bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and Activity of PolyPEPI1018 Combined with Maintenance Therapy in Metastatic Colorectal Cancer: an Open-Label, Multicenter, Phase Ib Study
Authors: Hubbard Joleen M. , Tőke Enikő R. , Moretto Roberto , Graham Rondell P. , Youssoufian Hagop , Lőrincz Orsolya , Molnár Levente , Csiszovszki Zsolt , Mitchell Jessica L. , Wessling Jaclynn , Tóth József , Cremolini Chiara 
Published: April 2022

Abstract

Purpose:
Although chemotherapy is standard of care for metastatic colorectal cancer (mCRC), immunotherapy has no role in microsatellite stable (MSS) mCRC, a “cold” tumor. PolyPEPI1018 is an off-the-shelf, multi-peptide vaccine derived from 7 tumor-associated antigens (TAA) frequently expressed in mCRC. This study assessed PolyPEPI1018 combined with first-line maintenance therapy in patients with MSS mCRC.

Patients and Methods:
Eleven patients with MSS mCRC received PolyPEPI1018 and Montanide ISA51VG adjuvant subcutaneously, combined with fluoropyrimidine/biologic following first-line induction with chemotherapy and a biologic (NCT03391232). In Part A of the study, 5 patients received a single dose; in Part B, 6 patients received up to three doses of PolyPEPI1018 every 12 weeks. The primary objective was safety; secondary objectives were preliminary efficacy, immunogenicity at peripheral and tumor level, and immune correlates.

Results:
PolyPEPI1018 vaccination was safe and well tolerated. No vaccine-related serious adverse event occurred. Eighty percent of patients had CD8+ T-cell responses against ≥3 TAAs. Increased density of tumor-infiltrating lymphocytes were detected post-treatment for 3 of 4 patients’ liver biopsies, combined with increased expression of immune-related gene signatures. Three patients had objective response according to RECISTv1.1, and 2 patients qualified for curative surgery. Longer median progression-free survival for patients receiving multiple doses compared with a single dose (12.5 vs. 4.6 months; P = 0.017) suggested a dose–efficacy correlation. The host HLA genotype predicted multi-antigen–specific T-cell responses (P = 0.01) indicative of clinical outcome.

Conclusions:
PolyPEPI1018 added to maintenance chemotherapy for patients with unresectable, MSS mCRC was safe and associated with specific immune responses and antitumor activity warranting further confirmation in a randomized, controlled setting.
A violência da (in)compreensão: notas sobre Foucault, psicanálise e a interpretação da loucura
Authors: Peters Gabriel 
Published: April 2022

A partir de um diálogo com Michel Foucault, o artigo aborda os aspectos analíticos e morais do problema da “compreensibilidade” da loucura. Os aspectos analíticos envolvem saber se a loucura é compreensível ou, pelo menos, quão compreensível ela pode ser tornada a um ponto de vista exterior. Os aspectos morais dizem respeito às atitudes normativas que é legítimo assumir em face de vivências, falas e práticas “loucas”, sobretudo quando estas se mostram opacas, ao menos a um primeiro olhar, diante de esquemas “normais” de interpretação. Entrecruzando a discussão está uma crítica – de alcance mais geral, porém também aplicável a Foucault – à tendência de certa filosofia, ciência social e psicanálise a negligenciar modalidades “apolíneas” de loucura em prol de suas formas “dionisíacas”, sejam as últimas patologizadas como “regressões” ou celebradas como subversões de dispositivos psíquicos de poder.
Association of Accelerometer‐Measured Sedentary Accumulation Patterns With Incident Cardiovascular Disease, Cancer, and All‐Cause Mortality
Authors: Dempsey Paddy C. , Strain Tessa , Winkler Elisabeth A. H. , Westgate Kate , Rennie Kirsten L. , Wareham Nicholas J. , Brage Soren , Wijndaele Katrien 
Published: April 2022

Background
Emerging evidence suggests accruing sedentary behavior (SB) in relatively more prolonged periods may convey additional cardiometabolic risks, but few studies have examined prospective outcomes. We examined the association of SB accumulation patterns with incident cardiovascular disease (CVD), cancer, and all‐cause mortality (ACM).

Methods and Results

Data were from 7671 EPIC‐Norfolk (European Prospective Investigation Into Cancer and Nutrition–Norfolk) cohort middle‐ to older‐aged adults who wore accelerometers on the right hip for 4 to 7 days. Cox proportional hazards regression modeled associations between 2 measures of SB accumulation and incident CVD, cancer, and ACM. These were usual SB bout duration (the midpoint of each individual’s SB accumulation curve, fitted using nonlinear regression) and alpha (hybrid measure of bout frequency and duration, with higher values indicating relatively shorter bouts and fewer long bouts). Models were adjusted for potential confounders, then further for 24‐hour time‐use compositions. During mean follow‐up time of 6.4 years, 339 ACM, 1106 CVD, and 516 cancer events occurred. Elevated rates of incident cancer and ACM were seen with more prolonged SB accumulation (lower alpha, higher usual SB bout duration) but not CVD. For usual SB bout duration and alpha, respectively, the confounder‐adjusted hazard ratios per SD of the exposure were 1.12 (95% CI, 1.02–1.23) and 0.88 (95% CI, 0.79–0.98) with incident cancer and 1.16 (95% CI, 1.07–1.26) and 0.80 (95% CI, 0.72–0.89) with ACM (all
P
<0.05). Further adjustment for 24‐hour time use weakened associations with ACM for usual bout duration (hazard ratio, 1.06; 95% CI, 0.97–1.16;
P
=0.209) and partially for alpha (hazard ratio, 0.87; 95% CI, 0.77–0.99;
P
=0.029).

Conclusions
Accruing SB in longer bout durations was associated with higher rates of incident cancer and ACM but not with incident CVD, with some evidence of direct SB accumulation effects independent of 24‐hour time use. Findings provide some support for considering SB accumulation as an adjunct target of messaging to “sit less and move more.”
Platelet Function Is Associated With Dementia Risk in the Framingham Heart Study
Authors: Ramos‐Cejudo Jaime , Johnson Andrew D. , Beiser Alexa , Seshadri Sudha , Salinas Joel , Berger Jeffrey S. , Fillmore Nathanael R. , Do Nhan , Zheng Chunlei , Kovbasyuk Zanetta , Ardekani Babak A. , Pomara Nunzio , Bubu Omonigho M. , Parekh Ankit , Convit Antonio , Betensky Rebecca A. , Wisniewski Thomas M. , Osorio Ricardo S. 
Published: April 2022

Background
Vascular function is compromised in Alzheimer disease (AD) years before amyloid and tau pathology are detected and a substantial body of work shows abnormal platelet activation states in patients with AD. The aim of our study was to investigate whether platelet function in middle age is independently associated with future risk of AD.

Methods and Results
We examined associations of baseline platelet function with incident dementia risk in the community‐based FHS (Framingham Heart Study) longitudinal cohorts. The association between platelet function and risk of dementia was evaluated using the cumulative incidence function and inverse probability weighted Cox proportional cause‐specific hazards regression models, with adjustment for demographic and clinical covariates. Platelet aggregation response was measured by light transmission aggregometry. The final study sample included 1847 FHS participants (average age, 53.0 years; 57.5% women). During follow‐up (median, 20.5 years), we observed 154 cases of incident dementia, of which 121 were AD cases. Results from weighted models indicated that platelet aggregation response to adenosine diphosphate 1.0 µmol/L was independently and positively associated with dementia risk, and it was preceded in importance only by age and hypertension. Sensitivity analyses showed associations with the same directionality for participants defined as adenosine diphosphate hyper‐responders, as well as the platelet response to 0.1 µmol/L epinephrine.

Conclusions
Our study shows individuals free of antiplatelet therapy with a higher platelet response are at higher risk of dementia in late life during a 20‐year follow‐up, reinforcing the role of platelet function in AD risk. This suggests that platelet phenotypes may be associated with the rate of dementia and potentially have prognostic value.
Ongoing Exercise Intolerance Following COVID‐19: A Magnetic Resonance–Augmented Cardiopulmonary Exercise Test Study
Authors: Brown James T. , Saigal Anita , Karia Nina , Patel Rishi K. , Razvi Yousuf , Constantinou Natalie , Steeden Jennifer A. , Mandal Swapna , Kotecha Tushar , Fontana Marianna , Goldring James , Muthurangu Vivek , Knight Daniel S. 
Published: April 2022

Background
Ongoing exercise intolerance of unclear cause following COVID‐19 infection is well recognized but poorly understood. We investigated exercise capacity in patients previously hospitalized with COVID‐19 with and without self‐reported exercise intolerance using magnetic resonance–augmented cardiopulmonary exercise testing.

Methods and Results

Sixty subjects were enrolled in this single‐center prospective observational case‐control study, split into 3 equally sized groups: 2 groups of age‐, sex‐, and comorbidity‐matched previously hospitalized patients following COVID‐19 without clearly identifiable postviral complications and with either self‐reported reduced (COVID
reduced
) or fully recovered (COVID
normal
) exercise capacity; a group of age‐ and sex‐matched healthy controls. The COVID
reduced
group had the lowest peak workload (79W [Interquartile range (IQR), 65–100] versus controls 104W [IQR, 86–148];
P
=0.01) and shortest exercise duration (13.3±2.8 minutes versus controls 16.6±3.5 minutes;
P
=0.008), with no differences in these parameters between COVID
normal
patients and controls. The COVID
reduced
group had: (1) the lowest peak indexed oxygen uptake (14.9 mL/minper kg [IQR, 13.1–16.2]) versus controls (22.3 mL/min per kg [IQR, 16.9–27.6];
P
=0.003) and COVID
normal
patients (19.1 mL/min per kg [IQR, 15.4–23.7];
P
=0.04); (2) the lowest peak indexed cardiac output (4.7±1.2 L/min per m
2
) versus controls (6.0±1.2 L/min per m
2
;
P
=0.004) and COVID
normal
patients (5.7±1.5 L/min per m
2
;
P
=0.02), associated with lower indexed stroke volume (SVi:COVID
reduced
39±10 mL/min per m
2
versus COVID
normal
43±7 mL/min per m
2
versus controls 48±10 mL/min per m
2
;
P
=0.02). There were no differences in peak tissue oxygen extraction or biventricular ejection fractions between groups. There were no associations between COVID‐19 illness severity and peak magnetic resonance–augmented cardiopulmonary exercise testing metrics. Peak indexed oxygen uptake, indexed cardiac output, and indexed stroke volume all correlated with duration from discharge to magnetic resonance–augmented cardiopulmonary exercise testing (
P
<0.05).

Conclusions
Magnetic resonance–augmented cardiopulmonary exercise testing suggests failure to augment stroke volume as a potential mechanism of exercise intolerance in previously hospitalized patients with COVID‐19. This is unrelated to disease severity and, reassuringly, improves with time from acute illness.
Diagnosing Discrepancies between Observations and Models of Surface Energy Fluxes in a Midlatitude Lake
Authors: Taebel Zachary W. , Reed David E. , Desai Ankur R. 
Published: April 2022

Abstract
The physical processes of heat exchange between lakes and the surrounding atmosphere are important in simulating and predicting terrestrial surface energy balance. Latent and sensible heat fluxes are the dominant physical process controlling ice growth and decay on the lake surface, as well as having influence on regional climate. While one-dimensional lake models have been used in simulating environmental changes in ice dynamics and water temperature, understanding the seasonal to daily cycles of lake surface energy balance and its relationship to lake thermal properties, atmospheric conditions, and how those are represented in models is still an open area of research. We evaluated a pair of one-dimensional lake models, Freshwater Lake (FLake) and the General Lake Model (GLM), to compare modeled latent and sensible heat fluxes against observed data collected by an eddy covariance tower during a 1-yr period in 2017, using Lake Mendota in Madison, Wisconsin, as our study site. We hypothesized transitional periods of ice cover as a leading source of model uncertainty, and we instead found that the models failed to simulate accurate values for large positive heat fluxes that occurred from late August into late December. Our results ultimately showed that one-dimensional models are effective in simulating sensible heat fluxes but are considerably less sensitive to latent heat fluxes than the observed relationships of latent heat flux to environmental drivers. These results can be used to focus future improvement of these lake models especially if they are to be used for surface boundary conditions in regional numerical weather models.

Significance Statement
While lakes consist of a small amount of Earth’s surface, they have a large impact on local climate and weather. A large amount of energy is stored in lakes during the spring and summer, and then removed from lakes before winter. The effect is particularly noticeable in high latitudes, when the seasonal temperature difference is larger. Modeling this lake energy exchange is important for weather models and measuring this energy exchange is challenging. Here we compare modeled and observed energy exchange, and we show there are large amounts of energy exchange happening in the fall, which models struggle to capture well. During periods of partial ice coverage in early winter, lake behavior can change rapidly.
Deep Learning Augmented Data Assimilation: Reconstructing Missing Information with Convolutional Autoencoders
Authors: Wang Yueya , Shi Xiaoming , Lei Lili , Fung Jimmy Chi-Hung 
Published: April 2022

Abstract
Remote sensing data play a critical role in improving numerical weather prediction (NWP). However, the physical principles of radiation dictate that data voids frequently exist in physical space (e.g., subcloud area for satellite infrared radiance or no-precipitation region for radar reflectivity). Such data gaps impair the accuracy of initial conditions derived from data assimilation (DA), which has a negative impact on NWP. We use the barotropic vorticity equation to demonstrate the potential of deep learning augmented data assimilation (DDA), which involves reconstructing spatially complete pseudo-observation fields from incomplete observations and using them for DA. By training a convolutional autoencoder (CAE) with a long simulation at a coarse “forecast” resolution (T63), we obtained a deep learning approximation of the “reconstruction operator,” which maps spatially incomplete observations to a model state with full spatial coverage and resolution. The CAE was applied to an incomplete streamfunction observation (∼30% missing) from a high-resolution benchmark simulation and demonstrated satisfactory reconstruction performance, even when only very sparse (1/16 of T63 grid density) observations were used as input. When only spatially incomplete observations are used, the analysis fields obtained from ensemble square root filter (EnSRF) assimilation exhibit significant error. However, in DDA, when EnSRF takes in the combined data from the incomplete observations and CAE reconstruction, analysis error reduces significantly. Such gains are more pronounced with sparse observation and small ensemble size because the DDA analysis is much less sensitive to observation density and ensemble size than the conventional DA analysis, which is based solely on incomplete observations.

Significance Statement
Data assimilation plays a critical role in improving the skills of modern numerical weather prediction by establishing accurate initial conditions. However, unobservable regions are common in observation data, particularly those derived from remote sensing. The nonlinear relationship between data from observable regions and the physical state of unobservable regions may impede DA efficiency. As a result, we propose that deep learning be used to improve data assimilation in such cases by reconstructing a spatially complete first guess of the physical state with deep learning and then applying data assimilation to the reconstructed field. Such deep learning augmentation is found effective in improving the accuracy of data assimilation, especially for sparse observation and small ensemble size.
Identifying Weather Patterns Associated with Increased Volcanic Ash Risk within British Isles Airspace
Authors: Harrison Samuel R. , Pope James O. , Neal Robert A. , Garry Freya K. , Kurashina Ryosuke , Suri Dan 
Published: April 2022

Abstract
Icelandic volcanic emissions have been shown historically and more recently to have an impact on public health and aviation across northern and western Europe. The severity of these impacts is governed by the prevailing weather conditions and the nature of the eruption. This study focuses on the former utilizing an existing set of 30 weather patterns produced by the Met Office. Associated daily historical classifications are used to assess which weather patterns are most likely to result in flow from Iceland into four flight information regions (FIRs) covering the British Isles and North Atlantic, which may lead to disruption to aviation during Icelandic volcanic episodes. High-risk weather patterns vary between FIRs, with a total of 14 weather patterns impacting at least one FIR. These high-risk types predominantly have a northwesterly or westerly flow from Iceland into British Isles airspace. Analysis of the historical classifications reveals a typical duration for high-risk periods of 3–5 days, when transitions between high-risk types are considered. High-risk periods lasting over a week are also possible in all four FIRs. Additionally, impacts are more likely in winter months for most FIRs. Knowledge of high-risk weather patterns for aviation can be used within existing operational probabilistic weather pattern forecasting tools. Combined probabilities for high-risk weather patterns can be derived for the medium-range (1–2 weeks ahead) and used to provide a rapid assessment as to the likelihood of flow from Iceland. This weather pattern forecasting application is illustrated using archived forecast data for the 2010 Eyjafjallajökull eruption.
Workarounds in the Shadow System: An Ethnographic Study of Requirements for Documentation and Cooperation in a Clinical Advisory Center
Authors: Mörike Frauke , Spiehl Hannah L. , Feufel Markus A. 
Published: April 2022

Objective Hospital information systems (HIS) are meant to manage complex work processes across healthcare organizations. We describe limitations of HIS to address local information requirements and how they are circumvented at different organizational levels. Results can be used to better support collaboration in socio-technical systems. Background Workarounds describe a mismatch between a technology’s purpose and its actual use, whereas shadow systems are unofficial IT systems circumventing limitations of official systems to support workflows. Boundary infrastructures are conceptualized as the entirety of all (in)formal digital and analog systems connecting different communities of practice in a socio-technical system. Methods An ethnographic study with observations and semi-structured interviews was conducted and analyzed through categorization and iterative coding. Results Several digital-analog workarounds are employed for documentation and a shared server functions as a shadow system to support workflows in ways the HIS cannot. For collaborative documentation, all (official and informal) information sources were used simultaneously as part of an interconnected boundary infrastructure. Conclusion Formal and informal IT systems are interconnected across different organizational levels and provide insights into unmet information requirements, effective and problematic work practices, and how to address them to improve system functioning. An integrated perspective on boundary infrastructures, workarounds, and shadow systems may advance system analysis, providing a more comprehensive picture of IT requirements than any concept alone. Application Workarounds and shadow systems highlight that HIS should support systemic and local needs. Customized interfaces in HIS to support search, access, and exchange of relevant data might help to mitigate current shortcomings.
Internet addiction, insomnia, and violence tendency in adolescents
Authors: Evli Mahmut , Şimşek Nuray , Işıkgöz Mahmut , Öztürk Halil İbrahim 
Published: April 2022

Introduction: There is limited information on how the tendency to violence in adolescents is affected by internet addiction and insomnia. This study will contribute to the literature in revealing the effect of internet addiction on insomnia and violence tendency in adolescents. Methods: The data were collected between 26/May/2021 and 06/July/2021. A total of 2,502 adolescents studying in 9th and 12th grades were included in the study. Data were collected with the adolescent information form, Internet Addiction Scale-Short Form, Bergen Insomnia Scale, and Violence Tendency Scale. Descriptive statistics, independent samples t-test, one-way analysis of variance, correlation, and simple linear regression analyzes were used in the analysis of data. Results: Participants were 15.92 ± 1.19 years old and 70.80% were women. While internet addiction do not change according to gender, and violence tendency mean scores do not change according to having a device to use the internet, the study variable mean score changes according to all the other socio-demographic variables included in our study. There is a positive relationship between internet addiction, violence tendency, and insomnia. Furthermore, while internet addiction explained 22.1% of insomnia scores, 18.8% of the variance changes in the violence tendency scores, insomnia explained 11.8% of violence tendency scores. Conclusion: Although the scale scores of the adolescents in our study were below the average, internet addiction is common problem necessitates working on the subject. In our study, there is a significant relationship between internet addiction, insomnia and tendency to violence, and internet addiction predicts other variables.
Potential energy as a new approach for detection and monitoring of fatigue damage in scarf adhesive joints modified with nanoparticles
Authors: Khashaba Usama A. 
Published: April 2022

In this study, fatigue results of the scarf adhesive joints (SAJs) were extensively analyzed regarding the effect of the adhesive materials (neat epoxy (NE), and SiC and Al2O3-nanocomposite), bond thickness (0.17 mm and 0.25 mm) on their dynamic properties, which include loss factor (tan δ), loss modulus ( E''), dissipated energy ( U d), potential energy ( U p), and storage modulus ( E'). Safe fatigue lives of the NE, SiC, and Al2O3-SAJs were estimated at different reliability levels. The experimental measurements revelated that reducing the adhesive layer thickness from 0.25 mm to 0.17 mm result in enhancing the tensile strength and stiffness of the SiC-SAJs by 9.6% and 4.4%, respectively, in return of 9.5% and 5.4% for the Al2O3-SAJ relative to the NE-SAJ. The strength and stiffness of the SiC-SAJs with 0.17 mm bond thickness are higher than those of the Al2O3-SAJ by 15.4% and 3.3%, respectively. The highest improvement of 22.0% in the fatigue strength was occurred for the SiC-SAJ with bond thickness of 0.17 mm in return of 4.8% for the Al2O3-SAJ. The U p was used for the first time (except author works) for monitoring and predicting the damage in the adhesive joints practically the change in the enclosed area of the hysteresis loop is too small to cause a large variation in the tan δ, E'', and U d. Damping factor of the NE-SAJs is marginally increased with the stress levels compared to the aggravated increase of both SiC and Al2O3-SAJs. Zhang model predicts well the potential energy and storage modulus specially at higher stress levels.