bluuebunny/crossref_metadata_2025_split huggingface dataset:
What is the prevalence of rheumatic disorders in general medical inpatients?
Authors: Hood C , Johnson J , Kelly C 
Published: December 2017

Abstract
It has been suggested that rheumatological disorders are underdiagnosed in patients with medical problems and that this might be rectified by incorporating a standard brief screening examination as part of the routine assessment of all patients admitted to hospital with medical conditions. Therefore the GALS screening examination was used to assess the prevalence of rheumatic disease in 100 patients admitted with acute medical problems and in a further 100 in the rehabilitative phase of their disease. The nature of locomotor dysfunction in all patients with a positive result was defined by an independent review and then sensitivity and specificity of the screening test was calculated for rheumatic disease in both populations.
The median age of the two populations were 63 and 78 years respectively, with more females in the rehabilitation group. The overall prevalence of a positive screening test was 53% in the acute and 94% in the chronic disease groups, although the false positive rate in the rehabilitation patients was 30% due to factors other than rheumatic disorders limiting locomotor function (mainly orthopaedic and neurological conditions). The diagnosis of a rheumatological disorder was made de novo in a significant minority (10%) of patients and was usually amenable to treatment. The commonest rheumatic disorder was osteoarthritis which accounted for 55% of all rheumatic disease, followed by inflammatory joint disease (16%), and osteoporosis (12%). In addition to osteoporosis, Paget's disease of bone and polymyalgia rheumatica were found more frequently in those patients undergoing rehabilitation than in those admitted with an acute medical problem. A number of clinically important associations between medical and rheumatic disorders were found, such as stroke disease with shoulder capsulitis and heart failure with gout.
The sensitivity of the GALS screening test was extremely high (92% and 100%), while its specificity fell in the rehabilitation group from 83% to 17%. None the less, it is felt that this study indicates that the routine use of this test should be considered as part of the assessment of all hospitalised patients with medical problems, whether acute or chronic.
Force-velocity test on a stationary cycle ergometer: methodological recommendations
Authors: Rudsits Briar L. , Hopkins Will G. , Hautier Christophe A. , Rouffet David M. 
Published: December 2017

Force-velocity tests performed on stationary cycle ergometers are widely used to assess the torque- and power-generating capacities of the lower limbs. The aim of this study was to identify how testing and modeling procedures influence the assessment of individual torque-cadence and power-cadence relationships. Seventeen males completed 62 ± 16 pedal cycles from six 6-s all-out efforts interspersed with 5 min of rest. True measures of maximal power for a particular cadence were obtained for 24 ± 3 pedal cycles, while power was only 94 ± 3% of the true maximum in 19 ± 5 pedal cycles. Pedal cycles showing maximal levels of power also displayed higher levels of electromyography (EMG: 89 ± 7 vs . 87 ± 7%) and coactivation (34 ± 11 vs . 31 ± 10 arbitrary units), as well as lower variability in crank torque and EMG profiles. Compared with the linear and second-order polynomial models that are traditionally used, a better goodness of fit was obtained when the torque-cadence and power-cadence relationships were predicted using second- and third-order polynomials, respectively. The later modeling procedures also revealed an asymmetry in the power-cadence relationship in most participants (i.e., 15 out of 17) and provided a better estimation of maximal cadence [Cmax: 214 ± 20 revolutions/min (rpm)] from the x-intercept of power-cadence relationships (C0: 214 ± 14 rpm). Therefore, we recommend predicting the individual shapes of torque- and power-cadence relationships using second- and third-order polynomial regressions after having selected pedal cycles during which true measures of cadence-specific maximal power were recorded. NEW & NOTEWORTHY This study is the first to demonstrate that suboptimal activation of the lower limb muscles accompanied reductions in cadence-specific levels of torque and power produced during a force-velocity test performed on a stationary cycle ergometer. This research is also the first to show that, in most noncyclist participants, torque-cadence relationships are not linear, whereas power-cadence relationships display asymmetric shapes, with power production decreasing rapidly when cadence increases beyond 180 revolutions/min.
ESR1 Methylation: A Liquid Biopsy–Based Epigenetic Assay for the Follow-up of Patients with Metastatic Breast Cancer Receiving Endocrine Treatment
Authors: Mastoraki Sophia , Strati Areti , Tzanikou Eleni , Chimonidou Maria , Politaki Eleni , Voutsina Alexandra , Psyrri Amanda , Georgoulias Vassilis , Lianidou Evi 
Published: December 2017

Abstract
Purpose: Liquid biopsy provides real-time monitoring of tumor evolution and response to therapy through analysis of circulating tumor cells (CTCs) and plasma-circulating tumor DNA (ctDNA). ESR1 epigenetic silencing potentially affects response to endocrine treatment. We evaluated ESR1 methylation in CTCs and paired plasma ctDNA. We evaluated ESR1 methylation in CTCs and paired plasma ctDNA as a potential biomarker for response to everolimus/exemestane treatment.
Experimental Design: A highly sensitive and specific real-time MSP assay for ESR1 methylation was developed and validated in (i) 65 primary breast tumors formalin-fixed paraffin-embedded (FFPE), (ii) EpCAM+ CTC fractions (122 patients and 30 healthy donors; HD), (iii) plasma ctDNA (108 patients and 30HD), and (iv) in CTCs (CellSearch) and in paired plasma ctDNA for 58 patients with breast cancer. ESR1 methylation status was investigated in CTCs isolated from serial peripheral blood samples of 19 patients with ER+/HER2− advanced breast cancer receiving everolimus/exemestane.
Results: ESR1 methylation was detected in: (i) 25/65 (38.5%) FFPEs, (ii) EpCAM+ CTC fractions: 26/112 (23.3%) patients and 1/30 (3.3%) HD, and (iii) plasma ctDNA: 8/108 (7.4%) patients and 1/30 (3.3%) HD. ESR1 methylation was highly concordant in 58 paired DNA samples, isolated from CTCs (CellSearch) and corresponding plasma. In serial peripheral blood samples of patients treated with everolimus/exemestane, ESR1 methylation was observed in 10/36 (27.8%) CTC-positive samples, and was associated with lack of response to treatment (P = 0.023, Fisher exact test).
Conclusions: We report for the first time the detection of ESR1 methylation in CTCs and a high concordance with paired plasma ctDNA. ESR1 methylation in CTCs was associated with lack of response to everolimus/exemestane regimen. ESR1 methylation should be further evaluated as a potential liquid biopsy-based biomarker. Clin Cancer Res; 24(6); 1500–10. ©2017 AACR.
Immunotherapy of Myelodysplastic Syndrome: You Can Run, but You Can't Hide
Authors: Fuchs Ephraim Joseph 
Published: December 2017

Abstract
The hypomethylating agent decitabine induces expression of the cancer/testis antigen NY-ESO-1 in the myeloid cells of patients with myelodysplastic syndrome (MDS). Patients with MDS treated with decitabine and an NY-ESO-1 vaccine developed NY-ESO-1–specific T-cell responses directed against their abnormal myeloid cells, raising hopes for combinatorial immunotherapy of this disease. Clin Cancer Res; 24(5); 991–3. ©2017 AACR.
See related article by Griffiths et al., p. 1019
Inhibition of MDM2 by a Rhein-Derived Compound AQ-101 Suppresses Cancer Development in SCID Mice
Authors: Gu Lubing , Zhang Hailong , Liu Tao , Draganov Alexander , Yi Sha , Wang Binghe , Zhou Muxiang 
Published: December 2017

Abstract
A novel small-molecule anthraquinone (AQ) analogue, AQ-101, which was synthesized through chemical modification of the core structures of rhein, exhibited potent anticancer activity. In the present study, we evaluated the cancer-inhibiting mechanism of AQ-101 and tested the therapeutic potential of this compound for treating cancer in mice. We found that AQ-101 was able to induce MDM2 protein degradation through a self-ubiquitination and proteasome-mediated mechanism. This AQ-101–induced MDM2 downregulation led to activation of p53, which contributed to apoptosis of acute lymphoblastic leukemia (ALL), especially those with a wild-type p53 phenotype and MDM2 expression in vitro and in vivo. When given for a period of 2 weeks (20 mg/kg/day, 3×/week), AQ-101 inhibited development of ALL in nude or SCID mice with a human ALL xenograft and achieved cure by the end of the 5-month experiment. Importantly, AQ-101 showed minimal or no inhibitory effect on normal human hematopoiesis in vitro and was well tolerated in vivo in animal models. Given that MDM2-overexpressing cancers are commonly refractory to current treatment options, our study results suggest that further development of AQ-101 is warranted, as it represents a potentially new, safe anticancer drug with a novel strategy for targeting MDM2. Mol Cancer Ther; 17(2); 497–507. ©2017 AACR.
Scavenger Receptor Type B1 and Lipoprotein Nanoparticle Inhibit Myeloid-Derived Suppressor Cells
Authors: Plebanek Michael P. , Bhaumik Debayan , Bryce Paul J. , Thaxton C. Shad 
Published: December 2017

Abstract
Myeloid-derived suppressor cells (MDSC) are innate immune cells that potently inhibit T cells. In cancer, novel therapies aimed to activate T cells can be rendered ineffective due to the activity of MDSCs. Thus, targeted inhibition of MDSCs may greatly enhance T-cell–mediated antitumor immunity, but mechanisms remain obscure. Here we show, for the first time, that scavenger receptor type B-1 (SCARB1), a high-affinity receptor for spherical high-density lipoprotein (HDL), is expressed by MDSCs. Furthermore, we demonstrate that SCARB1 is specifically targeted by synthetic high-density lipoprotein-like nanoparticles (HDL NP), which reduce MDSC activity. Using in vitro T-cell proliferation assays, data show that HDL NPs specifically bind SCARB1 to inhibit MDSC activity. In murine cancer models, HDL NP treatment significantly reduces tumor growth, metastatic tumor burden, and increases survival due to enhanced adaptive immunity. Flow cytometry and IHC demonstrate that HDL NP–mediated suppression of MDSCs increased CD8+ T cells and reduced Treg cells in the metastatic tumor microenvironment. Using transgenic mice lacking SCARB1, in vivo data clearly show that the HDL NPs specifically target this receptor for suppressing MDSCs. Ultimately, our data provide a new mechanism and targeted therapy, HDL NPs, to modulate a critical innate immune cell checkpoint to enhance the immune response to cancer. Mol Cancer Ther; 17(3); 686–97. ©2017 AACR.
Homozygous Familial Hypercholesterolemia Patients With Identical Mutations Variably Express the LDLR (Low-Density Lipoprotein Receptor)
Authors: Thedrez Aurélie , Blom Dirk J. , Ramin-Mangata Stéphane , Blanchard Valentin , Croyal Mikaël , Chemello Kévin , Nativel Brice , Pichelin Matthieu , Cariou Bertrand , Bourane Steeve , Tang Lihua , Farnier Michel , Raal Frederick J. , Lambert Gilles 
Published: December 2017

Objective—
Evolocumab, a PCSK9 (proprotein convertase subtilisin kexin type 9)–neutralizing antibody, lowers low-density lipoprotein cholesterol (LDL-C) in homozygous familial hypercholesterolemic (HoFH) patients with reduced LDLR (low-density lipoprotein receptor) function. However, their individual responses are highly variable, even among carriers of identical LDLR genetic defects. We aimed to elucidate why HoFH patients variably respond to PCSK9 inhibition.

Approach and Results—
Lymphocytes were isolated from 22 HoFH patients enrolled in the TAUSSIG trial (Trial Assessing Long Term Use of PCSK9 Inhibition in Subjects With Genetic LDL Disorders). Ten patients were true homozygotes (FH1/FH1) and 5 identical compound heterozygotes (FH1/FH2). Lymphocytes were plated with or without mevastatin, recombinant PCSK9 (rPCSK9), or a PCSK9-neutralizing antibody. Cell surface LDLR expression was analyzed by flow cytometry. All HoFH lymphocytes had reduced cell surface LDLR expression compared with non-FH lymphocytes, for each treatment modality. Lymphocytes from FH1/FH2 patients (LDLR defective/negative) displayed the lowest LDLR expression levels followed by lymphocytes from FH1/FH1 patients (defective/defective). Mevastatin increased, whereas rPCSK9 reduced LDLR expression. The PCSK9-neutralizing antibody restored LDLR expression. Lymphocytes displaying higher LDLR expression levels were those isolated from patients presenting with lowest levels of LDL-C and apolipoprotein B, before and after 24 weeks of evolocumab treatment. These negative correlations remained significant in FH1/FH1 patients and appeared more pronounced when patients with apolipoprotein E3/E3 genotypes were analyzed separately. Significant positive correlations were found between the levels of LDLR expression and the percentage reduction in LDL-C on evolocumab treatment.

Conclusions—
Residual LDLR expression in HoFH is a major determinant of LDL-C levels and seems to drive their individual response to evolocumab.
Impact of Prehospital Triage Scales to Detect Large Vessel Occlusion on Resource Utilization and Time to Treatment
Authors: Schlemm Ludwig , Ebinger Martin , Nolte Christian H. , Endres Matthias 
Published: December 2017

Background and Purpose—
Prehospital stroke severity scales may help to triage acute ischemic stroke patients with large vessel occlusion (LVO) for direct transportation to a comprehensive stroke center. The impact on resource use and time to reperfusion treatment for patients with and without LVO is unknown.

Methods—
Based on empirical distributions of stroke symptom severity, prehospital delay times, and stroke symptom severity-dependent likelihood of LVO, we simulate prehospital incidents of stroke-like symptoms in abstract geographical environments to estimate the impact of prehospital triage strategies based on different cutoffs of the rapid arterial occlusion evaluation scale.

Results—
Compared with transporting each patient to the nearest stroke center, implementation of a prehospital triage strategy based on a rapid arterial occlusion evaluation scale cutoff score ≥5 is associated with more patients with suspected acute stroke at comprehensive stroke centers and less patients at primary stroke centers (+11.7% [95% confidence interval: +8.1% to +15.3%] and −18.4% [−19.1% to −17.7%], respectively). Mean time to groin puncture is reduced by 29.6 minutes (−35.2 to −24.7 minutes) while mean time to thrombolysis does not change significantly (±0.0 minutes [−0.3 to +0.3 minutes]). The total number of secondary transfers is reduced by 60.9% (−62.8% to −59.0%); mean time of ambulance use per patient is unchanged. Results are robust with regards to variation in model parameters.

Conclusions—
Implementation of prehospital triage based on stroke severity scales would have strong impact on patient flow and distribution. The benefit of earlier thrombectomy for patients with LVO may outweigh the harm associated with delayed access to thrombolysis for some patients without LVO. Randomized trials using clinical stroke severity scales as a triage tool are needed to confirm our findings.
Contact Aspiration Versus Stent Retriever in Patients With Acute Ischemic Stroke With M2 Occlusion in the ASTER Randomized Trial (Contact Aspiration Versus Stent Retriever for Successful Revascularization)
Authors: Gory Benjamin , Lapergue Bertrand , Blanc Raphael , Labreuche Julien , Ben Machaa Malek , Duhamel Alain , Marnat Gautier , Saleme Suzana , Costalat Vincent , Bracard Serge , Desal Hubert , Mazighi Mikael , Consoli Arturo , Piotin Michel , Redjem Hocine , Ciccio Gabriele , Smajda Stanislas , Fahed Robert , Desilles Jean Philippe , Rodesch Georges , Coskun Oguzhan , Maria Federico Di , Bourdain Frédéric , Decroix Jean Pierre , Wang Adrien , Tchikviladze Maya , Evrard Serge , Turjman Francis , Labeyrie Paul Emile , Riva Roberto , Mounayer Charbel , Bonafé Alain , Eker Omer , Gascou Grégory , Dargazanli Cyril , Tonnelet Romain , Derelle Anne Laure , Anxionnat René , Bourcier Romain , Daumas-Duport Benjamin , Berge Jérome , Barreau Xavier , Djemmane Lynda 
Published: December 2017

Background and Purpose—
Middle cerebral artery M2-segment occlusions represent an important subgroup of patients with acute stroke with large-vessel occlusion. The safety of mechanical thrombectomy, especially contact aspiration (CA), in such distal intracranial occlusions is still under debate. We compared reperfusion, adverse events, neurological recovery, and functional outcome of patients with isolated M2 occlusions according to the first-line strategy mechanical thrombectomy devices (CA versus stent retriever [SR]).

Methods—
This is a post hoc analysis of the ASTER trial (Contact Aspiration Versus Stent Retriever for Successful Revascularization). The primary outcome was successful reperfusion at the end of all endovascular procedures, defined as modified Thrombolysis in Cerebral Infarction (mTICI) scores 2b/3. Secondary outcomes were mTICI 2c/3 and mTICI 3, 90-day functional outcome, assessed with the modified Rankin Scale score. Safety outcomes included 90-day mortality and any symptomatic intracerebral hemorrhage.

Results—

Seventy-nine patients were included: 48 were allocated to the CA group and 31 to the SR group. There were no significant differences between CA and SR groups in reperfusion after all endovascular procedures regarding mTICI 2b/3 (89.6% versus 83.9%;
P
=0.36), mTICI 2c/3 (54.2% versus 54.8%;
P
=0.90), and mTICI 3 (35.4% versus 41.9%;
P
=0.36) rates. There were no significant differences between CA and SR groups in 90-day modified Rankin Scale ≤2 rate (54.4% versus 50.0%;
P
=0.84), 24-hour change in National Institutes of Health Stroke Scale (mean difference, −3.9; 95% confidence interval, −7.9 to 0.01), and Alberta Stroke Program Early Computed Tomography score (mean difference, 0.9; 95% confidence interval, −0.1 to 2.0) scores. Safety parameters were well balanced between the 2 groups except for a higher 90-day mortality rate in the CA group (19.6% versus 3.3%;
P
=0.078).

Conclusions—
First-line mechanical thrombectomy with CA compared with SR did not result in an increased successful revascularization rate in patients with acute stroke with isolated M2 occlusion.
A comparison of tillage, direct drilling and lime on springtail communities in a long-term field trial in poland
Authors: Olejniczak Izabella , Lenart Stanisław 
Published: December 2017

In 2009 and 2010, we examined the effects of different tillage systems on springtail communities. The study was established on the experimental field, in which tillage and no-tillage cultivation had been conducted since 1975, of the Research Station of the Warsaw University of Life Sciences’ Department of Agronomy, located at Chylice, near Warsaw (52005’N, 20033’E).
The treatments considered were conventional tillage with a mouldboard plough (CT) and no-tillage (NT), and each method was divided between with and without liming. In 2009, the fields were sown with winter wheat, and spring barley was planted the following year. During both growing seasons, collembolan densities were higher under NT than CT, but the reverse was true after harvest. However, the time of the season had a significant effect on collembolan densities not only over the whole study period but also in particular years. Additionally, in fields that were limed, collembolan densities varied, with no clear trend. The dominant collembolan species in the CT and NT fields was Isotoma viridis Bourlet, 1839, while Paristoma notabilis (Schäffer, 1896) was prevalent when liming was used. The relative proportion of each of the two species in springtail communities was at least 20 percent. The species diversity of collembolan communities was similar in both study years, and it was higher in CT than in NT fields.
The study was financially supported as part of the MNiSW project No. N N305171136.
Prognostic significance of cytogenetic heterogeneity in patients with newly diagnosed multiple myeloma
Authors: Merz Maximilian , Jauch Anna , Hielscher Thomas , Bochtler Tilmann , Schönland Stefan Olaf , Seckinger Anja , Hose Dirk , Bertsch Uta , Neben Kai , Raab Marc Steffen , Hillengass Jens , Salwender Hans , Blau Igor Wolfgang , Lindemann Hans-Walter , Schmidt-Wolf Ingo G. H. , Scheid Christof , Haenel Mathias , Weisel Katja C. , Goldschmidt Hartmut 
Published: December 2017

Key Points
Clonal heterogeneity detected by iFISH is common in newly diagnosed MM. Treatment with bortezomib overcomes the negative impact of high-risk cytogenetic abnormalities if no further subclones are detected.
The clinical diagnosis of symptomatic forefoot neuroma in the general population: a Delphi consensus study
Authors: Dando Charlotte , Cherry Lindsey , Jones Lyndon , Bowen Catherine 
Published: December 2017

AbstractBackgroundThere is limited evidence for defining what specific method or methods should be used to clinically influence clinical decision making for forefoot neuroma. The aim of this study was to develop a clinical assessment protocol that has agreed expert consensus for the clinical diagnosis of forefoot neuroma.MethodsA four‐round Delphi consensus study was completed with 16 expert health professionals from either a clinical or clinical academic background, following completion of a structured literature review. Clinical experience ranged from 5 to 34 years (mean: 19.5 years). Consensus was sought on the optimal methods to achieve the clinical diagnosis of forefoot neuroma. Round 1 sought individual input with an open ended question. This developed a list of recommendations. Round 2 and 3 asked the participants to accept or reject each of the recommendations in the list in relation to the question: “What is the best way to clinically diagnose neuroma in the forefoot?” Votes that were equal to or greater than 60% were accepted into the next round; participant's votes equal to or less then 20% were excluded. The remaining participant's votes between 20 to 60% were accepted and placed into the following round for voting. Round 4 asked the participants to rank the list of recommendations according to the strength of recommendation they would give in relation to the question: “What is the best way to clinically diagnose neuroma in the forefoot?” The recruitment and Delphi rounds were conducted through email.ResultsIn round 1, the 16 participants identified 68 recommendations for the clinical diagnosis of forefoot neuroma. In round 2, 27 recommendations were accepted, 11 recommendations were rejected and 30 recommendations were assigned to be re‐voted on. In round 3, 36 recommendations were accepted, 22 recommendations were rejected and 11 recommendations were assigned to be re‐voted on. In round 4, 21 recommendations were selected by the participants to form the expert derived clinical assessment protocol for the clinical diagnosis of forefoot neuroma. From these 21 recommendations, a set of themes were established: location of pain, non weight bearing sensation, weight bearing sensation, observations, tests and imaging.ConclusionFollowing the identification of 21 method recommendations, a core set of clinical diagnostic methods have been prepared as a clinical assessment protocol for the diagnosis of forefoot neuroma. Based on expert opinion, the core set will assist clinicians in forming a clearer diagnosis of forefoot neuroma.