bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utility-value intervention with parents increases students’ STEM preparation and career pursuit
Authors: Rozek Christopher S. , Svoboda Ryan C. , Harackiewicz Judith M. , Hulleman Chris S. , Hyde Janet S. 
Published: January 2017

Significance
The need for students trained in science, technology, engineering, and mathematics (STEM) jobs is growing rapidly in the United States, yet students do not enroll in the necessary courses to prepare for STEM careers. In a randomized controlled trial, parents in the utility–value intervention group received materials detailing the importance of STEM for their adolescents in high school. The intervention increased mathematics and science ACT scores and course-taking in high school. This greater high-school STEM preparation was associated, 5 y later, with increased STEM career pursuit. These findings suggest that educational policies should promote the personal relevance of high-school mathematics and science courses and involve parents in helping to promote STEM preparation and career pursuit.
Harmonic template neurons in primate auditory cortex underlying complex sound processing
Authors: Feng Lei , Wang Xiaoqin 
Published: January 2017

Significance
Harmonicity is a fundamental element of music, speech, and animal vocalizations. How the brain extracts harmonic structures embedded in complex sounds remains largely unknown. We have discovered a unique population of harmonic template neurons in the core region of auditory cortex of marmosets, a highly vocal primate species. Responses of these neurons show nonlinear facilitation to harmonic complex sounds over inharmonic sounds and selectivity for particular harmonic structures. Such neuronal selectivity may form the basis of harmonic processing by the brain and has important implications for music and speech processing.
A natural product inhibits the initiation of α-synuclein aggregation and suppresses its toxicity
Authors: Perni Michele , Galvagnion Céline , Maltsev Alexander , Meisl Georg , Müller Martin B. D. , Challa Pavan K. , Kirkegaard Julius B. , Flagmeier Patrick , Cohen Samuel I. A. , Cascella Roberta , Chen Serene W. , Limbocker Ryan , Sormanni Pietro , Heller Gabriella T. , Aprile Francesco A. , Cremades Nunilo , Cecchi Cristina , Chiti Fabrizio , Nollen Ellen A. A. , Knowles Tuomas P. J. , Vendruscolo Michele , Bax Adriaan , Zasloff Michael , Dobson Christopher M. 
Published: January 2017

Significance
Parkinson’s disease is characterized by the presence in brain tissues of aberrant aggregates primarily formed by the protein α-synuclein. It has been difficult, however, to identify compounds capable of preventing the formation of such deposits because of the complexity of the aggregation process of α-synuclein. By exploiting recently developed highly quantitative in vitro assays, we identify a compound, squalamine, that blocks α-synuclein aggregation, and characterize its mode of action. Our results show that squalamine, by competing with α-synuclein for binding lipid membranes, specifically inhibits the initiation of the aggregation process of α-synuclein and abolishes the toxicity of α-synuclein oligomers in neuronal cells and in an animal model of Parkinson’s disease.
Field-scale experiments reveal persistent yield gaps in low-input and organic cropping systems
Authors: Kravchenko Alexandra N. , Snapp Sieglinde S. , Robertson G. Philip 
Published: January 2017

Significance
Meeting future food needs requires a substantial increase in the yields obtained from existing cropland. Prior global analyses have suggested that these gains could come from closing yield gaps—differences between yields from small-plot research versus those in farmer fields. However, closing this gap requires knowledge of causal factors not yet identified experimentally. Results here suggest that yield gaps can be closed using farming practices that use conventional synthetic chemicals, but practices that rely more on biological management—as is the case throughout much of the developing world and in organic agriculture—require renewed attention to field-scale resource demands and place greater emphasis on the importance of field-scale experimental research.
Repair shielding of platinum-DNA lesions in testicular germ cell tumors by high-mobility group box protein 4 imparts cisplatin hypersensitivity
Authors: Awuah Samuel G. , Riddell Imogen A. , Lippard Stephen J. 
Published: January 2017

Significance
High-mobility group box protein 4 (HMGB4) is a transcription repressor preferentially expressed in the testes and binds cisplatin-damaged DNA. Investigating the DNA-damage recognition potential of HMGB4 and its relevance to cancer is of clinical importance. In this study, we found that HMGB4 regulates the sensitivity of testicular germ cell tumors (TGCTs) to cisplatin treatment. HMGB4 imparts repair shielding of platinum-DNA lesions in human TGCTs, rendering lesions inaccessible to the nucleotide excision repair (NER) machinery. Our results show that cisplatin-resistant breast cancer cells complemented with HMGB4 become sensitive to cisplatin. Furthermore, the ability of HMGB4 to modulate the cell cycle response, NER, apoptosis, and MAPK suggests a critical role for this protein in conveying cisplatin hypersensitivity in TGCTs.
Human NF-κB repressing factor acts as a stress-regulated switch for ribosomal RNA processing and nucleolar homeostasis surveillance
Authors: Coccia Marta , Rossi Antonio , Riccio Anna , Trotta Edoardo , Santoro Maria Gabriella 
Published: January 2017

Significance
Quality control of ribosomal RNA (rRNA) processing is critical for ribosome biogenesis, nucleolar homeostasis, and cell survival; however, the molecular mechanisms governing rRNA processing under stress conditions are poorly understood. This study identifies human NF-κB repressing factor (NKRF) as a HSF1 target gene essential for nucleolar homeostasis during proteotoxic stress. Rather than preventing protein misfolding and/or aggregation, this unconventional stress protein has a critical role in preventing aberrant rRNA precursors and discarded fragment accumulation and directing rRNA processing dynamics. The findings highlight a key aspect of the human cell response to proteotoxic stress, opening new scenarios on ribosome biogenesis regulation.
An RNA-based signature enables high specificity detection of circulating tumor cells in hepatocellular carcinoma
Authors: Kalinich Mark , Bhan Irun , Kwan Tanya T. , Miyamoto David T. , Javaid Sarah , LiCausi Joseph A. , Milner John D. , Hong Xin , Goyal Lipika , Sil Srinjoy , Choz Melissa , Ho Uyen , Kapur Ravi , Muzikansky Alona , Zhang Huidan , Weitz David A. , Sequist Lecia V. , Ryan David P. , Chung Raymond T. , Zhu Andrew X. , Isselbacher Kurt J. , Ting David T. , Toner Mehmet , Maheswaran Shyamala , Haber Daniel A. 
Published: January 2017

Significance
The early detection of hepatocellular carcinoma (HCC) is of paramount importance for improving patient outcomes, yet an accurate, high-throughput screening methodology has yet to be developed. By combining microfluidic depletion of hematopoietic cells from blood specimens with absolute quantification of lineage-derived transcripts, we demonstrate the highly specific detection of circulating tumor cells, enabling noninvasive detection and clinical monitoring of HCC.
Mitochondrial fusion dynamics is robust in the heart and depends on calcium oscillations and contractile activity
Authors: Eisner Verónica , Cupo Ryan R. , Gao Erhe , Csordás György , Slovinsky William S. , Paillard Melanie , Cheng Lan , Ibetti Jessica , Chen S. R. Wayne , Chuprun J. Kurt , Hoek Jan B. , Koch Walter J. , Hajnóczky György 
Published: January 2017

Significance
Mitochondrial function is supported by dynamic quality control processes, such as mitochondrial fusion. Cardiac contractility depends on mitochondrial metabolism, yet in cardiomyocytes, mitochondria are confined among myofibrils, raising questions about the possibility of mitochondrial physical communication. Here we demonstrate that mitochondrial continuity is robust and fusion is frequent in freshly isolated rat ventricular myocytes, manifesting both as rapid content mixing events between adjacent organelles and slower, often long-distance events. We show that mitochondrial fusion decreases dramatically in culture because of the decay in contractile activity and, more specifically, the underlying calcium oscillations, which involve mitofusin 1 (Mfn1) abundance. In addition, we show that attenuation of cardiac contractility in vivo in alcoholic animals is also associated with depressed mitochondrial fusion.
Modification of host dendritic cells by microchimerism-derived extracellular vesicles generates split tolerance
Authors: Bracamonte-Baran William , Florentin Jonathan , Zhou Ying , Jankowska-Gan Ewa , Haynes W. John , Zhong Weixiong , Brennan Todd V. , Dutta Partha , Claas Frans H. J. , van Rood Jon J. , Burlingham William J. 
Published: January 2017

Significance
The induction of tolerance is still an ideal and largely unachieved goal in the transplantation and autoimmunity fields. Understanding natural allotolerance mechanisms could help realize this objective. In this study we found that maternal microchimerism generated “split” tolerance, stimulating classical alloreactivity (i.e., recognition of intact peptide/allo-MHC class II complexes by CD4 T cells), while silencing CD4 T cells responding to allopeptide in a self-MHC–restricted manner. These contrary activities could be attributed to the presence of separate antigenic microdomains with different costimulatory properties on the surface of a single host dendritic cell. The possibility that this state develops from interaction with a microchimerism-derived extracellular vesicle has important implications for cell biology, cancer immunotherapy, and molecular immunology.
α-Synuclein binds and sequesters PIKE-L into Lewy bodies, triggering dopaminergic cell death via AMPK hyperactivation
Authors: Kang Seong Su , Zhang Zhentao , Liu Xia , Manfredsson Fredric P. , He Li , Iuvone P. Michael , Cao Xuebing , Sun Yi E. , Jin Lingjing , Ye Keqiang 
Published: January 2017

Significance
We discovered that α-synuclein interacts with the neuroprotective protein phosphoinositide-3 kinase enhancer L (PIKE-L) in an S129 phosphorylation-dependent manner and sequesters PIKE-L in Lewy bodies, leading to the hyperactivation of AMP-activated protein kinase (AMPK) and subsequent dopaminergic neuronal cell death. Our findings may identify a molecular mechanism by which α-synuclein triggers dopaminergic neuronal cell death in Parkinson’s disease.
Human transposon insertion profiling: Analysis, visualization and identification of somatic LINE-1 insertions in ovarian cancer
Authors: Tang Zuojian , Steranka Jared P. , Ma Sisi , Grivainis Mark , Rodić Nemanja , Huang Cheng Ran Lisa , Shih Ie-Ming , Wang Tian-Li , Boeke Jef D. , Fenyö David , Burns Kathleen H. 
Published: January 2017

Significance
Much of our genome is repetitive sequence. This property poses challenges for investigators because differences in repetitive sequences are difficult to detect. With hundreds of thousands of similar repeats, it has been difficult to discern how one person’s genome differs from another person’s genome or how tumor DNA differs from normal DNA. To solve this issue, we developed methods to target next-generation sequencing to the insertion sites of the most variable repeats. Computational pipelines to make these studies scalable and more widely accessible were needed, however. Here, we report a pipeline that accomplishes this goal. We use it to demonstrate insertions of the long interspersed element-1 (LINE-1) acquired in ovarian cancer that may contribute to the development of these tumors.
Loss of astrocyte cholesterol synthesis disrupts neuronal function and alters whole-body metabolism
Authors: Ferris Heather A. , Perry Rachel J. , Moreira Gabriela V. , Shulman Gerald I. , Horton Jay D. , Kahn C. Ronald 
Published: January 2017

Significance
Cholesterol is important for normal brain function and it is believed that astrocytes produce most brain cholesterol. We have previously shown that diabetes results in decreased brain cholesterol synthesis by a reduction in the transcription factor sterol regulatory element-binding protein 2 (SREBP2). Using a mouse model in which SREBP2 has been knocked out in astrocytes, we show that astrocyte SREBP2 is required for normal brain development and behavior. Furthermore, this results in a shift in metabolism driven by increased brain glucose oxidation. Thus, SREBP2-mediated cholesterol synthesis in astrocytes plays an important role in brain development and function, and altered brain cholesterol synthesis may contribute to the interaction between diabetes and altered brain function.
Effects of pre-germinated brown rice treatment high-fat diet-induced metabolic syndrome in C57BL/6J mice
Authors: Yen Hsueh-Wei , Lin Hui-Li , Hao Chi-Long , Chen Fu-Chih , Chen Chun-Yun , Chen Jia-Hao , Shen Kuo-Ping 
Published: January 2017

Abstract
To investigate using pre-germinated brown rice (PGBR) to treat metabolic syndrome, we fed one group of mice standard-regular-diet (SRD) for 20 weeks and another group of mice high-fat-diet (HFD) for 16 weeks. We subdivided them into HFD group and HFD + PGBR group whose dietary carbohydrate was replaced with PGBR for 4 weeks. The HFD group gained more weight, had higher blood pressure, heart rate, blood glucose and lipids, liver levels of TG, feces TG and bile acid, lower adipose levels of adipocytokine, lower skeletal muscle IR, IRS-1, IRS-2, PI3 K, Akt/PKB, GLUT-1, GLUT-4, GCK and PPAR-γ; higher liver SREBP-1, SCD-1, FAS, HMGCR, LDLR, CYP7α1 and PPAR-α, and higher adipose SREBP-1, SCD-1, FAS, and lower adipose PPAR-α and adiponectin. The HFD + PGBR group had clearly improved blood pressure, biochemical parameters and above proteins expressions. PGBR successful treatment of metabolic syndrome was achieved through improvements in glucose and lipid synthesis and metabolism.
Greater Protein and Energy Intake May Be Associated With Improved Mortality in Higher Risk Critically Ill Patients: A Multicenter, Multinational Observational Study*
Authors: Compher Charlene , Chittams Jesse , Sammarco Therese , Nicolo Michele , Heyland Daren K. 
Published: January 2017

Objectives:
Controversy exists about the value of greater nutritional intake in critically ill patients, possibly due to varied patient nutritional risk. The objective of this study was to investigate whether clinical outcomes vary by protein or energy intake in patients with risk evaluated by the NUTrition Risk in the Critically Ill score.

Design:
Prospective observational cohort.

Setting:
A total of 202 ICUs.

Patients:
A total of 2,853 mechanically ventilated patients in ICU greater than or equal to 4 days and a subset of 1,605 patients in ICU greater than or equal to 12 days.

Interventions:
None.

Measurements and Main Results:
In low-risk (NUTrition Risk in the Critically Ill, < 5) and high-risk (NUTrition Risk in the Critically Ill, ≥ 5) patients, mortality and time to discharge alive up to day 60 were assessed relative to nutritional intake over the first 12 days using logistic regression and Cox proportional hazard regression, respectively. In high-risk but not low-risk patients, mortality was lower with greater protein (4-d sample: odds ratio, 0.93; 95% CI, 0.89–0.98; p = 0.003 and 12-d sample: odds ratio, 0.90; 95% CI, 0.84–0.96; p = 0.003) and energy (4-d sample: odds ratio, 0.93; 95% CI, 0.89–0.97; p < 0.001 and 12-d sample: odds ratio, 0.88; 95% CI, 0.83–0.94; p < 0.001) intake. In the 12-day sample, there was significant interaction among NUTrition Risk in the Critically Ill category, mortality, and protein and energy intake, whereas in the 4-day sample, the test for interaction was not significant. In high-risk but not low-risk patients, time to discharge alive was shorter with greater protein (4-d sample: hazard ratio, 1.05; 95% CI, 1.01–1.09; p = 0.01 and 12-d sample: hazard ratio, 1.09; 95% CI, 1.03–1.16; p = 0.002) and energy intake (4-d sample: hazard ratio, 1.05; 95% CI, 1.01–1.09; p = 0.02 and 12-d sample: hazard ratio, 1.09; 95% CI, 1.03–1.16; p = 0.002). In the 12-day sample, there was significant interaction among NUTrition Risk in the Critically Ill category, time to discharge alive, and protein and energy intake, whereas in the 4-day sample, the test for interaction was not significant.

Conclusions:
Greater nutritional intake is associated with lower mortality and faster time to discharge alive in high-risk, longer stay patients but not significantly so in nutritionally low-risk patients.
Vision-Related Quality of Life Before and After Deep Anterior Lamellar Keratoplasty
Authors: Yildiz Elvin , Toklu Meltem , Turan Vural Ece 
Published: January 2017

Objectives:
To determine changes in the vision-related quality of life in patients undergoing deep anterior lamellar keratoplasty (DALK) by using the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25).

Methods:
Thirty-five patients who were scheduled for DALK between March 1, 2013, and March 1, 2014 were asked to complete the NEI VFQ-25. NEI VFQ-25 was administered again at 6 months and at 1 year postoperatively. Data on patients' age, sex, preoperative diagnosis, preoperative and postoperative best-corrected visual acuity, and postoperative astigmatism were recorded.

Results:
Successful DALK with the Anwar big bubble technique was achieved in 23 of 35 (65.7%) patients. The indications for surgery were keratoconus in 15 patients (62.2%), stromal corneal dystrophies in 4 (17%), and corneal scar in 4 (17%). The mean preoperative NEI VFQ-25 composite score (55.2±19.7) improved significantly (76.9±11.6) at 6 months after DALK and continued to improve (84.3±6.6) at 1 year postoperatively (Friedman test, P=0.001). All NEI VFQ-25 subscale item scores increased significantly after surgery. The patients' age was significantly correlated with the NEI VFQ-25 subscale score of mental health at 6 month and at 1 year postoperatively (r=0.92, P=0.008 and r=0.94, P=0.005, respectively). There was a negative relationship between postoperative astigmatism at 1 year and NEI VFQ-25 ocular pain, social functioning, peripheral vision, and mental health subscale scores (r=−0.76, P=−0.07; r=−0.53, P=0.2; r=−0.53, P=0.27; r=−0.80, P=0.05).

Conclusion:
Vision-related quality of life improved significantly after DALK and continued to improve after suture removal.
The Characteristics of Excimer Laser Refractive Surgery Candidates
Authors: Hashemi Hassan , Khabazkhoob Mehdi , Pakzad Reza , Yekta Abbasali , Nojomi Marzieh , Nabovati Payam 
Published: January 2017

Purpose:
To determine the demographic and refractive characteristics of excimer laser refractive surgery candidates in Iran.

Methods:
This was a cross-sectional study between 2010 and 2014. All information was collected from 28 centers randomly selected from 12 provinces. Then, for each season of the year, one week was chosen through simple random selection, and within each week, 3 days were again chosen randomly. All excimer laser surgical procedures performed during these 3 days were identified by training staff, and data were extracted from patient charts.

Results:
A total of 14,569 charts were reviewed; 67.5% of the subjects were female and the rest were male. Of the total surgeries, 18.6% had been done in 2010 which reached to 19.1% in 2014. The mean age of people receiving refractive surgery showed an upward trend (P<0.001) and female patients were significantly younger than male patients (P<0.001). The 25 to 39 years age group received the highest number of surgeries (31.9% of the total) and there was a significant association with gender (P<0.001). The most common refractive error was compound myopic astigmatism with a prevalence of 79.3%. In 2010, 33.3% of the performed surgeries were covered by insurance policies, and this decreased to 30.2% in 2014 (P<0.001).

Conclusion:
Women with compound myopic astigmatism in the age range of 25 and 35 years are the most frequent users of excimer laser refractive surgery. Less than one-third of laser refractive surgeries are covered by insurance policies. Therefore, proper planning for improving services to this group must be given priority.
A Novel Treatment using an Intraventricular Stent Graft for Postinfarction Ventricular Septal Rupture in a Porcine Model
Authors: Nishida Yuji , Tomita Shigeyuki , Kiuchi Ryuta , Ohtake Hiroshi , Watanabe Go 
Published: January 2017

Objective Ventricular septal rupture (VSR) is a severe complication of acute myocardial infarction, and the conventional technique for repair is associated with high operative mortality. A novel intraventricular stent graft (IVSG) device was tested as a less invasive treatment for VSR; it does not require cardiopulmonary bypass, cardiac arrest, or left ventricular incision. Its effectiveness was assessed using animal experiments. Methods Six pigs were placed on cardiopulmonary bypass. The VSR model was created by making a hole in the interventricular septum via the right ventricle. Animals were weaned off the bypass. The sheath encasing the device was advanced over the guidewire, and the IVSG was placed in the left ventricle. Before and after rupture creation and after device deployment, left ventriculography was performed, hemodynamic data were collected, and Qp/Qs values were measured. Results All procedures were completed safely. The left-to-right shunt seen after rupture creation disappeared after device deployment. The pulmonary-to-systemic blood flow ratio after rupture was 3.35 ± 1.00, decreasing significantly to 1.09 ± 0.10 after device deployment (P = 0.007). Hemodynamic instability after rupture creation improved dramatically after deployment. Conclusions The use of our new IVSG in this VSR animal experiment model significantly decreased the left-to-right shunt. The new device was able to control the acute heart failure associated with VSR with a minimally invasive procedure during the hyperacute phase of heart failure. Potential improvements in VSR treatment outcomes are expected with its clinical application.