bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-Throughput Transcriptomic Analysis of Human Primary Hepatocyte Spheroids Exposed to Per- and Polyfluoroalkyl Substances as a Platform for Relative Potency Characterization
Authors: Rowan-Carroll Andrea , Reardon Anthony , Leingartner Karen , Gagné Remi , Williams Andrew , Meier Matthew J , Kuo Byron , Bourdon-Lacombe Julie , Moffat Ivy , Carrier Richard , Nong Andy , Lorusso Luigi , Ferguson Stephen S , Atlas Ella , Yauk Carole 
Published: March 2021

Abstract
Per- and poly-fluoroalkyl substances (PFAS) are widely found in the environment because of their extensive use and persistence. Although several PFAS are well studied, most lack toxicity data to inform human health hazard and risk assessment. This study focused on 4 model PFAS: perfluorooctanoic acid (PFOA; 8 carbon), perfluorobutane sulfonate (PFBS; 4 carbon), perfluorooctane sulfonate (PFOS; 8 carbon), and perfluorodecane sulfonate (PFDS; 10 carbon). Human primary liver cell spheroids (pooled from 10 donors) were exposed to 10 concentrations of each PFAS and analyzed at 4 time points. The approach aimed to: (1) identify gene expression changes mediated by the PFAS, (2) identify similarities in biological responses, (3) compare PFAS potency through benchmark concentration analysis, and (4) derive bioactivity exposure ratios (ratio of the concentration at which biological responses occur, relative to daily human exposure). All PFAS induced transcriptional changes in cholesterol biosynthesis and lipid metabolism pathways, and predicted PPARα activation. PFOS exhibited the most transcriptional activity and had a highly similar gene expression profile to PFDS. PFBS induced the least transcriptional changes and the highest benchmark concentration (ie, was the least potent). The data indicate that these PFAS may have common molecular targets and toxicities, but that PFOS and PFDS are the most similar. The transcriptomic bioactivity exposure ratios derived here for PFOA and PFOS were comparable to those derived using rodent apical endpoints in risk assessments. These data provide a baseline level of toxicity for comparison with other known PFAS using this testing strategy.
Syndecan‐3 enhances anabolic bone formation through WNT signaling
Authors: Johnson de Sousa Brito Francesca Manuela , Butcher Andrew , Pisconti Addolorata , Poulet Blandine , Prior Amanda , Charlesworth Gemma , Sperinck Catherine , Scotto di Mase Michele , Liu Ke , Bou‐Gharios George , Jurgen van 't Hof Robert , Daroszewska Anna 
Published: March 2021

AbstractOsteoporosis is the most common age‐related metabolic bone disorder, which is characterized by low bone mass and deterioration in bone architecture, with a propensity to fragility fractures. The best treatment for osteoporosis relies on stimulation of osteoblasts to form new bone and restore bone structure, however, anabolic therapeutics are few and their use is time restricted. Here, we report that Syndecan‐3 increases new bone formation through enhancement of WNT signaling in osteoblasts. Young adult Sdc3−/− mice have low bone volume, reduced bone formation, increased bone marrow adipose tissue, increased bone fragility, and a blunted anabolic bone formation response to mechanical loading. This premature osteoporosis‐like phenotype of Sdc3−/− mice is due to delayed osteoblast maturation and impaired osteoblast function, with contributing increased osteoclast‐mediated bone resorption. Indeed, overexpressing Sdc3 in osteoblasts using the Col1a1 promoter rescues the low bone volume phenotype of the Sdc3−/− mice, and also increases bone volume in WT mice. Mechanistically, SDC3 enhances canonical WNT signaling in osteoblasts through stabilization of Frizzled 1, making SDC3 an attractive target for novel bone anabolic drug development.
Identifying Core Components of EPA Implementation: A Path to Knowing if a Complex Intervention Is Being Implemented as Intended
Authors: Carraccio Carol , Martini Abigail , Van Melle Elaine , Schumacher Daniel J. 
Published: March 2021

Purpose
Competency-based assessment, using entrustable professional activities (EPAs), is rapidly being implemented worldwide without sufficient agreement on the essential elements of EPA-based assessment. The rapidity of implementation has left little time to understand what works in what circumstances and why or why not. The result is the attempted execution of a complex service intervention without a shared mental model for features needed to remain true to implementing an EPA assessment framework as intended. The purpose of this study was to identify the essential core components necessary to maintain integrity in the implementation of this intended intervention.

Method
A formal consensus-building technique, the Delphi process, was used to identify core components for implementing an EPA-based assessment framework. Twelve EPA experts from the United States, Canada, and the Netherlands participated in this process in February and March 2020. In each Delphi round, participants rated possible core components on a scale from 1 to 6, with 1 reflecting the worst fit and 6 the best fit for EPA-based assessment implementation. Predetermined automatic inclusion and exclusion criteria for candidate core components were set at ≥ 80% of participants assigning a value of 5 or 6 and ≥ 80% assigning a value of 1 or 2, respectively.

Results
After 3 rounds, participants prioritized 10 of 19 candidate core components for inclusion: performance prediction, shared local mental model, workplace assessment, high-stakes entrustment decisions, outcomes based, value of the collective, informed clinical competency committee members, construct alignment, qualitative data, and entrustment decision consequences. The study closed after 3 rounds on the basis of the rankings and comments.

Conclusions
Using the core components identified in this study advances efforts to implement an EPA assessment framework intervention as intended, which mitigates the likelihood of making an incorrect judgment that the intervention demonstrates negative results.
Four-level Anterior Cervical Discectomy and Fusions
Authors: Jack Megan M. , Lundy Paige , Reeves Alan R. , Arnold Paul M. 
Published: March 2021

Study Design:
A retrospective review of prospectively collected case series.

Objective:
This is a retrospective review of prospectively collected data regarding the clinical outcomes, complications, and fusion rates of patients who underwent a 4-level (C3–C7) anterior cervical discectomy and fusion (ACDF).

Summary of Background:
The use of multilevel ACDF for cervical spondylosis has been controversial. The literature regarding fusion rates and outcomes have been variable. This study intends to evaluate the outcomes following multilevel ACDF in a large cohort of patients.

Clinical Materials and Methods:
Between 1994 and 2011, 60 patients underwent a 4-level ACDF by a single surgeon. All patients were followed for a minimum of 12 months, and outcome measures included neurological findings, presence or absence of radiographic fusion, and complication rates. All patients had radiographic documentation of spinal cord stenosis at 4 consecutive cervical levels as well as myelopathy and/or radiculopathy symptoms.

Results:
Forty-eight patients underwent a single anterior procedure, only 5 patients underwent concurrent anterior and posterior fusion, and 7 patients required a second posterior surgery due to new-onset or residual symptoms or hardware complications after undergoing ACDF. Patients most commonly presented with paresthesias and were diagnosed with cervical stenosis. Overall, 18.3% reported early postoperative dysphagia; however, only 2 patients continued to have mild dysphagia symptoms on long-term follow-up. Other complications included hardware failure (11), residual neck pain (7), residual paresthesias (6), new-onset weakness (3), neck hematoma (1), cellulitis (1), and C5 radiculopathy (1). Overall, 88.3% of patients reported improvement in initial symptoms. Nurick scores were significantly lower following 4-level ACDF. The radiographic fusion rate for all levels was 95%. No patients required reoperation for pseudarthrosis.

Conclusion:
In appropriate patients, 4-level ACDF is a safe, efficacious method for treating multilevel cervical spinal cord compression, with acceptable complication rates and the ability to achieve neurological improvement and high fusion rates.
Surgical Treatment for Cervical Spine Fracture in Patients With Ankylosing Spondylitis
Authors: Liu Bingchuan , Ji Hongquan , Zhang Zhishan , Guo Yan , Lv Yang , Yang Zhongwei , Hou Guojin , Zhou Fang , Tian Yun 
Published: March 2021

Study Design:
A retrospective single-center study.

Objective:
We aimed to compare the clinical outcomes of cervical spine fracture accompanied with ankylosing spondylitis (ASCSF) treated by single posterior approach (PA) and combined anterior-posterior approach (CA) for patients who were followed up for >1 year,

Summary of Background Data:
For ASCSF patients, surgical treatment has been widely accepted as a recommendable therapeutic option. But the optimal surgical approach is still under controversy, and few studies have focused on the comparison between PA and CA.

Materials and Methods:
From February 2007 to March 2019, 53 patients were enrolled and divided into the PA group (34 cases) and CA group (19 cases). Their general characteristics and clinical materials were recorded. From the aspects of reduction distance, bone fusion, neurological functional restoration, and postoperative complications, patients’ surgical outcomes were evaluated qualitatively and quantitatively.

Results:
The reduction degree of dislocation (mean PA=2.05 mm, mean CA=2.36 mm, P=0.94) was close between the 2 groups. Besides, with a similar follow-up period (P=0.10), the rate of bone fusion (both 100%) and neurological functional restoration (PA=31.03%, CA=35.29%, P=0.77) were also without significant difference. The occurrence rate of postoperative complications tended to be higher in the CA group (31.58% vs. 23.53%) but with no significant difference (P=0.52). Nevertheless, the surgical duration time (mean=209.15 min) and blood loss (average=388.91 mL) of PA group were significantly less than CA group (mean duration time=285.34 min, mean blood loss=579.27 mL) (P<0.01).

Conclusions:
Compared with to the CA approach and with the equally significant outcome, surgery by single PA was feasible and should be positively recommended for ASCSF patients, especially for those accompanying with a severe chin-on-chest deformity or poor physical conditions which restrain patients from tolerating a long surgery or major surgical trauma.
Impact of Discharge to Rehabilitation on Postdischarge Morbidity Following Multilevel Posterior Lumbar Fusion
Authors: Song Junho , Katz Austen D. , Perfetti Dean , Job Alan , Morris Matthew , Goldstein Jeffrey , Virk Sohrab , Silber Jeff , Essig David 
Published: March 2021

Study Design:
This was a retrospective cohort study.

Objective:
The objective of this study was to compare 30-day postdischarge morbidity for 3-or-more level (multilevel) posterior lumbar fusion in patients who were discharged to home versus rehabilitation.

Summary of Background Data:
Spine surgery has been increasingly performed in the elderly population, with many of these patients being discharged to rehabilitation and skilled nursing facilities. However, research evaluating the safety of nonhome discharge following spine surgery is limited.

Materials and Methods:
Patients who underwent multilevel posterior lumbar fusion from 2005 to 2018 were identified using the National Surgical Quality Improvement Program (NSQIP) database. Regression was utilized to compare primary outcomes between discharge disposition and to evaluate for predictors thereof.

Results:
We identified 5276 patients. Unadjusted analysis revealed that patients who were discharged to rehabilitation had greater postdischarge morbidity (5.6% vs. 2.6%). After adjusting for baseline differences, discharge to rehabilitation no longer predicted postdischarge morbidity [odds ratio (OR)=1.409, confidence interval: 0.918–2.161, P=0.117]. Multivariate analysis also revealed that age (P=0.026, OR=1.023), disseminated cancer (P=0.037, OR=6.699), and readmission (P<0.001, OR=28.889) independently predicted postdischarge morbidity.

Conclusions:
Thirty days morbidity was statistically similar between patients who were discharged to home and rehabilitation. With appropriate patient selection, discharge to rehabilitation can potentially minimize 30-day postdischarge morbidity for more medically frail patients undergoing multilevel posterior lumbar fusion. These results are particularly important given an aging population, with a great portion of elderly patients who may benefit from postacute care facility discharge following spine surgery.
Immunohistochemical Expression of Galectin-3 in Pemphigus Vulgaris
Authors: Aghighi Maryam , Pukhalskaya Tatsiana , Smoller Bruce R. 
Published: March 2021

Abstract:
Pemphigus vulgaris (PV) is an autoimmune bullous disorder related to immunoglobulin-G autoantibodies against desmoglein-3. Galectin-3 is one of the main elements of the immunoglobulin-E group which is essential in the cell–cell or cell–matrix adhesion. Although the presence of immunoglobulin-E autoantibodies in PV has been observed, no studies have been performed to describe the role of galectin-3 in PV. We evaluated galectin-3 expression in PV as a first step in assessing its impact in the pathogenesis of this autoimmune blistering process. In a retrospective study, 56 specimens from 45 patients diagnosed with PV were stained with antibodies to galectin-3. The percentages of nuclear and cytoplasmic galectin-3 expression as well as staining intensity were evaluated around blisters and adjacent unaffected skin. We observed a significant decrease in galectin-3 cytoplasmic and nuclear expression as well as stain intensity around blisters compared with adjacent unaffected skin. Although autoantibodies against desmogleins trigger the blister formation in PV patients, loss of galectin-3 may play a role in the extension of blister formation by initiating cell–cell disassembly at the level of the intercellular keratinocyte desmosome. We demonstrated a lower expression of galectin-3 around the blisters in PV. The pathogenesis of the blister formation may be related to lower expression of galectin-3. Additional studies are necessary to clarify the result of this outcome and determine the accurate pathogenesis of blister formation in PV.
Radiation therapy for uveal melanoma: a review of treatment methods available in 2021
Authors: Reichstein David A. , Brock Anderson L. 
Published: March 2021

Purpose of review
Radiation therapy has become the standard of care for the treatment of uveal melanoma. We intend to outline the current radiation therapy methods that are employed to treat uveal melanoma. We will outline their relative benefits over one another. We will also provide some background about radiation therapy in general to accustom the ophthalmologists likely reading this review.

Recent findings
Four main options exist for radiation therapy of uveal melanoma. Because the eye is a small space, and because melanomas are relatively radioresistant, oncologists treating uveal melanoma must deliver highly focused doses in high amounts to a small space. Therapies incorporating external beams include proton beam therapy and stereotactic radiosurgery. Stereotactic radiosurgery comes in two forms, gamma knife therapy and cyberknife therapy. Radiation may also be placed directly on the eye surgically via plaque brachytherapy. All methods have been used effectively to treat uveal melanoma.

Summary
Each particular radiotherapy technique employed to treat uveal melanoma has its own set of benefits and drawbacks. The ocular oncologist can choose amongst these therapies based upon his or her clinical judgment of the relative risks and benefits. Availability of the therapy and cost to the patient remain significant factors in the ocular oncologist's choice.
New treatment algorithm for keratoconus and cataract: small-aperture IOL insertion with sequential topography-guided photorefractive keratectomy and simultaneous accelerated corneal crosslinking
Authors: Northey Luke C. , Holland Simon P. , Lin David T.C. , Moloney Gregory 
Published: March 2021

Purpose:
To describe a new treatment algorithm aimed at optimizing refractive outcomes for patients with keratoconus and cataract.

Setting:
Private practice in Sydney, Australia.

Design:
Retrospective case series.

Methods:
This procedural approach involves cataract extraction with small-aperture intraocular lens (IOL) insertion, IC-8 IOL (AcuFocus, Inc.), followed by topography-guided photorefractive keratectomy (T-PRK) with simultaneous corneal crosslinking (CXL). Cataract surgery was performed with an initial 2.4 mm clear corneal incision enlarged to 3.5 mm to accommodate IC-8 IOL insertion. Once eyes demonstrated stable corneal tomography and refraction, T-PRK was performed using Schwind excimer laser (500 Hz) with the Vancouver custom topographical neutralization technique, aiming to achieve low myopia. CXL was performed immediately after T-PRK using Optolink hypotonic riboflavin with LIGHTLink-CXL (Lightmed) with 5.4 J total energy delivered at an 18 mw/cm2 irradiance.

Results:
Outcomes of 4 eyes are reported with all achieving rigid gas-permeable (RGP) contact lens independence, improved corrected distance visual acuity (CDVA) and uncorrected distance visual acuity (UDVA), and regularization of corneal curvature with cone reduction. The mean CDVA improved from 0.43 preoperatively to 0.07 postoperatively (P = .00), and the mean UDVA improved from 0.81 preoperatively to 0.29 postoperatively (P = .04). Postoperative UNVA ranged from N.8 to N.12.

Conclusions:
This treatment algorithm demonstrates unique combination of existing corneal and cataract surgical procedures to achieve satisfactory refractive outcomes and RGP contact lens independence in patients with keratoconus and cataract.
Experimental study of occlusion break surge volume in 3 different phacoemulsification systems
Authors: Miller Kevin M. , Dyk David W. , Yalamanchili Satish 
Published: March 2021

Purpose:
To evaluate surge volume after occlusion breaks in 3 different phacoemulsification systems.

Setting:
Alcon Research LLC, Lake Forest, California.

Design:
Experimental study.

Methods:
A mechanical spring eye model was used to test the Centurion with Active Sentry, WhiteStar Signature Pro, and Stellaris PC. Raw oscilloscope data were converted to volumetric and pressure measurements. Fitted average surge traces were generated for each test condition and used to develop an interpolation algorithm to predict transient occlusion break surge events. Two-dimensional heat maps were generated.

Results:
During occlusion break surge, the Centurion with Active Sentry had smaller aqueous volume losses than the WhiteStar or Stellaris PC. Maximum surge volumes within the mechanical spring eye model displacement limit were 74.7 μL, 157.5 μL, and 151.7 μL using Centurion with Active Sentry, WhiteStar, and Stellaris PC, respectively. In the aphakic state, heat maps showed that Centurion with Active Sentry had less than 20% aqueous volume loss across all vacuum limits and target intraocular pressure; WhiteStar and Stellaris PC systems had up to 35% and 50% aqueous volume losses, respectively, at the higher vacuum limits. In the phakic state, Centurion with Active Sentry had up to 30% aqueous volume loss and WhiteStar and Stellaris PC systems had up to 50% aqueous volume losses. In addition, predicted transient traces demonstrated that Centurion with Active Sentry had the lowest percentage simulated aqueous volume loss compared with WhiteStar or Stellaris PC.

Conclusions:
Centurion with Active Sentry had lower aqueous volume losses after occlusion break than WhiteStar and Stellaris PC systems at all surgical settings.
Visual outcomes after optic exchange of a modular intraocular lens
Authors: Ang Robert Edward T. , Yoo Paul , Liu Jingbo 
Published: March 2021

Purpose:
To evaluate the effectiveness of the Harmoni Modular IOL (HMIOL).

Setting:
3 study sites.

Design:
Prospective, multicenter clinical study.

Methods:
HMIOL is a foldable, posterior chamber lens with separate base and exchangeable optic components. Eligible adults undergoing cataract surgery received HMIOL in the study eye (monovision target −1.50 diopters [D]) and standard monofocal IOL in contralateral eye (control). After 3 months, subjects could undergo optic exchange based on visual outcomes. End points included uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and manifest refractive spherical equivalent (MRSE). Follow-up was 12 months or greater postoperatively.

Results:
114 subjects had successful HMIOL implantation in study eye and control IOL in contralateral eye. At 3 months, subjects could undergo optic exchange if unsatisfied with monovision; 65 eyes had optic exchange (exchange cohort), and 49 eyes had no exchange (no exchange cohort). In exchange cohort, the proportion of eyes with UDVA of 20/40 or greater and of 20/20 or greater increased 3 months after optic exchange vs preexchange levels by 23% (97% vs 74%) and 40% (49% vs 9%), respectively. In all cohorts, 95% of subjects or greater achieved UDVA of 20/40 or greater after 12 months or greater. Control and no exchange cohorts achieved CDVA of 20/40 or greater by 3 months; 97% of eyes or greater had CDVA of 20/40 or greater at 12 months after optic exchange. In exchange cohort, the proportion of eyes with MRSE within ±0.50 D and ±1.00 D of target changed by 57% and 36%, respectively, from preexchange (20% and 59%, respectively) to 12 months postexchange (77% and 95%, respectively), reaching levels similar to control subjects (72% and 97%, respectively).

Conclusions:
HMIOL provided visual outcomes comparable with standard monofocal IOLs.
Encoding of cutaneous stimuli by lamina I projection neurons
Authors: Chisholm Kim I. , Lo Re Laure , Polgár Erika , Gutierrez-Mecinas Maria , Todd Andrew J. , McMahon Stephen B. 
Published: March 2021

Abstract
Lamina I of the dorsal horn, together with its main output pathway, lamina I projection neurons, has long been implicated in the processing of nociceptive stimuli, as well as the development of chronic pain conditions. However, the study of lamina I projection neurons is hampered by technical challenges, including the low throughput and selection biases of traditional electrophysiological techniques. Here we report on a technique that uses anatomical labelling strategies and in vivo imaging to simultaneously study a network of lamina I projection neurons in response to electrical and natural stimuli. Although we were able to confirm the nociceptive involvement of this group of cells, we also describe an unexpected preference for innocuous cooling stimuli. We were able to characterize the thermal responsiveness of these cells in detail and found cooling responses decline when exposed to stable cold temperatures maintained for more than a few seconds, as well as to encode the intensity of the end temperature, while heating responses showed an unexpected reliance on adaptation temperatures.