bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the deprivation gap in stillbirths and neonatal deaths by cause of death: a national population-based study
Authors: Best Kate E , Seaton Sarah E , Draper Elizabeth S , Field David J , Kurinczuk Jennifer J , Manktelow Bradley N , Smith Lucy K
Published: March 2019

Objective

To investigate socioeconomic inequalities in cause-specific stillbirth and neonatal mortality to identify key areas of focus for future intervention strategies to achieve government ambitions to reduce mortality rates.

Design

Retrospective cohort study.

Setting

England, Wales, Scotland and the UK Crown Dependencies.

Participants

All singleton births between 1 January 2014 and 31 December 2015 at ≥24 weeks’ gestation.

Main outcome measure

Cause-specific stillbirth or neonatal death (0–27 days after birth) per 10 000 births by deprivation quintile.

Results

Data on 5694 stillbirths (38.1 per 10 000 total births) and 2368 neonatal deaths (15.9 per 10 000 live births) were obtained from Mothers and Babies: Reducing Risk through Audits and Confidential Enquiries across the UK (MBRRACE-UK). Women from the most deprived areas were 1.68 (95% CI 1.56 to 1.81) times more likely to experience a stillbirth and 1.67 (95% CI 1.48 to 1.87) times more likely to experience a neonatal death than those from the least deprived areas, equating to an excess of 690 stillbirths and 231 neonatal deaths per year associated with deprivation. Small for gestational age (SGA) unexplained antepartum stillbirth was the greatest contributor to excess stillbirths accounting for 33% of the deprivation gap in stillbirths. Congenital anomalies accounted for the majority (59%) of the deprivation gap in neonatal deaths, followed by preterm birth not SGA (24–27 weeks, 27%).

Conclusions

Cause-specific mortality rates at a national level allow identification of key areas of focus for future intervention strategies to reduce mortality. Despite a reduction in the deprivation gap for stillbirths and neonatal deaths, public health interventions should primarily focus on socioeconomic determinants of SGA stillbirth and congenital anomalies.
Measuring 21 low-value hospital procedures: claims analysis of Australian private health insurance data (2010–2014)
Authors: Chalmers Kelsey , Pearson Sallie-Anne , Badgery-Parker Tim , Brett Jonathan , Scott Ian A , Elshaug Adam G
Published: March 2019

Objective

To examine the prevalence, costs and trends (2010–2014) for 21 low-value inpatient procedures in a privately insured Australian patient cohort.

Design

We developed indicators for 21 low-value procedures from evidence-based lists such as Choosing Wisely, and applied them to a claims data set of hospital admissions. We used narrow and broad indicators where multiple low-value procedure definitions exist.

Setting and participants

A cohort of 376 354 patients who claimed for an inpatient service from any of 13 insurance funds in calendar years 2010–2014; approximately 7% of the privately insured Australian population.

Main outcome measures

Counts and proportions of low-value procedures in 2014, and relative change between 2010 and 2014. We also report both the Medicare (Australian government) and the private insurance financial contributions to these low-value admissions.

Results

Of the 14 662 patients with admissions for at least 1 of the 21 procedures in 2014, 20.8%–32.0% were low-value using the narrow and broad indicators, respectively. Of the 21 procedures, admissions for knee arthroscopy were highest in both the volume and the proportion that were low-value (1607–2956; 44.4%–81.7%).

Seven low-value procedures decreased in use between 2010 and 2014, while admissions for low-value percutaneous coronary interventions and inpatient intravitreal injections increased (51% and 8%, respectively).

For this sample, we estimated 2014 Medicare contributions for admissions with low-value procedures to be between $A1.8 and $A2.9 million, and total charges between $A12.4 and $A22.7 million.

Conclusions

The Australian federal government is currently reviewing low-value healthcare covered by Medicare and private health insurers. Estimates from this study can provide crucial baseline data and inform design and assessment of policy strategies within the Australian private healthcare sector aimed at curtailing the high volume and/or proportions of low-value procedures.
Protocol for a systematic review and qualitative synthesis of information quality frameworks in eHealth
Authors: Fadahunsi Kayode Philip , Akinlua James Tosin , O’Connor Siobhan , Wark Petra A , Gallagher Joseph , Carroll Christopher , Majeed Azeem , O’Donoghue John
Published: March 2019

Introduction

Electronic health (eHealth) applications have become a very large repository of health information which informs critical decisions relating to the diagnosis, treatment and prognosis of patients. Poor information quality (IQ) within eHealth may compromise patient safety. Evaluation of IQ in eHealth is therefore necessary to promote patient safety. An IQ framework specifies what aspects of information to assess and how to conduct the assessment. This systematic review aims to identify dimensions within existing IQ frameworks in eHealth and develop a new IQ framework for the assessment of eHealth.

Method and analysis

We will search Embase, Medline, PubMed, Cumulative Index to Nursing and Allied Health Literature, Maternity and Infant Care, PsycINFO (American Psychological Association), Global Health, Scopus, ProQuest Dissertations and Theses Global, Health Management Information Consortium and reference lists of relevant publications for articles published in English until November 2018. Studies will be selected by two independent reviewers based on prespecified eligibility criteria. Two reviewers will independently extract data in each eligible study using a prepiloted Microsoft Excel data extraction form. Thematic synthesis will be employed to define IQ dimensions and develop a new IQ framework for eHealth.

Ethics and dissemination

Ethical approval is not required for this systematic review as primary data will not be collected. The result of the review will be disseminated through publication in an academic journal and scientific conferences.

PROSPERO registration number

CRD42018097142.
Patterns of statin utilisation for new users and market dynamics in South Korea: a 13-year retrospective cohort study
Authors: Son Kyung-Bok , Bae SeungJin
Published: March 2019

Objective

This study analysed utilisation of statins for new statin users and assessed market dynamics of statins in South Korea.

Design

This study is a retrospective cohort study.

Setting

The yearly claims data for statins were retrieved from the National Health Insurance Service-National Sample Cohort.

Main outcome measure

We are interested in new statin users during 2003–2015 in Korea. Information on prescribed statins, including intensity of statins and entry of new and follow-on statins in the market, and healthcare institutions that prescribed the statins were also collected. In time series analysis, we estimated the effect of introduction of generics in the market, specifically for newly prescribed statin users.

Results

This 13-year longitudinal study of a sample cohort provided by the National Health Insurance Service found that the incidence of new statin user increase from 838.1/100 000 persons in 2003 to 1626.9/100 000 persons in 2015. Most new users were initiated on a monotherapy that was prescribed at primary healthcare institutions. However, the statin market for new users were quite dynamic in Korea. First, the most commonly prescribed statin changed several times during the study period. Second, the use of moderate-intensity statins increased from 57% in 2003 to 92% in 2015. In line with this result, we could not observe substantial differences in prescription of statins in groups having selected diseases history. Lastly, we found market invasion or switch of statins among new statin users, specifically at primary healthcare institutions.

Conclusion

Similar to other countries, the incidence of new statin users has been increased in Korea. However, the statin market in Korea is quite dynamic compared with other countries. Interestingly, discounted price of originals after the introduction of generics immediately expand markets or substitute the market particularly in primary healthcare institutions in Korea.
Mechanisms of reversal of adriamycin resistance in human ovarian carcinoma cell line by ultrasound
Authors: Yu T. , Huang X. , Hu K. , Bai J. , Wang Z.
Published: March 2019

The aim of this study was to investigate the reversal of adriamycin resistance in human ovarian cancer cells by ultrasound exposure from perspectives of apoptosis andmdr1gene. Apoptosis was determined by flow cytometry andmdr1level by reverse transcription-polymerase chain reaction (RT-PCR). Apoptosis indexes were improved in groups in which ultrasound exposures were applied. RT-PCR did not support that insonation-decreasedmdr1level. These findings suggested that the ultrasound-enhanced therapeutic efficacy was not mediated via modulating gene expression, and ultrasound maybe lowered thresholds for apoptosis and oncosis in chemoresistant ovarian cancer cells.
Vulvar soft tissue tumors
Authors: Behranwala K. A. , Latifaj B. , Blake P. , Barton D. P. J. , Shepherd J. H. , Thomas J. M.
Published: March 2019

Objective

To report our incidence of soft tissue tumors at this site and to discuss various prognostic factors.

Methods

All patients with a diagnosis of vulvar soft tissue neoplasms were studied from a prospective database at the Royal Marsden Hospital between January 1985 and July 2001.

Results

Seventeen vulvar soft tissue neoplasms (11 malignant and six benign) were treated during this period. Leiomyosarcoma (n= 5) and aggressive angiomyxoma (n= 4) were the most frequent histologic types. According to the grade, there were four G3, three G2, three G1 and could not be assessed in one patient. Local recurrence occurred in six patients with sarcoma (three with high grade and one each with intermediate, low, and undetermined grade). In this group, five patients had negative microscopic margins and one patient had positive microscopic margins on excision. All three women with low-grade sarcomas are alive without evidence of disease. Three patients with aggressive angiomyxoma also had a local recurrence.

Conclusion

Surgical excision is the primary treatment where possible. The grade of the tumor is an important predictor for local recurrence and outcome. Aggressive angiomyxoma is a local problem. Leiomyosarcoma and aggressive angiomyxoma are the most frequent histologic types.
Unique use of botulinum toxin to decrease adductor tone and allow surgical excision of vulvar carcinoma
Authors: Guo Y. , Shin K.
Published: March 2019

Here, we present the case of an 86-year-old woman with vulvar carcinoma requiring surgical resection and with Parkinson's disease with severe spasticity and contractures of the lower extremities. Because of the patient's severe contractures and spasticity (her knees could only be separated by 2 cm with sustained abducting force), surgical positioning and access to the vulva were impossible. The patient was admitted, intending to undergo surgery after injection with botulinum toxin (BTX) to hip adductors and intensive physical therapy. After confirmed healed hip arthroplasty, the patient underwent BTX injection (400 U) to her bilateral adductor brevis, adductor longus, adductor magnus, and semimembranosus and semitendinosus muscles on day 2 of her hospital stay. On day 3, a physical therapist began a twice-a-day stretching program. An adjustable abduction brace was custom-made to provide sustained stretching. On day 9, the patient underwent wide local excision of vulvar carcinoma with the abductor brace in place. The patient tolerated the surgery well and was discharged home on day 11 with continuous physical therapy. Upon discharge, the distance between the patient's knees was 14 cm. This unique case demonstrated a new indication for BTX treatment in the preoperative setting to allow surgical positioning and access.
Inability of immunohistochemistry to predict clinical outcomes of endometrial cancer patients
Authors: Gossett D. R. , Alo P. , Bristow R. E. , Galati M. , Kyshtoobayeva A. , Fruehauf J. , Montz F. J.
Published: March 2019

Introduction

Despite optimal surgery, some patients with early endometrial carcinoma develop recurrence and die of disease. A number of immunohistochemical (IHC)-identified cell products (markers) have been proposed as predictors of recurrence. This study characterizes a large series of endometrial carcinomas with previously described markers as well as markers that have not been investigated in endometrial carcinoma.

Patients and methods

Women who had undergone surgery for endometrial carcinoma were identified and specimens accessed. Tissue blocks were evaluated for ten IHC markers. Results were correlated with last known clinical status.

Results

Mean follow-up was 43 months; complete data were available on 117 patients. Two women died of other causes; of the remaining 115, eight died of disease and six were alive with recurrence at last follow-up (12%). Vascular endothelial growth factor staining independently predicted recurrence and death. However, in multivariate analyses, only FIGO stage predicted outcome.

Discussion

Our goal was to identify markers to predict which women with endometrial carcinoma were likely to have disease recurrence. We evaluated cell-cycle regulatory proteins, growth factors, hormone receptors, and angiogenic factors, but did not identify any marker that independently predicted outcome in multivariate analysis. This may reflect the few negative outcomes in our population.
The role of neurosurgery in the treatment of cerebral metastases from choriocarcinoma: a report of two cases
Authors: Semple P. L. , Denny L. , Coughlan M. , Soeters R. , Van Wijk L.
Published: March 2019

Cerebral metastases from choriocarcinoma are a poor prognostic indicator of outcome in both the World Health Organization and FIGO classification systems. However, with the increased experience with chemotherapy and radiotherapy the prognosis of this group of patients has improved substantially. Neurosurgery remains an option for selected patients. We present two patients who underwent craniotomy as part of their management of choriocarcinoma, and review the role of neurosurgery in the treatment of gestational trophoblastic disease.
Relationship between children’s cognitions and later educational progress in rural South Africa: a longitudinal study
Authors: Cortina Melissa , Jack Helen E , Pearson Rebecca , Kahn Kathleen , Tollman Stephen , Hlungwani Tintswalo , Twine Rhian , Stein Alan , Fazel Mina
Published: March 2019

Background

Children in low-income and middle-income countries (LMICs) who remain in school have better health and employment outcomes. South Africa, like many LMICs, has a secondary school completion rate under 50%, leaving room for improvement if we can identify factors that affect educational attainment. This is the first longitudinal study to examine the effects of childhood mental health and cognitions on educational outcomes in LMIC.

Methods

Using the Strengths and Difficulties Questionnaire (SDQ) and Cognitive Triad Inventory for Children (CTI-C), we assessed the psychological functioning and cognition of children aged 10–12 in rural South Africa. We linked that data with measures of educational progress collected 5 years later and examined associations between educational progress and (1) behavioural and emotional problems and (2) cognitive interpretations, adjusting for possible confounders.

Results

Educational data were available for 443 individuals. 92% (n=408) of individuals had advanced three or fewer grades in 7 years. Having more positive cognitions (CTIC-C) was positively associated with progressing at least three grade levels (adjusted OR 1.43, 95% CI 1.14 to 1.79). There was no evidence for an association between emotional and behavioural problems (SDQ) and educational progress (OR 0.90, 95% CI 0.72 to 1.11).

Conclusion

If children in LMICs can develop more positive perspectives, they may be able to stay in school longer. Cognitions can be modified, and future studies should test interventions that work to improve cognition in childhood, guided, for example, by principles of cognitive–behavioural therapy.
Need for rescue treatment and its implication: stent retriever versus contact aspiration thrombectomy
Authors: Kang Dong-Hun , Kim Jin Woo , Kim Byung Moon , Heo Ji Hoe , Nam Hyo Suk , Kim Young Dae , Hwang Yang-Ha , Kim Yong-Won , Baek Jang-Hyun , Yoo Joonsang , Kim Dong Joon , Jeon Pyoung , Bang Oh Young , Baik Seung Kug , Suh Sang Hyun , Lee Kyung-Yul , Kwak Hyo Sung , Roh Hong Gee , Lee Young-Jun , Kim Sang Heum , Ryu Chang-Woo , Ihn Yon-Kwon , Kim Byungjun , Jeon Hong Jun , Byun Jun Soo , Suh Sangil , Park Jeong Jin , Roh Jieun
Published: March 2019

Backgroud

The need for rescue treatment (RT) may differ depending on first-line modality (stent retriever (SR) or contact aspiration (CA)) in endovascular thrombectomy (EVT). We aimed to investigate whether the type of first-line modality in EVT was associated with the need for RT.

Methods

We identified all patients who underwent EVT for anterior circulation large-vessel occlusion from prospectively maintained registries of 17 stroke centers. Patients were dichotomized into SR-first and CA-first. RT involved switching to the other device, balloon angioplasty, permanent stenting, thrombolytics, glycoprotein IIb/IIIa antagonist, or any combination of these. We compared clinical characteristics, procedural details, and final recanalization rate between the two groups and assessed whether first-line modality type was associated with RT requirement and if this affected clinical outcome.

Results

A total of 955 patients underwent EVT using either SR-first (n=526) or CA-first (n=429). No difference occurred in the final recanalization rate between SR-first (82.1%) and CA-first (80.2%). However, recanalization with the first-line modality alone and first-pass recanalization rates were significantly higher in SR-first than in CA-first. CA-first had more device passes and higher RT rate. The RT group had significantly longer puncture-to-recanalization time (93±48 min versus 53±28 min). After adjustment, CA-first remained associated with RT (OR, 1.367; 95% CI, 1.019 to 1.834). RT was negatively associated with good outcome (OR, 0.597; 95% CI, 0.410 to 0.870).

Conclusion

CA was associated with requiring RT, while recanalization with first-line modality alone and first-pass recanalization rates were higher with SR. RT was negatively associated with good outcome.
Effects of inbreeding depression on seed production in Scots pine (Pinus sylvestris)
Authors: Mullin Tim J. , Persson Torgny , Abrahamsson Sara , Andersson Gull Bengt
Published: March 2019

Like other outcrossing species, Scots pine (Pinus sylvestris L.) is thought to carry a “genetic load” of deleterious recessive alleles. When these alleles occur as homozygotes in inbred progeny, their expression can give rise to “inbreeding depression”. Although this phenomenon has been studied in several conifer species through selfing, few studies have quantified inbreeding depression in crosses with lower levels of relatedness between parents. We report here on the generation of a set of F3 study materials in Scots pine in which 142 families arose from a mating design among 49 F2 parents, representing nine levels of expected inbreeding coefficients between 0.0 and 0.5, and repeated over two consecutive seasons. Whereas the numbers of extractable seeds were unaffected by inbreeding, the proportion with fully developed embryos was strongly affected. This was expressed as inbreeding depression in the yield of full seeds per cone but not in their mean mass. Levels of germination of these full seeds were affected by inbreeding, but the depression was rather small and only weakly significant. The roles of pollen competition and polyembryony in mitigating the impact of inbreeding depression are discussed. The materials have been outplanted for future assessment of inbreeding depression on growth and survival.
MicroRNAs in brain development and cerebrovascular pathophysiology
Authors: Ma Qingyi , Zhang Lubo , Pearce William J.
Published: March 2019

MicroRNAs (miRNAs) are a class of highly conserved non-coding RNAs with 21–25 nucleotides in length and play an important role in regulating gene expression at the posttranscriptional level via base-paring with complementary sequences of the 3′-untranslated region of the target gene mRNA, leading to either transcript degradation or translation inhibition. Brain-enriched miRNAs act as versatile regulators of brain development and function, including neural lineage and subtype determination, neurogenesis, synapse formation and plasticity, neural stem cell proliferation and differentiation, and responses to insults. Herein, we summarize the current knowledge regarding the role of miRNAs in brain development and cerebrovascular pathophysiology. We review recent progress of the miRNA-based mechanisms in neuronal and cerebrovascular development as well as their role in hypoxic-ischemic brain injury. These findings hold great promise, not just for deeper understanding of basic brain biology but also for building new therapeutic strategies for prevention and treatment of pathologies such as cerebral ischemia.
Elevated myonuclear density during skeletal muscle hypertrophy in response to training is reversed during detraining
Authors: Dungan Cory M. , Murach Kevin A. , Frick Kaitlyn K. , Jones Savannah R. , Crow Samuel E. , Englund Davis A. , Vechetti Ivan J. , Figueiredo Vandre C. , Levitan Bryana M. , Satin Jonathan , McCarthy John J. , Peterson Charlotte A.
Published: March 2019

Myonuclei gained during exercise-induced skeletal muscle hypertrophy may be long-lasting and could facilitate future muscle adaptability after deconditioning, a concept colloquially termed “muscle memory.” The evidence for this is limited, mostly due to the lack of a murine exercise-training paradigm that is nonsurgical and reversible. To address this limitation, we developed a novel progressive weighted-wheel-running (PoWeR) model of murine exercise training to test whether myonuclei gained during exercise persist after detraining. We hypothesized that myonuclei acquired during training-induced hypertrophy would remain following loss of muscle mass with detraining. Singly housed female C57BL/6J mice performed 8 wk of PoWeR, while another group performed 8 wk of PoWeR followed by 12 wk of detraining. Age-matched sedentary cage-dwelling mice served as untrained controls. Eight weeks of PoWeR yielded significant plantaris muscle fiber hypertrophy, a shift to a more oxidative phenotype, and greater myonuclear density than untrained mice. After 12 wk of detraining, the plantaris muscle returned to an untrained phenotype with fewer myonuclei. A finding of fewer myonuclei simultaneously with plantaris deconditioning argues against a muscle memory mechanism mediated by elevated myonuclear density in primarily fast-twitch muscle. PoWeR is a novel, practical, and easy-to-deploy approach for eliciting robust hypertrophy in mice, and our findings can inform future research on the mechanisms underlying skeletal muscle adaptive potential and muscle memory.
Physiological cAMP-elevating secretagogues differentially regulate fluid and protein secretions in mouse submandibular and sublingual glands
Authors: Kondo Yusuke , Melvin James E. , Catalan Marcelo A.
Published: March 2019

The mechanisms underlying the functional differences in sympathetic and parasympathetic regulation of the major salivary glands have received little attention. The acute effects of parasympathetic muscarinic (carbachol)-dependent and combined parasympathetic-dependent plus cAMP-dependent pathways on fluid secretion rates, ion composition, and protein content were assessed using a newly developed ex vivo preparation that allows the simultaneous perfusion of the mouse submandibular (SMGs) and sublingual glands (SLGs). Our results confirm that the muscarinic-dependent pathway accounts for the bulk of salivation in SMGs and SLGs, whereas costimulation with a cAMP-increasing agent (forskolin, isoproterenol, or vasoactive intestinal peptide) did not increase the flow rate. Costimulation with carbachol plus the β-adrenergic agonist isoproterenol decreased the concentration of NaCl and produced a substantial increase in the protein and Ca2+ content of SMG but not SLG saliva, consistent with a sparse sympathetic innervation of the SLGs. On the other hand, forskolin, which bypasses receptors to increase intracellular cAMP by directly activating the enzyme adenylate cyclase, enhanced the secretion of protein and Ca2+ by both the SMGs and SLGs. In contrast, isoproterenol and vasoactive intestinal peptide specifically stimulated protein secretion in SMG and SLG salivas, respectively. In summary, cAMP-dependent signaling does not play a major role in the stimulation of fluid secretion in SMGs and SLGs, whereas each cAMP-increasing agonist behaves differently in a gland-specific manner suggesting differential expression of G protein-coupled receptors in the epithelial cells of SMGs and SLGs.
Calcium-sensing receptor activation attenuates collagen expression in renal proximal tubular epithelial cells
Authors: Wu Min , Feng Ye , Ye Guo-Xin , Han Yu-Chen , Wang Si-Si , Ni Hai-Feng , Wang Feng-Mei , Gao Min , Lv Lin-Li , Liu Bi-Cheng
Published: March 2019

316: F1006–F1015, 2019. First published March 6, 2019; doi: 10.1152/ajprenal.00413.2018 .—Experimental studies have shown that pharmacological activation of calcium-sensing receptor (CaSR) attenuates renal fibrosis in some animal models beyond modification of bone and mineral homeostasis; however, its underlying mechanisms remain largely unknown. Since excessive collagen deposition is the key feature of fibrosis, the present study aimed to examine whether CaSR was involved in the regulation of collagen expression in rats with adenine diet-induced renal fibrosis and in profibrotic transforming growth factor (TGF)-β1-treated renal proximal tubular epithelial cells (PTECs). The results showed that the CaSR agonist cinacalcet significantly attenuated renal collagen accumulation and tubular injury in adenine diet-fed rats. Additionally, the in vitro experiment showed that profibrotic TGF-β1 significantly increased the expression of collagen and decreased CaSR expression at the mRNA and protein levels in a concentration- and time-dependent manner. Furthermore, the CaSR CRISPR activation plasmid and cinacalcet partially abrogated the upregulation of collagen induced by TGF-β1 treatment. Blockade of CaSR by the CRISPR/Cas9 KO plasmid or the pharmacological antagonist Calhex231 further enhanced TGF-β1-induced collagen expression. Mechanistic experiments found that Smad2 phosphorylation and Snail expression were markedly increased in PTECs treated with TGF-β1, whereas the CaSR CRISPR activation plasmid and cinacalcet substantially suppressed this induction. In summary, this study provides evidence for a direct renal tubular epithelial protective effect of CaSR activation in renal fibrosis, possibly through suppression of collagen expression in PTECs.
Transcriptome-proteome integration of archival human renal cell carcinoma biopsies enables identification of molecular mechanisms
Authors: Koch Even , Finne Kenneth , Eikrem Øystein , Landolt Lea , Beisland Christian , Leh Sabine , Delaleu Nicolas , Granly Magnus , Vikse Bjørn Egil , Osman Tarig , Scherer Andreas , Marti Hans-Peter
Published: March 2019

Renal cell cancer is among the most common forms of cancer in humans, with around 35,000 deaths attributed to kidney carcinoma in the European Union in 2012 alone. Clear cell renal cell carcinoma (ccRCC) represents the most common form of kidney cancer and the most lethal of all genitourinary cancers. Here, we apply omics technologies to archival core biopsies to investigate the biology underlying ccRCC. Knowledge of these underlying processes should be useful for the discovery and/or confirmation of novel therapeutic approaches and ccRCC biomarker development. From partial or full nephrectomies of 11 patients, paired core biopsies of ccRCC-affected tissue and adjacent (“peritumorous”) nontumor tissue were both sampled and subjected to proteomics analyses. We combined proteomics results with our published mRNA sequencing data from the same patients and with published miRNA sequencing data from an overlapping patient cohort from our institution. Statistical analysis and pathway analysis were performed with JMP Genomics and Ingenuity Pathway Analysis (IPA), respectively. Proteomics analysis confirmed the involvement of metabolism and oxidative stress-related pathways in ccRCC, whereas the most affected pathways in the mRNA sequencing data were related to the immune system. Unlike proteomics or mRNA sequencing alone, a combinatorial cross-omics pathway analysis approach captured a broad spectrum of biological processes underlying ccRCC, such as mitochondrial damage, repression of apoptosis, and immune system pathways. Sirtuins, immunoproteasome genes, and CD74 are proposed as potential targets for the treatment of ccRCC.
Heart-kidney interactions: mechanistic insights from animal models
Authors: Liu Shan
Published: March 2019

Pathological changes in the heart or kidney can instigate the release of a cascade of cardiorenal mediators that promote injury in the other organ. Combined dysfunction of heart and kidney is referred to as cardiorenal syndrome (CRS) and has gained considerable attention. CRS has been classified into five distinct entities, each with different major pathophysiological changes. Despite the magnitude of the public health problem of CRS, the underlying mechanisms are incompletely understood, and effective intervention is unavailable. Animal models have allowed us to discover pathogenic molecular changes to clarify the pathophysiological mechanisms responsible for heart-kidney interactions and to enable more accurate risk stratification and effective intervention. Here, this article focuses on the use of currently available animal models to elucidate mechanistic insights in the clinical cardiorenal phenotype arising from primary cardiac injury, primary renal disease with special emphasis of chronic kidney disease-specific risk factors, and simultaneous cardiorenal/renocardiac dysfunction. The development of novel animal models that recapitulate more closely the cardiorenal phenotype in a clinical scenario and discover the molecular basis of this condition will be of great benefit.
On the reflex mechanisms of cervical transcutaneous spinal cord stimulation in human subjects
Authors: Milosevic Matija , Masugi Yohei , Sasaki Atsushi , Sayenko Dimitry G. , Nakazawa Kimitaka
Published: March 2019

Transcutaneous and epidural electrical spinal cord stimulation techniques are becoming more valuable as electrophysiological and clinical tools. Recently, remarkable recovery of the upper limb sensorimotor function during cervical spinal stimulation was demonstrated. In the present study, we sought to elucidate the neural mechanisms underlying the effects of transcutaneous spinal cord stimulation (tSCS) of the cervical spine. We hypothesized that cervical tSCS can be used to selectively activate the sensory route entering the spinal cord and transsynaptically converge on upper limb motor pools. To test this hypothesis, we applied cervical tSCS using paired stimuli (homosynaptic depression) and during passive muscle stretching of the wrist flexor (presynaptic inhibition via Ia afferents), voluntary hand muscle contraction (descending facilitation of motoneuron pool), and muscle-tendon vibration of the wrist (presynaptic inhibition via afferent occlusion). Our results demonstrate significant inhibition of the second evoked response during paired stimulus delivery, inhibition of responses during passive muscle stretching and muscle-tendon vibration, and facilitation during voluntary muscle contraction, which share similarities with responses evoked during lumbosacral tSCS. These results indicate that the route of the stimulation current transmission passes via afferents in the dorsal roots through the spinal cord to activate the motor pools and potentially interneuronal networks projecting to upper limb muscles. Using a novel stimulation paradigm, our study is the first to present evidence of the sensory neuronal pathway of the cervical tSCS propagation. Overall, our work demonstrates the utility and sensitivity of cervical tSCS to engage the sensory pathway projecting to the upper limbs.

NEW & NOTEWORTHY Despite therapeutic effects that have been demonstrated previously using noninvasive cervical spinal stimulation, it has been unclear whether, and to what degree, the stimulation can activate the sensory afferent system. Our study presents evidence that cervical transcutaneous spinal cord stimulation can engage the sensory pathways and transsynaptically converge on motor pools projecting to upper limb muscles, demonstrating the utility and sensitivity of cervical spinal stimulation for electrophysiological assessments and neurorehabilitation.
Strong Pullback Attractors of the Nonautonomous Suspension Bridge Equation with Variable Delay
Authors: Wang Suping , Ma Qiaozhen
Published: March 2019

In this paper, we consider the suspension bridge equation with variable delay. The long‐time dynamics of the solutions for the suspension equations without delay effects have been investigated by many authors. But there are few works on suspension equations with delay. Moreover there are not many studies on attractors for other systems with delay. Thus, we study the existence of pullback attractor for the suspension equation with variable delay by using the theory of attractors for multivalued dynamical systems.
Deceased Donor Renal Transplantation Combined with Bilateral Nephrectomy in a Patient with Tuberous Sclerosis and Renal Failure
Authors: Novotny R. , Chlupac J. , Marada T. , Bloudickova-Rajnochova S. , Vavrinova H. , Janousek L. , Fronek J.
Published: March 2019

Introduction. A 27-year-old female patient with known tuberous sclerosis complex (TSC), polycystic kidneys with multiple large bilateral angiomyolipomas, and failing renal functions with prehemodialysis values (urea: 19 mmol/L; creatinine: 317 μmol/L; CKD-EPI 0,27) was admitted to our department for pre-renal transplant evaluation. The patient was placed on the transplant waiting list as the living donor did not pass pretransplant workup and was subsequently contraindicated. Patient was placed on the “cadaverous kidney transplant waiting list”. Method. Computed tomography angiography revealed symptomatic PSA in the right kidney angiomyolipoma (AML). The patient underwent urgent transarterial embolisation of the PSA’s feeding vessel in the right kidney AML. Based on the “kidney transplant waiting list” order patient underwent a bilateral nephrectomy combined with transperitoneal renal allotransplantation of a cadaverous kidney graft through midline laparotomy, appendectomy, and cholecystectomy. Results. Postoperative period was complicated by delayed graft function caused by acute tubular necrosis requiring postoperative hemodialysis. The patient was discharged on the 17th postoperative day with a good renal graft function. Patient’s follow-up is currently 23 months with good graft function (urea: 9 mmol/L; creatinine: 100 μmol/L). Conclusion. Renal transplantation combined with radical nephrectomy provides a definitive treatment for TSC renal manifestations.
Mechanical Circulatory Support in Management of Cardiogenic Shock and Myxedema Coma
Authors: Arnautovic Jelena Z. , Connor-Schuler Randi , Ip Randy
Published: March 2019

The cardiovascular system is a major target of thyroid hormone action and the two systems are closely interlinked. It can be greatly impacted even with subtle alterations in thyroid function. Caution is needed when implementing thyroid hormone replacement in patients with severe hypothyroidism, especially in the setting of ischemic coronary artery disease. If not properly treated, myxedema may ensue. Given the high mortality of myxedema coma, supportive care may not always suffice and patients may require more invasive interventions. We present a challenging case of a patient with overt hypothyroidism with concurrent acute coronary syndrome which subsequently lead to myxedema coma and cardiogenic shock. A transcaval approach for the delivery of an Impella 5.0 (Abiomed Inc., Danvers, MA) was utilized in supporting this patient. To our knowledge, this is the first reported case that describes the use of a mechanical circulatory support in treating myxedema-induced cardiovascular collapse.
Centella asiaticaPrevents Increase of Hippocampal Tumor Necrosis Factor-αIndependently of Its Effect on Brain-Derived Neurotrophic Factor in Rat Model of Chronic Stress
Authors: Ar Rochmah Mawaddah , Harini Ika Murti , Septyaningtrias Dian Eurike , Sari Dwi Cahyani Ratna , Susilowati Rina
Published: March 2019

Centella asiaticaameliorates memory impairment and induces expression of hippocampal brain-derived neurotropic factor (BDNF) in chronically stressed rats. The relationship between the anti-inflammatory effect ofCentella asiaticaon hippocampal BDNF and the involvement of sirtuin-1, a BDNF expression regulator, in neuroprotective mechanisms ofCentella asiaticawarrants an investigation. We investigated the effect ofCentella asiaticaethanolic extracts (CA) on TNF-α, IL-10, and SIRT1 levels and whether these predicted BDNF expression in rat hippocampus after chronic stress. For the experiments, thirty male rats (Sprague Dawley) were divided into six groups: nonstressed-control, stressed-control, nonstressed +CA 300mg/kg/d, stressed +CA 150 mg/kg/d, stressed +CA 300 mg/kg/d, and stressed +CA 600 mg/kg/d. On day 28, rats were sacrificed and hippocampus was dissected out. Hippocampal TNF-α, IL-10, SIRT1, and BDNF were measured by enzyme-linked immunosorbent assay. Hippocampal TNF-αlevel was significantly higher in the stressed-control compared to nonstressed-control groups. Across all stress conditions, rats receiving the highest dose of CA had the lowest mean TNF-αand highest mean BDNF. There were no significant differences in IL-10 and SIRT1 levels between groups. Hippocampal TNF-αdid not predict hippocampal BDNF in a regression analysis. In conclusion, lower TNF-αand higher BDNF in the hippocampus support the hypothesis that these factors independently contribute toCentella asiatica’s neuroprotective effect in chronically stressed rats.
Effect of Abrasive Concentration on Impact Performance of Abrasive Water Jet Crushing Concrete
Authors: Liu Xiaohui , Tang Ping , Geng Qi , Wang Xuebin
Published: March 2019

It has been found that the impact performance of water jets can be changed by its properties, which include pressure, additive, and mode of jet. Thus, an abrasive water jet (AWJ) has been developed as a new method. However, there is little research on the effect of abrasive concentration on the impact performance of abrasive jets. Thus, the SPH method is used to establish an abrasive water jet crushing concrete model to study the effect of abrasive concentration on the impact force, concrete internal energy, abrasive particle distribution, crushing depth, and damage and crushing efficiencies under different concrete compressive strengths and abrasive densities. The results indicate that there is little effect of the abrasive concentration on the peak impact force under different compressive strengths and abrasive densities, while the mean impact force tends to increase linearly with the abrasive concentration. The internal energy of the concrete increases stepwise with the abrasive concentration under different compressive strengths and abrasive densities. The concentration of 10%∼20% is the rapid increasing stage. The crushing depth and damage efficiencies are all maximum at a concentration of 20% under different compressive strengths and abrasive densities. After the concrete was impacted by the water from the water jet, it is divided into rebounding particles and intrusive particles. The more the intrusive particles, the easier the concrete to be crushed and damaged.
Image Restoration by Second‐Order Total Generalized Variation and Wavelet Frame Regularization
Authors: Zhu Jianguang , Li Kai , Hao Binbin
Published: March 2019

It has been proved that total generalized variation (TGV) can better preserve edges while suppressing staircase effect. In this paper, we propose an effective hybrid regularization model based on second‐order TGV and wavelet frame. The proposed model inherits the advantages of TGV regularization and wavelet frame regularization, can eliminate staircase effect while protecting the sharp edge, and simultaneously has good capability of sparsely estimating the piecewise smooth functions. The alternative direction method of multiplier (ADMM) is employed to solve the new model. Numerical results show that our proposed model can preserve more details and get higher image visual quality than some current state‐of‐the‐art methods.
Megacolon due to Chronic Schistosomiasis: A Case Report and Review of Literature
Authors: Alzahrani Amer R. , Alawfi Homoud , Almeman Sara , Altayeb Thamer , Al-Dorzi Hasan M.
Published: March 2019

Although Schistosoma infection in humans commonly involves the intestines, megacolon is a rare finding. We report a 47-year-old patient who was found to have chronic megacolon. After failing conservative management, he underwent extended hemicolectomy with colorectal anastomosis. The colon pathology revealed chronic schistosomiasis and Schistosoma serology was positive.
Combination of DNN and Improved KNN for Indoor Location Fingerprinting
Authors: Dai Peng , Yang Yuan , Wang Manyi , Yan Ruqiang
Published: March 2019

Fingerprinting based on Wi-Fi Received Signal Strength Indicator (RSSI) has been widely studied in recent years for indoor localization. While current algorithms related to RSSI Fingerprinting show a much lower accuracy than multilateration based on time of arrival or the angle of arrival techniques, they highly depend on the number of access points (APs) and fingerprinting training phase. In this paper, we present an integrated method by combining the deep neural network (DNN) with improved K-Nearest Neighbor (KNN) algorithm for indoor location fingerprinting. The improved KNN is realized by boosting the weights on K-nearest neighbors according to the number of matching access points. This will overcome the limitation of the original KNN algorithm on ignoring the influence of the neighboring points, which directly affect localization accuracy. The DNN algorithm is first used to classify the Wi-Fi RSSI Fingerprinting dataset. Then these possible locations in a certain class are also classified by the improved KNN algorithm to determine the final position. The proposed method is validated inside a room within about 13⁎9 m2. To examine its performance, the presented method has been compared with some classical algorithms, i.e., the random forest (RF) based algorithm, the KNN based algorithm, the support vector machine (SVM) based algorithm, the decision tree (DT) based algorithm, etc. Our real-world experiment results indicate that the proposed method is less dependent on the dense of access points and indoor radio propagation interference. Furthermore, our method can provide some preliminary guidelines for the design of indoor Wi-Fi test bed.
A Unique Case of Complete Atrioventricular Block Rapidly Progressing to Diastolic and Systolic Dysfunction in Cardiac Sarcoidosis
Authors: Mbachi Chimezie U. , Ajiboye Oyintayo , Ezegwu Olisa , Mba Benjamin
Published: March 2019

Sarcoidosis is a multisystem granulomatous disease that most commonly affects the lungs but can affect other organs including the heart due to granuloma infiltration. Atrioventricular block is a common manifestation of cardiac sarcoidosis which can progress to sudden cardiac death. We report a case of cardiac sarcoidosis presenting as complete heart block, progressing to diastolic and systolic dysfunction without extracardiac manifestations early in the disease. This case stresses the importance of having a high index of suspicion for cardiac sarcoidosis in patients presenting with atrioventricular block of unknown etiology.
Adenosine A2A Receptor Mediates Inhibition of Synovitis and Osteoclastogenesis after Electroacupuncture in Rats with Collagen-Induced Arthritis
Authors: Du Zhong-heng , Zhang Chun-wu , Xie Wen-xia , Chen Yong , Cong Wen-jie , Wang Ze-dong , Wang En-pei , Wu Guang-yu , Ye Tian-shen
Published: March 2019

Background. This study was to investigate the role of adenosine A2A receptors (A2AR) in inhibiting the effect of electroacupuncture (EA) on osteoclastogenesis in collagen-induced arthritis (CIA).Methods. Wistar rats were divided into four groups: sham-control group, CIA-control group, CIA-EA group, and CIA-EA-SCH58261 (A2AR antagonist) group. We detected tumor necrosis factor-α(TNF-α), nuclear transcription factor-κB (NF-κB), receptor activator of NF-κB ligand (RANKL), protein kinase A (PKA), and extracellular regulatory protein kinase 1/2 (ERK1/2) in peripheral blood by ELISA. PKA, ERK1/2, and NF-κB in ankle joints were determined by western blotting. We evaluated the arthritis damage by histological examination and determined the number of osteoclasts by tartrate-resistant acid phosphatase (TRAP) staining.Results. EA treatment downregulated the expression of TNF-α, RANKL, PKA, ERK1/2, and NF-κB in peripheral blood but increased the levels of PKA and ERK1/2 in ankle joints. Importantly, EA treatment reduced bone erosion as evidenced by the histological findings and inhibited osteoclastogenesis as revealed by TRAP staining. All these effects of the EA treatment were reversed by combining EA treatment with the A2AR antagonist SCH58261.Conclusion. Our data suggest that EA treatment activated A2AR. The effects of the A2AR antagonist SCH58261 suggest that the inhibition of osteoclast formation, the inhibition of TNF-α, RANKL, and NF-κB expression, and the increase of ERK1/2 are all dependent on this EA-induced A2AR activation. It is therefore likely that these pathways with clearly defined roles in inflammation and bone erosion are at least partially involved in the mediation of the inhibition of synovitis and osteoclast formation induced by EA.
Exploring Chemical Basis of Toxicity Reduction for Processed Roots of Stellera chamaejasme L. Using Ultraperformance Liquid Chromatography–Triple Quadrupole Tandem Mass Spectrometry
Authors: Yang Wei , Ma Xiaoli , Wang Ludi , Wei Mengmeng , Wang Shuyao , Wu Siyang , Kang Chen , Li Yingfei
Published: March 2019

Some herbal medicines are treated with various processing methods to ensure their safe and effective use. However, chemical basis of toxicity reducing for most herbal medicines remains unclear. Stellera chamaejasme L., particularly the root (ruixianglangdu), is toxic. Thus, ruixianglangdu is commonly processed with vinegar or milk to reduce toxicity. Here, with help of multiple-ion monitoring (MIM)-based metabolomics, we comprehensively capture chemical information of ruixianglangdu. Then, 33 differential components between crude drugs and processed products were identified or tentatively characterized by multiple-ion monitoring–information dependent acquiring–enhanced product ion (MIM-IDA-EPI), whose level changed after being processed by vinegar or milk. It was found that flavonoids especially biflavonones could be the important chemical basis of toxicity reduction for processed ruixianglangdu. In addition, some coumarins and lignanoids could also play a role in reducing toxicity. It is believed that MIM-based metabolomics method was valuable for exploring chemical basis of toxicity reduction for processing. The data is critical to further study the mechanism of toxicity reducing for processed ruixianglangdu.