bluuebunny/crossref_metadata_2025_split huggingface dataset:
Paralytic and nonparalytic muscle adaptations to exercise training versus high-protein diet in individuals with long-standing spinal cord injury
Authors: Yarar-Fisher Ceren , Polston Keith F. L. , Eraslan Mualla , Henley Kathryn Y. , Kinikli Gizem I. , Bickel C. Scott , Windham Samuel T. , McLain Amie B. , Oster Robert A. , Bamman Marcas M. 
Published: March 2018

This study compares the effects of an 8-wk isocaloric high-protein (HP) diet versus a combination exercise (Comb-Ex) regimen on paralytic vastus lateralis (VL) and nonparalytic deltoid muscle in individuals with long-standing spinal cord injury (SCI). Fiber-type distribution, cross-sectional area (CSA), levels of translation initiation signaling proteins (Erk-1/2, Akt, p70S6K1, 4EBP1, RPS6, and FAK), and lean thigh mass were analyzed at baseline and after the 8-wk interventions. A total of 11 participants (C5-T12 levels, 21.8 ± 6.3 yr postinjury; 6 Comb-Ex and 5 HP diet) completed the study. Comb-Ex training occurred 3 days/wk and consisted of upper body resistance training (RT) in addition to neuromuscular electrical stimulation (NMES)-induced-RT for paralytic VL muscle. Strength training was combined with high-intensity arm-cranking exercises (1-min intervals at 85–90%, V̇o2peak) for improving cardiovascular endurance. For the HP diet intervention, protein and fat each comprised 30%, and carbohydrate comprised 40% of total energy. Clinical tests and muscle biopsies were performed 24 h before and after the last exercise or diet session. The Comb-Ex intervention increased Type IIa myofiber distribution and CSA in VL muscle and Type I and IIa myofiber CSA in deltoid muscle. In addition, Comb-Ex increased lean thigh mass, V̇o2peak, and upper body strength ( P < 0.05). These results suggest that exercise training is required to promote favorable changes in paralytic and nonparalytic muscles in individuals with long-standing SCI, and adequate dietary protein consumption alone may not be sufficient to ameliorate debilitating effects of paralysis. NEW & NOTEWORTHY This study is the first to directly compare the effects of an isocaloric high-protein diet and combination exercise training on clinical and molecular changes in paralytic and nonparalytic muscles of individuals with long-standing spinal cord injury. Our results demonstrated that muscle growth and fiber-type alterations can best be achieved when the paralyzed muscle is sufficiently loaded via neuromuscular electrical stimulation-induced resistance training.
Mechanisms for the age-related increase in fatigability of the knee extensors in old and very old adults
Authors: Sundberg Christopher W. , Kuplic Andrew , Hassanlouei Hamidollah , Hunter Sandra K. 
Published: March 2018

The mechanisms for the age-related increase in fatigability during high-velocity contractions in old and very old adults (≥80 yr) are unresolved. Moreover, whether the increased fatigability with advancing age and the underlying mechanisms differ between men and women is not known. The purpose of this study was to quantify the fatigability of knee extensor muscles and identify the mechanisms of fatigue in 30 young (22.6 ± 0.4 yr; 15 men), 62 old (70.5 ± 0.7 yr; 33 men), and 12 very old (86.0 ± 1.3 yr; 6 men) men and women elicited by high-velocity concentric contractions. Participants performed 80 maximal velocity contractions (1 contraction per 3 s) with a load equivalent to 20% of the maximum voluntary isometric contraction. Voluntary activation and contractile properties were quantified before and immediately following exercise (<10 s) using transcranial magnetic stimulation and electrical stimulation. Absolute mechanical power output was 97 and 217% higher in the young compared with old and very old adults, respectively. Fatigability (reductions in power) progressively increased across age groups, with a power loss of 17% in young, 31% in old, and 44% in very old adults. There were no sex differences in fatigability among any of the age groups. The age-related increase in power loss was strongly associated with changes in the involuntary twitch amplitude ( r = 0.75, P < 0.001). These data suggest that the age-related increased power loss during high-velocity fatiguing exercise is unaffected by biological sex and determined primarily by mechanisms that disrupt excitation contraction coupling and/or cross-bridge function. NEW & NOTEWORTHY We show that aging of the neuromuscular system results in an increase in fatigability of the knee extensors during high-velocity exercise that is more pronounced in very old adults (≥80 yr) and occurs similarly in men and women. Importantly, the age-related increase in power loss was strongly associated with the changes in the electrically evoked contractile properties suggesting that the increased fatigability with aging is determined primarily by mechanisms within the muscle for both sexes.
The RNA-binding Protein MEX3B Mediates Resistance to Cancer Immunotherapy by Downregulating HLA-A Expression
Authors: Huang Lu , Malu Shruti , McKenzie Jodi A. , Andrews Miles C. , Talukder Amjad H. , Tieu Trang , Karpinets Tatiana , Haymaker Cara , Forget Marie-Andrée , Williams Leila J. , Wang Zhe , Mbofung Rina M. , Wang Zhi-Qiang , Davis Richard Eric , Lo Roger S. , Wargo Jennifer A. , Davies Michael A. , Bernatchez Chantale , Heffernan Timothy , Amaria Rodabe N. , Korkut Anil , Peng Weiyi , Roszik Jason , Lizée Gregory , Woodman Scott E. , Hwu Patrick 
Published: March 2018

Abstract
Purpose: Cancer immunotherapy has shown promising clinical outcomes in many patients. However, some patients still fail to respond, and new strategies are needed to overcome resistance. The purpose of this study was to identify novel genes and understand the mechanisms that confer resistance to cancer immunotherapy.
Experimental Design: To identify genes mediating resistance to T-cell killing, we performed an open reading frame (ORF) screen of a kinome library to study whether overexpression of a gene in patient-derived melanoma cells could inhibit their susceptibility to killing by autologous tumor-infiltrating lymphocytes (TIL).
Results: The RNA-binding protein MEX3B was identified as a top candidate that decreased the susceptibility of melanoma cells to killing by TILs. Further analyses of anti–PD-1–treated melanoma patient tumor samples suggested that higher MEX3B expression is associated with resistance to PD-1 blockade. In addition, significantly decreased levels of IFNγ were secreted from TILs incubated with MEX3B-overexpressing tumor cells. Interestingly, this phenotype was rescued upon overexpression of exogenous HLA-A2. Consistent with this, we observed decreased HLA-A expression in MEX3B-overexpressing tumor cells. Finally, luciferase reporter assays and RNA-binding protein immunoprecipitation assays suggest that this is due to MEX3B binding to the 3′ untranslated region (UTR) of HLA-A to destabilize the mRNA.
Conclusions: MEX3B mediates resistance to cancer immunotherapy by binding to the 3′ UTR of HLA-A to destabilize the HLA-A mRNA and thus downregulate HLA-A expression on the surface of tumor cells, thereby making the tumor cells unable to be recognized and killed by T cells. Clin Cancer Res; 24(14); 3366–76. ©2018 AACR.
See related commentary by Kalbasi and Ribas, p. 3239
Histone Methyltransferase EZH2: A Therapeutic Target for Ovarian Cancer
Authors: Jones Bayley A. , Varambally Sooryanarayana , Arend Rebecca C. 
Published: March 2018

Abstract
Ovarian cancer is the fifth leading cause of cancer-related deaths in females in the United States. There were an estimated 22,440 new cases and 14,080 deaths due to ovarian cancer in 2017. Most patients present with advanced-stage disease, revealing the urgent need for new therapeutic strategies targeting pathways of tumorigenesis and chemotherapy resistance. While multiple genomic changes contribute to the progression of this aggressive disease, it has become increasingly evident that epigenetic events play a pivotal role in ovarian cancer development. One of the well-studied epigenetic modifiers, the histone methyltransferase EZH2, is a member of polycomb repressive complex 2 (PRC2) and is commonly involved in transcriptional repression. EZH2 is the enzymatic catalytic subunit of the PRC2 complex that can alter gene expression by trimethylating lysine 27 on histone 3 (H3K27). In ovarian cancer, EZH2 is commonly overexpressed and therefore potentially serves as an effective therapeutic target. Multiple small-molecule inhibitors are being developed to target EZH2, which are now in clinical trials. Thus, in this review, we highlight the progress made in EZH2-related research in ovarian cancer and discuss the potential utility of targeting EZH2 with available small-molecule inhibitors for ovarian cancer. Mol Cancer Ther; 17(3); 591–602. ©2018 AACR.
Ly6C
Hi
Blood Monocyte/Macrophage Drive Chronic Inflammation and Impair Wound Healing in Diabetes Mellitus
Authors: Kimball Andrew , Schaller Matthew , Joshi Amrita , Davis Frank M. , denDekker Aaron , Boniakowski Anna , Bermick Jennifer , Obi Andrea , Moore Bethany , Henke Peter K. , Kunkel Steve L. , Gallagher Katherine A. 
Published: March 2018

Objective—
Wound monocyte-derived macrophage plasticity controls the initiation and resolution of inflammation that is critical for proper healing, however, in diabetes mellitus, the resolution of inflammation fails to occur. In diabetic wounds, the kinetics of blood monocyte recruitment and the mechanisms that control in vivo monocyte/macrophage differentiation remain unknown.

Approach and Results—

Here, we characterized the kinetics and function of Ly6C
Hi
[Lin
−
(CD3
−
CD19
−
NK1.1
−
Ter-119
−
) Ly6G
−
CD11b
+
] and Ly6C
Lo
[Lin
−
(CD3
−
CD19
−
NK1.1
−
Ter-119
−
) Ly6G
−
CD11b
+
] monocyte/macrophage subsets in normal and diabetic wounds. Using flow-sorted
tdTomato
-labeled Ly6C
Hi
monocyte/macrophages, we show Ly6C
Hi
cells transition to a Ly6C
Lo
phenotype in normal wounds, whereas in diabetic wounds, there is a late, second influx of Ly6C
Hi
cells that fail transition to Ly6C
Lo
. The second wave of Ly6C
Hi
cells in diabetic wounds corresponded to a spike in MCP-1 (monocyte chemoattractant protein-1) and selective administration of anti-MCP-1 reversed the second Ly6C
Hi
influx and improved wound healing. To examine the in vivo phenotype of wound monocyte/macrophages, RNA-seq–based transcriptome profiling was performed on flow-sorted Ly6C
Hi
[Lin
−
Ly6G
−
CD11b
+
] and Ly6C
Lo
[Lin
−
Ly6G
−
CD11b
+
] cells from normal and diabetic wounds. Gene transcriptome profiling of diabetic wound Ly6C
Hi
cells demonstrated differences in proinflammatory and profibrotic genes compared with controls.

Conclusions—

Collectively, these data identify kinetic and functional differences in diabetic wound monocyte/macrophages and demonstrate that selective targeting of CD11b
+
Ly6C
Hi
monocyte/macrophages is a viable therapeutic strategy for inflammation in diabetic wounds.
Validation of the Acoustic Voice Quality Index Version 03.01 and the Acoustic Breathiness Index in the Spanish language
Authors: Delgado Hernández Jonathan , León Gómez Nieves M. , Jiménez Alejandra , Izquierdo Laura M. , Barsties v. Latoszek Ben 
Published: March 2018

Objective: The aim of this study was to validate the Acoustic Voice Quality Index 03.01 (AVQIv3) and the Acoustic Breathiness Index (ABI) in the Spanish language. Method: Concatenated voice samples of continuous speech (cs) and sustained vowel (sv) from 136 subjects with dysphonia and 47 vocally healthy subjects were perceptually judged for overall voice quality and breathiness severity. First, to reach a higher level of ecological validity, the proportions of cs and sv were equalized regarding the time length of 3 seconds sv part and voiced cs part, respectively. Second, concurrent validity and diagnostic accuracy were verified. Results: A moderate reliability of overall voice quality and breathiness severity from 5 experts was used. It was found that 33 syllables as standardization of the cs part, which represents 3 seconds of voiced cs, allows the equalization of both speech tasks. A strong correlation was revealed between AVQIv3 and overall voice quality and ABI and perceived breathiness severity. Additionally, the best diagnostic outcome was identified at a threshold of 2.28 and 3.40 for AVQIv3 and ABI, respectively. Conclusions: The AVQIv3 and ABI showed in the Spanish language valid and robust results to quantify abnormal voice qualities regarding overall voice quality and breathiness severity.
Imaging of symptomatic total knee arthroplasty with cone beam computed tomography
Authors: Jaroma Antti , Suomalainen Juha-Sampo , Niemitukia Lea , Soininvaara Tarja , Salo Jari , Kröger Heikki 
Published: March 2018

Background Computed tomography (CT) can be used to assess the rotational alignment of prosthesis components to identify possible underlying causes of symptomatic total knee arthroplasty (TKA). The use of cone beam computed tomography (CBCT) for the imaging of extremities is relatively new, although it has been widely used in dental imaging. Purpose To assess the intra- and inter-observer reproducibility of CBCT, as well as to validate CBCT for TKA component and periprosthetic bone diagnostics. Material and Methods CBCT scans were performed on 18 patients the day before a scheduled revision TKA, from which the intra- and inter-observer reproducibility were assessed. Component rotation and loosening were evaluated. Perioperative bone defects were classified. Results The inter-observer intraclass coefficient correlation (ICC) for femoral component rotation was 0.41 (95% confidence interval [CI] = 0.12–0.69). For the tibial component, the ICC was 0.87 (95% CI = 0.74–0.94). Intra-observer reproducibilities were 0.70 (95% CI = 0.35–0.87) and 0.92 (95% CI = 0.80–0.97), respectively. The sensitivity for tibial component loosening was 97% and the specificity was 85%. The reliability of bone defect classification was only weak to moderate. Conclusion Two-dimensional (2D) CBCT scanning provides reliable and reproducible data for determining the rotation of femoral and tibial components, while showing minor overestimation of tibial component loosening. CBCT is a promising new tool for the evaluation of symptomatic knee arthroplasty patients, with a substantially lower radiation dose compared to conventional 2D multi-slice CT.
Public awareness of the need to call emergency medical services following the onset of acute myocardial infarction and associated factors in Japan
Authors: Yonemoto Naohiro , Kada Akiko , Yokoyama Hiroyuki , Nonogi Hiroshi 
Published: March 2018

Objectives Early recognition of acute myocardial infarction (AMI) and early activation of emergency medical services (EMS) are essential to reduce delays in patient care. We investigated public awareness of the need to call EMS at onset of AMI and evaluated associated factors. Methods In January 2008, a nationwide population-based survey using quota sampling was conducted in Japan. The primary outcome measure was responsiveness to promptly calling EMS at AMI onset, subdivided by on-time (daytime) and off-time (nights and holidays) hours. Results In total, 1200 participants were surveyed. Their mean age was 46.3 years (standard deviation, 17.4), and 50.3% (n=604) were women. A total of 11.6% (n=139) answered that they would call EMS during on-time hours, and 27.5% (n=330) stated that they would call during off-time hours. Multivariable analysis showed that the participants’ age, female sex, education level, and self-confidence regarding their understanding of AMI were significant associated factors. The associated factors were almost identical during the off-time hours; only sex was no longer significant. Conclusions Public awareness of the need to call EMS at AMI onset in Japan was low. Previous intervention studies that were not effective may not have targeted groups with significant risk factors.
Association between Toxoplasma gondii infection and history of blood transfusion: a case-control seroprevalence study
Authors: Alvarado-Esquivel Cosme , Sánchez-Anguiano Luis Francisco , Hernández-Tinoco Jesús , Ramos-Nevarez Agar , Estrada-Martínez Sergio , Cerrillo-Soto Sandra Margarita , Medina-Heredia Gonzalo Elías , Guido-Arreola Carlos Alberto , Soto-Quintero Araceli Alejandra , Beristain-Garcia Isabel 
Published: March 2018

Objectives This study was performed to determine the association between seropositivity to Toxoplasma gondii and a history of blood transfusion. Methods Patients who had undergone blood transfusion (n = 410) and age- and sex-matched controls who had not undergone blood transfusion (n = 1230) were examined for anti- T. gondii IgG and IgM antibodies using enzyme-linked immunoassays. Results Anti- T. gondii IgG antibodies were detected in 57 (13.9%) patients and in 129 (10.5%) controls with a borderline difference [odds ratio (OR) = 1.37, 95% confidence interval (CI) = 0.98–1.92]. High anti- T. gondii IgG antibody levels (>150 IU/mL) were found in 27 (47.4%) of the 57 anti- T. gondii IgG-positive patients and in 37 (28.7%) of the 129 anti- T. gondii IgG positive controls with a significant difference (OR = 2.23, 95% CI = 1.17–4.26). Anti- T. gondii IgM antibodies were found in 13 (22.8%) of the 57 seropositive patients and in 37 (28.7%) of the 129 seropositive controls, but the difference was not significant (OR = 0.73, 95% CI = 0.35–1.52). Seroprevalence was significantly higher in patients aged >50 years than in controls of the same age and in female patients than in female controls. Conclusions These findings indicate that a history of blood transfusion is a risk factor for T. gondii infection.
Nanoscale Modulation of the Pore Dimensions, Size Distribution and Structure of a new Polysulfone-Based High-Flux Dialysis Membrane
Authors: Ronco C. , Bowry S. 
Published: March 2018

Current haemodialysis therapy modalities such as haemodiafiltration enhance the removal of larger uraemic solutes from the blood of patients on end-stage renal disease. A number of clinical investigations have demonstrated the clinical benefits of such therapies in contributing towards better patient survival rates and an improved quality of life. A fundamental prerequisite to the application of convective treatment modalities is the availability of appropriate, technologically-advanced high-flux dialysis membranes that are able to eliminate larger uraemic substances with high efficiency but without causing an excessive leakage of useful proteins. A new membrane, Helixone®, has been developed specifically to meet the present-day requirements of high-flux dialysis and haemodiafiltration therapies involving large substitution rates. The application of nanotechnology fabrication principles and procedures has enabled the development of a membrane having highly-defined inner, separating layer surface structures that offer minimal resistance to the removal of large molecular weight substances across the membrane; for the first time, pore size dimensions, pore size distribution and pore geometry have been modulated and controlled at the nanoscale level for Helixone®. This paper describes the characterisation of the essential structure- and permeation-related parameters of the new membrane using a number of physical analytical techniques.
The outcome of critically ill elderly patients with severe acute renal failure treated by continuous hemodiafiltration
Authors: Bellomo R. , Farmer M. , Boyce N. 
Published: March 2018

Objectives To study the outcome of critically ill elderly patients with severe acute renal failure managed by continuous hemodiafiltration. Design Prospective study. Setting Intensive Care Unit of tertiary institution Patients Seventy-two consecutive critically ill patients of 65 years or older admitted to the ICU with severe acute renal failure. Seventy similar control patients of age < 65 years. Intervention Treatment of all patients with continuous hemodiafiltration. Measurements and main results: Safety and effectiveness of therapy were assessed. Main outcome measures were duration of oliguria, of ICU stay, and hospital stay for survivors, and survival to ICU discharge and to hospital discharge. Mean APACHE II score on admission was 29.8 (95% confidence interval: 28.5 to 31.1) and mean organ failure score prior to initiation of continuous hemodiafiltration was 3.9 (95% confidence interval: 3.6 to 4.2). Sepsis was present in 51 cases (70.8%) and bacteremia or fungemia in 24 (33.3%). Fifty-three (73.6%) required mechanical ventilation for > 3 days. Vasopressor drugs were used in 65 (90.2%). Continuous hemodiafiltration controlled azotemia in all patients and was only associated with minor complications. Thirty-four patients (47.2%) survived to ICU discharge and 30 (41.6%) to hospital discharge. Among survivors, duration of oliguria was 11.6 days (95% confidence interval: 9.1 to 14.1), mean duration of ICU stay 8.6 days (95% confidence interval: 6.1 to 11.) and mean duration of hospital stay 33.1 days (95% confidence interval: 28.8 to 37.4). No statistically significant difference in survival was found when these patients were compared to a control group of similar but younger patients who also received ICU care and continuous hemodiafiltration for the treatment of severe acute renal failure. Conclusions A greater than 40% survival was achieved in critically ill elderly patients with severe acute renal failure by the use of continuous hemodiafiltration. These patients had an in hospital survival comparable to that of younger patients. These findings support an aggressive renal replacement approach in such patients and suggest that continuous hemodiafiltration may be ideally suited to their management.
Double-Opposing Z-Plasty for Secondary Surgical Management of Velopharyngeal Insufficiency Following Primary Furlow Palatoplasty
Authors: Gosain Arun K. , Chim Harvey , Sweeney Walter M. 
Published: March 2018

Objective: The present study investigates the efficacy of performing a “palate rerepair” utilizing a double-opposing z-palatoplasty (DOZ) following primary Furlow palatoplasty. Design: Retrospective study. Setting: Tertiary referral academic center for craniofacial surgery. Patients: 15 consecutive patients who presented with velopharyngeal insufficiency (VPI) after primary Furlow palatoplasty. Main Outcome Measures: All subjects were evaluated using the perceptual speech assessment (PSA) scale. Criteria for inclusion in the study were (1) velopharyngeal gap size on phonation of 7 mm or less and (2) lateral wall motion at least 40% normal. Results: Mean PSA score was 7.13 + 3.31 (range 3-13) preoperatively, and decreased to 1.80 + 2.83 (range 0-11; P < .001 vs baseline) 3 months or more after surgery. A sphincter pharyngoplasty was performed as a tertiary procedure in 2 patients due to persistent nasal air emission. There was no symptomatic airway compromise following secondary or tertiary management in all patients. Presence of a cleft lip, lateral wall motion, and velopharyngeal gap size did not impact outcomes. Conclusions: We have demonstrated that a DOZ performed secondarily is anatomically possible following Furlow palatoplasty and can restore function of the levator muscle despite significant scarring following primary repair. This approach respects anatomic principles of palatoplasty without eliminating the possibility for extrapalatal procedures should velopharyngeal competence not be achieved.