bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gait biofeedback and impairment‐based rehabilitation for chronic ankle instability
Authors: Koldenhoven Rachel M. , Jaffri Abbis H. , DeJong Alexandra F. , Abel Mark , Hart Joseph , Saliba Susan , Hertel Jay 
Published: September 2020

Our purpose was to analyze the effects of 4 weeks of visual gait biofeedback (GBF) and impairment‐based rehabilitation on gait biomechanics and patient‐reported outcomes (PROs) in individuals with chronic ankle instability (CAI). Twenty‐seven individuals with CAI participated in this randomized controlled trial (14 received no biofeedback (NBF), 13 received GBF). Both groups received 8 sessions of impairment‐based rehabilitation. The GBF group received visual biofeedback to reduce ankle frontal plane angle at initial contact (IC) during treadmill walking. The NBF group walked for equal time during rehabilitation but without biofeedback. Dependent variables included three‐dimensional kinematics and kinetics at the ankle, knee, and hip, electromyography amplitudes of 4 lower extremity muscles (tibialis anterior, fibularis longus, medial gastrocnemius, and gluteus medius), and PROs (Foot and Ankle Ability Measure Activities of Daily Living (FAAM‐ADL), FAAM‐Sport, Tampa Scale of Kinesiophobia (TSK), and Global Rating of Change (GROC)). The GBF group significantly decreased ankle inversion at IC (MD:‐7.3º, g = 1.6) and throughout the entire stride cycle (peak inversion: MD:‐5.9º, g = 1.2). The NBF group did not have significantly altered gait biomechanics. The groups were significantly different after rehabilitation for the FAAM‐ADL (GBF: 97.1 ± 2.3%, NBF: 92.0 ± 5.7%), TSK (GBF: 29.7 ± 3.7, NBF: 34.9 ± 5.8), and GROC (GBF: 5.5 ± 1.0, NBF:3.9 ± 2.0) with the GBF group showing greater improvements than the NBF group. There were no significant differences between groups for kinetics or electromyography measures. The GBF group successfully decreased ankle inversion angle and had greater improvements in PROs after intervention compared to the NBF group. Impairment‐based rehabilitation combined with visual biofeedback during gait training is recommended for individuals with CAI.
On the formation of magmatic sulphide systems in the lower crust by long‐lived mass transfer through the lithosphere: Insights from the Valmaggia pipe, Ivrea Verbano Zone, Italy
Authors: Locmelis Marek , Moroni Marilena , Denyszyn Steven W. , Webb Laura E. , Fiorentini Marco L. , Sessa Gianluca , Caruso Stefano , Mathur Ryan , Nanzad Bolorchimeg 
Published: September 2020

AbstractThe lower crustal domain of the Ivrea‐Verbano Zone (NW Italy) hosts five ~300‐m‐wide pipe‐like ultramafic intrusions that are metasomatized and exhibit Ni‐Cu‐PGE sulphide mineralization. To better constrain the role of metasomatism in the ore genesis, we studied the best‐preserved pipe at Valmaggia which was emplaced 249 Myrs ago. Phlogopite 40Ar/39Ar analyses show that the pipe was infiltrated by metasomatic fluids derived from the subcontinental lithospheric mantle (SCLM) in two pulses at ~208 Ma and ~189 Ma which introduced sulphides into the pipe. Consequently, the pipe repeatedly acted as a preferred path for mass transfer from the SCLM into the lower crust over >60 Myrs (i.e., emplacement to second metasomatic pulse). Uplifted block margins, such as the Ivrea‐Verbano Zone, are potentially important exploration targets for magmatic sulphides. We argue that exploration strategies should focus on structures such as pipes that can focus metasomatic agents during ascent through the lithosphere.
Patterns of trade restrictiveness in online platforms: A first look
Authors: Ferracane Martina Francesca , van der Marel Erik 
Published: September 2020

AbstractThis paper develops a digital platform restrictiveness index for 64 countries based on ECIPE’s Digital Trade Estimates database and the Digital Trade Restrictiveness Index. We identify specific restrictions that affect online platforms with a focus on online search, e‐commerce and social media. The results show that both OECD and non‐OECD countries show high levels of trade restrictions on online platforms. Moreover, some of the most restricted countries are characterised by large markets, signifying that a substantial part of the global economy gravitates towards restricting online platforms. Based on the platform restrictiveness index, we perform an econometric analysis showing that trade restrictions for online platforms are significantly associated with lower contributions of the ICT sector to productivity growth in the entire economy. The results suggest that reducing restrictions on online platforms can increase the ICT’s contribution to overall productivity growth towards a level seen before the global financial crisis. Sectors that would benefit the most are those that make wider use of online platforms and the Internet, including information services, business services and financial services.
American and Irish English speakers’ perceptions of the final particles so and but
Authors: Izutsu Mitsuko Narita , Izutsu Katsunobu 
Published: September 2020

AbstractThe retrospective (final‐particle) use of so and but (Thanks, but.) is documented in Irish English, but not in American English, which only has the prospective (final‐hanging) use (I could scream, but …). American English (AmE) speakers are expected to have communication difficulty in understanding the retrospective use of so and but. Interestingly, however, our questionnaire survey indicated a partially contradictory result: some AmE speakers were able to arrive at the retrospective‐scope interpretation of final so and but. To gain a more in‐depth understanding of how AmE speakers interpret such final‐particle uses, we conducted a qualitative analysis using data obtained from semi‐structured interviews with AmE speakers.
Contraction influences Per2 gene expression in skeletal muscle through a calcium‐dependent pathway
Authors: Small Lewin , Altıntaş Ali , Laker Rhianna C , Ehrlich Amy , Pattamaprapanont Pattarawan , Villarroel Julia , Pillon Nicolas J , Zierath Juleen R , Barrès Romain 
Published: September 2020

Key points
Exercising at different times of day elicits different effects on exercise performance and metabolic health. However, the specific signals driving the observed time‐of‐day specific effects of exercise have not been fully identified.
Exercise influences the skeletal muscle circadian clock, although the relative contribution of muscle contraction and extracellular signals is unknown.
Here, we show that contraction acutely increases the expression of the core circadian clock gene Period Circadian Regulator 2 (Per2) and phase‐shifts Per2 rhythmicity in muscle cells. This contraction effect on core clock genes is mediated through a calcium‐dependant mechanism;
The results obtained in the present study suggest that a proportion of the ability of exercise to entrain the skeletal muscle clock is driven directly by muscle contraction. Contraction interventions may be used to mimic some time‐of‐day specific effects of exercise on metabolism and muscle performance.
AbstractExercise entrains the central and peripheral circadian clocks, although the mechanism by which exercise modulates expression of skeletal muscle clock genes is unclear. The present study aimed to determine whether skeletal muscle contraction alone could directly influence circadian rhythmicity and uncover the underlying mechanism by which contraction modulates clock gene expression. We investigated the expression of core clock genes in human skeletal muscle after acute exercise, as well as following in vitro contraction in mouse soleus muscle and cultured C2C12 skeletal muscle myotubes. Additionally, we interrogated the molecular pathways by which skeletal muscle contraction could influence clock gene expression. Contraction acutely increased the expression of the core circadian clock gene Period Circadian Regulator 2 (Per2) and phase‐shifted Per2 rhythmicity in C2C12 myotubes in vitro. Further investigation revealed that pharmacologically increasing cytosolic calcium concentrations by ionomycin treatment mimicked the effect of contraction on Per2 expression. Similarly, treatment with a calcium channel blocker, nifedipine, blocked the effect of electric pulse stimulation‐induced contraction on Per2 expression. Increased calcium influx from contraction lead to binding of the phosphorylated form of cAMP response element‐binding protein (CREB) to the Per2 promoter, suggesting a role of CREB in contraction‐induced Per2 transcription. Thus, by dissociating the effect of muscle contraction alone from the whole effect of exercise, our investigations indicate that a proportion of the ability of exercise to entrain the skeletal muscle clock is driven directly by contraction.
Safety and efficacy of human milk-based fortifier in enterally fed preterm and/or low birthweight infants: a systematic review and meta-analysis
Authors: Grace Erin , Hilditch Cathie , Gomersall Judith , Collins Carmel T , Rumbold Alice , Keir Amy K 
Published: September 2020

ObjectiveTo conduct a systematic review and meta-analysis of the efficacy and safety of fortification of human milk with human milk-based fortifier versus cow’s milk-based fortifier for use in preterm and/or very low birthweight infants.DesignRandomised or quasi-randomised controlled trials comparing the effect of human milk fortification with human milk-based milk fortifier versus cow’s milk-based fortifier in infants born <34 weeks’ gestation and/or with birth weight <1500 g were identified by searching databases, clinical trial registries and reference lists until 5 November 2019. Two authors independently extracted data and assessed evidence quality. Meta-analyses were conducted using fixed or random effects models, as appropriate.Main outcome measuresNecrotising enterocolitis (Bell’s stage II or higher) and late-onset sepsis.ResultsOf 863 unique records identified, 16 full-text trials were screened and 2 trials involving 334 infants were included. Primary outcome data were available for 332 infants. Use of human milk-based fortifier compared with cow’s milk-based fortifier reduced the risk of necrotising enterocolitis (risk ratio 0.47, 95% CI 0.22 to 0.98). There was no clear evidence of an effect on late-onset sepsis or any other outcomes. The quality of evidence was low to very low due to imprecision and lack of blinding in one study.ConclusionsFindings suggest that there is a reduction in the incidence of necrotising enterocolitis with human milk-based fortifiers compared with cow’s milk-based fortifiers. The overall quality of evidence is low. Further appropriately powered trials are required before this intervention can be routinely recommended for preterm infants.
Primary adjunctive corticosteroid therapy is associated with improved outcomes for patients with Kawasaki disease with coronary artery aneurysms at diagnosis
Authors: Friedman Kevin G , Gauvreau Kimberlee , Baker Annette , Son Mary Beth , Sundel Robert , Dionne Audrey , Giorgio Thomas , De Ferranti Sarah , Newburger Jane W 
Published: September 2020

ObjectivePatients with Kawasaki disease (KD) with coronary artery enlargement at diagnosis are at the highest risk for persistent coronary artery aneurysms (CAAs) and may benefit from primary adjunctive anti-inflammatory therapy beyond intravenous immunoglobulin (IVIG). We evaluate the effect of primary adjunctive corticosteroid therapy on outcomes in patients with CAA at diagnosis.DesignSingle-centre, retrospective review.PatientsPatients with KD diagnosed within 10 days of fever onset and with baseline CA z-score ≥2.5.InterventionsPrimary treatment with IVIG (n=162) versus IVIG plus corticosteroids (n=48).Main outcome measuresTreatment resistance (persistent fever >36 hours after initial treatment), CAA regression rate.ResultsOf the 92 patients with KD who received corticosteroids at our institution from 2012 to 2019, 48 met the inclusion criteria for primary adjunctive therapy. The corticosteroid group was younger and had larger baseline CAAs compared with historical controls. Demographics and laboratory values were otherwise similar between groups. The corticosteroid group had a less treatment resistance (4% vs 30%, p=0.003) and a greater improvement in C reactive protein. After adjusting for baseline CA z-score, age and baseline bilateral versus unilateral CAA, the corticosteroid group had a higher odds of (OR 2.77 (1.04, 7.42), p=0.042) and a shorter time to CAA regression (HR 1.94 (1.27, 2.96), p=0.002).ConclusionPrimary adjunctive corticosteroid therapy is associated with decreased initial treatment resistance, greater improvement in inflammatory markers and higher likelihood of CAA regression in patients who have CAA at diagnosis. Multi-centre, randomised controlled trials are needed to confirm the benefits of corticosteroids in patients with CAA at diagnosis and to compare corticosteroids with other adjunctive therapies.
Computerised clinical decision support systems and absolute improvements in care: meta-analysis of controlled clinical trials
Authors: Kwan Janice L , Lo Lisha , Ferguson Jacob , Goldberg Hanna , Diaz-Martinez Juan Pablo , Tomlinson George , Grimshaw Jeremy M , Shojania Kaveh G 
Published: September 2020

Abstract

Objective
To report the improvements achieved with clinical decision support systems and examine the heterogeneity from pooling effects across diverse clinical settings and intervention targets.

Design
Systematic review and meta-analysis.

Data sources
Medline up to August 2019.

Eligibility criteria for selecting studies and methods
Randomised or quasi-randomised controlled trials reporting absolute improvements in the percentage of patients receiving care recommended by clinical decision support systems. Multilevel meta-analysis accounted for within study clustering. Meta-regression was used to assess the degree to which the features of clinical decision support systems and study characteristics reduced heterogeneity in effect sizes. Where reported, clinical endpoints were also captured.

Results

In 108 studies (94 randomised, 14 quasi-randomised), reporting 122 trials that provided analysable data from 1 203 053 patients and 10 790 providers, clinical decision support systems increased the proportion of patients receiving desired care by 5.8% (95% confidence interval 4.0% to 7.6%). This pooled effect exhibited substantial heterogeneity (I
2
=76%), with the top quartile of reported improvements ranging from 10% to 62%. In 30 trials reporting clinical endpoints, clinical decision support systems increased the proportion of patients achieving guideline based targets (eg, blood pressure or lipid control) by a median of 0.3% (interquartile range −0.7% to 1.9%). Two study characteristics (low baseline adherence and paediatric settings) were associated with significantly larger effects. Inclusion of these covariates in the multivariable meta-regression, however, did not reduce heterogeneity.

Conclusions
Most interventions with clinical decision support systems appear to achieve small to moderate improvements in targeted processes of care, a finding confirmed by the small changes in clinical endpoints found in studies that reported them. A minority of studies achieved substantial increases in the delivery of recommended care, but predictors of these more meaningful improvements remain undefined.
Transient radial paralysis occurring in a Belgian White Blue bull undergoing general anaesthesia for claw amputation
Authors: La Rosa Lavinia , Schauvliege Stijn 
Published: September 2020

A four‐year‐old, 973 kg Belgian White Blue bull was presented for further evaluation of a persistent right hindlimb lameness. The physical and radiographic examinations revealed osteitis of the medial second phalanx of the right hindlimb. A claw amputation was performed under general anaesthesia. The bull was premedicated with 0.17 mg/kg xylazine intramuscularly and general anaesthesia was induced with 2 mg/kg ketamine administered intravenously. During the recovery phase, the bull could not bear any weight on his left thoracic limb. Further examinations revealed left radial nerve paralysis. Treatment consists of a bolus of dexamethasone (0.05 mg/kg) intravenously in order to decrease the inflammation; fluid therapy in an attempt to improve muscle perfusion and to replace the fluid losses and cold showers to decrease the rise in temperature. After 90 minutes from the end of general anaesthesia, the radial paralysis resolved spontaneously without any major consequences.
Blunted blood pressure response to exercise and isolated muscle metaboreflex activation in patients with cirrhosis
Authors: Mira Pedro Augusto de Carvalho , Falci Maria Fernanda Almeida , Moreira Janaína Becari , Guerrero Rosa Virginia Diaz , Ribeiro Tarsila Campanha da Rocha , Barbosa Kátia Valéria Bastos Dias , Pace Fábio Heleno Lima , Martinez Daniel Godoy , Laterza Mateus Camaroti 
Published: September 2020

We sought to test the hypothesis that the cardiovascular responses to isolated muscle metaboreflex activation would be blunted in patients with cirrhosis. Eleven patients with cirrhosis and 15 healthy controls were evaluated. Blood pressure (BP; oscillometric method), contralateral forearm blood flow (FBF; venous occlusion plethysmography), and heart rate (HR; electrocardiogram) were measured during baseline, isometric handgrip at 30% of maximal voluntary contraction followed by postexercise ischemia (PEI). Forearm vascular conductance (FVC) was calculated as follows: (FBF / mean BP) × 100. Changes in HR during handgrip were similar between groups but tended to be different during PEI (controls: Δ 0.5 ± 1.1 bpm vs. cirrhotic patients: Δ 3.6 ± 1.0 bpm, P = 0.057). Mean BP response to handgrip (controls: Δ 20.9 ± 2.7 mm Hg vs. cirrhotic patients: Δ 10.6 ± 1.5 mm Hg, P = 0.006) and PEI was attenuated in cirrhotic patients (controls: Δ 16.1 ± 1.9 mm Hg vs. cirrhotic patients: Δ 7.2 ± 1.4 mm Hg, P = 0.001). In contrast, FBF and FVC increased during handgrip and decreased during PEI similarly between groups. These results indicate that an abnormal muscle metaboreflex activation explained, at least partially, the blunted pressor response to exercise exhibited by cirrhotic patients. Novelty: Patients with cirrhosis present abnormal muscle metaboreflex activation. BP response was blunted but forearm vascular response was preserved. HR response was slightly elevated.
Kinetic differences between macro- and microvascular measures of reactive hyperemia
Authors: Bartlett Miles F. , Oneglia Andrew , Jaffery Manall , Manitowabi-Huebner Shayla , Hueber Dennis M. , Nelson Michael D. 
Published: September 2020

NEW & NOTEWORTHY We extend our understanding of macro- versus microvascular hemodynamics in humans, by using near-infrared diffuse correlation spectroscopy (micro-) and Doppler ultrasound (macro-) to characterize reperfusion hemodynamics following experimental manipulation of the ischemic stimulus and tissue perfusion pressure. Our results suggest kinetic differences between macro- and microvascular reperfusion are largely determined by differences in fluid mechanical energy (i.e., pressure, gravitational, and kinetic energies) between the two compartments, rather than inherent differences between the macro- and microvasculature.
Dual Blockade of c-MET and the Androgen Receptor in Metastatic Castration-resistant Prostate Cancer: A Phase I Study of Concurrent Enzalutamide and Crizotinib
Authors: Tripathi Abhishek , Supko Jeffrey G. , Gray Kathryn P. , Melnick Zachary J. , Regan Meredith M. , Taplin Mary-Ellen , Choudhury Atish D. , Pomerantz Mark M. , Bellmunt Joaquim , Yu Channing , Sun Zijie , Srinivas Sandy , Kantoff Philip W. , Sweeney Christopher J. , Harshman Lauren C. 
Published: September 2020

Abstract

Purpose:
Androgen receptor (AR) inhibition can upregulate c-MET expression, which may be a resistance mechanism driving progression of castration-resistant prostate cancer (CRPC). We conducted a phase I trial investigating the safety and pharmacokinetics of a potent c-MET inhibitor, crizotinib, with the AR antagonist, enzalutamide, in CRPC.

Patients and Methods:
Employing a 3+3 dose-escalation design, we tested three dose levels of crizotinib (250 mg daily, 200 mg twice a day, and 250 mg twice a day) with standard-dose enzalutamide (160 mg daily). The primary endpoint was rate of dose-limiting toxicities (DLTs). Tolerability and pharmacokinetics profile were secondary endpoints.

Results:
Twenty-four patients were enrolled in the dose-escalation (n = 16) and dose-expansion (n = 8) phases. Two DLTs occurred in dose escalation (grade 3 alanine aminotransferase elevation). The MTD of crizotinib was 250 mg twice a day. Most frequent treatment-related adverse events were fatigue (50%), transaminitis (38%), nausea (33%), and vomiting, constipation, and diarrhea (21% each). Grade ≥3 events (25%) included transaminitis (n = 2), fatigue (n = 1), hypertension (n = 1), pulmonary embolism (n = 1), and a cardiac event encompassing QTc prolongation/ventricular arrhythmia/cardiac arrest. Median progression-free survival was 5.5 months (95% confidence interval, 2.8–21.2). Pharmacokinetics analysis at the MTD (n = 12) revealed a mean Cmaxss of 104 ± 45 ng/mL and AUCτss of 1,000 ± 476 ng•h/mL, representing a 74% decrease in crizotinib systemic exposure relative to historical data (Cmaxss, 315 ng/mL and AUCτss, 3,817 ng•h/mL).

Conclusions:
Concurrent administration of enzalutamide and crizotinib resulted in a clinically significant 74% decrease in systemic crizotinib exposure. Further investigation of this combination in CRPC is not planned. Our results highlight the importance of evaluating pharmacokinetics interactions when evaluating novel combination strategies in CRPC.
Promise and Potential Peril With Lumacaftor for the Trafficking Defective Type 2 Long-QT Syndrome-Causative Variants, p.G604S, p.N633S, and p.R685P, Using Patient-Specific Re-Engineered Cardiomyocytes
Authors: O’Hare Bailey J. , John Kim C.S. , Hamrick Samantha K. , Ye Dan , Tester David J. , Ackerman Michael J. 
Published: September 2020

Background:

The
KCNH2
-encoded Kv11.1 hERG (human ether-a-go-go related gene) potassium channel is a critical regulator of cardiomyocyte action potential duration (APD). The majority of type 2 long-QT syndrome (LQT2) stems from trafficking defective
KCNH2
mutations. Recently, Food and Drug Administration-approved cystic fibrosis protein trafficking chaperone, lumacaftor, has been proposed as novel therapy for LQT2. Here, we test the efficacy of lumacaftor treatment in patient-specific induced pluripotent stem cell-cardiomyocytes (iPSC-CMs) derived from 2 patients with known LQT2 trafficking defective mutations and a patient with novel KCNH2 variant, p.R685P.

Methods:
Patient-specific iPSC-CM models of KCNH2-G604S, KCNH2-N633S, and KCNH2-R685P were generated from 3 unrelated patients diagnosed with severe LQT2 (rate-corrected QT>500 ms). Lumacaftor efficacy was also tested by ANEPPS, FluoVolt, and ArcLight voltage dye-based APD90 measurements.

Results:
All 3 mutations were hERG trafficking defective in iPSC-CMs. While lumacaftor treatment failed to rescue the hERG trafficking defect in TSA201 cells, lumacaftor rescued channel trafficking for all mutations in the iPSC-CM model. All 3 mutations conferred a prolonged APD90 compared with control. While lumacaftor treatment rescued the phenotype of KCNH2-N633S and KCNH2-R685P, lumacaftor paradoxically prolonged the APD90 in KCNH2-G604S iPSC-CMs. Lumacaftor-mediated APD90 rescue was affected by rapidly activating delayed rectifier K+ current blocker consistent with the increase of rapidly activating delayed rectifier K+ current by lumacaftor is the underlying mechanism of the LQT2 rescue.

Conclusions:
While lumacaftor is an effective hERG channel trafficking chaperone and may be therapeutic for LQT2, we urge caution. Without understanding the functionality of the mutant channel to be rescued, lumacaftor therapy could be harmful.