bluuebunny/crossref_metadata_2025_split huggingface dataset:
The protective role of microRNA-21 against coxsackievirus B3 infection through targeting the MAP2K3/P38 MAPK signaling pathway
Authors: He Feng , Xiao Zonghui , Yao Hailan , Li Sen , Feng Miao , Wang Wei , Liu Zhewei , Liu Zhuo , Wu Jianxin 
Published: October 2019

Abstract

Background
The P38 mitogen-activated protein kinase (MAPK) pathway plays an essential role in CVB3-induced diseases. We previously demonstrated microRNA-21 has potential inhibitory effect on the MAP2K3 which locates upstream of P38 MAPK and was upregulated in mouse hearts upon CVB3 infection. However, the effect and underlying mechanism of miRNA-21 on CVB3 infection remain unclear.

Methods
We detected continuous changes of cellular miRNA-21 and P38 MAPK proteins expression profiling post CVB3 infection in vitro within 12 h. P38 MAPK signaling was inhibited by the specific inhibitor, small interfering RNA and miRNA-21 mimic in vitro, CVB3 replication, cell apoptosis rate and proliferation were detected. Viral load in the mice heart, cardiomyocyte apoptosis rate and histological of the heart were also detected in the mice model of viral myocarditis pretreated with miRNA-21-lentivirus.

Results
We observed significant upregulation of miRNA-21 expression followed by suppression of the MAP2K3/P38 MAPK signaling in CVB3-infected Hela cells. The inactivation of the MAP2K3/P38 MAPK signaling by P38 MAPK specific inhibitor, small interfering RNA against MAP2K3, or miRNA-21 overexpression significantly inhibited viral progeny release from CVB3-infected cells. Mechanistically, when compared with control miRNA, miRNA-21 showed no effect on capsid protein VP1 expression and viral load within host cells, while significantly reversing CVB3-induced caspase-3 activation and cell apoptosis rate, further promoting proliferation of infected cells, which indicates the inhibitory effect of miRNA-21 on CVB3 progeny release. In the in vivo study, when compared with control miRNA, miRNA-21 pretreatment remarkably inactivated the MAP2K3/P38 MAPK signaling in mice and protected them against CVB3 infection as evidenced by significantly alleviated cell apoptosis rate, reduced viral titers, necrosis in the heart as well as by remarkably prolonged survival time.

Conclusions
miRNA-21 were reverse correlated with P38 MAPK activation post CVB3 infection, miRNA-21 overexpression significantly inhibited viral progeny release and decreased myocytes apoptosis rate in vitro and in vivo, suggesting that miRNA-21 may serve as a potential therapeutic agent against CVB3 infection through targeting the MAP2K3/P38 MAPK signaling.
Natural Language Processing Approaches to Detect the Timeline of Metastatic Recurrence of Breast Cancer
Authors: Banerjee Imon , Bozkurt Selen , Caswell-Jin Jennifer Lee , Kurian Allison W. , Rubin Daniel L. 
Published: October 2019

PURPOSE Electronic medical records (EMRs) and population-based cancer registries contain information on cancer outcomes and treatment, yet rarely capture information on the timing of metastatic cancer recurrence, which is essential to understand cancer survival outcomes. We developed a natural language processing (NLP) system to identify patient-specific timelines of metastatic breast cancer recurrence. PATIENTS AND METHODS We used the OncoSHARE database, which includes merged data from the California Cancer Registry and EMRs of 8,956 women diagnosed with breast cancer in 2000 to 2018. We curated a comprehensive vocabulary by interviewing expert clinicians and processing radiology and pathology reports and progress notes. We developed and evaluated the following two distinct NLP approaches to analyze free-text notes: a traditional rule-based model, using rules for metastatic detection from the literature and curated by domain experts; and a contemporary neural network model. For each 3-month period (quarter) from 2000 to 2018, we applied both models to infer recurrence status for that quarter. We trained the NLP models using 894 randomly selected patient records that were manually reviewed by clinical experts and evaluated model performance using 179 hold-out patients (20%) as a test set. RESULTS The median follow-up time was 19 quarters (5 years) for the training set and 15 quarters (4 years) for the test set. The neural network model predicted the timing of distant metastatic recurrence with a sensitivity of 0.83 and specificity of 0.73, outperforming the rule-based model, which had a specificity of 0.35 and sensitivity of 0.88 ( P < .001). CONCLUSION We developed an NLP method that enables identification of the occurrence and timing of metastatic breast cancer recurrence from EMRs. This approach may be adaptable to other cancer sites and could help to unlock the potential of EMRs for research on real-world cancer outcomes.
Pregnancy Outcomes in Chronic Myeloid Leukemia: A Single Center Experience
Authors: Madabhavi Irappa , Sarkar Malay , Modi Mitul , Kadakol Nagaveni 
Published: October 2019

PURPOSE The aim of the current work was to report the effect of imatinib on pregnancy in patients with chronic myeloid leukemia (CML). METHODS Data were collected between January 1998 and December 2014. One hundred four patients met inclusion criteria, and we report the results of 104 pregnancies—conceived by the participant or partner—while being on imatinib therapy for CML. RESULTS Fifty-eight patients were male and 46 were female. Eighty-three patients, 20 patients, and one patient were had CML in the chronic phase, accelerated phase, or blast phase, respectively. Of 46 female patients, 21 underwent abortion (spontaneous, n = 36.9; elective termination, n = 8.6%). In the case of full-term pregnancy in the female partners of male patients with CML, all outcomes were uneventful. Of 46 female patients, 25 had full-term pregnancy outcomes. During the pre–imatinib era (total n = 6), patients were treated with hydroxyurea, interferon-alpha, and therapeutic leukapheresis. A total 10 of 19 pregnant patients continued on imatinib until their delivery and experienced the following outcomes: normal full-term deliveries (n = 7), preterm delivery (n = 1), omphalocele (n = 1), and craniosynostosis (n = 1). Of those who discontinued imatinib after counseling (n = 9), eight patients had full-term normal delivery, of which two patients required leukapheresis and one patient expired. All patients who continued on imatinib while pregnant were in complete cytogenetic response and major molecular response (MMR) before pregnancy, during pregnancy, and postpregnancy. Of nine patients who discontinued imatinib, two lost MMR during the third trimester and all of these patients were in complete cytogenetic response and MMR before pregnancy. CONCLUSION It is clear that there is no standard of care for the best treatment of CML in the case of pregnancy. Interferon and/or leukapheresis will be included as treatment options. Patients can have normal pregnancies even with the administration of imatinib at the risk of congenital anomalies, intervention for which can be done after birth.
Directly Observed Care: An Innovative Oncology Care Model in Belize
Authors: Valtis Yannis , Yacab Ramon , Huang Franklin 
Published: October 2019

PURPOSE Patients with cancer in low- and middle-income countries face complex socioeconomic barriers within health systems that can lead to poor oncologic outcomes. Patient navigation has been shown to reduce disparities in oncologic outcomes in the United States. Belize, a middle-income country in Central America, has recently launched its first-ever public medical oncology program. Here, we report on the development of Directly Observed Care (DOC), a pilot patient navigation care model for patients with cancer in Belize, inspired from directly observed treatment for tuberculosis. METHODS DOC will be a patient-centered program, where a nurse trained in patient navigation will assume responsibility for proactively identifying barriers that Belizean patients with cancer face in access to care and working to remove them. This process will include patient education on cancer and its treatment, identification of financial barriers to care and potential funding sources, assistance with care logistics such as transportation and childcare, and referral to psychosocial support services for patients who need them. DOC will rely on an electronic patient-tracking platform, which will allow real-time tracking of all oncology patients and identify patients who miss or delay treatments. This will allow timely intervention and continuous quality monitoring of the program. In addition to patient navigation, DOC will seek to reduce delays in patient care by liaising with pathology and radiology services. RESULTS The program is in its development and pilot phase. So far, approximately 100 patients have been seen for consultation. We intend to capture epidemiologic data about cancer in Belize, as well as real-time data about the progression of patients through their treatment course. We aim to identify critical delays to patients’ care and design interventions to address them. CONCLUSION We believe that the DOC program will be particularly beneficial for the oncology patient population in Belize, because this population has a high burden of socioeconomic barriers to care and is largely unfamiliar with the complexity of oncologic care. We hypothesize that DOC can improve treatment appropriateness and timeliness and, thereby, patient outcomes in Belize.
The Pupil
Authors: Bouffard Marc A. 
Published: October 2019

ABSTRACT

PURPOSE OF REVIEW
The goal of this article is to review the anatomy and physiology of pupillary function and then employ that information to develop a comprehensive framework for understanding and diagnosing pupillary disorders.

RECENT FINDINGS
The contribution of rods and cones to the pupillary light reflex has long been known. A third photosensitive cell type, the intrinsically photosensitive retinal ganglion cell, has recently been discovered. This cell type employs melanopsin to mediate a portion of the pupillary light reflex independent of rods and cones (the postillumination pupillary response) and photic regulation of circadian rhythm.

SUMMARY
The autonomic nervous system regulates pupil size in response to stimuli. The parasympathetic nervous system causes miosis in response to light and near visual stimuli. These stimuli activate supranuclear pathways that project to the Edinger-Westphal nuclei. The sympathetic nervous system causes mydriasis in response to a variety of arousing factors, both physiologic (wakefulness) and pathologic (pain). Abnormalities of physiologic function cause disturbances of pupil size, shape, and response to stimuli. The clinical approach to pupillary abnormalities should focus on the clinical and pharmacologic assessment of the pupil’s expected response to diverse stimuli.
Infectious Optic Neuropathies
Authors: Eggenberger Eric R. 
Published: October 2019

ABSTRACT

PURPOSE OF REVIEW
This article reviews common infectious optic neuropathies, focusing on the more common and globally important entities.

RECENT FINDINGS
Novel infections continue to emerge and drift geographically over time; not infrequently, these have important neurologic or ocular features. Malarial retinal findings comprise a relatively specific set of findings and serve as an invaluable aid in the diagnosis of cerebral malaria. Therapy continues to evolve and is best formulated in concert with an infectious disease expert.

SUMMARY
Infectious optic neuropathies are less common than inflammatory or ischemic optic neuropathies; may present with varied, overlapping, and nonspecific clinical appearances; and comprise an important differential consideration demanding specific therapy.
Chiasmal and Postchiasmal Disease
Authors: Moss Heather E. 
Published: October 2019

ABSTRACT

PURPOSE OF REVIEW
This article reviews the anatomy, symptoms, examination findings, and causes of diseases affecting the optic chiasm, optic tracts, optic radiations, and occipital lobes.

RECENT FINDINGS
Modern ophthalmic imaging can be used to monitor the effects of diseases of the optic chiasm and tract on the retinal ganglion cells. It can also be used to visualize transsynaptic degeneration of the anterior visual pathway in the setting of acquired retrogeniculate lesions. Visual prostheses that directly stimulate the occipital lobe are a potential strategy for rehabilitation that is in active clinical trials.

SUMMARY
Detecting and characterizing visual deficits due to optic chiasm and retrochiasmal disease are important for the diagnosis, localization, and monitoring of neurologic disease; identifying patient disability; and guiding rehabilitation.
Approach to Diplopia
Authors: Glisson Christopher C. 
Published: October 2019

ABSTRACT

PURPOSE OF REVIEW
“Double vision” is a commonly encountered concern in neurologic practice; the experience of diplopia is always sudden and is frequently a cause of great apprehension and potential disability for patients. Moreover, while some causes of diplopia are benign, others require immediate recognition, a focused diagnostic evaluation, and appropriate treatment to prevent vision- and life-threatening outcomes. A logical, easy-to-follow approach to the clinical evaluation of patients with diplopia is helpful in ensuring accurate localization, a comprehensive differential diagnosis, and optimal patient care. This article provides a foundation for formulating an approach to the patient with diplopia and includes practical examples of developing the differential diagnosis, effectively using confirmatory examination techniques, determining an appropriate diagnostic strategy, and (where applicable) providing effective treatment.

RECENT FINDINGS
Recent population-based analyses have determined that diplopia is a common presentation in both ambulatory and emergency department settings, with 850,000 such visits occurring annually. For patients presenting to an outpatient facility, diagnoses are rarely serious. However, potentially life-threatening causes (predominantly stroke or transient ischemic attack) can be encountered. In patients presenting with diplopia related to isolated cranial nerve palsy, immediate neuroimaging can often be avoided if an appropriate history and examination are used to exclude worrisome etiologies.

SUMMARY
Binocular diplopia is most often due to a neurologic cause. The onset of true “double vision” is debilitating for most patients and commonly prompts immediate access to health care services as a consequence of functional impairment and concern for worrisome underlying causes. Although patients may seek initial evaluation through the emergency department or from their primary care/ophthalmic provider, elimination of an ocular cause will not infrequently result in the patient being referred for neurologic consultation. A logical, localization-driven, and evidence-based approach is the most effective way to arrive at the correct diagnosis and provide the best outcome for the patient.
Perturbed development of cranial neural crest cells in association with reduced sonic hedgehog signaling underlies the pathogenesis of retinoic-acid-induced cleft palate
Authors: Wang Qi , Kurosaka Hiroshi , Kikuchi Masataka , Nakaya Akihiro , Trainor Paul A. , Yamashiro Takashi 
Published: October 2019

ABSTRACT
Cleft palate (CP) is one of the most common congenital craniofacial anomalies in humans and can be caused by either single or multiple genetic and environmental factor(s). With respect to environmental factors, excessive intake of vitamin A during early pregnancy is associated with increased incidence of CP in offspring both in humans and in animal models. Vitamin A is metabolized to retinoic acid (RA); however, the pathogenetic mechanism of CP caused by altered RA signaling during early embryogenesis is not fully understood. To investigate the detailed cellular and molecular mechanism of RA-induced CP, we administered all-trans RA to pregnant mice at embryonic day (E)8.5. In the RA-treated group, we observed altered expression of Sox10, which marks cranial neural crest cells (CNCCs). Disruption of Sox10 expression was also observed at E10.5 in the maxillary component of the first branchial arch, which gives rise to secondary palatal shelves. Moreover, we found significant elevation of CNCC apoptosis in RA-treated embryos. RNA-sequencing comparisons of RA-treated embryos compared to controls revealed alterations in Sonic hedgehog (Shh) signaling. More specifically, the expression of Shh and its downstream genes Ptch1 and Gli1 was spatiotemporally downregulated in the developing face of RA-treated embryos. Consistent with these findings, the incidence of CP in association with excessive RA signaling was reduced by administration of the Shh signaling agonist SAG (Smoothened agonist). Altogether, our results uncovered a novel mechanistic association between RA-induced CP with decreased Shh signaling and elevated CNCC apoptosis.
Induced pluripotent stem cells as a tool for comparative physiology: lessons from the thirteen-lined ground squirrel
Authors: Ou Jingxing , Rosa Sarah , Berchowitz Luke E. , Li Wei 
Published: October 2019

ABSTRACT
Comparative physiologists are often interested in adaptive physiological phenomena found in unconventional model organisms; however, research on these species is frequently constrained by the limited availability of investigative tools. Here, we propose that induced pluripotent stem cells (iPSCs) from unconventional model organisms may retain certain species-specific features that can consequently be investigated in depth in vitro; we use hibernating mammals as an example. Many species (including ground squirrels, bats and bears) can enter a prolonged state of physiological dormancy known as hibernation to survive unfavorable seasonal conditions. Our understanding of the mechanisms underpinning the rapid transition and adaptation to a hypothermic, metabolically suppressed winter torpor state remains limited partially because of the lack of an easily accessible model. To address the fascinating unanswered questions underlying hibernation biology, we have developed a powerful model system: iPSCs from a hibernating species, the thirteen-lined ground squirrel (Ictidomys tridecemlineatus). These stem cells can potentially be differentiated into any cell type, and can be used for the analysis of cell-autonomous mechanisms that facilitate adaptation to hibernation and for comparisons with non-hibernators. Furthermore, we can manipulate candidate molecular and cellular pathways underlying relevant physiological phenomena by pharmacological or RNAi-based methods, and CRISPR/Cas9 gene editing. Moreover, iPSC strategies can be applied to other species (e.g. seals, naked mole rats, humming birds) for in vitro studies on adaptation to extreme physiological conditions. In this Commentary, we discuss factors to consider when attempting to generate iPSCs from unconventional model organisms, based on our experience with the thirteen-lined ground squirrel.
Uma Aplicação de Opções Reais na Avaliação de Licença de Prestação de Serviços de Telefonia Móvel 3G no Brasil
Authors: Stille Rafael , Lemme Celso Funcia , Brandão Luiz Eduardo Teixeira 
Published: October 2019

Este trabalho avaliou as contribuições do método de opções reais ao processo decisório em projetos de telecomunicações, estudando um caso real de aquisição, em licitação pública, de
uma licença de prestação de serviços de telefonia móvel 3G no Brasil. Foi encontrada uma diferença de 64% em relação ao valor obtido pelo método do Fluxo de Caixa Descontado, o
que poderia justificar os altos ágios pagos pelas empresas vencedoras da licitação, incompatíveis com o valor obtido pelos métodos tradicionais de análise. Isso indica que a
metodologia aplicada, facilmente replicável e bastante intuitiva, pode ser uma ferramenta útil para apoiar o processo decisório destas empresas.
Family experiences of oncological palliative and supportive care in children: can we do better?
Authors: Plessis Jan , Stones David , Meiring Michelle 
Published: October 2019

Aims: Families were interviewed as a quality improvement assessment for palliative and supportive care services for children. Methods: This exploratory qualitative study of family members of children with cancer was conducted at an academic hospital in central South Africa and a grounded theory approach was used. Face-to-face interviews using a semi-structured interview guide were conducted with 16 family members of 16 children. Findings: Parents felt supported by the healthcare professionals who were caring for their child, but several shortcomings were identified. These included erratic psychosocial support, minimal financial support and poor parental access to basic needs and food provision, preventable errors in procedures and a lack of support available for siblings. It is also worth noting that healthcare professionals did not always seem sufficiently equipped to attend to palliative care patients. Conclusion: Strategies to improve supportive and palliative care are needed for children with cancer and their families in a hospital setting. The interviews identified a number of themes and current shortcomings that should be considered to improve services.
Acupoint-catgut embedment combined with medication does not decrease interleukin-6 levels serum in patients with gastroesophageal reflux disease: a randomized controlled clinical trial
Authors: Fitri Andalia , Abdullah Murdani , Rengganis Iris , Mihardja Hasan , Baginda Intan Suri , Masthura Ainil 
Published: October 2019

BACKGROUND Gastroesophageal reflux disease (GERD) is a pathological condition caused by the reflux of stomach contents into the esophagus. GERD is a multifactorial disorder with an increase in prevalence worldwide. Interleukin-6 (IL-6) is a proinflammatory cytokine that is commonly found in the esophageal mucosa of GERD patients and associated with esophageal motor disorders. Acupoint-catgut embedment has long been known as adjunctive therapy for GERD. This study was aimed to establish the effect of acupoint-catgut embedment combined with medication on the IL-6 serum levels of patients with GERD.
METHODS This single-blind randomized controlled trial involved 40 GERD patients from the Gastroenterology Outpatient Clinic of Cipto Mangunkusumo Hospital that were randomly allocated to either catgut-embedding therapy plus medication or sham acupuncture with medication. Catgut-embedding therapy was given two times at CV12 (Zhongwan), ST36 (Zusanli), and BL21 (Weishu) every 15 days. Serum levels of IL-6 were measured by enzyme-linked immunosorbent assay as research output.
RESULTS There were no significant differences in the baseline levels of proinflammatory (IL-6) mediators between the groups. After 1-month treatment, the median levels of IL-6 were statistically insignificant decreased in catgut-embedding therapy plus medication versus sham acupuncture with medication (0.15 versus -0.16 pg/ml, respectively; p = 0.14).
CONCLUSIONS The results suggest that catgut-embedding therapy has not been proven to statistically influence the levels of IL-6 in patients with GERD.