bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circular BANP knockdown inhibits the malignant progression of residual hepatocellular carcinoma after insufficient radiofrequency ablation
Authors: Li Guoming , Kong Jian , Dong Shuying , Niu Haigang , Wu Shilun , Sun Wenbing 
Published: January 2022

Abstract

Background:
Circular RNAs (circRNAs) are endogenous non-coding RNAs, some of which have pathological roles. The current study aimed to explore the role of circRNA BTG3-associated nuclear protein (circ-BANP) binding with let-7f-5p and its regulation of the toll-like receptor 4 (TLR4)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in residual hepatocellular carcinoma (HCC) after insufficient radiofrequency ablation (RFA).

Methods:
Circ-BANP, let-7f-5p, and TLR4 expressions in HCC samples were assessed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting. Bioinformatics prediction, RNA pull-down assay, and dual luciferase reporter gene assay were used to analyze the relationships among circ-BANP, let-7f-5p, and TLR4. Huh7 cells were used to generate an in vitro model of residual HCC, defined as Huh7-H cells, which were transfected with either a plasmid or the sequence of circ-BANP, let-7f-5p, or TLR4. Expression of circ-BANP, let-7f-5p, and TLR4 mRNA was determined by RT-qPCR. TLR4, STAT3, p-STAT3, vascular endothelial growth factor A, vascular endothelial growth factor receptor-2, and epithelial-mesenchymal transformation (EMT)-related factors proteins were determined by Western blotting. Cell proliferation was determined by cell counting kit-8 and 5-Ethynyl-2’-deoxyuridine (EdU) assay and cell migration and invasion by Transwell assay. Animal studies were performed by inducing xenograft tumors in nude mice.

Results:
Circ-BANP and TLR4 mRNAs were upregulated in HCC tissues (the fold change for circ-BANP was 1.958 and that for TLR4 was 1.736 relative to para-tumors) and expression further increased following insufficient RFA (fold change for circ- BANP was 2.407 and that of TLR4 was 2.224 relative to para-tumors). Expression of let-7f-5p showed an opposite tendency (fold change for let-7f-5p in HCC tissues was 0.491 and that in tumors after insufficient RFA was 0.300 relative to para-tumors). Competitive binding of circ-BANP to let-7f-5p was demonstrated and TLR4 was identified as a target of let-7f-5p (P < 0.01). Knockdown of circ-BANP or elevation of let-7f-5p expression inhibited the TLR4/STAT3 signaling pathway, proliferation, invasion, migration, angiogenesis, and EMT in Huh7 and Huh7-H cells (P < 0.01). The effects induced by circ-BANP knockdown were reversed by let-7f-5p inhibition. Overexpression of TLR4 reversed the impact of let-7f-5p upregulation on the cells (P < 0.01). Silencing of circ-BANP inhibited the in vivo growth of residual HCC cells after insufficient RFA (P < 0.01).

Conclusions:
Knockdown of circ-BANP upregulated let-7f-5p to inhibit proliferation, migration, and EMT formation in residual HCC remaining after insufficient RFA. Effects occur via regulation of the TLR4/STAT3 signaling pathway.
Population Pharmacokinetic Properties of Omecamtiv Mecarbil in Healthy Subjects and Patients With Heart Failure With Reduced Ejection Fraction
Authors: Chen Po-Wei , Trivedi Ashit , Lee Edward , Dutta Sandeep , Ahamadi Malidi 
Published: January 2022

Abstract:
Omecamtiv mecarbil is a small molecule that has been shown to improve cardiac function in patients with heart failure (HF) with reduced ejection fraction and is currently being developed as an oral modified release tablet for subjects with chronic HF. The objectives of this study were to analyze the pharmacokinetic (PK) properties of omecamtiv mecarbil and to investigate the effects of potential covariates on pertinent PK parameters using population PK modeling of data from 3 clinical trials in healthy subjects (n = 85) and 3 clinical trials in patients with HF (n = 4261). The population PK analysis was performed using a nonlinear mixed effects modeling approach. Omecamtiv mecarbil has a clearance of 11.7 L/h (0.701% relative standard error) and a central volume distribution of 275 L (2.12% relative standard error). The estimated half-life of omecamtiv mecarbil was 33 hours. Body weight and estimated glomerular filtration rate were significant covariates, but their effect on exposure was modest and lacked clinical relevance. Additional covariates, including sex, race, bilirubin, albumin, concomitant medications, New York Heart Association Functional Classification, N-terminal-pro hormone B-type natriuretic peptide, troponin I, creatine kinase MB, serum hemoglobin, tablet formulation, aspartate aminotransferase, and serum urea, were tested and found to have no impact on omecamtiv mecarbil exposures. The results of this integrated evaluation of the impact of covariates on the systemic exposure of omecamtiv mecarbil suggest that dose adjustment is not required for the studied subpopulations of patients with HF.
Assisted Living and Medication Adherence in Super-aged Patients With Heart Failure in the Japanese Population
Authors: Kawada Kei , Kubo Toru , Ishida Tomoaki , Jobu Kohei , Morisawa Shumpei , Hamada Tomoyuki , Baba Yuiti , Kawai Kazuya , Nakaoka Yoko , Yabe Toshikazu , Furuno Takashi , Yamada Eisuke , Fukuda Hitoshi , Ohta Tsuyoshi , Hayashi Toshinobu , Kitaoka Hiroaki , Miyamura Mitsuhiko 
Published: January 2022

Abstract:
Poor adherence to medication in patients with heart failure (HF) is associated with poor clinical outcomes. Although social support has been reported to improve medication adherence in patients with HF, the detailed underlying mechanism of this association is unclear. This study investigated appropriate social support types to ensure medication adherence, as well as patient characteristics that benefit from such social support in patients with HF. This was a retrospective observational study investigating the association of social support with medication adherence in 824 patients with HF who were registered in a prospective multicenter database. First, we analyzed the association between social support types and poor medication adherence leading to hospitalization. An interaction analysis was performed to detect patients' characteristics that benefited most from social support in terms of medical adherence. Fifty patients (6.1%) were hospitalized for poor adherence to medications. Multivariable analysis revealed that not receiving assisted living, which was defined as having supporting individuals at least once a week, was independently associated with poor medication adherence–related hospitalization. An interaction analysis revealed that patients with dementia benefited from assisted living significantly, whereas male patients or current smokers did not. Summarily, assisted living at least once a week was appropriate for improving medication adherence in patients with HF and was particularly effective in patients with dementia. Performed in a super-aging region in Japan, this study may also suggest the relevance of social support in preventing HF exacerbation in other developed countries that will experience an aging society in the near future.
EXUDATIVE RETINAL DETACHMENT AFTER INTRAVITREAL BROLUCIZUMAB INJECTION
Authors: Betsch Devin M. , Sarraf David , Francisconi Carolina L. M. 
Published: January 2022

Purpose:
To report an unusual case of a patient who presented with intraocular inflammation (IOI) and an exudative retinal detachment after first brolucizumab injection and to compare this case to the existing literature.

Methods:
An 80-year-old woman being treated for neovascular age-related macular degeneration presented 11 days after her first intravitreal injection of brolucizumab with IOI and an exudative retinal detachment. She was treated with systemic and topical steroids. The patient's chart was thoroughly reviewed, and notes were made on visual acuities and ocular examination findings at each relevant visit. Optical coherence tomography and ultra-widefield fluorescein angiography (UWFA) images were taken across multiple timepoints.

Results:
The patient's IOI and exudative retinal detachment resolved three weeks after brolucizumab injection. In the literature, the incidence of IOI has been reported to be higher with brolucizumab versus aflibercept, but most of these cases were considered to be mild to moderate in severity. More recently, reports of severe IOI and retinal vasculitis associated with brolucizumab have been published in postmarketing surveillance articles.

Conclusion:
To the authors' knowledge, this is the first report of exudative retinal detachment after intravitreal brolucizumab injection. As the experience with this new drug continues to grow, reports of these events are critical to increase the understanding, so that future management strategies can be developed to improve patient outcomes.
Licorice consumption causing severe hypokalemia-induced paresis
Authors: Bettini Luca , Parent Thibault , Serratrice Jacques 
Published: January 2022

Abstract

Rationale:
Licorice ingestion presenting with hypokalemia has been widely reported, yet life-threatening hypokalemia associated with both, paresis and electrocardiogram abnormalities secondary to licorice infusion tea, is rare.

Patient concerns:
We describe the case of an 84-year-old woman who presented with left-hand paresis, fatigue, and hypertension.

Diagnoses:
Anamnesis, low plasma renin, and aldosterone levels confirmed pseudo-hyperaldosteronism secondary to licorice consumption.

Interventions:
The patient was first treated with continuous intravenous potassium and magnesium and finally with spironolactone.

Outcomes:
After electrolyte correction (potassium, magnesium), electrocardiogram findings became normal, and paresis disappeared.

Lessons:
By presenting this case, we remind clinicians that intoxication should be considered in any patient with unexplained hypokalemia. Medical history taking, and rapid potassium correction are essential for good prognosis.
Understanding the Tradeoffs Between Travel Burden and Quality of Care for In-center Hemodialysis Patients
Authors: Salerno Stephen , Gremel Garrett , Dahlerus Claudia , Han Peisong , Affholter Jordan , Tong Lan , Wisniewski Karen , Roach Jesse , Li Yi , Hirth Richard A. 
Published: January 2022

Background:
Renal dialysis is a lifesaving but demanding therapy, requiring 3 weekly treatments of multiple-hour durations. Though travel times and quality of care vary across facilities, the extent to which patients are willing and able to engage in weighing tradeoffs is not known. Since 2015, Medicare has summarized and reported quality data for dialysis facilities using a star rating system. We estimate choice models to assess the relative roles of travel distance and quality of care in explaining patient choice of facility.

Research Design:
Using national data on 2 million patient-years from 7198 dialysis facilities and 4-star rating releases, we estimated travel distance to patients’ closest facilities, incremental travel distance to the next closest facility with a higher star rating, and the difference in ratings between these 2 facilities. We fit mixed effects logistic regression models predicting whether patients dialyzed at their closest facilities.

Results:
Median travel distance was 4 times that in rural (10.9 miles) versus urban areas (2.6 miles). Higher differences in rating [odds ratios (OR): 0.56; 95% confidence interval (CI): 0.50–0.62] and greater area deprivation (OR: 0.50; 95% CI: 0.48–0.53) were associated with lower odds of attending one’s closest facility. Stratified models were also fit based on urbanicity. For rural patients, excess travel was associated with higher odds of attending the closer facility (per 10 miles; OR: 1.05; 95% CI: 1.04–1.06). Star rating differences were associated with lower odds of receiving care from the closest facility among urban (OR: 0.57; 95% CI: 0.51–0.63) and rural patients (OR: 0.18; 95% CI: 0.08–0.44).

Conclusions:
Most dialysis patients have higher rated facilities located not much further than their closest facility, suggesting many patients could evaluate tradeoffs between distance and quality of care in where they receive dialysis. Our results show that such tradeoffs likely occur. Therefore, quality ratings such as the Dialysis Facility Compare (DFC) Star Rating may provide actionable information to patients and caregivers. However, we were not able to assess whether these associations reflect a causal effect of the Star Ratings on patient choice, as the Star Ratings served only as a marker of quality of care.
Minimally Invasive “Trocar-Free” Approach for Rear Mandibular Fractures Management
Authors: Abbate Vincenzo , Orabona Giovanni Dell’Aversana , Seidita Francesco , Bonavolontà Paola , Iaconetta Giorgio , Califano Luigi 
Published: January 2022

Abstract:
The request of minimally invasive surgery is progressively expanding the indications of endoscopically assisted intraoral access for mandibular traumas. The aim of our study is to assess how much the use of the angled drill may affect the outcome of patients treated for rear mandibular fracture. In our retrospective case-control trial we enrolled 36 patients with mandibular rear fractures treated through endoscopically assisted intraoral access. Eighteen patients were treated by using an angled drill ‘‘trocar free,’’ and 18 treated by linear drills placed through trocars. Surgical times, hospitalization times (HT), and major complications rate were compared between the 2 groups. Group 1 showed a significant reduction in HT (1.72 versus 2.22 days, P = 0.024) and an increase in the surgical times (3.0 versus 2.53 hours, P = 0.019). Significant reduction of total amount of complication was seen in group 1 versus group 2 (P = 0.007). The ‘‘trocar free’’ approach allowed by angled drills, in our hands, greatly reduces the invasiveness of the surgery resulting in a significant reduction in HT and smaller share of vascular-nervous sequelae. Our results suggest the ‘‘trocar free’’ approach as a valuable choice when indicated for the treatment of rear mandibular fractures.
Liver Transplantation for Hepatic Adenoma: A UNOS Database Analysis and Systematic Review of the Literature
Authors: Ziogas Ioannis A. , Tasoudis Panagiotis T. , Serifis Nikolaos , Alexopoulos Sophoclis P. , Montenovo Martin I. , Shingina Alexandra 
Published: January 2022

Background.
Liver transplantation (LT) has been employed for hepatic adenoma (HA) on a case-oriented basis. We aimed to describe the characteristics, waitlist, and post-LT outcomes of patients requiring LT for HA.

Methods.
All patients listed or transplanted for HA in the United States were identified in the United Network for Organ Sharing (UNOS) database (1987–2020). A systematic literature review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement.

Results.
A total of 199 HA patients were listed for LT in UNOS and the crude waitlist mortality was 9.0%. A total of 142 HA patients underwent LT; 118 of these were among those listed with an indication of HA who underwent LT, and 24 were diagnosed incidentally. Most did not experience hepatocellular carcinoma transformation (89.4%). Over a median follow-up of 62.9 mo, death was reported in 18.3%. The 1-, 3-, and 5-y patient survival rates were 94.2%, 89.7%, and 86.3% in the UNOS cohort. The systematic review yielded 61 articles reporting on 99 nonoverlapping patients undergoing LT for HA and 2 articles reporting on multicenter studies. The most common LT indications were suspected malignancy (39.7%), unresectable HA (31.7%), and increasing size (27.0%), whereas 53.1% had glycogen storage disease. Over a median follow-up of 36.5 mo, death was reported in 6.0% (n=5/84). The 1-, 3-, and 5-y patient survival rates were all 95.0% in the systematic review.

Conclusions.
LT for HA can lead to excellent long-term outcomes in well-selected patients. Prospective granular data are needed to develop more optimal selection criteria and further improve outcomes.
Severity of COVID-19 reinfection and associated risk factors: findings of a cross-sectional study in Bangladesh
Authors: Islam Md. Ziaul , Riaz Baizid Khoorshid , Akbar Ashrafi Shah Ali , Farjana Sharmin , Efa Syeda Sumaiya , Khan Mohammad Adnan 
Published: January 2022

AbstractBackgroundCOVID-19 reinfected patients suffer from diverse health consequences. Information on the severity of COVID-19 reinfection is scarce. The current study aimed to determine the proportion of COVID-19 reinfection and risk factors associated with its severity.MethodsThis cross-sectional study targeted all COVID-19 patients reported in May 2021 at the Health Information Unit (HIU) of the Directorate General of Health Services (DGHS) of Bangladesh. We identified 473 (1.14%) reinfected patients out of 41408 diagnosed cases by reviewing their medical records. Considering the selection criteria and informed consent, we enrolled 404 reinfected patients. Data were collected through telephone interviews and reviewing medical records using a semi-structured questionnaire and a checklist.ResultsThe majority of the reinfected patients were urban residents (98.0%). Around 13.0% of reinfected patients had <90% oxygen saturation, and 64.0% had an interval of 3-6 months between two attacks. The severity of reinfection included asymptomatic (12.9%), mild (8.9%), moderate (66.3%), and severe (11.9%) forms of infection. An interval of 3-6 months between two attacks had less chance of having mild (AOR=0.031, ρ=0.000), moderate (AOR=0.132, ρ=0.017), and severe (AOR=0.059, ρ=0.002) infections. Patients who maintained physical distance had less chance of moderate-intensity reinfection (AOR=0.137, ρ=0.013), while the vaccinated patients had a higher chance of moderate (AOR=16.127, ρ=0.001) and severe (AOR=3.894, ρ=0.047) intensity reinfection.ConclusionTo avert COVID-19 reinfection and its severity, patients should be vigilant about preventive practices even after recovery. The study suggests vibrant interventions aligned with exposure, physical distancing, vaccination, and comorbidities for mitigating reinfection.
A phase I study of oral vitamin D3 in boys with X-linked adrenoleukodystrophy
Authors: Van Haren Keith , Cunanan Kristen , Awani Avni , Gu Meng , Peña Dalia , Chromik Lindsay C. , Považan Michal , Rossi Nicole C. , Winterbottom Jennifer , Goodman Jordan , Sundaram Vandana , Raymond Gerald V , Cowan Tina , Enns Gregory M. , Waubant Emmanuelle , Steinman Lawrence , Barker Peter B. , Spielman Daniel , Fatemi Ali 
Published: January 2022

ABSTRACTObjectiveVitamin D status has been linked to risk of inflammatory brain lesions. We sought to assess the safety and pharmacokinetics of oral vitamin D dosing regimens in boys with X-linked adrenoleukodystrophy (ALD).MethodsIn this open-label, multi-center, phase I study, we enrolled 21 ALD males without brain lesions, aged 1.5 to 25 years to oral vitamin D supplementation for 12 months. Our primary outcome was attainment of plasma 25-hydroxyvitamin D levels in target range (40-80ng/ml) at 6 and 12 months. Secondary outcomes included safety and glutathione levels in brain and blood. Participants were initially assigned to a fixed dosing regimen starting at 2,000 IU daily, regardless of weight. Following a mid-study safety assessment, we modified the dosing regimen so all subsequent participants were assigned to a weight-stratified dosing regimen starting as low as 1,000 IU daily.ResultsBetween October 2016 and June 2019, we recruited 21 participants (n=12 fixed dose; n=9 weight-stratified) with a median age and weight of 6.7 years and 20 kilograms. Most participants achieved target plasma vitamin D levels at 6 and 12 months regardless of dosing regimen. In the fixed dose regimen, 6 of 12 participants had asymptomatic elevation in urine calcium:creatinine or plasma 25-hydroxyvitamin D; no laboratory deviations occurred with the weight-stratified regimen. Glutathione levels increased between baseline and 12 months in the brain but not in the blood.ConclusionsOur weight-stratified vitamin D dosing regimen was well-tolerated and achieved target 25-hydroxyvitamin D levels in most participants. Brain glutathione levels increased over the 12-month trial period.Clinicaltrials.govidentifierNCT02595489Classification of EvidenceThis study provides Class II evidence that a weight-stratified dosing regimen of vitamin D supplementation is safe, well-tolerated, and effective at achieving moderately high vitamin D levels in boys with ALD.Sources of fundingNIH/NINDS K23NS087151
Antibody binding and ACE2 binding inhibition is significantly reduced for the Omicron variant compared to all other variants of concern
Authors: Junker Daniel , Becker Matthias , Wagner Teresa R. , Kaiser Philipp D. , Maier Sandra , Grimm Tanja M. , Griesbaum Johanna , Marsall Patrick , Gruber Jens , Traenkle Bjoern , Heinzel Constanze , Pinilla Yudi T. , Held Jana , Fendel Rolf , Kreidenweiss Andrea , Nelde Annika , Maringer Yacine , Schroeder Sarah , Walz Juliane S. , Althaus Karina , Uzun Gunalp , Mikus Marco , Bakchoul Tamam , Schenke-Layland Katja , Bunk Stefanie , Haeberle Helene , Göpel Siri , Bitzer Michael , Renk Hanna , Remppis Jonathan , Engel Corinna , Franz Axel R. , Harries Manuela , Kessel Barbora , Strengert Monika , Krause Gerard , Zeck Anne , Rothbauer Ulrich , Dulovic Alex , Schneiderhan-Marra Nicole 
Published: January 2022

AbstractThe rapid emergence of the Omicron variant and its large number of mutations has led to its classification as a variant of concern (VOC) by the WHO(1). Initial studies on the neutralizing response towards this variant within convalescent and vaccinated individuals have identified substantial reductions(2-8). However many of these sample sets used in these studies were either small, uniform in nature, or were compared only to wild-type (WT) or, at most, a few other VOC. Here, we assessed IgG binding, (Angiotensin-Converting Enzyme 2) ACE2 binding inhibition, and antibody binding dynamics for the omicron variant compared to all other VOC and variants of interest (VOI)(9), in a large cohort of infected, vaccinated, and infected and then vaccinated individuals. While omicron was capable of binding to ACE2 efficiently, antibodies elicited by infection or immunization showed reduced IgG binding and ACE2 binding inhibition compared to WT and all VOC. Among vaccinated samples, antibody binding responses towards omicron were only improved following administration of a third dose. Overall, our results identify that omicron can still bind ACE2 while pre-existing antibodies can bind omicron. The extent of the mutations appear to inhibit the development of a neutralizing response, and as a result, omicron remains capable of evading immune control.
Retinal fundus photographs capture hemoglobin loss after blood donation
Authors: Mitani Akinori , Traynis Ilana , Singh Preeti , Corrado Greg S. , Webster Dale R. , Peng Lily H. , Varadarajan Avinash V. , Liu Yun , Hammel Naama 
Published: January 2022

AbstractRecently it was shown that blood hemoglobin concentration could be predicted from retinal fundus photographs by deep learning models. However, it is unclear whether the models were quantifying current blood hemoglobin level, or estimating based on subjects’ pretest probability of having anemia. Here, we conducted an observational study with 14 volunteers who donated blood at an on site blood drive held by the local blood center (ie, at which time approximately 10% of their blood was removed). When the deep learning model was applied to retinal fundus photographs taken before and after blood donation, it detected a decrease in blood hemoglobin concentration within each subject at 2-3 days after donation, suggesting that the model was quantifying subacute hemoglobin changes instead of predicting subjects’ risk. Additional randomized or controlled studies can further validate this finding.