bluuebunny/crossref_metadata_2025_split huggingface dataset:
Developmental exposure to the Parkinson’s disease-associated organochlorine pesticide dieldrin alters dopamine neurotransmission in α-synuclein pre-formed fibril (PFF)-injected mice
Authors: Boyd Sierra L , Kuhn Nathan C , Patterson Joseph R , Stoll Anna C , Zimmerman Sydney A , Kolanowski Mason R , Neubecker Joseph J , Luk Kelvin C , Ramsson Eric S , Sortwell Caryl E , Bernstein Alison I 
Published: August 2023

Abstract
Parkinson’s disease (PD) is the fastest-growing neurological disease worldwide, with increases outpacing aging and occurring most rapidly in recently industrialized areas, suggesting a role of environmental factors. Epidemiological, post-mortem, and mechanistic studies suggest that persistent organic pollutants, including the organochlorine pesticide dieldrin, increase PD risk. In mice, developmental dieldrin exposure causes male-specific exacerbation of neuronal susceptibility to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and synucleinopathy. Specifically, in the α-synuclein (α-syn) pre-formed fibril (PFF) model, exposure leads to increased deficits in striatal dopamine (DA) turnover and motor deficits on the challenging beam. Here, we hypothesized that alterations in DA handling contribute to the observed changes and assessed vesicular monoamine transporter 2 (VMAT2) function and DA release in this dieldrin/PFF 2-hit model. Female C57BL/6 mice were exposed to 0.3 mg/kg dieldrin or vehicle every 3 days by feeding, starting at 8 weeks of age and continuing throughout breeding, gestation, and lactation. Male offspring from independent litters underwent unilateral, intrastriatal injections of α-syn PFFs at 12 weeks of age, and vesicular 3H-DA uptake assays and fast-scan cyclic voltammetry were performed 4 months post-PFF injection. Dieldrin-induced an increase in DA release in striatal slices in PFF-injected animals, but no change in VMAT2 activity. These results suggest that developmental dieldrin exposure increases a compensatory response to synucleinopathy-triggered striatal DA loss. These findings are consistent with silent neurotoxicity, where developmental exposure to dieldrin primes the nigrostriatal striatal system to have an exacerbated response to synucleinopathy in the absence of observable changes in typical markers of nigrostriatal dysfunction and degeneration.
GNAQ R183Q somatic mutation contributes to aberrant arteriovenous specification in Sturge–Weber syndrome through Notch signaling
Authors: Huang Lulu , Sun Hao , Liu Yixin , Xu Li , Hu Menghan , Yang Yijie , Wang Ning , Wu Yue , Guo Wenyi 
Published: August 2023

AbstractEpiscleral vasculature malformation is a significant feature of Sturge–Weber syndrome (SWS) secondary glaucoma, the density and diameter of which are correlated with increased intraocular pressure. We previously reported that the GNAQ R183Q somatic mutation was located in the SWS episclera. However, the mechanism by which GNAQ R183Q leads to episcleral vascular malformation remains poorly understood. In this study, we investigated the correlation between GNAQ R183Q and episcleral vascular malformation via surgical specimens, human umbilical vein endothelial cells (HUVECs), and the HUVEC cell line EA.hy926. Our findings demonstrated a positive correlation between episcleral vessel diameter and the frequency of the GNAQ R183Q variant. Furthermore, the upregulation of genes from the Notch signaling pathway and abnormal coexpression of the arterial marker EphrinB2 and venous marker EphB4 were demonstrated in the scleral vasculature of SWS. Analysis of HUVECs overexpressing GNAQ R183Q in vitro confirmed the upregulation of Notch signaling and arterial markers. In addition, knocking down of Notch1 diminished the upregulation of arterial markers induced by GNAQ R183Q. Our findings strongly suggest that GNAQ R183Q leads to malformed episcleral vasculatures through Notch‐induced aberrant arteriovenous specification. These insights into the molecular basis of episcleral vascular malformation will provide new pathways for the development of effective treatments for SWS secondary glaucoma.
Clinical Practice Guideline Recommendations in Pediatric Orthopaedic Injury: A Systematic Review
Authors: Moore Lynne , Drager Justin , Freire Gabrielle , Yanchar Natalie , Miller Anna N. , Ben Abdel Anis , Bérubé Mélanie , Tardif Pier-Alexandre , Gnanvi Janyce , Stelfox Henry T. , Beaudin Marianne , Stang Antonia , Beno Suzanne , Weiss Matthew , Labrosse Melanie , Zemek Roger , Gagnon Isabelle J. , Beaulieu Emilie , Berthelot Simon , Klassen Terry , Turgeon Alexis F. , Lauzier François , Gabbe Belinda , Carsen Sasha 
Published: August 2023

Background:
Lack of adherence to recommendations on pediatric orthopaedic injury care may be driven by lack of knowledge of clinical practice guidelines (CPGs), heterogeneity in recommendations or concerns about their quality. We aimed to identify CPGs for pediatric orthopaedic injury care, appraise their quality, and synthesize the quality of evidence and the strength of associated recommendations.

Methods:
We searched Medline, Embase, Cochrane CENTRAL, Web of Science and websites of clinical organizations. CPGs including at least one recommendation targeting pediatric orthopaedic injury populations on any diagnostic or therapeutic intervention developed in the last 15 years were eligible. Pairs of reviewers independently extracted data and evaluated CPG quality using the Appraisal of Guidelines Research and Evaluation (AGREE) II tool. We synthesized recommendations from high-quality CPGs using a recommendations matrix based on the GRADE Evidence-to-Decision framework.

Results:
We included 13 eligible CPGs, of which 7 were rated high quality. Lack of stakeholder involvement and applicability (i.e., implementation strategies) were identified as weaknesses. We extracted 53 recommendations of which 19 were based on moderate or high-quality evidence.

Conclusions:
We provide a synthesis of recommendations from high-quality CPGs that can be used by clinicians to guide treatment decisions. Future CPGs should aim to use a partnership approach with all key stakeholders and provide strategies to facilitate implementation. This study also highlights the need for more rigorous research on pediatric orthopaedic trauma.

Level of Evidence:
Level II—therapeutic study.
The Evolving Therapeutics of Endothelial Disease
Authors: Huertas-Bello Marcela , Sabater Alfonso L. , Koo Ellen H. 
Published: August 2023

Abstract:
Endothelial dysfunction is one of the leading indications for corneal transplantation. Globally, there is a shortage of donor corneas, which is partly because of the lack of eye banking resources in emerging countries. Given this global shortage, there is naturally heightened interest surrounding pharmacological agents, genetic therapy, and endothelial cell–based therapeutic modalities. Endothelial cells have limited mitotic capacity in vivo, and thus, studies have been conducted for their ex vivo expansion using mitogens. Similarly, pluripotent stem cells have been used to differentiate into human corneal endothelial cells with varying degrees of success. Different strategies have also been developed for injecting and delivering these cells into the human eye. This review aims to compile the information published on the latest advances in endothelial disease therapy.
A Retrospective Study Analyzing Opioid Prescription Practices in Hand Surgery from 2013 to 2019
Authors: Rangel India , Harrington Maya T. , Movtchan Nellie V. , Kandi Lyndsay A. , Janbieh Javier , Pollock Jordan R. , Kruger Erwin , Ko Jason H. , Teven Chad M. 
Published: August 2023

Background:
The potential for opioid prescription medication addiction and abuse has been a growing concern in healthcare. It is not uncommon for hand surgery patients to be overprescribed opioid medication for postoperative pain management. The objective of this study was to characterize changes in opioid prescription practices of hand surgeons treating Medicare Part D patients from 2013 to 2019.

Methods:
A retrospective analysis of Medicare Part D prescriber data from 2013 to 2019 was conducted. This database provides information on drugs paid for under the Medicare Part D Prescription Drug Program. For each prescriber and medication, the dataset includes the total number of prescriptions dispensed (original prescriptions and number of refills), and total medication cost.

Results:
In 2013, the 10 most common medications prescribed totaled 114,409 prescriptions, with 89,701 (78.4%) opioid prescriptions. In 2019, the 10 most common medications prescribed totaled 164,955 prescriptions, with 109,665 (66.5%) opioid prescriptions. Although total opioid prescriptions dropped, there was a 22% increase in the total number of prescriptions written. The two most common medications prescribed, hydrocodone-acetaminophen and oxycodone-acetaminophen, totaled 75,796 in 2013, compared with 76,518 in 2019. The overall number of prescriptions for nonsteroidal anti-inflammatory drugs increased by 157%, and the percentage of total opioids prescribed declined by 7.9%.

Conclusions:
The increase in total opioid prescriptions from 2013 to 2019 by hand surgeons in the Medicare Part D Prescription Drug Program lags behind the recommended shift to nonopioid pain management. The reasons for the overall rise in prescriptions deserve further exploration.
Workplace Bias Affecting Applicants to Independent Plastic Surgery Residencies
Authors: Weidman Allan A. , Hernandez Alvarez Angelica , Valentine Lauren , Manstein Samuel M. , Comer Carly , Foppiani Jose , Sarac Benjamin A. , Janis Jeffrey E. , Lin Samuel J. 
Published: August 2023

Background:
This study explores factors that encourage residents to apply to independent plastic surgery residencies to gain insight into whether they faced bias as a result of this decision.

Methods:
Resident applicants who applied to two academic independent plastic surgery residencies in 2021 and 2022 were emailed a survey consisting of 25 questions. Responses were collected anonymously and analyzed. Descriptive statistics were performed, and subgroup analyses were conducted with Fisher exact and Pearson χ
2 testing.

Results:
Thirty-nine complete responses were included for analysis (response rate 22.7%). Participants were asked what encouraged them to go into plastic surgery during residency. The most common reasons were scrubbing in on plastic surgery cases and interactions with plastic surgery faculty/residents, with each reason cited by 30 respondents (76.8%). Further, 20.5% of residents agreed or strongly agreed that they felt unsupported by their program director in their decision to apply into plastic surgery. Likewise, 64.1% of respondents agreed or strongly agreed to having experienced demeaning comments or jokes by faculty about their choice of plastic surgery. Consequently, 17.9% agreed or strongly agreed that they developed stress or anxiety due to how co-residents and/or faculty treated them regarding their decision to pursue plastic surgery.

Conclusions:
General surgery residents planning to apply to independent plastic surgery residency may experience workplace biases related to their career decision. An important opportunity exists to support independent applicants and to provide mentorship.
Outcomes and Early Complications Using an Endothelium-in Pull-Through Descemet Membrane Endothelial Keratoplasty Technique With Preloaded Versus Surgeon-Loaded Donor Tissue in Fuchs Patients
Authors: Cho Kyongjin , Ali Muhammad , Heckenlaible Nicolas J. , Jabbour Samir , Jun Albert S. , Srikumaran Divya 
Published: August 2023

Purpose:
This study aimed to compare outcomes and early complications using an endothelium-in pull-through Descemet membrane endothelial keratoplasty (DMEK) technique with preloaded versus surgeon-loaded donor tissue.

Methods:
Data from 163 eyes of 125 patients at the Wilmer Eye Institute diagnosed with Fuchs endothelial corneal dystrophy who underwent DMEK with or without cataract extraction using surgeon-loaded tissue (n = 83) or preloaded tissue (n = 80) were reviewed. Best-corrected visual acuity and early postoperative complications including small graft detachment (less than one third of the graft area), large graft detachment (more than one third), graft failure, and rebubbling were compared.

Results:
Baseline characteristics including age, sex, and visual acuity were not statistically different between the groups. Small graft detachment was observed in 18.1% of the surgeon-loaded and 22.5% of the preloaded group (P = 0.48), whereas large detachment occurred in 12.0% and 5.0%, respectively (P = 0.11). Among these, rebubbling was performed in 18 (21.7%) in the surgeon-loaded compared with 12 (15.0%) in the preloaded group (P = 0.27). The rebubbling rate of the combined procedure (cataract surgery and DMEK) was 21.8% and of DMEK alone was 7.7% (P = 0.048). Primary graft failure occurred in 2 surgeon-loaded cases (2.4%) and 1 preloaded case (1.3%) (P = 0.58). There was no difference in postoperative best-corrected visual acuity at 1 year (logarithm of the minimum angle of resolution 0.21 ± 0.25 for the surgeon-loaded vs. 0.16 ± 0.16 for the preloaded group, P = 0.23).

Conclusions:
DMEK surgery using preloaded endothelium-in tissue has comparable outcomes with surgeon-loaded endothelium-in tissue. However, there was a trend toward the lower rebubbling rate in DMEK alone compared with combined procedures.
Extended frontalis orbicularis oculi muscle flap shortening for treating refractory apraxia of eyelid opening associated with blepharospasm
Authors: Wang Yu-Chi , Lai Ya-Wei , Lee Chia-Chen , Huang Shu-Hung , Kuo Yur-Ren , Lai Chung-Sheng 
Published: August 2023

Background:
Refractory apraxia of eyelid opening (AEO) is mostly unresponsive to botulinum toxin (BTx) and inevitably leads to functional blindness. To treat this challenging condition, an innovative surgical technique was proposed.

Methods:
The extended frontalis orbicularis oculi muscle (FOOM) flap shortening consisting of frontalis suspension, partial myectomy, and myotomy in situ of eyelid protractors was applied to treat refractory AEO associated with blepharospasm. The postoperative outcomes and patient satisfaction were evaluated.

Results:
Seven patients (mean ages 64.1 ± 3.9 years) of 14 eyelids in total had an average flap shortening distance of 24.4 ± 1.3 mm. During a mean follow-up of 31.6 ± 11.4 months, the average BTx dosage reduced from 58.6 ± 12. 1 units to 30.0 ± 8.2 units, with a mean injection interval decreasing from 2.3 ± 0.5 months to 4.1 ± 0.9 months (p < 0.05). Palpebral fissure height increased from 1.4 ± 0.5 mm to 7.9 ± 0.7 mm, and the disability scale decreased from 78.8% ± 7.2% to 12.6% ± 7.0% (p < 0.05). The postoperative BTx dosage and frequency were significantly reduced. All patients restored voluntary eyelid opening and reported high postoperative satisfaction (average Likert scale 4.6 ± 0.5).

Conclusion:
Extended FOOM flap shortening is an effective treatment to solve refractory AEO associated with blepharospasm.
Budd–Chiari Syndrome following COVID-19 infection: a case report
Authors: Sawaqed Seri S. , Urabi Heba M. , Al-thnaibat Mohammad H. , Bani-Hani Anas , Mohd Omar B. , Mohd Ahmed B. , Ghannam Reem A. , Hasan Hanan , Alabdallat Yasmeen J. , Khaity Abdulrhman 
Published: August 2023

Introduction and importance:
Budd–Chiari Syndrome (BCS) is a rare disorder that affects the liver and is caused by blockage of the hepatic veins. Coronavirus disease 2019 (COVID-19) has been linked to an increased risk of developing BCS due to its ability to cause inflammation in the body, which can lead to clotting disorders.

Case presentation:
A 43-year-old female presented to the emergency department complaining of severe epigastric and right upper quadrant pain and progressive abdominal distention. Upon examination, investigation, and triphasic liver computed tomography with contrast, the patient was diagnosed with BCS.

Clinical discussion:
The patient was started on anticoagulant therapy with low-molecular-weight heparin and supportive treatment. She was hospitalized for 3 weeks and discharged on oral warfarin 5 mg/day after showing clinical improvement.

Conclusion:
Hepatosplenomegaly and abdominal distention after COVID-19 infection raise suspicion for BCS. Therefore, early detection of these signs is essential for immediate management.
Genetic Correlations between Migraine and Carpal Tunnel Syndrome
Authors: Wiberg Akira , Lucey Maria A. , Kleeman Sam , Kang Youngjoo , Ng Mike , Furniss Dominic 
Published: August 2023

Background:
Surgical deactivation of extracranial nerve trigger sites is now well established as an effective treatment for migraine headache. Parallels have been drawn to median nerve decompression for carpal tunnel syndrome (CTS), and 2 previous studies have demonstrated an association between migraine and CTS. The authors sought to (1) substantiate these findings in a considerably larger UK cohort, and (2) investigate potential genetic associations between the 2 disorders.

Methods:
Nested case-control studies were conducted in the UK Biobank cohort of 401,656 individuals. Odds ratios were calculated for the association between migraine and CTS in the overall cohort and sex-stratified subsets. Genetic correlation between migraine and CTS was interrogated by linkage disequilibrium score regression, leveraging data from published genomewide association studies. Regions of genetic overlap were identified by multitrait analysis of genomewide association studies and cross-phenotype association.

Results:
Migraine and CTS show a significant epidemiologic association within UK Biobank (OR, 1.14, 95% CI, 1.04 to 1.25; P = 0.0058), which is specific to women (OR, 1.15; 95% CI, 1.04 to 1.28; P = 0.0057) and not men (OR, 1.07; 95% CI, 0.82 to 1.40; P = 0.61). Genetic analysis demonstrated a significant positive genetic correlation between the 2 disorders (r
g = 0.13; P = 0.0039), and implicated the TRIM32 locus on chromosome 9 as a region of genetic overlap.

Conclusions:
This study replicates past reports of an epidemiologic association between CTS and migraine, albeit in women only. This association is underpinned by a genetic correlation, with shared genetic susceptibility at the TRIM32 locus. The authors’ data add credibility to the notion that an element of entrapment neuropathy underlies migraine pathophysiology.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Risk, III.
Replacement of Shaped Textured Implants with Round Smooth Implants in Breast Reconstruction: Long-Term Outcomes
Authors: Ayyala Haripriya S. , Afifi Tarek , Castel Nikki , McCarthy Colleen , Cordeiro Peter G. 
Published: August 2023

Background:
The number of patients undergoing exchange of textured implants for smooth devices has greatly increased because of concern over breast implant–associated anaplastic large-cell lymphoma (BIA-ALCL). The authors examined long-term patient- and surgeon-reported outcomes in terms of aesthetics, comfort, and complications.

Methods:
Patients who underwent reconstruction with shaped, textured implants replaced with round, smooth implants between 1994 and 2022 and who had a minimum follow-up of 1 year were included. Patient-reported outcomes were collected using the BREAST-Q Reconstruction module and a survey evaluating aesthetics and comfort. Surgeon-reported outcomes included evaluation of aesthetics and capsular contracture.

Results:
A total of 530 patients were reviewed, and 307 patients were included. Pairwise comparison of BREAST-Q data demonstrated that psychosocial well-being (72.68 to 76.45; P = 0.0075) and physical well-being (78.79 to 81.88; P = 0.0078) increased significantly. Overall breast satisfaction (61.94 to 67.27; P = 0.0082) and sexual well-being (53.89 to 57.98; P = 0.0002) were also significantly higher in parallel with a clinically meaningful increase in BREAST-Q score of 5.33 and 4.09 points, respectively. Most patients felt they appeared better (56.4%) or similar (27.3%) and were more comfortable (54.4%) or similar (39.4%) after the exchange procedure. The senior surgeon (P.G.C.) rated 40.1% of patients as having a better aesthetic grade after replacement and 50.3% as the same; 36.8% of patients were rated as having a decrease in Baker capsular contracture grade; 2.9% of patients experienced a perioperative complication; and there were no reconstructive failures.

Conclusion:
Exchange of textured to smooth implants is safe, does not sacrifice aesthetic outcome, and provides a more comfortable and satisfactory outcome for patients with minimal complications.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, IV.
Bilateral Lumbar Artery Perforator Flaps for Breast Reconstruction: A Perforator Classification System
Authors: Haddock Nicholas T. , Lakatta Alexis C. , Teotia Sumeet S. 
Published: August 2023

Background:
Autologous breast reconstruction is continually evolving, with focus on the ideal donor site. This study presents 108 consecutive simultaneous lumbar artery perforator (LAP) flaps and a perforator classification system.

Methods:
A retrospective review of all LAP flaps was completed, and appropriate data were recorded. All simultaneous bilateral LAP flaps were included, and perforator patterns were assessed using CT angiography (CTA).

Results:
Fifty-four patients (108 flaps) were included in the final review. The mean patient age was 50.7 years, and the mean body mass index was 26.6. Mean ischemia times for all flaps and grafts were 130 ± 64.5 and 300.6 ± 97.3 minutes, respectively. The average pedicle length was 4.6 ± 1.5 cm, and the average composite graft length was 6.2 ± 1.7 cm. Donor-site complications consisted of seromas (10 patients [19%]), hematomas (6 patients [11%]), procedural wounds (4 patients [8%]), and infections (2 patients [4%]). The total flap loss rate was 2.8%. Perforators were classified into categories based on pedicle pattern, lumbar spine level, and clusters, all in relation to posterior iliac bone as seen per CTA. Vascular pedicle patterns were categorized as type 1 (43.9%), 2 (45.6%), 3 (8.8%), or 4 (1.8%). Perforators were dissected at lumbar spine level L3 in 51.8% of patients, L4 in 46.5%, and L5 in 1.8%.

Conclusions:
The authors present a CTA-directed anatomic perforator classification system to assist in preoperative planning, dissection, and choice of the composite graft best suited for particular perforator patterns or calibers. Simultaneous LAP flaps can be performed successfully with excellent outcomes in cases unsuitable for other flaps.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, IV.