bluuebunny/crossref_metadata_2025_split huggingface dataset:
Examining Practice and Learning Effects With Serial Administration of the Clinical Reaction Time Test in Healthy Young Athletes
Authors: Nguyen Cindy N. , Clements Reuben N. , Porter Lucas A. , Clements Nicole E. , Gray Matthew D. , Killian Dustin J. , Baker Russell T. 
Published: March 2018

Context: The clinical reaction time (RTclin) test has been recommended as a valid test for assessing concussion and determining recovery of reaction time function following concussion. However, it is unknown whether repeat assessment, as is used in postconcussion testing, is affected by learning or practice phenomena. Objective: To determine if a practice or learning effect is present with serial administration of the RTclin test. Design: Randomized control trial. Setting: University athletic training clinics. Participants: A total of 112 healthy collegiate athletes (age = 19.46 [1.34] y). Interventions: The control group completed the RTclin test on days 1 and 60. The experimental group completed the RTclin test on days 1, 2, 3, 7, and 60. Main Outcome Measure: Reaction time as measured with the RTclin test. Results: The difference in RTclin test performance from day 1 to day 60 was not significant (mean change = −2.77 [14.46] ms, P = .42, 95% confidence intervals, −6.40 to 0.862) between groups. The experimental group experienced significant improvement (λ = 0.784, F4,49 = 3.365, P = .02, η2 = .216, power = 0.81) with acute repeat testing. However, post hoc analysis did not reveal a significant difference between scores during the 5 test periods. Conclusions: The results suggest serial administration of the RTclin test does not produce a practice or learning effect. Clinicians, however, should be cautious as the results do provide evidence patients may demonstrate improved scores when testing occurs on repetitive days after initial exposure to the test.
One Intact Transmembrane Substrate Binding Site Is Sufficient for the Function of the Homodimeric Type I ATP-Binding Cassette Importer for Positively Charged Amino Acids Art(MP)
2
of Geobacillus stearothermophilus
Authors: Heuveling Johanna , Landmesser Heidi , Schneider Erwin 
Published: March 2018

ABSTRACT

ATP-binding cassette (ABC) transport systems comprise two transmembrane domains/subunits that form a translocation path and two nucleotide-binding domains/subunits that bind and hydrolyze ATP. Prokaryotic canonical ABC import systems require an extracellular substrate-binding protein for function. Knowledge of substrate-binding sites within the transmembrane subunits is scarce. Recent crystal structures of the ABC importer Art(QN)
2
for positively charged amino acids of
Thermoanerobacter tengcongensis
revealed the presence of one substrate molecule in a defined binding pocket in each of the transmembrane subunits, ArtQ (J. Yu, J. Ge, J. Heuveling, E. Schneider, and M. Yang, Proc Natl Acad Sci U S A 112:5243–5248, 2015,
https://doi.org/10.1073/pnas.1415037112
). This finding raised the question of whether both sites must be loaded with substrate prior to initiation of the transport cycle. To address this matter, we first explored the role of key residues that form the binding pocket in the closely related Art(MP)
2
transporter of
Geobacillus stearothermophilus
, by monitoring consequences of mutations in ArtM on ATPase and transport activity at the level of purified proteins embedded in liposomes. Our results emphasize that two negatively charged residues (E153 and D160) are crucial for wild-type function. Furthermore, the variant Art[M(L67D)P]
2
exhibited strongly impaired activities, which is why it was considered for construction of a hybrid complex containing one intact and one impaired substrate-binding site. Activity assays clearly revealed that one intact binding site was sufficient for function. To our knowledge, our study provides the first biochemical evidence on transmembrane substrate-binding sites of an ABC importer.

IMPORTANCE
Canonical prokaryotic ATP-binding cassette importers mediate the uptake of a large variety of chemicals, including nutrients, osmoprotectants, growth factors, and trace elements. Some also play a role in bacterial pathogenesis, which is why full understanding of their mode of action is of the utmost importance. One of the unsolved problems refers to the chemical nature and number of substrate binding sites formed by the transmembrane subunits. Here, we report that a hybrid amino acid transporter of
G. stearothermophilus
, encompassing one intact and one impaired transmembrane binding site, is fully competent in transport, suggesting that the binding of one substrate molecule is sufficient to trigger the translocation process.
Conformational Stability of the Hemagglutinin of H5N1 Influenza A Viruses Influences Susceptibility to Broadly Neutralizing Stem Antibodies
Authors: Wang Wei , Song Hyo Sook , Keller Paul W. , Alvarado-Facundo Esmeralda , Vassell Russell , Weiss Carol D. 
Published: March 2018

ABSTRACT
Vaccines that elicit broadly neutralizing antibodies to the conserved stem of hemagglutinin (HA) are being developed as universal influenza vaccines that protect against influenza across multiple years. However, different influenza virus strains, even those in the same subtype with identical stem sequences, can vary in susceptibility to broadly neutralizing stem antibodies, and the reasons are not understood. Here we studied potential mechanisms underlying the differing sensitivities of a panel of H5N1 HA pseudoviruses to broadly neutralizing stem antibodies. We found that greater HA conformational stability, as measured by thermal inactivation and pH triggering of conformational changes, correlates with reduced neutralization sensitivity and antibody binding to HA under neutral- and low-pH conditions. Our data indicate that the conformational stability of HA is an important attribute of susceptibility to broadly neutralizing stem antibodies and is influenced by residues outside the stem antibody epitopes.

IMPORTANCE
The influenza virus surface glycoprotein hemagglutinin (HA) mediates virus attachment and membrane fusion between virus and host cells, allowing the viral core to enter the host cell cytoplasm for replication. Fusion occurs when HA undergoes low-pH-induced-conformational changes during endocytosis. Broadly neutralizing antibodies targeted to the conserved stem region of HA interfere with conformational changes required for fusion. Vaccines that elicit such antibodies are being developed as novel universal influenza vaccines for multiyear protection. We investigated why H5N1 HAs from different strains differ in their sensitivity to broadly neutralizing stem antibodies despite having conserved epitopes. We report that HA conformational stability due to residues outside the antibody binding site accounted for much of the variation in susceptibility to neutralization by stem antibodies. These findings highlight the importance of nonepitope residues in influencing neutralization sensitivity to stem antibodies and the complexities in developing universal vaccines targeting conserved epitopes in the HA stem.
Estimating neonatal length of stay for babies born very preterm
Authors: Seaton Sarah E , Barker Lisa , Draper Elizabeth S , Abrams Keith R , Modi Neena , Manktelow Bradley N 
Published: March 2018

ObjectiveTo predict length of stay in neonatal care for all admissions of very preterm singleton babies.SettingAll neonatal units in England.PatientsSingleton babies born at 24–31 weeks gestational age from 2011 to 2014. Data were extracted from the National Neonatal Research Database.MethodsCompeting risks methods were used to investigate the competing outcomes of death in neonatal care or discharge from the neonatal unit. The occurrence of one event prevents the other from occurring. This approach can be used to estimate the percentage of babies alive, or who have been discharged, over time.ResultsA total of 20 571 very preterm babies were included. In the competing risks model, gestational age was adjusted for as a time-varying covariate, allowing the difference between weeks of gestational age to vary over time. The predicted percentage of death or discharge from the neonatal unit were estimated and presented graphically by week of gestational age. From these percentages, estimates of length of stay are provided as the number of days following birth and corrected gestational age at discharge.ConclusionsThese results can be used in the counselling of parents about length of stay and the risk of mortality.
FOXO3a expression is associated with lymph node metastasis and poor disease-free survival in triple-negative breast cancer
Authors: Rehman Abdul , Kim Yeseul , Kim Hyunsung , Sim Jongmin , Ahn Hyein , Chung Min Sung , Shin Su-Jin , Jang Kiseok 
Published: March 2018

AimsForkhead box O (FOXO) transcription factors, consisting of FOXO1, FOXO3a, FOXO4 and FOXO6, are involved in carcinogenesis and tumour progression. Recent studies have suggested that FOXOs act as tumour suppressors in a variety of human cancers. This study investigated the clinicopathological significance of FOXOs in triple-negative breast cancer (TNBC).MethodsFOXO protein expressions were assessed by immunohistochemistry in 125 TNBC tissues. Correlations between FOXO protein expression and various clinicopathological parameters, including patients’ survival, were investigated. MDA-MB-468 cell line was used for in vitro cell proliferation and migration assay.ResultsFOXO1 protein expression was not observed in all 125 TNBC tissues. FOXO4 and FOXO6 protein expressions were detected in 11 (8.8%) and 14 (11.2%) TNBC tissues, respectively. Loss of FOXO4 expression was significantly associated with high histological grade (P=0.014, χ2test), and TNBCs with positive FOXO6 expression correlated with high grade (P=0.020, χ2test). FOXO3a expression was detected in 40 (32%) TNBC cases and correlated with adverse clinicopathological features, such as lymph node metastasis (P=0.021, χ2test), perineural invasion (P=0.013, χ2test) and higher Ki-67 proliferation index (P=0.048, t-test). Additionally, FOXO3a expression was significantly associated with poor disease-free survival (P=0.015, log-rank test). In the in vitro study, siRNA-mediated FOXO3a knockdown in the MDA-MB-468 cell line inhibited cell proliferation and migration.ConclusionAmong FOXO members, FOXO3a may have a potential role in promoting tumour cell migration and proliferation and may serve as a prognostic biomarker and a potential therapeutic target for TNBC.
A novel homozygous frameshift mutation in theFUCA1gene causes both severe and mild fucosidosis
Authors: Saleh-Gohari Nasrollah , Saeidi Kolsoum , Zeighaminejad Roya 
Published: March 2018

AimsFucosidosis is a rare autosomal recessive lysosomal storage disorder caused by α-L-fucosidase deficiency as a result ofFUCA1gene mutations. Here, we studied clinical features and the molecular basis of fucosidosis in a family from Iran, including two probands and nine family members.MethodsDNA sample of two probands were screened for gene defects using a next generation sequencing technique. The sequencing processes were performed on an Illumina Hiseq 4000 platform. Sequence reads were analysed using BWA-GATK.ResultsNext generation sequencing revealed a frameshift mutation caused by 2 bp deletion (c.837_838 delTG; p.Cys279) in theFUCA1gene. The identified mutation was tested in all participants. Homozygous patients had almost all the complications associated with fucosidosis, while heterozygous carriers were unaffected.ConclusionsThe variant c.837_838 delTG; p.Cys279 has not been reported previously and is predicted to be pathogenic due to a premature stop codon.
IMGN779, a Novel CD33-Targeting Antibody–Drug Conjugate with DNA-Alkylating Activity, Exhibits Potent Antitumor Activity in Models of AML
Authors: Kovtun Yelena , Noordhuis Paul , Whiteman Kathleen R. , Watkins Krystal , Jones Gregory E. , Harvey Lauren , Lai Katharine C. , Portwood Scott , Adams Sharlene , Sloss Callum M. , Schuurhuis Gerrit Jan , Ossenkoppele Gert , Wang Eunice S. , Pinkas Jan 
Published: March 2018

Abstract
The myeloid differentiation antigen CD33 has long been exploited as a target for antibody-based therapeutic approaches in acute myeloid leukemia (AML). Validation of this strategy was provided with the approval of the CD33-targeting antibody–drug conjugate (ADC) gemtuzumab ozogamicin in 2000; the clinical utility of this agent, however, has been hampered by safety concerns. Thus, the full potential of CD33-directed therapy in AML remains to be realized, and considerable interest exists in the design and development of more effective ADCs that confer high therapeutic indices and favorable tolerability profiles. Here, we describe the preclinical characterization of a novel CD33-targeting ADC, IMGN779, which utilizes a unique DNA-alkylating payload to achieve potent antitumor effects with good tolerability. The payload, DGN462, is prototypical of a novel class of purpose-created indolinobenzodiazeprine pseudodimers, termed IGNs. With low picomolar potency, IMGN779 reduced viability in a panel of AML cell lines in vitro. Mechanistically, the cytotoxic activity of IMGN779 involved DNA damage, cell-cycle arrest, and apoptosis consistent with the mode of action of DGN462. Moreover, IMGN779 was highly active against patient-derived AML cells, including those with adverse molecular abnormalities, and sensitivity correlated to CD33 expression levels. In vivo, IMGN779 displayed robust antitumor efficacy in multiple AML xenograft and disseminated disease models, as evidenced by durable tumor regressions and prolonged survival. Taken together, these findings identify IMGN779 as a promising new candidate for evaluation as a novel therapeutic in AML. Mol Cancer Ther; 17(6); 1271–9. ©2018 AACR.
Transnational Travels of the Caterpillar Fungus in the Fifteenth through Nineteenth Centuries
Authors: Lu Di 
Published: March 2018

AbstractThe caterpillar fungus is representative of Chinese medicinal substances that are of Tibetan origin. From the early eighteenth century, due to people’s curiosity about exotic natural objects and their pursuit of new effective medicinal substances, the caterpillar fungus began to spread to Chinese society and even the rest of the world. Through intricate transnational networks of people, societies, and institutions, its specimens first arrived in France and Japan in the 1720s, Britain in about 1831, Russia in 1851, and America in 1891. The caterpillar fungus initiated European research on fungal parasitism in animals, and created new positions in the European natural order. European taxonomic identifications of the caterpillar fungus interacted with the European materia medica enterprise. Meanwhile, new European perceptions about its natural properties came to dominate Sino-Tibetan understandings of its properties and the nature of its cross-species transformation; but some Chinese medical knowledge about the caterpillar fungus was actively gathered in Europe due to its value as a medicinal substance. The tensions and negotiations surrounding the caterpillar fungus before the end of the nineteenth century can be seen as a prelude to the reconstruction of Chinese materia medica in the first half of the twentiethcentury.
Desiderata for the Principles of Compilation of a Canon of Buddhism and Medicine
Authors: Burton-Rose Daniel 
Published: March 2018

Abstract“Buddhist medicine” is a neologism that first took root in the mid-twentieth century and has been gaining traction over the last few decades. While specialists treat this phrase as a heuristic device best used with caution, the 100-volume compendium collectionComplete Works of Chinese Buddhist Medicine and Pharmacopeia(Zhongguo Fojiao yiyao quanshu中國佛教醫藥全書, 2011) is a concretization of vague terminology into an actual body of works. The present article reviews the claims of the editors of theComplete Works of Chinese Buddhist Medicine and Pharmacopeiaagainst the works actually included in the compendium to find that the selection criteria was inadequate and choice of exemplars haphazard. Attempting an intellectual history of the present, the article analyses the editors’ motivations in light of the politics of canon compilation in the late imperial period, finding that the claim of mastering a comprehensive body of knowledge remains institutionally attractive in the contemporary People’s Republic of China, even if it is divorced from critical scholarly abilities comparable to those of the editors of Qing dynasty scholars. Cognizant that Digital Humanities projects continue to rely on printed compendiums for the texts they digitize, the article closes with suggested guidelines for the compilation of future collections on Buddhism and medicine in order to make them more useful to present day scholars.
Rediscovery of the hadal species Amblyops magnus Birstein &amp; Tchindonova, 1958 (Crustacea: Mysida: Mysidae): first record from the Mariana Trench
Authors: KOU QI , LI XINZHENG , HE LISHENG , WANG YONG 
Published: March 2018

The blind deep-sea mysid Amblyops magnus Birstein & Tchindonova, 1958 is recorded for the first time from the Mariana Trench based on an adult female specimen collected near the Challenger Deep at a depth of 6555 m. The specimen was described, illustrated and compared with the type description as well as with the materials previously collected from the Japan Trench. The mitochondrial COI barcode was also obtained from the specimen and submitted to GenBank. This is the third discovery of this rare species and significantly extends its geographic distribution range to the low latitude hadal zone.
Argentine Documentary Film and the Politics of Presence: Jorge Prelorán’s Valle Fértil
Authors: Moore Christopher 
Published: March 2018

Jorge Prelorán’s experiences directing and distributing his 1972 film Valle Fértil force us to reconsider what we regard as the significance of documentary. Far too often the historiography of Argentine and Latin American cinema rests either on director biographies, wherein auteurs’ party allegiances define their work, or on textual analysis of the final cut, wherein we isolate finished products from the history of their making. The case of Valle Fértil suggests that the localized, personal interactions inherent to production and distribution are an equally relevant legacy of the filmmaking experience. Given that other documentaries at this time were similarly predicated on sustained contact with select populations, the work of filmmakers ranging from Fernando Birri to Fernando Solanas might then likewise be analyzed through such a lens. For this reason, Jorge Prelorán, so often seen as unique or as a counterexample in the history of Argentine film, becomes instead exemplary. La experiencia de Jorge Prelorán al dirigir y distribuir su película de 1972 Valle Fértil nos obliga a reconsiderar eso que entendemos como el significado del documental. Con demasiada frecuencia, la historiografía del cine argentino y latinoamericano descansa en las biografías de los directores, donde las lealtades partidarias de los autores definen su trabajo, o en el análisis textual del corte final, en el que aislamos el producto terminado de la historia de su creación. El caso de Valle Fértil sugiere que las interacciones locales y personales inherentes a la producción y distribución son un legado tan relevante como la experiencia cinematográfica. Dado que otros documentales del momento se basaban, similarmente, en un contacto sostenido con poblaciones particulares, el trabajo de cineastas que abarcan desde Fernando Birri a Fernando Solanas también podría ser analizado a través de dicho lente. Por esta razón, Jorge Prelorán, a menudo visto como un caso único o un contraejemplo en la historia del cine argentino, se convierte en un caso ejemplar.
Selling Off-Grid Light to Liquidity-Constrained Consumers
Authors: Uppari Bhavani Shanker , Popescu Ioana , Netessine Serguei 
Published: March 2018

Problem definition: A large proportion of the world’s population has no access to electricity and so relies on noxious kerosene for their lighting needs. Solar-based solutions require a large up-front investment and are often unaffordable in this market owing to consumers’ tight liquidity constraints. As an alternative, there are business models relying on rechargeable light bulbs that are sold at a subsidized price (which renders them affordable) and require regular micropayments for recharges (which eases liquidity constraints). These bulbs provide a cheaper and healthier light source than kerosene, yet their adoption is lower than expected, and some consumers continue to use kerosene. This paper explores the potential drivers of such preferences and proposes strategies to alter them. Academic/practical relevance: Unlike most of the existing operations management literature, which focuses on the problems in developed economies, our paper studies a problem specific to the poor population. Our novel modeling approach, which incorporates several operational features of the impoverished regions, could also serve as a template for other potential modeling attempts in similar settings. Methodology: We propose a stylized consumer behavior model that accounts for—in addition to the monetary cost incurred while using a particular light source—the inconvenience cost (resulting from repeated travel to the purchase center) and blackout cost (resulting from liquidity constraints) associated with that source to explain the consumer preference for kerosene and to recommend strategies that could mitigate that preference. Results: Although kerosene lighting is more expensive than bulbs, consumers who face either high inconvenience costs or high blackout costs prefer kerosene to bulbs because the former’s flexibility, with regard to quantity, helps reduce whichever cost is dominating. At the firm level, there is an optimal bulb capacity and recharge price pair that maximizes the firm’s revenue; furthermore, a firm can reverse the preferences for kerosene by increasing the flexibility of the bulbs (e.g., by allowing partial recharges). Although strategies—such as price discounts and mobile micropayments—which alleviate liquidity constraints are not in themselves sufficient to ensure higher adoption rates, increased bulb use becomes more likely when they are combined with inconvenience-reducing strategies. Managerial implications: Our paper sheds light on the structure of the market in which firms operate by identifying the characteristics of the market segments that prefer kerosene. It also helps the firms make better decisions by evaluating the efficacy of several strategies in terms of increasing the adoption of bulbs.The online appendix is available at https://doi.org/10.1287/msom.2017.0673 .This paper has been accepted for the Manufacturing & Service Operations Management Special Issue on Value Chain Innovations in Developing Economies.