bluuebunny/crossref_metadata_2025_split huggingface dataset:
A role for BDNF- and NMDAR-induced lysosomal recruitment of mTORC1 in the regulation of neuronal mTORC1 activity
Authors: Khamsing Dany , Lebrun Solène , Fanget Isabelle , Larochette Nathanaël , Tourain Christophe , de Sars Vincent , Brunstein Maia , Oheim Martin , Carrel Damien , Darchen François , Desnos Claire 
Published: July 2021

AbstractMemory and long term potentiation require de novo protein synthesis. A key regulator of this process is mTORC1, a complex comprising the mTOR kinase. Growth factors activate mTORC1 via a pathway involving PI3-kinase, Akt, the TSC complex and the GTPase Rheb. In non-neuronal cells, translocation of mTORC1 to late endocytic compartments (LEs), where Rheb is enriched, is triggered by amino acids. However, the regulation of mTORC1 in neurons remains unclear. In mouse hippocampal neurons, we observed that BDNF and treatments activating NMDA receptors trigger a robust increase in mTORC1 activity. NMDA receptors activation induced a significant recruitment of mTOR onto lysosomes even in the absence of external amino acids, whereas mTORC1 was evenly distributed in neurons under resting conditions. NMDA receptor-induced mTOR translocation to LEs was partly dependent on the BDNF receptor TrkB, suggesting that BDNF contributes to the effect of NMDA receptors on mTORC1 translocation. In addition, the combination of Rheb overexpression and artificial mTORC1 targeting to LEs by means of a modified component of mTORC1 fused with a LE-targeting motif strongly activated mTOR. To gain spatial and temporal control over mTOR localization, we designed an optogenetic module based on light-sensitive dimerizers able to recruit mTOR on LEs. In cells expressing this optogenetic tool, mTOR was translocated to LEs upon photoactivation. In the absence of growth factor, this was not sufficient to activate mTORC1. In contrast, mTORC1 was potently activated by a combination of BDNF and photoactivation. The data demonstrate that two important triggers of synaptic plasticity, BDNF and NMDA receptors, synergistically power the two arms of the mTORC1 activation mechanism, i.e., mTORC1 translocation to LEs and Rheb activation. Moreover, they unmask a functional link between NMDA receptors and mTORC1 that could underlie the changes in the synaptic proteome associated with long-lasting changes in synaptic strength.
Bradycardia in a newborn with accidental severe hypothermia: treat or don’t touch? A case report
Authors: Kuonen Astrid , Riva Thomas , Erdoes Gabor 
Published: July 2021

Abstract
Background
Hypothermia significantly affects mortality and morbidity of newborns. Literature about severe accidental hypothermia in neonates is limited. We report a case of a neonate suffering from severe accidental hypothermia. An understanding of the physiology of neonatal thermoregulation and hypothermia is important to decide on treatment.

Case presentation
A low-birth-weight newborn was found with severe accidental hypothermia (rectal temperature 25.7 °C) due to prolonged exposure to low ambient temperature. The newborn presented bradycardic, bradypnoeic, lethargic, pale and cold. Bradycardia, bradypnea and impaired consciousness were interpreted in the context of the measured body temperature. Therefore, no reanimation or intubation was initiated. The newborn was closely monitored and successfully treated only with active and passive rewarming.

Conclusion
Clinical parameters such as heart frequency, blood pressure, respiration and consciousness must be interpreted in light of the measured body temperature. Medical treatment should be adapted to the clinical presentation. External rewarming can be a safe and effective measure in neonatal patients.
Verbal intelligence is a more robust cross-sectional measure of cognitive reserve than level of education in healthy older adults
Authors: Boyle R. , Knight S. P. , De Looze C. , Carey D. , Scarlett S. , Stern Y. , Robertson I. H. , Kenny R. A. , Whelan R. 
Published: July 2021

Abstract
Background
Cognitive reserve is most commonly measured using socio-behavioural proxy variables. These variables are easy to collect, have a straightforward interpretation, and are widely associated with reduced risk of dementia and cognitive decline in epidemiological studies. However, the specific proxies vary across studies and have rarely been assessed in complete models of cognitive reserve (i.e. alongside both a measure of cognitive outcome and a measure of brain structure). Complete models can test independent associations between proxies and cognitive function in addition to the moderation effect of proxies on the brain-cognition relationship. Consequently, there is insufficient empirical evidence guiding the choice of proxy measures of cognitive reserve and poor comparability across studies.

Method
In a cross-sectional study, we assessed the validity of 5 common proxies (education, occupational complexity, verbal intelligence, leisure activities, and exercise) and all possible combinations of these proxies in 2 separate community-dwelling older adult cohorts: The Irish Longitudinal Study on Ageing (TILDA; N = 313, mean age = 68.9 years, range = 54–88) and the Cognitive Reserve/Reference Ability Neural Network Study (CR/RANN; N = 234, mean age = 64.49 years, range = 50–80). Fifteen models were created with 3 brain structure variables (grey matter volume, hippocampal volume, and mean cortical thickness) and 5 cognitive variables (verbal fluency, processing speed, executive function, episodic memory, and global cognition).

Results
No moderation effects were observed. There were robust positive associations with cognitive function, independent of brain structure, for 2 individual proxies (verbal intelligence and education) and 16 composites (i.e. combinations of proxies). Verbal intelligence was statistically significant in all models. Education was significant only in models with executive function as the cognitive outcome variable. Three robust composites were observed in more than two-thirds of brain-cognition models: the composites of (1) occupational complexity and verbal intelligence, (2) education and verbal intelligence, and (3) education, occupational complexity, and verbal intelligence. However, no composite had larger average effects nor was more robust than verbal intelligence alone.

Conclusion
These results support the use of verbal intelligence as a proxy measure of CR in cross-sectional studies of cognitively healthy older adults.
Ambiguous genitalia: clinical management of adult female with male assigned gender: a case report
Authors: Ali Mahamudu Ayamba , Maalman Raymond Saa-Eru , Donkor Yaw Otchere , Mensah James Edward 
Published: July 2021

AbstractBackgroundDisorders of sex development are anomalies in which the development of urogenital ridge is undifferentiated for the male and female child. Imaging plays a vital role in investigating the gross anatomy and associated anomalies. Ultrasonography, such as genitography and magnetic resonance, is the primary modality for demonstrating internal gonads and genitalia. Early multidisciplinary approach in the management of ambiguous genitalia including early surgical intervention is the predominant practice, with few current considerations on deferral of genital reconstruction until adolescent age.Case presentationWe report the rare case of a 24-year-old adult female from a majority ethnic group of the Volta region, Ghana who was diagnosed and raised as male, now requiring surgical restoration to the female gender. The surgical team decided to assign external genitalia to correspond with the already intact internal organs, thus constructing the vulva. Consent was given by the client and her family members for management and surgical intervention. The surgery was scheduled and duly performed with a successful outcome. Understanding and consent was sought from the patient for the purpose of using her images for teaching, scientific publication, and demonstrations.ConclusionThe advantages of deferring surgical reconstruction with psychological counseling after early assessment need to be considered to prevent inappropriate gender assignment.
A rational approach on the use of extracorporeal membrane oxygenation in severe hypoxemia: advanced technology is not a panacea
Authors: Akoumianaki Evangelia , Jonkman Annemijn , Sklar Michael C. , Georgopoulos Dimitris , Brochard Laurent 
Published: July 2021

AbstractVeno-venous extracorporeal membrane oxygenation (ECMO) is a helpful intervention in patients with severe refractory hypoxemia either because mechanical ventilation cannot ensure adequate oxygenation or because lung protective ventilation is not feasible. Since ECMO is a highly invasive procedure with several, potentially devastating complications and its implementation is complex and expensive, simpler and less invasive therapeutic options should be first exploited. Low tidal volume and driving pressure ventilation, prone position, neuromuscular blocking agents and individualized ventilation based on transpulmonary pressure measurements have been demonstrated to successfully treat the vast majority of mechanically ventilated patients with severe hypoxemia. Veno-venous ECMO has a place in the small portion of severely hypoxemic patients in whom these strategies fail. A combined analysis of recent ARDS trials revealed that ECMO was used in only 2.15% of patients (n = 145/6736). Nevertheless, ECMO use has sharply increased in the last decade, raising questions regarding its thoughtful use. Such a policy could be harmful both for patients as well as for the ECMO technique itself. This narrative review attempts to describe together the practical approaches that can be offered to the sickest patients before going to ECMO, as well as the rationale and the limitations of ECMO. The benefit and the drawbacks associated with ECMO use along with a direct comparison with less invasive therapeutic strategies will be analyzed.
Economics of contracts in African food systems: evidence from the malt barley sector in Ethiopia
Authors: Tefera Delelegne A. , Bijman Jos 
Published: July 2021

AbstractForeign direct investment (FDI) facilitates modernization of domestic agri-food systems in emerging economies through increased use of vertical coordination. This paper sheds lights on how international brewer investments in African food systems affect smallholder market participation and value chain development. In particular, we analyze the impact of contracts among malt barley producers in Ethiopia. Using cross-sectional survey data, we employ inverse probability-weighted regression adjustment (IPWRA) and propensity score matching (PSM) techniques to analyze the economic impact of contracting. We find that contrary to popular belief, contracting has positive and significant impact on malt barley production, intensification, commercialization, quality improvement, and farm gate prices, ultimately resulting in increased net income and spillover into the productivity of other food crops.
A national study of choanal atresia in tertiary care centers in Canada – part I: Clinical presentation
Authors: Paradis Josee , Dzioba Agnieszka , El-Hakim Hamdy , Hong Paul , Kozak Frederick K. , Nguyen Lily H. P. , Perera Demitri , Propst Evan Jon , Siu Jennifer M. , Wojtera Monika , Husein Murad ,   National Choanal Atresia Study Working Group
Published: July 2021

Background To evaluate the clinical presentation of choanal atresia (CA) in tertiary centers across Canada. Methods Multi-centre case series involving six tertiary care pediatric hospitals across Canada. Retrospective chart review of patients born between 1980 and 2010 diagnosed with CA at a participating center. Results The health charts of 215 patients (59.6% female) with CA were reviewed and included in this study. The mean age of patients at time of CA presentation was 0.4 months (range 0.1 to 7.2 months) for bilateral CA and 37.8 months (range 0.1 to 164.1 months) for unilateral cases. The most common presenting symptoms for bilateral CA in decreasing order were respiratory distress (96.4%), feeding difficulties (68.2%), and rhinorrhea (65.5%), and for unilateral cases in decreasing order were rhinorrhea (92.0%), feeding difficulties (24.7%), and respiratory distress (18.0%). For the majority of patients (73.2%), the obstruction comprised mixed bony and membranous tissue, with only 10.5% presenting with a purely membranous obstruction. Familial history of CA was confirmed in only 3.3% of cases. One half of patients with CA presented with one or more associated anomalies and 30.6% had a syndrome. Conclusions The present investigation is the first national multi-institutional study evaluating the clinical presentation of CA over three decades. The present cohort of CA patients presented with a breadth of co-morbidities with highly variable presentations, with bilateral cases being more severely affected than unilateral cases. Further investigation into hereditary linkages to CA development is warranted. Graphical Abstract
Design of more potent quinazoline derivatives as EGFRWT inhibitors for the treatment of NSCLC: a computational approach
Authors: Ibrahim Muhammad Tukur , Uzairu Adamu , Uba Sani , Shallangwa Gideon Adamu 
Published: July 2021

Abstract
Background
Lung cancer remains the leading and deadly type of cancer worldwide. It was estimated to account for about 25% of the 7 million people that died as a result of cancer-related issues/mortality every year in the world. Non-small cell lung cancer (NSCLC) is the lethal/deadly class of lung cancer with nearly 1.5 million reported cases and less than 20% survival rate. Therefore, it becomes necessary to explore more effective NSCLC drugs.

Result
A computational approach was employed here to design ten new EGFRWT inhibitors using compound 18 as a template for the design identified with the best binding affinity and good pharmacokinetic properties previously reported in our work. The modeled inhibitory activities of these newly designed EGFRWT inhibitors (range from 7.746966 to 11.09261) were better than that of the hit compound with pIC50 of 7.5639 and gefitinib the positive control with pIC50 of 5.879426. The ligand-binding interaction between these newly designed EGFRWT inhibitors and the EGFR tyrosine kinase receptor as shown in Table 3 was investigated and elucidated using molecular docking protocol. Based on the molecular docking results, the binding affinities of these newly designed EGFRWT inhibitors were found to be between − 8.8 and − 9.5 kcal/mol. The designed compound SFD10 has the highest binding affinity of − 9.5 kcal/mol followed by compound SFD8 (with a binding affinity of − 9.3 kcal/mol), then by compound SFD9 and 4 (each with a binding affinity of − 9.3 kcal/mol). None of them was found to have more than one violation of the filtering criterion used in this study thereby showing good ADMET properties.

Conclusion
The modeled inhibitory activities and binding affinities of these newly designed EGFRWT inhibitors were found to be higher than that of the template compound and the control (gefitinib) used in this research. They were also seen to be non-toxic with good pharmacokinetic properties.
A theory of pedestrian-induced footbridge vibration comfortability based on sensitivity model
Authors: Chen Deyi , Huang Shiping , Wang Zhenyu 
Published: July 2021

AbstractPedestrian-induced footbridge vibration comfort level is a complex problem that has been studied for a long time. However, no consensus has been reached on a quantitative calculation index for assessing vibration comfort level. Only simple comfort limits, rather than specific relationships between comfort level and the vibration endurance capacity of pedestrians, are currently available for assessing vibration comfort level of footbridges. This article aims to propose a sensitivity model for pedestrian-induced vibration comfort calculation based on the vibration endurance capacity of pedestrians and the vibration response of footbridges. The concepts of “human body resistance” and “vibration effect” were established according to the principle of probability and statistics. Mathematical definition of sensitivity was put forward. Calculation expressions for a pedestrian and pedestrians were deduced respectively. A theory of pedestrian-induced footbridge vibration comfort level was proposed. Field survey and experiment were conducted, the results of the field survey demonstrated that sensitivity values were in good agreement with the international vibration comfort standards. Furthermore, the field experiment results showed that the errors between the experimental results and the calculated results were within 6%. The proposed sensitivity theory can be used for pedestrian-induced footbridge vibration comfort quantitative calculation.
Health of the Nation Outcome Scales for Infants field trial: concurrent validity
Authors: Brann Peter , Culjak Gordana , Kowalenko Nick , Dickson Rosemary , Coombs Tim , Burgess Philip , Williams Anne Sved , Hoehn Elisabeth , Hoyland Margaret 
Published: July 2021

Background
A review of Australian mental health services identified a gap in routine outcome measures addressing social, emotional and behavioural domains for pre-schoolers and infants. A Child and Adolescent Mental Health Information Development Expert Advisory Panel working group developed the Health of the Nation Outcome Scales for Infants (HoNOSI), a clinician-reported routine outcome measure for infants 0–47 months. Prior face validity testing showed that the HoNOSI was considered useful in measuring mental health outcomes.

Aims
To examine the concurrent validity of the HoNOSI.

Method
Mental health clinicians providing assessment and treatment to infants in routine clinical practice participated in the study. The mental health status of 108 infants were rated by a minimum of 26 clinicians with the HoNOSI, the Parent-Infant Relationship Global Assessment Scale (PIR-GAS) and measures of symptom severity and distress.

Results
The HoNOSI was statistically significantly correlated with the PIR–;GAS, rs = −0.73; Clinical Worry, rs = 0.77; and Severity Judgement ratings, rs = 0.85; P < 0.001. A good level of internal consistency was found. Using the COsensus-based Standards for the selection of health Measurement INstruments (COSMIN) criteria for judging instrument acceptability, the HoNOSI meets the standard for both concurrent validity and internal consistency.

Conclusions
There has been a clear need for a routine outcome measure for use with infants. This study provides positive evidence of aspects of validity. These findings, along with those from the prior face validity study, support a controlled release of the HoNOSI accompanied by further research and development.
Development and Validation of a Simulation Model–Based Clinical Decision Tool: Identifying Patients Where 21-Gene Recurrence Score Testing May Change Decisions
Authors: Jayasekera Jinani , Sparano Joseph A. , O'Neill Suzanne , Chandler Young , Isaacs Claudine , Kurian Allison W. , Kushi Lawrence , Schechter Clyde B. , Mandelblatt Jeanne 
Published: July 2021

PURPOSE There is a need for industry-independent decision tools that integrate clinicopathologic features, comorbidities, and genomic information for women with node-negative, invasive, hormone receptor–positive, human epidermal growth factor receptor-2–negative (early-stage) breast cancer. METHODS We adapted an extant Cancer Intervention and Surveillance Modeling Network simulation model to estimate the 10-year risk of distant recurrence, breast cancer–specific mortality, other-cause mortality, and life-years gained with chemoendocrine versus endocrine therapy. We simulated outcomes for 1,512 unique patient subgroups based on all possible combinations of age, tumor size, grade, and comorbidity level; simulations were performed with and without 21-gene recurrence scores (RSs). Model inputs were derived from clinical trials, large US cohort studies, registry, and claims data. External validation was performed by comparing results to observed rates in two independent sources. We highlight results for one scenario where treatment choice may be uncertain. RESULTS Chemoendocrine versus endocrine therapy in a 65-69-year-old woman with a small (≤ 2 cm), intermediate-grade tumor, and mild comorbidities provides a 1.3% absolute reduction in 10-year distant recurrence risk, with 0.23 life-years gained. With these tumor features, a woman like this will have a 28% probability of having an RS 16-20, 18% RS 21-25, and 11% RS 26+. If testing is done, and her RS is 16-20, chemoendocrine therapy reduces 10-year distant recurrence risk to 1%, with 0.20 life-years gained, a similar result as without testing. The absolute benefits would increase to 4.8%-5.5% if the RS was 26+. The model closely reproduced observed rates in both independent data sets. CONCLUSION Our validated clinical decision tool is flexible, readily adaptable to include new therapies, and can support discussions about genomic testing and early breast cancer treatment.
Fast and robust particle shuttling for quantum science and technology
Authors: Qi L. , Chiaverini J. , Espinós H. , Palmero M. , Muga J. G. 
Published: July 2021

Abstract
We review methods to shuttle quantum particles fast and robustly. Ideal robustness amounts to the invariance of the desired transport results with respect to deviations, noisy or otherwise, from the nominal driving protocol for the control parameters; this can include environmental perturbations. “Fast” is defined with respect to adiabatic transport times. Special attention is paid to shortcut-to-adiabaticity protocols that achieve, in faster-than-adiabatic times, the same results of slow adiabatic driving.
Charging power and stability of always-on transitionless driven quantum batteries
Authors: Moraes Luiz F. C. , Saguia Andreia , Santos Alan C. , Sarandy Marcelo S. 
Published: July 2021

Abstract
The storage and transfer of energy through quantum batteries are key elements in quantum networks. Here, we propose a charger design based on transitionless quantum driving (TQD), which allows for inherent control over the battery charging time, with the speed of charging coming at the cost of the internal energy available to implement the dynamics. Moreover, the TQD-based charger is also shown to be locally stable, which means that the charger can be disconnected from the quantum battery (QB) at any time after the energy transfer to the QB, with no full energy backflow to the charger. This provides a highly charged QB in an always-on asymptotic regime. We illustrate the robustness of the QB charge against time fluctuations and the full control over the evolution time for a feasible TQD-based charger.
The Conquest of Española as a “Structure of Conjuncture”
Authors: Stone Erin W. 
Published: July 2021

AbstractThis article delves into the conquest and early years of colonization of Española from the perspective of the “structure of the conjuncture.” By doing so it prioritizes the Indigenous perspective of conquest, particularly that of the cacique Guacanagarí, who formed the first alliance with the Spaniards in 1492. The article follows the development of the historic alliance, digging beneath the surface of historical chronicles to reveal Indigenous cosmology and agency throughout the skirmishes and intrigue of colonization. In so doing it shows that during the first years of Caribbean colonization, the Spaniards were not in control as all actors were engaging in a novel environment, the structure of the conjuncture. The situation did change by the early 1500s, but the imprint of the structure of the conjuncture was felt for decades to come.