bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of lumbar extensor muscle strengthening and neuromuscular control retraining on disability in patients with chronic low back pain: a protocol for a randomised controlled trial
Authors: Farragher Joshua Brodie , Pranata Adrian , Williams Gavin , El-Ansary Doa , Parry Selina M , Kasza Jessica , Bryant Adam 
Published: August 2019

IntroductionChronic low back pain (CLBP) is the leading cause of disability worldwide. However, there is no consensus in the literature regarding optimal management. Exercise intervention is the most widely used treatment as it likely influences contributing factors such as physical and psychological. Literature evaluating the effects of exercise on CLBP is often generalised, non-specific and employs inconsistent outcome measures. Moreover, the mechanisms behind exercise-related improvements are poorly understood. Recently, research has emerged identifying associations between neuromuscular-biomechanical impairments and CLBP-related disability. This information can be used as the basis for more specific and, potentially more efficacious exercise interventions for CLBP patients.Methods and analysisNinety-four participants (including both males and females) with CLBP aged 18–65 who present for treatment to a Melbourne-based private physiotherapy practice will be recruited and randomised into one of two treatment groups. Following baseline assessment, participants will be randomly allocated to receive either: (i) strengthening exercises in combination with lumbar force accuracy training exercises or (ii) strengthening exercises alone. Participants will attend exercise sessions twice a week for 12 weeks, with assessments conducted at baseline, midway (ie, 6 weeks into the trial) and at trial completion. All exercise interventions will be supervised by a qualified physiotherapist trained in the intervention protocol. The primary outcome will be functional disability measured using the Oswestry Disability Index. Other psychosocial and mechanistic parameters will also be measured.Ethics and disseminationThis study was given approval by the University of Melbourne Behavioural and Social Sciences Human Ethics Sub-Committee on 8 August 2017, reference number 1 749 845. Results of the randomised controlled trial will be published in peer-reviewed journals.Trial registration numberACTRN12618000894291.
Causes of death in critically ill paediatric patients in Japan: a retrospective multicentre cohort study
Authors: Ishihara Tadashi , Tanaka Hiroshi 
Published: August 2019

ObjectivesThe primary objective is to clarify the clinical profiles of paediatric patients who died in intensive care units (ICUs) or paediatric intensive care units (PICUs), and the secondary objective is to ascertain the demographic differences between patients who died with and without chronic conditions.MethodsIn this retrospective multicentre cohort study, we collected data on paediatric death from the Japanese Registry of Pediatric Acute Care (JaRPAC) database. We included patients who were ≤16 years of age and had died in either a PICU or an ICU of a participating hospital between April 2014 and March 2017. The causes of death were compared between patients with and without chronic conditions.ResultsTwenty-three hospitals participated, and 6199 paediatric patients who were registered in the JaRPAC database were included. During the study period, 126 (2.1%) patients died (children without chronic illness, n=33; children with chronic illness, n=93). Twenty-five paediatric patients died due to an extrinsic disease, and there was a significant difference in extrinsic diseases between the two groups (children without chronic illness, 15 (45%); children with chronic illness, 10 (11%); p<0.01). Cardiovascular disease was the most common chronic condition (27/83, 29%). Eighty-three patients (85%) in the chronic group died due to an intrinsic disease, primarily congenital heart disease (14/93, 15%), followed by sepsis (13/93, 14%).ConclusionsThe majority of deaths were in children with a chronic condition. The major causes of death in children without a chronic illness were due to intrinsic factors such as cardiovascular and neuromuscular diseases, and the proportion of deaths due to extrinsic causes was higher in children without chronic illness.
Oral antibiotic use and risk of colorectal cancer in the United Kingdom, 1989–2012: a matched case–control study
Authors: Zhang Jiajia , Haines Charles , Watson Alastair J M , Hart Andrew R , Platt Mary Jane , Pardoll Drew M , Cosgrove Sara E , Gebo Kelly A , Sears Cynthia L 
Published: August 2019

BackgroundMicrobiome dysbiosis predisposes to colorectal cancer (CRC), but a population-based study of oral antibiotic exposure and risk patterns is lacking.ObjectiveTo assess the association between oral antibiotic use and CRC risk.DesignA matched case–control study (incident CRC cases and up to five matched controls) was performed using the Clinical Practice Research Datalink from 1989 to 2012.Results28 980 CRC cases and 137 077 controls were identified. Oral antibiotic use was associated with CRC risk, but effects differed by anatomical location. Antibiotic use increased the risk of colon cancer in a dose-dependent fashion (ptrend <0.001). The risk was observed after minimal use, and was greatest in the proximal colon and with antibiotics with anti-anaerobic activity. In contrast, an inverse association was detected between antibiotic use and rectal cancers (ptrend=0.003), particularly with length of antibiotic exposure >60 days (adjusted OR (aOR), 0.85, 95% CI 0.79 to 0.93) as compared with no antibiotic exposure. Penicillins, particularly ampicillin/amoxicillin increased the risk of colon cancer (aOR=1.09 (1.05 to 1.13)), whereas tetracyclines reduced the risk of rectal cancer (aOR=0.90 (0.84 to 0.97)). Significant interactions were detected between antibiotic use and tumour location (colon vs rectum, pinteraction<0.001; proximal colon versus distal colon, pinteraction=0.019). The antibiotic–cancer association was found for antibiotic exposure occurring >10 years before diagnosis (aOR=1.17 (1.06 to 1.31)).ConclusionOral antibiotic use is associated with an increased risk of colon cancer but a reduced risk of rectal cancer. This effect heterogeneity may suggest differences in gut microbiota and carcinogenesis mechanisms along the lower intestinal tract.
Bufalin, a Traditional Chinese Medicine Compound, Prevents Tumor Formation in Two Murine Models of Colorectal Cancer
Authors: Sun Xiao , Ng Tony T.H. , Sham Kathy W.Y. , Zhang Lin , Chan Matthew T.V. , Wu William K.K. , Cheng Christopher H.K. 
Published: August 2019

Abstract
Chemoprevention is cost-effective for colorectal cancer when targeted at intermediate- or high-risk populations. Bufalin is a cardiac glycoside extracted from the traditional Chinese medicine (TCM) “Chan Su,” which has been used as an anticancer agent. On the basis of the relative safety of bufalin, we investigated whether bufalin could act as a chemoprophylactic agent to prevent colon tumorigenesis in two murine models, namely colitis-associated colorectal cancer and Apc germline mutation-developed colorectal cancer. Our results revealed that long-term (12–16 weeks) administration of low-dose bufalin (0.5 mg/kg) effectively suppressed tumorigenesis in both colorectal cancer models, accompanied by attenuated epithelial cell proliferation (reduced bromodeoxyuridine incorporation, lower levels of cyclin A, cyclin D1, cyclin E, and cyclin-dependent kinases-2/4, and higher levels of p21 and p27) and promoted apoptosis (increased TUNEL positivity and caspase-3/9 cleavages, reduced levels of Bcl-2, Bcl-xL and survivin, and increased levels of Bax and Bak). Bufalin also suppressed the expression of proinflammatory mediators [reduced levels of cyclooxygenase-2, tumor TNFα, IL1β, IL6, C-X-C motif chemokine ligand (CXCL)-1, CXCL-2, and CXCL-5] in the colitis-associated colorectal cancer model. These effects were associated with the inhibition of oncogenic NF-κB and PI3K/Akt pathways. Our findings unveil a novel chemoprophylactic action of bufalin in colorectal cancer in vivo and provided efficacy data and mechanistic evidence for further clinical evaluation of this TCM compound for colorectal cancer chemoprevention in individuals at risk of colorectal cancer.
Cardiac α-Actin (
ACTC1
) Gene Mutation Causes Atrial-Septal Defects Associated With Late-Onset Dilated Cardiomyopathy
Authors: Frank Derk , Rangrez Ashraf Yusuf , Friedrich Corinna , Dittmann Sven , Stallmeyer Birgit , Yadav Pankaj , Bernt Alexander , Schulze-Bahr Ellen , Borlepawar Ankush , Zimmermann Wolfram-Hubertus , Peischard Stefan , Seebohm Guiscard , Linke Wolfgang A. , Baba Hideo A. , Krüger Marcus , Unger Andreas , Usinger Philip , Frey Norbert , Schulze-Bahr Eric 
Published: August 2019

Background:
Familial atrial septal defect (ASD) has previously been attributed primarily to mutations in cardiac transcription factors. Here, we report a large, multi-generational family (78 members) with ASD combined with a late-onset dilated cardiomyopathy and further characterize the consequences of mutant α-actin.

Methods:

We combined a genome-wide linkage analysis with cell biology, microscopy, and molecular biology tools to characterize a novel
ACTC1
(cardiac α-actin) mutation identified in association with ASD and late-onset dilated cardiomyopathy in a large, multi-generational family.

Results:

Using a genome-wide linkage analysis, the ASD disease locus was mapped to chromosome 15q14 harboring the
ACTC1
gene. In 15 affected family members, a heterozygous, nonsynonymous, and fully penetrant mutation (p. Gly247Asp) was identified in exon 5 of
ACTC1
that was absent in all healthy family members (n=63). In silico tools predicted deleterious consequences of this variant that was found absent in control databases. Ultrastructural analysis of myocardial tissue of one of the mutation carriers showed sarcomeric disarray, myofibrillar degeneration, and increased apoptosis, while cardiac proteomics revealed a significant increase in extracellular matrix proteins. Consistently, structural defects and increased apoptosis were also observed in neonatal rat ventricular cardiomyocytes overexpressing the mutant, but not native human ACTC1. Molecular dynamics studies and additional mechanistic analyses in cardiomyocytes confirmed actin polymerization/turnover defects, thereby affecting contractility.

Conclusions:
A combined phenotype of ASD and late-onset heart failure was caused by a heterozygous, nonsynonymous ACTC1 mutation. Mechanistically, we found a shared molecular mechanism of defective actin signaling and polymerization in both cardiac development and contractile function. Detection of ACTC1 mutations in patients with ASD may thus have further clinical implications with regard to monitoring for (late-onset) dilated cardiomyopathy.
Novel Role for Pleckstrin Homology‐Like Domain Family A, Member 3 in the Regulation of Pathological Cardiac Hypertrophy
Authors: Liu Jia , Liu Xiaoxiong , Hui Xuejun , Cai Lin , Li Xuebo , Yang Yang , Shu Shangzhi , Wang Fan , Xia Hao , Li Shuyan 
Published: August 2019

Background

Pleckstrin homology‐like domain family A, member 3 (
PHLDA
3), a crucial member of the
PHLDA
family, is involved in tumor suppression, kidney injury, liver injury, and glucose metabolism. However, the role of
PHLDA
3 in pathological cardiac hypertrophy and heart failure remains unclear.

Methods and Results

In the present study,
PHLDA
3 expression was downregulated in hypertrophic murine hearts and angiotensin
II
‐treated cardiomyocytes. Next, an in vitro study suggested, by using gain‐ and loss‐of‐function approaches, that
PHLDA
3 attenuates Ang
II
exposure‐induced cardiomyocyte hypertrophy. Consistent with the cell phenotype, disruption of
PHLDA
3 aggravated the effects of pressure overload‐induced pathological cardiac hypertrophy, fibrosis, and dysfunction. In contrast,
PHLDA
3 overexpression resulted in an attenuated hypertrophic phenotype. Molecular analysis revealed that
PHLDA
3 suppressed the activation of
AKT
‐
mTOR
‐
GSK
3β‐P70S6K signaling in response to hypertrophic stress, and the blockage of
AKT
activation rescued these adverse pathological effects of
PHLDA
3 deficiency‐induced by
AB
and Ang
II
, respectively, in vivo and in vitro.

Conclusions

Collectively, our data indicated that
PHLDA
3 could ameliorate pressure overload‐induced cardiac remodeling mainly by blocking the
AKT
signaling pathway, suggesting that
PHLDA
3 may represent a therapeutic target for the treatment of pathological cardiac hypertrophy and heart failure.
Heraclius’ War Propaganda and the Qurʾān’s Promise of Reward for Dying in Battle
Authors: Tesei Tommaso 
Published: August 2019

AbstractIn this article I compare the Qurʾānic promise of reward for those who die in battle with similar concepts found in contemporaneous Byzantine military circles, and specifically, the idea promoted by emperor Heraclius (r. 610-641 CE) that soldiers might obtain the “crown of martyrdom” for dying on the battlefield. This idea has almost no antecedent in late antique society. Previously the martyr had been a passive figure slain by an unfaithful enemy, rather than a soldier engaged in a fight to impose (or to avenge) the true faith. Heraclius’ understanding of military martyrdom was arguably a revolutionary innovation. Since no attempt was made to either canonize or popularize on a large scale this point of Heraclius’ propaganda, the concept of military martyrdom must have been limited to the narrow circle of persons who were actively involved in military activities. For this reason, it is surprising that very similar concepts occur in the Qurʾān – that was composed in the very same historical period. The question that I will ask is whether the ideas expressed in the Qurʾān have any relationship to those promoted by imperial propagandists and, if so, the channel or channels through which this transmission took place.
Meteorological Conditions Conducive to the Rapid Spread of the Deadly Wildfire in Eastern Attica, Greece
Authors: Lagouvardos K. , Kotroni V. , Giannaros T. M. , Dafis S. 
Published: August 2019

AbstractOn 23 July 2018, Attica, Greece, was impacted by a major wildfire that took place in a wildland–urban interface area and exhibited extreme fire behavior, characterized by a very high rate of spread. One-hundred civilian fatalities were registered, establishing this wildfire as the second-deadliest weather-related natural disaster in Greece, following the heat wave of July 1987. On the day of the deadly wildfire, a very strong westerly flow was blowing for more than 10 h over Attica. Wind gusts up to 30–34 m s−1occurred over the mountainous areas of Attica, with 20–25 m s−1in the city of Athens and surrounding suburban areas. This strong westerly flow interacted with the local topography and acted as downslope flow over the eastern part of Attica, with temperatures rising up to 39°C and relative humidity dropping to 19% prior to the onset of the wildfire. These weather elements are widely acknowledged as the major contributing factors to extreme fire behavior. WRF-SFIRE correctly predicted the spatiotemporal distribution of the fire spread and demonstrated its utility for fire spread warning purposes.
Observing and Modelling the Surface Radiative Budget and Cloud Radiative Forcing at the Cabauw Experimental Site for Atmospheric Research (CESAR), the Netherlands, 2009–17
Authors: Boers Reinout , Bosveld Fred , Baltink Henk Klein , Knap Wouter , van Meijgaard Erik , Wauben Wiel 
Published: August 2019

AbstractA dataset of 9 years in duration (2009–17) of clouds and radiation was obtained at the Cabauw Experimental Site for Atmospheric Research (CESAR) in the Netherlands. Cloud radiative forcings (CRF) were derived from the dataset and related to cloud cover and temperature. Also, the data were compared with RCM output. Results indicate that there is a seasonal cycle (i.e., winter, spring, summer, and autumn) in longwave (CRF-LW: 48.3, 34.4, 30.8, and 38.7 W m−2) and shortwave (CRF-SW: −23.6, −60.9, −67.8, and −32.9 W m−2) forcings at CESAR. Total CRF is positive in winter and negative in summer. The RCM has a cold bias with respect to the observations, but the model CRF-LW corresponds well to the observed CRF-LW as a result of compensating errors in the difference function that makes up the CRF-LW. The absolute value of model CRF-SW is smaller than the observed CRF-SW in summer, mostly because of albedo differences. The majority of clouds from above 2 km are present at the same time as low clouds, so the higher clouds have only a small impact on CRF whereas low clouds dominate their values. CRF-LW is a function of fractional cloudiness. CRF-SW is also a function of fractional cloudiness, if the values are normalized by the cosine of solar zenith angle. Expressions for CRF-LW and CRF-SW were derived as functions of temperature, fractional cloudiness, and solar zenith angle, indicating that CRF is the largest when fractional cloudiness is the highest but is also large for low temperature and high sun angle.
Using Self-Organizing Maps to Identify Coherent CONUS Precipitation Regions
Authors: Swenson Leif M. , Grotjahn Richard 
Published: August 2019

Abstract
Extreme precipitation events have major societal impacts. These events are rare and can have small spatial scale, making statistical analysis difficult; both factors are mitigated by combining events over a region. A methodology is presented to objectively define “coherent” regions wherein data points have matching annual cycles. Regions are found by training self-organizing maps (SOMs) on the annual cycle of precipitation for each grid point across the contiguous United States (CONUS). Using the annual cycle for our intended application minimizes problems caused by consecutive dry periods and localized extreme events. Multiple criteria are applied to identify useful numbers of regions for our future application. Criteria assess these properties for each region: having many more events than experienced by a single grid point, good connectedness and compactness, and robustness to changing the number of regions. Our methodology is applicable across datasets and is tested here on both reanalysis and gridded observational data. Precipitation regions obtained align with large-scale geographical features and are readily interpretable. Useful numbers of regions balance two conflicting preferences: larger regions contain more events and thereby have more robust statistics, but more compact regions allow weather patterns associated with extreme events to be aggregated with confidence. For 6-h precipitation, 12–15 regions over the CONUS optimize our metrics. The regions obtained are compared against two existing region archetypes. For example, a popular set of regions, based on nine groups of states, has less coherent regions than defining the same number of regions with our SOM methodology.
Characteristics of deaths associated with kratom use
Authors: Corkery John M , Streete Peter , Claridge Hugh , Goodair Christine , Papanti Duccio , Orsolini Laura , Schifano Fabrizio , Sikka Kanav , Körber Sophie , Hendricks Amy 
Published: August 2019

Background: Kratom ( Mitragyna speciosa Korth) use has increased in Western countries, with a rising number of associated deaths. There is growing debate about the involvement of kratom in these events. Aims: This study details the characteristics of such fatalities and provides a ‘state-of-the-art’ review. Methods: UK cases were identified from mortality registers by searching with the terms ‘kratom’, ‘mitragynine’, etc. Databases and online media were searched using these terms and ‘death’, ‘fatal*’, ‘overdose’, ‘poisoning’, etc. to identify additional cases; details were obtained from relevant officials. Case characteristics were extracted into an Excel spreadsheet, and analysed employing descriptive statistics and thematic analysis. Results: Typical case characteristics ( n = 156): male (80%), mean age 32.3 years, White (100%), drug abuse history (95%); reasons for use included self-medication, recreation, relaxation, bodybuilding, and avoiding positive drug tests. Mitragynine alone was identified/implicated in 23% of cases. Poly substance use was common (87%), typically controlled/recreational drugs, therapeutic drugs, and alcohol. Death cause(s) included toxic effects of kratom ± other substances; underlying health issues. Conclusions: These findings add substantially to the knowledge base on kratom-associated deaths; these need systematic, accurate recording. Kratom’s safety profile remains only partially understood; toxic and fatal levels require quantification.
Thoracic epidural anaesthesia and analgesia ameliorates surgery-induced stress response and postoperative pain in patients undergoing radical oesophagectomy
Authors: Wang Jing , Yin Yuehao , Zhu Yun , Xu Pingbo , Sun Zhirong , Miao Changhong , Zhong Jing 
Published: August 2019

Objective An acute severe stress response associated with major surgery can adversely affect the inflammatory and hormonal responses. We hypothesised that total intravenous anaesthesia (TIVA) combined with thoracic epidural anaesthesia and analgesia (TEA) attenuates the stress response and postoperative pain in patients undergoing radical oesophagectomy. Methods Forty patients scheduled for elective radical oesophagectomy were randomly assigned to one of two groups: TIVA or TIVA+TEA. The plasma levels of stress hormones and cytokines, consumption of fentanyl, postoperative visual analogue scale (VAS) scores within 48 hours, and extubation time were assessed. Results The plasma levels of interleukin-6, norepinephrine, cortisol, and adrenocorticotropic hormone at 3 hours after the beginning of surgery were significantly higher in the TIVA group than TIVA+TEA group. The plasma level of interleukin-10 at 3 hours after the beginning of surgery was significantly lower in the TIVA group than TIVA+TEA group. The consumption of fentanyl was significantly greater, VAS scores were significantly higher, and extubation time was significantly longer in the TIVA group than TIVA+TEA group. Conclusions The findings suggest that combination of TIVA and TEA may attenuate the intraoperative stress response and postoperative pain in patients undergoing radical oesophagectomy.