bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel survival nomograms for patients with lung metastatic clear cell renal cell carcinoma
Authors: Zhang Lei , Hou Guangdong , Gao Ming , Zheng Yu , Dun Xinlong , Hou Niuniu , Zheng Wanxiang , Yan Fei , Lu Jun , Meng Ping , Ju Dongen , Yuan Jiarui , Wei Di , Zhu Zheng , Wang Fuli , Yuan Jianlin 
Published: December 2020

Abstract
Survival heterogeneity is observed among renal cell carcinoma (RCC) patients with metastases in different organs. Moreover, almost all previous prognostic nomograms based on data from metastatic RCC patients did not take competing events, such as death from cerebrovascular and heart diseases, into account. We aimed to construct novel prognostic nomograms for patients with lung metastatic clear cell RCC (LMCCRCC).
Data of 712 non-Hispanic white LMCCRCC patients registered in the Surveillance, Epidemiology, and End Results database were retrospectively analyzed. Nomograms for predicting overall survival (OS) and disease-specific survival (DSS) were established using the Cox approach and Fine and Gray approach, respectively, and their performances were assessed using the concordance index (C-index), calibration plots, and an independent cohort comprising 181 Hispanic patients.
Sex, tumor grade, T stage, N stage, presence or absence of bone metastases, and presence or absence of brain metastases were independent predictors for both OS and DSS. Additionally, presence or absence of liver metastases was an independent predictor only for DSS. Meanwhile, age at diagnosis was independently associated with OS. The C-indexes of the nomograms were 0.702 for OS and 0.723 for DSS in internal validation. In external validation, the C-indexes were 0.700 for OS and 0.708 for DSS. Both internal and external calibration plots showed excellent consistency between the prediction and the observation.
The current study developed a novel nomogram for predicting individual OS in LMCCRCC patients. Moreover, we constructed an effective competing risk nomogram for predicting their individual DSS for the first time.
Effects of microvascular invasion on clinical outcomes after resection with curative intent for cholangiocarcinoma
Authors: Song Bo-Hye , Cha Boram , Park Jin-Seok , Jeong Seok , Lee Don Haeng 
Published: December 2020

Abstract
Surgery is the only curative treatment for cholangiocarcinoma, but even after surgery, survival rates are unsatisfactory. Recently, several reports have suggested microvascular invasion (MiVi) is associated with poor postoperative prognosis in hepatocellular carcinoma (HCC). We considered that MiVi might be associated with poor clinical outcomes in patients with surgically resectable cholangiocarcinoma.
The records of 91 patients who underwent resection with curative intent for cholangiocarcinoma at Inha University Hospital from 2007 to 2017 were comprehensively reviewed for clinicopathological characteristics, DFS, and overall survival (OS) relations between these factors and the presence of MiVi.
Forty-nine of the 91 study subjects had MiVi and 42 did not. Median overall survivals were 492 days in the MiVi group and 1008 days in the noMiVi group and median DFSs were 367 days and 760 days, respectively. Cumulative survival ratio and recurrence incidence rates were significantly different in the 2 groups (P = .012). Multivariable analysis showed the presence of MiVi was an independent risk factor of OS (hazard ratio [HR] 3.34; 95% confidence interval [CI], 1.40–7.97; P = .007).
Cholangiocarcinoma is known to have a poor prognosis. When microvascular invasion remains after surgery it is associated with poor clinical outcomes.
68Ga-FAPI PET/CT Versus 68Ga-DOTATATE PET/CT in the Evaluation of a Patient With Neuroendocrine Tumor
Authors: Kömek Halil , Gündoğan Cihan , Can Canan 
Published: December 2020

Abstract

68Ga-FAPI (fibroblast activation protein-specific inhibitor) PET/CT was performed in a 56-year-old man with multiple liver masses, which were confirmed grade 2 well-differentiated neuroendocrine tumors with liver Tru-Cut biopsy. With 68Ga-DOTATE PET/CT, primary tumor in the pancreas, multiple metastases in the liver and metastatic portocaval lymph node were detected. In 68Ga-FAPI PET/CT imaging performed for comparison, it was seen that metastatic lesions in the liver were distinguished much better because of low background activity, and the primary tumor and metastatic lymph node were clearly selected. This case suggested that FAPI-bounded radionuclides may be useful in the evaluation and targeted therapy of neuroendocrine tumors.
Using Administrative Data to Incorporate Age and Sex-Dependent Resource Use for COVID-19 Acute Care Resource Use Simulations in Ontario, Canada
Authors: Mac Stephen , Ximenes Raphael , Barrett Kali , Khan Yasin A. , Pechlivanoglou Petros , Rios Juan David , Naimark David , Sander Beate 
Published: December 2020

AbstractAs the COVID-19 pandemic has progressed, more local data has become available, enabling a more granular modeling approach. In March 2020, we developed a COVID-19 Resource Estimator (CORE) model to estimate the acute care resource use in Ontario, Canada. In this paper, we describe the evolution of CORE2.0 to incorporate age, sex, and time-dependent acute care resource use, length of stay, and mortality to simulate hospital occupancy. Demographics (e.g., age and sex) of infected cases are informed by 4-month averages between March-June, and July-October using 10-year age groups. The probability of hospitalization, ICU admission, and requiring mechanical ventilation are all age and sex-dependent. LOS for each acute care level ranges from 5.7 to 16.15 days in the ward, 6.5 to 10.7 days in the ICU without ventilation, and 14.8 to 21.6 days on the ventilator, depending on month of infection. We calibrated some LOS components to reported ward and ICU occupancy between June 15 and October 31, 2020. Furthermore, we demonstrate the use of CORE2.0 for a regional analysis of Region of Waterloo, Ontario, Canada to simulate the ward bed, ICU bed, and ventilator occupancies for 30 days starting December 2020 for three case trajectory scenarios. Moving forward, this model has become highly flexible and customizable to data updates, and can better inform acute care planning and public measures as the pandemic progresses.
Systematic review reveals multiple sexually antagonistic polymorphisms affecting human disease and complex traits
Authors: Harper Jon Alexander , Janicke Tim , Morrow Edward H. 
Published: December 2020

AbstractAn evolutionary model for sex differences in disease risk posits that alleles conferring higher risk in one sex may be protective in the other. These sexually antagonistic (SA) alleles are predicted to be maintained at frequencies higher than expected under purifying selection against unconditionally deleterious alleles, but there are apparently no examples in humans. Discipline-specific terminology, rather than a genuine lack of such alleles, could explain this disparity. We undertook a two-stage review of evidence for SA polymorphisms in humans using search terms from (i) evolutionary biology and (ii) biomedicine. While the first stage returned no eligible studies, the second revealed 51 genes with sex-opposite effects, 22 increased disease risk or severity in one sex but protected the other. Those with net positive effects occurred at higher frequencies. None were referred to as SA. Our review reveals significant communication barriers to fields as a result of discipline-specific terminology.
The role of changes in environmental quality in multitrait plastic responses to environmental and social change in the model microalgaChlamydomonas reinhardtii
Authors: Melero-Jiménez Ignacio J. , Flores-Moya Antonio , Collins Sinéad 
Published: December 2020

AbstractIntraspecific variation plays a key role in species’ responses to environmental change; however, little is known about the role of changes in environmental quality (the population growth rate an environment supports) on intraspecific trait variation. Here, we hypothesize that intraspecific trait variation will be higher in ameliorated environments than in degraded ones. We first measure the range of multitrait phenotypes over a range of environmental qualities for three strains and two evolutionary histories ofChlamydomonas reinhardtiiin laboratory conditions. We then explore how environmental quality and trait variation affect the predictability of lineage frequencies when lineage pairs are grown in indirect co-culture. Our results show that environmental quality has the potential to affect intraspecific variability both in terms of the variation in expressed trait values, and in terms of the genotype composition of rapidly growing populations. We found low phenotypic variability in degraded or same-quality environments and high phenotypic variability in ameliorated conditions. This variation can affect population composition, as monoculture growth rate is a less reliable predictor of lineage frequencies in ameliorated environments. Our study highlights that understanding whether populations experience environmental change as an increase or a decrease in quality relative to their recent history affects the changes in trait variation during plastic responses, including growth responses to the presence of conspecifics. This points towards a fundamental role for changes in overall environmental quality in driving phenotypic variation within closely-related populations, with implications for microevolution.
MAPPER: A new image analysis pipeline unmasks differential regulation ofDrosophilawing features
Authors: Kumar Nilay , Huizar Francisco , Robinett Trent , Farfán-Pira Keity J. , Soundarrajan Dharsan , Unger Maria , Brodskiy Pavel , Nahmad Marcos , Zartman Jeremiah J. 
Published: December 2020

SummaryPhenomics requires quantification of large volumes of image data, necessitating high throughput image processing approaches. Existing image processing pipelines forDrosophilawings, a powerful model for studying morphogenesis, are limited in speed, versatility, and precision. To overcome these limitations, we developed MAPPER, a fully-automated machine learning-based pipeline that quantifies high dimensional phenotypic signatures, with each dimension representing a unique morphological feature. MAPPER magnifies the power ofDrosophilagenetics by rapidly identifying subtle phenotypic differences in sample populations. To demonstrate its widespread utility, we used MAPPER to reveal new insights connecting patterning and growth acrossDrosophilagenotypes and species. The morphological features extracted using MAPPER identified the presence of a uniform scaling of proximal-distal axis length across four different species ofDrosophila. Observation of morphological features extracted by MAPPER fromDrosophilawings by modulating insulin signaling pathway activity revealed the presence of a scaling gradient across the anterior-posterior axis. Additionally, batch processing of samples with MAPPER revealed a key function for the mechanosensitive calcium channel, Piezo, in regulating bilateral symmetry and robust organ growth. MAPPER is an open source tool for rapid analysis of large volumes of imaging data. Overall, MAPPER provides new capabilities to rigorously and systematically identify genotype-to-phenotype relationships in an automated, high throughput fashion.Graphical abstract
Rate-of-change analysis in palaeoecology revisited: a new approach
Authors: Mottl Ondřej , Grytnes John-Arvid , Seddon Alistair W.R. , Steinbauer Manuel J. , Bhatta Kuber P. , Felde Vivian A. , Flantua Suzette G.A. , Birks H. John B. 
Published: December 2020

AbstractDynamics in the rate of compositional change (rate-of-change; RoC) of biotic or abiotic assemblages preserved in palaeoecological sequences, are thought to reflect changes due to exogenous drivers such as climate and human forcing as well as endogenous factors linked to local dynamics and biotic interactions. However, changes in sedimentation rates and sampling strategies can result in an uneven distribution of time intervals and are known to affect RoC estimates. Furthermore, there has been relatively little exploration of the implications of these challenges in quantifying RoC in palaeoecology.Here, we introduceR-Ratepol– an easy-to-use R package – that provides a robust numerical technique for detecting and summarising RoC patterns in complex multivariate time-ordered stratigraphical sequences. First, we compare the performance of common methods of estimating RoC and detecting periods of high RoC (peak-point) using simulated pollen-stratigraphical data with known patterns of compositional change and temporal resolution. In addition, we propose a new method of binning with a moving window, which shows a more than 5-fold increase in the correct detection of peak-points compared to the more traditional way of using individual levels.Next, we apply our new methodology to four representative European pollen sequences and show that our approach also performs well in detecting periods of significant compositional change during known onsets of human activity, early land-use transformation, and changes in fire frequency.Expanding the approach usingR-Ratepolto open-access paleoecological datasets in global databases, such as Neotoma, will allow future palaeoecological and macroecological studies to quantify major changes in biotic composition or in sets of abiotic variables across broad spatio-temporal scales.
Modelling conformational state dynamics and its role on infection for SARS-CoV-2 Spike protein variants
Authors: Teruel Natália , Mailhot Olivier , Najmanovich Rafael Josef 
Published: December 2020

AbstractThe SARS-CoV-2 Spike protein needs to be in an open-state conformation to interact with ACE2 as part of the viral entry mechanism. We utilise coarse-grained normal-mode analyses to model the dynamics of Spike and calculate transition probabilities between states for 17081 Spike variants. Our results correctly model an increase in open-state occupancy for the more infectious D614G via an increase in flexibility of the closed-state and decrease of flexibility of the open-state. We predict the same effect for several mutations on Glycine residues (404, 416, 504, 252) as well as residues K417, D467 and N501, including the N501Y mutation, explaining the higher infectivity of the B.1.1.7 and 501.V2 strains. This is, to our knowledge, the first use of normal-mode analysis to model conformational state transitions and the effect of mutations thereon. The specific mutations of Spike identified here may guide future studies to increase our understanding of SARS-CoV-2 infection mechanisms and guide public health in their surveillance efforts.
A possible molecular mechanism for mechanotransduction at cellular focal adhesion complexes
Authors: Kim Jichul 
Published: December 2020

AbstractMechanotransduction at focal adhesion complexes is key for various cellular events. Theoretical analyses were performed to predict a potential role of lipid membranes in modulating mechanotransduction at focal adhesions. Calculations suggest that the nanoscale geometric changes and mechanical pulling applied on lipid membranes affect the generation of cellular traction forces and signaling transduction at focal adhesions. This work provides predictions on how lipid membranes contribute to mechanotransduction at cellular focal adhesions.Significance statementFocal adhesion machinery formed across cell membranes orchestrates a variety of signaling and adhesive molecules to function for important cellular physiologies. Although there are evidences that lipid membranes are involved in mechanical transduction at focal adhesions, how the detailed mechanical response of membranes contributes to the process is not identified yet. With numerous data previously identified, predictions made by theoretical modeling suggest that the nonlinear pulling response of lipid membranes serves as a key factor to interpret mechanotransduction at focal adhesions.
Population dynamics and ranging behaviours of provisioned silvered langur (Trachypithecus cristatus) in Peninsular Malaysia
Authors: Mohd-Daut Norlinda , Matsuda Ikki , Abidin Kamaruddin Zainul , Md-Zain Badrul Munir 
Published: December 2020

AbstractTourists are attracted to the Bukit Melawati Kuala Selangor (BMKS) of Peninsular Malaysia, a small hill park, both for its status as a historical site and the free-ranging silvered langurs (Trachypithecus cristatus) that come for provisioning. We assessed the population trends and group sizes ofT. cristatusover 10 years in the BMKS and examined their ranging patterns. Comparisons of observed populations between 2005 (190 individuals) and 2017 (193 individuals) revealed the stable demography and group sizes of the sixT. cristatusgroups in the BMKS. Based on a total of 185 location points of the six groups in 2017, their mean ranging area was 3.6 ha with a range of 0.86 to 6.93 ha with extensive spatial overlap. We also found a significant positive relationship between the six groups’ ranges and group sizes in 2017. Additionally, qualitative ecological comparisons with a previous study onT. cristatusin 1965 (before provisioning) suggest that the artificial food supply in the study area could modify the population dynamics and socioecology ofT. cristatus. The modifications might alter their range size and territoriality in the BMKS. Overall, we found that provisioning had negative effects on the ecology ofT. cristatusin the BMKS. Therefore, modifying management policies, such as banning feeding and implementing educational programs, may contribute to their proper conservation.
Molecular diversity analysis of the spike glycoprotein (S) gene from Hong Kong - China
Authors: Da Silva Eduarda Doralice Alves Braz , Venâncio Dallynne Bárbara Ramos , de Albuquerque Rosane Maria , Ramos Robson da Silva , Felix Pierre Teodósio 
Published: December 2020

AbstractIn this work, 37 haplotypes of spike glycoprotein of SARS-CoV-2 from Hong Kong, China, were used. All sequences were publicly available on the Platform of the National Center for Biotechnology Information (NCBI) and were analyzed for their Molecular Variance (AMOVA), haplotypic diversity, mismatch, demographic and spatial expansion, molecular diversity and time of evolutionary divergence. The results suggested that there was a low diversity among haplotypes, with very low numbers of transitions, transversions, indels-type mutations and with total absence of population expansion perceived in the neutrality tests. The estimators used in this study supported the uniformity among all the results found and confirm the evolutionary conservation of the gene, as well as its protein product, a fact that stimulates the use of therapies based on neutralizing antibodies, such as vaccines based on protein S.
An enhanced yeast display platform demonstrates the binding plasticity under various selection pressures
Authors: Zahradník Jiří , Dey Debabrata , Marciano Shir , Schreiber Gideon 
Published: December 2020

AbstractYeast surface display is popularin vitroevolution method. Here, we enhanced the method by multiple rounds of DNA and protein engineering, resulting in increased protein stabilities, surface expression, and enhanced fluorescence. The pCTcon2 yeast display vector was rebuild, introducing surface exposure tailored reporters – eUnaG2 and DnbALFA, creating a new platform of C and N terminal fusion vectors. In addition to gains in simplicity, speed, and cost, new applications were included to monitor protein surface exposure and protein retention in the secretion pathway. The enhanced methodologies were applied to investigatede-novoevolution of protein-protein interaction sites. Selecting binding from a mix of 6 protein-libraries towards two targets using high stringency selection led to the isolations of single high-affinity binders to each of the targets, without the need for high complexity libraries. Conversely, low-stringency selection resulted in the creation of many solutions for weak binding, demonstrating the plasticity of weakde-novointeractions.
Virtual care with digital technologies for rural and remote Canadians living with cardiovascular disease
Authors: Buyting Ryan , Melville Sarah , Chatur Hanif , White Christopher W. , Légaré Jean-François , Lutchmedial Sohrab , Brunt Keith R. 
Published: December 2020

AbstractCanada is a wealthy nation with a geographically diverse population, seeking health innovations to better serve patients in accordance with the Canada Health Act. In this country, population and geography converge with social determinants, policy, procurement regulations, and technological advances, in order to achieve equity in the management and distribution of healthcare. Rural and remote patients are a vulnerable population; when managing chronic conditions such as cardiovascular disease, there is inequity when it comes to accessing specialist physicians at the recommended frequency—increasing the likelihood of poor health outcomes. Ensuring equitable care for this population is an unrealized priority of several provincial and federal government mandates. Virtual care technology may provide practical, economical, and innovative solutions to remedy this discrepancy. Here we review the literature pertaining to the use of virtual care technologies to monitor patients with cardiovascular disease living in rural areas of Canada. A search strategy was developed to identify the literature specific to this context across three bibliographic databases. 166 unique citations were ultimately assessed for eligibility, of which 36 met the inclusion criteria. In our assessment of these articles, we provide a summary of the interventions studied, their reported effectiveness in reducing adverse events and mortality, the challenges to implementation, and the receptivity of these technologies amongst patients, providers and policy makers. Further, we glean insight into the barriers and opportunities to ensure equitable care for rural patients and conclude that there is an ongoing need for clinical trials assessing virtual care technologies in this context.SummaryPatients living in rural and remote communities’ experience diverse challenges to receiving equitable healthcare as is mandated by the Canada Health Act. Advances in virtual care technology may provide practical, economical, and innovative solutions to ensure this for patients in remote and rural living situations. Here we provide a state-of-the-art review of virtual care technologies available to patients with cardiovascular disease living in rural areas of Canada.