bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ovariectomy and obesity have equal impact in causing mitochondrial dysfunction and impaired skeletal muscle contraction in rats
Authors: Sutham Wissuta , Sripetchwandee Jirapas , Minta Wanitchaya , Mantor Duangkamol , Pattanakuhar Sintip , Palee Siripong , Pratchayasakul Wasana , Chattipakorn Nipon , Chattipakorn Siriporn C. 
Published: July 2018

Abstract

Objective:
Previous studies have demonstrated that either an obese-insulin resistance condition or a condition involving loss of estrogen impaired skeletal muscle function as indicated by a decrease in muscle contraction. The differing effects of combined estrogen deficiency over obese-insulin resistance on skeletal muscle function have, however, not yet been determined. Our hypothesis was that estrogen deficiency aggravates skeletal muscle dysfunction in obese-insulin resistant rats, via increased muscle oxidative stress and mitochondrial dysfunction.

Methods:
Twenty-four female Wistar rats were divided into 2 groups and animals in each group were fed either a normal diet (ND) or a high-fat diet (HFD) for 24 weeks. At week 13, rats in each group were subdivided into 2 subgroups: sham-operated or ovariectomized (n = 6/subgroup). At the end of the experimental period the contraction of the gastrocnemius muscles was tested before the rats were sacrificed. Skeletal muscle was removed to assess oxidative stress and mitochondrial function.

Results:
We found that an obese-insulin resistant condition was observed in sham-operated HFD-fed rats, ovariectomized ND-fed rats, and ovariectomized HFD-fed rats. Skeletal muscle contractile function (peak-force ratio [g/g]; 25.40 ± 2.03 [ovariectomized ND-fed rats], 22.44 ± 0.85 [sham-operated HFD-fed rats] and 25.06 ± 0.61 [ovariectomized HFD-fed rats]), skeletal muscle mitochondrial function, and oxidative stress were equally significantly impaired in all 3 groups, when compared with those of sham-operated ND-fed rats (31.12 ± 1.88 g/g [NDS]; P < 0.05). Surprisingly, loss of estrogen did not aggravate these dysfunctions of skeletal muscles in HFD-fed rats.

Conclusions:
These findings suggest that skeletal muscle dysfunction may occur due to increased muscle oxidative stress and mitochondrial dysfunction as a result of ovariectomy and obese-insulin resistance. Loss of estrogen, however, did not aggravate these impairments in the muscle of rats with obese-insulin resistant condition.
The histological microstructure and in vitro mechanical properties of the human female postmenopausal perineal body
Authors: Kochová Petra , Cimrman Robert , Jansová Magdalena , Michalová Květoslava , Kalis Vladimir , Kubíková Tereza , Tonar Zbyněk 
Published: July 2018

Abstract

Objective:
The perineal body connects muscles from the pelvic floor and is critical for support of the lower part of the vagina and proper function of the anal canal. We determined mechanical parameters and volume fractions of main components of the human female postmenopausal perineal body.

Methods:
The specimens were taken from 15 fresh female cadavers (age 74 ± 10, mean ± standard deviation). Seventy-five specimens from five regions of the perineal body were processed histologically to assess volume fractions of tissue components using stereological point testing grid. Fifteen specimens taken from the midline region were loaded uniaxially with 6 mm/min velocity until tissue rupture to determine Young's modulus of elasticity, ultimate stresses, and strains.

Results:
The perineal body was composed of collagen (29%), adipose cells (27%), elastin (7%), smooth muscle (11%), and skeletal muscle (3%). The residual tissue (19%) constituted mostly peripheral nerves, lumina of blood vessels, fibroblasts, and fibrocytes. Young's modulus of elasticity at midline region was 18 kPa (median) at small and 232 kPa at large deformations, respectively. The ultimate stress was 172 kPa and the ultimate strain was 1.4.

Conclusions:
We determined the structural and mechanical parameters of the perineal body. The resultant data could be used as input for models simulating pelvic floor prolapse or dysfunction.
Postmenopausal hormone therapy is accompanied by elevated risk for uterine prolapse
Authors: Rahkola-Soisalo Päivi , Savolainen-Peltonen Hanna , Gissler Mika , Hoti Fabian , Vattulainen Pia , Ylikorkala Olavi , Mikkola Tomi S. 
Published: July 2018

Abstract

Objective:
Receptors for estrogen and progesterone are present in the pelvic floor, and therefore, postmenopausal hormone therapy may affect its function. We compared the former use of estradiol-progestogen postmenopausal hormone therapy in nonhysterectomized women with a uterine prolapse surgery (N = 12,072) and control women (N = 33,704).

Methods:
The women with a history of uterine prolapse operation were identified from the Finnish National Hospital Discharge Register, and the control women from the Finnish Central Population Register. The use of hormone therapy was traced from the national drug reimbursement register, and the odd ratios with 95% CIs for prolapse were calculated by using the conditional logistic regression analysis.

Results:
The women with uterine prolapse had used hormone therapy more often than control women (N = 4,127; 34.2% vs N = 9,189; 27.3%; P < 0.005). The use of hormone therapy was accompanied by significant (23%-53%) elevations in the risk for prolapse, being higher with longer exposure. The risk elevations (33%-23%) were comparable between sole norethisteroneacetate-estradiol and sole medroxyprogesteroneacetate-estradiol therapy. The use of estradiol in combination with a levonorgestrel releasing intrauterine device was accompanied by a 52% elevation.

Conclusions:
The postmenopausal use of estradiol in combination with various progestogen regimens may weaken the pelvic floor, resulting in uterine prolapse. This data should be incorporated into the information given to the users of estradiol-progestogen hormone therapy.
Analgesic effects of a novel pH-dependent μ-opioid receptor agonist in models of neuropathic and abdominal pain
Authors: Rodriguez-Gaztelumendi Antonio , Spahn Viola , Labuz Dominika , Machelska Halina , Stein Christoph 
Published: July 2018

Abstract
Recently, (±)-N-(3-fluoro-1-phenethylpiperidine-4-yl)-N-phenyl propionamide (NFEPP), a newly designed μ-opioid receptor (MOR) agonist with a low pKa, has been shown to produce injury-restricted analgesia in models of inflammatory and postoperative pain, without exhibiting typical opioid side effects. Here, we investigated MOR binding of NFEPP in brain and dorsal root ganglia, pH in injured tissues, and the analgesic efficacy of NFEPP compared with fentanyl in a chronic constriction injury model of neuropathic pain, and in the acetic acid–induced abdominal writhing assay in rats. Binding experiments revealed significantly lower affinity of NFEPP compared with fentanyl at pH 7.4. In vivo, pH significantly dropped both at injured nerves after chronic constriction injury and in the abdominal cavity after acetic acid administration. Intravenous NFEPP as well as fentanyl dose-dependently diminished neuropathy-induced mechanical and heat hypersensitivity, and acetic acid–induced abdominal constrictions. In both models, NFEPP-induced analgesia was fully reversed by naloxone methiodide, a peripherally restricted opioid receptor antagonist, injected at the nerve injury site or into the abdominal cavity. Our results indicate that NFEPP exerts peripheral opioid receptor–mediated analgesia exclusively in damaged tissue in models of neuropathic and abdominal pain.
Outcome and adverse events in patients with chronic hepatitis C treated with direct-acting antivirals: a clinical randomized study
Authors: Sølund Christina , Andersen Ellen S. , Mössner Belinda , Laursen Alex L. , Røge Birgit T. , Kjær Mette S. , Gerstoft Jan , Christensen Peer B. , Pedersen Martin S. , Schønning Kristian , Fahnøe Ulrik , Bukh Jens , Weis Nina 
Published: July 2018

Objective
New potent direct-acting antiviral (DAA) regimens against hepatitis C virus have been approved in recent years. However, information about the rate of adverse events (AEs) across different DAA regimens is limited. We aimed to evaluate differences in AEs and treatment efficacy in patients with chronic hepatitis C (CHC), genotype (GT) 1 or 3, randomized to two different treatment arms, correspondingly.

Patients and methods
We randomly assigned 96 patients in a 1 : 1 ratio, to treatment for 12 weeks with either paritaprevir/ombitasvir/ritonavir/dasabuvir/ribavirin (RBV) or ledipasvir/sofosbuvir (SOF)/RBV if infected with GT1 (72 patients) or to daclatasvir/SOF/RBV for 12 weeks or SOF/RBV for 24 weeks, if infected with GT3 (24 patients). Data on AEs were collected throughout the entire study period.

Results
A total of 70 (97%) patients with CHC with GT1 and 20 (83%) patients with GT3 achieved cure. The GT3 treatment arm was prematurely terminated, owing to change in national treatment guidelines. Thus, only AEs for GT1 patients are described. AEs occurred in 70 (97%) GT1 patients, and most common AEs were anemia (n=56/78%), fatigue (n=53/74%), and headache (n=33/46%). No difference was observed in relation to treatment group (P=1.0), anemia (P=1.0), or liver cirrhosis (P=0.53). In seven (11%) patients, AEs assessed by the investigator to be possibly related to the DAA regimen were still present 12 weeks after treatment.

Conclusions
We found no difference in AEs possibly related to the DAA regimen in patients with CHC, but surprisingly, AEs possibly related to the DAA regimen persisted in a significant number of patients after treatment. This finding can be of importance for clinicians in relation to patient information concerning AEs possibly related to DAA treatment.
Medial Plantar Flap for Hand Reconstruction
Authors: Troisi Luigi , Berner Juan E. , West Emily V. , Wilson Paul 
Published: July 2018

Abstract
The reconstruction of soft tissue defects on the volar aspect of the hand represents a special challenge for the hand surgeon. Even though local and regional options have been described, in some cases because of their complexity, a free flap is preferred. The medial plantar free flap offers a unique reconstructive alternative by providing glabrous skin resurfacing for the palm and digits. The aim of this article is to present a systematic literature review on the use of the medial plantar free flap for hand surgery and a case report in which this flap was used for reconstructing a thenar eminence defect after sarcoma excision. Twenty-five relevant articles were found, and their findings are included in our study. The fasciocutaneous medial plantar flap and its musculocutaneous, flow-through, venous, perforator, and chimeric variants offer a wide range of reconstructive options for complex hand injuries.
Evidence for the Role of the Cecal Microbiome in Maintenance of Immune Regulation and Homeostasis
Authors: Chhabra Preeti , Spano Anthony J. , Bowers Daniel , Ren Tiantian , Moore Daniel J. , Timko Michael P. , Wu Martin , Brayman Kenneth L. 
Published: July 2018

Objective (s):
Our objective was to investigate alterations in the cecal microbial composition during the development of type 1 diabetes (T1D) with or without IgM therapy, and correlate these alterations with the corresponding immune profile.

Methods:
(1) Female nonobese diabetic (NOD) mice treated with IgM or saline (n = 20/group) were divided into 5-week-old nondiabetic; 9 to 12-week-old prehyperglycemic stage-1; ≥13-week-old prehyperglycemic stage-2; and diabetic groups. 16S rRNA libraries were prepared from bacterial DNA and deep-sequenced. (2) New-onset diabetic mice were treated with IgM (200 μg on Days 1, 3, and 5) and their blood glucose monitored for 2 months.

Results:
Significant dysbiosis was observed in the cecal microbiome with the progression of T1D development. The alteration in microbiome composition was characterized by an increase in the bacteroidetes:firmicutes ratio. In contrast, IgM conserved normal bacteroidetes:firmicutes ratio and this effect was long-lasting. Furthermore, oral gavage using cecal content from IgM-treated mice significantly diminished the incidence of diabetes compared with controls, indicating that IgM specifically affected mucosa-associated microbes, and that the affect was causal and not an epiphenomenon. Also, regulatory immune cell populations (myeloid-derived suppressor cells and regulatory T cells) were expanded and insulin autoantibody production diminished in the IgM-treated mice. In addition, IgM therapy reversed hyperglycemia in 70% of new-onset diabetic mice (n = 10) and the mice remained normoglycemic for the entire post-treatment observation period.

Conclusions:
The cecal microbiome appears to be important in maintaining immune homeostasis and normal immune responses.
Morphological Factors Related to Nodal Metastases in Neuroendocrine Tumors of the Appendix
Authors: Brighi Nicole , La Rosa Stefano , Rossi Giulio , Grillo Federica , Pusceddu Sara , Rinzivillo Maria , Spada Francesca , Tafuto Salvatore , Massironi Sara , Faggiano Antongiulio , Antonuzzo Lorenzo , Santini Donatella , Sessa Fausto , Maragliano Roberta , Gelsomino Fabio , Albertelli Manuela , Vernieri Claudio , Panzuto Francesco , Fazio Nicola , De Divitiis Chiara , Lamberti Giuseppe , Colao Annamaria , Fave Gianfranco Delle , Campana Davide 
Published: July 2018

Objective:
The aim of this study was to evaluate clinical and morphological features related to nodal involvement in appendiceal neuroendocrine tumors (NETs), to identify patients who should be referred for oncological radicalization with hemicolectomy.

Background:
Appendiceal NETs are usually diagnosed accidentally after appendectomy; the indications for right hemicolectomy are currently based on several parameters (ie, tumor size, grading, proliferative index, localization, mesoappendiceal invasion, lymphovascular infiltration). Available guidelines are based on scarce evidence inferred by small, retrospective, single-institution studies, resulting in discordant recommendations.

Methods:
A retrospective analysis of a prospectively collected database was performed. Patients who underwent surgical resection of appendiceal NETs at 11 tertiary Italian centers, from January 1990 to December 2015, were included. Clinical and morphological data were analyzed to identify factors related to nodal involvement.

Results:
Four-hundred fifty-seven patients were evaluated, and 435 were finally included and analyzed. Of them, 21 had nodal involvement. Grading G2 [odds ratio (OR) 6.04], lymphovascular infiltration (OR 10.17), size (OR 18.50), and mesoappendiceal invasion (OR 3.63) were related to nodal disease. Receiver operating characteristic curve identified >15.5 mm as the best size cutoff value (area under the curve 0.747). On multivariate analysis, grading G2 (OR 6.98), lymphovascular infiltration (OR 8.63), and size >15.5 mm (OR 35.28) were independently related to nodal involvement.

Conclusions:
Tumor size >15.5 mm, grading G2, and presence of lymphovascular infiltration are factors independently related to nodal metastases in appendiceal NETs. Presence of ≥1 of these features should be considered an indication for oncological radicalization. Although these results represent the largest study currently available, prospective validation is needed.
Low Ligation of Inferior Mesenteric Artery in Laparoscopic Anterior Resection for Rectal Cancer Reduces Genitourinary Dysfunction
Authors: Mari Giulio M. , Crippa Jacopo , Cocozza Eugenio , Berselli Mattia , Livraghi Lorenzo , Carzaniga Pierluigi , Valenti Francesco , Roscio Francesco , Ferrari Giovanni , Mazzola Michele , Magistro Carmelo , Origi Matteo , Forgione Antonello , Zuliani Walter , Scandroglio Ildo , Pugliese Raffaele , Costanzi Andrea T. M. , Maggioni Dario 
Published: July 2018

Objectives:
The aim of the present study was to compare the incidence of genitourinary (GU) dysfunction after elective laparoscopic low anterior rectal resection and total mesorectal excision (LAR + TME) with high or low ligation (LL) of the inferior mesenteric artery (IMA). Secondary aims included the incidence of anastomotic leakage and oncological outcomes.

Background:
The criterion standard surgical approach for rectal cancer is LAR + TME. The level of artery ligation remains an issue related to functional outcome, anastomotic leak rate, and oncological adequacy. Retrospective studies failed to provide strong evidence in favor of one particular vascular approach and the specific impact on GU function is poorly understood.

Methods:
Between June 2014 and December 2016, patients who underwent elective laparoscopic LAR + TME in 6 Italian nonacademic hospitals were randomized to high ligation (HL) or LL of IMA after meeting the inclusion criteria. GU function was evaluated using a standardized survey and uroflowmetric examination. The trial was registered under the ClinicalTrials.gov Identifier NCT02153801.

Results:
A total of 214 patients were randomized to HL (n = 111) or LL (n = 103). GU function was impaired in both groups after surgery. LL group reported better continence and less obstructive urinary symptoms and improved quality of life at 9 months postoperative. Sexual function was better in the LL group compared to HL group at 9 months. Urinated volume, maximum urinary flow, and flow time were significantly (P < 0.05) in favor of the LL group at 1 and 9 months from surgery. The ultrasound measured post void residual volume and average urinary flow were significantly (P < 0.05) better in the LL group at 9 months postoperatively. Time of flow worsened in both groups at 9 months compared to baseline. There was no difference in anastomotic leak rate (8.1% HL vs 6.7% LL). There were no differences in terms of blood loss, surgical times, postoperative complications, and initial oncological outcomes between groups.

Conclusions:
LL of the IMA in LAR + TME results in better GU function preservation without affecting initial oncological outcomes. HL does not seem to increase the anastomotic leak rate.
Changes in the urinary proteome in a Patient-Derived Xenograft model
Authors: Liu Yongtao , Wang Youzhu , Cao Zhixiang , Gao Youhe 
Published: July 2018

AbstractIn this report, the urinary proteome from a patient-derived xenograft (PDX) model was compared at the peptide level to study the origins of urinary proteins in tumor-bearing nude mice. Urine was collected from the PDX mice before and after tumor implantation. A total of 515 mouse proteins were identified, of which 8 were differential proteins. Seventy-eight unambiguous human peptides from 42 human proteins were identified in the tumor-bearing group. Compared with the differential urinary proteins from the tumor-bearing immuno-competent rats, the differential proteins in the urine from the PDX model had no host immune response proteins in the very early stage urine in the tumor-bearing immuno-competent rat model.
Addition of Degenerate Bases to DNA-based Data Storage for Increased Information Capacity
Authors: Choi Yeongjae , Ryu Taehoon , Lee Amos C. , Choi Hansol , Lee Hansaem , Park Jaejun , Song Suk-Heung , Kim Seoju , Kim Hyeli , Park Wook , Kwon Sunghoon 
Published: July 2018

Introductory paragraphDNA-based data storage has emerged as a promising method to satisfy the exponentially increasing demand for information storage. However, practical implementation of DNA-based data storage remains a challenge because of the high cost of DNA per unit data. Here, we propose the use of eleven degenerate bases as encoding characters in addition to A, C, G, and T, which increases the information capacity (the amount of data that can be stored per length of DNA sequence designed) and reduce the cost of DNA per unit data. Using the proposed method, we experimentally achieved an information capacity of 3.37 bits/character, which is more than twice when compared to the highest information capacity previously achieved. Finally, the platform was projected to reduce the cost of DNA-based data storage by 50%.
A genetic perspective on Longobard-Era migrations
Authors: Vai Stefania , Brunelli Andrea , Modi Alessandra , Tassi Francesca , Vergata Chiara , Pilli Elena , Lari Martina , Rosa Susca Roberta , Giostra Caterina , Pejrani Baricco Luisella , Bedini Elena , Koncz István , Vida Tivadar , Gusztáv Mende Balázs , Winger Daniel , Loskotová Zuzana , Veeramah Krishna , Geary Patrick , Barbujani Guido , Caramelli David , Ghirotto Silvia 
Published: July 2018

AbstractFrom the first century AD, Europe has been interested by population movements, commonly known as Barbarian migrations. Among these processes, the one involving the Longobard culture interested a vast region, but its dynamics and demographic impact remains largely unknown. Here we report 87 new complete mitochondrial sequences coming from nine early-medieval cemeteries located along the area interested by the Longobard migration (Czech Republic, Hungary and Italy). From the same locations, we sampled necropolises characterized by cultural markers associated with the Longobard culture (LC) and coeval burials where no such markers were found (NLC). Population genetics analysis and ABC modeling highlighted a similarity between LC individuals, as reflected by a certain degree of genetic continuity between these groups, that reached 70% among Hungary and Italy. Models postulating a contact between LC and NLC communities received also high support, indicating a complex dynamics of admixture in medieval Europe.
Temporal Multiple Kernel Learning (tMKL) model for predicting resting state FC via characterizing fMRI connectivity dynamics
Authors: Surampudi Sriniwas Govinda , Misra Joyneel , Deco Gustavo , Surampudi Raju Bapi , Sharma Avinash , Roy Dipanjan 
Published: July 2018

AbstractOver the last decade there has been growing interest in understanding the brain activity in the absence of any task or stimulus captured by the resting-state functional magnetic resonance imaging (rsfMRI). These resting state patterns are not static, but exhibit complex spatio-temporal dynamics. In the recent years substantial effort has been put to characterize different FC configurations while brain states makes transitions over time. The dynamics governing this transitions and their relationship with stationary functional connectivity remains elusive. Over the last years a multitude of methods has been proposed to discover and characterize FC dynamics and one of the most accepted method is sliding window approach. Moreover, as these FC configurations are observed to be cyclically repeating in time there was further motivation to use of a generic clustering scheme to identify latent states of dynamics. We discover the underlying lower-dimensional manifold of the temporal structure which is further parameterized as a set of local density distributions, or latent transient states. We propose an innovative method that learns parameters specific to these latent states using a graph-theoretic model (temporal Multiple Kernel Learning, tMKL) and finally predicts the grand average functional connectivity (FC) of the unseen subjects by leveraging a state transition Markov model. tMKL thus learns a mapping between the underlying anatomical network and the temporal structure. Training and testing were done using the rs-fMRI data of 46 healthy participants and the results establish the viability of the proposed solution. Parameters of the model are learned via state-specific optimization formulations and yet the model performs at par or better than state-of-the-art models for predicting the grand average FC. Moreover, the model shows sensitivity towards subject-specific anatomy. The proposed model performs significantly better than the established models of predicting resting state functional connectivity based on whole-brain dynamic mean-field model, single diffusion kernel model and another version of multiple kernel learning model. In summary, We provide a novel solution that does not make strong assumption about underlying data and is generally applicable to resting or task data to learn subject specific state transitions and successful characterization of SC-dFC-FC relationship through an unifying framework.