bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional outcome of proximal fibular osteotomy in knee osteoarthritis: a prospective study
Authors: Mongia Aaditya Keerti , Singh Sukhmin , Adhikari Navneet , Budhiraja Mohit , Kumar Avinash , Singh Devendra 
Published: July 2022

Background:
Osteoarthritis of the knee joint causes a debilitating pain that hampers the daily activities of affected patients. Proximal fibular osteotomy provides an option in the disease’s early stages to prolong the life of the native joint.

Methods:
All consenting patients with diagnosed osteoarthritis of the knee were enrolled in the study. Preoperative radiographic and clinical assessment with functional scores was conducted. Proximal fibular osteotomy was performed at a distance of 6 to 8 cm from the fibular head. Osteotomy was done and postoperative functional scores (Visual Analogue Score, Knee Society Score, Oxford Knee Score) as well as radiographic parameters (medial and lateral joint spaces and the tibio-femoral angle) were evaluated at intervals of 2 wk, 3 mo, 6 mo and 12 mo. All data was statistically analyzed.

Results:
Sixty patients who completed the 12-month follow-up were included. Their mean age was 62.60±9.80. The Visual Analogue Score improved from 8.65±0.75 to 2.30±0.92 at 12 mo follow-up (P<0.001), showing a significant relief in overall pain. The Knee Society Score improved from 92.6±10.63 to 144.75±17.46, showing a significant improvement (P<0.001). Improvement was seen in medial joint space and lateral joint space, but it was not statistically significant.

Conclusions:
Proximal fibular osteotomy is a relatively less invasive procedure compared with knee replacement and has excellent outcomes. Furthermore, it improves the overall alignment of the joint with significant relief from pain. To improve the outcome of such procedures, an early osteoarthritic knee joint should be evaluated and chosen wisely.

Level of Evidence:
Level III.
Shoulder MRI lag times after implementation of the Affordable Care Act (ACA): a retrospective review
Authors: Fryberger Charles T. , Harper Christopher J. , Brolin Tyler J. , Bernholt David L. , Azar Frederick M. , Throckmorton Thomas W. 
Published: July 2022

Background:
With the Affordable Care Act (ACA), the challenge of expanding healthcare insurance to Americans without jeopardizing quality of care remains. This study was initiated to evaluate how the timing of magnetic resonance imaging (MRI) completion for shoulder pathology correlates with implementation of the ACA by comparing lag times between the initial visit and the date of MRI completion. In addition, the access to orthopaedic care after ACA implementation was evaluated by comparing shoulder MRI lag times among three cohorts based on insurer status.

Methods:
All shoulder and proximal upper extremity MRIs between 2009 and 2017 were reviewed, 5 yr before and 3 yr after ACA implementation. Patients were grouped into commercial, Medicare, and Medicaid cohorts. Average lag times for the pre- and post-ACA periods overall and among payor cohorts were calculated.

Results:
Included were 5900 MRIs, 1997 (33.8%) before and 3903 (66.2%) after ACA implementation. The difference in payor mix before and after ACA implementation was significantly different (P<0.001). Median lag time increased from 23 days pre-ACA to 31 days post-ACA (P<0.001). For commercial insurance, median lag time was 23 days pre-ACA compared with 28 days (P<0.001) post-ACA. Median lag time pre- and post-ACA in the Medicaid cohort was 8 days compared with 30.5 days (P<0.001), respectively. Pre- and post-ACA lag times in the Medicare cohort did not differ significantly (P=0.450).

Conclusions:
Lag times increased significantly after ACA implementation in patients with commercial and Medicaid insurance. This study provides valuable insight into unintended outcomes associated with the ACA legislation.

Level of Evidence:
Level III.
Standardized protocol for hip fracture care leads to similar short-term outcomes despite socioeconomic differences in patient populations: a retrospective cohort study
Authors: Bindner Corey T. , Wester Christopher J. , Ghanta Ramesh B. , Wininger Austin E. , Patel Aalok P. , Atassi Omar H. , Perkins Christopher H. , Dawson John R. 
Published: July 2022

Background:
Socioeconomic status is known to influence outcomes in healthcare. This study compares hip fracture care in patients of different socioeconomic status.

Methods:
A retrospective study of hip fracture patients over age 65 who received operative care by a single surgeon was undertaken at an academic level 1 trauma center (county group, n=47) and two private tertiary care hospitals (private group, n=78). A standardized hip fracture protocol was initiated for all patients upon admission with the goal of operative management in less than 48 hr. Time-to-surgery, length of stay, and short-term postoperative complications were compared between groups.

Results:
County patients were largely nonwhite (93.6%) with 12.8% uninsured, whereas 32.1% of private patients were nonwhite, and all were insured. County patients had longer time from presentation to surgery compared with private patients (30.5 hr vs 21.7 hr, respectively, P=0.003). Length of stay was equivalent between county and private patients (8.0 days vs 7.2 days, respectively, P=0.060). There was no significant difference in the rate of complications between county versus private groups (21.3% vs. 21.8%, respectively, P=0.946). Difference in 30-day mortality was not statistically significant (8.5% county vs. 3.9% private, respectively, P=0.424). No risk factors were associated with significantly increased risk of complications with logistic regression analysis.

Conclusions:
There was a similar length of stay, complication rate, and mortality rate after hip fracture surgery despite demographic differences between the groups. A fragility fracture protocol can lead to similar outcomes in patients of differing demographics and insurance payer mixes.

Level of Evidence:
Level III.
Effect of intravenous lidocaine on pain after head and neck cancer surgery (ELICO trial)
Authors: Wallon Grégoire , Erbacher Julien , Omar Edris , Bauer Christian , Axiotis Grégory , Thevenon Sylvie , Soubirou Jean-Luc , Aubrun Frédéric 
Published: July 2022

BACKGROUND
Treatment of postoperative pain after ear, nose and throat (ENT) cancer surgery is mainly morphine administration. Additional systemic lidocaine has shown promising results in some surgical procedures.

OBJECTIVE
The main objective was to evaluate morphine consumption in the first 48 postoperative hours after intra-operative lidocaine infusion during major ENT cancer surgery.

DESIGN
A randomised, double-blind, placebo-controlled trial.

SETTING
Bicentric study including a university hospital and a major cancer centre, conducted from December 2016 to December 2019.

PATIENTS
A total of 144 patients undergoing major ENT cancer surgery were included.

INTERVENTION
The patients were randomly assigned to receive intravenous lidocaine or placebo during surgery and in the recovery room.

MAIN OUTCOME MEASURES
Endpoints were postoperative morphine consumption in the first 24 and 48 h postoperatively, intra-operative remifentanil consumption, adverse events occurrence and assessment 3 to 6 months after surgery with the McGill pain questionnaire.

RESULTS
A total of 118 patients were included (lidocaine n = 57; placebo n = 61, 26 patients were excluded). There was no significant difference in morphine consumption during the first 48 postoperative hours in the lidocaine group compared with the placebo group with a median [IQR] of 0.60 [0.30 to 1.03] mg kg-1 vs. 0.57 [0.37 to 0.96] mg kg-1, total dose 44 [21 to 73.3] mg vs. 38 [23.3 to 56.5] mg, P = 0.92.
There was no significant difference between the two groups in any of the other endpoints, including at follow up 3 to 6 months after surgery.

CONCLUSION
Intravenous lidocaine in ENT cancer surgery did not show any additional analgesic or morphine-sparing effect 48 h after surgery. Three to six months after surgery, there was no significant difference in pain scores or consumption of analgesics. Patients treated pre-operatively with opioids were not evaluated in the study.

TRIAL REGISTRATION
Clinicaltrials.gov identifier: NCT02894710 and EUDRACT number 2015-005799-90.
The Impaired Mechanism and Facilitated Therapies of Efferocytosis in Atherosclerosis
Authors: Wang Zibin , Su Jin , Gong Fanglin , Xue Lingjing , Su Zhigui 
Published: July 2022

Abstract:
Cardiovascular disease is responsible for the largest number of deaths worldwide, and atherosclerosis is the primary cause. Apoptotic cell accumulation in atherosclerotic plaques leads to necrotic core formation and plaque rupture. Emerging findings show that the progression of atherosclerosis appears to suppress the elimination of apoptotic cells. Mechanistically, the reduced edibility of apoptotic cells, insufficient phagocytic capacity of phagocytes, downregulation of bridging molecules, and dysfunction in the polarization of macrophages lead to impaired efferocytosis in atherosclerotic plaques. This review focuses on the characteristics of efferocytosis in plaques and the therapeutic strategies aimed at promoting efferocytosis in atherosclerosis, which would provide novel insights for the development of antiatherosclerotic drugs based on efferocytosis.
Immune checkpoint inhibitors and kidney disease
Authors: Wang Qiyu , Moledina Dennis G. , Sise Meghan E. 
Published: July 2022

Purpose of review
Immune checkpoint inhibitors (ICIs) have changed the landscape of cancer treatment. However, use of ICIs can be limited by inflammatory toxicities referred to as immune-related adverse events (irAEs). ICI-associated acute kidney injury (ICI-associated AKI) affects 3–5% of ICI users.

Recent findings
With the rapidly growing indication of ICI, knowledge of ICI-associated kidney toxicity has also expanded from case series to large multicentre cohort studies. In this review, we discuss the clinical features, risk factors, clinicopathological correlations and prognosis of ICI-associated AKI from the most recent rigorously conducted retrospective cohort studies. We also discuss recent advances in diagnostic biomarker investigation, treatment and the unique challenge faced in the kidney transplant population.

Summary
With more comprehensive understanding of the clinical features and risk factors, ICI-associated AKI is commonly diagnosed clinically, especially given the inherent challenges performing a kidney biopsy in the cancer population; however, this highlights the urgent need for improved noninvasive diagnostic biomarkers to aid diagnosis and prognosis. Prospective studies are needed to better define the optimal treatment of ICI-associated AKI and to minimize the risk of graft loss in patients with kidney transplant who require ICIs.
WNK1 in the kidney
Authors: Bahena-Lopez Jessica Paola , Gamba Gerardo , Castañeda-Bueno María 
Published: July 2022

Purpose of review
The aim of this manuscript was to review recent evidence uncovering the roles of the With No lysine (K) kinase 1 (WNK1) in the kidney.

Recent findings
Analyses of microdissected mouse nephron segments have revealed the abundance of long-WNK1 and kidney-specific-WNK1 transcripts in different segments. The low levels of L-WNK1 transcripts in the distal convoluted tubule (DCT) stand out and support functional evidence on the lack of L-WNK1 activity in this segment. The recent description of familial hyperkalaemic hypertension (FHHt)-causative mutations affecting the acidic domain of WNK1 supports the notion that KS-WNK1 activates the Na+:Cl- cotransporter NCC. The high sensitivity of KS-WNK1 to KLHL3-targeted degradation and the low levels of L-WNK1 in the DCT, led to propose that this type of FHHt is mainly due to increased KS-WNK1 protein in the DCT. The observation that KS-WNK1 renal protein expression is induced by low K+ diet and recent reassessment of the phenotype of KS-WNK1-/- mice suggested that KS-WNK1 may be necessary to achieve maximal NCC activation under this condition. Evidences on the regulation of other renal transport proteins by WNK1 are also summarized.

Summary
The diversity of WNK1 transcripts in the kidney has complicated the interpretation of experimental data. Integration of experimental data with the knowledge of isoform abundance in renal cell types is necessary in future studies about WNK1 function in the kidney.
Measurement of tissue factor-positive extracellular vesicles in plasma: strengths and weaknesses of current methods
Authors: Mackman Nigel , Sachetto Ana Teresa Azevedo , Hisada Yohei 
Published: July 2022

Purpose of review
This review evaluates the different methods used to measure levels of tissue factor (TF) in plasma and on extracellular vesicles (EVs). Levels of TF-positive (TF+) EVs in blood are increased in a variety of diseases, such as cancer, sepsis, and viral infection, and are associated with thrombosis. Highly sensitive assays are required to measure the low levels of TF+ EVs in blood.

Recent findings
TF antigen levels in plasma have been measured using standard ELISAs, SimpleStep ELISA technology, and solid-phase proximity ligation assay. Some studies reported the detection of TF+ EVs in plasma by flow cytometry. In addition, TF+ EVs can be captured onto beads and chips using anti-TF antibodies. Several assays have been developed to measure TF activity in EVs isolated from plasma. Importantly, activity-based assays are more sensitive than antigen-based assays as a single TF/FVIIa complex can generate large amounts of FXa.

Summary
We recommend isolating EVs from plasma and measuring TF activity using a functional assay in the presence and absence of an anti-TF antibody. We do not recommend using antigen-based assays as these are not sensitive enough to detect the low levels of TF in plasma.
Quality Improvement Project to Improve the Timeliness of Care for Children With Testicular Torsion in the Emergency Department
Authors: Chinta Sri S. , Gray Matthew P. , Kopetsky Matthew , Baumer-Mouradian Shannon H. , Drendel Amy L. , Roth Elizabeth , Ferguson Catherine C. , Nimmer Mark , Boyd Kevin , Brousseau David C. 
Published: July 2022

Introduction:
Testicular torsion (TT) is a urologic emergency that requires timely diagnosis and surgery. We noted variation in the door-to-detorsion times for patients with TT at our institution and our orchiectomy rate was 25.8%. We aimed to decrease the mean door-to-detorsion time from 124.6 to 114.6 minutes or less over 12 months.

Methods:
A multidisciplinary team of pediatric emergency medicine, radiology, urology physicians, and nurses, was formed. Our key drivers were use of Testicular Workup for Ischemia and Suspected Torsion (TWIST) score, prompt urology consultation, and efficient transfer from emergency department (ED) to operating room. Our process measures were TWIST score documentation rate and early urology consultation rate, outcome measures were door-to-detorsion time and orchiectomy rate, and balancing measure was ultrasound utilization rate. Early urology consultation occurred when the ED provider documented telephone communication with urology, immediately after placing a testicular doppler ultrasound (TDUS) order and before TDUS result.

Results:
Over 2 years, 45 cases of TT were diagnosed. TWIST score documentation was implemented and was sustained at 78%. This improved early urology consultations from 40% to 60%. The mean door-to-detorsion time improved from 124.6 to 114.2 minutes. There was no reduction in the orchiectomy rate or TDUS utilization rate.

Conclusions:
A quality improvement project to improve the timeliness of care for children with TT resulted in expedited ED care but did not impact the orchiectomy rate.
A Quality Improvement Project Aimed at Standardizing the Prescribing of Fluconazole Prophylaxis in a Level IV Neonatal Intensive Care Unit
Authors: Smith Brandi , Rajapakse Nipunie , Sauer Hannah E. , Ellsworth Kevin , Dinnes Laura , Madigan Theresa 
Published: July 2022

Introduction:
Invasive candidiasis has a high morbidity and mortality among premature neonates. Antifungal prophylaxis with fluconazole significantly lowers the risk of invasive fungal infection in this population. We noted the use of fluconazole prophylaxis in our level IV neonatal intensive care unit (NICU) was variable and sought to standardize prescribing of prophylactic fluconazole.

Methods:
We formed a multidisciplinary team to develop an evidence-based protocol using literature and expert consensus to guide appropriate use of fluconazole prophylaxis in our level IV NICU. After determining baseline fluconazole prophylaxis prescribing before protocol implementation, we used plan-do-study-act (PDSA) cycles to introduce protocolized prescribing and incorporate it into daily practice. A 6-month intervention phase was followed by a 2-year control phase, in which monthly audits were performed to evaluate protocol adherence. Results were displayed in a statistical process control chart.

Results:
Before protocol implementation, fluconazole prophylaxis prescribing adhered to the protocol in 81% of patients. During the first PDSA cycle, adherence increased significantly to 94.5% (86/91 patients), which further increased to 98.7% (74/75 patients) during the second PDSA cycle and remained at 96% (120/125 patients) during the control phase (P < 0.0001).

Conclusions:
A multidisciplinary group-designed protocol was successful in standardizing fluconazole prophylaxis prescribing for infants in the level IV NICU. Adherence to protocol was high following implementation and was sustained for the duration of the project. There were no cases of invasive candidiasis noted.
Biological and Disease Hallmarks of Alzheimer’s Disease Defined by Alzheimer’s Disease Genes
Authors: Murakami Shin , Lacayo Patricia 
Published: July 2022

AbstractAn increasing number of genes associated with Alzheimer’s disease (AD) have been reported. However, despite previous studies, there is a lack of overview of the genetic relationship between AD and age-related comorbidities, such as hypertension, myocardial infarction, and diabetes, among others. Previously, we used Reactome analysis in conjunction with the genes that are associated with AD (AD genes) to identify both the biological pathways and the neurological diseases involved. Here we provide systematic updates on the genetic and disease hallmarks defined by AD genes. There are a total of 11 pathways (defined as genetic biological hallmarks) including 6 existing hallmarks and 5 newly updated hallmarks, the latter of which are developmental biology (axon and adipose development), gene expression (RNA transcription), metabolism of proteins (Amyloid formation, regulation of IGF-1/Insulin, and small ubiquitin-like modifiers/SUMOs), metabolism of RNA (mitochondrial tRNA and rRNA processing), and signal transduction (ErbB, NOTCH and p75 NTR death signaling). The AD genes further identified 20 diverse diseases that we define as disease hallmarks including: (1) existing hallmarks, including neurological diseases (Alzheimer’s disease, Amyotrophic Lateral Sclerosis, Parkinson’s Disease, and Schizophrenia); (2) as well as newly identified hallmarks, including Type 2 Diabetes, Cardiovascular diseases (Myocardial Infarction, Heart Disease, Hypertension, Cardiovascular system disease, Vascular Disease), Quantitative trait loci (lipoprotein and body mass index), Cancer (Breast cancer, Colorectal cancer, Prostate cancer, and Lung cancer); (3) and other health conditions; note that cancers reportedly have an inverse relation with AD. We previously suggested that a single gene is associated with multiple neurological diseases, and we are further extending the finding that AD genes are associated with common age-related comorbidities and others. This study indicates that heterogeneity of Alzheimer’s disease predicts complex clinical presentations in people living with AD. Taken together, the genes define AD as a part of age-related comorbidities with shared biological mechanisms and may raise awareness of a healthy lifestyle as potential prevention and treatment of the comorbidities.
Engineered Serum Markers for Noninvasive Monitoring of Gene Expression in the Brain
Authors: Lee Sangsin , Nouraein Shirin , Kwon James J. , Huang Zhimin , Szablowski Jerzy O. 
Published: July 2022

ABSTRACTNoninvasive efforts to map brain gene expression have been hampered by low sensitivity and limited access to the brain. Here, we introduce a new platform that enables multiplexed, noninvasive, and site-specific monitoring of brain gene expression through a novel class of engineered reporters called Released Markers of Activity (RMAs). Instead of detecting gene expression in the less accessible brain, RMA reporters exit from a known brain region into the blood, where they can be easily measured with biochemical techniques. Expressing RMAs at a single brain site, typically covering ∼1% of the brain volume, provides up to a 39,000-fold signal increase over the baselinein vivo. Further, expression of RMAs in as few as several hundred neurons was sufficient for their reliable detection. When placed under a promoter upregulated by neuronal activity, RMAs could be used to measure neuronal activity in specific brain regions with a simple blood draw. We found that chemogenetic activation of cells expressingFos-responsive RMA increased serum levels of RMA over 4-fold compared to non-activated controls. By contrast, a control RMA expressed under a constitutive neuronal promoter did not show such upregulation, demonstrating multiplexed ratiometric measurement with RMAs and proving specificity of neuronal activity discrimination. Together, our study pioneers a new noninvasive paradigm for repeatable and multiplexed monitoring of gene expression in an intact brain with sensitivity that is currently unavailable through other noninvasive gene expression reporter systems.
Genozip Dual-Coordinate VCF format enables efficient genomic analyses and alleviates liftover limitations
Authors: Lan Divon , Purnomo Gludhug , Tobler Ray , Souilmi Yassine , Llamas Bastien 
Published: July 2022

AbstractWe introduce Dual Coordinate VCF (DVCF), a file format that records genomic variants against two different reference genomes simultaneously and is fully compliant with the current VCF specification. As implemented in the Genozip platform, DVCF enables bioinformatics pipelines to seamlessly operate across two coordinate systems by leveraging the system most advantageous to each pipeline step, simplifying bioinformatics workflows and reducing file generation and associated data storage burden. Moreover, our benchmarking of Genozip DVCF shows that it produces more complete, less erroneous, and less biased translations across coordinate systems than two widely used alternative tools (i.e., LiftoverVcf and CrossMap).Availability and ImplementationAn open source (GPL) version of Genozip containing DVCF functionality but not compression functionality, and which includes scripts for reproducing the benchmarks presented here, is available athttps://github.com/divonlan/dvcf. Documentation is available athttps://genozip.com/dvcf.