bluuebunny/crossref_metadata_2025 huggingface dataset:
EXTraction of EMR numerical data: an efficient and generalizable tool to EXTEND clinical research
Authors: Cai Tianrun , Zhang Luwan , Yang Nicole , Kumamaru Kanako K. , Rybicki Frank J. , Cai Tianxi , Liao Katherine P.
Published: November 2019

Background

Electronic medical records (EMR) contain numerical data important for clinical outcomes research, such as vital signs and cardiac ejection fractions (EF), which tend to be embedded in narrative clinical notes. In current practice, this data is often manually extracted for use in research studies. However, due to the large volume of notes in datasets, manually extracting numerical data often becomes infeasible. The objective of this study is to develop and validate a natural language processing (NLP) tool that can efficiently extract numerical clinical data from narrative notes.

Results

To validate the accuracy of the tool EXTraction of EMR Numerical Data (EXTEND), we developed a reference standard by manually extracting vital signs from 285 notes, EF values from 300 notes, glycated hemoglobin (HbA1C), and serum creatinine from 890 notes. For each parameter of interest, we calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and F1 score of EXTEND using two metrics.

(1) completion of data extraction, and (2) accuracy of data extraction compared to the actual values in the note verified by chart review. At the note level, extraction by EXTEND was considered correct only if it accurately detected and extracted all values of interest in a note.

Using manually-annotated labels as the gold standard, the note-level accuracy of EXTEND in capturing the numerical vital sign values, EF, HbA1C and creatinine ranged from 0.88 to 0.95 for sensitivity, 0.95 to 1.0 for specificity, 0.95 to 1.0 for PPV, 0.89 to 0.99 for NPV, and 0.92 to 0.96 in F1 scores. Compared to the actual value level, the sensitivity, PPV, and F1 score of EXTEND ranged from 0.91 to 0.95, 0.95 to 1.0 and 0.95 to 0.96.

Conclusions

EXTEND is an efficient, flexible tool that uses knowledge-based rules to extract clinical numerical parameters with high accuracy. By increasing dictionary terms and developing new rules, the usage of EXTEND can easily be expanded to extract additional numerical data important in clinical outcomes research.
Identifying and addressing gaps in the implementation of a community care team for care of Patients with multiple chronic conditions
Authors: Boehmer Kasey R. , Holland Diane E. , Vanderboom Catherine E.
Published: November 2019

Background

Patients with multiple chronic conditions represent a growing segment for healthcare. The Chronic Care Model (CCM) supports leveraging community programs to support patients and their caregivers overwhelmed by their treatment plans, but this component has lagged behind the adoption of other model elements. Community Care Teams (CCTs) leverage partnerships between healthcare delivery systems and existing community programs to address this deficiency. There remains a gap in moving CCTs from pilot phase to sustainable full-scale programs. Therefore, the purpose of this study was to identify the cognitive and structural needs of clinicians, social workers, and nurse care coordinators to effectively refer appropriate patients to the CCT and the value these stakeholders derived from referring to and receiving feedback from the CCT. We then sought to translate this knowledge into an implementation toolkit to bridge implementation gaps.

Methods

Our research process was guided by the Assess, Innovate, Develop, Engage, and Devolve (AIDED) implementation science framework. During the Assess process we conducted chart reviews, interviews, and observations and in Innovate and Develop phases, we worked with stakeholders to develop an implementation toolkit. The Engage and Devolve phases disseminate the toolkit through social networks of clinical champions and are ongoing.

Results

We completed 14 chart reviews, 11 interviews, and 2 observations. From these, facilitators and barriers to CCT referrals and patient re-integration into primary care were identified. These insights informed the development of a toolkit with seven components to address implementation gaps identified by the researchers and stakeholders.

Conclusion

We identified implementation gaps to sustaining the CCT program, a community-healthcare partnership, and used this information to build an implementation toolkit. We established liaisons with clinical champions to diffuse this information. The AIDED Model, not previously used in high-income countries’ primary care settings, proved adaptable and useful.
Alopecia in Belgian Blue crossbred calves: a case series
Authors: Wieland Matthias , Mann Sabine , Gollnick Nicole S. , Majzoub-Altweck Monir , Knubben-Schweizer Gabriela , Langenmayer Martin C.
Published: November 2019

Background

Alopecia is defined as the partial or complete absence of hair from areas of the body where it normally grows. Alopecia secondary to an infectious disease or parasitic infestation is commonly seen in cattle. It can also have metabolic causes, for example in newborn calves after a disease event such as diarrhoea. In the article, the investigation of a herd problem of acquired alopecia in Belgian Blue (BB) crossbred calves is described.

Case presentation

Several BB crossbred calves had presented with moderate to severe non-pruritic alopecia in a single small herd located in Southern Germany. The referring veterinarian had ruled out infectious causes, including parasitic infection and had supplemented calves with vitamins (vitamins A, B1, B2, B3, B5, B6, B7, B9, B12, C, and K3) orally. Results of the diagnostic workup at the Clinic for Ruminants are presented for three affected calves and findings from a farm visit are discussed. Because of these investigations, an additional four calves were brought to the referral clinic within the first week of life, and before onset of alopecia, in order to study the course of the condition; however, these calves never developed any signs of alopecia during their clinic stay.

Conclusions

Because all other plausible differential diagnoses were ruled out during our investigation, we concluded that the documented alopecia was due to malabsorption of dietary fat and consecutive disruption of lipid metabolism leading to telogen or anagen effluvium. In this particular case, this was caused by a mixing error of milk replacer in conjunction with insufficiently tempered water. We conclude that nutritional, management or environmental factors alone can lead to moderate to severe alopecia in calves in the absence of a prior or concurrent disease event or infectious cause.
Role of the complement system in the tumor microenvironment
Authors: Zhang Ronghua , Liu Qiaofei , Li Tong , Liao Quan , Zhao Yupei
Published: November 2019

The complement system has traditionally been considered a component of innate immunity against invading pathogens and “nonself” cells. Recent studies have demonstrated the immunoregulatory functions of complement activation in the tumor microenvironment (TME). The TME plays crucial roles in tumorigenesis, progression, metastasis and recurrence. Imbalanced complement activation and the deposition of complement proteins have been demonstrated in many types of tumors. Plasma proteins, receptors, and regulators of complement activation regulate several biological functions of stromal cells in the TME and promote the malignant biological properties of tumors. Interactions between the complement system and cancer cells contribute to the proliferation, epithelial-mesenchymal transition, migration and invasion of tumor cells. In this review, we summarize recent advances related to the function of the complement system in the TME and discuss the therapeutic potential of targeting complement-mediated immunoregulation in cancer immunotherapy.
β-TrCP-mediated ubiquitination and degradation of Dlg5 regulates hepatocellular carcinoma cell proliferation
Authors: Wang Dongping , Zhang Qi , Li Fenfen , Wang Chan , Yang Changming , Yu Hong
Published: November 2019

Background

Discs large homolog 5 (Dlg5) is a member of the membrane-associated guanylate kinase (MAGUK) adaptor family of proteins and its deregulation has been implicated in the malignancy of several cancer types. Dlg5 was down-regulated in hepatocellular carcinoma (HCC) and lower Dlg5 expression was associated with poor survival of HCC patients. However, how to regulate Dlg5 remains largely unknown.

Methods

The co-immunoprecipitation assay was used to determine the interaction between Dlg5 and β-TrCP. The in vivo ubiquitination assay was performed to determine the regulation of Dlg5 by β-TrCP. CCK-8 and colony formation assay were implemented to detect the biological effect of Dlg5 on the growth of HCC cells in vitro. The effect of Dlg5 on HCC tumor growth in vivo was studied in a tumor xenograft model in mice.

Results

Here we report that Dlg5 is regulated by the ubiquitin proteasome system and depletion of either Cullin 1 or β-TrCP led to increased levels of Dlg5. β-TrCP regulated Dlg5 protein stability by targeting it for ubiquitination and subsequent destruction in a phosphorylation-dependent manner. We further demonstrated a crucial role of Ser730 in the non-canonical phosphodegron of Dlg5 in governing β-TrCP-mediated Dlg5 degradation. Importantly, failure to degrade Dlg5 significantly inhibited HCC cells proliferation both in vitro and in vivo.

Conclusion

Collectively, our finding provides a novel molecular mechanism for the negative regulation of Dlg5 by β-TRCP in HCC cells. It further suggests that preventing Dlg5 degradation could be a possible novel strategy for clinical treatment of HCC.
Highly versatile cancer photoimmunotherapy using photosensitizer-conjugated avidin and biotin-conjugated targeting antibodies
Authors: Shirasu Naoto , Shibaguchi Hirotomo , Yamada Hiromi , Kuroki Masahide , Yasunaga Shin’ichiro
Published: November 2019

Background

Photoimmunotherapy (PIT) employing antibody-photosensitizer conjugates is a promising treatment for cancer. However, the fixed antigen specificity severely limits the efficacy and the applicability. Here we describe a universal strategy for PIT of cancer by using a near-infrared (NIR) photosensitizer IRDye700DX-conjugated NeutrAvidin, designated as AvIR, together with various biotinylated antibodies (BioAbs) for cellular targeting.

Methods

Cytotoxicity of AvIR-mediated PIT was evaluated by fluorescence imaging and cell viability assay. Phototoxic effect on tumorigenicity was assessed by tumorsphere-formation assay and Matrigel invasion assay. Cancer stem cell-like side-population (SP) cells were identified by flow cytometry.

Results

CHO cells stably expressing carcinoembryonic antigen or EpCAM were pre-labeled with each BioAb for the corresponding antigen, followed by AvIR administration. NIR light irradiation specifically killed the targeted cells, but not off-targets, demonstrating that the AvIR-mediated PIT does work as expected. CSC-like subpopulation of MCF-7 cells (CD24low/CD44high) and SP of HuH-7 cells (CD133+/EpCAM+) were effectively targeted and photokilled by AvIR-PIT with anti-CD44 BioAb or anti-CD133/anti-EpCAM BioAbs, respectively. As results, the neoplastic features of the cell lines were sufficiently suppressed. Cancer-associated fibroblast (CAF)-targeted AvIR-PIT by using anti-fibroblast activation protein BioAb showed an abolishment of CAF-enhanced clonogenicity of MCF-7 cells.

Conclusions

Collectively, our results demonstrate that AvIR-mediated PIT can greatly broaden the applicable range of target specificity, with feasibility of efficacious and integrative control of CSC and its microenvironment.
Assessment of eye fatigue caused by head-mounted displays using eye-tracking
Authors: Wang Yan , Zhai Guangtao , Chen Sichao , Min Xiongkuo , Gao Zhongpai , Song Xuefei
Published: November 2019

Background

Head-mounted displays (HMDs) and virtual reality (VR) have been frequently used in recent years, and a user’s experience and computation efficiency could be assessed by mounting eye-trackers. However, in addition to visually induced motion sickness (VIMS), eye fatigue has increasingly emerged during and after the viewing experience, highlighting the necessity of quantitatively assessment of the detrimental effects. As no measurement method for the eye fatigue caused by HMDs has been widely accepted, we detected parameters related to optometry test. We proposed a novel computational approach for estimation of eye fatigue by providing various verifiable models.

Results

We implemented three classifications and two regressions to investigate different feature sets, which led to present two valid assessment models for eye fatigue by employing blinking features and eye movement features with the ground truth of indicators for optometry test. Three graded results and one continuous result were provided by each model, respectively, which caused the whole result to be repeatable and comparable.

Conclusion

We showed differences between VIMS and eye fatigue, and we also presented a new scheme to assess eye fatigue of HMDs users by analysis of parameters of the eye tracker.
Following the legacy of professors Barbara Starfield and Leiyu Shi in Brazil as health policy: the National Health Survey (PNS), led by the Brazilian National Institute of Geography and Statistics (IBGE) and the Primary Care Assessment Tool (PCAT)
Authors: Harzheim Erno , Felipe Pinto Luiz , D’Avila Otavio Pereira , Hauser Lisiane
Published: November 2019

We present to the scientific community the pioneering of Brazilian National Institute of Geography and Statistics (IBGE, the Brazilian Census Bureau) in partnership with the Ministry of Health, the largest fieldwork ever conducted in a single country in the world, using the PCAT in a national household sample survey, visiting more than 100,000 households and 40% of the country’s municipalities. In Brazil, PCAT is being consolidated as an instrument to support public policy for the evaluation of primary health care. We believe that it represents a virtuous example of dialogue between scientific community and health management, following the legacy of Professors Barbara Starfield and Leiyu Shi.
Association between prenatal exposure to perfluoroalkyl substances and asthma in 5-year-old children in the Odense Child Cohort
Authors: Beck Iben Have , Timmermann Clara Amalie Gade , Nielsen Flemming , Schoeters Greet , Jøhnk Camilla , Kyhl Henriette Boye , Høst Arne , Jensen Tina Kold
Published: November 2019

Background

Asthma is the most common non-communicable disease in children. Prenatal exposure to perfluoroalkyl substances (PFASs), a group of persistent environmental chemicals with endocrine disrupting abilities, has been associated with immunomodulation and may contribute to the aetiology of asthma. We investigated the associations between prenatal exposure to five PFASs and asthma in 5-year-old children.

Methods

We studied 981 mother-child pairs within the Odense Child Cohort (OCC), Denmark. We measured perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) in maternal serum donated in early pregnancy. A standardized questionnaire based on the International Study of Asthma and Allergies in Childhood (ISAAC) was used to assess wheeze, self-reported asthma and doctor-diagnosed asthma among children at age 5 years. Associations were examined using logistic regression analyses adjusting for parity, maternal educational level, maternal pre-pregnancy BMI, asthma predisposition and child sex.

Results

Among the 5-year-old children 18.6% reported wheeze and 7.1% reported asthma. We found no association between prenatal exposure to PFAS and doctor-diagnosed asthma or wheeze. Prenatal PFAS exposure was associated with self-reported asthma, although only significant for PFNA (OR = 1.84, 95% CI 1.03,3.23).

Conclusion

Our findings support the suggested immunomodulatory effects of PFASs, however, additional studies are warranted. In order to verify our findings, it is important to re-examine the children with postnatal measurements of serum PFAS concentrations and additional clinical diagnostic testing at an older age where an asthma diagnosis is more valid.
FoxO3 regulates hepatic triglyceride metabolism via modulation of the expression of sterol regulatory-element binding protein 1c
Authors: Wang Liu , Zhu Xiaopeng , Sun Xiaoyang , Yang Xinyu , Chang Xinxia , Xia Mingfeng , Lu Yan , Xia Pu , Yan Hongmei , Bian Hua , Gao Xin
Published: November 2019

Background

Excessive intrahepatic lipid accumulation is the major characteristic of nonalcoholic fatty liver disease (NAFLD). We sought to identify the mechanisms involved in hepatic triglyceride (TG) homeostasis. Forkhead box class O (FoxO) transcription factors have been shown to play an important role in hepatic metabolism. However, little is known about the effect of FoxO3 on hepatic TG metabolism.

Methods

Liver biopsy samples from patients with NALFD and liver tissues from high glucose and high sucrose (HFHS) fed mice, ob/ob mice and db/db mice were collected for protein and mRNA analysis. HepG2 cells were transfected with small interfering RNA to mediate FoxO3 knockdown, or adenovirus and plasmid to mediate FoxO3 overexpression. FoxO3-cDNA was delivered by adenovirus to the liver of C57BL/6 J male mice on a chow diet or on a high-fat diet, followed by determination of hepatic lipid metabolism. Sterol regulatory element-binding protein 1c (SREBP1c) luciferase reporter gene plasmid was co-transfected into HepG2 cells with FoxO3 overexpression plasmid.

Results

FoxO3 expression was increased in the livers of HFHS mice, ob/ob mice, db/db mice and patients with NAFLD. Knockdown of FoxO3 reduced whereas overexpression of FoxO3 increased cellular TG concentrations in HepG2 cells. FoxO3 gain-of-function caused hepatic TG deposition in C57BL/6 J mice on a chow diet and aggravated hepatic steatosis when fed a high-fat diet. Analysis of the transcripts established the increased expression of genes related to TG synthesis, including SREBP1c, SCD1, FAS, ACC1, GPAM and DGAT2 in mouse liver. Mechanistically, overexpression of FoxO3 stimulated the expression of SREBP1c, whereas knockdown of FoxO3 inhibited the expression of SREBP1c. Luciferase reporter assays showed that SREBP1c regulated the transcriptional activity of the SREBP1c promoter.

Conclusions

FoxO3 promotes the transcriptional activity of the SREBP1c promoter, thus leading to increased TG synthesis and hepatic TG accumulation.
Correction to: Feminisation of the health workforce and wage conditions of health professions: an exploratory analysis
Authors: Shannon Geordan , Minckas Nicole , Tan Des , Haghparast-Bidgoli Hassan , Batura Neha , Mannell Jenevieve
Published: November 2019

The original article [1] contained an error in the presentation of all figures and tables; each figure and table is now set out and designated appropriately in the original article.
Plasma concentration of interleukin-6 was upregulated in cancer cachexia patients and was positively correlated with plasma free fatty acid in female patients
Authors: Han Jun , Lu Chaocheng , Meng Qingyang , Halim Alice , Yean Thong Jia , Wu Guohao
Published: November 2019

Background

Cancer cachexia is a clinical manifestation in various advanced cancers that characterized by muscle atrophy and fat loss as its main features; it is frequently associated with systemic inflammatory response. However, the differences in inflammatory response and lipid metabolism of different genders remain unclear. This study explores the difference between cachexic and non-cachexic patients in different genders and cancer types and focus on the plasma inflammation factors levels and lipid metabolism parameters in different genders.

Methods

We first analyzed the general characteristics in 311 cancer patients between cachexic and non-cachexic patients, with an emphasis on expression levels related to inflammatory factors and lipid metabolism parameters. We then further analyzed these characteristics in different genders and cancer types. Lastly, the correlations between plasma interleukin-6 (IL-6) and lipid metabolism parameters in cachexia patients of different genders were analyzed.

Results

Among 311 patients, there were 74 cancer cachexia patients (50 males and 24 females) and 237non-cachexia patients (150 males and 87 females). Body mass index (BMI), TNM stage, plasma concentration of hemoglobin, platelet, lymphocyte count, total protein, albumin, prealbumin, total cholesterol, apolipoprotein E (ApoE), free fatty acid (FFA) and IL-6 were significantly different between cachexic and non-cachexic patients (allp < 0.05). In addition, these characteristics were different in different cancer types. When compared to male non-cachexic patients, male cachexic patients showed a significant increase in plasma levels of IL-6 and platelet, later TNM stage, with marked decrease in their plasma total protein, albumin, prealbumin, ApoE as well as their lymphocyte counts and hemoglobin levels (allp < 0.05). In comparison with female non-cachexic patients, female cachexic patients’ IL-6 levels and FFA were significantly elevated with noticeable decrease in their BMI, total cholesterol, ApoE and prealbumin, as well as later TNM stage (allp < 0.05). Correlation analysis revealed that IL-6 levels in female cachexic patients had a significant positive correlation with FFA expression, but this correlation not reflected in male patients.

Conclusion

This study demonstrates the different metabolic characteristics of male and female cancer cachexia patients. Future study about cancer cachexia should pay attention to different genders and cancer types.
Comparative effectiveness and safety of pharmacological and non-pharmacological interventions for insomnia: an overview of reviews
Authors: Rios Patricia , Cardoso Roberta , Morra Deanna , Nincic Vera , Goodarzi Zahra , Farah Bechara , Harricharan Sharada , Morin Charles M. , Leech Judith , Straus Sharon E. , Tricco Andrea C.
Published: November 2019

Background

This review aimed to assess the existing evidence regarding the clinical effectiveness and safety of pharmacological and non-pharmacological interventions in adults with insomnia and identify where research or policy development is needed.

Methods

MEDLINE, Embase, PsycINFO, The Cochrane Library, and PubMed were searched from inception until June 14, 2017, along with relevant gray literature sites. Two reviewers independently screened titles/abstracts and full-text articles, and a single reviewer with an independent verifier completed charting, data abstraction, and quality appraisal.

Results

A total of 64 systematic reviews (35 with meta-analysis) were included after screening 5024 titles and abstracts and 525 full-text articles. Eight of the included reviews were rated as high quality using the Assessment of Multiple Systematic Reviews 2 (AMSTAR2) tool, and over half of the included articles (n = 40) were rated as low or critically low quality. Consistent evidence of effectiveness across multiple outcomes based on more than one high- or moderate quality review with meta-analysis was found for zolpidem, suvorexant, doxepin, melatonin, and cognitive behavioral therapy (CBT), and evidence of effectiveness across multiple outcomes based on one high-quality review with meta-analysis was found for temazepam, triazolam, zopiclone, trazodone, and behavioral interventions. These interventions were mostly evaluated in the short term (< 16 weeks), and there was very little harms data available for the pharmacological interventions making it difficult to evaluate their risk-benefit ratio.

Conclusions

Assuming non-pharmacological interventions are preferable from a safety perspective CBT can be considered an effective first-line therapy for adults with insomnia followed by other behavioral interventions. Short courses of pharmacological interventions can be supplements to CBT or behavioral therapy; however, no evidence regarding the appropriate duration of pharmacological therapy is available from these reviews.

Systematic review registration

PROSPERO CRD42017072527.
Assessing the accuracy of machine-assisted abstract screening with DistillerAI: a user study
Authors: Gartlehner Gerald , Wagner Gernot , Lux Linda , Affengruber Lisa , Dobrescu Andreea , Kaminski-Hartenthaler Angela , Viswanathan Meera
Published: November 2019

Background

Web applications that employ natural language processing technologies to support systematic reviewers during abstract screening have become more common. The goal of our project was to conduct a case study to explore a screening approach that temporarily replaces a human screener with a semi-automated screening tool.

Methods

We evaluated the accuracy of the approach using DistillerAI as a semi-automated screening tool. A published comparative effectiveness review served as the reference standard. Five teams of professional systematic reviewers screened the same 2472 abstracts in parallel. Each team trained DistillerAI with 300 randomly selected abstracts that the team screened dually. For all remaining abstracts, DistillerAI replaced one human screener and provided predictions about the relevance of records. A single reviewer also screened all remaining abstracts. A second human screener resolved conflicts between the single reviewer and DistillerAI. We compared the decisions of the machine-assisted approach, single-reviewer screening, and screening with DistillerAI alone against the reference standard.

Results

The combined sensitivity of the machine-assisted screening approach across the five screening teams was 78% (95% confidence interval [CI], 66 to 90%), and the combined specificity was 95% (95% CI, 92 to 97%). By comparison, the sensitivity of single-reviewer screening was similar (78%; 95% CI, 66 to 89%); however, the sensitivity of DistillerAI alone was substantially worse (14%; 95% CI, 0 to 31%) than that of the machine-assisted screening approach. Specificities for single-reviewer screening and DistillerAI were 94% (95% CI, 91 to 97%) and 98% (95% CI, 97 to 100%), respectively. Machine-assisted screening and single-reviewer screening had similar areas under the curve (0.87 and 0.86, respectively); by contrast, the area under the curve for DistillerAI alone was just slightly better than chance (0.56). The interrater agreement between human screeners and DistillerAI with a prevalence-adjusted kappa was 0.85 (95% CI, 0.84 to 0.86%).

Conclusions

The accuracy of DistillerAI is not yet adequate to replace a human screener temporarily during abstract screening for systematic reviews. Rapid reviews, which do not require detecting the totality of the relevant evidence, may find semi-automation tools to have greater utility than traditional systematic reviews.
Migration routes and habitat use of a highly adaptable salmonid (sea trout, Salmo trutta) in a complex marine area
Authors: Kristensen Martin Lykke , Pedersen Martin Wæver , Thygesen Uffe Høgsbro , del Villar-Guerra Diego , Baktoft Henrik , Aarestrup Kim
Published: November 2019

Background

Understanding fish movements and migrations are paramount for management and conservation efforts. By applying Hidden Markov Models (HMMs) on records from electronic tags, migration routes of tagged fish can be reconstructed and new insights to the movement ecology of a species can be gained. We demonstrate the usability of HMMs on a widespread, iteroparous salmonid (sea trout, Salmo trutta) in a complex marine area with highly variable temperatures and salinities within small geographic distances. Understanding how the highly adaptable sea trout cope with these complex conditions could shed new light on factors driving the movement ecology of salmonids. Migration tracks of fish migrating at sea are reconstructed by applying an HMM on temperature and depth records from eight wild post-spawned sea trout from four Danish rivers.

Results

The fish migrated at sea for 47–142 days. Estimated positions of all fish were close to the coast (< 100 km) throughout the marine period, but migrations along coastlines up to 580 km away from the natal river occurred. Seven of eight individuals resided in or actively migrated into stratified or shallow marine areas that heat up fast during spring, while all eight individuals resided in deeper and more heterogeneous areas that heat up slow during summer. All fish entered the Skagerrak (located between Denmark and Norway) at some stage during summer. Migrations were directed into less saline areas during the first 15 days at sea for all individuals. Mean linear progression of the fish was 16 km day−1 (range 0–58 km day−1).

Conclusions

The results corroborate the expectation that sea trout are more coastally orientated than other salmonids, but also suggest that longer migrations occur in the seas surrounding Denmark compared to elsewhere. This could be a consequence of the fish seeking out habitats with optimal conditions (e.g. salinity, temperature, predation and foraging options) for growth in different parts of the year. The coinciding movement from shallow or stratified marine areas that heat up fast during spring to deeper, more well-mixed areas that heat up slow during summer suggested that some habitat selection had occurred. These results shed new light on factors influencing marine migrations in salmonids and demonstrate how HMMs can expand our knowledge on behaviour and movement ecology of marine fishes.
Cancer biomarkers for targeted therapy
Authors: Liu Delong
Published: November 2019

Tumor-associated antigens (TAA) or cancer biomarkers are major targets for cancer therapies. Antibody- based agents targeting the cancer biomarkers include monoclonal antibodies (MoAbs), radiolabeled MoAbs, bispecific T cell engagers, and antibody-drug conjugates. Antibodies targeting CD19, CD20, CD22, CD30, CD33, CD38, CD79B and SLAMF7 are in clinical applications for hematological malignancies. CD123, CLL-1, B cell maturation antigen, and CD138 are targets for cancer immunotherapeutic agents, including the chimeric antigen receptor - engineered T cells. Immune checkpoint inhibitors (ICIs) against PD-1, PD-L1, and CTLA-4 have led to the revolution of cancer immunotherapy. More ICIs targeting IDO, LAG3, TIM-3, TIGIT, SIGLECs, VISTA and CD47 are being explored. Small molecule inhibitors (SMIs) against tyrosine kinase oncoproteins such as BCR-ABL, JAK2, Bruton tyrosine kinase, FLT3, EGFR, ALK, HER2, VEGFR, FGFR, MEK, and MET have fundamentally changed the landscape of cancer therapy. SMIs against BCL-2, IDHs, BRAF, PI3 kinase, mTOR, PARP, and CDKs have become the mainstay in the treatment of a variety of cancer types. To reduce and avoid off-tumor toxicities, cancer-specific TAAs such as CD33 are being manufactured through systems biology approach. Search for novel biomarkers and new designs as well as delivery methods of targeted agents are fueling the next wave of advances in cancer therapy.
Multi-modal liquid biopsy platform for cancer screening: screening both cancer-associated rare cells and cancer cell-derived vesicles on the fabric filters for a reliable liquid biopsy analysis
Authors: Bu Jiyoon , Shim Jae-Eul , Lee Tae Hee , Cho Young-Ho
Published: November 2019

Circulating tumor cells (CTCs) are receiving a great amount of scientific interest as a diagnostic biomarker for various types of cancer. Despite the recent progress in the development of highly sensitive CTC isolation devices, post-capture analysis of CTCs is still hindered by technical challenges associated with their rarity. Herein, we present a multi-modal CTC screening platform which is capable to analyze CTCs and CTC-derived extracellular vesicles (EVs), simultaneously from a single sample. Cytochalasin B (CB) treatment promotes cells to release large number of EVs from their surface, as demonstrated by CB-treated cells (5 µg/mL for 3 h) secreting 3.5-fold more EVs, compared to the non-treated cells. CB further generates 1.7-fold more EVs from the cells captured on our CTC filtration device (the fabric filter), compared to those from the cell culture flasks, owing to its multiple pore structure design which reduces the non-specific binding of EVs. Both CB-treated cancer cells and CB-induced EVs are found to overexpress tumor-associated markers, demonstrating a potential for the development of CTC dual-screening platform. Collectively, the results presented in this study reveal that our multi-modal cancer screening platform can synergistically improve the reliability and efficacy of the current CTC analysis systems.
Diffusion-weighted imaging for identifying patients at high risk of tumor recurrence following liver transplantation
Authors: Chuang Yi-Hsuan , Ou Hsin-You , Yu Chun-Yen , Chen Chao-Long , Weng Ching-Chun , Tsang Leo Leung-Chit , Hsu Hsien-Wen , Lim Wei-Xiong , Huang Tung-Liang , Cheng Yu-Fan
Published: November 2019

Background

Tumor recurrence is the major risk factor affecting post-transplant survival. In this retrospective study, we evaluate the prognostic values of magnetic resonance (MR) diffusion-weighted imaging (DWI) in liver transplantation for hepatocellular carcinoma (HCC).

Methods

From April 2014 to September 2016, 106 HCC patients receiving living donor liver transplantation (LDLT) were enrolled. Nine patients were excluded due to postoperative death within 3 months and incomplete imaging data. The association between tumor recurrence, explant pathologic findings, and DWI parameters was analyzed (tumor-to-liver diffusion weighted imaging ratio, DWIT/L; apparent diffusion coefficients, ADC). The survival probability was calculated using the Kaplan–Meier method.

Results

Sixteen of 97 patients (16%) developed tumor recurrence during the follow-up period (median of 40.9 months; range 5.2–56.5). In those with no viable tumor (n = 65) on pretransplant imaging, recurrence occurred only in 5 (7.6%) patients. Low minimum ADC values (p = 0.001), unfavorable tumor histopathology (p <  0.001) and the presence of microvascular invasion (p <  0.001) were risk factors for tumor recurrence, while ADCmean (p = 0.111) and DWIT/L (p = 0.093) showed no significant difference between the groups. An ADCmin ≤ 0.88 × 10− 3 mm2/s was an independent factor associated with worse three-year recurrence-free survival (94.4% vs. 23.8%) and overall survival rates (100% vs. 38.6%).

Conclusions

Quantitative measurement of ADCmin is a promising prognostic indicator for predicting tumor recurrence after liver transplantation.
In vivo and in vitro pharmacological activities of Tacca integrifolia rhizome and investigation of possible lead compounds against breast cancer through in silico approaches
Authors: Ahmed Shahriar , Rakib Ahmed , Islam Md. Ashiqul , Khanam Bibi Humayra , Faiz Farhana Binta , Paul Arkajyoti , Chy Md. Nazim Uddin , Bhuiya N. M. Mahmudul Alam , Uddin Mir Muhammad Nasir , Ullah S. M. Amanat , Rahman Md. Atiar , Emran Talha Bin
Published: November 2019

Background

The study was conducted to evaluate the analgesic, anti-inflammatory, antipyretic properties of ethanolic extract of Tacca integrifolia rhizome (EETI) in mice and cytotoxic effects in brine shrimp nauplii followed by a PASS prediction study for some isolated compounds of T. integrifolia. Additionally, this experiment included the in silico molecular docking and ADME/T property analyses of some phytochemicals.

Methods

Formalin- induced paw licking test and acetic acid-induced writhing test for analgesic activity, carrageenan-induced paw edema test for anti-inflammatory potential and Brewer’s yeast-induced pyrexia test for antipyretic activity were applied. Antinociceptive and antineoplastic activity for breast cancer were revealed with PASS program. Schrodinger suite 2015 was used to evaluate the binding interaction and ADME/T properties of selected phytoconstituents with estrogen receptor alpha.

Results

In formalin-induced paw licking test, EETI at the doses of 200 and 400 mg/kg BW showed highly significant inhibition of writhing in both neurogenic and inflammatory phases. While EETI also exhibited highly significant, compared to control, writhing inhibition for both the doses in acetic acid-induced writhing test. Moderate anti-inflammatory effect at a dose of 400 mg/kg BW was noticed in paw-edema test. It also showed 77.51% of maximum antipyretic effect which was significantly effective compared to standard drug paracetamol (150 mg/kg) in Brewer’s yeast-induced pyrexia test. The EETI showed potential cytotoxic activity with LC50 value of 114.46 μg/mL. The PASS prediction revealed the potential antinociceptive and antineoplastic activity of target compounds. The compounds betulinic acid, quercetin-3-α-arabinoside, catsanogenin were found to be effective in molecular docking study.

Conclusion

It is evident that the EETI possesses highly significant analgesic activity with remarkable anti-inflammatory and antipyretic activity. The phytoconstituents have potential antinociceptive and antineoplastic (breast cancer) activity.

Graphical abstract
Compelling therapy of LVH: straight (and not-so-straight) inferences from evidence
Authors: Mehta Ravi Tejraj , Pareek Anil , Dharmadhikari Shruti
Published: November 2019

We have read with interest the Korean Society of Hypertension guidelines for the management of hypertension and congratulate the Society for an extensive review of literature while drafting the guidelines. The guidelines indicate preferring ACE-I and CCB over diuretics in patients with left ventricle hypertrophy. However, in landmark head-to-head comparison trials, the thiazide-like diuretic chlorthalidone has been shown to be superior to ACE-I and CCB in decreasing left ventricle mass and preventing heart failure in hypertensive patients. Also, we put forth the paradoxical finding that mere regression of LVH may not always translate into reduction in risk of HF; and that the pleiotropic effects of chlorthalidone may be the explanation behind its beneficial action in HF.
A review on the definitions of terms of sedimentary facies
Authors: Feng Zeng-Zhao
Published: November 2019

In recent years, in some papers and manuscripts published in and submitted to the Journal of Palaeogeography (Chinese Edition and English Edition), the authors named the rocks or rock types as “microfacies” or “lithofacies”, named the microfeatures in thin-sections under microscope as “microfacies”, and named the macrofeatures of rocks as “macrofacies”. I wrote two short papers “Words of the Editor-in-Chief — Rocks are not microfacies” (Feng, Journal of Palaeogeography 19(5):II 2017) and “Words of the Editor-in-Chief — Rocks are not lithofacies” (Feng, Journal of Palaeogeography 20(3):452–452, 2018) which were in Chinese and published in the Journal of Palaeogeography (Chinese Edition). However, they did not attract much attention of readers in China and outside China. In addition, in 1980s, some Chinese sedimentologists proposed “subfacies” and “microfacies” based on the macrofeatures of rocks from outcrops and drilling cores. However, the definition of this “microfacies” is totally different from the “microfacies” proposed by foreign sedimentologists in 1940s based on the microfeatures in thin-sections under microscope.

These problems appeared repeatedly and forced me, as the Editor-in-Chief of the Journal of Palaeogeography (Chinese Edition and English Edition), to observe the policy of “A hundred flowers blossom and a hundred schools of thought contend” , to write new papers “A review on the definitions of terms of sedimentary facies” both in Chinese and in English, to clarify the definitions of the terms of sedimentary facies, i.e., “facies”, “lithofacies”, two “microfacies”, “macrofacies”, “subfacies”, etc. I hope that the new papers will attract attention of readers worldwide and they can write papers and participate in the discussion and contending of these problems, strive for getting some common understandings, and therefore promote the progress and development of sedimentology and palaeogeography.
“What Will I Experience in My College STEM Courses?” An Investigation of Student Predictions about Instructional Practices in Introductory Courses
Authors: Meaders Clara L. , Toth Emma S. , Lane A. Kelly , Shuman J. Kenny , Couch Brian A. , Stains Marilyne , Stetzer MacKenzie R. , Vinson Erin , Smith Michelle K.
Published: November 2019

The instructional practices used in introductory college courses often differ dramatically from those used in high school courses, and dissatisfaction with these practices is cited by students as a prominent reason for leaving science, technology, engineering, and mathematics (STEM) majors. To better characterize the transition to college course work, we investigated the extent to which incoming expectations of course activities differ based on student demographic characteristics, as well as how these expectations align with what students will experience. We surveyed more than 1500 undergraduate students in large introductory STEM courses at three research-intensive institutions during the first week of classes about their expectations regarding how class time would be spent in their courses. We found that first-generation and first-semester students predict less lecture than their peers and that class size had the largest effect on student predictions. We also collected classroom observation data from the courses and found that students generally underpredicted the amount of lecture observed in class. This misalignment between student predictions and experiences, especially for first-generation and first-semester college students and students enrolled in large- and medium-size classes, has implications for instructors and universities as they design curricula for introductory STEM courses with explicit retention goals.
Imaging vertical structures using Marchenko methods with vertical seismic-profile data
Authors: Lomas Angus , Singh Satyan , Curtis Andrew
Published: November 2019

Marchenko methods use seismic data acquired at or near the surface of the earth to estimate seismic signals as if the receiver (now a virtual receiver) was at an arbitrary point inside the subsurface of the earth. This process is called redatuming, and it is central to subsurface imaging. Marchenko methods estimate the multiply scattered components of these redatumed signals, which is not the case for most other redatuming techniques that are based on single-scattering assumptions. As a result, images created using Marchenko redatumed signals contain a reduction in the artifacts that usually contaminate migrated seismic images due to improper handling of internal multiples. We exploit recent theoretical advances that enable virtual sources and virtual receivers to be placed at arbitrary points inside the subsurface as a means to incorporate vertical seismic profile (VSP) data into Marchenko methods. The advantage of including this type of data is that the additional acquisition boundary increases subsurface illumination, which in turn enables vertical interfaces and steeply dipping structures to be imaged. We develop this methodology using two synthetic data sets. The first is created using a simple variable density but constant velocity subsurface model. In this example, we find that our newly devised VSP Marchenko imaging methodology enables imaging of horizontal and vertical structures and that optimal results are achieved by combining these images with those created using standard Marchenko imaging. A second example demonstrates that the method can be applied to more realistic subsurface structures, in this case a modified version of the Marmousi 2 model. We determine the applicability of the methods to image fault structures with the final imaging result containing reduced contamination due to internal multiples and an improvement in the imaging of fault structures when compared to other standard imaging methods alone.
Yoga for psychiatric disorders: from fad to evidence-based intervention?
Authors: Varambally Shivarama , George Sanju , Gangadhar Bangalore Nanjundaiah
Published: November 2019

There is growing evidence for yoga's neurobiological effects in people with psychiatric disorders. Postulated mechanisms of action include: (a) modulation of the hypothalamic–pituitary–adrenal (HPA) axis; (b) enhancement of GABAergic neurotransmission; (c) autonomic modulation; and (d) neuroendocrinological effects. Yoga as a therapeutic intervention in psychiatric disorders appears promising and merits further attention in clinical practice and research.
Identifying ERBB2 Activating Mutations in HER2-Negative Breast Cancer: Clinical Impact of Institute-Wide Genomic Testing and Enrollment in Matched Therapy Trials
Authors: Exman Pedro , Garrido-Castro Ana C. , Hughes Melissa E. , Freedman Rachel A. , Li Tianyu , Trippa Lorenzo , Bychkovsky Brittany L. , Barroso-Sousa Romualdo , Di Lascio Simona , Mackichan Colin , Lloyd Max R. , Krevalin Max , Cerami Ethan , Merrill Margaret S. , Santiago Rebecca , Crowley Lindsey , Kuhnly Nicole , Files Janet , Lindeman Neal I. , MacConaill Laura E. , Kumari Priti , Tolaney Sara M. , Krop Ian E. , Bose Ron , Johnson Bruce E. , Ma Cynthia X. , Dillon Deborah A. , Winer Eric P. , Wagle Nikhil , Lin Nancy U.
Published: November 2019

PURPOSE

The yield of comprehensive genomic profiling in recruiting patients to molecular-based trials designed for small subgroups has not been fully evaluated. We evaluated the likelihood of enrollment in a clinical trial that required the identification of a specific genomic change based on our institute-wide genomic tumor profiling.

PATIENTS AND METHODS

Using genomic profiling from archived tissue samples derived from patients with metastatic breast cancer treated between 2011 and 2017, we assessed the impact of systematic genomic characterization on enrollment in an ongoing phase II trial (ClinicalTrials.gov identifier: NCT01670877 ). Our primary aim was to describe the proportion of patients with a qualifying ERBB2 mutation identified by our institutional genomic panel (OncoMap or OncoPanel) who enrolled in the trial. Secondary objectives included median time from testing result to trial registration, description of the spectrum of ERBB2 mutations, and survival. Associations were calculated using Fisher’s exact test.

RESULTS

We identified a total of 1,045 patients with metastatic breast cancer without ERBB2 amplification who had available genomic testing results. Of these, 42 patients were found to have ERBB2 mutation and 19 patients (1.8%) were eligible for the trial on the basis of the presence of an activating mutation, 18 of which were identified by OncoPanel testing. Fifty-eight percent of potentially eligible patients were approached, and 33.3% of eligible patients enrolled in the trial guided exclusively by OncoPanel testing.

CONCLUSION

More than one half of eligible patients were approached for trial participation and, significantly, one third of those were enrolled in NCT01670877. Our data illustrate the ability to enroll patients in trials of rare subsets in routine clinical practice and highlight the need for these broadly based approaches to effectively support the success of these studies.