bluuebunny/crossref_metadata_2025_split huggingface dataset:
Small‐Conductance Calcium‐Activated Potassium Current in Normal Rabbit Cardiac Purkinje Cells
Authors: Reher Thomas A. , Wang Zhuo , Hsueh Chia‐Hsiang , Chang Po‐Cheng , Pan Zhenwei , Kumar Mohineesh , Patel Jheel , Tan Jian , Shen Changyu , Chen Zhenhui , Fishbein Michael C. , Rubart Michael , Boyden Penelope , Chen Peng‐Sheng 
Published: May 2017

Background

Purkinje cells (
PC
s) are important in cardiac arrhythmogenesis. Whether small‐conductance calcium‐activated potassium (
SK
) channels are present in
PC
s remains unclear. We tested the hypotheses that subtype 2
SK
(
SK
2) channel proteins and apamin‐sensitive SK currents are abundantly present in
PC
s.

Methods and Results

We studied 25 normal rabbit ventricles, including 13 patch‐clamp studies, 4 for Western blotting, and 8 for immunohistochemical staining. Transmembrane action potentials were recorded in current‐clamp mode using the perforated‐patch technique. For
PC
s, the apamin (100 nmol/L) significantly prolonged action potential duration measured to 80% repolarization by an average of 10.4 ms (95%
CI
, 0.11–20.72) (n=9,
P
=0.047). Voltage‐clamp study showed that apamin‐sensitive
SK
current density was significantly larger in
PC
s compared with ventricular myocytes at potentials ≥0 mV. Western blotting of
SK
2 expression showed that the
SK
2 protein expression in the midmyocardium was 58% (
P
=0.028) and the epicardium was 50% (
P
=0.018) of that in the pseudotendons. Immunostaining of
SK
2 protein showed that PCs stained stronger than ventricular myocytes. Confocal microscope study showed
SK
2 protein was distributed to the periphery of the
PC
s.

Conclusions

SK
2 proteins are more abundantly present in the
PC
s than in the ventricular myocytes of normal rabbit ventricles. Apamin‐sensitive
SK
current is important in ventricular repolarization of normal
PC
s.
Contralesional Brain–Computer Interface Control of a Powered Exoskeleton for Motor Recovery in Chronic Stroke Survivors
Authors: Bundy David T. , Souders Lauren , Baranyai Kelly , Leonard Laura , Schalk Gerwin , Coker Robert , Moran Daniel W. , Huskey Thy , Leuthardt Eric C. 
Published: May 2017

Background and Purpose—
There are few effective therapies to achieve functional recovery from motor-related disabilities affecting the upper limb after stroke. This feasibility study tested whether a powered exoskeleton driven by a brain–computer interface (BCI), using neural activity from the unaffected cortical hemisphere, could affect motor recovery in chronic hemiparetic stroke survivors. This novel system was designed and configured for a home-based setting to test the feasibility of BCI-driven neurorehabilitation in outpatient environments.

Methods—
Ten chronic hemiparetic stroke survivors with moderate-to-severe upper-limb motor impairment (mean Action Research Arm Test=13.4) used a powered exoskeleton that opened and closed the affected hand using spectral power from electroencephalographic signals from the unaffected hemisphere associated with imagined hand movements of the paretic limb. Patients used the system at home for 12 weeks. Motor function was evaluated before, during, and after the treatment.

Results—
Across patients, our BCI-driven approach resulted in a statistically significant average increase of 6.2 points in the Action Research Arm Test. This behavioral improvement significantly correlated with improvements in BCI control. Secondary outcomes of grasp strength, Motricity Index, and the Canadian Occupational Performance Measure also significantly improved.

Conclusions—
The findings demonstrate the therapeutic potential of a BCI-driven neurorehabilitation approach using the unaffected hemisphere in this uncontrolled sample of chronic stroke survivors. They also demonstrate that BCI-driven neurorehabilitation can be effectively delivered in the home environment, thus increasing the probability of future clinical translation.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT02552368.
Comparison of subjective and fully automated methods for measuring mammographic density
Authors: Moshina Nataliia , Roman Marta , Sebuødegård Sofie , Waade Gunvor G , Ursin Giske , Hofvind Solveig 
Published: June 2017

Background Breast radiologists of the Norwegian Breast Cancer Screening Program subjectively classified mammographic density using a three-point scale between 1996 and 2012 and changed into the fourth edition of the BI-RADS classification since 2013. In 2015, an automated volumetric breast density assessment software was installed at two screening units. Purpose To compare volumetric breast density measurements from the automated method with two subjective methods: the three-point scale and the BI-RADS density classification. Material and Methods Information on subjective and automated density assessment was obtained from screening examinations of 3635 women recalled for further assessment due to positive screening mammography between 2007 and 2015. The score of the three-point scale (I = fatty; II = medium dense; III = dense) was available for 2310 women. The BI-RADS density score was provided for 1325 women. Mean volumetric breast density was estimated for each category of the subjective classifications. The automated software assigned volumetric breast density to four categories. The agreement between BI-RADS and volumetric breast density categories was assessed using weighted kappa (kw). Results Mean volumetric breast density was 4.5%, 7.5%, and 13.4% for categories I, II, and III of the three-point scale, respectively, and 4.4%, 7.5%, 9.9%, and 13.9% for the BI-RADS density categories, respectively ( P for trend < 0.001 for both subjective classifications). The agreement between BI-RADS and volumetric breast density categories was kw = 0.5 (95% CI = 0.47–0.53; P < 0.001). Conclusion Mean values of volumetric breast density increased with increasing density category of the subjective classifications. The agreement between BI-RADS and volumetric breast density categories was moderate.
A Good Idea May Not Be Good Enough: Stakeholder Buy In to QuitConnect, a National Smokers’ Registry
Authors: Macauda Mark M. , Thrasher James F. , Saul Jessie E. , Celestino Paula , Cummings K. Michael , Strayer Scott M. 
Published: June 2017

Purpose: To examine interest and concerns among those who fund and operate state-run smoking cessation helplines (quitlines) about the concept of creating a centralized smokers’ registry that could be used to reengage smokers after they receive initial quitline support services. Design: We conducted 3, hour-long focus groups with stakeholders, covering the perceived benefits and barriers to creating a smokers’ registry. Setting: The focus groups were conducted via telephone. Participants: Three groups participated: quitline service providers (n = 14), quitline funders (n = 9), and national quitline partners (n = 8). Method: Data collection: Focus groups were recorded, transcribed, and coded for major relevant themes. Analysis Strategies: We used a grounded theory approach. Results: Stakeholders were generally positive about the concept of a centralized smokers’ registry (ie, QuitConnect), especially with its potential to link relapsed smokers to ongoing research studies designed to help smokers achieve abstinence from tobacco. However, stakeholders expressed concern about QuitConnect duplicating services already offered by state quitlines. Conclusion: Despite a common goal, many state quitline stakeholders had strong reservations about the creation of a centralized smokers’ registry unless they could see clear evidence that the registry added value and was not duplicative of their existing services.
A Retrospective Study of Patient Factors That Indicate Provider Nonadherence to an Institutional Clostridium difficile Treatment Guideline
Authors: Siehnel Jeremy T. , Lavigne Jill E. , Rightmier Elizabeth A. , Bossard Will T. , Li Na , Slish Judianne C. 
Published: June 2017

Background: Clostridium difficile infection (CDI) is treated most often with metronidazole or vancomycin. Both have been effective in treatment of mild to moderate infection. In more severe cases, vancomycin may be more effective. Objectives: The primary objectives were to quantify the severity of CDI and to describe overall adherence to the institutional CDI guideline. Secondary objectives were to assess factors associated with adherence to the guidelines. Methods: Retrospective analysis of the electronic medical record was used to evaluate adherence to institutional guidelines. Data collected included demographics and other factors potentially contributing to adherence: Charlson comorbidity index, severity of infection, recurrence, intensive care unit (ICU) admission, infectious diseases (ID) consult, total duration and number of antibiotics, alternative therapies, and acid suppression. Descriptive statistics and bivariate analyses were used to describe and compare factors associated with guideline adherence; multivariate logistic regression assessed independent predictors of adherence. Results: A total of 387 patients met the inclusion criteria. CDI severity was 55.8% mild/moderate cases, 42.4% severe, 0.5% fulminant, and 1.3% prophylaxis. Overall, institutional guideline adherence was 51.9%. In bivariate analyses, 5 factors were associated with nonadherence to guidelines: older age, ICU admission, duration of antibiotics, mild/moderate and severe infection (all P < .05). In the logistic regression model, severe infection ( P < .001) and longer duration of antibiotics ( P < .05) were independently associated with guideline nonadherence. Conclusion: In this study, 42.4% of the patients met criteria for severe infection. Providers for patients with severe infection and longer duration of antibiotic therapy were less likely to adhere to the institutional guideline.
Newly developed dilute Russell’s viper venom reagents for lupus anticoagulant detection with improved specificity
Authors: Moore G W , Peyrafitte M , Dunois C , Amiral J 
Published: May 2017

Background Dilute Russell’s viper venom time (dRVVT) is indispensible in lupus anticoagulant (LA) detection yet commercial reagents from different suppliers perform variably, no gold standard assays exist and therapeutic anticoagulation interference is problematic. Objective The objective of this study was to compare a new formulation dRVVT with two currently available dRVVTs. Materials and methods Life Diagnostics (LD) dRVVT and Stago PTT-LA were routinely used for lupus anticoagulant detection, plus Taipan snake venom time/ecarin time (TSVT/ET) for patients on warfarin or rivaroxaban. Siemens dRVVT and the new HYPHEN BioMed (HBM) dRVVT were tested with 193 patient samples. Group 1, 59 non-anticoagulated patients (NAPs) LA-positive in LD dRVVT; Group 2, 15 PTT-LA-positive/dRVVT-negative NAPs; Group 3, 24 LA-positive warfarinized patients; Group 4, 13 patients on rivaroxaban; Group 5, 62 LA-negative thrombotic NAPs; Group 6, 20 warfarinized, non-antiphospholipid syndrome patients. Results Accepting that the Life Diagnostics reagents were acting as a pseudo-gold standard, Siemens dRVVT detected 56/59, (95%) Group 1 LA and HBM dRVVT 46/59, (76%), one each from Group 2, and Siemens dRVVT detected one in Group 5. The lower HBM dRVVT detection rate mainly concerned weaker LA, where between-reagent concordance is problematic. All Group 3 patients appeared LA-positive in undiluted plasma with Siemens dRVVT, as did 16/24 (67%) with HBM dRVVT but the fewer LA-positives in mixing tests better mapped to clear LA-positives with LD dRVVT. LD and Siemens dRVVTs exhibited 87% and 95% false-positivity for Group 6 whilst HBM dRVVT had none. Increasing the cut-off improved accuracy. Applying higher cut-offs improved accuracy in Group 4 patients. Conclusion HBM dRVVT exhibited improved specificity, mainly due to less interference by anticoagulation, but reduced sensitivity, compared to the other dRVVTs employed.
Supramalleolar Osteotomy for Tibial Component Malposition in Total Ankle Replacement
Authors: Deforth Manja , Krähenbühl Nicola , Zwicky Lukas , Knupp Markus , Hintermann Beat 
Published: May 2017

Background: Persistent pain despite a total ankle replacement is not uncommon. A main source of pain may be an insufficiently balanced ankle. An alternative to the revision of the existing arthroplasty is the use of a corrective osteotomy of the distal tibia, above the stable implant. This strictly extraarticular procedure preserves the integrity of the replaced joint. The aim of this study was to review a series of patients in whom a corrective supramalleolar osteotomy was performed to realign a varus misaligned tibial component in total ankle replacement. We hypothesized that the supramalleolar osteotomy would correct the malpositioned tibial component, resulting in pain relief and improvement of function. Methods: Twenty-two patients (9 male, 13 female; mean age, 62.6 years; range, 44.7-80) were treated with a supramalleolar osteotomy to correct a painful ankle with a varus malpositioned tibial component. Prospectively recorded radiologic and clinical outcome data as well as complications and reoperations were analyzed. Results: The tibial anterior surface angle significantly changed from 85.2 ± 2.5 degrees preoperatively to 91.4 ± 2.9 degrees postoperatively ( P < .0001), the American Orthopaedic Foot & Ankle Society hindfoot score significantly increased from 46 ± 14 to 66 ± 16 points ( P < .0001) and the patient’s pain score measured with the visual analog scale significantly decreased from 5.8 ± 1.9 to 3.3 ± 2.4 ( P < .001). No statistical difference was found in the tibial lateral surface angle and the range of motion of the ankle when comparing the preoperative to the postoperative measurements. The osteotomy healed in all but 3 patients on first attempt. Fifteen patients (68%) were (very) satisfied, 4 moderately satisfied, and 3 patients were not satisfied with the result. Conclusion: The supramalleolar osteotomy was found to be a reliable treatment option for correcting the varus misaligned tibial component in a painful replaced ankle. However, nonunion (14%) should be mentioned as a possible complication of this surgery. Nonetheless, as a strictly extraarticular procedure, it did not compromise function of the previously replaced ankle, and it was shown to relieve pain without having to have revised a well-fixed ankle arthroplasty. Level of evidence: Level IV, case series.
Peripheral KV7 channels regulate visceral sensory function in mouse and human colon
Authors: Peiris Madusha , Hockley James RF , Reed David E , Smith Ewan St. John , Bulmer David C , Blackshaw L Ashley 
Published: June 2017

Background Chronic visceral pain is a defining symptom of many gastrointestinal disorders. The KV7 family (KV7.1–KV7.5) of voltage-gated potassium channels mediates the M current that regulates excitability in peripheral sensory nociceptors and central pain pathways. Here, we use a combination of immunohistochemistry, gut-nerve electrophysiological recordings in both mouse and human tissues, and single-cell qualitative real-time polymerase chain reaction of gut-projecting sensory neurons, to investigate the contribution of peripheral KV7 channels to visceral nociception. Results Immunohistochemical staining of mouse colon revealed labelling of KV7 subtypes (KV7.3 and KV7.5) with CGRP around intrinsic enteric neurons of the myenteric plexuses and within extrinsic sensory fibres along mesenteric blood vessels. Treatment with the KV7 opener retigabine almost completely abolished visceral afferent firing evoked by the algogen bradykinin, in agreement with significant co-expression of mRNA transcripts by single-cell qualitative real-time polymerase chain reaction for KCNQ subtypes and the B2 bradykinin receptor in retrogradely labelled extrinsic sensory neurons from the colon. Retigabine also attenuated responses to mechanical stimulation of the bowel following noxious distension (0–80 mmHg) in a concentration-dependent manner, whereas the KV7 blocker XE991 potentiated such responses. In human bowel tissues, KV7.3 and KV7.5 were expressed in neuronal varicosities co-labelled with synaptophysin and CGRP, and retigabine inhibited bradykinin-induced afferent activation in afferent recordings from human colon. Conclusions We show that KV7 channels contribute to the sensitivity of visceral sensory neurons to noxious chemical and mechanical stimuli in both mouse and human gut tissues. As such, peripherally restricted KV7 openers may represent a viable therapeutic modality for the treatment of gastrointestinal pathologies.
Ryk receptors on unmyelinated nerve fibers mediate excitatory synaptic transmission and CCL2 release during neuropathic pain induced by peripheral nerve injury
Authors: Yang Qing Ou , Yang Wen-Jing , Li Jian , Liu Fang-Ting , Yuan Hongbin , Ou Yang Yue-Ping 
Published: June 2017

Background Neuropathic pain is a major pathology of the central nervous system associated with neuroinflammation. Ryk (receptor-like tyrosine kinase) receptors act as repulsive axon-guidance molecules during development of central nervous system and neural injury. Increasing evidence suggests the potential involvement of Wnt/Ryk (wingless and Int) signaling in the pathogenesis of neuropathic pain. However, its underlying mechanism remains unknown. Results The expression and location of Ryk receptor as well as its ligand Wnt1 were detected by qPCR, Western blot, and immunohistochemistry. We found that Ryk, a specific Wnt receptor, was expressed in IB4+ (Isolectin B4) and CGRP+ (calcitonin gene-related peptide) dorsal root ganglia neurons and their ascending unmyelinated fibers in the dorsal horn of the spinal cord. Ryk was upregulated after spinal nerve ligation surgery. Wnt1 was also increased in activated astrocytes in the dorsal horn after spinal nerve ligation. The presynaptic mechanism of Ryk in regulation of neuropathic pain was determined by electrophysiology in spinal slice. Spinal nerve ligation model was established, and the therapeutic potential of inhibiting Ryk receptor was determined. Spine-specific blocking of the Wnt/Ryk receptor signaling attenuated the spinal nerve ligation-induced mechanical allodynia but not thermal hyperalgesia. Further, it also blocked Ca2+-dependent signals including CaMKII and PKCγ, subsequent release of CCL2 (CCR-like protein) in the dorsal horn. An in vitro study showed that inactivating Ryk receptors with anti-Ryk antibodies or lentiviral Ryk shRNA led to the inactivation of Wnt1 for excitatory synaptic transmission in spinal slices and subsequent decrease in CCL2 expression in the dorsal root ganglia neurons. Conclusion These studies demonstrate the existence of critical crosstalk between astrocytes and unmyelinated fibers, which indicate the presynaptic mechanism of Ryk in cytokine transmission of neuropathic pain and the therapeutic potential for Wnt/Ryk signaling pathway in the treatment of neuropathic pain.
Diabetes and Prediabetes Classification Using Glycemic Variability Indices From Continuous Glucose Monitoring Data
Authors: Acciaroli Giada , Sparacino Giovanni , Hakaste Liisa , Facchinetti Andrea , Di Nunzio Giorgio Maria , Palombit Alessandro , Tuomi Tiinamaija , Gabriel Rafael , Aranda Jaime , Vega Saturio , Cobelli Claudio 
Published: June 2017

Background: Tens of glycemic variability (GV) indices are available in the literature to characterize the dynamic properties of glucose concentration profiles from continuous glucose monitoring (CGM) sensors. However, how to exploit the plethora of GV indices for classifying subjects is still controversial. For instance, the basic problem of using GV indices to automatically determine if the subject is healthy rather than affected by impaired glucose tolerance (IGT) or type 2 diabetes (T2D), is still unaddressed. Here, we analyzed the feasibility of using CGM-based GV indices to distinguish healthy from IGT&T2D and IGT from T2D subjects by means of a machine-learning approach. Methods: The data set consists of 102 subjects belonging to three different classes: 34 healthy, 39 IGT, and 29 T2D subjects. Each subject was monitored for a few days by a CGM sensor that produced a glucose profile from which we extracted 25 GV indices. We used a two-step binary logistic regression model to classify subjects. The first step distinguishes healthy subjects from IGT&T2D, the second step classifies subjects into either IGT or T2D. Results: Healthy subjects are distinguished from subjects with diabetes (IGT&T2D) with 91.4% accuracy. Subjects are further subdivided into IGT or T2D classes with 79.5% accuracy. Globally, the classification into the three classes shows 86.6% accuracy. Conclusions: Even with a basic classification strategy, CGM-based GV indices show good accuracy in classifying healthy and subjects with diabetes. The classification into IGT or T2D seems, not surprisingly, more critical, but results encourage further investigation of the present research.
AL amyloidosis patients with low amyloidogenic free light chain levels at first diagnosis have an excellent prognosis
Authors: Dittrich Tobias , Bochtler Tilmann , Kimmich Christoph , Becker Natalia , Jauch Anna , Goldschmidt Hartmut , Ho Anthony D. , Hegenbart Ute , Schönland Stefan O. 
Published: May 2017

Key PointsAL patients with an initial dFLC <50 mg/L represent a distinct clinical subgroup with mostly renal disease and a favorable prognosis. These patients are evaluable for hematologic response including a novel low-dFLC partial response, which predict renal and overall survival.
A phase 1/2 study of the oral proteasome inhibitor ixazomib in relapsed or refractory AL amyloidosis
Authors: Sanchorawala Vaishali , Palladini Giovanni , Kukreti Vishal , Zonder Jeffrey A. , Cohen Adam D. , Seldin David C. , Dispenzieri Angela , Jaccard Arnaud , Schönland Stefan O. , Berg Deborah , Yang Huyuan , Gupta Neeraj , Hui Ai-Min , Comenzo Raymond L. , Merlini Giampaolo 
Published: May 2017

Abstract
This phase 1/2 study assessed the safety, tolerability, and preliminary efficacy of the oral proteasome inhibitor (PI) ixazomib in patients with relapsed/refractory immunoglobulin light chain (AL) amyloidosis. Ixazomib was administered to adult patients with relapsed/refractory AL amyloidosis after 1 or more prior lines of therapy (including bortezomib) on days 1, 8, and 15 of 28-day cycles, for up to 12 cycles. Patients with less than partial response after 3 cycles received oral dexamethasone (40 mg, days 1-4) from cycle 4. A 3+3 dose-escalation phase was followed by 2 expansion cohorts (PI-naive and PI-exposed patients) at the maximum tolerated dose (MTD). Twenty-seven patients were enrolled: 11 during dose escalation (6 at 4.0 mg and 5 at 5.5 mg) and 16 during dose expansion (4.0 mg). Three patients experienced dose-limiting toxicities: 1 at 4.0 mg and 2 at 5.5 mg; the MTD was determined as 4.0 mg. Most common adverse events (AEs) included nausea, skin and subcutaneous tissue disorders (SSTD), diarrhea, and fatigue; grade 3 or higher AEs included dyspnea, fatigue, and SSTD. Overall, the hematologic response rate was 52% in patients treated at the MTD (n = 21). Organ responses were seen in 56% of patients (5 cardiac, 5 renal). Median hematologic progression-free survival was 14.8 months; 1-year progression-free and overall survival rates were 60% and 85%, respectively (median follow-up, 16.9 months). Weekly oral ixazomib appears to be active in patients with relapsed/refractory AL amyloidosis, with a generally manageable safety profile. The study was registered at clinicaltrials.gov as #NCT01318902. A phase 3 study is ongoing (#NCT01659658).
A population-based longitudinal study on the implication of demographic changes on blood donation and transfusion demand
Authors: Greinacher Andreas , Weitmann Kerstin , Schönborn Linda , Alpen Ulf , Gloger Doris , Stangenberg Wolfgang , Stüpmann Kerstin , Greger Nico , Kiefel Volker , Hoffmann Wolfgang 
Published: May 2017

Key Points
Demographic changes have a direct impact on the blood supply, and demography can be used to predict blood donation rates in the future. The transfusion demand cannot be predicted from demography.