bluuebunny/crossref_metadata_2025_split huggingface dataset:
Consumer Awareness and Comfort with Resident-run Cosmetic Clinics: A Crowdsourcing Study
Authors: Hemal Kshipra , Cignetti Natalie E. , Newsom Megan R. , David Lisa R. 
Published: July 2021

Background:
Resident cosmetic clinics (RCCs) are the training modality of choice among both residents and faculty and are a mainstay at most residency programs.
1–4
Despite this, knowledge of RCCs among plastic surgery consumers remains untested. We hypothesize that the public would be aware of and receptive to RCCs.

Methods:
Participants with prior cosmetic procedures or interest in future cosmetic procedures were recruited using Amazon Mechanical Turk and asked to complete a survey in September 2020. First, prior awareness of RCCs was assessed. After a brief description of RCCs, perceptions of safety and preferences for care were assessed.

Results:
After screening for quality, 815 responses were included. Forty-five percent of consumers were aware of RCCs. Seventy-six percent of consumers believed that RCCs were just as safe as attending clinics and 65% were comfortable receiving care from fourth-year residents or higher. Belief in RCC safety was associated with 4.8 times higher odds of feeling comfortable receiving care at an RCC [95% confidence interval (3.3–7.1), P < 0.001]. When given a hypothetical choice between residents and attendings in two scenarios, 46% of consumers chose residents for abdominoplasty and 60% chose residents for Botox injections. Belief in RCC safety was associated with choosing a resident or being indifferent in both scenarios.

Conclusions:
Consumer preference regarding RCCs has largely been untested. This study shows that belief in RCC safety influences consumers’ perceived comfort with receiving care at an RCC. This knowledge can help guide RCC practice and maximize learning opportunities for surgeons-in-training.
Comparison of Complication Risk for Open Carpal Tunnel Release: In-office versus Operating Room Settings
Authors: Randall Dustin J. , Peacock Kate , Nickel Katelin B. , Olsen Margaret , Tyser Andrew R. , Kazmers Nikolas H. 
Published: July 2021

Background:
Performing open carpal tunnel release (oCTR) in an office-based procedure room setting (PR) decreases surgical costs when compared with the operating room (OR). However, it is unclear if the risk of major medical, wound, and iatrogenic complications differ between settings. Our purpose was to compare the risk of major medical complications associated with oCTR between PR and OR settings.

Methods:
Utilizing the MarketScan Database, we identified adults undergoing isolated oCTR between 2006 and 2015 performed in PR and OR settings. ICD-9-CM and/or CPT codes were used to identify major medical complications, surgical site complications, and iatrogenic complications within 90 days of oCTR. Multivariable logistic regression was used to compare complication risk between groups.

Results:
Of the 2134 PR and 76,216 OR cases, the risk of major medical complications was 0.89% (19/2134) and 1.20% (914/76,216), respectively, with no difference observed in the multivariable analysis (adjusted odds ratio [OR] 0.84; 95% CI 0.53–1.33; P = 0.45). Risk of surgical site complications was 0.56% (12/2134) and 0.81% (616/76,216) for the PR and OR, respectively, with no difference in the multivariable analysis (OR 0.68; 95% C.I. 0.38–1.22; P = 0.19). Iatrogenic complications were rarely observed (PR 1/2134 [0.05%], OR 71/76,216 [0.09%]), which precluded multivariable modeling.

Conclusion:
These results support a similar safety profile for both the PR and OR surgical settings following oCTR with similar pooled major medical complications, pooled wound/surgical site complications, and iatrogenic complications.
Antagonism of the mu-delta opioid receptor heterodimer enhances opioid antinociception by activating Src and calcium/calmodulin-dependent protein kinase II signaling
Authors: Keresztes Attila , Olson Keith , Nguyen Paul , Lopez-Pier Marissa A. , Hecksel Ryan , Barker Natalie K. , Liu Zekun , Hruby Victor , Konhilas John , Langlais Paul R. , Streicher John M. 
Published: July 2021

Abstract
The opioid receptors are important regulators of pain, reward, and addiction. Limited evidence suggests the mu and delta opioid receptors form a heterodimer (MDOR), which may act as a negative feedback brake on opioid-induced analgesia. However, evidence for the MDOR in vivo is indirect and limited, and there are few selective tools available. We recently published the first MDOR-selective antagonist, D24M, allowing us to test the role of the MDOR in mice. We thus cotreated CD-1 mice with D24M and opioids in tail flick, paw incision, and chemotherapy-induced peripheral neuropathy pain models. D24M treatment enhanced oxymorphone antinociception in all models by 54.7% to 628%. This enhancement could not be replicated with the mu and delta selective antagonists CTAP, naltrindole, and naloxonazine, and D24M had a mild transient effect in the rotarod test, suggesting this increase is selective to the MDOR. However, D24M had no effect on morphine or buprenorphine, suggesting that only specific opioids interact with the MDOR. To find a mechanism, we performed phosphoproteomic analysis on brainstems of mice. We found that the kinases Src and CaMKII were repressed by oxymorphone, which was restored by D24M. We were able to confirm the role of Src and CaMKII in D24M-enhanced antinociception using small molecule inhibitors (KN93 and Src-I1). Together, these results provide direct in vivo evidence that the MDOR acts as an opioid negative feedback brake, which occurs through the repression of Src and CaMKII signal transduction. These results further suggest that MDOR antagonism could be a means to improve clinical opioid therapy.
Orai1 is a crucial downstream partner of group I metabotropic glutamate receptor signaling in dorsal horn neurons
Authors: Xia Jingsheng , Dou Yannong , Mei Yixiao , Munoz Frances M. , Gao Ruby , Gao Xinghua , Li Daling , Osei-Owusu Patrick , Schiffenhaus James , Bekker Alex , Tao Yuan-Xiang , Hu Huijuan 
Published: July 2021

Abstract
Group I metabotropic glutamate receptors (group I mGluRs) have been implicated in several central nervous system diseases including chronic pain. It is known that activation of group I mGluRs results in the production of inositol triphosphate (IP3) and diacylglycerol that leads to activation of extracellular signal-regulated kinases (ERKs) and an increase in neuronal excitability, but how group I mGluRs mediate this process remains unclear. We previously reported that Orai1 is responsible for store-operated calcium entry and plays a key role in central sensitization. However, how Orai1 is activated under physiological conditions is unknown. Here, we tested the hypothesis that group I mGluRs recruit Orai1 as part of its downstream signaling pathway in dorsal horn neurons. We demonstrate that neurotransmitter glutamate induces STIM1 puncta formation, which is not mediated by N-Methyl-D-aspartate (NMDA) or α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. Glutamate-induced Ca2+ entry in the presence of NMDA or AMPA receptor antagonists is eliminated in Orai1-deficient neurons. Dihydroxyphenylglycine (DHPG) (an agonist of group I mGluRs)-induced Ca2+ entry is abolished by Orai1 deficiency, but not affected by knocking down of transient receptor potential cation channel 1 (TRPC1) or TRPC3. Dihydroxyphenylglycine-induced activation of ERKs and modulation of neuronal excitability are abolished in cultured Orai1-deficient neurons. Moreover, DHPG-induced nociceptive behavior is markedly reduced in Orai1-deficient mice. Our findings reveal previously unknown functional coupling between Orai1 and group I mGluRs and shed light on the mechanism underlying group I mGluRs-mediated neuronal plasticity.
A Buthus martensii Karsch scorpion sting targets Nav1.7 in mice and mimics a phenotype of human chronic pain
Authors: Lu Wuguang , Cheng Xiaoyang , Chen Jiao , Wang Mingyuan , Chen Yonggen , Liu Jinman , Sang Ming , Zhao Ningwei , Yan Huaijiang , Cheng Xiaolan , Zhou Qian , Ye Juan , Wang Jin , Xu Erjin , Tang Zongxiang , Zhou Xi , Rong Mingqiang , Nilsen Erik A. , Dib-Hajj Sulayman D. , Waxman Stephen G. , Yu Ye , Cao Peng 
Published: July 2021

Abstract
Gain-of-function and loss-of-function mutations in Nav1.7 cause chronic pain and pain insensitivity, respectively. The preferential expression of Nav1.7 in the peripheral nervous system and its role in human pain signaling make Nav1.7 a promising target for next-generation pain therapeutics. However, pharmacological agents have not fully recapitulated these pain phenotypes, and because of the lack of subtype-selective molecular modulators, the role of Nav1.7 in the perception of pain remains poorly understood. Scorpion venom is an excellent source of bioactive peptides that modulate various ion channels, including voltage-gated sodium (Nav) channels. Here, we demonstrate that Buthus martensii Karsch scorpion venom (BV) elicits pain responses in mice through direct enhancement of Nav1.7 activity and have identified Makatoxin-3, an α-like toxin, as a critical component for BV-mediated effects on Nav1.7. Blocking other Nav subtypes did not eliminate BV-evoked pain responses, supporting the pivotal role of Nav1.7 in BV-induced pain. Makatoxin-3 acts on the S3–S4 loop of voltage sensor domain IV (VSD4) of Nav1.7, which causes a hyperpolarizing shift in the steady-state fast inactivation and impairs inactivation kinetics. We also determined the key residues and structure–function relationships for the toxin–channel interactions, which are distinct from those of other well-studied α toxins. This study not only reveals a new mechanism underlying BV-evoked pain but also enriches our knowledge of key structural elements of scorpion toxins that are pivotal for toxin–Nav1.7 interactions, which facilitates the design of novel Nav1.7 selective modulators.
Genetic and functional evidence for gp130/IL6ST-induced transient receptor potential ankyrin 1 upregulation in uninjured but not injured neurons in a mouse model of neuropathic pain
Authors: Kalpachidou Theodora , Malsch Philipp , Qi Yanmei , Mair Norbert , Geley Stephan , Quarta Serena , Kummer Kai K. , Kress Michaela 
Published: July 2021

Abstract
Peripheral nerve injuries result in pronounced alterations in dorsal root ganglia, which can lead to the development of neuropathic pain. Although the polymodal mechanosensitive transient receptor potential ankyrin 1 (TRPA1) ion channel is emerging as a relevant target for potential analgesic therapies, preclinical studies do not provide unequivocal mechanistic insight into its relevance for neuropathic pain pathogenesis. By using a transgenic mouse model with a conditional depletion of the interleukin-6 (IL-6) signal transducer gp130 in Nav1.8 expressing neurons (SNS-gp130−/−), we provide a mechanistic regulatory link between IL-6/gp130 and TRPA1 in the spared nerve injury (SNI) model. Spared nerve injury mice developed profound mechanical hypersensitivity as indicated by decreased withdrawal thresholds in the von Frey behavioral test in vivo, as well as a significant increase in mechanosensitivity of unmyelinated nociceptive primary afferents in ex vivo skin-nerve recordings. In contrast to wild type and control gp130fl/fl animals, SNS-gp130−/− mice did not develop mechanical hypersensitivity after SNI and exhibited low levels of Trpa1 mRNA in sensory neurons, which were partially restored by adenoviral gp130 re-expression in vitro. Importantly, uninjured but not injured neurons developed increased responsiveness to the TRPA1 agonist cinnamaldehyde, and neurons derived from SNS-gp130−/− mice after SNI were significantly less responsive to cinnamaldehyde. Our study shows for the first time that TRPA1 upregulation is attributed specifically to uninjured neurons in the SNI model, and this depended on the IL-6 signal transducer gp130. We provide a solution to the enigma of TRPA1 regulation after nerve injury and stress its significance as an important target for neuropathic pain disorders.
Intersectional identity approach to chronic pain disparities using latent class analysis
Authors: Newman Andrea K. , Thorn Beverly E. 
Published: July 2021

Abstract
Research on intersectionality and chronic pain disparities is very limited. Intersectionality explores the interconnections between multiple aspects of identity and provides a more accurate image of disparities. This study applied a relatively novel statistical approach (ie, Latent Class Analysis) to examine chronic pain disparities with an intersectional identity approach. Cross-sectional data were analyzed using pretreatment data from the Learning About My Pain trial, a randomized comparative effectiveness study of group-based psychosocial interventions (Patient-Centered Outcomes Research Institute Contract #941, Beverly Thorn, PI; clinicaltrials.gov identifier NCT01967342) for patients receiving care for chronic pain at low-income clinics in rural and suburban Alabama. Latent Class Analysis results suggested a 5-class model. To easily identify each class, the following labels were created: older adults, younger adults, severe disparity, older Black or African American, and Working Women. The latent disparity classes varied by pretreatment chronic pain functioning. Overall, the severe disparity group had the lowest levels of functioning, and the Working Women group had the highest levels of functioning. Although younger and with higher literacy levels, the younger adults group had similar levels of pain interference and depressive symptoms to the severe disparity group (P's < 0.05). The younger adults group also had higher pain catastrophizing than the older adults group (P < 0.005). Results highlighted the importance of the interactions between the multiple factors of socioeconomic status, age, and race in the experience of chronic pain. The intersectional identity theory approach through Latent Class Analysis provided an integrated image of chronic pain disparities in a highly understudied and underserved population.
Mental Health, Cognitive, and Neuropsychiatric Needs in Children and Young People With Wilson Disease
Authors: Day Jemma , Samyn Marianne , Proctor Sarah Ellen , Joshi Deepak , Pissas Eleanna , Chanpong Atchariya , Hedderly Tammy , Dhawan Anil 
Published: July 2021

Objective:Wilson disease (WD) is associated with neurological, psychiatric, cognitive, and psychosocial difficulties, but there is little data regarding the nature and prevalence of these problems in children and young people (CYP).Methods:A single-center case-note review to establish the incidence and nature of these issues in CYP with WD, managed before and after multidisciplinary team (MDT) clinics, was established.Results:Out of 69 (43 males) CYP with WD, 37.8% presented with acute liver failure, 48.6% with chronic liver disease and 13.5% after family screening. Medical treatment was with penicillamine (40), trientene (18), zinc and penicillamine/trientene (11), and zinc monotherapy (2). Twenty-one underwent liver transplantation. After a median follow-up of 9.8 (IQR 6.4–16.9) years, 86% are alive. Six died posttransplantation and 7 grafts were lost. Mental health difficulties were recorded in 49.3%, particularly prevalent in the acute liver failure group (70.8%). Nonadherence was common (50.7%) and associated with greater mental health prevalence. Neurological issues were reported in 36.2% and poor cognition/attainment in 14.5%, consistent across modes of presentation. Four patients had diagnoses of autism spectrum conditions, all diagnosed pre WD. CYP seen within an MDT-clinic had more frequent documentation of all issues examined, but lower levels of late graft loss (94% versus 80%,P= 0.07).Conclusion:Our data highlight the need to offer management in WD patients especially as these aspects are underrecognized in CYP presenting with liver involvement. We aim to highlight the importance of multidisciplinary input when looking after this population beyond transition through to adult services.
Repeat Biopsy to Assess Duodenal Healing in Children With Celiac Disease and Eosinophilic Gastrointestinal Disorders
Authors: Payne Kaitlin , Ramharack Lydia , Bierly Patricia , Feigenbaum Kara , Steinhoff Janel , Hlywiak Karen , Farrara Ann , Verma Ritu , Singh Arunjot , Fahey Lisa M. 
Published: July 2021

Objectives:
The aim of the study was to determine the correlation between duodenal mucosal biopsies and tissue transglutaminase immunoglobulin A (tTG-IgA) levels in pediatric patients with biopsy-confirmed celiac disease (CD) and eosinophilic gastrointestinal disorders (EGID) who have had repeat duodenal biopsies after initiating a gluten-free diet.

Methods:
A retrospective chart review was performed of children with CD and EGID seen at the Children’s Hospital of Philadelphia between 2003 and 2018. Data collected included duodenal biopsy pathology, celiac serology including tTG-IgA, and symptom reports. Duodenal healing was defined as normal villous architecture and no intraepithelial lymphocytes. These data were compared with tTG-IgA level. Data were analyzed with Fisher exact test and t test methods.

Results:
Thirty-nine patients had normal IgA and diagnoses of both CD and EGID. At second biopsy, 44% (17/39) of patients showed no histologic evidence of active CD and 36% (14/39) of patients had negative tTG-IgA values. Sixty percent (9/15) of patients with no evidence of CD on biopsy had abnormal tTG-IgA levels, and 57% (8/14) of patients with normal tTG-IgA levels had evidence of active disease on biopsy.

Conclusions:
The data show that an abnormal tTG-IgA drawn after initiation of a gluten-free diet is not correlated with duodenal mucosal injury in pediatric patients with CD and EGID. This suggests that serologic surveillance with tTG-IgA is not sufficient to monitor CD intestinal healing in this patient cohort. Persistent elevations of tTG-IgA in CD patients with normal duodenal biopsies should prompt investigation into other potential causes.
Sex-chromosome evolution in frogs: what role for sex-antagonistic genes?
Authors: Perrin Nicolas 
Published: July 2021

Sex-antagonistic (SA) genes are widely considered to be crucial players in the evolution of sex chromosomes, being instrumental in the arrest of recombination and degeneration of Y chromosomes, as well as important drivers of sex-chromosome turnovers. To test such claims, one needs to focus on systems at the early stages of differentiation, ideally with a high turnover rate. Here, I review recent work on two families of amphibians, Ranidae (true frogs) and Hylidae (tree frogs), to show that results gathered so far from these groups provide no support for a significant role of SA genes in the evolutionary dynamics of their sex chromosomes. The findings support instead a central role for neutral processes and deleterious mutations.
This article is part of the theme issue ‘Challenging the paradigm in sex chromosome evolution: empirical and theoretical insights with a focus on vertebrates (Part I)’.
Predicted Norovirus Resurgence in 2021-2022 Due to the Relaxation of Nonpharmaceutical Interventions Associated with COVID-19 Restrictions in England: A Mathematical Modelling Study
Authors: O’Reilly Kathleen M , Sandman Frank , Allen David , Jarvis Christopher I , Gimma Amy , Douglas Amy , Larkin Lesley , Wong Kerry LM , Baguelin Marc , Baric Ralph S , Lindesmith Lisa C , Goldstein Richard A , Breuer Judith , Edmunds W John 
Published: July 2021

AbstractBackgroundTo reduce the coronavirus disease burden in England, along with many other countries, the Government implemented a package of non-pharmaceutical interventions (NPIs) that have also impacted other transmissible infectious diseases such as norovirus. It is unclear what future norovirus disease incidence is likely to look like upon lifting these restrictions.MethodsHere we use a mathematical model of norovirus fitted to community incidence data in England to project forward expected incidence based on contact surveys that have been collected throughout 2020-2021.ResultsWe report that susceptibility to norovirus infection has likely increased between March 2020 to mid-2021. Depending upon assumptions of future contact patterns incidence of norovirus that is similar to pre-pandemic levels or an increase beyond what has been previously reported is likely to occur once restrictions are lifted. Should adult contact patterns return to 80% of pre-pandemic levels the incidence of norovirus will be similar to previous years. If contact patterns return to pre-pandemic levels there is a potential for the expected annual incidence to be up to 2-fold larger than in a typical year. The age-specific incidence is similar across all ages.ConclusionsContinued national surveillance for endemic diseases such as norovirus will be essential after NPIs are lifted to allow healthcare services to adequately prepare for a potential increase in cases and hospital pressures beyond what is typically experienced.
Gastric Neurons in the Nucleus Tractus Solitarius are Selective to the Orientation of Gastric Electrical Stimulation
Authors: Cao Jiayue , Wang Xiaokai , Powley Terry L. , Liu Zhongming 
Published: July 2021

AbstractGastric electrical stimulation (GES) is a bioelectric intervention for gastroparesis, obesity, and other functional gastrointestinal disorders. In a potential mechanism of action, GES activates the nerve endings of vagal afferent neurons and induces the vago-vagal reflex through the nucleus tractus solitarius (NTS) in the brainstem. However, it is unclear where and how to stimulate in order to optimize the vagal afferent responses. To address this question with electrophysiology in rats, we applied mild electrical currents to two serosal targets on the distal forestomach with dense distributions of vagal intramuscular arrays that innervated the circular and longitudinal smooth muscle layers. During stimulation, we recorded single and multi-unit responses from gastric neurons in NTS and evaluated how the recorded responses depended on the stimulus orientation and amplitude. We found that NTS responses were highly selective to the stimulus orientation for a range of stimulus amplitudes. The strongest responses were observed when the applied current flowed in the same direction as the intramuscular arrays in parallel with the underlying smooth muscle fibers. Our results suggest that gastric neurons in NTS may encode the orientation-specific activity of gastric smooth muscles relayed by vagal afferent neurons. This finding suggests that the orientation of GES is critical to effective engagement of vagal afferents and should be considered in light of the structural phenotypes of vagal terminals in the stomach.