bluuebunny/crossref_metadata_2025_split huggingface dataset:
CHARGE syndrome: genetic aspects and dental challenges, a review and case presentation
Authors: Chetty Manogari , Roberts Tina Sharon , Elmubarak Mona , Bezuidenhout Heidre , Smit Liani , Urban Mike 
Published: May 2020

Abstract
Background
CHARGE syndrome (CS) is a rare genetic condition (OMIM #214800). The condition has a variable phenotypic expression. Historically, the diagnosis of CHARGE syndrome was based on the presence of specific clinical criteria. The genetic aetiology of CS has since been elucidated and attributed to pathogenic variation in the CHD7 gene (OMIM 608892) at chromosome locus 8q12.

Case presentation
A South African female of mixed ancestry heritage, aged 4 years, was referred for dental assessment to the Faculty of Dentistry, University of the Western Cape, in 2018. She had a diagnosis of CHARGE syndrome confirmed by a Medical Geneticist from the Division of Molecular Biology and Human Genetics at the University of Stellenbosch.
The patient had a long prior history of health and developmental problems, with the correct diagnosis becoming apparent over time. She presented with many oral and craniofacial features warranting consideration by the dentist including micrognathia, hypoplastic nasal bones, cranial nerve dysfunction, bruxism, craniofacial anomalies and compromised sensory perception. The treatment was mainly preventive and, although she fed through a percutaneous endoscopic gastrostomy tube (PEG), maintenance of her oral hygiene was necessitated.
Conclusion: CS is a multisystem condition and the optimal care for an individual is with a specialist multidisciplinary team. The numerous systemic problems affecting these individuals take precedence in their care, and often there is neglect of their dental concerns. Given the abnormalities frequently present in the oral and craniofacial region, the authors recommend that a team of dental and other medical specialists be involved in the management of individuals with CS.
Successful COVID-19 rescue therapy by extra-corporeal membrane oxygenation (ECMO) for respiratory failure: a case report
Authors: Firstenberg Michael S. , Stahel Philip F. , Hanna Jennifer , Kotaru Chakradhar , Crossno Joseph , Forrester Joseph 
Published: May 2020

Abstract
Background
The value of extracorporeal membrane oxygenation (ECMO) for patients suffering from novel coronavirus disease 2019 (COVID-19) as a rescue therapy for respiratory failure remains controversial and associated with high mortality rates of 50 to 82% in early reports from Wuhan, China. We hypothesized that patient outcomes would be improved at our tertiary cardiothoracic surgery referral center with a protocolized team-approach for ECMO treatment of patients with severe COVID-19 disease.

Case presentation
A 51-year-old healthy female developed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) bilateral pneumonia while vacationing in Colorado with her family. She was transferred to our facility for a higher level of care. Her respiratory status continued to deteriorate despite maximized critical care, including prone positioning ventilation and nitric oxide inhalation therapy. Veno-venous ECMO was initiated on hospital day 7 in conjunction with a 10-day course of compassionate use antiviral treatment with remdesivir. The patient’s condition improved significantly and she was decannulated from ECMO on hospital day 17 (ECMO day 11). She was successfully extubated and eventually discharged to rehabilitation on hospital day 28.

Conclusion
This case report demonstrates a positive outcome in a young patient with COVID-19 treated by the judicious application of ECMO in conjunction with compassionate use antiviral treatment (remdesivir). Future prospective multi-center studies are needed to validate these findings in a larger cohort of patients.
Foot exercise plus education versus wait and see for the treatment of plantar heel pain (FEET trial): a protocol for a feasibility study
Authors: Franettovich Smith Melinda M. , Collins Natalie J. , Mellor Rebecca , Grimaldi Alison , Elliott James , Hoggarth Mark , Weber Kenneth A. , Vicenzino Bill 
Published: May 2020

AbstractBackgroundPlantar heel pain (PHP) is present in a wide range of individuals and creates significant burden to quality of life and participation in physical activity. The high recurrence rates and persistence of PHP suggests current management options may not address all potentially modifiable factors associated with the condition. Reports of intrinsic foot muscle (IFM) atrophy in individuals with PHP, together with biomechanical evidence of their important contribution to optimal foot function, suggests that an intervention focused on IFM training may be beneficial in managing PHP. We will test the feasibility of a prospective, assessor‐blinded, parallel‐group, randomised clinical trial that compares foot exercise plus education to brief advice in individuals with PHP.MethodsTwenty participants with PHP will be randomly allocated to one of two groups for a 12‐week intervention period: (i) foot exercise plus education, or (ii) brief advice. The foot exercise plus education group will attend eight sessions with a physiotherapist and receive detailed education on self‐management strategies as well as a progressive exercise program for the IFMs. The brief advice group will attend one session with a physiotherapist and receive brief information about self‐management strategies and reassurance. Outcome measures will be obtained at baseline and the primary end‐point of 12 weeks. Primary outcomes will be the feasibility of conducting a full‐scale randomised clinical trial (RCT), and the credibility and acceptability of the foot exercise plus education intervention. Secondary outcomes will explore treatment effects, which will consist of pain, physical function, physical activity level, pain self‐efficacy, perceived treatment effect, magnetic resonance and ultrasound image measurement of IFM morphology, ultrasound imaging measurement of plantar fascia thickness, IFM motor performance, foot posture, foot mobility, ankle dorsiflexion range of motion, toe flexor and plantar flexor strength/endurance.DiscussionTo reduce the burden of PHP on individuals and society, there is a need to establish effective treatments that are feasible and accepted by patients and health professionals. This trial will be the first to evaluate the feasibility of conducting a full‐scale RCT, as well as the credibility, acceptability, and treatment effects, of education and foot exercise for PHP. The findings of this study will inform the development of a full‐scale RCT.Trial registrationThe trial protocol was prospectively registered with the Australia and New Zealand Clinical Trial Registry (ACTRN12619000987167) on 11th July 2019.
Anopheles gambiae (s.l.) exhibit high intensity pyrethroid resistance throughout Southern and Central Mali (2016–2018): PBO or next generation LLINs may provide greater control
Authors: Sovi Arthur , Keita Chitan , Sinaba Youssouf , Dicko Abdourhamane , Traore Ibrahim , Cisse Moussa B. M. , Koita Ousmane , Dengela Dereje , Flatley Cecilia , Bankineza Elie , Mihigo Jules , Belemvire Allison , Carlson Jenny , Fornadel Christen , Oxborough Richard M. 
Published: May 2020

Abstract
Background
Millions of pyrethroid LLINs have been distributed in Mali during the past 20 years which, along with agricultural use, has increased the selection pressure on malaria vector populations. This study investigated pyrethroid resistance intensity and susceptible status of malaria vectors to alternative insecticides to guide choice of insecticides for LLINs and IRS for effective control of malaria vectors.

Methods
For 3 years between 2016 and 2018, susceptibility testing was conducted annually in 14–16 sites covering southern and central Mali. Anopheles gambiae (s.l.) were collected from larval sites and adult mosquitoes exposed in WHO tube tests to diagnostic doses of bendiocarb (0.1%) and pirimiphos-methyl (0.25%). Resistance intensity tests were conducted using CDC bottle bioassays (2016–2017) and WHO tube tests (2018) at 1×, 2×, 5×, and 10× the diagnostic concentration of permethrin, deltamethrin and alpha-cypermethrin. WHO tube tests were conducted with pre-exposure to the synergist PBO followed by permethrin or deltamethrin. Chlorfenapyr was tested in CDC bottle bioassays at 100 µg active ingredient per bottle and clothianidin at 2% in WHO tube tests. PCR was performed to identify species within the An. gambiae complex.

Results
In all sites An. gambiae (s.l.) showed high intensity resistance to permethrin and deltamethrin in CDC bottle bioassay tests in 2016 and 2017. In 2018, the WHO intensity tests resulted in survivors at all sites for permethrin, deltamethrin and alpha-cypermethrin when tested at 10× the diagnostic dose. Across all sites mean mortality was 33.7% with permethrin (0.75%) compared with 71.8% when pre-exposed to PBO (4%), representing a 2.13-fold increase in mortality. A similar trend was recorded for deltamethrin. There was susceptibility to pirimiphos-methyl, chlorfenapyr and clothianidin in all surveyed sites, including current IRS sites in Mopti Region. An. coluzzii was the primary species in 4 of 6 regions.

Conclusions
Widespread high intensity pyrethroid resistance was recorded during 2016–2018 and is likely to compromise the effectiveness of pyrethroid LLINs in Mali. PBO or chlorfenapyr LLINs should provide improved control of An. gambiae (s.l.). Clothianidin and pirimiphos-methyl insecticides are currently being used for IRS as part of a rotation strategy based on susceptibility being confirmed in this study.
Alzheimer’s disease progression characterized by alterations in the molecular profiles and biogenesis of brain extracellular vesicles
Authors: Gallart-Palau Xavier , Guo Xue , Serra Aida , Sze Siu Kwan 
Published: May 2020

Abstract
Background
The contributions of brain intercellular communication mechanisms, specifically extracellular vesicles (EV), to the progression of Alzheimer’s disease (AD) remain poorly understood.

Methods
Here, we investigated the role(s) of brain EV in the progressive course of AD through unbiased proteome-wide analyses of temporal lobe-derived EV and proteome-label quantitation of complementary remaining brain portions. Furthermore, relevant proteins identified were further screened by multiple reaction monitoring.

Results
Our data indicate that EV biogenesis was altered during preclinical AD with the genesis of a specific population of EV containing MHC class-type markers. The significant presence of the prion protein PrP was also manifested in these brain vesicles during preclinical AD. Similarly, sequestration of amyloid protein APP in brain EV coincided with the observed PrP patterns. In contrast, active incorporation of the mitophagy protein GABARAP in these brain vesicles was disrupted as AD progressed. Likewise, disrupted incorporation of LAMP1 in brain EV was evident from the initial manifestation of AD clinical symptoms, although the levels of the protein remained significantly upregulated in the temporal lobe of diseased brains.

Conclusions
Our findings indicate that impaired autophagy in preclinical AD coincides with the appearance of proinflammatory and neuropathological features in brain extracellular vesicles, facts that moderately remain throughout the entire AD progression. Thus, these data highlight the significance of brain EV in the establishment of AD neuropathology and represent a further leap toward therapeutic interventions with these vesicles in human dementias.
On the axiomatic foundation of carbon and energy footprints
Authors: Kuhn Thomas , Pestow Radomir , Zenker Anja 
Published: May 2020

Abstract
Background
A wide variety of footprint concepts is proposed in the scientific literature giving rise to a selection problem.

Method
The objective of this paper is to provide an axiomatic foundation to the concept of ecological footprint indices, in particular carbon and energy footprints. For this purpose, we define five axioms representing general properties which any ecological footprint measure should fulfill.

Results
It can be shown that there exists a unique index which is characterized by the given set of axioms. Its functional form is determined, and an economic interpretation is given. The most prominent empirical application is discussed.

Conclusion
We find that the proposed index as a generalization of more specific indices like carbon and energy footprint indices may confirm some important issues discussed in the literature. First, it incorporates a trade component indicating the ecological footprint of economic activities embodied in the trade pattern of a country or region. Moreover, the productivity of land use in production as a means to mitigate the pressure on the ecological system is reflected. But, most importantly, from a methodological point of view, there is no longer the need for designing ecological footprint indices ad hoc, in particular for the sake of empirical application.
Soil-plant co-stimulation during forest vegetation restoration in a subtropical area of southern China
Authors: Chen Chan , Fang Xi , Xiang Wenhua , Lei Pifeng , Ouyang Shuai , Kuzyakov Yakov 
Published: May 2020

AbstractBackgroundSoil and vegetation have a direct impact on the process and direction of plant community succession, and determine the structure, function, and productivity of ecosystems. However, little is known about the synergistic influence of soil physicochemical properties and vegetation features on vegetation restoration. The aim of this study was to investigate the co-evolution of soil physicochemical properties and vegetation features in the process of vegetation restoration, and to distinguish the primary and secondary relationships between soil and vegetation in their collaborative effects on promoting vegetation restoration in a subtropical area of China.MethodsSoil samples were collected to 40 cm in four distinct plant communities along a restoration gradient from herb (4–5 years), to shrub (11–12 years), toPinus massonianaconiferous and broadleaved mixed forest (45–46 years), and to evergreen broadleaved forest (old growth forest). Measurements were taken of the soil physicochemical properties and Shannon–Wiener index (SD), diameter at breast height (DBH), height (H), and biomass. Principal component analysis, linear function analysis, and variation partitioning analysis were then performed to prioritize the relative importance of the leading factors affecting vegetation restoration.ResultsSoil physicochemical properties and vegetation features showed a significant trend of improvement across the vegetation restoration gradient, reflected mainly in the high response rates of soil organic carbon (SOC) (140.76%), total nitrogen (TN) (222.48%), total phosphorus (TP) (59.54%), alkaline hydrolysis nitrogen (AN) (544.65%), available phosphorus (AP) (53.28%), species diversity (86.3%), biomass (2906.52%), DBH (128.11%), andH(596.97%). The soil properties (pH, SOC, TN, AN, and TP) and vegetation features (biomass, DBH, andH) had a clear co-evolutionary relationship over the course of restoration. The synergistic interaction between soil properties and vegetation features had the greatest effect on biomass (55.55%–72.37%), and the soil properties contributed secondarily (3.30%–31.44%). The main impact factors of biomass varied with the restoration periods.ConclusionsIn the process of vegetation restoration, soil and vegetation promoted each other. Vegetation restoration was the cumulative result of changes in soil fertility and vegetation features.
Imaging-AMARETTO: An Imaging Genomics Software Tool to Interrogate Multiomics Networks for Relevance to Radiography and Histopathology Imaging Biomarkers of Clinical Outcomes
Authors: Gevaert Olivier , Nabian Mohsen , Bakr Shaimaa , Everaert Celine , Shinde Jayendra , Manukyan Artur , Liefeld Ted , Tabor Thorin , Xu Jishu , Lupberger Joachim , Haas Brian J. , Baumert Thomas F. , Hernaez Mikel , Reich Michael , Quintana Francisco J. , Uhlmann Erik J. , Krichevsky Anna M. , Mesirov Jill P. , Carey Vincent , Pochet Nathalie 
Published: May 2020

PURPOSE The availability of increasing volumes of multiomics, imaging, and clinical data in complex diseases such as cancer opens opportunities for the formulation and development of computational imaging genomics methods that can link multiomics, imaging, and clinical data. METHODS Here, we present the Imaging-AMARETTO algorithms and software tools to systematically interrogate regulatory networks derived from multiomics data within and across related patient studies for their relevance to radiography and histopathology imaging features predicting clinical outcomes. RESULTS To demonstrate its utility, we applied Imaging-AMARETTO to integrate three patient studies of brain tumors, specifically, multiomics with radiography imaging data from The Cancer Genome Atlas (TCGA) glioblastoma multiforme (GBM) and low-grade glioma (LGG) cohorts and transcriptomics with histopathology imaging data from the Ivy Glioblastoma Atlas Project (IvyGAP) GBM cohort. Our results show that Imaging-AMARETTO recapitulates known key drivers of tumor-associated microglia and macrophage mechanisms, mediated by STAT3, AHR, and CCR2, and neurodevelopmental and stemness mechanisms, mediated by OLIG2. Imaging-AMARETTO provides interpretation of their underlying molecular mechanisms in light of imaging biomarkers of clinical outcomes and uncovers novel master drivers, THBS1 and MAP2, that establish relationships across these distinct mechanisms. CONCLUSION Our network-based imaging genomics tools serve as hypothesis generators that facilitate the interrogation of known and uncovering of novel hypotheses for follow-up with experimental validation studies. We anticipate that our Imaging-AMARETTO imaging genomics tools will be useful to the community of biomedical researchers for applications to similar studies of cancer and other complex diseases with available multiomics, imaging, and clinical data.
SAT-094 Evaluation of IGF-1 as a Biomarker to Inform Phase 3 Clinical Trial Design and Dose Selection in Patients Born Small for Gestational Age Who Fail to Demonstrate Catch-Up Growth by Age 2–4 Years
Authors: Liu Tao , Penzenstadler Justin , Cicali Brain , Zemskova Marina S , Vaidyanathan Jayabharathi , Sahajwalla Chandrahas 
Published: May 2020

Abstract
Insulin-like growth factor-1 (IGF-1) is a key hormone in mediating the physiological response to endogenous and exogenous growth hormone (GH). Current clinical guidelines suggest use of IGF-1 for dose titration in adults with GH deficiency and for safety monitoring in adults and pediatric patients. Several GH drug development programs for pediatric indications have collected IGF-1, height standard deviation score (HSDS), and height velocity (HV), to support dose selection in Phase 3 clinical trials. In this analysis, patients born small for gestational age (SGA) who fail to demonstrate catch-up growth by age 2–4 years from different growth hormone product development programs were included. A total of 663 patients from 8 clinical trials were included in this analysis, with 7 placebo arms and 15 growth hormone treated arms. The growth hormone dosing regimen ranged from 33 ug/kg/day to 100 ug/kg/day. Both boys and girls throughout a wide range of ages (3 to 7 years old on average) were represented in this analysis. The average patient was 3 to 4 standard deviations below the age- and sex- adjusted mean height at baseline. IGF-1 was collected and standardized according to age and sex, so called the IGF-1 standard deviation score (IGF-1 SDS). At baseline, the average patient had normal IGF-1 (-1 to 0 on average). Based on preliminary findings, IGF-1 SDS change from baseline (CFB) at 6 months was correlated with HSDS CFB at 12 months. HSDS CFB at 3 months and 6 months were also correlated with HSDS CFB at 12 months, respectively. These findings were consistent across the three GH products included in the analysis, as well as age and gender. However, IGF-1 SDS CFB had much larger variability than HSDS CFB. Both HSDS CFB at 3 months and 6 months precisely and accurately predicted HSDS CFB at 12 months. IGF-1 SDS was more variable and did not add any further contribution in the prediction of HSDS at 12 months and therefore IGF-1 may not be sufficient in informing Phase 3 dose selection in such trials.
Reference: 1. Shoshana Yakar, Clifford J. Rosen, Wesley G. Beamer, et al. Circulating levels of IGF-1 directly regulate bone growth and density. J Clin Invest. 2002 Sep 15; 110(6): 771–781. 2. Locatelli V, Bianchi VE. Effect of GH/IGF-1 on Bone Metabolism and Osteoporosis. Int J Endocrinol. 2014;2014:235060 Nothing to Disclose: TL, JP, BC, MZ, JV, CS
SUN-248 Estradiol Changes Angiotensin II-Induced ERK1/2 Phosphorylation by Different Pathways in the Hypothalamus and Lamina Terminalis
Authors: Almeida-Pereira Gislaine , Elias Lucila Leico Kagohara , Antunes-Rodrigues José 
Published: May 2020

Abstract
Female gonadal hormones, especially 17β-estradiol (E2), are known to mediate hydromineral homeostasis and blood pressure mainly by attenuating renin-angiotensin system (RAS) actions. The RAS plays an essential role in the maintenance of hydromineral and cardiovascular homeostasis via angiotensin II (ANGII), a key component of the RAS. However, the cellular mechanisms of the interaction between E2 and ANGII and its physiological role are not fully elucidated. Recently, our group showed that ERK1/2 is involved in sodium intake and vasopressin release induced by ANGII in female rats. In addition, E2 decreases ERK1/2 phosphorylation induced by ANGII in the hypothalamus and in structures of the lamina terminalis (LT). Thus, the goal of the present study was evaluated some mechanisms that could be involved in ERK1/2 dephosphorylation induced by E2 in response to ANGII, such as MAPK phosphatase 1 (MKP-1) and GRK5. For this, Wistar female rats (~250g) were submitted to ovariectomy and on the following day they were treated with estradiol cypionate (10µg/rat, sc) or vehicle (corn oil, 0.1mL/rat, sc) for eight days. On the eighth day, the rats received an intracerebroventricular (icv, lateral ventricle) injection of angiotensin II (25ng/2μL/rat) or vehicle (0.9% saline, 2μL/rat). After five min of ANGII injection the animals were decapitated for brain collection for MKP-1 and GRK5 expression analysis by western blot. Data were analyzed using ANOVA two or three-way, followed by Newman-Keuls post-test and the level of significance was set at 5%. It was observed that E2 increased MKP-1 expression only in hypothalamus (F1,18=24.3, p&lt;0.001) in ovariectomized rats, independent of ANGII stimulus. Because the inhibitory effect of E2 on vasopressin release induced by ANGII was reversed by PKC inhibition, it was analyzed the role of PKC on MKP-1 expression and it was observed that PKC inhibition (Chelerythrine, 100µM/2µL/rat) reversed the positive effect of E2 on MKP-1 expression (F1,30=4.7, p&lt;0.05) in the hypothalamus. In addition, E2 decreased GRK5 expression only in the LT (F1,21=12.7, p&lt;0.01) in response to ANGII. Taken together, these results suggest that E2 requires PKC/MKP-1 pathway to decrease ERK1/2 phosphorylation in the hypothalamus and consequent vasopressin release induced by ANGII. While in the LT, the inhibitory effect of E2 involves decreasing GRK5 expression compromising ERK1/2 phosphorylation and sodium intake induced by ANGII. A significant contribution of this work is the identification of some steps of ANGII signaling modulated by E2, which can explain, at least in part, its regulation on the central ANGII effects.