bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combining measures of immune infiltration shows additive effect on survival prediction in high-grade serous ovarian carcinoma
Authors: Montfort Anne , Barker-Clarke Rowan J. , Piskorz Anna M. , Supernat Anna , Moore Luiza , Al-Khalidi Sarwah , Böhm Steffen , Pharoah Paul , McDermott Jacqueline , Balkwill Frances R. , Brenton James D. 
Published: April 2020

Abstract
Background
In colorectal and breast cancer, the density and localisation of immune infiltrates provides strong prognostic information. We asked whether similar automated quantitation and combined analysis of immune infiltrates could refine prognostic information in high-grade serous ovarian carcinoma (HGSOC) and tested associations between patterns of immune response and genomic driver alterations.

Methods
Epithelium and stroma were semi-automatically segmented and the infiltration of CD45RO+, CD8+ and CD68+ cells was automatically quantified from images of 332 HGSOC patient tissue microarray cores.

Results
Epithelial CD8 [p = 0.027, hazard ratio (HR) = 0.83], stromal CD68 (p = 3 × 10−4, HR = 0.44) and stromal CD45RO (p = 7 × 10−4, HR = 0.76) were positively associated with survival and remained so when averaged across the tumour and stromal compartments. Using principal component analysis, we identified optimised multiparameter survival models combining information from all immune markers (p = 0.016, HR = 0.88). There was no significant association between PTEN expression, type of TP53 mutation or presence of BRCA1/BRCA2 mutations and immune infiltrate densities or principal components.

Conclusions
Combining measures of immune infiltration provided improved survival modelling and evidence for the multiple effects of different immune factors on survival. The presence of stromal CD68+ and CD45RO+ populations was associated with survival, underscoring the benefits evaluating stromal immune populations may bring for prognostic immunoscores in HGSOC.
Cerebrospinal Fluid Interaction with Cerebral Cortex during Pediatric Abusive Head Trauma
Authors: Toma Milan , Dehesa-Baeza Alfonso , Chan-Akaley Rosalyn , Nguyen Paul D. H. , Zwibel Hallie 
Published: April 2020

AbstractAbusive head trauma is the leading cause of fatal brain injuries in children younger than 2 years. It is a preventable and severe form of physical child abuse often linked to the forceful shaking of an infant or toddler. Victims of abusive head trauma can suffer permanent neurological damage, resulting in developmental delay and disability. The long-term effects of abusive head trauma are difficult to diagnose and predict. In this model, we use a high-order finite element method paired with the most comprehensive and current head/brain model and next-generation smoothed particle hydrodynamics. This is one of the first fluid–structure interaction frameworks that uses fluid material properties to represent the cerebrospinal fluid (CSF) while including all major anatomical features of the brain. The interaction of CSF with the brain cortex during abusive head trauma is demonstrated during multiple shaking cycles. A comprehensive and precise model that calculates for the role of CSF in neurological trauma will be useful both in the prevention and treatment of abusive head trauma and the determination of prognosis and patient outcomes.
Variation and dynamics of “complementizer agreement” in German
Authors: Fingerhuth Matthias , Lenz Alexandra N. 
Published: April 2020

Abstract
To date, there has been limited empirical research on complementizer agreement (CA). We investigate CA drawing on
a corpus of 144 speakers from 13 locations across Austria that was elicited through computer supported language production
experiments and recorded in conversations. We investigate the linguistic factors that govern the occurrence of CA, as well as its
areal distribution. We further explore the role of CA in speakers’ linguistic repertoires. The study finds evidence for the hypothesis that the
(non-)occurrence of CA is strongly dependent on the structure of its hosting C-elements and finds regional patterns. It also
identifies CA as a phenomenon which speakers place in a non-standard register. We use the collected data to test a theory of the
emergence of CA from clitic pronouns for Bavarian varieties of German.
Language contact through translation
Authors: Pang Shuangzi , Wang Kefei 
Published: April 2020

AbstractThis article investigates the role of translations from English in language change in Chinese. It employs a new corpus, the Chinese Diachronic Composite Corpus (CDCC), which incorporates a parallel corpus and comparable corpus in three sampling periods in the twentieth century, and a refe­rence corpus as a starting point in the timeframe. We examine whether explicitness in English–Chinese translations has exerted an impact on the target language, focusing on adversative conjunctions as a measure of explicitness. The results of the study demonstrate that: (1) translated Chinese texts have changed in step with original Chinese texts in the frequency of adversative conjunctions; (2) translated Chinese texts and original Chinese texts are interrelated throughout the three periods, but the correlation between them has changed perceptibly over the three sample points; and (3) source language interference found in translated Chinese texts increases over the three periods.
Impact of frailty on health-related quality of life 1 year after transcatheter aortic valve implantation
Authors: Goudzwaard Jeannette A , de Ronde-Tillmans Marjo J A G , van Hoorn Fleurance E D , Kwekkeboom Eline H C , Lenzen Mattie J , van Wiechen Maarten P H , Ooms Joris F W , Nuis Rutger-Jan , Van Mieghem Nicolas M , Daemen Joost , de Jaegere Peter P T , Mattace-Raso Francesco U S 
Published: April 2020

Abstract

Background
Transcatheter aortic valve implantation (TAVI) brings symptom relief and improvement in health-related quality of life (HRQoL) in the majority of patients treated for symptomatic, severe aortic stenosis. However, there is a substantial group of patients that do not benefit from TAVI. The aim of this study is to investigate the impact of frailty on HRQoL 1 year after TAVI.

Methods
The TAVI Care & Cure Program is an ongoing, prospective, observational study including patients referred for TAVI to our institution. A comprehensive geriatric assessment was performed to evaluate existence of frailty using the Erasmus Frailty Score (EFS). HRQoL was assessed using the EQ-5D-5 L at baseline and 1 year after TAVI.

Results
239 patients underwent TAVI and completed HRQoL assessment 1 year after TAVI. Seventy (29.3%) patients were classified as frail (EFS ≥ 3). In non-frail patients, the EQ-5D-5 L index did not change (0.71(± 0.22) to 0.68(± 0.33) points, P = 0.22); in frail patients, the EQ-5D-5 L index decreased from 0.55(±0.26) to 0.44 points (±0.33) (P = 0.022). Frailty was an independent predictor of deteriorated HRQoL 1 year after TAVI (OR 2.24, 95% CI 1.07–4.70, P = 0.003). In frail patients, the absence of peripheral artery disease (OR 0.17, 95% 0.05–0.50, P = 0.001) and renal dysfunction (OR 0.13, 95% CI 0.04–0.41, P = &lt;0.001) at baseline was associated with improved HRQoL 1 year after TAVI.

Conclusion
Frailty is associated with deterioration of HRQoL 1 year after TAVI. Notably, HRQoL did improve in frail patients with no peripheral arterial disease or renal impairment at baseline.
The Internal Limits on Fiduciary Loyalty
Authors: Gold Andrew S 
Published: April 2020

Abstract:
In the abstract, the limits on a lawyer’s loyalty obligations could take several forms. For example, constraints on a fiduciary’s loyalty obligations may be derived from a correct understanding of that fiduciary’s loyalty itself. Indeed, violations might count as a form of disloyalty to the client. Alternatively, such constraints could stem from obligations owed to parties other than a lawyer’s client, or even something more abstract like the rule of law. Notably, such constraints could be derived from legal principles that have nothing to do with fiduciary law. Each of these options is a conceptual possibility, contingent on the choices made by a given legal system. Constraints on a loyalty obligation that are implications of that loyalty obligation itself are defined here as internal. Constraints imposed from outside a given fiduciary loyalty obligation are defined as external. This paper seeks to deepen our understanding of a particular type of fiduciary loyalty (the loyalty owed by lawyers) by focusing on the role of such internal constraints, and in the process to elaborate on the scope of loyalty obligations more generally. This paper will also indicate why we should care about the internal/external distinction. Among other things, this distinction helps determine whether lawyers are better seen as private or public fiduciaries, and in practice it may bear on both judicial reasoning and legal compliance.
Improving the Service to Aboriginal and Torres Strait Islanders through Innovative Practices Between Aboriginal Hospital Liaison Officers and Social Workers in Hospitals in Victoria, Australia†
Authors: Bnads Helen , Orr Elizabeth , Clements C John 
Published: April 2020

Abstract
Aboriginal and Torres Strait Islanders have suffered violence and extreme prejudice in every walk of life as a result of the European colonisation of Australia. We acknowledge the ongoing colonial legacy to this suffering and discuss how cultural safety is a solution to overcoming some elements of the disadvantages that still beset Aboriginal and Torres Strait Islander people in terms of accessing health care. Accessible and culturally safe health services are critical in reducing health inequalities for First Nations’ people because of the burden of ill-health they experience. ‘Cultural safety’ in this context refers to approaches that strengthen and respectfully engage with Aboriginal and Torres Strait Islander cultures in mainstream services. Alongside holistic Indigenous health and primary prevention approaches, a broad range of medical, socio-cultural and allied health support is needed to alleviate these inequalities. In this article, we describe how the working relationship between Aboriginal Hospital Liaison Officers and Social Workers in public hospitals in Victoria, Australia, contributes to cultural safety, and thereby improves the quality of care and a reduction in discharges against medical advice by Aboriginal patients. We conclude that elements of this model may be applicable to improving care for First Nation peoples in other countries.
SER-109, an Investigational Microbiome Drug to Reduce Recurrence After Clostridioides difficile Infection: Lessons Learned From a Phase 2 Trial
Authors: McGovern Barbara H , Ford Christopher B , Henn Matthew R , Pardi Darrell S , Khanna Sahil , Hohmann Elizabeth L , O’Brien Edward J , Desjardins Christopher A , Bernardo Patricia , Wortman Jennifer R , Lombardo Mary-Jane , Litcofsky Kevin D , Winkler Jonathan A , McChalicher Christopher W J , Li Sunny S , Tomlinson Amelia D , Nandakumar Madhumitha , Cook David N , Pomerantz Roger J , Auninš John G , Trucksis Michele 
Published: April 2020

Abstract

Background
Recurrent Clostridioides difficile infection (rCDI) is associated with loss of microbial diversity and microbe-derived secondary bile acids, which inhibit C. difficile germination and growth. SER-109, an investigational microbiome drug of donor-derived, purified spores, reduced recurrence in a dose-ranging, phase (P) 1 study in subjects with multiple rCDIs.

Methods
In a P2 double-blind trial, subjects with clinical resolution on standard-of-care antibiotics were stratified by age (&lt; or ≥65 years) and randomized 2:1 to single-dose SER-109 or placebo. Subjects were diagnosed at study entry by PCR or toxin testing. Safety, C. difficile–positive diarrhea through week 8, SER-109 engraftment, and bile acid changes were assessed.

Results
89 subjects enrolled (67% female; 80.9% diagnosed by PCR). rCDI rates were lower in the SER-109 arm than placebo (44.1% vs 53.3%) but did not meet statistical significance. In a preplanned analysis, rates were reduced among subjects ≥65 years (45.2% vs 80%, respectively; RR, 1.77; 95% CI, 1.11–2.81), while the &lt;65 group showed no benefit. Early engraftment of SER-109 was associated with nonrecurrence (P &lt; .05) and increased secondary bile acid concentrations (P &lt; .0001). Whole-metagenomic sequencing from this study and the P1 study revealed previously unappreciated dose-dependent engraftment kinetics and confirmed an association between early engraftment and nonrecurrence. Engraftment kinetics suggest that P2 dosing was suboptimal. Adverse events were generally mild to moderate in severity.

Conclusions
Early SER-109 engraftment was associated with reduced CDI recurrence and favorable safety was observed. A higher dose of SER-109 and requirements for toxin testing were implemented in the current P3 trial.

Clinical Trials Registration
NCT02437487, https://clinicaltrials.gov/ct2/show/NCT02437487?term=SER-109&draw= 2&rank=4.
Encoder–Decoder Couplet Generation Model Based on ‘Trapezoidal Context’ Character Vector
Authors: Gao Rui , Zhu Yuanyuan , Li Mingye , Li Shoufeng , Shi Xiaohu 
Published: April 2020

Abstract
This paper studies the couplet generation model which automatically generates the second line of a couplet by giving the first line. Unlike other sequence generation problems, couplet generation not only considers the sequential context within a sentence line but also emphasizes the relationships between the corresponding words of first and second lines. Therefore, a trapezoidal context character embedding the vector model has been developed firstly, which considers the ‘sequence context’ and the ‘corresponding word context’ simultaneously. Afterwards, we chose the typical encoder–decoder framework to solve the sequence–sequence problems, of which the encoder and decoder are used by bi-directional GRU and GRU, respectively. In order to further increase the semantic consistency of the first and second lines of couplets, the pre-trained sentence vector of the first line is added to the attention mechanism in the model. To verify the effectiveness of the method, it is applied to the real data set. Experimental results show that our proposed model can compete with the up-to-date methods, and both adding sentence vectors to attention and using trapezoidal context character vectors can improve the effectiveness of the algorithm.
Integrated in silico and 3D in vitro model of macrophage migration in response to physical and chemical factors in the tumor microenvironment
Authors: Lee Sharon Wei Ling , Seager R J , Litvak Felix , Spill Fabian , Sieow Je Lin , Leong Penny Hweixian , Kumar Dillip , Tan Alrina Shin Min , Wong Siew Cheng , Adriani Giulia , Zaman Muhammad Hamid , Kamm and Roger D 
Published: April 2020

AbstractMacrophages are abundant in the tumor microenvironment (TME), serving as accomplices to cancer cells for their invasion. Studies have explored the biochemical mechanisms that drive pro-tumor macrophage functions; however the role of TME interstitial flow (IF) is often disregarded. Therefore, we developed a three-dimensional microfluidic-based model with tumor cells and macrophages to study how IF affects macrophage migration and its potential contribution to cancer invasion. The presence of either tumor cells or IF individually increased macrophage migration directedness and speed. Interestingly, there was no additive effect on macrophage migration directedness and speed under the simultaneous presence of tumor cells and IF. Further, we present an in silico model that couples chemokine-mediated signaling with mechanosensing networks to explain our in vitro observations. In our model design, we propose IL-8, CCL2, and β-integrin as key pathways that commonly regulate various Rho GTPases. In agreement, in vitro macrophage migration remained elevated when exposed to a saturating concentration of recombinant IL-8 or CCL2 or to the co-addition of a sub-saturating concentration of both cytokines. Moreover, antibody blockade against IL-8 and/or CCL2 inhibited migration that could be restored by IF, indicating cytokine-independent mechanisms of migration induction. Importantly, we demonstrate the utility of an integrated in silico and 3D in vitro approach to aid the design of tumor-associated macrophage-based immunotherapeutic strategies.
Factors Associated with Poor Quality of Life in a Canadian Cohort of Patients with Inflammatory Bowel Disease: A Cross-sectional Study
Authors: Nazarian Amir , Bishay Kirles , Gholami Reza , Scaffidi Michael A , Khan Rishad , Cohen-Lyons Daniel , Griller Nadia , Satchwell Joshua B , Baker Jeffrey P , Grover Samir C , Irvine Elizabeth Jan 
Published: April 2020

Abstract

Background
Health-related quality of life (QoL) is often adversely affected in patients with inflammatory bowel disease (IBD). We aimed to identify factors associated with poor QoL among Canadian patients with IBD in clinical remission.

Methods
We enrolled patients at a single academic tertiary care center with inactive IBD. All eligible patients completed a series of questionnaires that included questions on demographics, disease activity, anxiety, depression and the presence of irritable bowel syndrome (IBS) symptoms. Stool sample for fecal calprotectin (FC) was also collected to assess for subclinical inflammation. The primary outcome measure was QoL assessed by the short inflammatory bowel disease questionnaire (SIBDQ), with planned subgroup comparisons for fatigue, anxiety, depression and IBS symptoms.

Results
Ninety-three patients were eligible for inclusion in this study. The median SIBDQ scores were lower in patients with anxiety (P &lt; 0.001), depression (P = 0.004), IBS symptoms (P &lt; 0.001) and fatigue (P = 0.018). Elevated FC in patients in clinical remission did not impact QoL. These findings were consistent on multivariate linear regression.

Conclusions
Anxiety, depression, fatigue and IBS symptoms are all independently associated with lower QoL in patients with inactive IBD. Clinicians are encouraged to screen for these important factors as they may detrimentally impact QoL in IBD patients even in clinical remission.
Manipulation of long-shaft stapler in robotic-assisted thoracoscopic surgery lung resection
Authors: Mitsuboshi Shota , Ogihara Akira , Katagiri Sayaka , Maeda Hideyuki , Aoshima Hiroe , Matsumoto Takako , Isaka Tamami , Kanzaki Masato 
Published: April 2020

Abstract
The number of robotic surgical procedures for thoracic disease is increasing. The automatic linear stapler has become a necessary device in endoscopic surgery. A 67-year-old man with a history of smoking was referred to our hospital for an abnormal finding on chest x-ray. Computer tomography of the chest revealed a ground glass nodule in the right middle lobe. We performed right middle wedge resection through the assistant port using a long-shaft stapler (LSS). Because the nodule was diagnosed as an adenocarcinoma on the intraoperative frozen section, the patient underwent robotic-assisted thoracoscopic surgery (RATS) right middle lobectomy using the da Vinci® Xi system. The pulmonary arteries, veins, right middle bronchus and minor fissure were divided using the LSS through the utility thoracotomy or assistant port. The postoperative course was uncomplicated. This case suggests that the LSS can be used in RATS lung resection for cancer.
The effects of knee arthroplasty on plasma vitamin C concentrations and cognitive function: a case study
Authors: Travica Nikolaj , Ried Karin , Pipingas Andrew , Hudson Irene , Young David , Scholey Andrew , Sali Avni 
Published: April 2020

AbstractPost-operative neurocognitive disorders are becoming well-documented conditions, with their pathogenesis remaining unclear. Vitamin C is a molecule that has recently demonstrated both a potential link with cognitive function and a significant post-operative decline. Here, we present a case study of a 72-year-old male who underwent total knee replacement surgery. The patient demonstrated a substantial decline in plasma vitamin C concentrations, indicative of a severe deficiency, during the first post-operative week (post-operative Days 3 and 7). Similarly, at these time points, a number of validated paper and pen tests revealed a substantial decline in cognition on tasks relating to total recall, delayed recall, motor speed, recognition and motor speed, with no signs of delirium. These results provide the justification for larger, cohort studies to determine whether post-operative plasma vitamin C depletions could contribute to cognitive deficits post-operatively.
Electrical Stimulation Therapies for Active Duty Military with Patellofemoral Pain Syndrome: A Randomized Trial
Authors: Talbot Laura A , Solomon Zack , Webb Lee , Morrell Christopher , Metter E Jeffrey 
Published: April 2020

Abstract

Introduction
Patellofemoral pain syndrome (PFPS) is a common musculoskeletal disorder among military service members that causes knee pain, quadriceps strength loss, and impaired motor performance in otherwise healthy individuals. PFPS poses a threat to the health, fitness, and subsequent readiness of the total force. The goal of rehabilitation for military service members with PFPS is to regain physical capacity of strength and function and to reduce pain, in order to restore readiness in this population. The randomized controlled trial reported here compared an active home exercise program (HEP) alone with three different electrical stimulation treatment regimens implemented concurrently with HEP postulated improvements in lower extremity strength and physical functional performance while also reducing pain in active duty military diagnosed with PFPS.

Materials and Methods
After baseline testing, 130 active duty military members with PFPS were randomized to 1 of 4 treatment groups: (1) neuromuscular electrical stimulation (NMES) with HEP; (2) transcutaneous electrical nerve stimulation (TENS) with HEP; (3) combined NMES/TENS with HEP; (4) active HEP only. The primary outcome measure was degree of change in knee flexion and extension strength over 9 weeks. Secondary outcomes were physical functional performance and knee pain. The primary analyses used repeated measures, linear mixed-effects models with a random effect for subject, time as a continuous variable, group as a categorical variable, and a group and time interaction to test for differences in change over time among the groups.

Results
All three electrical stimulation treatment groups improved in knee extension strength in the PFPS limb to a greater extent than the HEP alone group over the 9-week treatment period. The NMES and NMES/TENS groups improved to a greater extent than the HEP alone group in knee flexion strength in the PFPS limb. The reported pain improved over time for all treatment groups with no significant group differences. All three stimulation groups performed better on the 6-min walk test than the HEP alone group.

Conclusion
The findings from this study showed that all three electrical stimulation with HEP treatment groups showed greater improvement in strength compared to the HEP alone group. These findings could offer alternative forms of rehabilitation for AD military with PFPS as these treatment regimens can be easily implemented at home station or during deployment.