bluuebunny/crossref_metadata_2025_split huggingface dataset:
The PI3K/Akt/mTOR pathway as a preventive target in melanoma brain metastasis
Authors: Tehranian Cedric , Fankhauser Laura , Harter Patrick N , Ratcliffe Colin D H , Zeiner Pia S , Messmer Julia M , Hoffmann Dirk C , Frey Katharina , Westphal Dana , Ronellenfitsch Michael W , Sahai Erik , Wick Wolfgang , Karreman Matthia A , Winkler Frank 
Published: June 2021

Abstract

Background
Brain metastases (BM) are a frequent complication of malignant melanoma (MM), with limited treatment options and poor survival. Prevention of BM could be more effective and better tolerated than treating established BM in various conditions.

Methods
To investigate the temporospatial dynamics of PI3K/Akt/mTOR (PAM) pathway activation during BM formation and the preventive potential of its inhibition, in vivo molecular imaging with an Akt biosensor was performed, and long-term intravital multiphoton microscopy through a chronic cranial window in mice.

Results
In vivo molecular imaging revealed invariable PAM pathway activation during the earliest steps of brain colonization. In order to perform a long-term intravascular arrest and to extravasate, circulating MM cells needed to activate their PAM pathway during this process. However, the PAM pathway was quite heterogeneously activated in established human brain metastases, and its inhibition with the brain-penetrant PAM inhibitor GNE-317 resulted in only modest therapeutic effects in mice. In contrast, giving GNE-317 in preventive schedules that included very low doses effectively reduced the growth rate and number of BM in two MM mouse models over time, and led to an overall survival benefit. Longitudinal intravital multiphoton microscopy found that the first, rate-limiting steps of BM formation—permanent intravascular arrest, extravasation, and initial perivascular growth—are most vulnerable to dual PI3K/mTOR inhibition.

Conclusion
These findings establish a key role of PAM pathway activation for critical steps of early metastatic brain colonization and reveal its pharmacological inhibition as a potent avenue to prevent the formation of clinically relevant BM.
Recurrent Tuberculosis Disease in Singapore
Authors: Gan Suay Hong , KhinMar Kyi Win , Ang Li Wei , Lim Leo K Y , Sng Li Hwei , Wang Yee Tang , Chee Cynthia B E 
Published: June 2021

Abstract

Background
Previously treated (ie, recurrent) tuberculosis (TB) cases account for approximately 7%–8% of incident TB globally and in Singapore. Molecular fingerprinting has enabled the differentiation of these patients into relapsed or reinfection cases.

Methods
Patient demographics, disease characteristics, and treatment information were obtained from the national TB notification registry and TB Control Unit. We performed a retrospective, case-control study to evaluate factors associated with recurrent TB disease in Singapore citizens and permanent residents with culture-positive TB from 2006 to 2013 and who developed a second episode of culture-positive TB up to 2016 using multivariable logistic regression analyses.

Results
Ninety-one cases with culture-positive first and recurrent TB disease episodes were identified. Recurrent TB was associated with age ≥60 years (adjusted odds ratio [aOR], 1.98 [95% confidence interval {CI}, 1.09–3.61), male sex (aOR, 2.29 [95% CI, 1.22–4.51]), having concomitant pulmonary and extrapulmonary TB (aOR, 3.10 [95% CI, 1.59–6.10]) and extrapulmonary TB alone (aOR, 3.82 [95% CI, 1.12–13.31]), and was less likely in non-Malays (aOR, 0.52 [95% CI, .27–.99]). DNA fingerprinting results for both episodes in 49 cases differentiated these into 28 relapsed and 21 reinfection cases. Relapse was associated with having concomitant pulmonary and extrapulmonary TB (aOR, 9.24 [95% CI, 2.50–42.42]) and positive sputum acid-fast bacilli smear (aOR, 3.95 [95% CI, 1.36–13.10]).

Conclusions
Relapse and reinfection contributed to 57% and 43%, respectively, of recurrent TB in Singapore. Our study highlights the underappreciated association of concomitant pulmonary and extrapulmonary TB as a significant risk factor for disease relapse.
Robotic Applications in Cranial Neurosurgery: Current and Future
Authors: Ball Tyler , González-Martínez Jorge , Zemmar Ajmal , Sweid Ahmad , Chandra Sarat , VanSickle David , Neimat Joseph S , Jabbour Pascal , Wu Chengyuan 
Published: June 2021

Abstract
Robotics applied to cranial surgery is a fast-moving and fascinating field, which is transforming the practice of neurosurgery. With exponential increases in computing power, improvements in connectivity, artificial intelligence, and enhanced precision of accessing target structures, robots are likely to be incorporated into more areas of neurosurgery in the future—making procedures safer and more efficient. Overall, improved efficiency can offset upfront costs and potentially prove cost-effective. In this narrative review, we aim to translate a broad clinical experience into practical information for the incorporation of robotics into neurosurgical practice. We begin with procedures where robotics take the role of a stereotactic frame and guide instruments along a linear trajectory. Next, we discuss robotics in endoscopic surgery, where the robot functions similar to a surgical assistant by holding the endoscope and providing retraction, supplemental lighting, and correlation of the surgical field with navigation. Then, we look at early experience with endovascular robots, where robots carry out tasks of the primary surgeon while the surgeon directs these movements remotely. We briefly discuss a novel microsurgical robot that can perform many of the critical operative steps (with potential for fine motor augmentation) remotely. Finally, we highlight 2 innovative technologies that allow instruments to take nonlinear, predetermined paths to an intracranial destination and allow magnetic control of instruments for real-time adjustment of trajectories. We believe that robots will play an increasingly important role in the future of neurosurgery and aim to cover some of the aspects that this field holds for neurosurgical innovation.
Characterization of Nannochloropsis oceanica Rose Bengal Mutants Sheds Light on Acclimation Mechanisms to High Light When Grown in Low Temperature
Authors: Ben-Sheleg Avraham , Khozin-Godberg Inna , Yaakov Beery , Vonshak Avigad 
Published: June 2021

Abstract
A barrier to realizing Nannochloropsis oceanica’s potential for omega-3 eicosapentaenoic acid (EPA) production is the disparity between conditions that are optimal for growth and those that are optimal for EPA biomass content. A case in point is temperature: higher content of polyunsaturated fatty acid, and especially EPA, is observed in low-temperature (LT) environments, where growth rates are often inhibited. We hypothesized that mutant strains of N. oceanica resistant to the singlet-oxygen photosensitizer Rose Bengal (RB) would withstand the oxidative stress conditions that prevail in the combined stressful environment of high light (HL; 250 μmol photons m−2 s−1) and LT (18°C). This growth environment caused the wild-type (WT) strain to experience a spike in lipid peroxidation and an inability to proliferate, whereas growth and homeostatic reactive oxygen species levels were observed in the mutant strains. We suggest that the mutant strains’ success in this environment can be attributed to their truncated photosystem II antennas and their increased ability to diffuse energy in those antennas as heat (non-photosynthetic quenching). As a result, the mutant strains produced upward of four times more EPA than the WT strain in this HL–LT environment. The major plastidial lipid monogalactosyldiacylglycerol was a likely target for oxidative damage, contributing to the photosynthetic inhibition of the WT strain. A mutation in the NO10G01010.1 gene, causing a subunit of the 2-oxoisovalerate dehydrogenase E1 protein to become non-functional, was determined to be the likely source of tolerance in the RB113 mutant strain.
Comparison of Remote Electrical Neuromodulation and Standard-Care Medications for Acute Treatment of Migraine in Adolescents: A Post Hoc Analysis
Authors: Hershey Andrew D , Irwin Samantha , Rabany Liron , Gruper Yaron , Ironi Alon , Harris Dagan , Sharon Roni , McVige Jennifer 
Published: June 2021

Abstract

Objective
There is an unmet need for new, efficacious, well-tolerated, acute treatments for migraine in adolescents. Remote electrical neuromodulation (REN) is a novel, nonpharmacological treatment that provides significant symptom relief with good tolerability. The current post hoc analysis compared the efficacy of REN to that of standard-care medications for the acute treatment of migraine in adolescents.

Design
Within-participant post hoc analysis of data from a clinical trial.

Setting
Data from a clinical trial.

Subjects
Data from 35 adolescent participants were analyzed.

Methods
Efficacy was compared between a run-in phase, in which attacks were treated with standard-care medications (triptans or over-the-counter medications), and an intervention phase, in which attacks were treated with REN. Efficacy was compared within participants through the use of McNemar’s test at four endpoints (2 hours after treatment): single-treatment pain freedom and pain relief, and consistency of pain freedom and pain relief (defined as response in at least 50% of the available first four treatments).

Results
At 2 hours after treatment, pain freedom was achieved by 37.1% of the participants with REN, vs 8.6% of the participants with medications (P = 0.004). Pain relief was achieved by 71.4% with REN, vs 57.1% with medications (P = 0.225). Consistency of pain freedom was achieved by 40% with REN, vs 8.6% with medications (P &lt; 0.001). Consistency of pain relief was achieved by 80.0% with REN, vs 57.2% with medications (P = 0.033).

Conclusions
Our results suggest that REN may have higher efficacy than certain standard-care medications for the acute treatment of migraine in adolescents. A larger-scale, blinded comparative-effectiveness and tolerability study is needed.
Effectiveness of High-Frequency Transcranial Magnetic Stimulation and Physical Exercise in Women With Fibromyalgia: A Randomized Controlled Trial
Authors: Izquierdo-Alventosa Ruth , Inglés Marta , Cortés-Amador Sara , Gimeno-Mallench Lucia , Sempere-Rubio Núria , Serra-Añó Pilar 
Published: June 2021

Abstract

Objective
Fibromyalgia (FM) is characterized by chronic widespread pain and both physical and emotional alterations, which in turn may affect the individual’s quality of life. Thus, interventions aimed at treating such symptoms, without increasing fatigue, are needed. The aim of this study was to explore the effect of high-frequency transcranial magnetic stimulation (HF-TMS) and physical exercise (PE) on pain, impact of FM, physical conditioning, and emotional status in women with FM.

Methods
Forty-nine women with FM were randomly allocated to: (1) a PE group (PEG, n = 16), who underwent an 8-week (two 60-minute sessions/wk) low-intensity PE program; (2) a TMS group (TMSG, n = 17) receiving a 2-week (five 20-minute sessions/wk) HF-TMS intervention; and (3) a control group (CG, n = 16). Pain (ie, perceived pain and average pressure pain threshold), perceived impact of FM (ie, overall impact, symptoms, and perceived physical function), physical conditioning (ie, endurance and functional capacity, fatigue, gait velocity, and power), and emotional status (ie, anxiety, depression, stress, and satisfaction) were assessed at baseline (T0) and after the intervention (T1, at 2 weeks for TMSG and at 8 weeks for PEG and CG).

Results
The TMSG showed significant improvement in all studied variables after the intervention except for satisfaction, whereas the PEG showed improved average pressure pain threshold, perceived overall impact of FM and total score, endurance and functional capacity, velocity and power, anxiety, depression, and stress. In contrast, the CG showed no improvements in any variable.

Conclusion
Both PE and HF-TMS are effective in improving pain, impact of FM, physical conditioning, and emotional status in people with FM; HF-TMS achieved larger improvements in emotional status than PE.

Impact
TMS and PE have similar benefits for physical status, whereas TMS has greater benefits than PE for emotional status in women with FM.
Biologic use in psoriatic arthritis and ankylosing spondylitis patients: a descriptive epidemiological study using linked, routine data in Wales, UK
Authors: Cooksey Roxanne , Rahman Muhammad Azizur , Kennedy Jonathan , Brophy Sinead , Choy Ernest 
Published: June 2021

Abstract

Objectives
PsA and AS are chronic diseases associated with significant morbidities. National and international management guidelines include treatment with biologic therapies to improve outcomes and quality of life. There are limited real-world data on the patients’ journey from symptom onset to diagnosis and treatment in the UK. We use real-life, linked health data to explore patient pathways and the impact of biologics on patient outcomes.

Methods
Data from the Secure Anonymised Information Linkage databank in Wales were used to assess diagnosis and treatment of patients ≥18 years of age with at least one International Classification of Diseases, Tenth Revision code present for PsA/AS in rheumatology clinic data and at least one Read code present in primary care records. We investigated the use of biologics while exploring demographics, comorbidities and surgical procedures of 641 AS patients and 1312 PsA patients.

Results
AS patients were significantly younger at diagnosis and were predominantly male. The average time from presenting symptoms to diagnosis of AS and PsA was 7.9 (s.d. 5.5) and 9.3 (s.d. 5.5) years, respectively. The proportion of patients receiving biologic treatment was significantly higher in AS (46%) compared with PsA patients (28.8%); of these, 23.1% of AS and 22.2% of PsA patients stopped/switched a biologic. There was a significant reduction in primary care involvement, sick notes and disability living allowance for both AS and PsA patients following biologic initiation.

Conclusion
This real-world descriptive study confirms that patients treated with biologics have reduced disability and time off work despite being initiated ∼13 years after the first symptoms and 6 years after diagnosis.
Evaluating Species Delimitation Methods in Radiations: The Land SnailAlbinaria cretensisComplex on Crete
Authors: Bamberger Sonja , Xu Jie , Hausdorf Bernhard 
Published: June 2021

AbstractDelimiting species in radiations is notoriously difficult because of the small differences between the incipient species, the star-like tree with short branches between species, incomplete lineage sorting, and the possibility of introgression between several of the incipient species. Next-generation sequencing data may help to overcome some of these problems. We evaluated methods for species delimitation based on genome-wide markers in a land snail radiation on Crete. Species delimitation in the Albinaria cretensis group was based exclusively on shell characters until now and resulted in classifications distinguishing 3–9 species. We generated sequences of 4270 loci for 140 specimens of the A. cretensis group from 48 populations by double-digest restriction site-associated DNA sequencing. We evaluated three methods for species discovery. The multispecies coalescent approach implemented in the program Bayesian Phylogenetics and Phylogeography resulted in a drastic overestimating of the number of species, whereas Gaussian clustering resulted in an overlumping. Primary species hypotheses based on the maximum percentage of the genome of the individuals derived from ancestral populations as estimated with the program ADMIXTURE moderately overestimated the number of species, but this was the only approach that provided information about gene flow between groups. Two of the methods for species validation that we applied, BFD* and delimitR, resulted in an acceptance of almost all primary species hypotheses, even such based on arbitrary subdivisions of hypotheses based on ADMIXTURE. In contrast, secondary species hypotheses, resulting from an evaluation of primary species hypotheses based on ADMIXTURE with isolation by distance tests, approached the morphological classification, but also uncovered two cryptic species and indicated that some of the previously delimited units should be combined. Thus, we recommend this combination of approaches that provided more detailed insights in the distinctness of barriers between the taxa of a species complex and the spatial distribution of admixture between them than the other methods. The recognition and delimitation of undersampled species remained a major challenge. [ADMIXTURE; Clausiliidae; delimitR, Gaussian clustering; isolation-by-distance; land snails; multispecies coalescent; species delimitation.]
Effects of dietary chromium propionate and space allowance on performance and carcass responses of growing-finishing pigs
Authors: Santos Alexandre P , Tokach Mike D , Kiefer Charles , Goodband Robert D , Woodworth Jason C , DeRouchey Joel M , Dritz Steve S , Gebhardt Jordan T 
Published: June 2021

Abstract
In a 72-d trial, 256 pigs (Line 600 × 241, DNA Columbus, NE) were used to determine the effect of dietary Cr (Cr propionate; Kemin Industries, Des Moines, IA) and physical space restriction on performance and carcass characteristics of finishing pigs. Pens were blocked by initial weight and randomly assigned to treatments with eight pigs per pen and eight pens per treatment. Treatments were arranged in a 2 × 2 factorial with main effects of Cr (control and Cr propionate, 200 µg/kg added Cr) and space allowances (0.91 m2/animal: normal and 0.63 m2/animal: restricted). Pigs were fed in three dietary phases and pigs were weighed approximately every 14 d throughout the study. Feed efficiency was calculated as both a standard gain to feed ratio and as an adjusted G:F ratio at a common final bodyweight. There were no evidence of space allocation × Cr interactions for any measured responses (P &gt; 0.05). Space restriction decreased (P &lt; 0.001) daily weight gain, final body weight, hot carcass weight, and daily feed intake, but increased carcass yield (P = 0.009) and decreased backfat depth (P = 0.003). Feed efficiency was greater for pigs provided a normal space allowance when adjusted for a common final bodyweight (P = 0.021), although no evidence of a difference was observed for unadjusted G:F (P = 0.687). Adding Cr to the diet reduced G:F on both an adjusted and unadjusted basis (P ≤ 0.021). There was marginally significant evidence that pigs provided Cr had lower average daily gain (P = 0.079) and final bodyweight (P = 0.056) compared to pigs not provided added Cr. There was marginally significant evidence that Cr resulted in greater backfat depth (P = 0.069), although no evidence of a difference in other carcass parameters were observed (P &gt; 0.10). These results demonstrated that there were no interactions between Cr propionate and space allocation, illustrating that under the conditions of this study Cr propionate did not provide an advantage in growth performance or carcass characteristics in either adequate or restricted space allocation.
HCV/HIV coinfected Egyptian patients: a cross-sectional study of their main characteristics and barriers to HCV treatment initiation
Authors: Eletreby Rasha , Esmat Gamal , Elsharkawy Aisha , Alsehemy Lamiaa , Mohamed Rahma , Alem Shereen Abdel , Yousof Hanaa , Cordie Ahmed , Lithy Rania M 
Published: June 2021

Abstract

Background
This study investigates different barriers preventing a cohort of Egyptian HIV/HCV coinfected patients from accessing HCV treatment, despite being available and free of charge, aiming to improve the long-term outcomes of coinfected patients and decreasing their liver-related morbidity and mortality.

Methods
This study included HIV patients who were referred to Kasr Alainy Viral Hepatitis Center to receive HCV treatment and who had to continue pretreatment assessment in order to receive direct acting antiviral agents free of charge. Patients who did not attend within 90 d were questioned via a telephone interview. Questions addressed sociodemographic status, HIV status and the main barriers to accessing healthcare.

Results
Overall, 474 HIV/HCV coinfected patients were eligible for HCV treatment and 223 (47.1%) patients did not complete work-up for HCV treatment. Fear of community stigma concerning HIV/HCV was the most important barrier to compliance with treatment (73.3%), followed by lack of a supportive work environment and employment opportunities (51.5%), whereas 39.3% stopped follow-up due to the lack of integrated services in the healthcare facility.

Conclusions
Managing HCV in HCV/HIV coinfected patients still represents a major challenge, not only for healthcare providers, but also at a community level, to improve community awareness and manage the major obstacle facing those patients regarding community stigma.
Automatic identification of bird females using egg phenotype
Authors: Šulc Michal , Hughes Anna E , Troscianko Jolyon , Štětková Gabriela , Procházka Petr , Požgayová Milica , Piálek Lubomír , Piálková Radka , Brlík Vojtěch , Honza Marcel 
Published: June 2021

Abstract
Individual identification is crucial for studying animal ecology and evolution. In birds this is often achieved by capturing and tagging. However, these methods are insufficient for identifying individuals/species that are secretive or difficult to catch. Here, we employ an automatic analytical approach to predict the identity of bird females based on the appearance of their eggs, using the common cuckoo (Cuculus canorus) as a model species. We analysed 192 cuckoo eggs using digital photography and spectrometry. Cuckoo females were identified from genetic sampling of nestlings, allowing us to determine the accuracy of automatic (unsupervised and supervised) and human assignment. Finally, we used a novel analytical approach to identify eggs that were not genetically analysed. Our results show that individual cuckoo females lay eggs with a relatively constant appearance and that eggs laid by more genetically distant females differ more in colour. Unsupervised clustering had similar cluster accuracy to experienced human observers, but supervised methods were able to outperform humans. Our novel method reliably assigned a relatively high number of eggs without genetic data to their mothers. Therefore, this is a cost-effective and minimally invasive method for increasing sample sizes, which may facilitate research on brood parasites and other avian species.