bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic pain susceptibility is associated with anhedonic behavior and alterations in the accumbal ubiquitin-proteasome system
Authors: Guimarães Marco Rafael , Anjo Sandra Isabel , Cunha Ana Margarida , Esteves Madalena , Sousa Nuno , Almeida Armando , Manadas Bruno , Leite-Almeida Hugo 
Published: January 2021

Abstract
It remains unknown why on similar acute/subacute painful conditions, pain persists in some individuals while in others it resolves. Genetic factors, mood, and functional alterations, particularly involving the mesolimbic network, seem to be key. To explore potential susceptibility or resistance factors, we screened a large population of rats with a peripheral neuropathy and we isolated a small subset (<15%) that presented high thresholds (HTs) to mechanical allodynia (reduced pain manifestation). The phenotype was sustained over 12 weeks and was associated with higher hedonic behavior when compared with low-threshold (LT) subjects. The nucleus accumbens of HT and LT animals were isolated for proteomic analysis by Sequential Window Acquisition of All Theoretical Mass Spectra. Two hundred seventy-nine proteins displayed different expression between LT and HT animals or subjects. Among several protein families, the proteasome pathway repeatedly emerged in gene ontology enrichment and KEGG analyses. Several alpha and beta 20S proteasome subunits were increased in LT animals when compared with HT animals (eg, PSMα1, PSMα2, and PSMβ5). On the contrary, UBA6, an upstream ubiquitin-activating enzyme, was decreased in LT animals. Altogether these observations are consistent with an overactivation of the accumbal proteasome pathway in animals that manifest pain and depressive-like behaviors after a neuropathic injury. All the proteomic data are available through ProteomeXchange with identifier PXD022478.
Projections from the lateral parabrachial nucleus to the lateral and ventral lateral periaqueductal gray subregions mediate the itching sensation
Authors: Li Jia-Ni , Ren Jia-Hao , He Cheng-Bo , Zhao Wen-Jun , Li Hui , Dong Yu-Lin , Li Yun-Qing 
Published: January 2021

Abstract
Lateral and ventral lateral subregions of the periaqueductal gray (l/vlPAG) have been proved to be pivotal components in descending circuitry of itch processing, and their effects are related to the subclassification of neurons that were meditated. In this study, lateral parabrachial nucleus (LPB), one of the most crucial relay stations in the ascending pathway, was taken as the input nucleus to examine the modulatory effect of l/vlPAG neurons that received LPB projections. Anatomical tracing, chemogenetic, optogenetic, and local pharmacological approaches were used to investigate the participation of the LPB-l/vlPAG pathway in itch and pain sensation in mice. First, morphological evidence for projections from vesicular glutamate transporter-2-containing neurons in the LPB to l/vlPAG involved in itch transmission has been provided. Furthermore, chemogenetic and optogenetic activation of the LPB-l/vlPAG pathway resulted in both antipruritic effect and analgesic effect, whereas pharmacogenetic inhibition strengthened nociceptive perception without affecting spontaneous scratching behavior. Finally, in vivo pharmacology was combined with optogenetics which revealed that AMPA receptor-expressing neurons in l/vlPAG might play a more essential role in pathway modulation. These findings provide a novel insight about the connections between 2 prominent transmit nuclei, LPB and l/vlPAG, in both pruriceptive and nociceptive sensations and deepen the understanding of l/vlPAG modulatory roles in itch sensation by chosen LPB as source of ascending efferent projections.
Mechanical sensitization, increased axonal excitability, and spontaneous activity in C-nociceptors after ultraviolet B irradiation in pig skin
Authors: Werland Fiona , de Col Roberto , Hirth Michael , Turnquist Brian , Schmelz Martin , Obreja Otilia 
Published: January 2021

Abstract
Ultraviolet B (UVB) irradiation induces hyperalgesia in human and animal pain models. We investigated mechanical sensitization, increase in axonal excitability, and spontaneous activity in different C-nociceptor classes after UVB in pig skin. We focused on units with receptive fields covering both irradiated and nonirradiated skin allowing intraindividual comparisons. Thirty-five pigs were irradiated in a chessboard pattern, and extracellular single-fibre recordings were obtained 10 to 28 hours later (152 fibers). Units from the contralateral hind limb served as a control (n = 112). Irradiated and nonirradiated parts of the same innervation territory were compared in 36 neurons; low threshold C-touch fibers (n = 10) and sympathetic efferents (n = 2) were unchanged, but lower mechanical thresholds and higher discharge frequency at threshold were found in mechanosensitive nociceptors (n = 12). Half of them could be activated with nonnoxious brush stimuli in the sunburn. Four of 12 mechanoinsensitive nociceptors were found sensitized to mechanical stimulation in the irradiated part of the receptive field. Activity-dependent slowing of conduction was reduced in the irradiated and in the nonirradiated skin as compared with the control leg, whereas increased ability to follow high stimulation frequencies was restricted to the sunburn (108.5 ± 37 Hz UVB vs 6.3 ± 1 Hz control). Spontaneous activity was more frequent in the sunburn (72/152 vs 31/112). Mechanical sensitization of primary nociceptors and higher maximum after frequency are suggested to contribute to primary hyperalgesia, whereas the spontaneous activity of silent nociceptors might offer a mechanistic link contributing to ongoing pain and facilitated induction of spinal sensitization.
The Use of Methylphenidate for Cognitive Enhancement in Young Healthy Adults
Authors: Koren Gideon , Korn Liat 
Published: January 2021

Abstract

Objective
Methylphenidate (MP), a drug of choice for attention-deficit/hyperactivity disorder (ADHD), is a federally restricted substance CII in the United States because of abuse and dependence, and similar restrictions are practiced in Canada and around the world. This designation is given to drugs with medical value that present a high potential for abuse. In view of these severe restrictions, it is concerning to find out that a large group of healthy young adults, at least as large as the ADHD group of patients, take MP for cognitive enhancement, in an attempt to improve their academic achievements during studies and examinations. These young adults buy MP illegally and consume it without any medical supervision. The objective of the present debate piece is to present the ethical and clinical issues that need to be addressed in an attempt to solve this dilemma.

Methods
The issues presented here are systematically reviewed and discussed along the following lines: MP effectiveness in enhancing cognitive achievements in healthy people; “As these are normal healthy people, what is the duty of physicians to ‘treat’ them?”; potential benefits of cognitive enhancement to healthy people; the risks of MP; “How do these young people get their MP?”; and “What can be done?”

Results
Methylphenidate is widely used for cognitive enhancement without medical supervision. The effectiveness of MP for cognitive enhancement is well documented along a dose-response curve. Congruent with the results of the randomized trials, repeated studies based on interviews suggest that numerous young people report that cognitive enhancement helps them in improving their academic achievements, and hence also improve their feeling of well-being. Presently, most regulatory and medical organizations limit the use of MP to ADHD and narcolepsy. Yet, the American Academy of Neurology ruled that there is a moral, ethical, and legal basis to prescribe the drug for cognitive enhancement. The drug has known dose-dependent adverse effects that can have serious ramifications and may often lead to poor adherence. The relative risk of MP causing sudden death/arrhythmia is 1.46 (95% confidence interval, 1.03–2.07), and there are estimated 20 million college and university students in the United States in 2020. The rate of sudden death/arrhythmias in this age group ranges between 1 and 10 per 100,000. This translates to an excess of 146 deaths caused by MP every year in the United States considering postsecondary students only.

Discussion
We propose that an ethical-clinical debate should be followed by an action plan to ensure that the present reality of millions of young people taking unsupervised MP is not accepted as a force majeure that cannot be changed.
Clinical Implications of Horizontal Beating Nystagmus Induced by Dix-Hallpike Test in the Diagnosis of Horizontal Canal Benign Paroxysmal Positional Vertigo
Authors: Kong Tae Hoon , Song Mee Hyun , Shim Dae Bo 
Published: January 2021

Objectives:
The purpose of this study was to identify the diverse patterns of nystagmus during the Dix-Hallpike test (DHT) and analyze their clinical significance in horizontal canal benign paroxysmal positional vertigo (HC-BPPV).

Study Design:
Retrospective medical records review.

Patients:
Two hundred ninety-five patients diagnosed with HC-BPPV.

Methods:
Various nystagmus patterns identified during the DHT in patients with HC-BPPV were analyzed. The correlation between the affected side of HC-BPPV and the direction of the horizontal beating nystagmus (HBN) during the DHT was also analyzed.

Results:
The nystagmus pattern during the DHT in 128 patients with geotropic HC-BPPV demonstrated, direction-changing positional nystagmus on both sides in 48 (37.5%) patients, HBN toward one side in 25 (19.6%) patients, and no nystagmus in 55 (42.9%) patients. In 144 patients with apogeotropic HC-BPPV, 54 (37.5%) patients presented with direction-changing positional nystagmus on both sides, 27 (18.8%) patients presented with HBN toward one side, and 63 (43.7%) patients did not show nystagmus during the DHT. The direction of HBN provoked by the DHT was significantly correlated with the affected side in each subtype of HC-BPPV (geotropic type, p = 0.049; apogeotropic type, p = 0.040; respectively).

Conclusion:
More than half of the patients with HC-BPPV (56.6%) showed HBN during the DHT. When HBN was present during the DHT, it may provide a clue for determining the subtype and affected side in diagnosis of HC-BPPV before performing the supine roll test.
Postural Sway Predicts Growth in Untreated Vestibular Schwannoma: A Retrospective Volumetric Study
Authors: Nilsen Kathrin Skorpa , Dhayalan Dhanushan , Lund-Johansen Morten , Goplen Frederik Kragerud 
Published: January 2021

Background:
One in three vestibular schwannomas (VS) will grow within 3 years after diagnosis, but no reliable baseline parameter has been found to predict such growth.

Objective:
To determine if postural sway is associated with growth of untreated VS.

Methods:
Patients with newly diagnosed sporadic VS assigned to a wait-and-scan protocol were identified from a prospectively maintained database. Postural sway was measured by posturography at baseline and patients were classified as steady or unsteady. Observer-blinded volumetric tumor measurements were performed on the diagnostic MRI and a 3-year control MRI. Tumor growth quantified as relative growth (%) and volume-doubling time (VDT and VDT−1) were investigated as dependent variables against baseline parameters.

Results:
Out of 204 VS patients, 53 (26%) were classified as unsteady on the platform at baseline. Median tumor volume was 0.32 cm3 (range 0.02–4.79), and 51% demonstrated significant growth within 3 years. Unsteady patients had significantly faster-growing tumors, with a mean relative growth of 172.5% compared to 79.5% in steady patients (p < 0.006). Seventy-seven percent of unsteady patients had >20% volume increase, compared to 42% in steady patients (p < 0.001). Mean VDT−1 was 0.65 doublings per year for unsteady patients, and 0.22 for steady patients (p < 0.001). Multivariate regression analysis including demographic and clinical parameters showed an OR of 5.6 (95% CI 2.6, 11.8) for growth in unsteady patients.

Conclusions:
This is the first demonstrated association between a measurable parameter and future growth in untreated VS. Our findings may help clinicians identify patients with a higher risk for tumor growth and provide closer monitoring or early treatment.
Cerebrospinal Fluid Leak Following Translabyrinthine Vestibular Schwannoma Surgery—Is Mesh Cranioplasty Necessary for Prevention?
Authors: Selleck Anne Morgan , Hodge Sarah E. , Brown Kevin D. 
Published: January 2021

Objective:
Evaluate the incidence of cerebrospinal fluid leak following vestibular schwannoma surgery for mesh cranioplasty closure versus periosteal closure in the translabyrinthine approach. Determine nonsurgical variables associated with higher rates of cerebrospinal fluid leak following vestibular schwannoma surgery.

Study Design:
Retrospective chart review.

Setting:
Tertiary academic referral center.

Patients:
One hundred thirty-two patients with adequate documentation who underwent sporadic vestibular schwannoma resection via a translabyrinthine approach between 2000 and 2019.

Intervention:
Translabyrinthine excision of vestibular schwannoma with mesh cranioplasty closure or watertight periosteal closure.

Main Outcome Measures:
Primary outcome measures included the incidence of postoperative cerebrospinal fluid leak, total length of hospital stay (including the initial hospital stay as well as hospital days during any readmission within 30 days), and total operative time.

Results:
Our overall cerebrospinal fluid leak rate was 9.1% with a leak rate of 12.8% in our translabyrinthine titanium mesh closure group and 0% in our translabyrinthine periosteal closure. There was no statistically significant effect of age, body mass index, or size of tumor on the incidence of cerebrospinal fluid leak. There was also no statistically significantly difference between the two groups on length of operative time or number of days spent in the intensive care unit.

Conclusion:
Mesh cranioplasty is not a prerequisite for achieving a low cerebrospinal fluid leak rate following translabyrinthine approach for vestibular schwannoma resection. In our series, a significantly lower cerebrospinal fluid leak rate was demonstrated with the periosteal closure.
Stereotactic Radiosurgery for Vestibular Schwannoma Outcomes in Patients With Perfect Word Recognition—A Retrospective Cohort Study
Authors: Fouad Ayman , Tran Emma D. , Feng Austin Y. , Alyono Jennifer C. , Ma Yifei , Blevins Nikolas H. , Jackler Robert K. , Santa Maria Peter L. 
Published: January 2021

Objectives:
To investigate tumor control rate and hearing outcomes following stereotactic radiosurgery (SRS) for vestibular schwannoma (VS) cases with perfect (100%) word recognition score (WRS).

Study Design:
A retrospective cohort study.

Setting:
Tertiary referral center.

Patients:
Inclusion criteria were receiving primary SRS, a pretreatment WRS of 100%, and availability of both pre- and posttreatment audiometric data for evaluation.

Intervention:
SRS delivered by Cyberknife.

Main Outcome Measures:
Tumor growth rates and audiological outcomes after SRS.

Results:
The cohort consisted of 139 patients, with more than 1-year follow-up (mean 6.1 yrs). SRS tumor control rate was 87% for the whole cohort. Growth before SRS was documented in 24% (n = 34 of 139). The proportion of sporadic VS cases who maintained hearing (decline <10 dB of pure-tone audiometry or <20% of WRS) at 3 years was 50%, at 5 years was 45%, and at 10 years was 42%. In multivariate analysis, increased age was found to be predictive of increased hearing loss (p = 0.03), while the following factors were shown not to be significant: sex (p = 0.5), tumor size (p = 0.2), pre-SRS tumor growth (p = 0.5), and target volume (p = 0.42).

Conclusions:
Among patients with VS who had perfect WRS and underwent SRS, the overall tumor control rate was 87% comparable to observation. Hearing maintenance and preservation of “serviceable” hearing rates after 5 years in VS patients with perfect WRS treated by SRS is less than that when comparing to similar observation cohorts. Given this finding we do not advocate using SRS to preserve hearing, over observation, in tumors with perfect WRS.
Investigating Predictors of Increased Length of Stay After Resection of Vestibular Schwannoma Using Machine Learning
Authors: Dang Sabina , Manzoor Nauman F. , Chowdhury Naweed , Tittman Sarah M. , Yancey Kristen L. , Monsour Meredith A. , O’Malley Matthew R. , Rivas Alejandro , Haynes David S. , Bennett Marc L. 
Published: January 2021

Objective:
To evaluate the predictors of prolonged length of stay (LOS) after vestibular schwannoma resection.

Study Design:
Retrospective chart review.

Setting:
Tertiary referral center.

Patients:
Patients who underwent vestibular schwannoma resection between 2008 and 2019.

Interventions:
Variables of interest included age, body mass index, comorbidities, symptoms, previous intervention, microsurgical approach, extent of resection, operative time, preoperative tumor volume, and postoperative complications. Predictive modeling was done through multivariable linear regression and random forest models with 80% of patients used for model training and the remaining 20% used for performance testing.

Main Outcome Measures:
LOS was evaluated as the number of days from surgery to discharge.

Results:
Four hundred one cases from 2008 to 2019 were included with a mean LOS of 3.0 (IQR = 3.0–4.0). Postoperatively, 14 (3.5%) of patients had LOS greater than two standard deviations from the mean (11 days). In a multivariate linear regression model (adjusted R2 = 0.22; p < 0.001), preoperative tumor volume (p < 0.001), coronary artery disease (p = 0.002), hypertension (p = 0.029), and any major complication (p < 0.001) were associated with increased LOS (by 0.12, 3.79, 0.87, and 3.20 days respectively). A machine learning analysis using a random forest identified several potential nonlinear relationships between LOS and preoperative tumor dimensions (length, volume) and operative time that were not captured on regression. The random forest model had lower prediction error compared to the regression model (RMSE 5.67 vs. 44.59).

Conclusions:
Tumor volume, coronary artery disease, hypertension, and major complications impact LOS. Machine learning methods may identify nonlinear relationships worthy of targeted clinical investigation and allow for more accurate patient counseling.
Performance With an Adhesive Bone Conduction Device in Active Transcutaneous Bone Conduction Implant Users
Authors: Dahm Valerie , Traxler Stefanie , Liepins Rudolfs , Auinger Alice B. , Sterrer Elisabeth , Kaider Alexandra , Riss Dominik , Arnoldner Christoph 
Published: January 2021

Objectives:
The aim of this study was to evaluate the performance and limits of an adhesive bone conduction hearing aid in patients implanted with an active transcutaneous bone conduction implant. Therefore, hearing performance and subjective benefit of patients with mixed and conductive hearing loss were assessed with both bone conduction devices.

Study Design and Patients:
This cohort study was conducted at a tertiary care center. Fifteen subjects, who had been implanted with an active transcutaneous device previously, were included and used the adhesive hearing device for 3 weeks instead of the implant. Subjects underwent two sets of audiological tests as well as assessments of quality of life at the beginning and at the end of the testing period.

Results:
Audiological results showed a significantly greater improvement in regards to functional hearing gain and word recognition scores with the transcutaneous bone conduction device than the nonimplantable adhesive device. Regression analysis showed a trend toward greater improvement with the transcutaneous device compared with the adhesive device in patients with an increasing bone conduction threshold. Hearing-specific and general quality-of-life questionnaires revealed no significant difference between the two devices.

Conclusion:
Patients with mixed or conductive hearing loss experience hearing gain with both, the adhesive device and the active transcutaneous device. The adhesive device may be a valuable alternative to the active transcutaneous device, depending on the individual bone conduction threshold.
Evaluation of the efficiency and safety of botulinum toxin A injection on improving facial scars
Authors: Xu Dan , Zhang Da-Song , Hu Xue-Feng , Hu Meng-Yao 
Published: January 2021

Abstract

Background:
Botulinum toxin A injection is an established method of treatment. Clinical practitioners use it widely in their practice to prevent the occurrence of facial scars. However, the effectiveness and safeness of has not been comprehensively established. The objective of the current systematic review is to evaluate the efficacy and safety of using botulinum toxin A injection to improve facial scars.

Methods and analysis:
This systematic review involves browsing a number of electronic databases to search for related articles. The search will include databases in both English (PubMed, EMBASE, Web of Science, Spocus, and Cochrane Central Register of Controlled Trials) and Chinese (WanFang database, China Nation Knowledge Infrastructure, and VIP database), the periods of searching will be from inception till the 15th of September 2020. Completing the search in databases allows to consider randomized controlled studies that compares botulinum toxin A interventions to any comparison interventions in those who have facial scars. The review will be inclusive of papers in both languages, English and Chinese. The independent screening of studies for eligibility is conducted by 2 independent authors. Discussion was used to resolve discrepancies between the authors. The Cochrane Risk of Bias Tool V.2.0 is adopted for evaluating the methodological quality of each study. Data extraction was performed by 2 independent authors. For dichotomous outcomes, the were expressed as relative risk (RR) with 95% confidence intervals (CI). For continuous outcomes the results were expressed as the mean difference (MD) or standardized mean difference (SMD) with 95% CI. The statistical analysis of the present study is carried out in RevMan 5.3 software.

Results:
This study will output a comprehensive synthesis of existing evidence in relation to botulinum toxin A. Moreover, the results will also provide an interpretation of the effectiveness and safety of botulinum toxin A.

Conclusion:
The present review contributes to the existing body of knowledge by adding more evidence to evaluate if botulinum toxin A is effective and safe to be used as an intervention for improving facial scars.

OSF registration number:
DOI 10.17605/OSF.IO/94TXP (https://osf.io/94TXP/).