bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunotherapy-based combinations: an update
Authors: Fucà Giovanni , de Braud Filippo , Di Nicola Massimo
Published: July 2018

Purpose of review

The advent of immunotherapy significantly improved clinical outcomes in cancer patients, although immune checkpoint blockade (ICB) still lack of efficacy in a consistent proportion of treated patients. The purpose of this article is to review the most innovative and clinically promising ICB-based combinations designed to improve the efficacy of cancer immunotherapy.

Recent findings

First-line combinatorial treatment with ipilimumab and nivolumab has recently shown to be superior to the standard of care in a subset of metastatic nonsmall cell lung cancer (NSCLC) and renal cell carcinoma (RCC). The combination of programmed cell death protein 1 (PD-1)/PD-L1 blockade with antiangiogenics has demonstrated a consistent clinical efficacy, especially for the combination of bevacizumab and atezolizumab as first-line therapy in metastatic RCC. The sequential combination of definitive chemoradiotherapy followed by durvalumab maintenance in advanced, unresectable NSCLC became the new standard of care, while the addition of pembrolizumab to first-line chemotherapy in metastatic NSCLC significantly improves overall survival. Despite promising results for the combination of ICBs with v-raf murine sarcoma viral oncogene homolog B/MAPK/ERK kinase inhibitors or epidermal growth factor receptor inhibitors, especially in melanoma and NSCLC, safety concerns slowed down the development of such strategies.

Immunotherapy-based combinations are becoming the standard of care for cancer treatment, in particularly for advanced melanoma, NSCLC and RCC.
Effectiveness of Animal-Assisted Therapy in the Pediatric Population: Systematic Review and Meta-Analysis of Controlled Studies
Authors: Charry-Sánchez Jesús David , Pradilla Iván , Talero-Gutiérrez Claudia
Published: July 2018

Objective:

To synthesize the results of controlled studies evaluating the effectiveness of animal-assisted therapy (AAT) in children.

Methods:

Eleven databases were searched following the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement recommendations, and references from included studies and previous reviews were examined. No date or language filters were applied. Only controlled study designs, including those using wait-list controls, that studied a specific condition or illness were included. Study quality was assessed using the Cochrane Risk of Bias Tool.

Results:

Twenty-six studies that met the inclusion criteria were retrieved. Nine were conducted in children with autism spectrum disorders, 10 in cerebral palsy (CP), 2 in Down syndrome, 3 in pain, and 2 in other conditions. Qualitative synthesis showed a small but significant contribution of AAT to the management of these conditions. Meta-analysis showed a mean difference in improvement in the Gross Motor Function Measure-66 scale in children with CP of 1.61 (95% confidence interval [CI] −2.00 to 5.23) and a mean difference for 5-point pain scales of −0.81 (95% CI −1.32 to 0.30), both favoring AAT.

Conclusion:

Animal-assisted therapy may be useful as a complementary intervention in the management of children with CP and pain. Although results are in general positive for the management of children with Down syndrome and autism, the diversity of scales used to measure outcomes makes it difficult to establish true effectiveness. The application of simple corrective measures in the randomization process would greatly improve the quality of evidence. It is necessary to reach a consensus between AAT researchers regarding appropriate instruments to provide higher-quality evidence in further studies.
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

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

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

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

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

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.
Successful Development and Implementation of a Surgical Response Team for Emergent Surgical Cases
Authors: Pichoff Amy M. , Shah Abha , Baer John , Staab Jared
Published: July 2018

At our institution, we recognized a need for a standardized, efficient approach to safely evaluate, prepare, and transport patients in need of emergent surgery. With the establishment of an Emergency Surgery Transport and Assessment Team, we were able to substantially reduce our median transport time to the OR. We believe other institutions can establish an efficient team using existing resources to expedite care of the emergent surgical patient.
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.
Evidence of sociality in the timing and location of foraging in a colonial seabird
Authors: Jones Teri B. , Patrick Samantha C. , Arnould John P. Y. , Rodríguez-Malagón Marlenne A. , Wells Melanie R. , Green Jonathan A.
Published: July 2018

Social foraging behaviours, which range from cooperative hunting to local enhancement, can result in increased prey capture and access to information, which may significantly reduce time and energy costs of acquiring prey. In colonial species, it has been proposed that the colony itself may act as a site of social information transfer and group formation. However, conclusive evidence from empirical studies is lacking. In particular, most studies in colonial species have generally focussed on behaviours either at the colony or at foraging sites in isolation, and have failed to directly connect social associations at the colony to social foraging. In this study, we simultaneously tracked 85% of a population of Australasian gannets (
Morus serrator
) over multiple foraging trips, to study social associations at the colony and test whether these associations influence the location of foraging sites. We found that gannets positively associate with conspecifics while departing from the colony and that co-departing gannets have more similar initial foraging patches than individuals that did not associate at the colony. These results provide strong evidence for the theory that the colony may provide a source of information that influences foraging location.
Growth potential can affect timing of maturity in a long-lived semelparous fish
Authors: Yokouchi Kazuki , Daverat Françoise , Miller Michael J. , Fukuda Nobuto , Sudo Ryusuke , Tsukamoto Katsumi , Elie Pierre , Poole W. Russell
Published: July 2018

Many diadromous fishes such as salmon and eels that move between freshwater and the ocean have evolved semelparous reproductive strategies, but both groups display considerable plasticity in characteristics. Factors such as population density and growth, predation risk or reproduction cost have been found to influence timing of maturation. We investigated the relationship between female size at maturity and individual growth trajectories of the long-lived semelparous European eel,
Anguilla anguilla
. A Bayesian model was applied to 338 individual growth trajectories of maturing migration-stage female silver eels from France, Ireland, the Netherlands and Hungary. The results clearly showed that when growth rates declined, the onset of maturation was triggered, and the eels left their growth habitats and migrated to the spawning area. Therefore, female eels tended to attain larger body size when the growth conditions were good enough to risk spending extra time in their growth habitats. This flexible maturation strategy is likely related to the ability to use diverse habitats with widely ranging growth and survival potentials in the catadromous life-history across its wide species range.
Age-specific patterns of maternal investment in common gull egg yolk
Authors: Urvik Janek , Rattiste Kalev , Giraudeau Mathieu , Okuliarová Monika , Hõrak Peeter , Sepp Tuul
Published: July 2018

While the general patterns of age-specific changes in reproductive success are quite well established in long-lived animals, we still do not know if allocation patterns of maternally transmitted compounds are related to maternal age. We measured the levels of yolk testosterone, carotenoids and vitamins A and E in a population of known-aged common gulls (
Larus canus
) and found an age-specific pattern in yolk lutein and vitamin A concentrations. Middle-aged mothers allocated more of these substances to yolk compared to young and old mothers. These results can be explained through differences in age-specific foraging, absorption or deposition patterns of carotenoids and vitamins into yolk. If these molecules play a role in antioxidant defence and immune modulation, our results suggest a possible physiological pathway underlying the age-specific changes in reproductive success of long-lived birds in the wild.
Functional capacity of kangaroo rat hindlimbs: adaptations for locomotor performance
Authors: Rankin Jeffery W. , Doney Kelsey M. , McGowan Craig P.
Published: July 2018

Many cursorial and large hopping species are extremely efficient locomotors with various morphological adaptations believed to reduce mechanical demand and improve movement efficiency, including elongated distal limb segments. However, despite having elongated limbs, small hoppers such as desert kangaroo rats (Dipodomys deserti) are less efficient locomotors than their larger counterparts, which may be in part due to avoiding predators through explosive jumping movements. Despite potentially conflicting mechanical demands between the two movements, kangaroo rats are both excellent jumpers and attain high hopping speeds, likely due to a specialized hindlimb musculoskeletal morphology. This study combined experimental dissection data with a static analysis of muscle moment generating capacities using a newly developed musculoskeletal model to characterize kangaroo rat hindlimb musculoskeletal architecture and investigate how morphology has evolved to meet hopping and jumping mechanical demands. Hindlimb morphology appears biased towards generating constant moment arms over large joint ranges of motion in this species, which may balance competing requirements by reducing the need for posture and movement specific excitation patterns. The ankle extensors are a major exception to the strong positive relationship exhibited by most muscles between muscle architecture parameters (e.g.Lfibre) and joint moment arms. These muscles appear suited to meeting the high moments required for jumping: the biarticular nature of the ankle extensors is leveraged to reduce MTU strain and create a four-bar linkage that facilitates proximal force transfer. The kangaroo rat hindlimb provides an interesting case study for understanding how morphology balances the sometimes competing demands of hopping and jumping.
Changes in the urinary proteome in a Patient-Derived Xenograft model
Authors: Liu Yongtao , Wang Youzhu , Cao Zhixiang , Gao Youhe
Published: July 2018

In 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 paragraph

DNA-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

From 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

Over 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.
Identification of Novel Genes and Variations Associated to Glycolytic Potential Based on Pig Model
Authors: Wu Wangjun , Zhang Zengkai , Chao Zhe , Li Bojiang , Ning Caibo , Jiang Aiwen , Dong Chao , Wei Wei , Chen Jie , Liu Honglin
Published: July 2018

In livestock, glycolytic potential (GP) is a critical indicator for evaluating the meat quality. To date, two major genes protein kinase AMP-activated γ3 non-catalytic subunit gene (PRKAG3) and phosphorylase kinase catalytic subunit gamma 1(PHKG1), and corresponding cause mutations influencing GP have been confirmed in pigs. Therefore, the aim of this study to identify the novel candidate genes and variations related to GP-related traits using a four-hybrid pig model [Pietrain (P)× Duroc (D)] ×[(Landrace) ×(Yorkshire)]. We totally constructed six RNA-seq libraries using longissimus dorsi (LD) muscles, and each library contained two higher GP (H) or two lower GP (L) individuals. A total of 525, 698 and 135 differentially expressed genes (DEGs) were identified between H11 vs L11, H9 vs L9, and H5 vs L5 groups using PossionDis method, respectively. Notably, we found 97 non-redundant DEGs were mapped to GP related QTLs from three paired comparison groups. Moreover, 69 DEGs were identified between H (H11, H9 and H5) and L (L11, L9 and L5) groups using NOIseq method. Additionally, 1,076 potential specific SNPs were figured out between H and L groups, and approximately 40 large Indels with a length ≥ 5bp were identified in each sequencing library. In conclusion, our data provide foundation for further confirming the key genes and the functional mutations affecting GP-related traits in pigs, and also pave the way for elucidating the underling molecular regulatory mechanisms of glycogen metabolism in future study. Moreover, this study might provide valuable information for study on human glycogen storage diseases.
Interactive innovative tool for early diagnosis of global pre-crisis processes (based on measurement and assessment of the virtual intellectual capital)
Authors: Vahanyan Grigori Arshaluys , Vahanyan Hovhannes , Ghazaryan Margarita
Published: July 2018

Purpose

The purpose of this paper is to present the great importance and impact of the virtual intellectual capital (VIC) in the frameworks of digital economics, e-governance and business, e-trading and commerce, virtual organizations and enterprises, and information communication technologies development (based on the comparative case studies of the world, Russian and Armenian economics). These conditions increase the importance of the measurement and assessment of the VIC.

Design/methodology/approach

The research findings are obtained through the method of comparative analysis of the complex models of the VIC. The features are studied through measuring and assessing the VIC parameters of virtual representations on the internet. The data are complemented through virtual cluster analysis, a multidimensional statistical procedure that collects data containing information on facility selection. Three cluster groups are used in the study: the clusters of the TNCs and their virtual representations; the clusters of the network of the leading innovation centers and their virtual representations; and the clusters of the leading universities and their virtual representations.

Findings

The paper establishes the research findings of the growth forecasts of the IC clusters in the world, Russian and Armenian economic processes. This is extremely important to ensuring sustainable growth of the country’s competitiveness, economy and general welfare. The paper proposes a new model of the virtual national or transnational intellectual capital (VNTIC). The VNTIC model presents three general components: virtual representations of universities, innovation center networks and transnational corporations in global networks. The research findings show that the interactive innovative tools (IIT) can be used for early diagnosis of the world economic and financial processes.

Originality/value

The authors developed for the first time the IIT for measuring and assessing the three intellectual capital components. The paper presents a new approach and a more reliable tool for short-term forecasting at global and national levels based on QI ranking of the VIC clusters of the commercial enterprises, universities and networks of innovation centers.
Emerging organizational parameters and their roles in implementation of organizational change
Authors: Aslam Usman , Muqadas Farwa , Imran Muhammad Kashif , Saboor Abdul
Published: July 2018

Purpose

The purpose of this paper is to investigate new emerging organizational parameters and their roles in successful change implementation. These organizational parameters are rarely investigated especially in the context of organizational change (OC) in private and public sector organizations.

Design/methodology/approach

In cumulative, 403 valid responses have been obtained randomly from public sector workers by using self-administered questionnaires.

Findings

The results reveal that knowledge sharing regarding incremental and radical changes can helpful for effective OC implementation. Findings highlight the significant role of emotional and social intelligence in managing resistance and bringing openness to change in these organizations. It is also found that social media has become an important emerging organizational parameter to foster effective communication and knowledge sharing during OC implementation. Apart from the direct effects, readiness to change has multiple effects coupled with emerging organizational parameters to implement change successfully.

Research limitations/implications

The results of the current study offer diversified implications for theory, practice and global society. The theoretical base is taken from the well-known theories of management (i.e. Lewin’s three-step model, field theory, intelligence theory, cost-effective theory, social exchange theory, social network theory and social penetration theory). Emerging organizational parameters that have a potential impact on effective change implementation are identified. The findings suggest that global organizations should have to initiate effective networking structure using social media applications and social intelligence skills to remain connected and get positive responses about change formulation and implementation decision.

Originality/value

A majority of studies have presented the research model on OC implementation in the context of developed countries, which form 30 percent of the world’s population, mostly the Americas and Europe. It is observed that a developing country, such as Pakistan, has a culture that is based on power distance, collectivism and more political influence as compared to developed countries. Triandis et al. (1980) argued that any theoretical contribution without considering the cultural aspect can lead to bias findings. There is limited research available in the world that is conducted to examine the interactive effects of readiness to change on the relationship between effective change implementation, knowledge sharing, intelligence and social media. These findings are useful to plan and execute OC using new emerging organizational parameters.
Workplace bullying across the globe: a cross-cultural comparison
Authors: Salin Denise , Cowan Renee , Adewumi Oluwakemi , Apospori Eleni , Bochantin Jaime , D’Cruz Premilla , Djurkovic Nikola , Durniat Katarzyna , Escartín Jordi , Guo Jing , Išik Idil , Koeszegi Sabine T. , McCormack Darcy , Monserrat Silvia Inés , Zedlacher Eva
Published: July 2018

Purpose

The purpose of this paper is to analyze cross-national and cross-cultural similarities and differences in perceptions and conceptualizations of workplace bullying among human resource professionals (HRPs). Particular emphasis was given to what kind of behaviors are considered as bullying in different countries and what criteria interviewees use to decide whether a particular behavior is bullying or not.

Design/methodology/approach

HRPs in 13 different countries/regions (n=199), spanning all continents and all GLOBE cultural clusters (House et al., 2004), were interviewed and a qualitative content analysis was carried out.

Findings

Whereas interviewees across the different countries largely saw personal harassment and physical intimidation as bullying, work-related negative acts and social exclusion were construed very differently in the different countries. Repetition, negative effects on the target, intention to harm, and lack of a business case were decision criteria typically used by interviewees across the globe – other criteria varied by country.

Practical implications

The results help HRPs working in multinational organizations understand different perceptions of negative acts.

Originality/value

The findings point to the importance of cultural factors, such as power distance and performance orientation, and other contextual factors, such as economy and legislation for understanding varying conceptualizations of bullying.
An empirical study of elder abuse in the state of Uttar Pradesh of India
Authors: Patel Avanish Bhai , Mishra Anindya J.
Published: July 2018

Purpose

Elder abuse is the matter of grave concern in recent times in India. Today, older people are facing the abusive behaviour such as maltreatment, mental and physical torture and heedless ignominy from the family and the society. The purpose of this paper is to examine the nature of elder abuse in Indian socio-cultural context and also focuses on the causes of elder abuse and abusers.

Design/methodology/approach

Mixed method design has been applied in this paper. The study has been conducted from October 2012-January 2013 on a sample of 220 older people living in both rural and urban areas of Lucknow, India. The data have been analysed through descriptive and narrative analysis.

Findings

The study finds that the emotional abuse is more common among the older people, which raises the feeling of insecurity, depression and isolation. The study also points out that the respect, honour, status and authority which were enjoyed by the elderly in the traditional society, have gradually started declining. Moreover, the study finds that the family members, do not provide proper food, clothing and medical facilities in rural areas.

Research limitations/implications

Since the sample of older respondents was small and focused on those living in a particular area of one state, the authors cannot generalise from this study to include the great diversity of experience and difference in perceptions among the older people even within a particular state. However, widespread and diverse types of accounts of elder abuse were reported even in these settings, which can help indicate areas for future research and policies.

Originality/value

This is an original paper, which is based on the experiences of older people living in rural-urban areas and discussed the elder abuse in socio-cultural context.
Internationalization process through an opportunity lens
Authors: Rezende Sérgio , Galdino Kátia , Lamont Bruce
Published: July 2018

Purpose

The purpose of this paper is to establish a conversation between international business and international entrepreneurship literatures by analyzing if and how international opportunities are related to the internationalization process of the firm.

Design/methodology/approach

This paper reports finding from a backward-looking longitudinal, qualitative, embedded case study of an internationalized Brazilian firm, covering all 13 foreign markets where the firm has operated over 18 years.

Findings

Modal shifts within foreign markets were rare. Over time, the firm learned how to refine, rather than change, the servicing modes within each foreign market; it also learned how to better develop internal and exploitative opportunities, manage a portfolio of servicing modes across foreign markets, and use more complex mode servicing packages. Overall, international opportunities and the internationalization process of the firm were inextricably connected.

Research limitations/implications

The authors acknowledge limitations related to the statistical generalizability of the research method and suggest that statistical validation is needed as the research on opportunities and the internationalization process of the firm progresses.

Practical implications

Internationalizing firms should carefully consider the choice of entry mode in foreign markets. They should also understand that learning is not necessarily associated with change.

Originality/value

The authors show that the internationalization process of a traditional firm can be analyzed through an opportunity lens. This means associating characteristics of international opportunities with mode continuation and modal shifts in all foreign markets where the firm operates.