bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fatty liver and mortality: a cohort population study in South Italy
Authors: Caruso Maria Gabriella , Veronese Nicola , Notarnicola Maria , Cisternino Anna Maria , Reddavide Rosa , Inguaggiato Rosa , Guerra Vito , Donghia Rossella , Logroscino Antonio , Rotolo Ornella , Chiloiro Marisa , Leandro Gioacchino , De Leonardis Giampiero , Tutino Valeria , Misciagna G , Bonfiglio Caterina , Guerra Rocco , Osella Alberto 
Published: June 2019

ObjectiveAlcoholic fatty liver (AFLD) and non-alcoholic fatty liver (NAFLD) are two common conditions. However, if they can increase the risk of death is poorly explored. We therefore aimed to investigate the potential association between the presence and severity of liver steatosis and mortality in a large sample of older people.DesignProspective.SettingCommunity.ParticipantsWomen and men randomly sampled from the electoral rolls of the population of Castellana Grotte, a town in Southern Italy (Apulia region) between 2005 and 2006. Among 1942 initially contacted, 1708 (=87.9%) participated to the baseline survey (Multicentrica Colelitiasi III (MICOL III)). This specific study included 1445 older participants (mean age=65.2 years, females=44.2%).ExposureNAFLD or AFLD.Primary and secondary outcomesMortality (all-cause and specific-cause).ResultsAfter a median of 12 years, 312 participants (=21.6%) died. After adjusting for nine potential confounders, the presence of steatosis was not associated with any increased risk of death in both NAFLD and AFLD. The severity of liver steatosis was not associated with any increased risk of mortality in NAFLD, while in AFLD, the presence of moderate steatosis significantly increased the risk of overall (HR=2.16; 95% CI 1.19 to 3.91) and cancer-specific (HR=3.54; 95% CI 1.16 to 10.87) death.ConclusionsLiver steatosis is not associated with any increased risk of death in NAFLD, while moderate steatosis could be a risk factor for mortality (particularly due to cancer) in people affected by AFLD.
What is the evidence that differences in ‘control over destiny’ lead to socioeconomic inequalities in health? A theory-led systematic review of high-quality longitudinal studies on pathways in the living environment
Authors: Orton Lois Catherine , Pennington Andy , Nayak Shilpa , Sowden Amanda , Petticrew Mark , White Martin , Whitehead Margaret 
Published: June 2019

BackgroundLow control and high demand in the places where people work has been shown to partially explain why those in lower socioeconomic positions experience poorer health than their counterparts in higher socioeconomic positions. It would seem likely then that experiences of control in the wider living environment, beyond people’s places of work, might also play a role in shaping these health inequalities. Our recent review of theory revealed potential pathways by which low control in the living environment might explain the social patterning of health via low control beliefs and low actual control.MethodsBased on the potential pathways identified in our review of theory, we conducted a systematic review of longitudinal studies on the relationship between low control in the living environment and social inequalities in health published by January 2019, in English.ResultsSix studies were included in the review. Taken together, they provide evidence that lower social positions are associated with lower control beliefs and poorer health outcomes, in terms of heart disease, anxiety, depression and self-rated health, and that some of the association between low social position and health outcomes is explained by low control beliefs. No studies investigated the pathway from low actual control to poorer health in more disadvantaged groups.ConclusionThere is strong evidence from a small number of high-quality longitudinal studies that low perceived control in the living environment may play an important role in the pathways leading from low social position to poorer health and well-being. Further studies are needed to distinguish between the effects of having low control beliefs and having actual low control.
Clinicopathological characteristics of subtypes of chronic inflammatory demyelinating polyradiculoneuropathy
Authors: Ikeda Shohei , Koike Haruki , Nishi Ryoji , Kawagashira Yuichi , Iijima Masahiro , Katsuno Masahisa , Sobue Gen 
Published: June 2019

ObjectiveTo evaluate the clinical and pathological correlations characterising each clinical subtype of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).MethodsWe assessed 106 consecutive patients who had CIDP fulfilling the European Federation of Neurological Societies and Peripheral Nerve Society criteria and had been referred for sural nerve biopsy. Patients with anti-neurofascin 155, anti-contactin 1 and anti-LM1 antibodies were excluded.Results55 patients were classified as having typical CIDP. Regarding atypical CIDP, the multifocal acquired demyelinating sensory and motor (MADSAM) (n=15), distal acquired demyelinating symmetric (DADS) (n=16) and pure sensory (n=15) forms were major subtypes, while the pure motor (n=4) and focal (n=1) forms were rare. Nerve conduction studies revealed that distal motor latencies and F-wave latencies were markedly prolonged in the typical CIDP group but relatively preserved in the MADSAM group. Motor conduction velocity was conspicuously slowed in the DADS group, and distal motor latencies were markedly prolonged in the pure sensory group. Sural nerve biopsy specimens from patients with MADSAM, DADS and pure sensory type tended to show extreme variation in myelinated fibre density among fascicles due to focal myelinated fibre loss or onion-bulb formation, whereas patients with typical CIDP tended to show mild fascicular variation. Epineurial lymphocytic infiltration was conspicuous in cases with marked fascicular variation in myelinated fibre density.ConclusionsPreferential involvement of distal and proximal segments and uniform pathological features in typical CIDP indicate a role of humoral factors at sites where the blood–nerve barrier is deficient. By contrast, focal lesions in MADSAM, DADS and pure sensory forms may share neuropathic mechanisms primarily affecting the nerve trunk.
Damage control resuscitation and surgery for indigenous combat casualties: a prospective observational study
Authors: Campbell Kieran , Naumann D N , Remick K , Wright C 
Published: June 2019

IntroductionSpecialist units that assist indigenous forces (IF) in their strategic aims are supported by medical teams providing point of injury emergency care for casualties, including IF and civilians (Civ). We investigated the activities of a Coalition Forces far-forward medical facility, in order to inform medical providers about the facilities and resources required for medical support to IF and Civ during such operations.MethodsA prospective observational study (June to August 2017) undertaken at a far-forward Coalition Forces medical support unit (12 rotating personnel) recorded patient details (IF or Civ), mechanism of injury (MOI), number of blood products used, damage control resuscitation (DCR) and damage control surgery (DCS), number of mass casualty (MASCAL) scenarios, resuscitative thoracotomy, resuscitative endovascular balloon occlusion of the aorta (REBOA) and whole blood emergency donor panels (EDP).Results680 casualties included 478 IF and 202 Civ (45.5% of the Civ were paediatric). Most common MOIs were blast (n=425; 62.5%) and gunshot wound (n=200; 29.4%). Fifteen (2.2%) casualties died; 627 (92.2%) were transferred to local hospitals. DCR was used for 203 (29.9%), and DCS for 182 (26.8%) casualties. There were 23 MASCAL scenarios, 1220 transfusions and 32 EDPs. REBOA was performed eight times, and thoracotomy was performed 27 times.ConclusionsA small medical team provided high-tempo emergency resuscitative care for hundreds of IF and Civ casualties within a short space of time using state-of-the-art resuscitative modalities. DCR and DCS were undertaken with a large number of EDPs, and a high survival-to-transfer rate.
User click fraud detection method based on Top-Rank-k frequent pattern mining
Authors: Pan Lijiao , Mu Shibiao , Wang Yingyan 
Published: June 2019

A user click fraud detection method based on Top-Rank-k frequent pattern mining algorithm is presented to solve the click fraud problem appearing in current online advertising. Firstly, this method combines the click frequency of event samples, calculates the real evaluation score of click stream, and the click stream density function and evaluation score expression under multi-dimensional variables, and further obtains the time complexity of the next user’s click fraud process. Secondly, according to the Top-Rank-k frequent pattern, the process of click fraud detection algorithm is designed, and the click fraud user is analyzed and obtained. The results show that this method has good efficiency and correctness, and is superior to other similar algorithms.
Celebrating 50 years since the publication of
Folding and Fracturing of Rocks
by J. G. Ramsay
Authors: Bond Clare E. , Lebit Hermann D. 
Published: June 2019

Abstract

John G. Ramsay's book
Folding and Fracturing of Rocks
was first published in 1967. It set the research agenda for, and the approaches to, modern structural geology. It is recognized as one of the most influential texts in the subject area and was underpinned by significant research publications by the author; its weight added to by later texts and articles. John was also an enthusiastic teacher of structural geology, and many of his tutees have gone on to forge their own careers in structural geology, inspired to do so by John, his teaching and approaches. This Special Publication serves as a golden 50 year celebration of the book, and also of John's life-long work and career as an innovative scientist, inspiring mentor, excellent teacher, and great field structural geologist.
Central and peripheral factors mechanistically linked to exercise intolerance in heart failure with reduced ejection fraction
Authors: Craig Jesse C. , Colburn Trenton D. , Caldwell Jacob T. , Hirai Daniel M. , Tabuchi Ayaka , Baumfalk Dryden R. , Behnke Bradley J. , Ade Carl J. , Musch Timothy I. , Poole David C. 
Published: June 2019

Exercise intolerance is a primary symptom of heart failure (HF); however, the specific contribution of central and peripheral factors to this intolerance is not well described. The hyperbolic relationship between exercise intensity and time to exhaustion (speed-duration relationship) defines exercise tolerance but is underused in HF. We tested the hypotheses that critical speed (CS) would be reduced in HF, resting central functional measurements would correlate with CS, and the greatest HF-induced peripheral dysfunction would occur in more oxidative muscle. Multiple treadmill-constant speed runs to exhaustion were used to quantify CS and D′ (distance coverable above CS) in healthy control (Con) and HF rats. Central function was determined via left ventricular (LV) Doppler echocardiography [fractional shortening (FS)] and a micromanometer-tipped catheter [LV end-diastolic pressure (LVEDP)]. Peripheral O2 delivery-to-utilization matching was determined via phosphorescence quenching (interstitial Po2, Po2 is) in the soleus and white gastrocnemius during electrically induced twitch contractions (1 Hz, 8V). CS was lower in HF compared with Con (37 ± 1 vs. 44 ± 1 m/min, P < 0.001), but D′ was not different (77 ± 8 vs. 69 ± 13 m, P = 0.6). HF reduced FS (23 ± 2 vs. 47 ± 2%, P < 0.001) and increased LVEDP (15 ± 1 vs. 7 ± 1 mmHg, P < 0.001). CS was related to FS ( r = 0.72, P = 0.045) and LVEDP ( r = −0.75, P = 0.02) only in HF. HF reduced soleus Po2 is at rest and during contractions (both P < 0.01) but had no effect on white gastrocnemius Po2 is ( P > 0.05). We show in HF rats that decrements in central cardiac function relate directly with impaired exercise tolerance (i.e., CS) and that this compromised exercise tolerance is likely due to reduced perfusive and diffusive O2 delivery to oxidative muscles. NEW & NOTEWORTHY We show that critical speed (CS), which defines the upper boundary of sustainable activity, can be resolved in heart failure (HF) animals and is diminished compared with controls. Central cardiac function is strongly related with CS in the HF animals, but not controls. Skeletal muscle O2 delivery-to-utilization dysfunction is evident in the more oxidative, but not glycolytic, muscles of HF rats and is explained, in part, by reduced nitric oxide bioavailability.
Impact of pulmonary endarterectomy on pulmonary arterial wave propagation and reservoir function
Authors: Su Junjing , Hughes Alun D. , Simonsen Ulf , Nielsen-Kudsk Jens Erik , Parker Kim H. , Howard Luke S. , Mellemkjaer Soren 
Published: June 2019

High wave speed and large wave reflection in the pulmonary artery have previously been reported in patients with chronic thromboembolic pulmonary hypertension (CTEPH). We assessed the impact of pulmonary endarterectomy (PEA) on pulmonary arterial wave propagation and reservoir function in patients with CTEPH. Right heart catheterization was performed using a combined pressure and Doppler flow sensor-tipped guidewire to obtain simultaneous pressure and flow velocity measurements in the pulmonary artery in eight patients with CTEPH before and 3 mo after PEA. Wave intensity and reservoir-excess pressure analyses were then performed. Following PEA, mean pulmonary arterial pressure (PAPm; ∼49 vs. ∼32 mmHg), pulmonary vascular resistance (PVR; ∼11.1 vs. ∼5.1 Wood units), and wave speed (∼16.5 vs. ∼8.1 m/s), i.e., local arterial stiffness, markedly decreased. The changes in the intensity of the reflected arterial wave and wave reflection index (pre: ∼28%; post: ∼22%) were small, and patients post-PEA with and without residual pulmonary hypertension (i.e., PAPm ≥ 25 mmHg) had similar wave reflection index (∼20 vs. ∼23%). The reservoir and excess pressure decreased post-PEA, and the changes were associated with improved right ventricular afterload, function, and size. In conclusion, although PVR and arterial stiffness decreased substantially following PEA, large wave reflection persisted, even in patients without residual pulmonary hypertension, indicating lack of improvement in vascular impedance mismatch. This may continue to affect the optimal ventriculoarterial interaction, and further studies are warranted to determine whether this contributes to persistent symptoms in some patients. NEW & NOTEWORTHY We performed wave intensity analysis in the pulmonary artery in patients with chronic thromboembolic pulmonary hypertension before and 3 mo after pulmonary endarterectomy. Despite substantial reduction in pulmonary arterial pressures, vascular resistance, and arterial stiffness, large pulmonary arterial wave reflection persisted 3 mo postsurgery, even in patients without residual pulmonary hypertension, suggestive of lack of improvement in vascular impedance mismatch.
Children with orthostatic intolerance exhibit elevated markers of inflammation in the dorsal medulla
Authors: Wagoner Ashley L. , Olson John D. , Westwood Brian M. , Fortunato John E. , Diz Debra I. , Shaltout Hossam A. 
Published: June 2019

Children with orthostatic intolerance (OI) have exaggerated decreases in heart rate variability (HRV) and suppression of baroreflex sensitivity (BRS) with standing. Accompanying brain transmitter and metabolite profiles are unknown. In this study, we used proton (1H) magnetic resonance spectroscopy (1H-MRS) to quantify markers of neuronal and glial integrity in a pilot study of children with OI compared with asymptomatic controls. Eighteen participants ages 10–18 yr were evaluated for blood pressure, heart rate (HR), and calculated indexes of autonomic function in supine and upright positions and, within an average of 2 wk, underwent1H-MRS scans of dorsal medulla on a clinical 3T magnet while supine. As a result, of the 18 participants, 11 tested positive for OI and 7 did not. OI subjects exhibited higher HR and lower HRV and high-frequency α-index (HFα), an index of parasympathetic vagal tone, during standing compared with non-OI. HRV, sequence all (Seq All), high- and low-frequency (HFα and LFα) estimates of the spontaneous BRS decreased significantly, while BP variabilty increased significantly during standing only in subjects with OI. OI subjects had higher myoinositol (mIns) and total choline (tCho), markers of glial inflammation. Upright HFα and Seq All inversely correlated to supine tCho and mIns, respectively, independent of age and sex. In conclusions, in this pilot study, children with OI exhibit higher mIns and tCho in the dorsal medulla while supine that may reflect the well-established impairment in regulation of the autonomic nervous system upon standing. Neuroinflammation as an underlying cause or consequence of autonomic dysfunction is an intriguing possibility requiring further study.NEW & NOTEWORTHY (1H) magnetic resonance spectroscopy detected elevated markers of neuroinflammation in the dorsal medulla in children with impaired autonomic responses to head upright tilt. This first report of altered brain metabolites in this population provides a basis for future clinical studies using this methodology to aide in understanding complex autonomic disease states.
Radiosensitization by Histone H3 Demethylase Inhibition in Diffuse Intrinsic Pontine Glioma
Authors: Katagi Hiroaki , Louis Nundia , Unruh Dusten , Sasaki Takahiro , He Xingyao , Zhang Ali , Ma Quanhong , Piunti Andrea , Shimazu Yosuke , Lamano Jonathan B. , Carcaboso Angel M. , Tian Xiao , Seluanov Andrei , Gorbunova Vera , Laurie Kathryn L. , Kondo Akihide , Wadhwani Nitin R. , Lulla Rishi , Goldman Stewart , Venneti Sriram , Becher Oren J. , Zou Lihua , Shilatifard Ali , Hashizume Rintaro 
Published: June 2019

Abstract

Purpose:
Radiotherapy (RT) has long been and remains the only treatment option for diffuse intrinsic pontine glioma (DIPG). However, all patients show evidence of disease progression within months of completing RT. No further clinical benefit has been achieved using alternative radiation strategies. Here, we tested the hypothesis that histone demethylase inhibition by GSK-J4 enhances radiation-induced DNA damage, making it a potential radiosensitizer in the treatment of DIPG.
Experimental Design: We evaluated the effects of GSK-J4 on genes associated with DNA double-strand break (DSB) repair in DIPG cells by RNA sequence, ATAC sequence, and quantitative real-time PCR. Radiation-induced DNA DSB repair was analyzed by immunocytochemistry of DSB markers γH2AX and 53BP1, DNA-repair assay, and cell-cycle distribution. Clonogenic survival assay was used to determine the effect of GSK-J4 on radiation response of DIPG cells. In vivo response to radiation monotherapy and combination therapy of RT and GSK-J4 was evaluated in patient-derived DIPG xenografts.

Results:
GSK-J4 significantly reduced the expression of DNA DSB repair genes and DNA accessibility in DIPG cells. GSK-J4 sustained high levels of γH2AX and 53BP1 in irradiated DIPG cells, thereby inhibiting DNA DSB repair through homologous recombination pathway. GSK-J4 reduced clonogenic survival and enhanced radiation effect in DIPG cells. In vivo studies revealed increased survival of animals treated with combination therapy of RT and GSK-J4 compared with either monotherapy.

Conclusions:
Together, these results highlight GSK-J4 as a potential radiosensitizer and provide a rationale for developing combination therapy with radiation in the treatment of DIPG.
Prognostic Implications of PD-L1 Expression in Breast Cancer: Systematic Review and Meta-analysis of Immunohistochemistry and Pooled Analysis of Transcriptomic Data
Authors: Matikas Alexios , Zerdes Ioannis , Lövrot John , Richard François , Sotiriou Christos , Bergh Jonas , Valachis Antonios , Foukakis Theodoros 
Published: June 2019

Abstract

Purpose:
Conflicting data have been reported on the prognostic value of PD-L1 protein and gene expression in breast cancer.
Experimental Design: Medline, Embase, Cochrane Library, and Web of Science Core Collection were searched, and data were extracted independently by two researchers. Outcomes included pooled PD-L1 protein positivity in tumor cells, immune cells, or both, per subtype and per antibody used, and its prognostic value for disease-free and overall survival. A pooled gene expression analysis of 39 publicly available transcriptomic datasets was also performed.

Results:
Of the initial 4,184 entries, 38 retrospective studies fulfilled the predefined inclusion criteria. The overall pooled PD-L1 protein positivity rate was 24% (95% CI, 15%–33%) in tumor cells and 33% (95% CI, 14%– 56%) in immune cells. PD-L1 protein expression in tumor cells was prognostic for shorter overall survival (HR, 1.63; 95% CI, 1.07–2.46; P = 0.02); there was significant heterogeneity (I2 = 80%, Pheterogeneity &lt; 0.001). In addition, higher PD-L1 gene expression predicted better survival in multivariate analysis in the entire population (HR, 0.82; 95% CI, 0.74–0.90; P &lt; 0.001 for OS) and in basal-like tumors (HR, 0.64; 95% CI, 0.52–0.80; P &lt; 0.001 for OS; Pinteraction 0.005).

Conclusions:
The largest to our knowledge meta-analysis on the subject informs on PD-L1 protein positivity rates and its prognostic value in breast cancer. Standardization is needed prior to routine implementation. PD-L1 gene expression is a promising prognostic factor, especially in basal-like breast cancer. Discrepant prognostic information might be related to PD-L1 gene expression in the stroma.
MEN1309/OBT076, a First-In-Class Antibody–Drug Conjugate Targeting CD205 in Solid Tumors
Authors: Merlino Giuseppe , Fiascarelli Alessio , Bigioni Mario , Bressan Alessandro , Carrisi Corrado , Bellarosa Daniela , Salerno Massimiliano , Bugianesi Rossana , Manno Rosanna , Bernadó Morales Cristina , Arribas Joaquin , Bisht Arnima , Kaplan Angelo , Boyd Robert , Do Uyen T. , Swaminathan Sudha , Attanasio Nickolas , Lou San Lin , Dusek Rachel L. , Ackroyd James E. , Pham Phuoc Huy , Awdew Rahel , Aud Dee , Trang Michael , Lynch Carmel M. , Terrett Jonathan , Wilson Keith E. , Rohlff Christian , Manzini Stefano , Pellacani Andrea , Binaschi Monica 
Published: June 2019

Abstract
CD205 is a type I transmembrane glycoprotein and is a member of the C-type lectin receptor family. Analysis by mass spectrometry revealed that CD205 was robustly expressed and highly prevalent in a variety of solid malignancies from different histotypes. IHC confirmed the increased expression of CD205 in pancreatic, bladder, and triple-negative breast cancer (TNBC) compared with that in the corresponding normal tissues. Using immunofluorescence microscopy, rapid internalization of the CD205 antigen was observed. These results supported the development of MEN1309/OBT076, a fully humanized CD205-targeting mAb conjugated to DM4, a potent maytansinoid derivate, via a cleavable N-succinimidyl-4-(2-pyridyldithio) butanoate linker. MEN1309/OBT076 was characterized in vitro for target binding affinity, mechanism of action, and cytotoxic activity against a panel of cancer cell lines. MEN1309/OBT076 displayed selective and potent cytotoxic effects against tumor cells exhibiting strong and low to moderate CD205 expression. In vivo, MEN1309/OBT076 showed potent antitumor activity resulting in durable responses and complete tumor regressions in many TNBC, pancreatic, and bladder cancer cell line–derived and patient-derived xenograft models, independent of antigen expression levels. Finally, the pharmacokinetics and pharmacodynamic profile of MEN1309/OBT076 was characterized in pancreatic tumor–bearing mice, demonstrating that the serum level of antibody–drug conjugate (ADC) achieved through dosing was consistent with the kinetics of its antitumor activity. Overall, our data demonstrate that MEN1309/OBT076 is a novel and selective ADC with potent activity against CD205-positive tumors. These data supported the clinical development of MEN1309/OBT076, and further evaluation of this ADC is currently ongoing in the first-in-human SHUTTLE clinical trial.