bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biomarkers identified by serum metabolomic analysis to predict biologic treatment response in rheumatoid arthritis patients
Authors: Takahashi Soshi , Saegusa Jun , Onishi Akira , Morinobu Akio 
Published: April 2019

Abstract

Objectives
Biologic treatment has recently revolutionized the management of RA. Despite this success, ∼30–40% of the patients undergoing biologic treatment respond insufficiently. The aim of this study was to identify several specific reliable metabolites for predicting the response of RA patients to TNF-α inhibitors (TNFi) and abatacept (ABT), using capillary electrophoresis-time-of-flight mass spectrometry (CE-TOFMS).

Methods
We collected serum from RA patients with moderate or high disease activity prior to biologic treatment, and obtained the serum metabolomic profiles of these samples using CE-TOFMS. The patients' response was determined 12 weeks after starting biologic treatment, according to the EULAR response criteria. We compared the metabolites between the response and non-response patient groups and analysed their discriminative ability.

Results
Among 43 total patients, 14 of 26 patients in the TNFi group and 6 of 17 patients in the ABT group responded to the biologic treatment. Of the metabolites separated by CE-TOFMS, 196 were identified as known substances. Using an orthogonal partial least-squares discriminant analysis, we identified five metabolites as potential predictors of TNFi responders and three as predictors of ABT responders. Receiver operating characteristic analyses for multiple biomarkers revealed an area under the curve (AUC) of 0.941, with a sensitivity of 85.7% and specificity of 100% for TNFi, and an AUC of 0.985, with a sensitivity of 100% and specificity of 90.9% for ABT.

Conclusion
By metabolomic analysis, we identified serum biomarkers that have a high ability to predict the response of RA patients to TNFi or ABT treatment.
Involvement of CesA4, CesA7-A/B and CesA8-A/B in secondary wall formation in Populus trichocarpa wood
Authors: Abbas Manzar , Peszlen Ilona , Shi Rui , Kim Hoon , Katahira Rui , Kafle Kabindra , Xiang Zhouyang , Huang Xiong , Min Douyong , Mohamadamin Makarem , Yang Chenmin , Dai Xinren , Yan Xiaojing , Park Sunkyu , Li Yun , Kim Seong H , Davis Mark , Ralph John , Sederoff Ronald R , Chiang Vincent L , Li Quanzi 
Published: April 2019

Abstract
Cellulose synthase A genes (CesAs) are responsible for cellulose biosynthesis in plant cell walls. In this study, functions of secondary wall cellulose synthases PtrCesA4, PtrCesA7-A/B and PtrCesA8-A/B were characterized during wood formation in Populus trichocarpa (Torr. & Gray). CesA RNAi knockdown transgenic plants exhibited stunted growth, narrow leaves, early necrosis, reduced stature, collapsed vessels, thinner fiber cell walls and extended fiber lumen diameters. In the RNAi knockdown transgenics, stems exhibited reduced mechanical strength, with reduced modulus of rupture (MOR) and modulus of elasticity (MOE). The reduced mechanical strength may be due to thinner fiber cell walls. Vessels in the xylem of the transgenics were collapsed, indicating that water transport in xylem may be affected and thus causing early necrosis in leaves. A dramatic decrease in cellulose content was observed in the RNAi knockdown transgenics. Compared with wildtype, the cellulose content was significantly decreased in the PtrCesA4, PtrCesA7 and PtrCesA8 RNAi knockdown transgenics. As a result, lignin and xylem contents were proportionally increased. The wood composition changes were confirmed by solid-state NMR, two-dimensional solution-state NMR and sum-frequency-generation vibration (SFG) analyses. Both solid-state nuclear magnetic resonance (NMR) and SFG analyses demonstrated that knockdown of PtrCesAs did not affect cellulose crystallinity index. Our results provided the evidence for the involvement of PtrCesA4, PtrCesA7-A/B and PtrCesA8-A/B in secondary cell wall formation in wood and demonstrated the pleiotropic effects of their perturbations on wood formation.
Exploring the effect of PAs on physician trainee learning
Authors: Polansky Maura N. , Govaerts Marjan J.B. , Stalmeijer Renée E. , Eid Ahmed , Bodurka Diane C. , Dolmans Diana H.J.M. 
Published: April 2019

ABSTRACT

Background:
Physician assistants (PAs) often have been embedded in academic medical centers to help ensure an adequate patient care workforce while supporting compliance with work-hour restrictions for residents and fellows (also called trainees). Limited studies have explored the effect of PAs on trainee learning. This qualitative study explored, from the perspective of physician faculty and PAs, how PAs working in the clinical learning environment can enhance or hinder trainee learning.

Methods:
Using purposive sampling, 12 PAs and 12 physician faculty members in one US teaching hospital were selected for semistructured interviews. Data collection and analysis were characterized by an iterative process. Data analysis was informed by principles of conventional content analysis.

Results:
Participants identified various ways in which PAs may affect trainee learning, intrinsically linked to the roles PAs assume in the clinical learning environment: clinician, teammate, and clinical teacher. Trainee learning may be enhanced because learning time can be optimized by having PAs in the clinical learning environment. Trainees can learn about PAs and how to collaborate with them, and PAs can enculturate and provide clinical instruction to trainees. Trainee learning may be hindered if learning opportunities for trainees go to PAs, trainees feel intimidated by experienced PAs, or trainees become too dependent on PAs.

Conclusions:
Our findings demonstrate enhancements and hindrances to trainees' learning linked to three key roles PAs perform in the clinical learning environment. These findings can inform how PAs are integrated into teaching services. Further investigation is needed to understand how PAs can balance their professional roles to foster effective collaborative practice and learning.
Validating a Quick Spectral Modulation Detection Task
Authors: Landsberger David M. , Dwyer Robert T. , Stupak Natalia , Gifford René H. 
Published: April 2019

Objectives:
The Quick Spectral Modulation Detection (QSMD) test provides a quick and clinically implementable spectral resolution estimate for cochlear implant (CI) users. However, the original QSMD software (QSMD(MySound)) has technical and usability limitations that prevent widespread distribution and implementation. In this article, we introduce a new software package EasyQSMD, which is freely available software with the goal of both simplifying and standardizing spectral resolution measurements.

Design:
QSMD was measured for 20 CI users using both software packages.

Results:
No differences between the two software packages were detected, and based on the 95% confidence interval of the difference between tests, the difference between the tests is expected to be <2% points. The average test duration was under 4 minutes.

Conclusions:
EasyQSMD is considered functionally equivalent to QSMD(MySound) providing a clinically feasible and quick estimate of spectral resolution for CI users.
Impact of Lexical Parameters and Audibility on the Recognition of the Freiburg Monosyllabic Speech Test
Authors: Winkler Alexandra , Carroll Rebecca , Holube Inga 
Published: April 2019

Objective:
Correct word recognition is generally determined by audibility, but lexical parameters also play a role. The focus of this study was to examine both the impact of audibility and lexical parameters on speech recognition of test words of the clinical German Freiburg monosyllabic speech test, and subsequently on the perceptual imbalance of test lists observed in the literature.

Design:
For 160 participants with normal hearing that were divided into three groups with different simulated hearing thresholds, monaural speech recognition for the Freiburg monosyllabic speech test was obtained via headphones in quiet at different presentation levels. A software manipulated the original speech material to simulate two different hearing thresholds. All monosyllables were classified according to their frequency of occurrence in contemporary language and the number of lexical neighbors using the Cross-Linguistic Easy-Access Resource for Phonological and Orthographic Neighborhood Density database. Generalized linear mixed-effects regression models were used to evaluate the influences of audibility in terms of the Speech Intelligibility Index and lexical properties of the monosyllables in terms of word frequency (WF) and neighborhood density (ND) on the observed speech recognition per word and per test list, respectively.

Results:
Audibility and interactions of audibility with WF and ND correctly predicted identification of the individual monosyllables. Test list recognition was predicted by test list choice, audibility, and ND, as well as by interactions of WF and test list, audibility and ND, ND and test list, and audibility per test list.

Conclusions:
Observed differences in speech recognition of the Freiburg monosyllabic speech test, which are well reported in the literature, depend not only on audibility but also on WF, neighborhood density, and test list choice and their interactions. The authors conclude that future creations of speech test material should take these lexical parameters into account.
Low-Dose Versus Therapeutic Anticoagulation in Patients on Extracorporeal Membrane Oxygenation: A Pilot Randomized Trial
Authors: Aubron Cécile , McQuilten Zoe , Bailey Michael , Board Jasmin , Buhr Heidi , Cartwright Bruce , Dennis Mark , Hodgson Carol , Forrest Paul , McIlroy David , Murphy Deirdre , Murray Lynne , Pellegrino Vincent , Pilcher David , Sheldrake Jayne , Tran Huyen , Vallance Shirley , Cooper D. James ,   endorsed by the International ECMO Network (ECMONet)
Published: April 2019

Objectives:
To determine whether randomization of patients undergoing extracorporeal membrane oxygenation to either therapeutic or a low-dose anticoagulation protocol results in a difference in activated partial thromboplastin time and anti-Xa.

Design:
Randomized, controlled, unblinded study.

Setting:
Two ICUs of two university hospitals.

Patients:
Patients admitted to the ICU, who required extracorporeal membrane oxygenation (venovenous or venoarterial) and who did not have a preexisting indication for therapeutic anticoagulation.

Interventions:
Therapeutic anticoagulation with heparin (target activated partial thromboplastin time between 50 and 70 s) or lower dose heparin (up to 12,000 U/24 hr aiming for activated partial thromboplastin time < 45 s).

Measurements and Main Results:
Thirty-two patients were randomized into two study groups that were not significantly different in demographics and extracorporeal membrane oxygenation characteristics. There was a significant difference in the daily geometric mean heparin dose (11,742 U [95% CI, 8,601–16,031 U] vs 20,710 U [95% CI, 15,343–27,954 U]; p = 0.004), daily geometric mean activated partial thromboplastin time (48.1 s [95% CI, 43.5–53.2 s] vs 55.5 s [95% CI, 50.4–61.2 s]; p = 0.04), and daily geometric mean anti-Xa (0.11 international units/mL [95% CI, 0.07–0.18] vs 0.27 [95% CI, 0.17–0.42]; p = 0.01). We found similar results when considering only venovenous extracorporeal membrane oxygenation episodes; however, no difference in daily geometric mean activated partial thromboplastin time between groups when considering only venoarterial extracorporeal membrane oxygenation episodes.

Conclusions:
Allocating patients on extracorporeal membrane oxygenation to two different anticoagulation protocols led to a significant difference in mean daily activated partial thromboplastin time and anti-Xa levels between groups. When considering subgroups analyses, these results were consistent in patients on venovenous extracorporeal membrane oxygenation. Our results support the feasibility of a larger trial in patients undergoing venovenous extracorporeal membrane oxygenation to compare different anticoagulation protocols; however, this study does not provide evidence on the optimal anticoagulation protocol for patients undergoing extracorporeal membrane oxygenation.
The Effectiveness of α2 Agonists As Sedatives in Pediatric Critical Care: A Propensity Score-Matched Cohort Study
Authors: Hayden John C. , Doherty Dermot R. , Dawkins Ian , Leacy Finbarr P. , Healy Martina , Breatnach Cormac V. , Cousins Gráinne , Gallagher Paul J. 
Published: April 2019

Objectives:
There is limited evidence supporting the widespread use of α2 agonists (clonidine and dexmedetomidine) in pediatric critical care sedation. This study sought to test the association between the use of α2 agonists and enhanced sedation.

Design:
A retrospective observational cohort study was conducted. Noninferiority of time adequately sedated (COMFORT Behavior Score 11–16) while mechanically ventilated was assessed. Secondarily, dosing of opioids and benzodiazepines was examined.

Setting:
Two tertiary PICUs.

Patients:
Children were classified into an exposed group, who received an α2 agonist as part of their sedation regimen, and an unexposed group. Groups were matched using propensity score analysis.

Interventions:
None.

Measurements and Main Results:
One-thousand eighty-five patients were included. The exposed group were adequately sedated 74% (95% CI, 72–75%) of the study time compared with the unexposed group at 70% (95% CI, 67–72%) giving a ratio of 1.06 (95% CI, 1.02–1.10) and a noninferior time adequately sedated. A decrease in time oversedated was observed with 8.1% (95% CI, 4.3–11.9%) less time classified as oversedated in the exposed group. Reduction in morphine use of 0.25 μg/kg/hr (95% CI, –0.68 to 1.18 μg/kg/hr) was not statistically significant. Midazolam use did not decrease and was statistically higher.

Conclusions:
Use of α2 agonists was associated with similar time adequately sedated as a matched unexposed group although no reduction in morphine or benzodiazepine coadministration was observed. There was a shift toward lighter sedation with α2 agonist use.
Adjuvant treatment of pancreatic cancer
Authors: Conroy Thierry , Ducreux Michel 
Published: April 2019

Purpose of review
Pancreatic cancer will soon become one of the most common causes of cancer death. Early detection of pancreatic cancer remains impossible and only 20% of patients are suitable for surgery once diagnosed. Even in this specific subgroup of patients, and despite improvements in surgery, overall survival remains poor, with an 80% recurrence rate. Consequently, many attempts have been made to prevent recurrence by adding chemotherapy, radiotherapy, or both.

Recent findings
Here, we will focus on results of randomized trials evaluating the role of different postoperative treatments. Over 15 years ago, a trial demonstrated that chemoradiotherapy has a deleterious effect on survival. The same trial recommended adjuvant chemotherapy with fluorouracil as standard of care. Subsequent trials sought to identify better chemotherapy regimens. Two recently published trials evaluated the role of combination therapies for resected pancreatic cancer and demonstrated better outcomes with a gemcitabine and capecitabine combination and a fluorouracil, oxaliplatin, and irinotecan combination (FOLFIRINOX) versus gemcitabine alone.

Summary
Results from recent trials suggest that FOLFIRINOX should be considered standard of care for fit patients.
Immunotherapy of heterogenous sarcomas: questions and strategies
Authors: Dufresne Armelle , Meurgey Alexandra , Brahmi Mehdi 
Published: April 2019

Purpose of review
Development of immune therapy in sarcoma faces the rarity and heterogeneity of the disease. This review analyses the data available from published clinical trials, and the new clinical strategies under assessment, developed in parallel to the exploration of biological mechanisms underlying the efficacy of immune therapy.

Recent findings
Published data of four clinical trials assessing the efficacy of immune therapy in metastatic bone and soft-tissue sarcoma and associated translational programs are available. Response rate and progression-free survival with single-agent immune check point blockade in unselected sarcoma are low. No biomarkers of efficacy have been identified so far. To increase the efficacy of such treatments, combination of immune check point blockade with chemotherapy, radiotherapy or targeted therapy is currently assessed. Signal of specific sensibility of some histological subtypes is explored. Adoptive cell therapy or vaccine seems particularly promising in translocation-associated sarcoma.

Summary
Characterization of immune environment, mechanism of action of combined regimen and identification of biomarkers will be key steps to build the next clinical trials to improve the efficacy of such strategy.
Intraoperative SPY Reduces Post-mastectomy Skin Flap Complications: A Systematic Review and Meta-Analysis
Authors: Liu Edward H. , Zhu Sarah L. , Hu Jiayi , Wong Nathan , Farrokhyar Forough , Thoma Achilles 
Published: April 2019

Background:
Indocyanine-green and laser-assisted fluorescence angiography, known as the SPY system, is a recently developed tool that has shown promise in assessing tissue perfusion. Its intraoperative use is becoming more common particularly in breast surgery. This systematic review aims to determine whether SPY technology can reduce postoperative complications related to tissue ischemia, specifically skin necrosis of the mastectomy native breast skin flaps.

Methods:
A systematic review of the literature was performed based on the PRISMA guideline. All studies that involved use of the SPY system to assess perfusion of postmastectomy skin flaps from January 1, 1960, to March 1, 2018 were included. Postoperative complications, including mastectomy skin flap necrosis were extracted from the selected studies. The perfusion-related complication rates and unexpected reoperation rates across multiple studies were then reviewed.

Results:
Five relevant articles were identified including 902 patients undergoing mastectomy and native breast flap reconstructive procedures. Groups that used indocyanine-green angiography had statistically less incidence of native breast skin flap necrosis and unexpected reoperations due to perfusion-related complications compared with groups that monitored flaps with only clinical observation (odds ratio 0.54 for skin necrosis, and 0.36 for reoperation).

Conclusions:
In this systematic review, the incidence of native breast skin flap necrosis and unexpected reoperations were found to be statistically lower in cases where SPY was used. However, more prospective studies are required to establish SPY angiography as an accurate and cost-effective tool for assessment of tissue perfusion.
Quality of Life after Flap Reconstruction of the Distal Lower Extremity: Is There a Difference Between a Pedicled Suralis Flap and a Free Anterior Lateral Thigh Flap?
Authors: Schmidt Karsten , Jakubietz Michael Gregor , Gilbert Fabian , Hausknecht Franca , Meffert Rainer Heribert , Jakubietz Rafael Gregor 
Published: April 2019

Background:
Flap reconstruction of the distal lower extremity is challenging. Especially, the concept of perforator surgery has increased available surgical options. Although results are generally judged in terms of objective facts, patients-perceived quality of life has largely remained unexamined. The aim of the study was to compare quality of life after lower extremity reconstruction with pedicled and free flaps.

Methods:
Patients were evaluated retrospectively after reconstruction of defects of the distal lower extremity either with distally based adipofascial sural flap (pedicled reverse sural flap) or an anterior lateral thigh (ALT) flap. A specific questionnaire was developed to measure the patient’s quality of life, based on short form health survey-12, Dresden Body Image Score-35, Patient Health Questionnaire-4, and X-SMFA questionnaires with additional specific questions. Furthermore, results, secondary surgeries, and complications were analyzed.

Results:
Thirty-seven patients with reconstruction of lower limb defects treated with a pedicled reverse sural flap and 34 patients treated with an ALT flap were included in the study. There was no statistical significant difference in the overall satisfaction with the procedure in the long-term follow-up between both groups, but patients with ALT showed a higher satisfaction with the treatment in the initial postoperative period. Both groups demonstrated approximately similar results in the long term for self-acceptance and vitality.

Conclusions:
Although anatomic situation may dictate flap choice coverage with free flaps, a less-complicated flap is by no means regarded as an inferior treatment option in patient’s estimation. Despite the intuitive speculation that patients with more advanced reconstruction methods should have better function and subsequently higher quality of life, this assumption was clearly not supported by data in this study.
Unusual “Dumbbell”-Shaped Hibernoma
Authors: Tsapralis Nikolaos , Pham Hien , Vlachogiorgos Apostolos , Sangar Vijay , Mowatt David 
Published: April 2019

Summary:
Hibernoma is considered as a rare soft tissue benign tumor originating from brown fat. Few cases have been described so far in the literature; hibernoma was first described by Merkel in 1906, but it was named by Gery in 1914. We present the case of 33-year-old woman who presented with a palpable lump over superior aspect of her thigh associated with pain. Magnetic resonance imaging examination reported a “dumbbell”-shaped soft tissue tumor involving the right side of the pelvis and adductor compartment passing through the obturator foramen into the adductor compartment infiltrating the hip joint. Clinical and imaging features initially suggested liposarcoma, but ultrasound-guided biopsy and final surgical resection yielded the diagnosis of hibernoma. This rare soft tissue tumor can imitate malignancy, but magnetic resonance imaging and possibly guided biopsy are essential for preoperative planning as surgical resection remains the best management pathway.
Alternative Approach for Occipital Headache Surgery: The Use of a Transverse Incision and “W” Flaps
Authors: Afifi Ahmed M. , Carbullido Mary K. , Israel Jacqueline S. , Sanchez Ruston J. , Albano Nicholas J. 
Published: April 2019

Summary:
The most commonly used approach for a greater occipital nerve decompression is through a vertical midline incision, with multiple authors reporting favorable long-term outcomes. A transverse approach to the occipital nerves has been described, yet it does not include the use of fat flaps to insulate the decompressed nerves. In this study, we describe the use of a single transverse incision with modified “W” fat flaps to decompress both the greater and lesser occipital nerves. This allows for wider exposure of the nerves without the need for an additional incision to access the lesser occipital nerve. The described technique provides increased reach and versatility of the fat flap, allowing for coverage over a longer course of the nerve and further cephalad, close to the bony skull base. In addition, the fat flaps cover the greater occipital nerve closer to its native position, as opposed to bringing the nerve into a subcutaneous position. This, theoretically, keeps the nerve in a more protected deep position and technically makes it easier to avoid any tendency for kinking the nerves while wrapping them with the fat flap. Our experience has demonstrated that this modified technique is not only safe but also efficacious in affecting a statistically significant reduction (70% improvement, P = 0.004) in migraine headache index and HIT-6 scores. This study provides further evidence that nerve decompression for headache following the principles described by Guyuron is an efficacious and reproducible procedure and that a proper nerve decompression is effective in reducing headache.