bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mouse models to study genes involved in hematological malignancies
Authors: Przybylski Grzegorz K. 
Published: November 2020

Abstract
Hematological malignancies, including leukemia and lymphoma, consist a group of highly heterogeneous neoplasms characterized by numerous genetic lesions specific for the type of the disease. In order to understand, the role of a particular alteration in the development of a malignancy functional studies have to be carried out in vitro, in cell lines derived from primary cancer cells. Further efforts to understand the mechanisms underlying blood disorders including malignant transformation and progression relies on model organism research. Numerous transgenic mouse models, carrying human oncogenes have been generated resembling distinct types of hematological disorders. Recent technological advances revolutionized the generation of animal models making it much easier, faster, and precise. The introduction of the CRISPR-Cas9 technology allows for rapid generation of novel knockout or transgenic animals, and the development of conditional site- and time-specific Cre-Lox gene targeting technology, allows studying the function of genes which are relevant to normal hematopoiesis and development of hematological malignancies, but lethal when knocked out in embryonic cells. Besides the studies on gene function, mouse models of human leukemia allow for discovery and testing of novel antileukemic drugs. These new technologies are deepening our understanding of disease pathophysiology and treatment resistance, as well as are leading to novel therapeutic strategies for improved outcomes in patients.
Two-step protocol for regeneration of immunocompetent T cells from mouse pluripotent stem cells
Authors: Wang Tongjie , Lv Cui , Hu Fangxiao , Liu Lijuan , Wang Jinyong 
Published: November 2020

Abstract
Numerous efforts have been attempted to regenerate T cells in culture dish from pluripotent stem cells (PSCs). However, in vitro generated T cells exhibited extremely low activity and compromised immunocompetency in vivo. Here, we describe a two-step protocol for regenerating functional T cells using an inducible Runx1-Hoxa9-PSC (iR9-PSCs) line. The procedure mainly includes generation of induced hematopoietic progenitor cells (iHPCs) in vitro, transplantation, and development of functional induced T cells (iT) in vivo via transplantation. The entire induction process in vitro requires 21 days before iHPCs transplantation. The development of mature T cells in vivo takes 4 to 6 weeks post-transplantation. We provide a simple and reproducible approach for functional T cell regeneration from iR9-PSCs for research purpose.
Country-based Comparison of Atrial Fibrillation Patients' Preferences for Oral Anticoagulation: An Evaluation of Discrete Choice Experiments in Five Different Countries
Authors: Henry Maren , Wosnitza Melanie , Thate-Waschke Inga-Marion , Bauersachs Rupert , Ueng Kwo-Chang , Chang Kuan-Cheng , Wilke Thomas 
Published: November 2020

Abstract:
The aim of this study was to examine atrial fibrillation (AF) patients' preferences regarding oral anticoagulation (OAC) characteristics and to investigate differences across 5 different countries. A multicenter discrete choice experiment was conducted in Germany, Sweden, Switzerland, Spain, and Taiwan. Study sites enrolled patients with nonvalvular AF who received continuous OAC therapy. The discrete choice experiment design considered the following 4 attributes with 2 attribute levels each: need for bridging (yes/no), interactions with food/alcohol (yes/no), need for regular international normalized ratio (INR) assessments, and frequency of intake (once/twice daily). Generally, patients (n = 1391) preferred treatment alternatives that were characterized by “no need of bridging,” “no need for regular INR controls,” “no interactions with food/alcohol,” and “once daily intake.” For this desired treatment regimen, patients were willing to accept a substantially higher travel distance/time. German patients with AF were strongly impacted in their hypothetical treatment decision by the frequency of intake (37.5%). Swedish patients on the other hand gave little importance to intake frequency (12.6%). In Switzerland, patients were especially concerned with food/alcohol interactions of the medication (34.7%), whereas this was the least important attribute for Taiwanese patients (18.9%), who ascribed the most homogenous importance to the different treatment attributes overall. In Spain, the need for regular INR assessments especially impacted the patient's treatment decision (31.9%). Patients of all countries attributed a moderate importance to the need for bridging (25.9%–34.2%). These findings may facilitate country-specific consideration of patients' preferences regarding OAC therapy, potentially increasing treatment acceptance on the patient's side with the ultimate goal of improving treatment adherence and persistence.
Quantitation of Tacrolimus in Human Whole Blood Samples Using the MITRA Microsampling Device
Authors: Undre Nasrullah , Hussain Imran , Meijer John , Stanta Johannes , Swan Gordon , Dawson Ian 
Published: November 2020

Background:
The calcineurin inhibitor tacrolimus is a narrow therapeutic index medication, which requires therapeutic drug monitoring to optimize dose on the basis of systemic exposure. MITRA microsampling offers a minimally invasive approach for the collection of capillary blood samples from a fingerprick as an alternative to conventional venous blood sampling for quantitation of tacrolimus concentrations.

Methods:
A bioanalytical method for the quantitation of tacrolimus in human whole blood samples collected on MITRA tips was developed, using liquid–liquid extraction followed by liquid chromatography with tandem mass spectrometry detection. Validation experiments were performed according to the current Food and Drug Administration and European Medicines Agency guidelines on validation of bioanalytical methods. Validation criteria included assay specificity and sensitivity, interference, carryover, accuracy, precision, dilution integrity, matrix effect, extraction recovery, effect of hematocrit and hyperlipidemia, and stability.

Results:
All assay validation results were within the required acceptance criteria, indicating a precise and accurate tacrolimus quantitation method. The validated assay range was 1.00–50.0 ng/mL. No interference, carryover or matrix effect was observed. Extraction recovery was acceptable across the assay range. Samples were stable for up to 96 days at −20°C and 20°C, and 28 days at 40°C. Hematocrit, hyperlipidemia, and lot-to-lot differences in the nominal absorption volume of the 10-μL MITRA tips were shown not to influence tacrolimus quantitation by this assay method.

Conclusions:
The bioanalytical method validated in this study is appropriate and practical for the quantitation of tacrolimus in human whole blood samples collected using the MITRA microsampling device.
Antirotational plating combined with bone grafting for nonisthmal femoral shaft nonunion after intramedullary nailing: a retrospective study
Authors: Ma Xianzhi , Liu Ying , Zhou Qiyun , Ma Jianwu , Wang Kai 
Published: November 2020

Objective:Exchange nailing for aseptic femoral shaft nonunion is currently a standard orthopedic treatment modality. However, according to recent studies there is occasionally a high failure rate when exchange nailing is used. In the present study, augmentative locked plating and bone graft was used as an alternative method for treating such cases. The purpose of this study was to report the treatment outcomes of antirotational plating (ARP) combined with bone grafting with a retained nail left in situ for nonisthmal femoral shaft nonunion after femoral nailing.Materials and Methods:Fifty-three patients presenting with nonisthmal femoral shaft nonunion after femoral nailing were selected (according to inclusion criteria) for a retrospective study from April 2012 to June 2016. All patients received treatment with ARP entailing a nail left in situ and combined with bone grafting. Main result measures include union time, union rate, and operation time, amount of bleeding during operation. Follow-ups, including radiologic and clinical function examinations, were carried out at 1, 2, 3, 4, 6, and 12 months after surgery and then once a year, to monitor callus growth and functional recovery of the injured limb.Results:All patients achieved bone union by 6.4 months clinically (4–8 mo) on average and 5.2 months radiologically (2–16 mo), without any intervening measures during follow-up. Mean operation time was 99.3±27.8 minutes (range=50–215 min), and mean blood loss was 494.9±281.3 mL (20–1400 mL). The average follow-up time was 18.7 months (12–26 mo). All patients in the current study achieved bone union (100%). We observed no postoperative complications, such as failure of internal fixation, infections, angular or rotational malunion. Physicians removed the intramedullary nail and plate from 5 patients 11–16 months after the operation without any refracture. During the last follow-up, all patients could flex their knees >100 degrees.Conclusions:AR with a nail left in situ, combined with bone grafting, is an effective treatment option for nonisthmal femoral shaft nonunions.
Effect of 808-nm Laser Photobiomodulation Treatment in Blepharitis Rat Model
Authors: Kim Hoon , Kim Hong-Bee , Seo Jae-Hwi , Kim Hongbin , Cho Kyong Jin 
Published: November 2020

Purpose:
Blepharitis, simply defined as eyelid inflammation, is one of the common ocular conditions associated with discomfort and irritation. Because blepharitis causes meibomian gland dysfunction and dry eye, this study aimed to confirm the effect of photobiomodulation (PBM) on blepharitis.

Methods:
A total of 20 rats were randomly assigned to 4 equal groups, including control, blepharitis, PBM, and eye drop. Blepharitis was induced in rats by injecting complete Freund's adjuvant in the eyelid margins. PBM intervention was given every 3 days after blepharitis induction. Clinical signs including tear volume, tear breakup time (TBUT), meibomian gland swelling, fluorescein, telangiectasia, and meibomian gland secretion scores were measured every week, and the rats were killed for histological analysis after 4 weeks. Immunohistochemistry was performed to compare the level of inflammatory cytokines, interleukin-1β and tumor necrosis factor-α, and terminal deoxynucleotidyl transferase dUTP nick end labeling staining on retina was performed to observe any retinal damage.

Results:
Tear volume and TBUT increased with PBM intervention, and with improved eyelid swelling, corneal staining, telangiectasia, and meibomian gland secretion scores increased. Hematoxylin and eosin staining showed no structural abnormalities of meibomian gland caused by blepharitis induction. Immunohistochemistry revealed that the levels of inflammatory cytokines interleukin-1β and tumor necrosis factor-α were lowered with PBM treatment in both eyelid and conjunctiva. Terminal deoxynucleotidyl transferase dUTP nick end labeling staining showed no retinal damage.

Conclusions:
Laser PBM at 808 nm was effective in alleviating ocular signs and controlling inflammation in blepharitis rat model. The in vivo results suggest that PBM has the potential to be used in treating blepharitis patients.
Service Involvement Across Multiple Sectors Among People Who Use Opioids, Methamphetamine, or Both, United States—2015–2018
Authors: Howell Benjamin A. , Bart Gavin , Wang Emily A. , Winkelman Tyler N.A. 
Published: November 2020

Background:
The fourth wave of the opioid crisis is characterized by increased use and co-use of methamphetamine. How opioid and methamphetamine co-use is associated with health care use, housing instability, social service use, and criminal justice involvement has not been studied and could inform future interventions and partnerships.

Objectives:
To estimate service involvement across sectors among people who reported past year opioid and methamphetamine co-use, methamphetamine use, opioid use, or neither opioid nor methamphetamine use.

Research Design:
We examined 2015–2018 data from the National Survey on Drug Use and Health. We used multivariable negative binomial and logistic regression models and predictive margins, adjusted for sociodemographic and clinical characteristics.

Subjects:
Nonelderly US adults aged 18 or older.

Measures:
Hospital days, emergency department visits, housing instability, social service use, and criminal justice involvement in the past year.

Results:
In adjusted analyses, adults who reported opioid and methamphetamine co-use had 99% more overnight hospital days, 46% more emergency department visits, 2.1 times more housing instability, 1.4 times more social service use, and 3.3 times more criminal justice involvement compared with people with opioid use only. People who used any methamphetamine, with opioids or alone, were significantly more likely be involved with services in 2 or more sectors compared with those who used opioids only (opioids only: 11.6%; methamphetamine only: 19.8%; opioids and methamphetamine: 27.6%).

Conclusions:
Multisector service involvement is highest among those who use both opioids and methamphetamine, suggesting that partnerships between health care, housing, social service, and criminal justice agencies are needed to develop, test, and implement interventions to reduce methamphetamine-related morbidity.
Microbiome modulation as a novel therapeutic approach in chronic kidney disease
Authors: Sumida Keiichi , Lau Wei Ling , Kovesdy Csaba P. , Kalantar-Zadeh Kamyar , Kalantar-Zadeh Kourosh 
Published: November 2020

Purpose of review
Gut dysbiosis has been implicated in the pathogenesis of chronic kidney disease (CKD). Interventions aimed at restoring gut microbiota have emerged as a potential therapeutic option in CKD. This review summarizes the current evidence on gut microbiota-targeted strategies in patients with CKD.

Recent findings
A growing number of studies have shown that plant-based diets, low-protein diets, prebiotic, probiotic, and synbiotic supplementation, and constipation treatment may lead to favorable alterations in the gut microbiota. Current evidence suggests that the implementation of both plant-based and low-protein diets has potential benefits for the primary prevention of CKD, and for slowing CKD progression, with minimal risk of hyperkalemia and/or cachexia. The use of prebiotics, probiotics, and synbiotics and laxatives may have beneficial effects on uremic toxin generation, but their evidence is limited for the prevention and treatment of CKD. Recent advances in diagnostic technologies (e.g., high-throughput sequencing and nanotechnology) could enhance rapid diagnosis, monitoring, and design of effective therapeutic strategies for mitigating gut dysbiosis in CKD.

Summary
Plant-based and low-protein diets, prebiotic, probiotic, and synbiotic supplementation, and constipation treatment represent novel gut microbiota-targeted strategies in the conservative management of CKD, which could improve clinical outcomes in CKD.
Race, History of Abuse, and Homelessness Are Associated With Forced Medication Administration During Psychiatric Inpatient Care
Authors: THOMAS TINA E. , LANE SCOTT D. , ELKHATIB RANIA M. , HAMILTON JANE E. , PIGOTT TERESA A. 
Published: November 2020

Objective:
Although previous research has suggested that racial disparities exist in the administration of forced medication (FM) in psychiatric inpatients, data remain scarce regarding other contributing variables. Therefore, this study examined sociodemographic and clinical variables associated with FM administration in psychiatric inpatients.

Methods:
Electronic medical records from 57,615 patients admitted to an academic psychiatric hospital between 2010 and 2018 were reviewed to identify patients who received FM. These records indicated that FM petitions were requested and approved for ∼6200 patients. Patients were excluded from the analysis if they met the following exclusion criteria: under 18 years of age, presence of intellectual/developmental disability, dementia, or other neurological condition, or primary diagnosis of a nonpsychiatric medical condition or a substance-induced mood or psychotic disorder. After data on those patients were excluded, the final sample included records from 2569 patients (4.5% of the total records) in which the administration of FM was petitioned for and approved. The FM group was compared with a control group of 2569 patients matched in terms of age, sex, and admission date (no-forced medication group; NFM) via propensity scoring matching. Group comparisons (FM vs. NFM group) examined sociodemographic factors (race, age, sex, living situation), clinical features (diagnosis, substance abuse, history of abuse), and outcomes (length of stay, readmission rate). Regression analyses examined the association between FM and sociodemographic, clinical, and outcome variables.

Results:
Compared with the NFM group, the FM group contained significantly more African Americans (P<0.001), homeless individuals (P<0.001), and individuals with histories of abuse (P<0.001). Having received FM was a significant predictor of a longer length of stay (P<0.001) and higher readmission rates (P<0.001).

Discussion:
These results suggest that FM is more likely to be instituted in psychiatric inpatients who are of a minority race (African American), are in a homeless living situation, and/or have a history of abuse. Moreover, FM may be associated with poorer clinical outcomes at least as measured by the length of stay and higher readmission rates. We discuss possible reasons for these results and the importance of culturally competent and trauma-focused care.
Lithium Prescribing and Therapeutic Drug Monitoring in Bipolar Disorder: A Survey of Current Practices and Perspectives
Authors: FERNANDES VIRGINIA , AL-SUKHNI MAYCE , LAWSON ANDREA , CHANDLER GREGORY 
Published: November 2020

Objective:
The goal of this survey study was to assess specific aspects of lithium therapy for bipolar disorder, including psychiatrists’ prescribing practices, understanding of therapeutic drug monitoring, and concerns and perspectives regarding lithium therapy.

Methods:
A 14-item survey was electronically distributed to 225 staff psychiatrists at 8 academic hospitals.

Results:
The survey was completed by 85 psychiatrists (38% of the 225 psychiatrists to whom the survey was distributed), with between 81 and 85 respondents completing the different items. When asked about the agents with which they initiated therapy, 49 (61%) reported initiating therapy with an atypical antipsychotic and 34 (42%) reported starting with lithium therapy in 50% or more of patients newly diagnosed with bipolar disorder. When prescribing lithium, most of the respondents (n=68, 82%) reported that they used once daily dosing, and 67 respondents (79%) indicated that they ordered lithium blood levels 12 hours postdose. When interpreting lithium levels, 46 respondents (55%) reported “always” changing a clinically stable patient’s lithium dose when the level was above the therapeutic range, compared with 4 (5%) who reported always changing the dose when the level was below the therapeutic range. When asked about their concerns regarding lithium therapy, more than half of the respondents reported that they were especially concerned about toxicity, organ dysfunction, and other adverse effects, as well as therapeutic drug monitoring.

Conclusion:
Shifts in prescribing practices, inconsistent interpretation of lithium levels, and concerns about safety and therapeutic drug monitoring highlight the need for evidence-informed guidelines reflective of current practice.
Three-Dimensional Computed Tomographic Study on the Vessels of the Zygomatic Region: Arterial Variations and Clinical Relevance
Authors: Zhao Wei-Rui , Duan Jing , Chen Chun-Lin , Luo Cheng-En , Zhan Wen-Feng , Kong Xiang-Xue , Luo Sheng-Kang 
Published: November 2020

Background:
Injection-based techniques for “cheek augmentation” have gained popularity in recent years. The aim of this study was to perform a topographic analysis of the depth and distribution of the vessels in the zygomatic region to facilitate clinical procedures.

Methods:
The external carotid arteries of seven cadaveric heads were infused with lead oxide contrast medium. The facial and superficial temporal arteries of another 12 cadaveric heads were injected sequentially with the same medium. Computed tomographic scanning was then performed, and three-dimensional computed tomographic scans were reconstructed using validated algorithms.

Results:
The vessels on the zygomatic arch received a double blood supply from across the upper and lower borders of the arch, and the number of the vessels varied from one to four. Ninety percent of the vessels on the zygomatic arch were at a depth of 1 to 2.5 mm, and 75 percent were at a depth of 10 to 30 percent of the soft-tissue thickness. The vessels were concentrated on the midline of the zygomatic arch and the lateral margin of the frontal process. All samples showed a vessel travel along the lateral margin of the frontal process that eventually merged into the superior marginal arcades.

Conclusions:
This study reported a topographic analysis of the depth and distribution of the vessels in the zygomatic region based on three-dimensional scanning. The results indicated that injection on the zygomatic arch should be performed deep to the bone, and the vascular zones anterior or posterior to the midline of the zygomatic arch were relatively safe injection areas.
Implementation of Novel Protocols in an Ophthalmic Ambulatory Surgical Center to Resume Surgical Procedures During COVID-19
Authors: Berkenstock Meghan K. , Ishii Lisa , Giessler Brian , Quaty John , Biggs Madalyn , Buck Pamela , Ebrado Alfred , Kalendek Laurie , Lazoff Karen , Martin Michael , McCullough Chanda , Jampel Henry , Scott Adrienne W. 
Published: November 2020

Background and Objectives:
With the resumption of elective ophthalmic surgery during COVID-19, revised protocols were mandated to protect both staff and patients from transmission while increasing case numbers. We discuss a widely generalizable and in-depth protocol intended to safely allow the restart of elective procedures in 2 dedicated ophthalmic ambulatory surgical centers (ASCs) using monitored anesthesia care.

Methods:
A single-center review of protocols and practices designed to limit COVID-19 transmission.

Results:
All patients were tested within 72 hours prior to the procedure with a COVID-19 nasal swab to assess for active disease. A distance of 6 ft between each stretcher and the staff within the ASC was maintained when possible. Preoperative anesthetizing and dilating eye drops were administered from multiuse bottles without contact with surfaces. Surgical cases were restarted at a reduced capacity of a maximum of 7 per day to distance patient arrivals. Removal of waiting room chairs and the creation of new break areas allowed for social distancing.

Conclusion:
As recommendations change on the basis of an increased understanding of the COVID-19 virus, ophthalmologists and ASC staff need to tailor protocols and workflows to limit transmission of virus with resumption of ocular surgery.