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Background: Patella baja is a known complication of total knee arthroplasty (TKA). There is a limited understanding of the association between patellar resurfacing and the incidence of patella baja. We aimed to compare rates of patella baja between unresurfaced and resurfaced patellas in patients undergoing TKA. Methods: A retrospective review of patients who underwent TKA between October 2009 and January 2020 was performed. Patients were included if they had at least one preoperative radiograph and a 1-year follow-up radiograph. Blackburne-Peel index (BPI) and Insall-Salvati ratios (ISRs) were measured on preoperative and 1-year postoperative radiographs and were used to define patella baja vs pseudopatella baja. Statistical analysis was performed using a linear model analysis of variance and the Fisher’s exact test. Results: Three hundred eighteen TKAs were included, with 176 being resurfaced and 142 unresurfaced patellas. Of the resurfaced group, 4% (7/176) had true patella baja, compared to 5.6% (8/142) of the unresurfaced patellas. Of the resurfaced patellas, 8% (14/176) had pseudopatella baja, compared to 7% (10/142) in the unresurfaced group. Patellar resurfacing was not associated with a higher incidence of patella baja (P = .60) or pseudopatella baja (P = .83). Lower preoperative ISRs (P = .04) and BPIs (0.03) were highly predictive of a higher incidence of patella baja post-TKA. Conclusions: Patellar resurfacing in TKA is not associated with a higher incidence of patella baja in TKA when compared to unresurfaced patellas. Lower preoperative ISRs and BPIs are highly predictive of a higher incidence of postoperative patella baja.

Purpose: To use Google trends to explore differences in public interest among types of anterior cruciate ligament (ACL) autografts, specifically quadriceps tendon, patellar tendon, and hamstring tendon autografts, between 2008 and 2019. Methods: Data were obtained by querying Google Trends for key terms and phrases for online search data ranging from January 2008 to December 2019. Relative search volumes were created based on searches related to ACL reconstruction with comparative analysis generated for search terms related to quadriceps ACL, patellar tendon ACL, and hamstring ACL autografts. Statistical analysis included linear regression analysis, comparison of quarterly search volume trends over time, and comparison of cumulative annual search volumes for 2008 versus 2019. Results: Linear models for respective search terms were statistically significant for the quadriceps (P < .001) and patellar (P = .007) tendon autograft groups but not the hamstring group (P = .129). The quadriceps autograft group demonstrated a 12-year search volume trend change of 0.56, which was significantly greater than the hamstring (0.07; P < .001) and patellar tendon (0.168; P < .001) groups. There was no significant difference in the trend change between hamstring and patellar tendon groups (P = .20). Percent change in cumulative relative annual search volumes between 2008 and 2019 was 112% for the quadriceps tendon group, 12.9% for the hamstring group, and 18.6% for the patellar tendon group. Conclusions: This study indicates a consistently increasing public interest in quadriceps tendon autograft for ACL reconstruction. The quadriceps autograft group demonstrated a significantly greater 12-year online search volume, greater linear correlation, and larger percent change between 2008 and 2019 compared with patellar tendon or hamstring autograft groups. Clinical Relevance: Awareness of patient perceptions has value in informing shared decision-making, aligning patient expectations, and guiding areas of future research. Each of these has an impact on patient care. Being aware of patient interest and expectations is particularly important in areas with controversial or emerging research.

Background: Phthalate exposure may contribute to hypertensive disorders of pregnancy (HDP), including preeclampsia/eclampsia (PE/E), but epidemiologic studies are lacking. Objectives: To evaluate associations of pregnancy phthalate exposure with development of PE/E and HDP. Methods: Using data from 3,430 participants in eight Environmental influences on Child Health Outcomes (ECHO) Program cohorts (enrolled from 1999 to 2019), we quantified concentrations of 13 phthalate metabolites (8 measured in all cohorts, 13 in a subset of four cohorts) in urine samples collected at least once during pregnancy. We operationalized outcomes as PE/E and composite HDP (PE/E and/or gestational hypertension). After correcting phthalate metabolite concentrations for urinary dilution, we evaluated covariate-adjusted associations of individual phthalates with odds of PE/E or composite HDP via generalized estimating equations, and the phthalate mixture via quantile-based g-computation. We also explored effect measure modification by fetal sex using stratified models. Effect estimates are reported as odds ratios (OR) with 95% confidence intervals (95% CIs). Results: In adjusted analyses, a doubling of mono-benzyl phthalate (MBzP) and of mono (3-carboxypropyl) phthalate (MCPP) concentrations was associated with higher odds of PE/E as well as composite HDP, with somewhat larger associations for PE/E. For example, a doubling of MCPP was associated with 1.12 times the odds of PE/E (95%CI 1.00, 1.24) and 1.02 times the odds of composite HDP (95%CI 1.00, 1.05). A quartile increase in the phthalate mixture was associated with 1.27 times the odds of PE/E (95%CI 0.94, 1.70). A doubling of mono-carboxy isononyl phthalate (MCiNP) and of mono-carboxy isooctyl phthalate (MCiOP) concentrations were associated with 1.08 (95%CI 1.00, 1.17) and 1.11 (95%CI 1.03, 1.19) times the odds of PE/E. Effect estimates for PE/E were generally larger among pregnancies carrying female fetuses. Discussion: In this study, multiple phthalates were associated with higher odds of PE/E and HDP. Estimates were precise and some were low in magnitude. Interventions to reduce phthalate exposures during pregnancy may help mitigate risk of these conditions.

Concurrent opioid and benzodiazepine users are at increased risk of overdose death, compared to opioid-only users. The objective of this study was to understand recent time trends in opioid and benzodiazepine concurrent use, misuse, and schedule-I drug use, and how these differ by age, sex and geographic region. Commercial, United States medical insurance claims data and urine drug test results from 2013 to 2019 were used to study the outcomes of concurrent use (n = 756,258), schedule-I drug use (n = 746,672) and prescription misuse (n = 452,523). Drug use outcomes were studied at quarterly time points for each year.Data analysis included joinpoint regression models to estimate quarterly drug use rates, determined by positive urine tests for corresponding drug categories, and was conducted from November 2021 through January 2022. Concurrent use decreased from 19.3% to 9.8%, misuse generally decreased from 75.6% to 55.1%, and schedule-I use increased from 8.9% to 13.8%, from 2013 to 2019. Concurrent use decreased at greater rates after 2016, after the Centers for Disease Control and Food and Drug Administration guidelines against concurrent use were released, while schedule-I use increased, notably after the 2014 hydrocodone reschedule. This indicates a potential shift from prescription use to non-prescribed drug use, where most affected groups included males, younger individuals, and those residing in Northeastern regions.Study results support public health initiatives focused on policy that increases access to multimodal pain management and substance use disorder management programs—critical steps in preventing patients from seeking non-prescribed drugs for self- medicating due to pain or addiction.

Background: The purpose of this analysis was to assess the public interest in total hip arthroplasty (THA) based on approach by analyzing Google Trends online search volume trends between 2007 and 2021. Methods: Data were obtained by querying the Google Trends online search tool for key terms and phrases relating to anterior, posterior, lateral, and minimally invasive approaches to THA. Data from January 2007 to December 2021 were utilized. Relative search volume (RSV) was generated for each THA approach group based on historical search volume trends in the United States. Results: Over the 15-year period, Google Trends Search Data demonstrated a statistically significant increase (P < .001) in the RSV for all 4 major hip arthroplasty approaches. The growth in public interest for anterior hip arthroplasty was significantly greater than the growth for posterior (P = .02) and minimally invasive hip arthroplasty (P = .02). The difference in RSV growth between lateral and anterior approaches was not significant (P = .88). The average RSV for anterior hip arthroplasty was 59.0, which was significantly greater than the average RSV of all other groups. Conclusions: The anterior approach to hip arthroplasty has demonstrated a consistent and statistically significant increase in RSV over the past 15 years that has outpaced the increases observed in the posterior and minimally invasive approaches. Despite the increase in public awareness and interest for anterior approach hip arthroplasty, it is yet to demonstrate any long-term clinical benefits over other approaches.

A 46-year-old male presented with a localized left renal mass and underwent an open radical nephrectomy via a midline incision. He recovered uneventfully and was discharged. After one month he reported persistent incisional pain; CT demonstrated heterotopic bone formation under the fascial closure. He underwent resection of calcified preperitoneal fat. Final pathology revealed benign bone tissue. He received a course of celecoxib. The patient developed recurrence of a smaller calcification. He underwent a second resection and was treated with adjuvant radiation. The patient had improvement of pain and no ossification visualized on CT imaging at 1-year follow up.

Purpose: To quantify and analyze public interest trends in platelet-rich plasma (PRP) therapy for shoulder pathology between 2011 and 2020 using Google Trends data. Methods: Google Trends data were queried for online search data ranging from January 2011 to December 2020. Various combinations of terms related to PRP and shoulder pathology were queried. Terms related to corticosteroid therapy in association with shoulder pathology were also generated for comparative analysis. Analyses were performed regarding trends in online search volumes. Results: Linear models were generated to evaluated trends in the volume of online searches for PRP and corticosteroid therapy for shoulder pathology. For both the PRP and steroid groups, linear models showed a statistically significant increase in search volume for the period studied (P < .001). The PRP group showed a significantly greater growth rate than the steroid group (P < .001). There were no statistically significant differences in online search volume when compared between different geographic and socioeconomic locations. Conclusions: This study indicates consistently increasing public interest in PRP injections in the shoulder. The rate of online search volume growth of PRP is significantly greater than that of corticosteroid injections for the period studied. Clinical Relevance: Awareness of patient perceptions has value in informing shared decision making, aligning patient expectations, and guiding areas of future research. Each of these has an impact on patient care. Being aware of patient interest and expectations is particularly important in areas with controversial or emerging research.

Summary: Among all RNA viruses, coronavirus RNA transcription is the most complex and involves a process termed “discontinuous transcription” that results in the production of a set of 3′-nested, co-terminal genomic and subgenomic RNAs during infection. While the expression of the classic canonical set of subgenomic RNAs depends on the recognition of a 6- to 7-nt transcription regulatory core sequence (TRS), here, we use deep sequence and metagenomics analysis strategies and show that the coronavirus transcriptome is even more vast and more complex than previously appreciated and involves the production of leader-containing transcripts that have canonical and noncanonical leader-body junctions. Moreover, by ribosome protection and proteomics analyses, we show that both positive- and negative-sense transcripts are translationally active. The data support the hypothesis that the coronavirus proteome is much vaster than previously noted in the literature.

Purpose: To report a rare case of a solitary fibrous tumor (SFT) of the lacrimal sac and discuss considerations for management of similar cases. Observations: We present the case of a 41-year-old woman who presented with a primary lacrimal sac SFT for which she underwent en-bloc surgical resection. We discuss management options for SFTs and our surgical approach for this case: bilobed flap reconstruction of the medial canthus and inferior orbit. Conclusions: We present an uncommon presentation of a rare tumor and a successful one-stage reconstruction with a bilobed flap.

Objective: Proximal endovascular reintervention after prior endovascular aortic repair (EVAR) or open abdominal aortic aneurysm repair (OR) can be challenging due to the short distance to the visceral branches. We present a novel solution to allow the use of the commercially available ZFEN device using a double-barrel, kissing-limb technique. Methods: Patients who underwent fenestrated repair for proximal failure after EVAR or OR were identified. The ZFEN device is deployed above the prior graft flow divider. Once the visceral branches are secured, kissing limbs are used to connect with the prior graft limbs. The distal diameter of the standard ZFEN is 24 mm, accommodating two 20 mm components according to the formula 2πDLIMB = πDZFEN + 2DZFEN. Results: Of 235 patients who underwent repair using ZFEN from 2012 to 2021 at a single institution, 28 were treated for proximal failure of prior repairs, with 13 treated using the double-barrel technique (8 EVAR, 5 OR). The distance from the flow divider to the lowest renal artery was 67 ± 24.4 mm (range, 39-128 mm), and the distance to the superior mesenteric artery (SMA) was 87 ± 30.5 mm (range, 60-164 mm). Technical success was 100%. Seven patients had standard ZFEN builds (2 renal small fenestrations, SMA large fen/scallop). The minimum distance to the lowest renal artery and SMA to accommodate a standard ZFEN build was 56 and 60 mm, respectively. Four patients required adjunctive snorkel grafts and two required laser fenestrations. Two patients had gutter leaks at 1 month that self-resolved; one patient developed a late type 1a endoleak. Freedom from reintervention was 90%, 72%, and 48% at 1, 2, and 3 years, respectively. Conclusions: This double-barrel technique allows for distal seal of commercial ZFEN devices into prior open or endovascular repairs with good technical success. Long-term outcomes remain to be quantified.

Summary: The accumulation of dysfunctional mitochondria is a hallmark of neurodegenerative diseases, yet the dynamics of mitochondrial turnover in neurons are unclear. Here, we describe a protocol to monitor the degradation of spectrally distinct, “aged” mitochondrial populations. We describe the preparation and transfection of primary rat hippocampal neuron cultures. We detail a mitochondrial-damaging assay, a SNAP pulse-chase labeling paradigm, and live imaging to visualize the mitochondrial network. Finally, we provide steps to quantify mitochondrial turnover via lysosomal fusion.For complete details on the use and execution of this protocol, please refer to Evans and Holzbaur (2020a). : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Background: Recent evidence suggests that patients prefer subjective and crowd-sourced information over data-driven or quality-based outcomes when choosing a surgeon. Online physician rating and review websites continue to increase in popularity, and over half of patients use them to research physicians. Specifically, Yelp.com is the most frequently utilized online resource by patients. Data regarding the characteristics of negative reviews for spine surgeons and practices is lacking. Methods: Orthopedic Spine surgeons and practices in 8 major US metropolitan regions were surveyed for one-star reviews on Yelp.com. The factors noted in the reviews were recorded and they were classified according to their clinical or nonclinical nature. Reviews were also subclassified into nonsurgical or surgical episodes of care. Results: A total of 6,286 Yelp reviews were discovered, 671 (10.6%) of which were rated one-star. The majority of negative reviews (76.4%) were from patients who did not report surgery by the surgeon or practice. Of all comments, 491 (77.6%) related to nonclinical complaints. The most common factors noted in negative reviews were related to bedside manner, rude or unprofessional staff, and wait time. Conclusion: Choosing a surgeon is a complex process for patients. The large majority of negative reviews were related to nonclinical issues such as poor bedside manner or rude staff and most of these were written by patients that did not undergo a surgical procedure. This may explain the large discrepancy that has been observed between quality metrics and online crowd-sourced reviews. Paying attention to these nonclinical factors may represent the most feasible and valuable targets to improve a surgeon's practice and attract future patients.

Background: Total shoulder arthroplasty (TSA) has increased in utilization over the past several decades. Anemia is a common preoperative condition among patients undergoing TSA and has been associated with poorer outcomes in other surgical procedures. To the best of our knowledge, no study has analyzed the association between anemia severity and TSA outcomes. Therefore, the purpose of this study is to determine the effects that increasing severity of anemia may have on the postoperative outcomes in patients receiving primary TSA. Methods: A retrospective analysis was performed using the American College of Surgeons National Surgery Quality Improvement Project database from the years 2015 to 2018. Current Procedure Terminology code 23472 was used to identify all primary TSA procedures recorded during this time frame. Patients with greater than 38% preoperative hematocrit (HCT) were classified as having normal HCT levels. Patients with HCT values between 33% and 38% were classified as having mild anemia. All patients with less than 33% HCT were classified as having moderate/severe anemia. Patient demographic information, preoperative risk factors, and postoperative outcomes were compared among the 3 cohorts. A multivariate logistic regression including demographic factors and comorbidities was performed to determine whether increasing severity of anemia is independently associated with poorer postoperative outcomes. Results: Of the 15,185 patients included in this study, 11,404 had normal HCT levels, 2962 patients were mildly anemic, and 819 patients had moderate to severe anemia. With increasing severity of anemia, there was an increased average hospital length of stay (1.6 vs. 2.1 vs. 3.0 days, P

Purpose: To analyze the top-100 cited articles on sports-related concussions together with a bibliometric analysis to determine citations by year, level of evidence, study design, and several other factors related to the top referenced articles in sports concussions. Methods: The Clarivate Analytics Web of Knowledge database was used to gather data using Boolean queries to capture all possible iterations of sports-related concussion research. Articles were organized in descending order based on the number of citations and included or excluded based on relevance to concussion. Collected information included author name, publication year, country of origin, journal name, article type, study focus, and the level of evidence. Results: The top-100 articles were cited 31,197 times with an average of 312.0 citations per publication. More than one half were published in 2006 or later (52). Cohort studies and descriptive articles were the most prevalent study types (22 each). Studies with Level V evidence were the most common (33). The most common areas of study were symptomatology (short term, long term) with 17 articles, followed by epidemiology/demographics with 16 articles. The least common area of study was concussion prevention (2 articles), followed by management/treatment, diagnostics (labs, imaging) with 4 articles each. Conclusions: We identified the most influential studies in sports-related concussion based on number of citations and citation density. A majority of these articles were published in the United States after 2006 and are most commonly cohort studies (Level IV evidence) and descriptive articles (Level V evidence). Current research focuses most heavily on the symptomatology and epidemiology/demographics of sports concussion. Clinical Relevance: This study serves to identify the most influential articles in sports-related concussion and identify research topics with general deficiencies within the field of sports-related concussion research.

Purpose: To determine the objective characteristics of orthopaedic foot and ankle fellowship directors (FDs) by concentrating on the demographic characteristics, academic background, institutional history, research experience, and professional affiliations of these leaders. Methods: Data for each FD were collected by searching institutional biographies, personal websites, or publicly available curricula vitae. Data collection included the following variables: age, sex, race/ethnicity, previous training institutions, residency and fellowship graduation years, advanced degrees, military affiliation, institutional loyalty, year hired, FD career timeline, total number of publications, total number of citations, and h-index. Results: Of the 47 FDs, 44 (93.6%) were men and 3 (6.4%) were women. The mean age was 50.8 ± 9.4 years. Most orthopaedic foot and ankle FDs were white (n = 42, 89.4%), followed by Asian (n = 4, 8.5%) and black or African American (n = 1, 2.1%). The mean Scopus h-index, total number of publications, and total number of citations for all foot and ankle FDs were 13.3 ± 9.5, 47.5 ± 45.8, and 898.1 ± 1,040.3, respectively. Among all foot and ankle FDs, the mean tenure in the FD position was 5.8 ± 4.6 years. Conclusions: Orthopaedic foot and ankle FDs are primarily white men in their 50s, with minimal female and minority representations. These FDs are distinguished by their high level of research productivity. Additionally, orthopaedic foot and ankle training backgrounds seem to play an important role, given that most of the appointed FDs trained in only a few select programs. Clinical Relevance: This study outlines some of the most important characteristics among foot and ankle FDs and identifies important disparities within this population of leaders that may have detrimental effects on the field.

Purpose: To describe and compare the epidemiology of lumbar spine injuries (LSIs) in women’s and men’s ice hockey during the 2009-2010 to 2013-2014 academic years and to investigate sex-specific differences, using data from the National Collegiate Athletic Association (NCAA) Injury Surveillance Program (ISP) database. Methods: The incidence and characteristics of LSIs were identified utilizing the NCAA ISP. Rates of injury were calculated as number of injuries divided by total number of athlete exposures (AEs). AEs were defined as any student participation in one NCAA-sanctioned practice or competition. Incidence rate ratios (IRRs) were calculated to compare rates of injury between season, event type, mechanism, injury recurrence, and time lost from sport, and injury proportion ratios (IPRs) were calculated to examine the differences in injury rates between men and women. Results: There were a total of 165 LSIs from an average of 10 and 19 women’s and men’s teams, respectively, calculated to 1,254 LSIs nationally. Women were 2.48 times more likely to suffer a noncontact injury than men (95% CI: 1.33-4.61), whereas men were more likely than women to suffer contact LSIs (IPR: .51 [95% CI: .28-.92]). In Divisions II and III, women were 6.64 (95% CI: 4.14-10.64) and 1.28 (95% CI: 1.12-1.46) times more likely to suffer LSIs than men, respectively. Conclusions: Women and men were similarly likely to suffer an LSI, but sex-specific differences existed in a mechanism of injury and likelihood of injury within NCAA Divisions.

Purpose: To analyze recent trends in orthopaedic surgery consolidation and quantify these changes temporally and geographically from 2012 to 2020. Methods: We performed a retrospective cross-sectional analysis of orthopaedic surgeon practice size in the United States using 2012 and 2020 data obtained from the Physician Compare database. Results: Although we observed an increase from 21,216 unique orthopaedic surgeons in 2012 to 21,553 in 2020 (1.6% increase), the number of practices experienced a large decrease from 7,299 practices in 2012 to 5,829 in 2020 (20.1% decrease). The proportion of orthopaedic surgeons working in solo practices decreased from 13.2% (2,790) in 2012 to 7.4% (1,595) in 2020, and the proportion of orthopaedic surgeons working in groups sized 2 to 24 decreased from 35.3% (7,482) in 2012 to 22.2% (4,775) in 2020. In contrast, groups sized 25 to 99 have grown from 20.7% (4,387) of all orthopaedic surgeons to 23.4% (5,048) in 2020. Groups sized 100 to 499 have increased from 16.9% (3,593) in 2012 to 24.1% (5,190) in 2020, whereas groups sized 500 or greater have grown from 14% (2,964) in 2012 to 22.9% (4,945) in 2020. The number of unique group practices showed a significant decrease in the number of solo groups, which comprised 43.8% (3,200) of the total number of individual practices in 2012, decreasing to 32% (1,886) in 2020. All other groups increased in number and proportionally from 2012 to 2020. Conclusions: This study shows that over the period from 2012 to 2020, there has been a substantial trend of orthopaedic surgeons shifting to increasing practice sizes, potentially indicating that more orthopaedic surgeons are working for large health care organizations rather than small independent practices. Clinical Relevance: The impact of these changes should be examined to determine large-scale effects on patient care, payment models, access, and outcomes, along with physician compensation, lifestyle, and satisfaction.

Background: Urinary biomarkers are often corrected for sample dilution using creatinine, which is influenced by sociodemographic factors and certain health conditions. It is unknown whether these factors similarly influence specific gravity. Objectives: To identify predictors of specific gravity and creatinine and compare methods for correcting estimated chemical concentrations for sample dilution using these measures. Methods: We assessed predictors of urinary specific gravity and creatinine among NHANES 2007–2008 participants (n = 7257). We corrected concentrations of mono-n-butyl phthalate (MnBP) for dilution using two methods, each applied to both specific gravity and creatinine: correction using a sample mean of the dilution indicator (i.e., specific gravity or creatinine) and covariate-adjusted standardization. We compared distributions and assessed the agreement of uncorrected or corrected concentrations visually using Bland-Altman plots and statistically by Kendall’s τa. We stratified all analyses by age category (i.e., 6–19 or 20+ years of age). Results: Gender, race/ethnicity, body mass index, and height were associated with urinary specific gravity and creatinine. Distributions of corrected MnBP concentrations were comparable for both methods and dilution indicators, but agreement between methods was greater for specific gravity. Additionally, specific gravity- and creatinine-corrected MnBP concentrations had slightly greater agreement with each other when corrected using a covariate-adjusted standardization method. Discussion: Specific gravity, like creatinine, is associated with sociodemographic and body composition variables. Accounting for these factors as part of the dilution correction method may be important to minimize bias.

Summary: Pseudomonas aeruginosa notoriously adapts to the airways of people with cystic fibrosis (CF), yet how infection-site biogeography and associated evolutionary processes vary as lifelong infections progress remains unclear. Here we test the hypothesis that early adaptations promoting aggregation influence evolutionary-genetic trajectories by examining longitudinal P. aeruginosa from the sinuses of six adults with CF. Highly host-adapted lineages harbored mutator genotypes displaying signatures of early genome degradation associated with recent host restriction. Using an advanced imaging technique (MiPACT-HCR [microbial identification after passive clarity technique]), we find population structure tracks with genome degradation, with the most host-adapted, genome-degraded P. aeruginosa (the mutators) residing in small, sparse aggregates. We propose that following initial adaptive evolution in larger populations under strong selection for aggregation, P. aeruginosa persists in small, fragmented populations that experience stronger effects of genetic drift. These conditions enrich for mutators and promote degenerative genome evolution. Our findings underscore the importance of infection-site biogeography to pathogen evolution.

Summary: Hepatocellular carcinoma (HCC) remains one of the deadliest malignancies worldwide. One major obstacle to treatment is a lack of effective molecular-targeted therapies. In this study, we find that EphA2 expression and signaling are enriched in human HCC and associated with poor prognosis. Loss of EphA2 suppresses the initiation and growth of HCC both in vitro and in vivo. Furthermore, CRISPR/CAS9-mediated EphA2 inhibition significantly delays tumor development in a genetically engineered murine model of HCC. Mechanistically, we discover that targeting EphA2 suppresses both AKT and JAK1/STAT3 signaling, two separate oncogenic pathways in HCC. We also identify a small molecule kinase inhibitor of EphA2 that suppresses tumor progression in a murine HCC model. Together, our results suggest EphA2 as a promising therapeutic target for HCC.

Purpose: To determine the 50 most frequently cited studies in the orthopaedic shoulder arthroscopy literature and to conduct a bibliometric analysis of these studies. Methods: The Clarivate Analytics Web of Knowledge database was used to gather data and metrics using Boolean queries to capture all possible iterations of shoulder arthroscopy research. The search list was sorted so that articles were organized in descending order based on the number of citations and included or excluded based on relevance to shoulder arthroscopy. The information extracted for each article included author name, publication year, country of origin, journal name, article type, and the level of evidence. Results: For these 50 studies, the total number of citations was calculated to be 13,910, with an average of 278.2 citations per paper. The most-cited article was cited 1134 times, whereas the second- and third-most cited articles were cited 920 and 745 times, respectively. All 50 articles were published in English and came from 7 different orthopaedic journals. The United States was responsible for most of the included articles (31), followed by France (9) and Japan (3). Conclusions: The majority of the most-cited articles in shoulder arthroscopy are case series and descriptive studies originating from the United States. In addition, more than one half of the top 50 most-cited studies were published after 2004, which suggests that article age may be less important in the accumulation of citations for a rapidly growing field like shoulder arthroscopy. Clinical Relevance: The top 50 most-cited studies list will provide researchers, medical students, residents, and fellows with a foundational list of the most important and influential academic contributions to shoulder arthroscopy.

Advanced LIGO and Advanced Virgo are monitoring the sky and collecting gravitational-wave strain data with sufficient sensitivity to detect signals routinely. In this paper we describe the data recorded by these instruments during their first and second observing runs. The main data products are gravitational-wave strain time series sampled at 16384 Hz. The datasets that include this strain measurement can be freely accessed through the Gravitational Wave Open Science Center at http://gw-openscience.org, together with data-quality information essential for the analysis of LIGO and Virgo data, documentation, tutorials, and supporting software.

Summary: Iterative liver injury results in progressive fibrosis disrupting hepatic architecture, regeneration potential, and liver function. Hepatic stellate cells (HSCs) are a major source of pathological matrix during fibrosis and are thought to be a functionally homogeneous population. Here, we use single-cell RNA sequencing to deconvolve the hepatic mesenchyme in healthy and fibrotic mouse liver, revealing spatial zonation of HSCs across the hepatic lobule. Furthermore, we show that HSCs partition into topographically diametric lobule regions, designated portal vein-associated HSCs (PaHSCs) and central vein-associated HSCs (CaHSCs). Importantly we uncover functional zonation, identifying CaHSCs as the dominant pathogenic collagen-producing cells in a mouse model of centrilobular fibrosis. Finally, we identify LPAR1 as a therapeutic target on collagen-producing CaHSCs, demonstrating that blockade of LPAR1 inhibits liver fibrosis in a rodent NASH model. Taken together, our work illustrates the power of single-cell transcriptomics to resolve the key collagen-producing cells driving liver fibrosis with high precision. : Dobie et al. use scRNA-seq to reveal spatial and functional zonation of hepatic stellate cells (HSCs) across the hepatic lobule, identifying central vein-associated HSCs as the dominant pathogenic collagen-producing cells during centrilobular injury-induced fibrosis. This illustrates the power of scRNA-seq to resolve the key collagen-producing cells driving liver fibrosis. Keywords: liver fibrosis, mesenchyme, hepatic stellate cells, single-cell RNA sequencing, zonation

The Beclin-1 protein is essential for the initiation of autophagy, and recent studies suggest this function may be compromised in Alzheimer's disease (AD). In addition, in vitro studies have supported a loss of function of Beclin-1 due to proteolytic modification by caspases. In the present study, we examined whether caspase-cleavage of Beclin-1 occurs in the AD brain by designing a site-directed caspase-cleavage antibody based upon a known cleavage site within the protein at position D149. We confirmed that Beclin-1 is an excellent substrate for caspase-3 and demonstrates cleavage led to the formation of a 35-kDa C-terminal fragment labeled by our novel antibody following Western blot analysis. Application of this antibody termed Beclin-1 caspase-cleavage product antibody or BeclinCCP in frontal cortex tissue sections revealed strong immunolabeling within astrocytes that localized with plaque regions and along blood vessels in all AD cases examined. In addition, weaker, more variable BeclinCCP labeling was also observed within neurofibrillary tangles that colocalized with the early tau conformational marker, MC-1 as well as the late tangle marker, PHF-1. Collectively, these data support a depletion of Beclin-1 in AD following caspase-cleavage. This article is part of a Special Issue entitled “Autophagy and protein degradation in neurological diseases.”