bluuebunny/crossref_metadata_2025 huggingface dataset:
Precision medicine for cervical cancer
Authors: Manrriquez Erica N. , Zakhour Mae , Salani Ritu
Published: October 2021

Purpose of review

To summarize the data on precision medicine for cervical cancer including the use of potential biomarkers. We also review ongoing areas of research in cervical cancer therapeutics.

Recent findings

In the current clinical practice, programmed death ligand 1 (PD-L1) expression is used to select patients with cervical cancer for treatment with checkpoint inhibitors. However, more recently presented data suggest that PD-L1 may not be a fully accurate biomarker for selection and further analysis is warranted. With the publication of the molecular landscape of cervical cancer, tumor profile-based therapy selection is of greater interest (i.e. targeting PI3K and HER2).

In this review, we discuss the role of potential biomarkers for cervical cancer that may assist with the selection of precision therapies. Enrolling patients on active clinical trials will help clarify the role of targeting specific mutations.
Children Have Similar Reverse Transcription Polymerase Chain Reaction Cycle Threshold for Severe Acute Respiratory Syndrome Coronavirus 2 in Comparison With Adults
Authors: Polese-Bonatto Márcia , Sartor Ivaine Tais Sauthier , Varela Fernanda Hammes , Giannini Gabriela Luchiari Tumioto , Azevedo Thaís Raupp , Kern Luciane Beatriz , Fernandes Ingrid Rodrigues , Zavaglia Gabriela Oliveira , de David Caroline Nespolo , Santos Amanda Paz , de Almeida Walquiria Aparecida Ferreira , Porto Victor Bertollo Gomes , Scotta Marcelo Comerlato , Stein Renato T. ,   for the COVIDa Study Group
Published: October 2021

Background:

The viral dynamics and the role of children in the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not completely understood. Our aim was to evaluate reverse transcription polymerase chain reaction (RT-PCR) cycle threshold (Ct) values among children with confirmed SARS-CoV-2 compared with that of adult subjects.

Methods:

Patients (from 2 months to ≤18 years of age and adults) with signs and symptoms of acute SARS-CoV-2 infection for less than 7 days were prospectively enrolled in the study from May to November 2020. All participants performed RT-PCR assay for SARS-CoV-2 detection; Ct values of ORF1ab, N and S gene targets and the average of all the 3 probes were used as surrogates of viral load.

Results:

There were 21 infants (2 months to <2 years), 40 children (≥2 to <12 years), 22 adolescents (≥12 to <18 years) and 293 adults of 376 participants with confirmed SARS-CoV-2 infections. RT-PCR Ct values from all participants less than 18 years of age, as well as from all childhood subgroups, were not significantly different from adults, comparing ORF1ab, N, S and all the gene targets together (P = 0.453).

Conclusions:

Ct values for children were comparable with that of adults. Although viral load is not the only determinant of SARS-CoV-2 transmission, children may play a role in the spread of coronavirus disease 2019 in the community.
Visual outcomes of a new nondiffractive extended depth-of-focus intraocular lens targeted for minimonovision: 3-month results of a prospective cohort study
Authors: van Amelsfort Thomas , Webers Valentijn S.C. , Bauer Noël J.C. , Clement Laurentius H.H. , van den Biggelaar Frank J.H.M. , Nuijts Rudy M.M.A.
Published: October 2021

Purpose:

To evaluate visual outcomes, spectacle independence, and optical phenomena after bilateral implantation of a nondiffractive extended depth-of-focus (EDoF) intraocular lens (IOL) targeted for minimonovision.

Setting:

University Eye Clinic Maastricht, the Netherlands.

Design:

Prospective case series.

Methods:

Patients with age-related cataract were bilaterally implanted with a nondiffractive EDoF IOL (Alcon AcrySof IQ Vivity), targeted for minimonovision. Outcome measures were the uncorrected distance visual acuity (UDVA), corrected distance visual acuity, uncorrected intermediate visual acuity (UIVA), uncorrected near visual acuity (UNVA), distance corrected intermediate visual acuity, distance corrected near visual acuity, refractive outcomes, defocus curves, spectacle independence, photic phenomena, and Catquest-9SF questionnaire.

Results:

44 eyes of 22 patients were included. The mean binocular UDVA, UIVA, and UNVA were −0.07 (±0.10), 0.04 (±0.09), and 0.23 (±0.12) logMAR, respectively. The percentage of eyes within ±1.0 diopters (D) and ±0.5 D of target was 100% and 95% for the dominant eye and 100% and 86% for the nondominant eye, respectively. The binocular defocus curve was better than 0.10 logMAR over a range from −2.0 D to +0.5 D. The percentage of patients who reported not or rarely using spectacles for distance, intermediate, and near viewing distance was 96%, 68%, and 38%, respectively. The percentage of patients who experienced no halos, glare, or starbursts were 91%, 91%, and 100%, respectively. The Catquest-9SF showed a high patient satisfaction for daily life activities.

Conclusions:

Bilateral AcrySof IQ Vivity IOL implantation targeted for minimonovision provided good visual acuity results for far and intermediate with functional near vision, high level of patient satisfaction and spectacle independence, and a monofocal disturbance profile.
Fill levels, cost comparisons, and expulsion force requirements of commonly used topical ophthalmic steroids
Authors: Gill Mohsain S. , Murphy David A. , Dvorak Justin D. , Shah Simren V. , Riaz Kamran M.
Published: October 2021

Purpose:

To determine volume fill levels, estimated costs, and force expulsion requirements per bottle of topical ophthalmic steroids commonly used in the United States.

Setting:

Tertiary care academic referral center.

Design:

Prospective laboratory investigation.

Methods:

8 commercially available medications were tested: loteprednol 0.5%, loteprednol gel 0.5%, loteprednol gel 0.38%, difluprednate 0.05%, generic fluorometholone 0.1%, branded fluorometholone 0.1%, generic prednisolone 1.0%, and branded prednisolone 1.0%. 10 bottles of each medication were tested. A double-blinded method was used to measure actual bottle fill volume and number of drops dispensed per bottle. The total perioperative cost per drop was calculated for each medication using a mean cash price. Force requirements were measured using a customized force gauge apparatus. Formulations were compared using Kruskal-Wallis 1way analysis of variances.

Results:

All formulations were able to cover postoperative periods commensurate with commonly used dosing regimens for cataract surgery. All medications had greater than sticker volume. Loteprednol 0.5% suspension and branded fluorometholone had the highest and lowest number of drops among the medications tested, respectively. Loteprednol 0.38% gel was the most expensive medication, whereas generic prednisolone 1.0% was the least expensive. Gel and branded formulations of ophthalmic steroids required less expulsion force compared with other tested formulations.

Conclusions:

Volume fill levels, patient-incurred costs, and expulsion force requirements per bottle of topical steroid medications vary widely. Clinicians may wish to consider these findings when determining their perioperative prescribing regimen.
Physician burnout in ophthalmology: U.S. survey
Authors: Sedhom Jessica A. , Patnaik Jennifer L. , McCourt Emily A. , Liao Sophie , Subramanian Prem S. , Davidson Richard S. , Palestine Alan G. , Kahook Malik Y. , Seibold Leonard K.
Published: October 2021

Purpose:

To determine the prevalence of physician burnout among ophthalmologists in the United States and identify associated risks.

Setting:

All practice types within the United States.

Design:

Cross-sectional study.

Methods:

A survey was distributed through email listservs to several national ophthalmology societies. Participants completed a modified Mini Z Burnout Survey, a 10-item questionnaire measured in 5-point Likert scales, followed by demographic questions. The Mini Z Burnout survey assessed 3 main outcomes: stress, burnout, and work satisfaction. The percentage of subgroups experiencing burnout were presented and comparisons made with odds ratios from logistic regression modeling.

Results:

Of the 592 ophthalmologists responding to the survey, 37.8% (224) self-reported symptoms of burnout with a low of 30.8% (12/39) for vitreoretinal specialists to a high of 45.4% (30/66) for uveitis specialists. Most of those reporting burnout were categorized as mild (65.2% [146/224]), followed by moderate (29.5% [66/224]) and severe (5.4% [12/224]). Women had almost twice the odds of reporting burnout (odds ratio [OR] = 1.9 [95% CI: 1.3-2.7]; P = .0005). Physicians employed in academic (OR = 2.0 [95% CI: 1.2-3.2]; P = 0.007) and hospital facilities (OR = 2.4 [95% CI: 1.3-4.6]; P = .008) reported higher rates of burnout compared with those in large private groups. Burnout was associated with self-reported low work control, insufficient time for documentation, and misalignment with departmental leaders (P < .0001).

Conclusions:

Ophthalmologists exhibited a high degree of self-reported burnout in the U.S. This study highlights sex, employment autonomy, and practice type as major factors associated with burnout.
Identification of hub genes and candidate drugs in hepatocellular carcinoma by integrated bioinformatics analysis
Authors: Chen Xiaolong , Xia Zhixiong , Wan Yafeng , Huang Ping
Published: October 2021

Background:

Hepatocellular carcinoma (HCC) is the third cancer-related cause of death in the world. Until now, the involved mechanisms during the development of HCC are largely unknown. This study aims to explore the driven genes and potential drugs in HCC.

Methods:

Three mRNA expression datasets were used to analyze the differentially expressed genes (DEGs) in HCC. The bioinformatics approaches include identification of DEGs and hub genes, Gene Ontology terms analysis and Kyoto encyclopedia of genes and genomes enrichment analysis, construction of protein–protein interaction network. The expression levels of hub genes were validated based on The Cancer Genome Atlas, Gene Expression Profiling Interactive Analysis, and the Human Protein Atlas. Moreover, overall survival and disease-free survival analysis of HCC patients were further conducted by Kaplan–Meier plotter and Gene Expression Profiling Interactive Analysis. DGIdb database was performed to search the candidate drugs for HCC.

Results:

A total of 197 DEGs were identified. The protein–protein interaction network was constructed using Search Tool for the Retrieval of Interacting Genes software, 10 genes were selected by Cytoscape plugin cytoHubba and served as hub genes. These 10 genes were all closely related to the survival of HCC patients. DGIdb database predicted 29 small molecules as the possible drugs for treating HCC.

Conclusion:

Our study provides some new insights into HCC pathogenesis and treatments. The candidate drugs may improve the efficiency of HCC therapy in the future.
Comprehensive analysis of prognostic immune-related genes in the tumor microenvironment of hepatocellular carcinoma (HCC)
Authors: Li Mengting , Li Hongliang , Zhou Canxin , Li Xianpeng , Gong Jiande , Chen Changxi , Zhang Yi
Published: October 2021

Growing evidence supports that the tumor microenvironment plays a key role in the development and progression of tumors. But immune microenvironment of hepatocellular carcinoma (HCC) has not yet been fully explored. In the present investigation, the clinical value and prognostic significance of immune-related genes in HCC were investigated.

The immune and stromal scores of HCC were calculated through the application of Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data Algorithm based on the Cancer Genome Atlas database. Differentially expressed genes were identified using the “edgeR” package of the R software. Functional annotation and pathway enrichment were performed using “ggplots2” and “clusterProfiler” packages in R software. Protein-protein interaction network was constructed using STRING, and the hub genes were identified through the Cytoscape. Survival analysis was performed using Kaplan-Meier methods. Tumor Immune Estimation Resource algorithm was used to view the immune landscape of the microenvironment in HCC.

Firstly, the immune and stromal scores of HCC were calculated and we found that the immune and stromal scores of HCC were closely related to the patients’ prognosis. Then the differentially expressed genes were identified respectively stratified by the median value of the immune and stromal scores, and the immune-related genes that related to the prognosis in HCC patients were further identified. Functional enrichment analysis and protein-protein interaction networks further showed that these genes mainly participated in immune-related biological process. In addition, dendritic cells were found to be the most abundant in the microenvironment of HCC through Tumor Immune Estimation Resource algorithm and were significantly associated with the patients’ prognosis. To robust the results, the immune-related genes were validated in an independent dataset from the Gene Expression Omnibus database.

We arrived at a more comprehensive understanding of the microenvironment of HCC and extracted 7 immune-related genes that were significantly associated with the recurrence survival of HCC.
Vitreoretinal lymphoma occurring after systemic chemotherapy for primary conjunctival diffuse large B cell lymphoma
Authors: Niidome Erina , Usui Yoshihiko , Takahashi Reisuke , Nagao Toshitaka , Goto Hiroshi
Published: October 2021

Introduction:

Ocular adnexal lymphoma and vitreoretinal lymphoma are rare forms of non-Hodgkin lymphoma. They are regarded as distinct disease entities due to the differences in molecular mechanism, management, and outcome. We present a rare case of conjunctival diffuse large B cell lymphoma (DLBCL) that developed to vitreoretinal lymphoma after systemic chemotherapy.

Patient concerns:

A 60-year-old man presented with a left salmon-colored conjunctival mass.

Diagnosis:

A biopsy was performed, and histopathologic examination showed DLBCL. Immunohistochemical staining was positive for CD20 with increased κ to λ light chain ratio.

Interventions:

Bone marrow biopsy also revealed DLBCL. Gallium-67 scintigraphy showed abnormal uptake only in the left orbital lesion. Ann Arbor stage was estimated as IV. The patient underwent systemic combination chemotherapy and immunotherapy.

Outcomes:

Four months after the last course of chemotherapy, primary conjunctival DLBCL relapsed, manifesting vitreous opacity. Diagnostic vitrectomy confirmed a diagnosis of vitreoretinal lymphoma.

Lessons:

Conjunctival DLBCL and vitreoretinal lymphoma are both DLBCL. After systemic chemotherapy for conjunctival DLBCL, the lymphoma may relapse in intraocular sites as secondary vitreoretinal lymphoma.
Comparison of the sixth, seventh, and eighth editions of the American Joint Committee on Cancer Tumor-Node-Metastasis staging system for gastric cancer
Authors: Chen Mei-Wen , Yen Hsu-Heng
Published: October 2021

In 2018, the eighth edition of the American Joint Committee on Cancer Tumor-Node-Metastasis classification and staging system was implemented. Few reports were made comparing the performance of different editions of the American Joint Committee on Cancer (AJCC) system. Therefore, this study aimed to examine the prognostic predictability from the sixth to the eighth editions of the AJCC staging system for gastric cancer.

A total of 414 patients with gastric cancer who underwent surgery at Changhua Christian Hospital from January 2007 to December 2017 were enrolled in the study. To identify the prognostic factors for gastric cancer death, univariate and multivariate analyses were performed. The homogeneity and discrimination abilities of the sixth to eighth editions of the staging system were compared using the likelihood ratio chi-square test, linear trend chi-square test, and Akaike information criterion.

The sixth edition of the staging system had the lowest Akaike information criterion value, suggesting a better prognostic stratification than other editions. From the result of the likelihood ratio chi-square test, the T and N staging systems of the seventh and eighth editions had better homogeneity and discriminatory ability than the sixth edition. The eighth edition had better prognostic performance in patients at stage III compared with the seventh edition.

The AJCC seventh and eighth editions had improved prognostic predictability of the T and N factors compared with the sixth edition. However, the overall staging performance of the eighth edition is not superior compared to the sixth edition. Further studies with larger sample size should be conducted to compare the performance of different editions of the AJCC staging system for different ethnic populations.
Baseline neutrophil-lymphocyte ratio is associated with outcomes in patients with castration-resistant prostate cancer treated with Docetaxel in South China
Authors: Jiang Zhi-guo , Liao Shao-Guang
Published: October 2021

The aim of this study is to investigate the association between baseline neutrophil-to-lymphocyte ratio (NLR) and progression-free survival (PFS), overall survival (OS) and radiological response in castration-resistant prostate cancer patients treated with docetaxel.

Forty-one prostate cancer patients who were treated with docetaxel were selected. Univariable and multivariable Cox regression models were used to predict the association of baseline NLR as a dichotomous variable with PFS and OS after chemotherapy initiation.

In Kaplan–Meier analysis, the median PFS (9.8 vs 7.5 months, P = .039, Fig. 1) and OS (17.6 vs 14.2 months, P = .021, Fig. 2) was higher in patients who did not have an elevated NLR than in those with an elevated NLR. In univariate analysis, the pretreatment NLR was significantly associated with PFS (P = .049) and OS (P = .023). In multivariable analysis, patients with a NLR of >3 were at significantly higher risk of tumor progress (hazard ratio 2.458; 95% confidence interval 1.186–5.093; P = .016) and death (hazard ratio 3.435; 95% CI 1.522–7.750; P = .003)than patients with a NLR of ⩽3.

NLR may be an independent predictor of PFS and OS in castration-resistant prostate cancer patients treated with docetaxel. The findings require validation in further prospective, big sample-sized studies.
Gliflozins for the prevention of stroke in diabetes and cardiorenal diseases
Authors: Zhao Li-Min , Huang Jia-Nan , Qiu Mei , Ding Liang-Liang , Zhan Ze-Lin , Ning Jie
Published: October 2021

Background:

Individual randomized trials are not powered to assess the relationship between use of sodium–glucose transporter 2 inhibitors and risk of stroke. We sought to explore this issue by a meta-analysis incorporating relevant trials including several latest trials.

Methods:

Cardiovascular outcome trials of gliflozins were included. Primary outcome was stroke, while secondary outcome was major adverse cardiovascular events (MACE), which was a composite of stroke, myocardial infarction, or cardiovascular death. Meta-analysis was conducted stratified by with/without chronic kidney disease (CKD), with/without heart failure (HF), and with/without atherosclerotic cardiovascular disease (ASCVD), and stratified by different gliflozins.

Results:

We included 9 trials in this meta-analysis. Compared with placebo, gliflozins significantly lowered stroke (hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.55–0.84) and MACE (HR 0.77, 95% CI 0.69–0.86) in type 2 diabetes (T2D) patients with CKD, but did not significantly affect stroke (HR 1.00, 95% CI 0.86–1.16) and MACE (HR 0.94, 95% CI 0.86–1.02) in T2D patients without CKD. Gliflozins had no significant effects on the stroke risk (HR 0.94, 95% CI 0.82–1.07) in T2D patients regardless of HF status (P
subgroup = .684) and ASCVD status (P
subgroup = .915), but significantly lowered MACE (HR 0.89, 95% CI 0.83–0.96) in T2D patients regardless of HF status (P
subgroup = .428) and ASCVD status (P
subgroup = .423). Canagliflozin (HR 0.84, 95% CI 0.69–1.01) showed the trend of a reduction in the stroke risk versus placebo, and sotagliflozin (HR 0.73, 95% CI 0.54–0.98) significantly lowered the stroke risk; whereas the other 3 gliflozins did not significantly affect that risk. Ertugliflozin (HR 0.97, 95% CI 0.85–1.11) had no significant effects on the MACE risk, whereas the other 4 gliflozins significantly lowered that risk.

Conclusions:

Gliflozins, especially canagliflozin and sotagliflozin, should be recommended in T2D patients with CKD to prevent stroke. Most gliflozins lower the risk of MACE in T2D patients regardless of HF status and ASCVD status, whereas ertugliflozin is not observed to lower that risk.
Workplace bullying among Nigerian artisans in building and construction industry
Authors: Omeje Hyginus Osita , Okereke Godwin Keres Okoro , Okeke Somtochukwu A.C. , Asogwa Japel Onyekachi , Obe Pauline Ijeoma , Nwaodo Samson Ikenna , Chukwu Uchenna Daniel , Ike Joshua Onyedikachi , Udogu Kingsley Chimezia , Ede Augustina Obioma , Ilechukwu Leonard C. , Kanu Catherine Chiugo , Ogbonna George Nwachukwu , Njoku Sylvanus Umunakwe
Published: October 2021

Bullying is a growing problem in the workplace. This study investigated the bullying experience of building and construction industry artisans.

We employed a cross-sectional analytic design to study 240 artisans in respect of workplace bullying (WPB) experience using a self-report questionnaire. Percentage, mean and standard deviation were used for data analysis and interpretation.

According to the study, a significant percentage (96.1%) of the artisans perceived themselves as victims of WPB within the past 6 months and these experiences also occurred once or more times weekly.

WPB is a considerable problem among building and construction industry artisans in Nigeria. Further studies that can influence the construction industry to create valuable programs to minimize bullying among artisans are required.
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

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

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.
Is amplification bias consequential in transposon sequencing (TnSeq) assays? A case study with a Staphylococcus aureus TnSeq library subjected to PCR-based and amplification-free enrichment methods
Authors: Alkam Duah , Wongsurawat Thidathip , Nookaew Intawat , Richardson Anthony R. , Ussery David , Smeltzer Mark S. , Jenjaroenpun Piroon
Published: October 2021

As transposon sequencing (TnSeq) assays have become prolific in the microbiology field, it is of interest to scrutinize their potential drawbacks. TnSeq data consist of millions of nucleotide sequence reads that are generated by PCR amplification of transposon-genomic junctions. Reads mapping to the junctions are enumerated thus providing information on the number of transposon insertion mutations in each individual gene. Here we explore the possibility that PCR amplification of transposon insertions in a TnSeq library skews the results by introducing bias into the detection and/or enumeration of insertions. We compared the detection and frequency of mapped insertions when altering the number of PCR cycles, and when including a nested PCR, in the enrichment step. Additionally, we present nCATRAs - a novel, amplification-free TnSeq method where the insertions are enriched via CRISPR/Cas9-targeted transposon cleavage and subsequent Oxford Nanopore MinION sequencing. nCATRAs achieved 54 and 23% enrichment of the transposons and transposon-genomic junctions, respectively, over background genomic DNA. These PCR-based and PCR-free experiments demonstrate that, overall, PCR amplification does not significantly bias the results of TnSeq insofar as insertions in the majority of genes represented in our library were similarly detected regardless of PCR cycle number and whether or not PCR amplification was employed. However, the detection of a small subset of genes which had been previously described as essential is sensitive to the number of PCR cycles. We conclude that PCR-based enrichment of transposon insertions in a TnSeq assay is reliable, but researchers interested in profiling putative essential genes should carefully weigh the number of amplification cycles employed in their library preparation protocols. In addition, nCATRAs is comparable to traditional PCR-based methods (Kendall’s correlation=0.896–0.897) although the latter remain superior owing to their accessibility and high sequencing depth.
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

Background

Maintenance 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.

Methods

Using 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.

Results

Up 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.

Conclusions

Maintenance 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

Methodologies 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 summary

Functional 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

RNA-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.