bluuebunny/crossref_metadata_2025_split huggingface dataset:
Significant increase of high-risk chromosome 1q gain and 6q loss at recurrence in posterior fossa group A ependymoma: A multicenter study
Authors: Donson Andrew M , Bertrand Kelsey C , Riemondy Kent A , Gao Dexiang , Zhuang Yonghua , Sanford Bridget , Norris Gregory A , Chapman Rebecca J , Fu Rui , Willard Nicholas , Griesinger Andrea M , Ribeiro de Sousa Graziella , Amani Vladimir , Grimaldo Enrique , Hankinson Todd C , Booker Ffyona , Sill Martin , Grundy Richard G , Pajtler Kristian W , Ellison David W , Foreman Nicholas K , Ritzmann Timothy A 
Published: May 2023

AbstractBackgroundEpendymoma (EPN) posterior fossa group A (PFA) has the highest rate of recurrence and the worst prognosis of all EPN molecular groups. At relapse, it is typically incurable even with re-resection and re-irradiation. The biology of recurrent PFA remains largely unknown; however, the increasing use of surgery at first recurrence has now provided access to clinical samples to facilitate a better understanding of this.MethodsIn this large longitudinal international multicenter study, we examined matched samples of primary and recurrent disease from PFA patients to investigate the biology of recurrence.ResultsDNA methylome derived copy number variants (CNVs) revealed large-scale chromosome gains and losses at recurrence in PFA. CNV changes were dominated by chromosome 1q gain and/or 6q loss, both previously identified as high-risk factors in PFA, which were present in 23% at presentation but increased to 61% at first recurrence. Multivariate survival analyses of this cohort showed that cases with 1q gain or 6q loss at first recurrence were significantly more likely to recur again. Predisposition to 1q+/6q− CNV changes at recurrence correlated with hypomethylation of heterochromatin-associated DNA at presentation. Cellular and molecular analyses revealed that 1q+/6q− PFA had significantly higher proportions of proliferative neuroepithelial undifferentiated progenitors and decreased differentiated neoplastic subpopulations.ConclusionsThis study provides clinically and preclinically actionable insights into the biology of PFA recurrence. The hypomethylation predisposition signature in PFA is a potential risk-classifier for trial stratification. We show that the cellular heterogeneity of PFAs evolves largely because of genetic evolution of neoplastic cells.
Stepwise changes in flavonoids in spores/pollen contributed to terrestrial adaptation of plants
Authors: Xue Jing-Shi , Qiu Shi , Jia Xin-Lei , Shen Shi-Yi , Shen Chong-Wen , Wang Shui , Xu Ping , Tong Qi , Lou Yu-Xia , Yang Nai-Ying , Cao Jian-Guo , Hu Jin-Feng , Shen Hui , Zhu Rui-Liang , Murray Jeremy D , Chen Wan-Sheng , Yang Zhong-Nan 
Published: May 2023

Abstract
Protecting haploid pollen and spores against UV-B light and high temperature, 2 major stresses inherent to the terrestrial environment, is critical for plant reproduction and dispersal. Here, we show flavonoids play an indispensable role in this process. First, we identified the flavanone naringenin, which serves to defend against UV-B damage, in the sporopollenin wall of all vascular plants tested. Second, we found that flavonols are present in the spore/pollen protoplasm of all euphyllophyte plants tested and that these flavonols scavenge reactive oxygen species to protect against environmental stresses, particularly heat. Genetic and biochemical analyses showed that these flavonoids are sequentially synthesized in both the tapetum and microspores during pollen ontogeny in Arabidopsis (Arabidopsis thaliana). We show that stepwise increases in the complexity of flavonoids in spores/pollen during plant evolution mirror their progressive adaptation to terrestrial environments. The close relationship between flavonoid complexity and phylogeny and its strong association with pollen survival phenotypes suggest that flavonoids played a central role in the progression of plants from aquatic environments into progressively dry land habitats.
How to treat VEXAS syndrome: a systematic review on effectiveness and safety of current treatment strategies
Authors: Boyadzhieva Zhivana , Ruffer Nikolas , Kötter Ina , Krusche Martin 
Published: May 2023

Abstract

Objectives
To evaluate the effectiveness and safety of current treatment strategies for the vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome.

Methods
A protocolized systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was performed. Three databases were searched for reports on treatment strategies for VEXAS. Data from the included publications was extracted and a narrative synthesis was performed. Treatment response was recorded as complete (CR), partial (PR) or none (NR) depending on changes in clinical symptoms and laboratory parameters. Patient characteristics, safety data and previous treatments were analysed.

Results
We identified 36 publications with a total of 116 patients; 113 (98.3%) were male. The identified reports included azacytidine (CR 9/36, 25%; PR 14/36, 38.9%), Janus kinase inhibitors (JAKi) (CR 11/33, 33%; PR 9/33, 27.3%), tocilizumab (CR 3/15, 20%; PR 6/15, 40%), allogeneic stem cell transplantation (CR 6/7, 85.7%; one patient died), anakinra (CR 4/5, 80%; NR 1/5, 20%), canakinumab (CR 1/2, 50%; PR 1/2, 50%) and glucocorticoid monotherapy (CR 1/6, 16.7%; PR 4/6, 66.7%). Individual reports were available for TNF inhibitors, rituximab and MTX. Data on adverse events were available for 67 patients (67/116, 57.8%) and included: pneumonia (12/67, 17.9%), other infections (9/67, 13.4%), venous thromboembolisms (6/67, 8.9%), cytopenias (4/67, 5.9%), and acute (4/67, 5.9%) and chronic graft-vs-host-disease (2/67, 2.9%).

Conclusion
Current data on VEXAS treatment are limited and inhomogeneous. Treatment decisions should be individualized. For the devolvement of treatment algorithms clinical trials are needed. Adverse events remain a challenge, especially an elevated risk for venous thromboembolism associated to JAKi treatment should be carefully considered.
Sociodemographic Trends in Telemedicine Visit Completion in Spine Patients During the COVID-19 Pandemic
Authors: Owolo Edwin , Petitt Zoey , Rowe Dana , Luo Emily , Bishop Brandon , Poehlein Emily , Green Cynthia L. , Cook Chad , Erickson Melissa , Goodwin C. Rory 
Published: May 2023

Study Design:
Retrospective cohort study

Objective:
This study identifies potential disparities in telemedicine utilization in the wake of the COVID-19 pandemic and its aftermath in patients receiving spine surgery.

Summary of Background Data:
COVID-19 led to the rapid uptake of telemedicine in the spine surgery patient population. While previous studies in other medical subspecialties have identified sociodemographic disparities in telemedicine uptake, this is the first study to identify disparities in patients undergoing spine surgery.

Materials and Methods:
This study included patients who underwent spine surgery between June 12, 2018 and July 19, 2021. Patients were required to have at least one scheduled patient visit, either virtual (video or telephone visit) or in-person. Binary socioeconomic variables used for modeling included: urbanicity, age at the time of the procedure, sex, race, ethnicity, language, primary insurer, and patient portal utilization. Analyses were conducted for the entire cohort and separately for cohorts of patients who had visits scheduled within specific timeframes: Pre–COVID-19 surge, initial COVID-19 surge, and post–COVID-19 surge.

Results:
After adjusting for all variables in our multivariable analysis, patients who utilized the patient portal had higher odds of completing a video visit compared with those who did not (OR: 5.21; 95% CI: 1.28, 21.23). Hispanic patients (OR: 0.44; 95% CI: 0.2, 0.98) or those living in rural areas (OR: 0.58; 95% CI: 0.36, 0.93) had lower odds of completing a telephone visit. Patients with no insurance or on public insurance had higher odds of completing a virtual visit of either type (OR: 1.88; 95% CI: 1.10, 3.23).

Conclusion:
This study demonstrates the disparity in telemedicine utilization across different populations within the surgical spine patient population. Surgeons may use this information to guide interventions aimed at reducing existing disparities and work with certain patient populations to find a solution.
Assessment of the External Validity of Dialogue Support for Predicting Lumbar Spine Surgery Outcomes in a US Cohort
Authors: Carreon Leah Y. , Glassman Steven D. , Mummaneni Praveen , Bydon Mohamad , Chan Andrew K. , Asher Anthony 
Published: May 2023

Study Design.
External validation using prospectively collected data.

Objectives.
To determine the model performance of “Dialogue Support” (DS) in predicting outcomes after lumbar spine surgery.

Summary of Background Data.
To help clinicians discuss risk versus benefit with patients considering lumbar fusion surgery, DS has been made available online. As DS was created using a Swedish sample, there is a need to study how well DS performs in alternative populations.

Patients and Methods.
Preoperative data from patients enrolled in the Quality Outcomes Database were entered into DS. The probability for each patient to report satisfaction, achieve success (leg pain improvement ≥3), or have no leg pain 12 months after surgery was extracted and compared with their actual 12-month postoperative data. The ability of DS to identify patients in the Quality Outcomes Database who report satisfaction, achieve success, or have no leg pain 12 months after surgery was determined using Receiver operating characteristic curve analysis, goodness-of-fit tests, and calibration plots.

Results.
There was a significant improvement in all outcomes in 23,928 cases included in the analysis from baseline to 12 months postoperative. Most (84%) reported satisfaction, 67% achieved success, and 44% were pain-free 12 months postoperative. Receiver operating characteristic analysis showed that DS had a low ability to predict satisfaction [area under the curve (AUC) = 0.606], success (AUC = 0.546), and being pain-free (AUC = 0.578) at 12 months postoperative; poor fit for satisfaction (<0.001) and being pain-free (P = 0.004), but acceptable fit for success (P = 0.052). Calibration plots showed underestimation for satisfaction and success, but acceptable estimates for being pain-free.

Conclusion.
DS is not directly transferable to predict satisfaction and success after lumbar surgery in a US population. This may be due to differences in patient characteristics, weights of the variables included, or the exclusion of unknown variables associated with outcomes. Future studies to better understand and improve the transferability of these models are needed.
Percutaneous Transforaminal Endoscopic Discectomy Learning Curve
Authors: Maayan Omri , Pajak Anthony , Shahi Pratyush , Asada Tomoyuki , Subramanian Tejas , Araghi Kasra , Singh Nishtha , Korsun Maximillian K. , Singh Sumedha , Tuma Olivia C. , Sheha Evan D. , Dowdell James E. , Qureshi Sheeraz A. , Iyer Sravisht 
Published: May 2023

Study Design.
Retrospective review of prospectively collected data.

Objective.
To describe the learning curve for percutaneous transforaminal endoscopic discectomy (PTED) and demonstrate its efficacy in treating lumbar disc herniation.

Summary of Background Data.
The learning curve for PTED has not yet been standardized in the literature.

Patients and Methods.
Consecutive patients who underwent lumbar PTED by a single surgeon between December 2020 and 2022 were included. Cumulative sum analysis was applied to operative and fluoroscopy time to assess the learning curve. Inflection points were used to divide cases into early and late phases. The 2 phases were analyzed for differences in operative and fluoroscopy time, length of stay, complications, and patient-reported outcome measures (PROMs). Patient characteristics and operative levels were also compared. PROMs entailed the Oswestry Disability Index, Patient-Reported Outcomes Measurement Information System, Visual Analog Scale Back/Leg, and 12-item Short Form Survey at preoperative, early postoperative (<6 mo), and late postoperative (≥6 mo) time points. PROMs between PTED cases and a comparable cohort of tubular microdiscectomy cases, performed by the same surgeon, were compared.

Results.
Fifty-five patients were included. Cumulative sum analysis indicated that both operative and fluoroscopy time diminished rapidly after case 31, suggesting a learning curve of 31 cases (early phase: n = 31; late phase: n = 24). Late-phase cases exhibited significantly lower operative times (85.7 vs. 62.2 min, P = 0.001) and fluoroscopy times (131.0 vs. 97.2 s, P = 0.001) compared with the early-phase cases. Both early and late-phase cases showed significant improvement in all PROMs. There were no differences in PROMs between the patients who underwent PTED and tubular microdiscectomy.

Conclusion.
The PTED learning curve was found to be 31 cases and did not impact PROMs or complication rates. Although this learning curve reflects the experiences of a single surgeon and may not be broadly applicable, PTED can serve as an effective modality for the treatment of lumbar disc herniation.
Hippo (YAP)–autophagy axis protects against hepatic ischemia-reperfusion injury through JNK signaling
Authors: Zhu Shuguang , Wang Xiaowen , Chen Haoqi , Zhu Wenfeng , Li Xuejiao , Cui Ruiwen , Yi Xiaomeng , Chen Xiaolong , Li Hua , Wang Genshu 
Published: May 2023

Abstract

Background:
Hepatic ischemia-reperfusion injury (HIRI) remains a common complication during liver transplantation (LT) in patients. As a key downstream effector of the Hippo pathway, Yes-associated protein (YAP) has been reported to be involved in various physiological and pathological processes. However, it remains elusive whether and how YAP may control autophagy activation during ischemia-reperfusion.

Methods:
Human liver tissues from patients who had undergone LT were obtained to evaluate the correlation between YAP and autophagy activation. Both an in vitro hepatocyte cell line and in vivo liver-specific YAP knockdown mice were used to establish the hepatic ischemia-reperfusion models to determine the role of YAP in the activation of autophagy and the mechanism of regulation.

Results:
Autophagy was activated in the post-perfusion liver grafts during LT in patients, and the expression of YAP positively correlated with the autophagic level of hepatocytes. Liver-specific knockdown of YAP inhibited hepatocytes autophagy upon hypoxia-reoxygenation and HIRI (P <0.05). YAP deficiency aggravated HIRI by promoting the apoptosis of hepatocytes both in the in vitro and in vivo models (P <0.05). Attenuated HIRI by overexpression of YAP was diminished after the inhibition of autophagy with 3-methyladenine. In addition, inhibiting autophagy activation by YAP knockdown exacerbated mitochondrial damage through increasing reactive oxygen species (P <0.05). Moreover, the regulation of autophagy by YAP during HIRI was mediated by AP1 (c-Jun) N-terminal kinase (JNK) signaling through binding to the transcriptional enhanced associate domain (TEAD).

Conclusions:
YAP protects against HIRI by inducing autophagy via JNK signaling that suppresses the apoptosis of hepatocytes. Targeting Hippo (YAP)–JNK–autophagy axis may provide a novel strategy for the prevention and treatment of HIRI.
Regional analgesia for lung transplantation
Authors: Azem Karam , Mangoubi Eitan , Zribi Benjamin , Fein Shai 
Published: May 2023

Lung transplantation (LTx) is the definitive treatment for end-stage pulmonary disease. About 4500 LTxs are performed annually worldwide.
It is considered challenging and complex surgery regarding anaesthesia and pain management. While providing adequate analgesia is crucial for patient comfort, early mobilisation and prevention of postoperative pulmonary complications, standardising an analgesic protocol is challenging due to the diversity of aetiologies, surgical approaches and the potential use of extracorporeal life support (ECLS).
Although thoracic epidural analgesia is commonly considered the gold standard, concerns regarding procedural safety and its potential for devastating consequences have led physicians to seek safer analgesic modalities such as thoracic nerve blocks.
The advantages of thoracic nerve blocks for general thoracic surgery are well established. However, their utility in LTx remains unclear.
Considering paucity of relevant literature, this review aims to raise awareness about the literature gap in the field and highlight the need for further high-quality studies determining the effectiveness of available techniques.
IncobotulinumtoxinA for Glabellar Frown Lines in Chinese Subjects: A Randomized, Double-blind, Active-Controlled Phase-3 Study
Authors: Wu Yan , Roll Susanna , Klein Gudrun , Geister Thorin L. , Makara Michael A. , Li Bi 
Published: May 2023

Background:
This study evaluated the efficacy and safety of IncobotulinumtoxinA 20 U for treatment of glabellar frown lines in Chinese subjects.

Methods:
This was a prospective, randomized, double-blind, active-controlled, phase-3 study conducted in China. Subjects with moderate to severe glabellar frown lines at maximum frown were randomized to receive IncobotulinumtoxinA (N = 336) or OnabotulinumtoxinA (N = 167).

Results:
For the primary efficacy endpoint at day 30, response rates at maximum frown (score “none” or “mild”) on the Merz Aesthetic Scales Glabella Lines – Dynamic were comparable between IncobotulinumtoxinA (92.5%) and OnabotulinumtoxinA (95.1%) per investigator’s live rating. Noninferiority of IncobotulinumtoxinA versus OnabotulinumtoxinA was successfully demonstrated, as the two-sided 95% confidence interval of −0.97% to 0.43% for the difference in Merz Aesthetic Scales-based response rates (−0.27%) lay completely above the predefined noninferiority margin of −15%. For the secondary efficacy endpoints assessed at day 30, Merz Aesthetic Scales-based response rates (score “none” or “mild”) at maximum frown were similarly comparable between both groups per subject (>85%) and independent review panel (>96%) rating. Per Global Impression of Change Scales, greater than 80% of subjects and greater than 90% of investigators in both groups rated treatment results as at least “much improved” at day 30 compared with baseline. Safety profiles were consistent between groups; IncobotulinumtoxinA was well tolerated, and no new safety concerns were identified in Chinese subjects.

Conclusion:
IncobotulinumtoxinA 20 U is safe and effective for treatment of moderate to severe glabellar frown lines at maximum frown in Chinese subjects and is noninferior to OnabotulinumtoxinA 20 U.
Artificial or Augmented Authorship? A Conversation with a Chatbot on Base of Thumb Arthritis
Authors: Seth Ishith , Sinkjær Kenney Peter , Bulloch Gabriella , Hunter-Smith David J. , Bo Thomsen Jørn , Rozen Warren M. 
Published: May 2023

Summary:
ChatGPT is an open artificial intelligence chat box that could revolutionize academia and augment research writing. This study had an open conversation with ChatGPT and invited the platform to evaluate this article through series of five questions on base of thumb arthritis to test if its contributions and contents merely add artificial unusable input or help us augment the quality of the article. The information ChatGPT-3 provided was accurate, albeit surface-level, and lacks analytical ability to dissect for important limitations about base of thumb arthritis, which would not be conducive to potentiating creative ideas and solutions in plastic surgery. ChatGPT failed to provide relevant references and even “created” references instead of indicating its inability to perform the task. This highlights that as an AI-generator for medical publishing text, ChatGPT-3 should be used cautiously.
Reductions in Childhood Pneumonia Mortality After Vaccination in the United States
Authors: Paternina-Caicedo Angel , Smith Adrian D , Buchanich Jeanine , Garcia-Calavaro Christian , Alvis-Guzman Nelson , Narvaez Javier , de Oliveira Lucia Helena , De la Hoz-Restrepo Fernando 
Published: May 2023

Background:
We aim to estimate the magnitude of the reduction in pneumococcal pneumonia and meningitis mortality after the mass introduction of pneumococcal conjugate vaccine (PCV)7 and PCV13 in children in the United States.

Methods:
We assessed the trends in mortality rates from pneumococcal pneumonia and meningitis, in the United States between 1994 and 2017. We fitted an interrupted time-series negative binomial regression model (adjusted by trend, seasonality, PCV7/PCV13 coverage, and H. influenzae type b vaccine coverage) to estimate the counterfactual rates without vaccination. We reported a percent reduction in mortality estimates relative to the projected no-vaccination scenario, using the formula 1 minus the incidence risk ratio, with 95% confidence intervals (CIs).

Results:
Between 1994 and 1999 (the prevaccination period), the all-cause pneumonia mortality rate for 0–1-month-old children was 2.55 per 100,00 pop., whereas for 2–11 months-old children, this rate was 0.82 deaths per 100,000 pop. During the PCV7-period in 0–59-month-old children in the United States, the adjusted reduction of all-cause pneumonia was 13% (95% CI: 4–21) and 19% (95% CI: 0–33) of all-cause meningitis For PCV13, the reductions in this age group were 21% (95% CI: 4–35) for all-cause pneumonia mortality and 22% (95% CI: −19 to 48) for all-cause meningitis mortality. PCV13 had greater reductions of all-cause pneumonia than PCV13 in 6–11-month-old infants.

Conclusions:
The universal introduction of PCV7, and later PCV13, for children 0–59 months old in the United States was associated with decreases in mortality due to all-cause pneumonia.
Mental Health Matters: A Cross-Sectional Survey on Depression and Anxiety Symptoms and the Female and Male Athlete Triad
Authors: Olson Emily Miller , Miro Emily , Roche Megan , Mehta Shayna , Sainani Kristin , Kraus Emily 
Published: May 2023

Objective:
To determine the relationship between the female and male athlete triad with depression and anxiety symptoms.

Design:
Cross-sectional survey.

Setting:
Survey distributed online through social media to participants.

Participants:
Male and female high school, collegiate, and postcollegiate athletes.

Interventions:
Participants completed a survey assessing components of the female athlete triad and the Patient-Reported Outcomes Measurement Information System depression and anxiety short-form questionnaires.

Main Outcome Measures:
Participants were classified into those with no, mild, moderate, or severe depression symptoms or anxiety symptoms. A female athlete triad (Triad) cumulative risk score was calculated. Multinomial logistic regressions were used to assess the relationship between triad score and depression/anxiety.

Results:
Two hundred fifty-four men and 780 women completed the survey; 66.6% of women and 41.3% of men reported at least mild anxiety symptoms; 54.2% of women and 38.7% of men reported at least mild depression symptoms. Triad risk score was significantly related to moderate and severe depression symptoms (P < 0 .0001) and moderate (P = 0.003) and severe (P < 0 .0001) anxiety symptoms in women. We found no significant associations between Triad risk score and depression or anxiety symptoms in men.

Conclusions:
We found a correlation between the female athlete triad and moderate and severe depression and anxiety symptoms in women. Depression and anxiety symptoms were most strongly related to the low energy availability component of the Triad risk score and to the presence of eating disorders/disordered eating. This suggests that mental health illness is most tied to the behavioral aspects of the Triad.

Clinical Relevance:
This study demonstrates the importance of screening for and treating mental health illness in those diagnosed with low energy availability, disordered eating, and/or the female athlete triad in addition to focusing on a nutrition intervention.