bluuebunny/crossref_metadata_2025_split huggingface dataset:
Successful treatment with lorlatinib in a patient with meningeal carcinomatosis of ALK-positive non-small cell lung cancer resistant to alectinib and brigatinib
Authors: Nakashima Koki , Demura Yoshiki , Kurokawa Kosuke , Takeda Toshihiro , Jikuya Norihiro , Oi Masahiro , Tada Toshihiko , Akai Masaya , Ishizuka Tamotsu 
Published: October 2021

Abstract

Rationale:
Although anaplastic lymphoma kinase (ALK) inhibitors are effective treatment options for ALK-positive non-small cell lung cancer (NSCLC) with central nervous system (CNS) metastasis, achieving long-term survival in patients with NSCLC with meningeal carcinomatosis resistant to ALK inhibitors is difficult. Lorlatinib, a third-generation ALK inhibitor, was designed for selective CNS penetration, and exerts potent antitumor activity against tumors resistant to first- and/or second-generation ALK inhibitors. However, there is limited information about the activity of lorlatinib in ALK inhibitor-resistant meningeal carcinomatosis. Here, we report a case of ALK-positive lung adenocarcinoma with meningeal carcinomatosis in which lorlatinib was used after resistance to alectinib and brigatinib.

Patients concerns:
A 55-year-old woman with no history of smoking presented to our hospital with a swelling on the left neck. Clinical imaging and histopathological examination revealed a tumor of adenocarcinoma histology in the left upper lung with no CNS metastasis.

Diagnoses:
The patient was diagnosed with ALK-positive lung adenocarcinoma (cT3N3M1b: stage IVA).

Interventions:
She received the second-generation ALK inhibitors, alectinib and brigatinib, in the first and second-line settings, respectively. However, she developed meningeal carcinomatosis. Hence, treatment with lorlatinib was initiated in the third-line setting.

Outcomes:
The symptoms associated with meningeal carcinomatosis, such as disturbance of consciousness and diplopia, improved dramatically. At 8 months from the initiation of lorlatinib, the patient remained well without disease progression.

Lessons:
Lorlatinib is an effective treatment option for patient with ALK-positive NSCLC who develop meningeal carcinomatosis resistant to second-generation ALK inhibitors. Therefore, lorlatinib should be considered in such cases, even when patients exhibit serious symptoms associated with meningeal carcinomatosis.
Bilateral retinal pigment epithelial tears in acute central serous chorioretinopathy without bullous retinal detachment
Authors: Lee Woo Hyuk , Kim Bum Jun , Han Yong Seop 
Published: October 2021

Abstract

Rationale:
Several reports have described retinal pigment epithelial (RPE) tears in central serous chorioretinopathy (CSC). However, there have been no reports of spontaneously large RPE tears in acute CSC without bullous retinal detachment (RD). Herein, we report and provide sequential images of a case of bilateral spontaneous large RPE tears in patient with acute CSC without bullous RD.

Patient Concerns:
An 88-year-old female patient was admitted with impaired vision in both eyes, which began 10 days prior. The visual acuity was 0.4 and 0.5 in the right and left eye, respectively. She had started taking oral steroids 2 weeks prior for polymyalgia.

Diagnosis:
Ophthalmologic examinations, including fundus photography, optical coherence tomography, and fluorescence angiography, were performed, and she was diagnosed with steroid-induced acute CSC in both eyes with large pigment epithelial detachment (PED) of approximately 4-disc diameter. Discontinuation of steroids and follow-up ophthalmic examinations were performed. However, a spontaneous large RPE tear occurred in the right eye.

Interventions:
We performed follow-ups more frequently and CSC treatment such as laser photocoagulation, photodynamic therapy, and anti-vascular endothelial growth factor injections were not performed.

Outcomes:
Nine months later, a spontaneous large RPE tear occurred sequentially in the left eye. Her final visual acuity was 0.3 and 0.15 in the right and left eye, respectively.

Lessons:
Patients may spontaneously develop large RPE tears in both eyes, despite no treatment for acute CSC with non-bullous RD. Large PED and old age may affect this. Therefore, for a CSC patient with a large PED and advanced age, attention must be paid when determining treatment.
Examining Patients’ Capacity to Use Patient Portals
Authors: McAlearney Ann Scheck , Sieck Cynthia J. , Gregory Megan E. , Di Tosto Gennaro , MacEwan Sarah R. , DePuccio Matthew J. , Lee Jennifer A. , Huerta Timothy R. , Walker Daniel M. 
Published: October 2021

Background:
The increase in telehealth in response to the coronavirus disease 2019 pandemic highlights the need to understand patients’ capacity to utilize this care modality. Patient portals are a tool whose use requires similar resources and skills as those required for telehealth. Patients’ capacity to use patient portals may therefore provide insight regarding patients’ readiness and capacity to use telehealth.

Objective:
The aim of this study was to examine factors related to patients’ capacity to use a patient portal and test the impact of these factors on patients’ portal use.

Research Design and Subjects:
Using data from a large-scale pragmatic randomized controlled trial of patient portal use, 1081 hospitalized patients responded to survey items that were then mapped onto the 4 dimensions of the Engagement Capacity Framework: self-efficacy, resources, willingness, and capabilities.

Measures:
The outcome variable was frequency of outpatient portal use. We evaluated associations between Engagement Capacity Framework dimensions and patient portal use, using regression analyses.

Results:
Patients with fewer resources, fewer capabilities, lower willingness, and lower overall capacity to use patient portals used the portal less; in contrast, those with lower perceived self-efficacy used the portal more.

Conclusions:
Our findings highlight differences in patients’ capacity to use patient portals, which provide an initial understanding of factors that may influence the use of telehealth and offer important guidance in efforts to support patients’ telehealth use. Offering patients training tailored to the use of telehealth tools may be particularly beneficial.
Association of a Medicare Outpatient Payment Reform With Hospital-Primary Care Integration
Authors: Post Brady 
Published: October 2021

Background:
Hospital-physician integration increased rapidly in the past decade, threatening the affordability of care with minimal gains in quality. Medicare recently reformed its facility fee payments to hospitals for office consultations delivered by hospital-integrated physicians. This policy reform, affecting 200 million office visits annually, may have inadvertently encouraged hospitals to integrate with certain primary care physicians.

Objective:
The objective of this study was to determine whether the policy reform was associated with hospital-primary care integration.

Research Design:
I used a large sample of primary care physicians (n=98,884) drawn from Medicare claims data. I estimated cross-sectional multivariable linear probability models to measure whether the change in physicians’ value-to-hospitals was associated with integration.

Results:
The reform created heterogenous results: some physicians’ value-to-hospitals decreased, while others increased (first percentile to 99th percentile, −$16,000 to $47,000). This change in value had a small association with integration: for every $10,000 increase, a physician was about 0.34 percentage points (95% confidence interval: 0.16–0.52) more likely to become integrated. Among high-volume physicians, the reform had larger effects: physicians whose value-to-hospitals grew by $20,000 or more were nearly 3 percentage points more likely to become integrated. Changes in value had no effect in concentrated hospital markets and rural areas.

Conclusions:
Effects of Medicare’s site-based payments on hospital-primary care integration were concentrated among a small subset of physicians. Reforms to Medicare payment policy could influence integration among this group.
Clinical and Ergonomic Comparison Between a Robotic Assisted Transfer Device and a Mobile Floor Lift During Caregiver-Assisted Wheelchair Transfers
Authors: Greenhalgh Mark , Blaauw Eline , Deepak Nikitha , St Laurent Matthew , Cooper Rosemarie , Bendixen Roxanna , Grindle Garrett G. , Koontz Alicia M. , Cooper Rory A. 
Published: October 2021

Background
The robotic assisted transfer device was developed as an updated lift technology to reduce adjustments in posture while increasing capabilities offered by transfer devices. The purpose of this study was to compare the trunk biomechanics of a robotic assisted transfer device and a mechanical floor lift in the transfer of a care recipient by a caregiver during essential transfer tasks.

Methods
Investigators enrolled 28 caregiver/care recipient dyads to complete 36 transferring tasks. Surface electromyography for the back muscles and motion data for trunk range of motion were collected for selected surfaces, phase, and direction tasks using a robotic assisted transfer device and a mechanical floor lift.

Results
Robotic assisted transfer device transfers required significantly smaller range of trunk flexion (P < 0.001), lateral bend (P < 0.001), and axial rotation (P = 0.01), in addition to smaller distance covered (P < 0.001), average instantaneous velocity (P = 0.01), and acceleration (P < 0.001) compared with a mobile floor lift. The robotic assisted transfer device transfers required significantly smaller peak erector spinae (left: P = 0.001; right: P < 0.001) and latissimus dorsi (right: P < 0.001) and integrated erector spinae left (P = 0.001) and latissimus dorsi right (P = 0.01) electromyography signals compared with the floor lift.

Conclusions
The robotic assisted transfer device provides additional benefits to mobile floor lifts which, coupled with statistically lower flexion, extension, and rotation, may make them an appealing alternative intervention.
Personality Predictors of Sports-Related Concussion Incidence
Authors: Weishaar Megan G. , Stephens Jaclyn A. , Conner Bradley T. 
Published: October 2021

Objective
Studies investigating the associations between personality and sports-related concussion are limited. The current study aimed to address this gap by examining whether specific personality dimensions predicted self-reported sports-related concussion outcomes.

Design
This study included 1141 undergraduate students (M
age = 19.47, SD = 2.14, female = 64.5%) who completed a battery of online personality measures and self-reported sports-related concussion items. The self-reported sports-related concussion outcomes included a single diagnosed sports-related concussion incident (i.e., “diagnosed sports-related concussion incidence”) and incidents of multiple diagnosed sports-related concussions (i.e., “multiple diagnosed sports-related concussion incidents”). Analyses included splitting data randomly into training and validation data sets. Multivariate logistic regression models were then fit to each data set to determine predictors of sports-related concussion.

Results
In both training and validation data sets, extraversion and experience seeking were found to be positively and most strongly associated with both sports-related concussion outcomes, whereas motor inhibition was found to be negatively associated with both outcomes. Additional personality dimensions showed differential relations with each sports-related concussion outcome.

Conclusions
The current study highlights the importance of considering personality dimensions in the context of self-reported sports-related concussion outcomes, as there are differential relations between personality dimensions and these outcomes. Thus, prevention efforts for sports-related concussion may benefit from evaluating additional athlete factors, like personality traits.
Probiotics to HIV-Infected Immunological Nonresponders: Altered Mucosal Immunity and Microbial Diversity Restricted to Ileum
Authors: Meyer-Myklestad Malin Holm. , Medhus Asle W. , Stiksrud Birgitte , Lorvik Kristina B. , Seljeflot Ingebjørg , Hansen Simen H. , Holm Kristian , Hov Johannes R. , Kvale Dag , Dyrhol-Riise Anne Margarita. , Kummen Martin , Trøseid Marius , Reikvam Dag Henrik. 
Published: October 2021

Background:
HIV-infected immunological nonresponders (INRs) have increased risk of non-AIDS morbidity and compromised gut barrier immunity. Probiotics are widely used to improve health. We assessed the effects of probiotics in INRs with a comprehensive analysis of gut immunity and microbiome in terminal ileum and sigmoid colon.

Methods:
The study involved clinical intervention with five-strain probiotic capsules (1.2 × 1010 CFUs/d) for 8 weeks in 20 INRs with CD4+ T-cell counts <400 cells/µL and plasma HIV RNA <50 copies/mL for more than 3.5 years. Colonoscopy with sampling of gut biopsies from terminal ileum and sigmoid colon and fecal and blood sampling were performed before and after the intervention. Flow cytometry (cytokine production, immune activation, and exhaustion), ELISA (inflammation, microbial translocation, and enterocyte damage), and 16S rRNA sequencing analyses were applied.

Results:
In the terminal ileum, increased alpha diversity, increased abundance of Bifidobacterium sp., and decreased frequencies of IL-22+ CD4+ T cells were observed. The increased abundance of Bifidobacterium sp. in the terminal ileum correlated with increased fraction of CD4+ T cells in the same compartment (r = 0.54, P = 0.05) and increased CD4/CD8 ratio in peripheral blood (r = 0.49, P = 0.05). There were no corresponding changes in the sigmoid colon and no changes in fecal microbiome. Probiotic intervention did not affect peripheral blood CD4 count, viral load, or soluble markers of inflammation and microbial translocation.

Conclusions:
Probiotics induced segment-specific changes in the terminal ileum but did not affect systemic CD4 counts in INRs. Further clinical studies are warranted to recommend probiotics to INRs.
Genital Mucosal Drug Concentrations and anti-HIV Activity in Tenofovir-Based PrEP Products: Intravaginal Ring vs. Oral Administration
Authors: Ouattara Louise A. , Thurman Andrea R. , Jacot Terry A. , Cottrell Mackenzie , Sykes Craig , Blake Kimberly , Fang Xi , Ju Susan , Vann Nikolas C. , Schwartz Jill , Doncel Gustavo F. 
Published: October 2021

Objective:
To describe and compare systemic and local pharmacokinetics (PK) and cervicovaginal (CV) pharmacodynamics (PD) of oral tenofovir disoproxil fumarate (TDF) in combination with emtricitabine (FTC) with tenofovir (TFV) intravaginal ring (IVR).

Design:
Phase I, randomized, parallel-group study. Women (n = 22) used TDF/FTC oral tablets daily or TFV IVR continuously and were assessed at baseline and 14 days.

Methods:
TFV and FTC concentrations were measured in plasma, CV fluid (CVF), and CV tissue. TFV-diphosphate and FTC-triphosphate were assessed in CV tissue. In vitro PD antiviral activities of TFV and FTC (using in vivo concentration ranges) were modeled in the CVF and by infecting CV tissue explants ex vivo with HIV-1BaL.

Results:
Adverse events (AEs) were more common with oral TDF/FTC use (P < 0.01). The median CVF TFV concentrations were 106 ng/mL after use of TFV IVR vs. 102 ng/mL for TDF/FTC. The median TFV and TFV-diphosphate concentrations in CV tissue were >100-fold higher among IVR users. The median CVF FTC concentrations were 103 ng/mL. FTC and FTC-triphosphate were detected in all CV tissues from TDF/FTC users. HIV inhibitory activity of CVF increased significantly with treatment in both cohorts (P < 0.01) but was higher in TFV IVR users (P < 0.01). In vitro inhibition of tissue infection with ex vivo administration of TFV and FTC was dose dependent, with maximal efficacy achieved with 10 µg/mL TFV, 1 µg/mL FTC, and 0.1 µg/mL of TFV and FTC combined.

Conclusions:
Both products were safe and increased mucosal HIV inhibitory activity. In addition to systemic protection, oral TDF/FTC displays a PK/PD profile compatible with CV mucosal antiviral activity. TFV IVR resulted in fewer AEs, lower TFV plasma concentrations, higher CVF and tissue TFV and TFV-DP concentrations, and greater anti-HIV activity in CVF.
Effect of common maintenance drugs on the risk and severity of COVID-19 in elderly patients
Authors: Fung Kin Wah , Baik Seo H. , Baye Fitsum , Zheng Zhaonian , Huser Vojtech , McDonald Clement J. 
Published: October 2021

AbstractBackgroundMaintenance drugs are used to treat chronic conditions. Several classes of maintenance drugs have attracted attention because of their potential to affect susceptibility to and severity of COVID-19.MethodsUsing claims data on 20% random sample of Part D Medicare enrollees from April to December 2020, we identified patients diagnosed with COVID-19. Using a nested case-control design, non-COVID-19 controls were identified by 1:5 matching on age, race, sex, dual-eligibility status and geographical region. We identified usage of angiotensin-converting enzyme inhibitors (ACEI), angiotensin-receptor blockers (ARB), warfarin, direct factor Xa inhibitors, clopidogrel, famotidine and hydroxychloroquine based on Medicare prescription claims data. Using extended Cox regression models with time-varying propensity score adjustment we examined the independent effect of each study drug on contracting COVID-19. For severity of COVID-19, we performed extended Cox regressions on all COVID-19 patients, using COVID-19-related hospitalization and all-cause mortality as outcomes. Covariates included gender, age, race, geographic region, low-income indicator and co-morbidities. To compensate for indication bias related to the use of hydroxychloroquine for the prophylaxis or treatment of COVID-19, we censored patients who only started on hydroxychloroquine in 2020.ResultsUp to December 2020, our sample contained 374,229 Medicare patients over 65 who were diagnosed with COVID-19. Among the COVID-19 patients, 209,208 (55.9%) were on at least one study drug. The three most common study drugs were ACEI 97,872 (26.1%), ARB 83,329 (22.3%) and clopidogrel 38,203 (10.2%). Current users of ACEI, ARB, warfarin, direct factor Xa inhibitor and clopidogrel were associated with reduced risk of getting COVID-19 (3-13%), and reduced risk of dying after a COVID-19 diagnosis (8-19%). Famotidine did not show consistent significant effects. Hydroxychloroquine did not show significant effects after censoring of recent starters.ConclusionsMaintenance use of ACEI, ARB, warfarin, direct factor Xa inhibitor and clopidogrel was associated with reduction in risk of acquiring COVID-19 and dying from it.
Anin vitro- agent-based modelling approach to optimisation of culture medium for generating muscle cells
Authors: Hardman David , Hennig Katharina , Gomes Edgar R , Roman William , Bernabeu Miguel O 
Published: October 2021

AbstractMethodologies for culturing muscle tissue are currently lacking in terms of quality and quantity of mature cells produced. We analyse images fromin vitroexperiments to quantify the effects of culture media composition on mouse-derived myoblast behaviour and myotube quality. Computational modelling was used to predict an optimum media composition for culturing. Metrics of early indicators of cell quality were defined. Images of muscle cell differentiation reveal that altering culture media significantly affects quality indicators and myoblast migratory behaviours. To predict cell quality from early-stage myoblast behaviours, metrics drawn from experimental images or inferred by Approximate Bayesian Computation were applied as inputs to an agent-based model (ABM) of differentiation with quality indicator metrics as outputs. We describe cell behaviours as a set of functions of media composition to predict cell quality using the ABM. Our results suggest that culturing muscle cells in neural cell differentiation medium reduces cell-cell fusion but does not diminish cell quality and that increasing serum concentration increases myoblast fusion implying a trade-off between the quantity and quality of cells produced when choosing a culture medium. Our model provided a good prediction of experimental results for media with 5% serum provided the myoblast proliferation rate was known.Author summaryFunctional skeletal muscle tissue can be grown in the lab but is most useful if the constituent muscle cells behave as they wouldin vivo. Optimising the conditions to promote precursor muscle cell fusion and growth is therefore vital. With many different factors influencing cell growth finding optimal conditions through rounds of experimentation alone is difficult especially as we strive to complexify our cultures with multiple cell types. We created metrics quantifying mature muscle cell quality at an early stage of development and applied them to experiments with a variety of culture media compositions. Changing the concentration of serum and proportion of neuron differentiation medium produced differences in the behaviour of fusing cells and in the quality and quantity of mature cells. From these results we created phenomenological models describing the behaviour of fusing cells for any combination of serum and neuron medium concentration. We integrated these models into a multiscale agent-based computational model of cell fusion to predict cell quality and quantity through virtual experiments in an emergent fashion. Our model suggests that choosing culture media composition will involve fundamental compromises between cell quantity and quality and that cells which initially fuse quickly may produce less final yield.
De novo prediction of RNA-protein interactions with Graph Neural Networks
Authors: Arora Viplove , Sanguinetti Guido 
Published: October 2021

AbstractRNA-binding proteins (RBPs) are key co- and post-transcriptional regulators of gene expression, playing a crucial role in many biological processes. Experimental methods like CLIP-seq have enabled the identification of transcriptome-wide RNA-protein interactions for select proteins, however the time- and resource-intensive nature of these technologies call for the development of computational methods to complement their predictions. Here we leverage recent, large-scale CLIP-seq experiments to construct a de novo predictor of RNA-protein interactions based on graph neural networks (GNN). We show that the GNN method allows not only to predict missing links in an RNA-protein network, but to predict the entire complement of targets of previously unassayed proteins, and even to reconstruct the entire network of RNA-protein interactions in different conditions based on minimal information. Our results demonstrate the potential of modern machine learning methods to extract useful information on post-transcriptional regulation from large data sets.