bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epidemiologic application of verbal autopsy to investigate the high occurrence of cancer along Huai River Basin, China
Authors: Wan Xia , Zhou Maigeng , Tao Zhuang , Ding Ding , Yang Gonghuan 
Published: August 2011

Abstract

Background
In 2004, the media repeatedly reported water pollution and "cancer villages" along the Huai River in China. Due to the lack of death records for more than 30 years, a retrospective survey of causes of death using verbal autopsy was carried out to investigate cancer rates in this area.

Methods
An epidemiologic study was designed to compare numbers of deaths and causes of death between the study areas with water pollution and the control areas without water pollution in S County and Y District in 2005. The study areas were selected based on the distribution of the Huai River and its tributaries. Verbal autopsy was used to assist cause of death (COD) diagnoses and to verify mortality rates. The standard mortality rates (SMRs) of cancer in the study area were compared with those in the control areas. In order to verify the difference between mortality rates due to cancers in the study and the control areas, patients who reported having cancer in the survey received a second diagnosis by national and provincial oncologists with pathological and laboratory examinations. Comparisons were made to determine if differential cancer prevalence rates in the study and control areas were similar to the difference in mortality due to cancer in these study and control areas. Mortality rates of cancers in study and control areas were also compared with national statistics for the rural population of China.

Results
Over five years, 3,301 deaths were identified, including 1,158 cancer deaths. The annual average SMRs of cancer in the study areas of S County and Y District were 277.8/100,000 and 223.6/100,000, respectively, which is three to four times higher than those in the control areas. In addition, a total of 626 cases of cancer in the study and control areas were confirmed. The prevalence rates of cancer were 545/100,000 and 128.1/100,000 per year in the study and control areas in S County, respectively, and 440.9/100,000 and 200/100,000 per year in the study and control areas in Y District, respectively. The mortality and prevalence rates of digestive cancers were higher in the study areas than the control areas. In 2000, the SMR for cancer in rural areas nationwide was 120.9/100,000, and in study areas in S County and Y District, the excess rates of deaths were 184/100,000 and 138.8/100,000, respectively.

Conclusions
The death rates of digestive cancers were much higher in the study areas of S County and Y District. The patterns for between-area differences in prevalence and mortality rates of cancer were similar. Verbal autopsy is shown to be a useful tool in retrospective mortality surveys in low-resource areas with limited access to health care.
Assessing quality of medical death certification: Concordance between gold standard diagnosis and underlying cause of death in selected Mexican hospitals
Authors: Hernández Bernardo , Ramírez-Villalobos Dolores , Romero Minerva , Gómez Sara , Atkinson Charles , Lozano Rafael 
Published: August 2011

Abstract

Background
In Mexico, the vital registration system relies on information collected from death certificates to generate official mortality figures. Although the death certificate has high coverage across the country, there is little information regarding its validity. The objective of this study was to assess the concordance between the underlying cause of death in official statistics obtained from death certificates and a gold standard diagnosis of the same deaths derived from medical records of hospitals.

Methods
The study sample consisted of 1,589 deaths that occurred in 34 public hospitals in the Federal District and the state of Morelos, Mexico in 2009. Neonatal, child, and adult cases were selected for causes of death that included infectious diseases, noncommunicable diseases, and injuries. We compared the underlying cause of death, obtained from medical death certificates, against a gold standard diagnosis derived from a review of medical records developed by the Population Health Metrics Research Consortium. We used chance-corrected concordance and accuracy as metrics to evaluate the quality of performance of the death certificate.

Results
Analysis considering only the underlying cause of death resulted in a median chance-corrected concordance between the cause of death in medical death certificates versus the gold standard of 54.3% (95% uncertainty interval [UI]: 52.2, 55.6) for neonates, 38.5% (37.0, 40.0) for children, and 66.5% (65.9, 66.9) for adults. The accuracy resulting from the same analysis was 0.756 (0.747, 0.769) for neonates, 0.683 (0.663, 0.701) for children, and 0.780 (0.774, 0.785) for adults. Median chance-corrected concordance and accuracy increased when considering the mention of any cause of death in the death certificate, not just the underlying cause. Concordance varied substantially depending on cause of death, and accuracy varied depending on the true cause-specific mortality fraction composition.

Conclusions
Although we cannot generalize our conclusions to Mexico as a whole, the results demonstrate important problems with the quality of the main source of information for causes of death used by decision-makers in settings with highly technological vital registration systems. It is necessary to improve death certification procedures, especially in the case of child and neonatal deaths. This requires an important commitment from the health system and health institutions.
Pulmonary medium vessel vasculitis in an 11 year old boy: Hughes Stovin syndrome as a variant of polyarteritis nodosa?
Authors: de Vries Willemien , Koppelman Gerard H , Roofthooft Marc TR , Bootsma Hendrika , Leijsma Martha K , Armbrust Wineke 
Published: August 2011

Abstract
We present the case of an 11-year-old boy presenting with haemoptysis, dyspnoea and weight loss as a manifestation of isolated pulmonary vasculitis, leading to pulmonary hypertension. He also appeared to have a longstanding dural venous sinus thrombosis. This rare presentation, especially in childhood, might represent a case of the seldomly reported Hughes-Stovin syndrome. The patient achieved remission after therapy with cyclophosphamide pulses and high-dose steroids. Based on the presented case and review of the literature, we propose that this syndrome might be a variant of polyarteritis nodosa. This report highlights diagnostic issues and describes a successful treatment regimen.
The PPAR-γ agonist pioglitazone modulates inflammation and induces neuroprotection in parkinsonian monkeys
Authors: Swanson Christine R , Joers Valerie , Bondarenko Viktoriya , Brunner Kevin , Simmons Heather A , Ziegler Toni E , Kemnitz Joseph W , Johnson Jeffrey A , Emborg Marina E 
Published: August 2011

Abstract

Background
Activation of the peroxisome proliferator-activated receptor gamma (PPAR-γ) has been proposed as a possible neuroprotective strategy to slow down the progression of early Parkinson's disease (PD). Here we report preclinical data on the use of the PPAR-γ agonist pioglitazone (Actos®; Takeda Pharmaceuticals Ltd.) in a paradigm resembling early PD in nonhuman primates.

Methods
Rhesus monkeys that were trained to perform a battery of behavioral tests received a single intracarotid arterial injection of 20 ml of saline containing 3 mg of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Twenty-four hours later the monkeys were assessed using a clinical rating scale, matched accordingly to disability, randomly assigned to one of three groups [placebo (n = 5), 2.5 (n = 6) or 5 (n = 5) mg/kg of pioglitazone] and their treatments started. Three months after daily oral dosing, the animals were necropsied.

Results
We observed significant improvements in clinical rating score (P = 0.02) in the animals treated with 5 mg/kg compared to placebo. Behavioral recovery was associated with preservation of nigrostriatal dopaminergic markers, observed as higher tyrosine hydroxylase (TH) putaminal optical density (P = 0.011), higher stereological cell counts of TH-ir (P = 0.02) and vesicular monoamine transporter-2 (VMAT-2)-ir nigral neurons (P = 0.006). Stereological cell counts of Nissl stained nigral neurons confirmed neuroprotection (P = 0.017). Pioglitazone-treated monkeys also showed a dose-dependent modulation of CD68-ir inflammatory cells, that was significantly decreased for 5 mg/kg treated animals compared to placebo (P = 0.018). A separate experiment to assess CSF penetration of pioglitazone revealed that 5 mg/kg p.o. induced consistently higher levels than 2.5 mg/kg and 7.5 mg/kg. p.o.

Conclusions
Our results indicate that oral administration of pioglitazone is neuroprotective when administered early after inducing a parkinsonian syndrome in rhesus monkeys and supports the concept that PPAR-γ is a viable target against neurodegeneration.
Nef-mediated enhancement of cellular activation and human immunodeficiency virus type 1 replication in primary T cells is dependent on association with p21-activated kinase 2
Authors: Olivieri Kevin C , Mukerji Joya , Gabuzda Dana 
Published: August 2011

Abstract

Background
The HIV-1 accessory protein Nef is an important determinant of lentiviral pathogenicity that contributes to disease progression by enhancing viral replication and other poorly understood mechanisms. Nef mediates diverse functions including downmodulation of cell surface CD4 and MHC Class I, enhancement of viral infectivity, and enhancement of T cell activation. Nef interacts with a multiprotein signaling complex that includes Src family kinases, Vav1, CDC42, and activated PAK2 (p21-activated kinase 2). Although previous studies have attempted to identify a biological role for the Nef-PAK2 signaling complex, the importance of this complex and its constituent proteins in Nef function remains unclear.

Results
Here, we show that Nef mutants defective for PAK2-association, but functional for CD4 and MHC Class I downmodulation and infectivity enhancement, are also defective for the ability to enhance viral replication in primary T cells that are infected and subsequently activated by sub-maximal stimuli (1 μg/ml PHA-P). In contrast, these Nef mutants had little or no effect on HIV-1 replication in T cells activated by stronger stimuli (2 μg/ml PHA-P or anti-CD3/CD28-coated beads). Viruses bearing wild-type Nefs, but not Nef mutants defective for PAK2 association, enhanced NFAT and IL2 receptor promoter activity in Jurkat cells. Moreover, expression of wild-type Nefs, but not mutant Nefs defective for PAK2 association, was sufficient to enhance responsiveness of primary CD4 and CD8 T cells to activating stimuli in Nef-expressing and bystander cells. siRNA knockdown of PAK2 in Jurkat cells reduced NFAT activation induced by anti-CD3/CD28 stimulation both in the presence and absence of Nef, and expression of a PAK2 dominant mutant inhibited Nef-mediated enhancement of CD25 expression.

Conclusion
Nef-mediated enhancement of cellular activation and viral replication in primary T cells is dependent on PAK2 and on the strength of the activating stimuli, and correlates with the ability of Nef to associate with PAK2. PAK2 is likely to play a role in Nef-mediated enhancement of viral replication and immune activation in vivo.
Behavioral Evidence for the Differential Regulation of p-p38 MAPK and p-NF-κB in Rats with Trigeminal Neuropathic Pain
Authors: Lee Min K , Han Seung R , Park Min K , Kim Min J , Bae Yong C , Kim Sung K , Park Jae S , Ahn Dong K 
Published: August 2011

Background: We investigated the differential regulation of p-p38 MAPK or p-NF- κB in male Sprague-Dawley rats with inferior alveolar nerve injury resulting from mal-positioned dental implants. For this purpose, we characterized the temporal expression of p-p38 MAPK or p-NF- κB in the medullary dorsal horn and examined changes in nociceptive behavior after a blockade of p-p38 MAPK or p-NF- κB pathways in rats with trigeminal neuropathic pain. Results: Under anesthesia, the left lower second molar was extracted and replaced with a mini dental implant to intentionally injure the inferior alveolar nerve. Western and immunofluorescence analysis revealed that p-p38 MAPK is upregulated in microglia following nerve injury and that this expression peaked on postoperative day (POD) 3 through 7. However, the activation of p-NF- κB in astrocyte peaked on POD 7 through 21. The intracisternal administration of SB203580 (1 or 10 μg), a p38 MAPK inhibitor, on POD 3 but not on POD 21 markedly inhibits mechanical allodynia and the p-p38 MAPK expression. However, the intracisternal administration of SN50 (0.2 or 2 ng), an NF- κB inhibitor, on POD 21 but not on POD 3 attenuates mechanical allodynia and p-NF- κB expression. Dexamethasone (25 mg/kg) decreases not only the activation of p38 MAPK but also that of NF- κB on POD 7. Conclusions: These results suggest that early expression of p-p38 MAPK in the microglia and late induction of p-NF- κB in astrocyte play an important role in trigeminal neuropathic pain and that a blockade of p-p38 MAPK at an early stage and p-NF- κB at a late stage might be a potential therapeutic strategy for treatment of trigeminal neuropathic pain.
Medicinal plants used for traditional veterinary in the Sierras de Córdoba (Argentina): An ethnobotanical comparison with human medicinal uses
Authors: Martínez Gustavo J , Luján María C 
Published: August 2011

Abstract
Background
This is a first description of the main ethnoveterinary features of the peasants in the Sierras de Córdoba. The aim of this study was to analyze the use of medicinal plants and other traditional therapeutic practices for healing domestic animals and cattle. Our particular goals were to: characterize veterinary ethnobotanical knowledge considering age, gender and role of the specialists; interpret the cultural features of the traditional local veterinary medicine and plant uses associated to it; compare the plants used in traditional veterinary medicine, with those used in human medicine in the same region.

Methods
Fieldwork was carried out as part of an ethnobotanic regional study where 64 informants were interviewed regarding medicinal plants used in veterinary medicine throughout 2001-2010. Based participant observation and open and semi-structured interviews we obtained information on the traditional practices of diagnosis and healing, focusing on the veterinary uses given to plants (part of the plant used, method of preparation and administration). Plants speciemens were collected with the informants and their vernacular and scientific names were registered in a database. Non-parametric statistic was used to evaluate differences in medicinal plant knowledge, use, and valorization by local people. A comparison between traditional veterinary medicine and previous human medicine studies developed in the region was performed by analyzing the percentages of common species and uses, and by considering Sorensen's Similarity Index.

Results
A total of 127 medicinal uses were registered, corresponding to 70 species of plants belonging to 39 botanic families. Veterinary ethnobotanical knowledge was specialized, restricted, in general, to cattle breeders (mainly men) and to a less degree to healers, and was independent of the age of the interviewees. Native plants were mostly used as skin cicatrizants, disinfectants or for treating digestive disorders. Together with a vast repertoire of plant pharmacopoeia, the therapies also involve religious or ritualistic practices and other popular remedies that evidence the influence of traditional Hispanic-European knowledge. Although the traditional veterinary knowledge seems to be similar or else is inlcuded in the local human ethnomedicine, sharing a common group of plants, it has distinct traits originated by a constant assessment of new applications specifically destined to the treatment of animals.

Conclusions
Veterinary medicine is a fountain of relevant vernacular knowledge, a permanent source for testing new applications with valuable ethnobotanical interest. Knowledge on medicinal applications of native plants will allow future validations and tests for new homeopathic or phytotherapeutic preparations.
A retrosynthetic biology approach to metabolic pathway design for therapeutic production
Authors: Carbonell Pablo , Planson Anne-Gaëlle , Fichera Davide , Faulon Jean-Loup 
Published: August 2011

Abstract

Background
Synthetic biology is used to develop cell factories for production of chemicals by constructively importing heterologous pathways into industrial microorganisms. In this work we present a retrosynthetic approach to the production of therapeutics with the goal of developing an in situ drug delivery device in host cells. Retrosynthesis, a concept originally proposed for synthetic chemistry, iteratively applies reversed chemical transformations (reversed enzyme-catalyzed reactions in the metabolic space) starting from a target product to reach precursors that are endogenous to the chassis. So far, a wider adoption of retrosynthesis into the manufacturing pipeline has been hindered by the complexity of enumerating all feasible biosynthetic pathways for a given compound.

Results
In our method, we efficiently address the complexity problem by coding substrates, products and reactions into molecular signatures. Metabolic maps are represented using hypergraphs and the complexity is controlled by varying the specificity of the molecular signature. Furthermore, our method enables candidate pathways to be ranked to determine which ones are best to engineer. The proposed ranking function can integrate data from different sources such as host compatibility for inserted genes, the estimation of steady-state fluxes from the genome-wide reconstruction of the organism's metabolism, or the estimation of metabolite toxicity from experimental assays. We use several machine-learning tools in order to estimate enzyme activity and reaction efficiency at each step of the identified pathways. Examples of production in bacteria and yeast for two antibiotics and for one antitumor agent, as well as for several essential metabolites are outlined.

Conclusions
We present here a unified framework that integrates diverse techniques involved in the design of heterologous biosynthetic pathways through a retrosynthetic approach in the reaction signature space. Our engineering methodology enables the flexible design of industrial microorganisms for the efficient on-demand production of chemical compounds with therapeutic applications.
An improved kinetic model for the acetone-butanol-ethanol pathway of Clostridium acetobutylicum and model-based perturbation analysis
Authors: Li Ru-Dong , Li Yuan-Yuan , Lu Ling-Yi , Ren Cong , Li Yi-Xue , Liu Lei 
Published: August 2011

Abstract

Background
Comprehensive kinetic models of microbial metabolism can enhance the understanding of system dynamics and regulatory mechanisms, which is helpful in optimizing microbial production of industrial chemicals. Clostridium acetobutylicum produces solvents (acetone-butanol–ethanol, ABE) through the ABE pathway. To systematically assess the potential of increased production of solvents, kinetic modeling has been applied to analyze the dynamics of this pathway and make predictive simulations. Up to date, only one kinetic model for C. acetobutylicum supported by experiment has been reported as far as we know. But this model did not integrate the metabolic regulatory effects of transcriptional control and other complex factors. It also left out the information of some key intermediates (e.g. butyryl-phosphate).

Results
We have developed an improved kinetic model featured with the incorporation of butyryl-phosphate, inclusion of net effects of complex metabolic regulations, and quantification of endogenous enzyme activity variations caused by these regulations. The simulation results of our model are more consistent with published experimental data than the previous model, especially in terms of reflecting the kinetics of butyryl-phosphate and butyrate. Through parameter perturbation analysis, it was found that butyrate kinase has large and positive influence on butanol production while CoA transferase has negative effect on butanol production, suggesting that butyrate kinase has more efficiency in converting butyrate to butanol than CoA transferase.

Conclusions
Our improved kinetic model of the ABE process has more capacity in approaching real circumstances, providing much more insight in the regulatory mechanisms and potential key points for optimization of solvent productions. Moreover, the modeling strategy can be extended to other biological processes.
Perceptions and viewpoints on proceedings of the Fifteenth Assembly of Heads of State and Government of the African Union Debate on Maternal, Newborn and Child Health and Development, 25–27 July 2010, Kampala, Uganda
Authors: Sambo Luis Gomes , Kirigia Joses Muthuri , Ki-Zerbo Georges 
Published: August 2011

Abstract

Background
Out of 358000 maternal deaths that occurred globally in 2008, 57.8% occurred in continental Africa. Africa had a maternal mortality ratio of 590 compared to 14 in developed regions, 68 in Latin America and Caribbean, and 190 in Asia. This article reflects on the discussions held during the Fifteenth Assembly of the Heads of State and Government of the African Union on the reasons why the maternal mortality ratio is so high in Africa and what can be done to reduce it.

Methods
Methods employed included panel and open public discussions among the Heads of State and Government of the African Union. The article uses the WHO health systems strengthening framework, which consists of six pillars (information systems, leadership and governance, health workforce, financing, and medical products, vaccines and technologies, and health services) to describe the proceedings of the discussions.

Discussion
The high maternal mortality ratios in countries were attributed to weak national health information systems; leadership and governance challenges related to poverty, health illiteracy, poor transport networks and communications infrastructure, risky cultural practices, armed conflicts and domestic violence, dearth of women empowerment; inadequate levels of skilled birth attendants; inadequate domestic and external funding; stock-outs of consumable inputs; and limited coverage of maternal and child health interventions.
In order to accelerate progress towards MDGs 4 and 5, the Heads of State and Government recommended that countries should make maternal deaths notifiable and institutionalize maternal death audits; develop, fund and implement policies and strategies geared at improving maternal, newborn and child health; accelerate inter-sectoral action to address the broad health determinants; increase the number of skilled birth attendants; fulfil commitment to allocate at least 15% of the national budget to the health sector and allocate adequate resources to prevent stock-outs of essential medicines and reproductive health commodities; leverage health promotion approaches to raise national awareness; and ensure that there is a health centre within a radius of four kilometres equipped to provide good quality integrated maternal, newborn and child health services.

Conclusions
There was consensus among the discussants that there was urgent need to speed up actions for strengthening health systems to improve coverage of maternal, newborn and child health services; and to address broad determinants of women, newborn and children’s health for sustained improvements in health and other development goals.