bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiorgan Crystal Deposition of an Amphoteric Drug in Rats Due to Lysosomal Accumulation and Conversion to a Poorly Soluble Hydrochloride Salt
Authors: Lenz Barbara , Brink Andreas , Mihatsch Michael J , Altmann Bernd , Niederhauser Urs , Steinhuber Bernd , Wyttenbach Nicole , Fischer Holger 
Published: December 2020

Abstract
Poor solubility of drug candidates mainly affects bioavailability, but poor solubility of drugs and metabolites can also lead to precipitation within tissues, particularly when high doses are tested. RO0728617 is an amphoteric compound bearing basic and acidic moieties that has previously demonstrated good solubility at physiological pH but underwent widespread crystal deposition in multiple tissues in rat toxicity studies. The aim of our investigation was to better characterize these findings and their underlying mechanism(s), and to identify possible screening methods in the drug development process. Main microscopic features observed in rat RO0728617 toxicity studies were extensive infiltrates of crystal-containing macrophages in multiple organs. Matrix-assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry revealed that these crystals contained the orally administered parent compound, and locality was confirmed to be intracytoplasmic and partly intralysosomal by electron microscopic examination. Crystal formation was explained by lysosomal accumulation of the compound followed by precipitation of the hydrochloride salt under physiological conditions in the lysosomes, which have a lower pH and higher chloride concentration in comparison to the cytosol. This study demonstrates that risk of drug precipitation can be assessed by comparing the estimated lysosomal drug concentration at a given dose with the solubility of the compound at lysosomal conditions.
Increasing Cardiac Rehabilitation Participation Through a “Nearer to Home” Patient Referral Program
Authors: Bryant Joseph , Rubenfire Melvyn , Katona Aimee M. , Graves Christopher , Fink Samantha , Kline-Rogers Eva , Barber Andrew , Zhang Min , Weinstein David G. , Walden Patrick 
Published: December 2020

Purpose:
Time to travel to cardiac rehabilitation (CR) centers is a barrier to participation, and tertiary referral centers often care for patients living at a substantial distance. We sought to determine the impact of referring eligible patients to CR centers closer to home or workplace on overall participation rate.

Methods:
An observational review was conducted in patients from a large cardiovascular program who were referred to CR (January 1, 2015, through December 31, 2016). Those declining participation due to distance from their home were identified and provided coordinated referral to a CR program they chose near their home or workplace.

Results:
Of the 2912 patients referred to CR, 673 (23%) participated and 1900 declined due to distance. Contact was made in 2017 with 1237 of the 1900 of whom 1083 recalled a discussion of distance referral and completed the phone survey. Participants mean age was 64 yr, predominantly White (88%), male (65%), married (66%), and 70% had ≥ comorbidity. Out of the 1083 referred to a local CR program, 78% reported attending. Of those who attended CR, 55% (469/849) would not have attended had they not been referred to a program closer to their home or workplace. Overall participation increased from 23% to >50% of those referred from our institution.

Conclusions:
Coordinating CR referrals from the discharging facility to facilities closer to home or workplace is an effective means for increasing participation. The very low-cost effort has the potential to have a very meaningful impact on the long-term outcome of cardiovascular patients.
A Comparison of Exercise Intensity in Hybrid Versus Standard Phase Two Cardiac Rehabilitation
Authors: Keteyian Steven J. , Grimshaw Crystal , Brawner Clinton A. , Kerrigan Dennis J. , Reasons Lisa , Berry Robert , Peterson Edward L. , Ehrman Jonathon K. 
Published: December 2020

Purpose:
To compare exercise training intensity during standard cardiac rehabilitation (S-CR) versus hybrid-CR (combined clinic- and remote home-/community-based).

Methods:
The iATTEND (improving ATTENDance to cardiac rehabilitation) trial is currently enrolling subjects and randomizing patients to S-CR versus hybrid-CR. This substudy involves the first 47 subjects who completed ≥18 CR sessions. Patients in S-CR completed all visits in a typical phase II clinic-based setting and patients in hybrid-CR completed up to 17 of their sessions remotely using telehealth (TH). Exercise training intensity in both CR settings is based on heart rate (HR) data from each CR session, expressed as percent HR reserve.

Results:
Among patients in both study groups, there were no serious adverse events or falls that required hospitalization during or within 3 hr after completing a CR session. Expressed as a percentage of HR reserve, the overall mean exercise training intensities during both the S-CR sessions and the TH-CR sessions from hybrid-CR were not significantly different at 63 ± 12% and 65 ± 10%, respectively (P = .29).

Conclusion:
This study showed that hybrid-CR delivered using remote TH results in exercise training intensities that are not significantly different from S-CR.
Measurement of Natural Radionuclides and Assessment of Radiation Hazard in Coal from Parts of China
Authors: Li Wenhong , Wang Shuo , Yang Baolu , Tuo Fei 
Published: December 2020

Abstract
To study the content of radionuclides in coal and to assess its associated radiological impact on the environment for potential radiological risk assessment, a total of 40 coal samples were collected from various mining areas in eight provinces of China. The specific activities of 226Ra, 232Th, 40K, 210Pb, and 238U were measured in all samples using an HPGe gamma-ray spectrometer, and results were compared with available data from other similar studies. The results reveal that the radium equivalent activity was 74.20 Bq kg−1, external hazard index was 0.20, internal hazard index was 0.27, representative gamma index was 0.52, and indoor and outdoor annual effective dose rates were 0.16 nSv y−1 and 0.04 nSv y−1, respectively. Absorbed gamma dose rate in air was 32.87 nGy h−1. In general, these values are lower than the respective threshold limits recommended by UNSCEAR, and the radiation risk to the public is extremely small.
MLH1 c.199G>A, a Known Mutation for Lynch Syndrome, Is Also Associated with Sebaceous Neoplasm
Authors: Li Wei-Sheng , Li Yan , Zhou Nai-Hui , Liu Jing-Liu , Yang Zi-Liang , Sun Miao , Li Min 
Published: December 2020

Abstract

Introduction:
Muir-Torre syndrome is a phenotypic variant of Lynch syndrome characterized by a predisposition for the development of visceral malignant disease and sebaceous gland neoplasms, and it is caused by germline mutations in the mismatch repair genes MSH2 and MLH1.
Here, we reported a patient with sebaceous neoplasm containing MLH1 c.199G>A mutation.

Case presentation:
The proband was a 42-year-old man who had undergone surgical resection of colorectal adenocarcinoma at 28 years. He presented with macular rashes and red papule. Histological examination of the lesion on his head revealed a sebaceoma at 37 years. Follow-up of the family history revealed that the proband's 65-year-old mother had been highly suspected to have Lynch syndrome with colorectal cancer at 40 years of age. The proband's daughter underwent colonoscopy because of blood in the stool at the age of 13 years, but no abnormalities were found.

Discussion:
We have herein reported a pathogenic missense mutation c.199G>A (p.Gly67Arg) in exon 2 of MLH1 in patients with MTS. This mutation has been reported in patients with Lynch syndrome who have no skin tumors. However, we also found that some patients with MTS had no history of any internal malignancy or skin tumor. Our data support the idea that a hiatus of many years may pass before both elements-a sebaceous neoplasm and an internal cancer-are present in a patient, thus finally allowing the diagnosis of MTS.

Conclusion:
A pathogenic Lynch syndrome mutation c.199G>A in exon 2 of the MLH1 gene was found in a patient with MTS who presented with a sebaceous neoplasm.
Frequency of Falls and Associated Risk Factors in People Living With HIV: A Systematic Review With Meta-Analysis and Meta-Regression
Authors: Tolentino Arthur , Amaral Sávio , S. Souza Lucca , Zeballos Diana , Brites Carlos 
Published: December 2020

Background:
Falls are considered as a predictive marker of poorer outcomes for people living with HIV (PLWHIV). However, the available evidences on the predictive value of falls are controversial. Our aim is to summarize the existing data about falls in PLWHIV.

Methods:
A literature search was conducted using electronic databases (MEDLINE, Embase, and LILACS) for original observational studies. The primary outcome was any and recurrent falls' frequency in PLWHIV, and secondary outcomes were factors associated with falls. We conducted a random-effects meta-analysis with meta-regression to obtain a summary frequency of falls and recurrent falls.

Results:
The pooled frequency for any fall was 26% [95% confidence interval (CI): 19% to 34%], compared with 14% for recurrent falls (95% CI: 9% to 22%). In studies comparing PLWHIV and people without HIV, we found no difference for any (pooled odds ratio 1.03, 95% CI: 0.90 to 1.17) or recurrent falls (pooled odds ratio 1.08, 95% CI: 0.92 to 1.27) between groups, but falls in middle-aged PLWHIV might be more associated with subjacent clinical conditions such as cognitive impairment, polypharmacy, use of medications with action in the central nervous system, and frailty, classic risk factors for falls in the elderly.

Conclusions:
The overall frequency of falls in PLWHIV seems to be lower than that presented by some initial studies, and several factors associated with falls are shared with elderly adults. Although both PLWHIV and people without HIV presented similar frequency of falls, we found that these events might be qualitatively different; therefore, an appropriate method to evaluate falls in this population to prevent adverse outcomes is warranted.
Prevalence, Management, and Outcomes Related to Preoperative Medical Orders for Life Sustaining Treatment (MOLST) in an Adult Surgical Population
Authors: Tanious Mariah , Lindvall Charlotta , Cooper Zara , Tukan Natalie , Peters Stephanie , Streid Jocelyn , Fields Kara , Bader Angela 
Published: December 2020

Objective:
To determine prevalence of documented preoperative code status discussions and postoperative outcomes (specifically mortality, readmission, and discharge disposition) of patients with completed MOLST forms before surgery.

Summary of Background Data:
A MOLST form documents patient care preference regarding treatment limitations. When considering surgery in these patients, preoperative discussion is necessary to ensure concordance of care. Little is known about prevalence of these discussions and postoperative outcomes.

Methods:
A retrospective cohort study was conducted consisting of all patients having surgery during a 1-year period at a tertiary care academic center in Boston, Massachusetts.

Results:
Among 21,787 surgical patients meeting inclusion criteria, 402 (1.8%) patients had preoperative MOLST. Within the MOLST, 224 (55.7%) patients had chosen to limit cardiopulmonary resuscitation and 214 (53.2%) had chosen to limit intubation and mechanical ventilation. Code status discussion was documented presurgery in 169 (42.0%) patients with MOLST. Surgery was elective or nonurgent for 362 (90%), and median length of stay (Q1, Q3) was 5.1 days (1.9, 9.9). The minority of patients with preoperative MOLST were discharged home [169 (42%), and 103 (25.6%) patients were readmitted within 30 days. Patients with preoperative MOLST had a 30-day mortality of 9.2% (37 patients) and cumulative 90-day mortality of 14.9% (60 patients).

Conclusions:
Fewer than half of surgical patients with preoperative MOLST have documented code status discussions before surgery. Given their high risk of postoperative mortality and the diversity of preferences found in MOLST, thoughtful discussion before surgery is critical to ensure concordant perioperative care.
QFEA - A Method for Assessing the Filtration Efficiency of Face Mask Materials for Early Design Prototypes and Home Mask Makers
Authors: O’Kelly Eugenia , Arora Anmol , O’Kelly Corinne , Pearson Charlotte , Ward James , Clarkson P John 
Published: December 2020

Abstract
The COVID-19 pandemic has led to a surge in the design and production of fabric face coverings. There are few published methods which enable mask designers, makers and purchasers to assess the relative filtration ability of mask making materials. Those methods which do exist are prohibitively expensive and difficult to conduct. As a result, mask makers, non-profits, and small-scale designers face difficult decisions when designing face coverings for personal and commercial use. In this paper, we propose a novel method, the Qualitative Filtration Efficiency Assessment (QFEA), for easily and inexpensively comparing the filtration efficiency of common materials. This method provides a highly affordable and readily available way to assess potential mask materials.
Development of a Conceptual Model of Childhood Asthma to Inform Asthma Prevention Policies
Authors: Adibi Amin , Turvey Stuart E , Lee Tae Yoon , Sears Malcolm R , Becker Allen B , Mandhane Piush J , Moraes Theo J , Subbarao Padmaja , Sadatsafavi Mohsen 
Published: December 2020

AbstractBackgroundThere is no definitive cure for asthma; as such, prevention remains a major goal. Decision-analytic models are routinely used to evaluate the value-for-money proposition of interventions. Following best practice standards in decision-analytic modeling, the objective of this study was to solicit expert opinion to develop a concept map for a policy model for primary prevention of asthma.MethodsWe reviewed currently available decision-analytic models for asthma prevention. A steering committee of economic modelers, allergists, and respirologists was then convened to draft a conceptual model of pediatric asthma. A modified Delphi method was followed to define the context of the problem at hand (evaluation of asthma prevention strategies) and develop the concept map of the model.ResultsConsensus was achieved after three rounds of discussions, followed by concealed voting. In the final conceptual model, asthma diagnosis was based on three domains of lung function, atopy, and their symptoms. The panel recommended several markers for each domain. These domains were in turn affected by several risk factors. The panel clustered all risk factors under three groups of ‘patient characteristic’, ‘family history’, and ‘environmental factors’. To be capable of modeling the interplay among risk factors, the panel recommended the use of microsimulation, with an open-population approach that would enable modeling phased implementation and gradual and incomplete uptake of the intervention.ConclusionsEconomic evaluation of childhood interventions for preventing asthma will require modeling of several co-dependent risk factors and multiple domains that affect the diagnosis. The conceptual model can inform the development and validation of a policy model for childhood asthma prevention.FundingGenome Canada Large-Scale Applied Research Project
A standardized non-visual behavioral event is broadcasted homogeneously across cortical visual areas without modulating visual responses
Authors: Ramadan Mahdi , Lee Eric Kenji , de Vries Saskia , Caldejon Shiella , Kato India , Roll Kate , Griffin Fiona , Nguyen Thuyanh V. , Larkin Josh , Rhoads Paul , Mace Kyla , Kriedberg Ali , Howard Robert , Berbesque Nathan , Lecoq Jérôme 
Published: December 2020

AbstractMultiple recent studies have shown that motor activity greatly impacts the activity of primary sensory areas like V1. Yet, the role of this motor related activity in sensory processing is still unclear.Here we dissect how these behavior signals are broadcast to different layers and areas of the visual cortex. To do so, we leveraged a standardized and spontaneous behavioral fidget event in passively viewing mice. Importantly, this behavior event had no relevance to any ongoing task allowing us to compare its neuronal correlate with visually relevant behavior like running.A large two-photon Ca2+ imaging database of neuronal responses uncovered four neural response types during fidgets that were surprisingly consistent in their proportion and response patterns across all visual areas and layers of the visual cortex. Indeed, the layer and area identity could not be decoded above chance level based only on neuronal recordings. In contrast to running behavior, fidget evoked neural responses were independent to visual processing.The broad availability of visually orthogonal standardized behavior signals could be a key component in how the cortex selects, learns and binds local sensory information with motor outputs. Contrary to relevant motor outputs, irrelevant motor signals would use a separate neural subspaces.Significance StatementRecent studies have shown contextual and behavioral variables to dominate brain-wide activity, but yet it is unknown how this information is broadcast across cortical layers and areas. Using a large two-photon dataset collected in mice passively viewing a battery of visual stimuli, we characterized the neuronal response of neurons of the visual cortex to a standardized fidget behavior. We found that as much as 47% of excitatory neurons show significant co-activity with fidgets. Throughout all areas and layers we recorded from, those responses were distributed across surprisingly consistent three neural response types. Further analysis showed no interaction between fidget neural events and cells’ visual stimulus responses, contrasting with feedback neural signals induced by running. These contrasting response distribution patterns suggest that behavioral neuronal correlates are broadly available but will modulate sensory responses depending on their relevance to local sensory inputs.
The Persistence of Vaccine Hesitancy: COVID-19 Vaccination Intention
Authors: Thaker Jagadish 
Published: December 2020

AbstractBuilding public trust and willingness to vaccinate against COVID-19 is as important as developing an effective vaccine. However, a significant minority of the public are unwilling or hesitant to take a COVID-19 vaccine, when available. A nationally representative sample survey (N=1040) was conducted in July 2020 in New Zealand to identify factors associated with COVID-19 vaccine intention. Trust in experts and general vaccine hesitancy were significantly associated with COVID-19 vaccine intention. A communication campaign from trusted scientific experts, with information that addresses prevailing concerns about vaccines, is likely to help increase COVID-19 vaccine uptake.
Potential Relationship Between eGFRcystatin C/eGFRcreatinine-ratio and Glomerular Basement Membrane Thickness in Diabetic Kidney Disease
Authors: Öberg Carl M. , Lindström Martin , Grubb Anders , Christensson Anders 
Published: December 2020

ABSTRACTBackgroundDiabetic nephropathy (DN) is a leading cause of end stage renal disease and renal replacement therapy worldwide. A pathophysiological hallmark of DN is glomerular basal membrane (GBM) thickening, whereas this feature is absent in minimal change disease. Theoretically, a thicker GBM will impede the diffusion of middle-molecules such as cystatin C, potentially leading to a lower estimated GFR (eGFR) from cystatin C compared to that of creatinine. Here we test the hypothesis that thickening of the glomerular filter leads to an increased diffusion length, and lower clearance, of cystatin C.MethodsTwenty-nine patients with a kidney biopsy diagnosis of either DN (n=17) or minimal change disease (MCD) (n=12) were retrospectively included in the study. GBM thickness was measured at 20 separate locations in the biopsy specimen and plasma levels of cystatin C and creatinine were retrieved from health records. A modified two-pore model was used to simulate the effects of a thicker GBM on glomerular water and solute transport.ResultsThe mean age of the patients was 52 years, and 38% were women. The mean eGFRcystatin C/eGFRcreatinine-ratio was 74% in DKD compared to 98% in MCD (P < 0.001). Average GBM thickness was strongly inversely correlated to the eGFRcystatin C/eGFRcreatinine-ratio (Pearson’s r=-0.61, P < 0.01). Two-pore modeling predicted a eGFRcystatin C/eGFRcreatinine-ratio of 78% in DN.ConclusionsWe provide clinical and theoretical evidence suggesting that thickening of the glomerular filter, increasing the diffusion length of cystatin C, lowers the eGFRcystatin C/eGFRcreatinine-ratio in DN.Significance statementIncreased thickness of the glomerular basement membrane (GBM) is an early structural abnormality in diabetes, and has been identified as an independent risk factor for progression to diabetic nephropathy (DN). Increased GBM thickness will increase the diffusion length of mid-sized molecules like cystatin C across the renal filter, potentially leading to increased plasma concentrations and lower estimated GFR from cystatin C. The authors show theoretically that estimated GFR from cystatin C (eGFRcystatin C) is lower than that of creatinine (eGFRcreatinine) in DN to a degree directly depending on GBM thickness. In line with theory, they provide clinical data showing a lower eGFRcystatin Cin diabetic patients with the eGFRcystatin C/eGFRcreatinine-ratio being inversely correlated to GBM thickness assessed from electron micrographs.