobility aids to improve their independence in their day-to-day activities. Assistive Technology (AT) devices were not considered as a part of rehabilitation as therapists lacked the knowledge and resources in prescribing appropriate technological solutions to their clients. The services of the Specialised Assistive Technology Centre (ATC) at the Society for the Physically Disabled (SPD) have changed this perspective and greatly improved service provision and awareness. This article highlights the role of occupational therapists in the provision of AT to complement rehabilitation therapy services for persons with disabilities and in improving rehabilitation outcomes related to AT usage for this population.
Recent advances in the production of recombinant subunit vaccines in Pichia pastoris

ABSTRACT Recombinant protein subunit vaccines are formulated using defined protein antigens that can be produced in heterologous expression systems. The methylotrophic yeast Pichia pastoris has become an important host system for the production of recombinant subunit vaccines. Although many basic elements of P. pastoris expression system are now well developed, there is still room for further optimization of protein production. Codon bias, gene dosage, endoplasmic reticulum protein folding and culture condition are important considerations for improved production of recombinant vaccine antigens. Here we comment on current advances in the application of P. pastoris for the synthesis of recombinant subunit vaccines.
Optimizing object classification under ambiguity/ignorance: application to the credit rating problem

A nascent technique for object classification is employed to exposit the classification of US banks to their financial strength ratings, presented by the Moody's Investors Services. The classification technique primarily utilized, called CaRBS (classification and ranking belief simplex), allows for the presence of ignorance to be inherent. The modern constrained optimization method, trigonometric differential evolution (TDE), is adopted to configure a CaRBS system. Two different objective functions are considered with TDE to measure the level of optimization achieved, which utilize differently the need to reduce ambiguity and/or ignorance inherently during the optimization process. The appropriateness of the CaRBS system to analyse incomplete data is also highlighted, with no requirement to impute any missing values or remove objects with missing values inherent. Comparative results are also presented using the well-known multivariate discriminant analysis and neural network models. The findings in this study identify a novel dimension to the issue of object classification optimization, with the discernment between the concomitant notions of ambiguity and ignorance. Copyright © 2005 John Wiley & Sons, Ltd.
Type III polyketide synthases in natural product biosynthesis

Polyketides represent an important class of biologically active and structurally diverse compounds in nature. They are synthesized from acyl‐coenzyme A substrates by polyketide synthases (PKSs). PKSs are classified into three groups: types I, II, and III. This article introduces recent studies on type III PKSs identified from plants, bacteria, and fungi, and describes the catalytic functions of these enzymes in detail. Plant type III PKSs have been widely studied, as exemplified by chalcone synthase, which plays an important role in the synthesis of plant metabolites. Bacterial type III PKSs fall into five groups, many of which were identified from Streptomyces, a genus that has been well known for its production of bioactive molecules and genetic alterability. Although it was believed that type III PKSs exist exclusively in plants and bacteria, recent fungal genome sequencing projects and biochemical studies revealed the presence of type III PKSs in filamentous fungi, which provides a new chance to study fungal secondary metabolism and synthesize “unnatural” natural products. Type III PKSs have been used for the biosynthesis of novel molecules through precursor‐directed and structure‐based mutagenesis approaches. © 2012 IUBMB Life, 64(4): 285–295, 2012
Response to folic acid article

AUSTRALIAN AND NEW ZEALAND JOURNAL OF PUBLIC HEALTH 2012 vol. 36 no. 5 © 2012 The Authors. ANZJPH © 2012 Public Health Association of Australia smoke or immunisation currency (Table 1). Data from the NT and IIHS CHCs were collected for primarily clinical purposes and do not represent a random sample of Indigenous children. This, together with the missing data, may affect these results. Many known risk factors for middle ear disease were not available from one or both sites in this research. These include lack of breastfeeding, child care and socioeconomic factors such as overcrowding. Previous research reports that almost all Aboriginal children in the NT have been breastfed at some stage, thus breastfeeding rates are likely to be higher in the NT than the rate of 67% among IIHS participants. Additionally, very little formal child care is used in remote areas, almost certainly less than the rate of 77% for IIHS participants. While breastfeeding rates and use of child care appear unlikely to explain the higher prevalence of abnormal middle ear appearance in the NT participants, nearly one-quarter of Aboriginal households in the NT are overcrowded, almost five times more than Queensland rates. The eight Indigenous-specific recommendations from the 2010 senate inquiry into Australia’s hearing health were focused on better access to hearing and ear specialist services. None dealt with socioeconomic issues including overcrowding. However, the inquiry was told that ear health should not be treated in isolation to the reality of people’s lives and that greater involvement of Indigenous communities was necessary. Indigenous communities and policy makers, working together, need to continue to promote the resolution of socioeconomic issues in remote NT communities, enlarging on initiatives such as the National Partnership Agreement on Remote Indigenous Housing in order to reduce the prevalence of Indigenous middle ear disease, rather than simply reacting to its consequences.