bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of surgery on lymphoscintigraphy drainage patterns from the canine brachium in a simulated tumor model
Authors: Hlusko Katelyn C. , Cole Robert , Tillson David Michael , Boothe Harry W. , Almond Greg T. , Coggeshall Whitney S. , Matz Brad M. 
Published: June 2020

AbstractObjectiveTo determine the effect of surgery on lymphoscintigraphy drainage patterns from the canine brachium.Study designExperimental study.AnimalsEight healthy research beagles.MethodsA predefined area of skin measuring 2 × 1.5 cm in dimension was designated on either the right or left brachium. Preoperative lymphoscintigraphy was performed with technetium sulfur colloid injected into the subcutaneous tissues around the predefined anatomic location in a four‐quadrant technique. Dogs underwent surgery for excision of the predefined area of skin, subcutis, and fascia of the lateral head of the triceps muscle with 1‐cm margins. Eighteen days after surgery, lymphoscintigraphy was again performed with technetium sulfur colloid injected into the subcutaneous tissues around the surgical scar in a four‐quadrant technique.ResultsSentinel lymph nodes were identified in eight of eight dogs preoperatively and in eight of eight dogs postoperatively. Agreement between the results of the preoperative and postoperative lymphoscintigraphy studies was identified as complete in four of eight dogs and partial in four of eight dogs. Sentinel lymph node identification occurred immediately in three of eight dogs preoperatively and in eight of eight dogs postoperatively.ConclusionSentinel lymph node identification occurred faster postoperatively. Agreement or partial agreement between the results of the preoperative and postoperative lymphoscintigraphy studies was observed in eight of eight dogs.Clinical significanceSurgery appears to have an effect on lymphoscintigraphy drainage patterns. Additional studies are required to compare preoperative and postoperative sentinel lymph node mapping patterns in tumor‐bearing dogs. However, this study provides preliminary information regarding the effect of surgery on sentinel lymph node identification.
Correlations of Permeability and Geological Characteristics Based on Mercury Intrusion Data and Hierarchical Statistical Models: A Case Study
Authors: Li Zihao , Gao Wenyu , Li Xiangming 
Published: June 2020

Abstract
The mercury intrusion technique is a crucial in-lab method to investigate the porous medium properties. The potentiality of mercury intrusion data has not been explored significantly in the traditional interpretation. Thus, a hierarchical statistical model that not only captures the quantitative relationship between petrophysical properties but also accounts for different geological members is developed to interpret mercury intrusion data. This multilevel model is established from almost 800 samples with specific geological characteristics. We distinguish the fixed effects and the random effects in this mixed model. The overall connection between the selected petrophysical parameters is described by the fixed effects at a higher level, while variations due to different geological members are accommodated as the random effects at a lower level. The selected petrophysical parameters are observed through hypothesis testing and model selection. In this case study, five petrophysical parameters are selected into the model. Essential visualizations are also provided to assist the interpretations of the probabilistically model. The final model reveals the quantitative relationship between permeability and other petrophysical properties in each member and the order of relative importance for each property. With this studied relationship and advanced model, the geological reservoir simulation can be greatly detailed and accurate in the future.
Direct coupling between carbon release and weathering during the Toarcian oceanic anoxic event
Authors: Kemp David B. , Selby David , Izumi Kentaro 
Published: June 2020

AbstractSilicate weathering represents a major feedback mechanism in the Earth’s climate system, helping to stabilize atmospheric CO2 levels and temperature on million-year time scales. On shorter time scales of greater relevance to understanding the fate of anthropogenic CO2, the efficacy and responsiveness of weathering is less clear. Here, we present high-resolution osmium-isotope data that reflect global chemical weathering from a stratigraphically thick record of the early Toarcian oceanic anoxic event (T-OAE; ca. 182 Ma). A pronounced decrease in the carbon-isotope composition of exogenic carbon reservoirs during this event has been linked to the large-scale release of 12C-enriched carbon. Our data indicate that the flux of radiogenic osmium to the oceans increased in lockstep with the decrease in carbon-isotope values, demonstrating a geologically synchronous coupling between massive carbon release and enhanced global continental crust weathering. We show that abrupt shifts in carbon isotopes, previously interpreted as millennial-scale methane hydrate melting or terrestrial carbon-release events, are coeval with rapid increases in weathering. Global weathering may have increased by &gt;40% across each of these intervals of rapid carbon injection. Our results help to reconcile previous estimates of weathering change during the T-OAE, and support the view that, overall, global weathering rates may have increased six-fold through the entire event.
Academic criteria for promotion and tenure in biomedical sciences faculties: cross sectional analysis of international sample of universities
Authors: Rice Danielle B , Raffoul Hana , Ioannidis John P A , Moher David 
Published: June 2020

AbstractObjectiveTo determine the presence of a set of pre-specified traditional and non-traditional criteria used to assess scientists for promotion and tenure in faculties of biomedical sciences among universities worldwide.DesignCross sectional study.SettingInternational sample of universities.Participants170 randomly selected universities from the Leiden ranking of world universities list.Main outcome measurePresence of five traditional (for example, number of publications) and seven non-traditional (for example, data sharing) criteria in guidelines for assessing assistant professors, associate professors, and professors and the granting of tenure in institutions with biomedical faculties.ResultsA total of 146 institutions had faculties of biomedical sciences, and 92 had eligible guidelines available for review. Traditional criteria of peer reviewed publications, authorship order, journal impact factor, grant funding, and national or international reputation were mentioned in 95% (n=87), 37% (34), 28% (26), 67% (62), and 48% (44) of the guidelines, respectively. Conversely, among non-traditional criteria, only citations (any mention in 26%; n=24) and accommodations for employment leave (37%; 34) were relatively commonly mentioned. Mention of alternative metrics for sharing research (3%; n=3) and data sharing (1%; 1) was rare, and three criteria (publishing in open access mediums, registering research, and adhering to reporting guidelines) were not found in any guidelines reviewed. Among guidelines for assessing promotion to full professor, traditional criteria were more commonly reported than non-traditional criteria (traditional criteria 54.2%, non-traditional items 9.5%; mean difference 44.8%, 95% confidence interval 39.6% to 50.0%; P=0.001). Notable differences were observed across continents in whether guidelines were accessible (Australia 100% (6/6), North America 97% (28/29), Europe 50% (27/54), Asia 58% (29/50), South America 17% (1/6)), with more subtle differences in the use of specific criteria.ConclusionsThis study shows that the evaluation of scientists emphasises traditional criteria as opposed to non-traditional criteria. This may reinforce research practices that are known to be problematic while insufficiently supporting the conduct of better quality research and open science. Institutions should consider incentivising non-traditional criteria.Study registrationOpen Science Framework (https://osf.io/26ucp/?view_only=b80d2bc7416543639f577c1b8f756e44).
Estimating deaths from foodborne disease in the UK for 11 key pathogens
Authors: Holland Darren , Thomson Laura , Mahmoudzadeh Nazmina , Khaled Abdul 
Published: June 2020

ObjectiveTo estimate the number of deaths from foodborne disease in the UK from 11 key pathogens.DesignFour different models were developed using data from a range of sources. These included enhanced surveillance, outbreaks, death certificates and hospital episode statistics data. For each model, median estimates were produced with 95% credible intervals (CrI). The results from the different models were compared.ResultsThe estimates for foodborne deaths for each pathogen from the different models were consistent, with CrIs largely overlapping. Based on the preferred model for each pathogen, foodborne norovirus is estimated to cause 56 deaths per year (95% CrI 32 to 92), foodborneSalmonella33 deaths (95% CrI 7 to 159), foodborneListeria monocytogenes26 deaths (95% CrI 24 to 28), foodborneClostridium perfringens25 deaths (95% CrI 1 to 163) and foodborneCampylobacter21 deaths (95% CrI 8 to 47). The considerable overlap in the CrIs means it is not possible to make any firm conclusions on ranking. Most of these deaths occur in those aged over 75 years. Foodborne deaths fromShigella,Cryptosporidium,Giardia,adenovirus, astrovirus and rotavirus are all rare.ConclusionsWe estimate that there are 180 deaths per year in the UK (95% CrI 113 to 359) caused by foodborne disease based on these 11 pathogens. While this is a small fraction of the estimated 2.4 million cases of foodborne illness per year it still illustrates the potential severity of these illnesses demonstrating the importance in continuing efforts to reduce these infections.
Intestinal stem cells promote crypt fission during postnatal growth of the small intestine
Authors: Dudhwala Zenab Mustansir , Hammond Paul D , Howarth Gordon S , Cummins Adrian Gerard 
Published: June 2020

ObjectiveWnt-β-catenin signalling is essential for intestinal stem cells. Our aim was to investigate the relationship between intestinal stem cells and crypt fission which peaks during infancy.DesignDuodenal biopsies were obtained during endoscopy to assess the severity of reflux oesophagitis of 15 infants, children and teenagers, which would not affect the duodenum. Samples of small intestine were also obtained from rats 7–72 days of life. Crypt fission was assessed using microdissection of 100 whole crypts and recording the percentage of bifid crypts. Intestinal LGR5+ stem cells were identified by in situ hybridisation. Rats were treated with Dickkopf to block Wnt-β-catenin signalling.ResultsCrypt fission peaked during infancy before declining after 3–4 years in humans and after 21 days of life in rats. Occasional mitotic figures were seen in bifid crypts during early fission. Stem cells were elevated for a greater period during infancy and childhood in humans. Clustering of Paneth cells was present around the stem cells at the crypt base. Dickkopf reduced the number of stem cells and crypt fission to 45% and 29%, respectively, of control values, showing dependence of both crypt fission and Lgr5+ stem cells on Wnt signalling. However, Dickkopf did not decrease mitotic count per crypt, indicating a difference in signalling between stem cells and their progeny in the transit amplifying zone.ConclusionCrypt fission peaks during infancy and is dependent on intestinal stem cells. This is relatively hidden by ‘a cloak of invisibility’ due to the low proliferation of stem cells.
Burden of care in caregivers of patients with alcohol use disorder and schizophrenia and its association with anxiety, depression and quality of life
Authors: Vadher Sneha , Desai Rishi , Panchal Bharat , Vala Ashok , Ratnani Imran Jahangirali , Rupani Mihir P , Vasava Kinjal 
Published: June 2020

BackgroundCaregivers play a pivotal role in providing care for mentally ill patients. Increase in caregiver burden can make them vulnerable to mental illness themselves.AimsWe assessed the severity of burden of care and its association with depression, anxiety and quality of life among caregivers of patients with alcohol use disorder (AUD) and schizophrenia.MethodsThis was an observational, cross-sectional, single-centred study of 50 consecutive caregivers of patients with AUD and schizophrenia. Participants were recruited from the psychiatry outpatient department of a tertiary care hospital between January and June 2017. The caregivers were further assessed by demographic details, Hospital Anxiety Depression Scale for assessment of depression and anxiety, Zarit Burden Interview for assessment of caregiver burden and WHO Quality Of Life-BREF for assessment of quality of life. Statistical data were analysed using GraphPad InStat V.3.06 (California). Multiple linear regression analysis was applied to identify the predictors of caregiver burden.ResultsBurden of care experienced by caregivers of patients with AUD is as high as that of caregivers of patients with schizophrenia (U=1142.5, p=0.46). Caregivers experiencing high burden of care are likely to have symptoms of anxiety (U=22, p<0.001), depression (U=32, p<0.001) and poor quality of life (U=84.5, p<0.001). Female caregivers are likely to experience higher burden of care (U=819.5, p=0.006). For caregivers of patients with schizophrenia, anxiety, environmental health, socioeconomic status and patients’ occupation can predict burden of care, while for caregivers of patients with AUD, depression and environmental health can predict burden of care.ConclusionOur study suggests that caregivers of patients with AUD experience burden of care as high as that of caregivers of patients with schizophrenia. Caregivers with high burden of care are more likely to have depression, anxiety and poor quality of life.Trial registration numberCTRI/2017/03/008224.
Bivalent therapeutic vaccine against HPV16/18 genotypes consisting of a fusion protein between the extra domain A from human fibronectin and HPV16/18 E7 viral antigens
Authors: Arribillaga Laura , Echeverria Iciar , Belsue Viriginia , Gomez Timothy , Lozano Teresa , Casares Noelia , Villanueva Lorea , Domingos-Pereira Sonia , Romero Pedro J , Nardelli-Haefliger Denise , Hervás-Stubbs Sandra , Sarobe Pablo , Rodriguez María Josefa , Carrascosa José L , Zürcher Thomas , Lasarte Juan José 
Published: June 2020

BackgroundIn vivo targeting of human papillomavirus (HPV) derived antigens to dendritic cells might constitute an efficient immunotherapeutic strategy against cervical cancer. In previous works, we have shown that the extra domain A from murine fibronectin (mEDA) can be used to target antigens to toll-like receptor 4 (TLR4) expressing dendritic cells and induce strong antigen-specific immune responses. In the present study, we have produced a bivalent therapeutic vaccine candidate consisting of the human EDA (hEDA) fused to E7 proteins from HPV16 and HPV18 (hEDA-HPVE7-16/18) and evaluate its potential as a therapeutic vaccine against cervical cancer.Materials and methodsRecombinant fusion proteins containing HPV E7 proteins from HPV16 and HPV18 virus subtypes fused to hEDA were produced and tested in vitro on their capacity to bind TLR4 and induce the production of tumor necrosis factor-α or interleukin (IL)-12 by human monocytes and dendritic cells. The immunogenicity and potential therapeutic activity of the vaccine in combination with cisplatin or with the TLR3 agonist molecules polyinosinic‐polycytidylic acid (Poly IC) or Poly ICLC was evaluated in mice bearing subcutaneous or genital orthotopic HPV16 TC-1 tumors.ResultshEDA-HPVE7-16/18 prototype vaccine binds human TLR4 and stimulate TLR4-dependent signaling pathways and IL-12 production by human monocyte-derived dendritic cell. Vaccination with hEDA-HPVE7-16/18 induced strong HPVE7-specific Cytotoxic T lymphocyte (CTL) responses and eliminated established tumors in the TC-1-based tumor model. The antitumor efficacy was significantly improved by combining the fusion protein with cisplatin or with the TLR-3 ligand Poly IC and especially with the stabilized analog Poly ICLC. Moreover, hEDA-HPVE7-16/18+Poly ICLC induced full tumor regression in 100% of mice bearing orthotopic genital HPV tumors.ConclusionOur results suggest that this therapeutic vaccine formulation may be an effective treatment for cervical tumors that do not respond to current therapies.
Immune checkpoint inhibitor-associated celiac disease
Authors: Badran Yousef , Shih Angela , Leet Donna , Mooradian Meghan J , Coromilas Alexandra , Chen Jonathan , Kem Marina , Zheng Hui , Borowsky Jennifer , Misdraji Joseph , Mino-Kenudson Mari , Dougan Michael 
Published: June 2020

BackgroundRare cases of immune checkpoint inhibitor (ICI)-associated celiac disease (ICI-CeD) have been reported, suggesting that disruption of tolerance mechanisms by ICIs can unmask celiac disease (CeD). This study aims to characterize the clinicopathological and immunophenotypic features of ICI-CeD in comparison to ICI-associated duodenitis (ICI-Duo) and usual CeD.MethodsA medical and pathological records search between 2015 and 2019 identified eight cases of ICI-CeD, confirmed by tTG-IgA. Nine cases of ICI-Duo, 28 cases of moderate CeD, as well as 5 normal controls were used as comparison groups. Clinical information was collected from the electronic medical records. Immunohistochemistry for CD3, CD8, T-cell receptor gamma/delta (γδ), programmed death ligand 1 (PD-L1), and programmed death 1 (PD-1) were performed, with quantification of intraepithelial lymphocyte (IEL) subsets in three well-oriented villi. CD68, PD-L1, and PD-1 were assessed as a percentage of lamina propria surface area infiltrated by positive cells. Statistical significance was calculated by the Student’s t-test and Fisher’s exact test.ResultsThe eight patients with ICI-CeD (F:M=1:3) and nine patients with ICI-Duo (F:M=5:4) presented similarly with diarrhea (13/17) and abdominal pain (11/17) after a median of 1.6 months on ICI therapy. In patients with ICI-CeD, tTG-IgA ranged from 104 to >300 IU/mL. Histological findings in ICI-CeD and ICI-Duo were similar and included expansion of the lamina propria, active neutrophilic duodenitis, variably increased IELs, and villous blunting. Immunohistochemistry showed that the average number of IELs per 100 enterocytes is comparable between ICI-CeD and ICI-Duo, with increased CD3+CD8+T cells compared with normal duodenum but decreased γδ T cells compared with CeD. Average PD-L1 percentage was 9% in ICI-CeD and 18% in ICI-Duo, in comparison to <1% in CeD and normal duodenum; average PD-1 percentage was very low to absent in all cases (<3%). On follow-up, five patients with ICI-CeD improved on a gluten-free diet (GFD) as the sole therapeutic intervention (with down-trending tTG-IgA) while the other three required immunosuppression. All patients who developed ICI-Duo received immunosuppression with variable improvement in symptoms.ConclusionsICI-CeD resembles ICI-Duo clinically and histologically but shares the serological features and response to gluten withdrawal with classic CeD. Immunophenotyping of IELs in ICI-CeD and ICI-Duo also shows similar CD3, CD8, γδ T cell subsets, and PD-L1 populations, all of which differed quantitatively from usual CeD. We conclude that ICI-CeD is biologically similar to ICI-Duo and is likely a variant of ICI-Duo, but treatment strategies differ, with ICI-CeD often improving with GFD alone, whereas ICI-Duo requires systemic immunosuppression.
Mechanical thrombectomy in patients with acute cancer-related stroke: is the stent retriever alone effective?
Authors: Jeon Yejin , Baik Sung Hyun , Jung Cheolkyu , Kim Jun Yup , Kim Beom Joon , Kang Jihoon , Bae Hee-Joon , Kim Jae Hyoung 
Published: June 2020

BackgroundThe optimal first-line mechanical thrombectomy (MT) method in cancer-related stroke (CRS) patients with emergent large vessel occlusion (ELVO) remains largely unknown. The aim of this study is to evaluate the efficacy and safety between contact aspiration (CA) first-line thrombectomy and stent retriever (SR) first-line thrombectomy in CRS patients.MethodsSixty-two CRS patients with ELVO, who underwent MT between January 2013 and October 2019 at our institution, were retrospectively analyzed. Patients were divided into two groups based on the first-line MT method and compared: the CA group (n=28), which included those who received CA alone or combined CA with SR, and the SR group (n=34), which included those who received conventional SR alone.ResultsOverall, reperfusion was successful in 75.8% (47/62) of CRS patients, and a good clinical outcome at 90 days was observed in 17.7%. The CA group showed a higher rate of successful reperfusion (89.3% vs 64.7%, P=0.025) shorter procedure time (22 vs 42 min; P=0.029), higher rate of first pass effect (35.7% vs 11.8%, P=0.025), and lower number of passes (1 vs 3, P=0.023) when compared with the SR group. The procedural and hemorrhagic complication rates were similar between the CA and SR groups. The first-line contact aspiration (OR 11.624, 95% CI 1.041 to 129.752; P=0.046) was an independent predictor of successful reperfusion.ConclusionsAmong patients with CRS, CA – whether alone or in combination with SR – as first-line MT seems to provide more rapid and successful reperfusion when compared with SR.
Role of adjuvant carotid ultrasound in women undergoing stress echocardiography for the assessment of suspected coronary artery disease
Authors: Gurunathan Sothinathan , Shanmuganathan Mayooran , Hampson Reinette , Khattar Rajdeep , Senior Roxy 
Published: June 2020

ObjectiveDue to the low prevalence of obstructive coronary artery disease (CAD) in women, stress testing has a relatively low predictive value for this. Additionally, conventional cardiovascular risk scores underestimate risk in women. This study sought to evaluate the role of atherosclerosis assessment using carotid ultrasound (CU) in women attending for stress echocardiography (SE).MethodsThis was a prospective study in which consecutive women with recent-onset suspected angina, who were referred for clinically indicated SE, underwent CU.Results415 women (mean age 61±10 years, 29% diabetes mellitus, mean body mass index 28) attending for SE underwent CU. 47 women (11%) had inducible wall motion abnormalities, and carotid disease (CD) was present in 46% (carotid plaque in 41%, carotid intima-media thickness >75th percentile in 15%). Women with CD were older (65 vs 58 years, p<0.001), and more likely to have diabetes (41% vs 21%, p=0.001), hypertension (67% vs 36%, p<0.01) and a higher pretest probability of CAD (59% vs 41%, p<0.001). 40% of women classified as low Framingham risk were found to have evidence of CD.The positive predictive value of SE for flow-limiting CAD was 51%, but with the presence of carotid plaque, this was 71% (p<0.01). Carotid plaque (p=0.004) and ischaemia (p=0.01) were the only independent predictors of >70% angiographic stenosis. In women with ischaemia on SE and no carotid plaque, the negative predictive value for flow-limiting disease was 88%.During a follow-up of 1058±234 days, there were 15 events (defined as all-cause mortality, non-fatal myocardial infarction, heart failure admissions and late coronary revascularisation). Age (HR 1.07 (1.00–1.15), p=0.04), carotid plaque burden (HR 1.65 (1.36–2.00), p<0.001) and ischaemic burden (HR 1.41 (1.18–1.68), p<0.001) were associated with outcome. There was a stepwise increase in events/year from 0.3% when there were no ischaemia and atherosclerosis, 1.1% when there was atherosclerosis and no ischaemia, 2.2% when there was ischaemia and no atherosclerosis and 10% when there were both ischaemia and atherosclerosis (p<0.001).ConclusionCU significantly improves the accuracy of SE alone for identifying flow-limiting disease on coronary angiography, and improves risk stratification in women attending for SE, as well identifying a subset of women who may benefit from primary preventative measures.