bluuebunny/crossref_metadata_2025 huggingface dataset:
A pilot study of the efficacy and safety of empiric daptomycin therapy in oncology patients with fever and severe neutropenia
Authors: Bubalo Joseph S. , Kullar Ravina , Maziarz Richard T.
Published: September 2013

Objectives:

Patients with extended periods of time spent with low or absent absolute neutrophil counts (ANCs) are at risk for bacterial infections. Febrile neutropenia is a complication in this patient population, requiring administration of antibiotics. The use of daptomycin in treating patients with febrile neutropenia is not well described. Our objective was to describe the clinical course of febrile neutropenic patients that received daptomycin therapy.

Methods:

This was an open-labeled, pilot study of 30 patients with documented febrile neutropenia treated with empiric daptomycin. Eligible patients received daptomycin 6 mg/kg/day, in addition to concomitant broad-spectrum antimicrobials. The Kaplan–Meier method was used to estimate the median days to reach an afebrile state and negative bacterial cultures.

Results:

A total of 30 febrile neutropenic patients were enrolled and received daptomycin as part of an empiric antimicrobial regimen. All patients had severe neutropenia with ANC <100 cells/mm3. Two patients were removed from study due to the development of pneumonia. Clinically, 87% patients improved on daptomycin in combination with Gram-negative coverage, with 73% of patients succeeding therapy. A total of 18 of 19 (95%) subjects with positive blood cultures had microbiological eradication, with the median time to reach an afebrile state of 4.3 days (range 1–13). Four patients were discontinued from daptomycin due to a suspected related adverse event or to clinical failure.

Conclusions:

This pilot study supports future evaluation of the use of empiric daptomycin therapy in combination with Gram-negative coverage compared with vancomycin in patients with neutropenic fever in a large, randomized controlled trial.
Transcriptional regulation of the Ikzf1 locus
Authors: Yoshida Toshimi , Landhuis Esther , Dose Marei , Hazan Idit , Zhang Jiangwen , Naito Taku , Jackson Audrey F. , Wu Jeffrey , Perotti Elizabeth A. , Kaufmann Christoph , Gounari Fotini , Morgan Bruce A. , Georgopoulos Katia
Published: September 2013

Key Points

Multiple enhancers identified at the Ikzf1 locus with shared and distinct epigenetic and transcriptional properties. Transcription factor networks that distinguish between LMPP-specific and T cell–specific Ikzf1 enhancers.
Noninvasive ventilation in the management of acute hypercapnic respiratory failure
Authors: Dwarakanath Akshay , Elliott Mark W.
Published: September 2013

Educational aims

To discuss the role of noninvasive ventilation (NIV) in the management of acute hypercapnic respiratory failure in various conditions.

To discuss the common problems encountered during NIV.

To provide practical considerations for setting up and delivering an optimal NIV service.

Noninvasive ventilation (NIV) is considered the standard of care in the management of acute hypercapnic respiratory failure secondary to chronic obstructive pulmonary disease. It can be delivered safely in any dedicated setting ranging from emergency and medical admissions departments to high-dependency and intensive care units. It reduces the demand for invasive mechanical ventilation, decreases in-hospital mortality and shortens hospital stay. The way the NIV service is delivered will depend on the model of hospital care and this varies greatly from country to country. Adequately trained staff and appropriate monitoring facilities, available around the clock, are important. A successful outcome is dependent on good patient selection and the correct implementation of NIV.
Pathway-PDT: a flexible pathway analysis tool for nuclear families
Authors: Park Yo Son , Schmidt Michael , Martin Eden R , Pericak-Vance Margaret A , Chung Ren-Hua
Published: September 2013

Background

Pathway analysis based on Genome-Wide Association Studies (GWAS) data has become popular as a secondary analysis strategy. Although many pathway analysis tools have been developed for case-control studies, there is no tool that can use all information from raw genotypes in general nuclear families. We developed Pathway-PDT, which uses the framework of Pedigree Disequilibrium Test (PDT) for general family data, to perform pathway analysis based on raw genotypes in family-based GWAS.

Results

Simulation results showed that Pathway-PDT is more powerful than the p-value based method, ALIGATOR. Pathway-PDT also can be more powerful than the PLINK set-based test when analyzing general nuclear families with multiple siblings or missing parents. Additionally, Pathway-PDT has a flexible and convenient user interface, which allows users to modify their analysis parameters as well as to apply various types of gene and pathway definitions.

Conclusions

The Pathway-PDT method is implemented in C++ with POSIX threads and is computationally feasible for pathway analysis with large scale family GWAS datasets. The Windows binary along with Makefile and source codes for the Linux are available at https://sourceforge.net/projects/pathway-pdt/.
Human amniotic fluid stem cells have a potential to recover ovarian function in mice with chemotherapy-induced sterility
Authors: Lai Dongmei , Wang Fangyuan , Chen Yifei , Wang Li , Wang Yanlin , Cheng Weiwei
Published: September 2013

Background

Human amniotic fluid cells (hAFCs) may differentiate into multiple cell lineages and thus have a great potential to become a donor cell source for regenerative medicine. The ability of hAFCs to differentiate into germ cell and oocyte-like cells has been previously documented. Herein we report the potential use of hAFCs to help restore follicles in clinical condition involving premature ovarian failure.

Results

Human amniotic fluid was obtained via amniocentesis, yielding a subpopulation of cloned hAFCs that was able to form embryoid bodies (EBs) and differentiate into three embryonic germ layers. Moreover, culture of EBs in medium containing human follicular fluid (HFF) or a germ cell maturation factor cocktail (FAC), expressed germ cells markers such as BLIMP1, STELLA, DAZL, VASA, STRA8, SCP3, SCP1, and GDF9. Furthermore, one cell line was grown from clone cells transfected with lentivirus-GFP and displaying morphological characteristics of mesenchymal cells, had the ability to restore ovarian morphology following cell injection into the ovaries of mice sterilized by intraperitoneal injection of cyclophosphamide and busulphan. Restored ovaries displayed many follicle-enclosed oocytes at all stages of development, but no oocytes or follicles were observed in sterilized mice whose ovaries had been injected with medium only (control). Notably, identification of GFP-labeled cells and immunostaining with anti–human antigen-specific antibodies demonstrated that grafted hAFCs survived and differentiated into granulosa cells which directed oocyte maturation. Furthermore, labeling of ovarian tissue for anti-Müllerian hormone expression, a functional marker of folliculogenesis, was strong in hAFCs-transplanted ovaries but inexistent in negative controls.

Conclusion

These findings highlight the possibility of using human amniotic fluid-derived stem cells in regenerative medicine, in particular in the area of reproductive health.
A structural comparison of lipopolysaccharide biosynthesis loci of Legionella pneumophila serogroup 1 strains
Authors: Petzold Markus , Thürmer Alexander , Menzel Susan , Mouton Johan W , Heuner Klaus , Lück Christian
Published: September 2013

Background

The lipopolysaccharide (LPS) is the major immuno-dominant antigen of all Legionella species including L. pneumophila. Its diversity is the basis for the classification of L. pneumophila into serogroups and monoclonal subgroups and is thought to be involved in strain specific virulence. The understanding of the genetic basis of the LPS-antigen is incomplete. Thus, we analyzed the genetic locus involved in LPS-biosynthesis of L. pneumophila serogroup 1 (Sg1) strains with the focus on strain specific gene composition.

Results

The LPS-biosynthesis loci of 14 L. pneumophila Sg1 strains comprise two distinct regions: A 15 kb region containing LPS-biosynthesis genes that can be found in all L. pneumophila strains and a Sg1-specific 18 kb region. The 15 kb region is highly conserved among Sg1 strains as reflected by high homologies of single ORFs and by a consistent ORF arrangement. In contrast, the Sg1 specific 18 kb region is variable and partially disrupted by phage related genes. We propose that the region spanning from ORF 6 to ORF 11 of the Sg1-specific region is likely involved in late LPS-modification. Due to the high variability of this small region and various combinations of single ORFs within this region a strain specific LPS-structure could be synthesized including modifications of legionaminic acid derivates.

Conclusions

Our data clearly demonstrate that the gene structure of the LPS-biosynthesis locus of L. pneumophila Sg1 strains show significant interstrain variability. These data can be used for further functional analysis of the LPS synthesis to understand pathogenesis and reactivity with monoclonal antibodies. Moreover, variable but strain specific regions can serve as basis for the development of novel genotyping assays.
A prospective cohort study of prognosis for newly diagnosed epilepsy in east China
Authors: Zhang Yanfang , Yu Nian , Su Lingying , Di Qing
Published: September 2013

Background

Limited data are available on the outcome of antiepileptic drug treatment response in patients of Chinese Han ethnicity with newly diagnosed epilepsy. We sought to explore the prognosis with antiepileptic drug treatment and to identify the predictors of poor drug control of seizures in these patients.

Methods

For at least 2 years, we prospectively followed up a cohort of patients with newly diagnosed epilepsy and analyzed the response to each antiepileptic drug. Cumulative risk for seizure relapse after initial remission achieved was estimated. The patients were divided into two groups (poor and good control) and compared for clinical characteristics.

Results

A total of 180 patients were included. Early remission was reached in 125 (69.44%) patients, 19 (10.56%) patients entered late remission, while 36 (20%) patients failed to achieve remission. The relapse rates were 19.5% at 2 years and 31.9% at 3 years of the follow-up. The response rates of the first throughout the fourth treatment regimens were 60.0%, 16.1%, 2.8%, and 0.6%, respectively. Multiple seizure types and changes in seizure type during treatment were significantly (p = 0.013 and 0.047, respectively) associated with a poor control.

Conclusions

The prognosis of the majority of patients with newly diagnosed epilepsy is good and the clinical pattern of epilepsy during treatment is complex. The chances of seizure control declines with each subsequent treatment regimen. The prognosis for patients with multiple seizure types and seizure type changes during treatment is unfavorable.
Estrogenic and mutagenic activities of Crotalaria pallida measured by recombinant yeast assay and Ames test
Authors: Boldrin Paula Karina , Resende Flávia Aparecida , Höhne Ana Paula Oliveira , de Camargo Mariana Santoro , Espanha Lívia Greghi , Nogueira Catarine Haidê , Melo Maria do Socorro F , Vilegas Wagner , Varanda Eliana Aparecida
Published: September 2013

Background

Crotalaria pallida Ailton is a plant belonging to the Fabaceae family, popularly known as “rattle or rattlesnake” and used in traditional medicine to treat swelling of the joints and as a vermifuge. Previous pharmacological studies have also reported anti-inflammatory, antimicrobial and antifungal activities. Nevertheless, scientific information regarding this species is scarce, and there are no reports related to its possible estrogenic and mutagenic effects. Thus, the purpose of the present study was to investigate the estrogenic potential of C. pallida leaves by means of the Recombinant Yeast Assay (RYA), seeking an alternative for estrogen replacement therapy during menopause; and to reflect on the safe use of natural products to assess the mutagenic activity of the crude extract from C. pallida leaves, the dichloromethane fraction and stigmasterol by means of the Ames test.

Methods

The recombinant yeast assay with the strain BY4741 of Saccharomyces cerevisiae, was performed with the ethanolic extract, dichloromethane fraction and stigmasterol isolated from the leaves of C. pallida. Mutagenic activity was evaluated by the Salmonella/microsome assay (Ames test), using the Salmonella typhimurium tester strains TA100, TA98, TA97 and TA102, with (+S9) and without (-S9) metabolization, by the preincubation method.

Results

All samples showed estrogenic activity, mainly stigmasterol. The ethanolic extract from C. pallida leaves showed mutagenic activity in the TA98 strain (-S9), whereas dichloromethane fraction and stigmasterol were found devoid of activity.

Conclusion

Considering the excellent estrogenic activity performed by stigmasterol in the RYA associated with the absence of mutagenic activity when evaluated by the Ames test, stigmasterol becomes a strong candidate to be used in hormone replacement therapy during menopause.
Current practices in library/informatics instruction in academic libraries serving medical schools in the western United States: a three-phase action research study
Authors: Eldredge Jonathan D , Heskett Karen M , Henner Terry , Tan Josephine P
Published: September 2013

Background

To conduct a systematic assessment of library and informatics training at accredited Western U.S. medical schools. To provide a structured description of core practices, detect trends through comparisons across institutions, and to identify innovative training approaches at the medical schools.

Methods

Action research study pursued through three phases. The first phase used inductive analysis on reported library and informatics skills training via publicly-facing websites at accredited medical schools and the academic health sciences libraries serving those medical schools. Phase Two consisted of a survey of the librarians who provide this training to undergraduate medical education students at the Western U.S. medical schools. The survey revealed gaps in forming a complete picture of current practices, thereby generating additional questions that were answered through the Phase Three in-depth interviews.

Results

Publicly-facing websites reviewed in Phase One offered uneven information about library and informatics training at Western U.S. medical schools. The Phase Two survey resulted in a 77% response rate. The survey produced a clearer picture of current practices of library and informatics training. The survey also determined the readiness of medical students to pass certain aspects of the United States Medical Licensure Exam. Most librarians interacted with medical school curricular leaders through either curricula committees or through individual contacts. Librarians averaged three (3) interventions for training within the four-year curricula with greatest emphasis upon the first and third years. Library/informatics training was integrated fully into the respective curricula in almost all cases. Most training involved active learning approaches, specifically within Problem-Based Learning or Evidence-Based Medicine contexts. The Phase Three interviews revealed that librarians are engaged with the medical schools' curricular leaders, they are respected for their knowledge and teaching skills, and that they need to continually adapt to changes in curricula.

Conclusions

This study offers a long overdue, systematic view of current practices of library/informatics training at Western U.S. medical schools. Medical educators, particularly curricular leaders, will find opportunities in this study's results for more productive collaborations with the librarians responsible for library and informatics training at their medical schools.
Medical practices display power law behaviors similar to spoken languages
Authors: Paladino Jonathan D , Crooke Philip S , Brackney Christopher R , Kaynar A Murat , Hotchkiss John R
Published: September 2013

Background

Medical care commonly involves the apprehension of complex patterns of patient derangements to which the practitioner responds with patterns of interventions, as opposed to single therapeutic maneuvers. This complexity renders the objective assessment of practice patterns using conventional statistical approaches difficult.

Methods

Combinatorial approaches drawn from symbolic dynamics are used to encode the observed patterns of patient derangement and associated practitioner response patterns as sequences of symbols. Concatenating each patient derangement symbol with the contemporaneous practitioner response symbol creates “words” encoding the simultaneous patient derangement and provider response patterns and yields an observed vocabulary with quantifiable statistical characteristics.

Results

A fundamental observation in many natural languages is the existence of a power law relationship between the rank order of word usage and the absolute frequency with which particular words are uttered. We show that population level patterns of patient derangement: practitioner intervention word usage in two entirely unrelated domains of medical care display power law relationships similar to those of natural languages, and that–in one of these domains–power law behavior at the population level reflects power law behavior at the level of individual practitioners.

Conclusions

Our results suggest that patterns of medical care can be approached using quantitative linguistic techniques, a finding that has implications for the assessment of expertise, machine learning identification of optimal practices, and construction of bedside decision support tools.
Prediction consistency and clinical presentations of breast cancer molecular subtypes for Han Chinese population
Authors: Huang Chi-Cheng , Tu Shih-Hsin , Lien Heng-Hui , Jeng Jaan-Yeh , Liu Jung-Sen , Huang Ching-Shui , Wu Yih-Yiing , Liu Chih-Yi , Lai Liang-Chuan , Chuang Eric Y
Published: September 2013

Background

Breast cancer is a heterogeneous disease in terms of transcriptional aberrations; moreover, microarray gene expression profiles had defined 5 molecular subtypes based on certain intrinsic genes. This study aimed to evaluate the prediction consistency of breast cancer molecular subtypes from 3 distinct intrinsic gene sets (Sørlie 500, Hu 306 and PAM50) as well as clinical presentations of each molecualr subtype in Han Chinese population.

Methods

In all, 169 breast cancer samples (44 from Taiwan and 125 from China) of Han Chinese population were gathered, and the gene expression features corresponding to 3 distinct intrinsic gene sets (Sørlie 500, Hu 306 and PAM50) were retrieved for molecular subtype prediction.

Results

For Sørlie 500 and Hu 306 intrinsic gene set, mean-centring of genes and distance-weighted discrimination (DWD) remarkably reduced the number of unclassified cases. Regarding pairwise agreement, the highest predictive consistency was found between Hu 306 and PAM50. In all, 150 and 126 samples were assigned into identical subtypes by both Hu 306 and PAM50 genes, under mean-centring and DWD. Luminal B tended to show a higher nuclear grade and have more HER2 over-expression status than luminal A did. No basal-like breast tumours were ER positive, and most HER2-enriched breast tumours showed HER2 over-expression, whereas, only two-thirds of ER negativity/HER2 over-expression tumros were predicted as HER2-enriched molecular subtype. For 44 Taiwanese breast cancers with survival data, a better prognosis of luminal A than luminal B subtype in ER-postive breast cancers and a better prognosis of basal-like than HER2-enriched subtype in ER-negative breast cancers was observed.

Conclusions

We suggest that the intrinsic signature Hu 306 or PAM50 be used for breast cancers in the Han Chinese population during molecular subtyping. For the prognostic value and decision making based on intrinsic subtypes, further prospective study with longer survival data is needed.
New differential fault analysis on PRESENT
Authors: Bagheri Nasour , Ebrahimpour Reza , Ghaedi Navid
Published: September 2013

In this paper, we present two differential fault analyses on PRESENT-80 which is a lightweight block cipher. The first attack is a basic attack which induces a fault on only one bit of intermediate states, and we can obtain the last subkey of the block cipher, given 48 faulty cipher texts on average. The second attack can retrieve the master key of the block cipher, given 18 faulty cipher texts on average. In the latter attack, we assume that we can induce faults on a single nibble of intermediate states. Given those faulty cipher texts, the computational complexity of attacks is negligible.
Diversity is maintained by seasonal variation in species abundance
Authors: Shimadzu Hideyasu , Dornelas Maria , Henderson Peter A , Magurran Anne E
Published: September 2013

Background

Some of the most marked temporal fluctuations in species abundances are linked to seasons. In theory, multispecies assemblages can persist if species use shared resources at different times, thereby minimizing interspecific competition. However, there is scant empirical evidence supporting these predictions and, to the best of our knowledge, seasonal variation has never been explored in the context of fluctuation-mediated coexistence.

Results

Using an exceptionally well-documented estuarine fish assemblage, sampled monthly for over 30 years, we show that temporal shifts in species abundances underpin species coexistence. Species fall into distinct seasonal groups, within which spatial resource use is more heterogeneous than would be expected by chance at those times when competition for food is most intense. We also detect seasonal variation in the richness and evenness of the community, again linked to shifts in resource availability.

Conclusions

These results reveal that spatiotemporal shifts in community composition minimize competitive interactions and help stabilize total abundance.
Evolution and heterogeneity of multiple serotypes of Dengue virus in Pakistan, 2006–2011
Authors: Koo Carmen , Nasir Amna , Hapuarachchi Hapuarachchige Chanditha , Lee Kim-Sung , Hasan Zahra , Ng Lee-Ching , Khan Erum
Published: September 2013

Background

Even though dengue has been recognized as one of the major public health threats in Pakistan, the understanding of its molecular epidemiology is still limited. The genotypic diversity of Dengue virus (DENV) serotypes involved in dengue outbreaks since 2005 in Pakistan is not well studied. Here, we investigated the origin, diversity, genetic relationships and geographic distribution of DENV to understand virus evolution during the recent expansion of dengue in Pakistan.

Methods

The study included 200 sera obtained from dengue-suspected patients from 2006 to 2011. DENV infection was confirmed in 94 (47%) sera by a polymerase chain reaction assay. These included 36 (38.3%) DENV-2, 57 DENV-3 (60.6%) and 1 DENV-4 (1.1%) cases. Sequences of 13 whole genomes (6 DENV-2, 6 DENV-3 and 1 DENV-4) and 49 envelope genes (26 DENV-2, 22 DENV-3 and 1 DENV-4) were analysed to determine the origin, phylogeny, diversity and selection pressure during virus evolution.

Results

DENV-2, DENV-3 and DENV-4 in Pakistan from 2006 to 2011 shared 98.5-99.6% nucleotide and 99.3-99.9% amino acid similarity with those circulated in the Indian subcontinent during the last decade. Nevertheless, Pakistan DENV-2 and DENV-3 strains formed distinct clades characterized by amino acid signatures of NS2A-I116T + NS5-K861R and NS3-K590R + NS5-S895L respectively. Each clade consisted of a heterogenous virus population that circulated in Southern (2006–2009) and Northern Pakistan (2011).

Conclusions

DENV-2, DENV-3 and DENV-4 that circulated during 2006–2011 are likely to have first introduced via the southern route of Pakistan. Both DENV-2 and DENV-3 have undergone in-situ evolution to generate heterogenous populations, possibly driven by sustained local DENV transmission during 2006–2011 periods. While both DENV-2 and DENV-3 continued to circulate in Southern Pakistan until 2009, DENV-2 has spread in a Northern direction to establish in Punjab Province, which experienced a massive dengue outbreak in 2011.
Misplaced links in the chain of survival due to an incorrect manual for the emergency call at public facilities
Authors: Takei Yutaka , Nishi Taiki , Takase Keiko , Kamikura Takahisa , Inaba Hideo
Published: September 2013

Background

The incidence of delayed emergency calls and the outcome of out-of-hospital cardiac arrest (OHCA) may differ among public facilities when emergency calls are placed by institutional staff. The purpose of this study was to identify the actions prescribed in the rules and/or manuals of public facilities and to clarify whether the incidence of delayed emergency call placement and the outcome of OHCA differ among these facilities.

Methods

We performed a questionnaire-based survey regarding emergency calls in public facilities in our community and analyzed our regional Utstein-based OHCA database.

Results

Our questionnaire survey disclosed that the most common actions prescribed in the manuals or rules applied in care facilities and educational institutions are to report the situation when a cardiac arrest occurs and to follow the directions of a custodian or supervisor. The international web search disclosed that these actions are rarely prescribed in medical emergency manuals in other countries. Most of these manuals simply say that staff should make an emergency call immediately upon detecting a serious illness or medical emergency. Analysis of the Utstein-based database from our community revealed that the time interval between collapse and emergency call placement is prolonged and the outcome of cardiac arrest poor in care facilities. A prompt emergency call and cardiopulmonary resuscitation (CPR) after arrest are associated with improved 1-year survival following OHCA. Contrary to accepted wisdom, staff who recognize a cardiac arrest may consult their supervisor and then continue CPR until they receive instructions from him or her.

Conclusions

Manuals or rules for making emergency calls in our public facilities may contain incorrect information, and emergency calls may be delayed owing to correctable human factors. Such manuals should be checked and revised.
Expression of non-protein-coding antisense RNAs in genomic regions related to autism spectrum disorders
Authors: Velmeshev Dmitry , Magistri Marco , Faghihi Mohammad Ali
Published: September 2013

Background

Autism spectrum disorders (ASD) manifest with neurodevelopmental phenotypes including communicative, social and behavioral impairments that affect as many as 1 in 88 children. The majority of autism cases have no known genetic cause, suggesting complex genetics of the disorder, but a few genes of large effect have been identified.

Methods

In order to identify novel ASD genetic correlates, we investigated non-protein coding RNAs (ncRNAs) which are abundantly transcribed from the human genome, enriched in the brain, and have been implicated in neurodevelopmental disorders. Using an algorithm that we developed, we examined a publicly available transcriptomics database, AceView, to identify the natural antisense transcripts (NATs) that overlap with known autism-related genes. We validated the presence and differential expression of NATs in different brain regions of ASD and control brains using qRT-PCR. Additionally, we investigated the subcellular localization of these transcripts in a neuronal cell line using RNA-sequencing (RNA-seq).

Results

We found noncoding antisense RNA transcripts at approximately 40% of loci previously implicated in ASD. We confirmed the expression of 10 antisense RNAs in different postmortem human brain tissues. The expression of five antisense transcripts was found to be region-specific, suggesting a role for these ncRNAs in the development and function of specific brain regions. Some antisense RNAs overlapping suspected ASD genes exhibited concordant expression relative to their sense protein-coding genes, while other sense-antisense pairs demonstrate a discordant relationship. Interestingly, the antisense RNA corresponding to the SYNGAP1 locus (SYNGAP1-AS) was found to be differentially expressed in brain regions of patients with ASD compared to control individuals. RNA-seq analysis of subcellular compartments from SH-SY5Y human neuroblastoma cells demonstrated that antisense RNAs to ASD candidate genes are predominantly expressed in the nucleoplasmic or chromatin compartments, implying their involvement in nuclear-associated processes.

Conclusions

Our data suggests that NATs are abundantly expressed from ASD-related loci and provide evidence for their roles in target gene regulation, neurodevelopment and autism pathogenesis. This class of RNA should therefore be considered in functional studies aimed at understanding genetic risk factors for ASD.
Sociomicrobiome of wood decay in a tropical rain forest: unraveling complexity
Authors: Santiago-Rodriguez Tasha M , Toranzos Gary A , Bayman Paul , Massey Steven E , Cano Raul J
Published: September 2013

Given that microbial interactions in nature are very complex, we propose that quorum-sensing, as well as quorum-quenching, phenazine and secondary metabolite production, resistance and toxin-antitoxin systems within a microbial community should all comprise the battery of processes involving the study of what we would define as the “sociomicrobiome”. In the present study the genes/molecules, subsystems and taxonomic breakup of the mentioned processes were identified in decaying tropical wood from the El Yunque rainforest in Puerto Rico, and soil using a shotgun metagenomic approach. The rapid decomposition of wood and litter in tropical regions suggests that processes in these settings are governed by unexplored microbes with the potential of being further studied and exploited for various purposes. Both ecosystems were characterized by the presence of specific genes/molecules, subsystems and microbes associated with the mentioned processes, although the average abundances for specific processes differed. Of the sociomicrobiomes studied, that from El Yunque was found to be the most complex. The approach considered in the present study could also be applied to study the sociomicrobiome of other ecosystems.
How do people with knee osteoarthritis use osteoarthritis pain medications and does this change over time? Data from the Osteoarthritis Initiative
Authors: Kingsbury Sarah R , Hensor Elizabeth MA , Walsh Ceara AE , Hochberg Marc C , Conaghan Philip G
Published: September 2013

Introduction

The aim of this analysis was to describe comprehensively the cross-sectional and longitudinal patterns of analgesic and nutraceutical medication use for knee osteoarthritis (OA) in a contemporary US cohort and to investigate associated demographic and clinical factors.

Methods

Baseline, 12, 24 and 36 month data were obtained retrospectively from the National Institutes of Health Osteoarthritis Initiative. Participants had symptomatic radiographic knee OA. Multiple binary logistic regression models identified characteristics independently associated with the use of analgesics or nutraceuticals.

Results

We included 987 subjects (55.9% female, mean age 61.5 years, 71.0% white). At baseline, 68.2% reported frequent use of a conventional analgesic or nutraceutical for joint pain (for more than half of the previous month). Non-prescription non-steroidal anti-inflammatory drugs (NSAIDs) were the most frequently reported medications (26.8%), even in those more than 75-years old. Multiple conventional analgesics were used by 11.9%. Frequent analgesic use was more likely in women (odds ratio (OR) 1.8 (95% confidence interval (CI) 1.3 to 2.3)) and people with more pain (moderate 1.7 (1.2 to 2.4); severe 3.1 (2.1 to 4.7)); nutraceutical use was less likely in non-whites (0.4 (0.3 to 0.6)), those more than 74-years old (0.6 (0.3 to 0.9)) and those with comorbidities (0.6 (0.5 to 0.9)) and more likely in people with Kellgren-Lawrence (KL) grade 4 (2.2 (1.5 to 3.3)). Overall there was no change in the proportion of participants frequently using prescription or over the counter (OTC) analgesics at 36 months, although most people had changed medication type; of those using a traditional analgesic at baseline approximately one third were still using the same type at 36 months (ranging from 26.2% of baseline prescription NSAID users to 40.6% of baseline acetaminophen users). All participants reporting baseline analgesic use also reported 36 month analgesic use. Female participants (OR 95% CI 1.2 to 3.2, P = 0.009), those with high body mass index (1.2 to 4.8, P = 0.010) and those with moderate (1.6 to 2.6, P = 0.090) or severe (1.8 to 12.0, P = 0.002) baseline pain were more likely to use pain medication during the 36 month follow-up period; participants more than 75-years old were less likely (0.2 to 1.0, P = 0.053).

Conclusions

Most people with knee OA used pharmacological therapies frequently, and use appeared to be according to American College of Rheumatology recommendations. Change in medication type used was common. Persistent non-prescription NSAID use in older people is an area of concern.
Association between mammographic density and basal-like and luminal A breast cancer subtypes
Authors: Razzaghi Hilda , Troester Melissa A , Gierach Gretchen L , Olshan Andrew F , Yankaskas Bonnie C , Millikan Robert C
Published: September 2013

Introduction

Mammographic density is a strong risk factor for breast cancer overall, but few studies have examined the association between mammographic density and specific subtypes of breast cancer, especially aggressive basal-like breast cancers. Because basal-like breast cancers are less frequently screen-detected, it is important to understand how mammographic density relates to risk of basal-like breast cancer.

Methods

We estimated associations between mammographic density and breast cancer risk according to breast cancer subtype. Cases and controls were participants in the Carolina Breast Cancer Study (CBCS) who also had mammograms recorded in the Carolina Mammography Registry (CMR). A total of 491 cases had mammograms within five years prior to and one year after diagnosis and 528 controls had screening or diagnostic mammograms close to the dates of selection into CBCS. Mammographic density was reported to the CMR using Breast Imaging Reporting and Data System categories. The expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 1 and 2 (HER1 and HER2), and cytokeratin 5/6 (CK5/6) were assessed by immunohistochemistry and dichotomized as positive or negative, with ER+ and/or PR+, and HER2- tumors classified as luminal A and ER-, PR-, HER2-, HER1+ and/or CK5/6+ tumors classified as basal-like breast cancer. Triple negative tumors were defined as negative for ER, PR and HER2. Of the 491 cases 175 were missing information on subtypes; the remaining cases included 181 luminal A, 17 luminal B, 48 basal-like, 29 ER-/PR-/HER2+, and 41 unclassified subtypes. Odds ratios comparing each subtype to all controls and case-case odds ratios comparing mammographic density distributions in basal-like to luminal A breast cancers were estimated using logistic regression.

Results

Mammographic density was associated with increased risk of both luminal A and basal-like breast cancers, although estimates were imprecise. The magnitude of the odds ratio associated with mammographic density was not substantially different between basal-like and luminal A cancers in case–control analyses and case-case analyses (case-case OR = 1.08 (95% confidence interval: 0.30, 3.84)).

Conclusions

These results suggest that risk estimates associated with mammographic density are not distinct for separate breast cancer subtypes (basal-like/triple negative vs. luminal A breast cancers). Studies with a larger number of basal-like breast cancers are needed to confirm our findings.
Changes in dental plaque following hospitalisation in a critical care unit: an observational study
Authors: Sachdev Mishal , Ready Derren , Brealey David , Ryu Jung Hyun , Bercades Georgia , Nagle Janette , Borja-Boluda Susana , Agudo Elisa , Petrie Aviva , Suvan Jean , Donos Nikos , Singer Mervyn , Needleman Ian
Published: September 2013

Introduction

Previous research has suggested that deterioration in oral health can occur following hospitalisation. The impact of such deterioration could increase the risk of oral disease, reduce quality of life and increase the potential for healthcare-associated infections (HCAI) such as healthcare-associated pneumonia (HAP). However, the strength of the evidence is limited by, amongst other factors, the few observational studies published that assess oral health longitudinally. In view of the microbiological component of oral diseases and HCAIs, the objective of this study was to investigate the microbiological changes in dental plaque following hospitalisation in a Critical Care Unit (CCU): (1) total number of cultivable bacteria and (2) presence and changes in specific HAP pathogens.

Methods

We conducted a prospective, longitudinal observational study in the CCU of University College Hospital, London. Study participants were recruited within 24 hours of admission. Dental plaque samples were collected from up to six sites per patient. The primary outcome was microbiological change from baseline to seven days with additional analysis for participants still present at day 14.

Results

50 patients were recruited with 36 available for review at one week, with early discharge accounting for much of the loss to follow-up. The median total viable count of the plaque microbiota at baseline was 4.40 × 105 cfu/ml and increased at week one to 3.44 × 106 cfu/ml. The total viable microbe counts increased by a median of 2.26 × 106 cfu/ml from baseline to week one (95% CI: 3.19 × 106, 1.24 × 107) and this was statistically significant (P < 0.01). Specific HAP bacteria were detected in 26% of participants sampled, although accounted for a relatively low proportion of the total viable bacteria.

Conclusion

Total bacterial count of dental plaque increases during hospitalisation in CCU. This finding, together with the colonisation of dental plaque by HAP bacteria strengthens the evidence for a deterioration in oral health in CCU and a risk factor for negative health and quality of life outcomes.
Experiences of Mentors Training Underrepresented Undergraduates in the Research Laboratory
Authors: Prunuske Amy J. , Wilson Janelle , Walls Melissa , Clarke Benjamin
Published: September 2013

Successfully recruiting students from underrepresented groups to pursue biomedical science research careers continues to be a challenge. Early exposure to scientific research is often cited as a powerful means to attract research scholars with the research mentor being critical in facilitating the development of an individual's science identity and career; however, most mentors in the biological sciences have had little formal training in working with research mentees. To better understand mentors’ experiences working with undergraduates in the laboratory, we conducted semistructured interviews with 15 research mentors at a public university in the Midwest. The interviewed mentors were part of a program designed to increase the number of American Indians pursuing biomedical/biobehavioral research careers and represented a broad array of perspectives, including equal representation of male and female mentors, mentors from underrepresented groups, mentors at different levels of their careers, and mentors from undergraduate and professional school departments. The mentors identified benefits and challenges in being an effective mentor. We also explored what the term underrepresented means to the mentors and discovered that most of the mentors had an incomplete understanding about how differences in culture could contribute to underrepresented students’ experience in the laboratory. Our interviews identify issues relevant to designing programs and courses focused on undergraduate student research.
Contraindicated Use of Bevacizumab and Toxicity in Elderly Patients With Cancer
Authors: Hershman Dawn L. , Wright Jason D. , Lim Emerson , Buono Donna L. , Tsai Wei Yann , Neugut Alfred I.
Published: September 2013

Purpose

Drugs are approved on the basis of randomized trials conducted in selected populations. However, once approved, these treatments are usually expanded to patients ineligible for the trial.

Patients and Methods

We used the SEER-Medicare database to identify subjects older than 65 years with metastatic breast, lung, and colon cancer, diagnosed between 2004 and 2007 and undergoing follow-up to 2009, who received bevacizumab. We defined a contraindication as having at least two billing claims before bevacizumab for thrombosis, cardiac disease, stroke, hemorrhage, hemoptysis, or GI perforation. We defined toxicity as first development of one of these conditions after therapy.

Results

Among 16,085 metastatic patients identified, 3,039 (18.9%) received bevacizumab. Receipt of bevacizumab was associated with white race, later year of diagnosis, tumor type, and decreased comorbid conditions. Of patients who received bevacizumab, 1,082 (35.5%) had a contraindication. In multivariate analysis, receipt of bevacizumab with a contraindication was associated with black race (odds ratio [OR] = 2.6; 95% CI, 1.4 to 4.9), increased age, comorbidity, later year of diagnosis, and lower socioeconomic status. Patients with lung (OR = 1.7; 95% CI, 1.1 to 2.4) and colon cancer (OR = 1.4; 95% CI, 1.1 to 1.9) were more likely to have a contraindication. In the group with no contraindication, 30% had a complication after bevacizumab; black patients were more likely to have a complication than were white patients (OR = 1.9; 95% CI, 1.21 to 2.93).

Conclusion

Our study demonstrates widespread use of bevacizumab among patients who had contraindications. Black patients were less likely to receive the drug, but those who did were more likely to have a contraindication. Efforts to understand toxicity and efficacy in populations excluded from clinical trials are needed.
Effect of Antiviral Treatment With Nucleotide/Nucleoside Analogs on Postoperative Prognosis of Hepatitis B Virus–Related Hepatocellular Carcinoma: A Two-Stage Longitudinal Clinical Study
Authors: Yin Jianhua , Li Nan , Han Yifang , Xue Jie , Deng Yang , Shi Jie , Guo Weixing , Zhang Hongwei , Wang Hongyang , Cheng Shuqun , Cao Guangwen
Published: September 2013

Purpose

Postoperative prognosis of hepatitis B virus (HBV) –related hepatocellular carcinoma (HCC) is poor. The effect of nucleotide/nucleoside analog (NA) treatment on the prognosis has not been fully clarified.

Patients and Methods

We carried out a two-stage longitudinal study that included a randomized clinical trial (RCT) to evaluate the effect of NA treatment on postoperative prognosis of HBV-HCC. Seven hundred eighty patients (163 in the RCT) were enrolled onto this study following radical hepatectomy. Lamivudine, adefovir dipivoxil, or entecavir were postoperatively administered to antiviral groups. Surgical specimens were examined immunohistochemically for carboxylic acid–terminal truncated HBV X protein (Ct-HBx).

Results

In the nonrandomized cohort, high viral load (≥ 104 copies/mL) significantly predicted unfavorable overall survival and recurrence-free survival (RFS), whereas antiviral treatment significantly improved both types of survival. In the RCT, antiviral treatment significantly decreased HCC recurrence and HCC-related death, with hazard ratios (HRs) of 0.48 (95% CI, 0.32 to 0.70) and 0.26 (95% CI, 0.14 to 0.50), respectively, in multivariate Cox analyses. Patients who received antiviral treatment had significantly decreased early recurrence (HR, 0.41; 95% CI, 0.27 to 0.62) and improved liver function 6 months after surgery compared with the controls (P < .001). Those with recovered liver function had a higher 2-year RFS rate than those without (P = .003). Ct-HBx expression in adjacent hepatic tissues significantly predicted an unfavorable RFS in the antiviral group (P < .001).

Conclusion

Although it might not affect the HCC-promoting potential of Ct-HBx, NA treatment is effective in normalizing liver function, decreasing HBV-HCC recurrence, and improving postoperative survival. This effect should be validated in a multicenter phase III RCT.
Phase I Study of ARN-509, a Novel Antiandrogen, in the Treatment of Castration-Resistant Prostate Cancer
Authors: Rathkopf Dana E. , Morris Michael J. , Fox Josef J. , Danila Daniel C. , Slovin Susan F. , Hager Jeffrey H. , Rix Peter J. , Chow Maneval Edna , Chen Isan , Gönen Mithat , Fleisher Martin , Larson Steven M. , Sawyers Charles L. , Scher Howard I.
Published: September 2013

Purpose

ARN-509 is a novel androgen receptor (AR) antagonist for the treatment of castration-resistant prostate cancer (CRPC). ARN-509 inhibits AR nuclear translocation and AR binding to androgen response elements and, unlike bicalutamide, does not exhibit agonist properties in the context of AR overexpression. This first-in-human phase I study assessed safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of ARN-509 in men with metastatic CRPC.

Patients and Methods

Thirty patients with progressive CRPC received continuous daily oral ARN-509 at doses between 30 and 480 mg, preceded by administration of a single dose followed by a 1-week observation period with pharmacokinetic sampling. Positron emission tomography/computed tomography imaging was conducted to monitor [18F]fluoro-α-dihydrotestosterone (FDHT) binding to AR in tumors before and during treatment. Primary objective was to determine pharmacokinetics, safety, and recommended phase II dose.

Results

Pharmacokinetics were linear and dose proportional. Prostate-specific antigen declines at 12 weeks (≥ 50% reduction from baseline) were observed in 46.7% of patients. Reduction in FDHT uptake was observed at all doses, with a plateau in response at ≥ 120-mg dose, consistent with saturation of AR binding. The most frequently reported adverse event was grade 1/2 fatigue (47%). One dose-limiting toxicity event (grade 3 abdominal pain) occurred at the 300-mg dose. Dose escalation to 480 mg did not identify a maximum-tolerated dose.

Conclusion

ARN-509 was safe and well tolerated, displayed dose-proportional pharmacokinetics, and demonstrated pharmacodynamic and antitumor activity across all dose levels tested. A maximum efficacious dose of 240 mg daily was selected for phase II exploration based on integration of preclinical and clinical data.