bluuebunny/crossref_metadata_2025_split huggingface dataset:
Give what is due: the need to prioritize healthcare workers in response to COVID-19 pandemic
Authors: Punsalan Mairre Louie D 
Published: December 2020

Abstract
In a recent correspondence published in this journal, the need to prioritize healthcare workers by the government must be considered. Various negative effects were seen from non-prioritization of healthcare workers. With this, healthcare workers heed distress calls affecting their physical and mental well-being. If prioritization is given and initiatives are done, the needs of healthcare workers will be sufficed so that they will be working at maximum to mitigate the spread of COVID-19.
Contextualizing temporal arterial magnetic resonance angiography in the diagnosis of giant cell arteritis: a retrospective cohort study
Authors: Junek Mats , Hu Angela , Garner Stephanie , Rebello Ryan , Legault Kim , Beattie Karen , Khalidi Nader 
Published: December 2020

Abstract

Objectives
Imaging modalities have become common in evaluating patients for a possible diagnosis of GCA. This study seeks to contextualize how temporal arterial magnetic resonance angiography (TA-MRA) can be used in facilitating the diagnosis of GCA.

Methods
A retrospective cohort study was performed on patients who had been previously referred to a rheumatologist for evaluation of possible GCA in Hamilton, Ontario, Canada. Data including clinical features, inflammatory markers, imaging, and biopsy results were extracted. Multivariable logistic regression model to predict the diagnosis of GCA. Using these models, the utility of TA-MRA in series with or in parallel to clinical evaluation was demonstrated across the cohort as well as in subgroups defined by biopsy and imaging status.

Results
In total 268 patients had complete data. Those diagnosed with biopsy- and/or imaging-positive GCA were more likely to demonstrate classic features including jaw claudication and vision loss. Clinical multivariable modelling allowed for fair discriminability [receiver operating characteristic (ROC) 0.759, 95% CI: 0.703, 0.815] for diagnosing GCA; there was excellent discriminability in facilitating the diagnosis of biopsy-positive GCA (ROC 0.949, 0.898–1.000). When used in those with a pre-test probability of 50% or higher, TA-MRA had a positive predictive value of 93.0%; in those with a pre-test probability of 25% or less TA-MRA had a negative predictive value of 89.5%.

Conclusion
In those with high disease probability, TA-MRA can effectively rule in disease (and replace temporal artery biopsy). In those with low to medium probability, TA-MRA can help rule out the disease, but this continues to be a challenging diagnostic population.
An uncommon cause of sepsis following dog exposure
Authors: Hexter Madison A. 
Published: December 2020

ABSTRACT

Capnocytophaga canimorsus is a bacteria commonly found in the normal oral cavity of dogs that can cause bacteremia in immunocompromised patients following a dog bite. This case describes sepsis and disseminated intravascular coagulation associated with C. canimorsus in a patient with a history of alcohol abuse. Clinicians must be alert to the risk factors for this infection and provide appropriate prophylaxis following dog bites.
Prompt evaluation and treatment of third-trimester bleeding
Authors: Cunningham Jill W. 
Published: December 2020

ABSTRACT
Third-trimester bleeding is an obstetric emergency and is associated with significant maternal and fetal morbidity and mortality. The two most common causes for third-trimester bleeding are placental abruption and placenta previa, which account for about half of all cases. Clinicians should have a thorough understanding of the risk factors, clinical presentation, and appropriate management of these conditions. Timely management is necessary for the survival of mother and fetus and to reduce the incidence of neonatal complications.
Triple-Methyl Blockade With Recombinant Methioninase, Cycloleucine, and Azacitidine Arrests a Pancreatic Cancer Patient-Derived Orthotopic Xenograft Model
Authors: Sugisawa Norihiko , Yamamoto Jun , Han Qinghong , Tan Yuying , Tashiro Yoshihiko , Nishino Hiroto , Inubushi Sachiko , Hamada Kazuyuki , Kawaguchi Kei , Unno Michiaki , Bouvet Michael , Hoffman Robert M. 
Published: December 2020

Objectives
Methionine addiction is a fundamental and general hallmark of cancer caused by enhanced methyl flux. In the present study, we effected a novel methionine-methylation blockade to target a patient-derived orthotopic xenograft model of pancreatic cancer.

Methods
The pancreatic cancer patient-derived orthotopic xenograft mouse models were randomized into 6 groups of 8 mice each and treated for 2 weeks: untreated control; azacitidine; oral recombinant methioninase (o-rMETase); o-rMETase plus cycloleucine; o-rMETase plus cycloleucine plus azacitidine (triple-methyl blockade therapy); and gemcitabine (positive control).

Results
Triple-methyl blockade therapy arrested tumor growth (mean relative tumor volume, 1.03 [standard deviation, 0.36]) and was significantly more effective compared with azacitidine (P = 0.0001); o-rMETase (P = 0.007); or o-rMETase plus cycloleucine (P = 0.04). Gemcitabine alone also inhibited but did not arrest tumor growth (mean relative tumor volume, 1.50 [standard deviation, 0.30]). The percentage of cancer cells that were negative for 5-methylcytosine staining in immunohistochemistry, indicating reduction of DNA methylation, increased with triple-methyl blockade therapy (37.5%), compared with gemcitabine (1.8%); o-rMETase (2.8%); azacitidine (9.0%); or o-rMETase plus cycloleucine (10.6%).

Conclusions
This new concept of triple-methyl blockade therapy has clinical potential for pancreatic cancer, which is currently a recalcitrant disease.
Delayed Processing of Secretin-Induced Pancreas Fluid Influences the Quality and Integrity of Proteins and Nucleic Acids
Authors: Cruz-Monserrate Zobeida , Gumpper Kristyn , Kaul Sabrina , Badi Niharika , Terhorst Samantha , Dubay Kelly , Lesinski Gregory B. , Fisher William , McElhany Amy , Lara Luis F. , Krishna Somashekar , Mace Thomas , Higuita-Castro Natalia , Ortega-Pineda Lilibeth , Freitas Michael A. , Hinton Alice , Yadav Dhiraj , Hart Phil A. , Pandol Stephen J. , Ahmed Saima , Fatou Benoit , Steen Hanno , Conwell Darwin L. ,   on behalf of the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer##
Published: December 2020

Objectives
Endoscopic pancreatic function tests are used to diagnose pancreatic diseases and are a viable source for the discovery of biomarkers to better characterize pancreatic disorders. However, pancreatic fluid (PF) contains active enzymes that degrade biomolecules. Therefore, we tested how preservation methods and time to storage influence the integrity and quality of proteins and nucleic acids.

Methods
We obtained PF from 9 subjects who underwent an endoscopic pancreatic function test. Samples were snap frozen at the time of collection; after 1, 2, and 4 hours on ice; or after storage overnight at 4°C with or without RNase or protease inhibitors (PIs). Electrophoresis and mass spectrometry analysis determined protein abundance and quality, whereas nucleic acid integrity values determined DNA and RNA degradation.

Results
Protein degradation increased after 4 hours on ice and DNA degradation after 2 hours on ice. Adding PIs delayed degradation. RNA was significantly degraded under all conditions compared with the snap frozen samples. Isolated RNA from PF-derived exosomes exhibited similar poor quality as RNA isolated from matched PF samples.

Conclusions
Adding PIs immediately after collecting PF and processing the fluid within 4 hours of collection maintains the protein and nucleic acid integrity for use in downstream molecular analyses.
Albumin–to–Alkaline Phosphatase Ratio
Authors: Acikgoz Yusuf , Bal Oznur , Dogan Mutlu 
Published: December 2020

Objectives
Neuroendocrine tumors (NETs) are very heterogeneous tumors. This study aimed to evaluate prognostic value of an albumin–to–alkaline phosphatase (ALP) ratio (AAPR) in well-differentiated NETs.

Methods
A total of 110 patients were included in this study. Albumin–to–alkaline phosphatase ratio was calculated by dividing albumin concentration (g/dL) to ALP level (U/L). Cutoff value for AAPR was determined by receiver operating characteristic analysis. Survival analysis was performed by Kaplan-Meier method with the log-rank test. A P value of less than 0.05 was considered statistically significant.

Results
The optimum cutoff value for AAPR was 0.028. Patients were divided into 2 groups as patients with AAPR of 0.028 or less (n = 22, 20%) and with AAPR of greater than 0.028 (n = 88, 80%). Patients with AAPR of greater than 0.028 had statistically longer overall survival compared with patients with 0.028 or less (not reached vs 96.8 months, P = 0.001). In addition, AAPR has been shown to be an independent prognostic factor for overall survival in multivariate analysis (hazard ratio, 3.99; 95% confidence interval, 1.26–12.61, P = 0.018).

Conclusions
Patients with higher AAPR had more favorable prognosis compared with patients with lower AAPR. We demonstrated that AAPR can be of prognostic value in well-differentiated NETs.
Survival Outcomes of Adjuvant Chemotherapy Combined With Radiation Versus Chemotherapy Alone After Pancreatectomy for Distal Pancreatic Adenocarcinoma
Authors: Batukbhai Bhavina , Herman Joseph M. , Zahurak Marianna , Laheru Daniel A. , Le Dung T. , Wolfgang Christopher Lee , Zheng Lei , De Jesus-Acosta Ana 
Published: December 2020

Objective
We evaluated survival outcomes in patients with distal pancreatic ductal adenocarcinoma (D-PDAC) after distal pancreatectomy (DP) and adjuvant chemotherapy or chemoradiation.

Methods
A retrospective analysis of patients who underwent DP for D-PDAC from 2000 to 2015 at the Johns Hopkins Hospital was performed. Demographics, baseline risk factors, and type of adjuvant treatment were assessed for associations with overall survival (OS) and disease-free survival (DFS). Comparisons were made with log-rank tests and Cox proportional hazards regression models.

Results
A total of 294 patients underwent DP for D-PDAC. Of these, 105 patients were followed at the Johns Hopkins Hospital. Forty-five patients received chemotherapy only and 60 patients received chemoradiation. The median OS with chemoradiation was 33.6 months and 27.9 months (P = 0.54) with chemotherapy only. The median DFS was 15.3 months with chemoradiation and 19.8 months with chemotherapy only (P = 0.89). Elevated carbohydrate antigen 19-9, stage II to III disease, splenic vein involvement, and vascular invasion were significant risk factors in multivariate analyses.

Conclusions
In this retrospective analysis, there were no significant differences in OS or DFS with chemoradiation compared with chemotherapy alone after DP in patients with D-PDAC.
Long-Term TDF-Inclusive ART and Progressive Rates of HBsAg Loss in HIV-HBV Coinfection—Lessons for Functional HBV Cure?
Authors: Audsley Jennifer , Avihingsanon Anchalee , Littlejohn Margaret , Bowden Scott , Matthews Gail V. , Fairley Christopher K. , Lewin Sharon R. , Sasadeusz Joe 
Published: December 2020

Background:
Tenofovir disoproxil fumarate (TDF) is effective in suppressing HIV and hepatitis B virus (HBV) replication in HIV-HBV coinfection although HBV DNA can persist in some individuals on TDF-containing antiretroviral therapy (ART). We initiated a prospective longitudinal study to determine durability of HBV virological control and clinical outcomes after prolonged TDF-based ART in HIV-HBV coinfection.

Methods:
Ninety-two HIV-HBV coinfected participants on, or about to commence, TDF-containing ART from Australia (n = 41) and Thailand (n = 52) were enrolled. Participants were followed 6-monthly for 2 years, then annually to 5 years. Laboratory and clinical assessments and a serum sample were collected at each study visit. These analyses compare follow-up at 2 and 5 years.

Results:
12.0% (95% confidence interval 6.8 to 20.2) of total study entry cohort (n = 92) or 15.3% (95% confidence interval: 8.8 to 25.3) of those with data to year 5 (n = 72) lost hepatitis B surface antigen (HBsAg). The only statistically significant association with HBsAg loss was lower study entry quantitative HBsAg. CD4 T-cell count increased by a median 245 cells/mm3 between the preTDF sample and 5 years of follow-up. By year 5, 98.5% of the cohort had undetectable HBV DNA (<15 IU/mL) and 91.4% had undetectable HIV RNA (<20 copies/mL).

Conclusions:
HBsAg loss was high and ongoing over 5 years of follow-up in HIV-HBV coinfected individuals on TDF-containing ART and undetectable HBV was almost universal. Although the pattern of HBsAg loss temporarily parallels immune reconstitution, we could not identify predictive immune markers. The high rate of HBsAg loss in HIV-HBV coinfection may offer valuable insights into the search for a functional HBV cure.
The Risk of Presarcopenia Is Increased Among Female Patients With Primary Sjögren’s Syndrome
Authors: Colak Seda , Tekgoz Emre , Hayme Serhat , Sonaeren Ilknur , Cinar Muhammet , Yilmaz Sedat 
Published: December 2020

Objectives
Sarcopenia is a progressive and generalized loss of muscle mass and function. The aim of this study was to evaluate the frequency of sarcopenia among patients with primary Sjögren’s syndrome (SS) and the factors related with sarcopenia.

Methods
Forty-four female patients with primary SS and 44 female control subjects were included in this cross-sectional study between February and August 2019. Sarcopenia was evaluated by the handgrip test, Skeletal Muscle Mass Index, and gait speed test.

Results
Eleven patients (25.0%) had presarcopenia in the SS group and 2 (4.5%) in the control group (p = 0.007). Compared with control subjects, SS patients had lower results of hand grip and gait speed tests (p = 0.005 and p < 0.001, respectively). According to the Mini Nutritional Assessment Short Form, patients with presarcopenia had higher risk of malnutrition compared with patients without sarcopenia (p = 0.043). Patients with presarcopenia had higher scores in the European League Against Rheumatism Sjögren’s Syndrome Patient-Reported Index pain domain and patient visual analog scale for global disease activity compared with patients without sarcopenia (p = 0.044 and p = 0.036, respectively). In multivariate regression analysis, European League Against Rheumatism Sjögren’s Syndrome Patient-Reported Index pain was associated with hand grip strength (p = 0.016, R
2 = 0.13) and Mini Nutritional Assessment Short Form was associated with Skeletal Muscle Mass Index (p = 0.005).

Conclusions
Risk of sarcopenia is increased in patients with SS. Pain and malnutrition may contribute to presarcopenia. Evaluating pain and patient's global disease activity may help physicians to determine patients with increased risk of sarcopenia. Controlling disease activity and pain and preventing malnutrition may reduce the risk of development of sarcopenia.
Characterization of human embryonic stem cells in animal component-free medium
Authors: Machida Masakazu , Abutani Rie , Miyajima Hiroshi , Sasaki Tetsuji , Abe Yoshiko , Akutsu Hidenori , Umezawa Akihiro 
Published: December 2020

AbstractClinical use of human embryonic stem cells (ESCs) as a raw material requires good manufacturing practice-compliant axillary materials such as culture medium. To this end, animal components should not be used and contamination of virus/bacteria/fungus and allergens are a concern. In addition, animal components such as albumin and fetal bovine serum pose difficulties such as a lot-to-lot variation. However, only a limited number of animal component-free media have been developed to date. In this study, we investigated whether SEES2 ESCs can be stably propagated for 16 passages (54 population doublings) over a period of 60 days in a newly established Stem-Partner®ACF medium. SEES2 ESC maintained their intact karyotype, i.e. 46,XX, and their undifferentiated phenotypes after long-term culture. An in vitro differentiation assay revealed that SEES2 ESCs exhibited multipotency, i.e. endodermal, mesodermal and ectodermal differentiation. Subcutaneous implantation of SEES2 ESCs generated mature teratomas without malignant transformation. These results show that SEES2 ESCs in the Stem-Partner®ACF medium can be used to establish master cell banks for future regenerative medicine as well as other ESCs in the previously reported culture medium.
Complex eco-evolutionary dynamics induced by the coevolution of predator-prey movement strategies
Authors: Netz Christoph , Hildenbrandt Hanno , Weissing Franz J. 
Published: December 2020

AbstractThe coevolution of predators and prey has been the subject of much empirical and theoretical research, which has produced intriguing insights into the intricacies of eco-evolutionary dynamics. Mechanistically detailed models are rare, however, because the simultaneous consideration of individual-level behaviour (on which natural selection is acting) and the resulting ecological patterns is challenging and typically prevents mathematical analysis. Here we present an individual-based simulation model for the coevolution of predators and prey on a fine-grained resource landscape. Throughout their lifetime, predators and prey make repeated movement decisions on the basis of heritable and evolvable movement strategies. We show that these strategies evolve rapidly, inducing diverse ecological patterns like spiral waves and static spots. Transitions between these patterns occur frequently, induced by coevolution rather than by external events. Regularly, evolution leads to the emergence and stable coexistence of qualitatively different movement strategies. Although the strategy space considered is continuous, we often observe discrete variation. Accordingly, our model includes features of both population genetic and quantitative genetic approaches to coevolution. The model demonstrates that the inclusion of a richer ecological structure and higher number of evolutionary degrees of freedom results in even richer eco-evolutionary dynamics than anticipated previously.
Specialized coding patterns among dorsomedial prefrontal neuronal ensembles predict conditioned reward seeking
Authors: Grant Roger I. , Doncheck Elizabeth M. , Vollmer Kelsey M. , Winston Kion T. , Romanova Elizaveta V. , Siegler Preston N. , Bowen Christopher W. , Otis James M. 
Published: December 2020

ABSTRACTNon-overlapping cell populations within dorsomedial prefrontal cortex (dmPFC), defined by gene expression or projection target, control dissociable aspects of reward seeking through unique activity patterns. However, even within these defined cell populations considerable cell-to-cell variability is found, suggesting that greater resolution is needed to understand information processing in dmPFC. Here we use two-photon calcium imaging in awake, behaving mice to monitor the activity of dmPFC excitatory neurons throughout Pavlovian sucrose conditioning. We characterize five unique neuronal ensembles that each encode specialized information related to a reward, reward-predictive cues, and behavioral responses to reward-predictive cues. The ensembles differentially emerge across learning – and stabilize after learning – in a manner that improves the predictive validity of dmPFC activity dynamics for deciphering variables related to behavioral conditioning. Our results characterize the complex dmPFC neuronal ensemble dynamics that relay learning-dependent signals for prediction of reward availability and initiation of conditioned reward seeking.
Regional and age-dependent Effects of Cortical Magnetic Stimulation on Unconstrained Reaching Behavior
Authors: Urbin M.A. , Tian Jing , McKernan Gina P. , Kortzorg Nick , Wyers Lore , van Halewijck Florian , Boisgontier Matthieu P. , Levin Oron , Swinnen Stephan P. , Jonkers Ilse , Wittenberg George F. 
Published: December 2020

AbstractBackgroundThe specific and dynamic contributions of premotor and supplementary motor areas to reaching movements in aging humans are not well understood.ObjectiveTo better understand the role of cortical motor regions and age on the control of unconstrained reaches against gravity by neurologically intact, younger and older adults.MethodsDouble pulse transcranial magnetic stimulation (TMS) was applied at locations targeting primary motor cortex (M1), dorsal premotor area (PMA), supplementary motor area (SMA), or dorsolateral prefrontal cortex (DLPFC). Paired stimuli were delivered before or after a visual cue was presented to initiate self-paced right-handed reaches to one of three, vertically oriented target locations.ResultsRegional stimulation effects on movement amplitude were observed both early and late in the reach. PMA stimulation increased reach distance to a greater extent than M1, SMA, and DLPFC stimulation. M1 and PMA stimulation increased deviation from the straight-line path around the time of peak velocity to an extent that was greater than SMA and DLPFC stimulation. Cortical stimulation increased the time that elapsed after, but not before, peak velocity. Despite stronger effects of stimulation on reaches in the younger group, this group had shorter times to reach the target after reaching peak velocity.ConclusionThese results provide support for a role of PMA in visually guided movementaftermovement initiation. For older subjects, the increased time to arrive at the target after peak velocity despite weaker stimulation effects suggests an age-related reduction in sensorimotor processing flexibility for online control of unconstrained reaching.HighlightsDorsal premotor area stimulation at any time during the reaction-time period and early reaching affected early reach kinematics at least as much as stimulation of primary motor cortex.Older individuals had more stimulation-related interference in the late components of reaching despite having less early effect of stimulation, suggesting a reduction in flexibility of dynamic motor control due to aging.The antigravity component of unconstrained reaching did not have special aspects for regional cortical effects of stimulation.
The interaction of curiosity and reward on long-term memory in younger and older adults
Authors: Swirsky Liyana T. , Shulman Audrey , Spaniol Julia 
Published: December 2020

AbstractLong-term memory is sensitive to both intrinsic and extrinsic motivation, but little is known about the relative influence of these two sources of motivation on memory performance across the adult lifespan. The study examined the effects of extrinsic motivation, manipulated via monetary reward, and curiosity, a form of intrinsic motivation, on long-term memory in healthy younger and older adults. During the incidental encoding phase on Day 1, 60 younger and 53 older participants viewed high- and low-curiosity trivia items as well as unrelated face stimuli. Half of the participants in each age group received financial rewards for correctly guessing trivia answers. On Day 2, participants completed a trivia recall test and an old-new recognition test for the face stimuli. Both curiosity and reward were associated with enhanced trivia recall, but the effects were interactive, such that only low-curiosity items benefitted from monetary reward. Neither curiosity nor reward affected face recognition performance in either age group. These findings indicate that individual and joint effects of intrinsic and extrinsic motivation on long-term memory are relatively preserved in healthy aging, a finding that highlights the viability of motivational strategies for memory enhancement into old age. Identifying conditions under which memory for unrelated information benefits from motivational spillover effects in younger and older adults is a priority for future research.