bluuebunny/crossref_metadata_2025_split huggingface dataset:
NF1 mutation-driven neuronal hyperexcitability sets a threshold for tumorigenesis and therapeutic targeting of murine optic glioma
Authors: Anastasaki Corina , Chatterjee Jit , Koleske Joshua P , Gao Yunqing , Bozeman Stephanie L , Kernan Chloe M , Marco Y Marquez Lara I , Chen Ji-Kang , Kelly Caitlin E , Blair Connor J , Dietzen Dennis J , Kesterson Robert A , Gutmann David H 
Published: April 2024

Abstract

Background
With the recognition that noncancerous cells function as critical regulators of brain tumor growth, we recently demonstrated that neurons drive low-grade glioma initiation and progression. Using mouse models of neurofibromatosis type 1 (NF1)-associated optic pathway glioma (OPG), we showed that Nf1 mutation induces neuronal hyperexcitability and midkine expression, which activates an immune axis to support tumor growth, such that high-dose lamotrigine treatment reduces Nf1-OPG proliferation. Herein, we execute a series of complementary experiments to address several key knowledge gaps relevant to future clinical translation.

Methods
We leverage a collection of Nf1-mutant mice that spontaneously develop OPGs to alter both germline and retinal neuron-specific midkine expression. Nf1-mutant mice harboring several different NF1 patient-derived germline mutations were employed to evaluate neuronal excitability and midkine expression. Two distinct Nf1-OPG preclinical mouse models were used to assess lamotrigine effects on tumor progression and growth in vivo.

Results
We establish that neuronal midkine is both necessary and sufficient for Nf1-OPG growth, demonstrating an obligate relationship between germline Nf1 mutation, neuronal excitability, midkine production, and Nf1-OPG proliferation. We show anti-epileptic drug (lamotrigine) specificity in suppressing neuronal midkine production. Relevant to clinical translation, lamotrigine prevents Nf1-OPG progression and suppresses the growth of existing tumors for months following drug cessation. Importantly, lamotrigine abrogates tumor growth in two Nf1-OPG strains using pediatric epilepsy clinical dosing.

Conclusions
Together, these findings establish midkine and neuronal hyperexcitability as targetable drivers of Nf1-OPG growth and support the use of lamotrigine as a potential chemoprevention or chemotherapy agent for children with NF1-OPG.
Nasal septum-derived chondroprogenitor cells control mandibular condylar resorption consequent to orthognathic surgery: a clinical trial
Authors: Tesch Ricardo de Souza , Takamori Esther Rieko , Menezes Karla , Carias Rosana Bizon Vieira , Rebelatto Carmen Lucia Kuniyoshi , Senegaglia Alexandra Cristina , Daga Debora Regina , Fracaro Leticia , Robert Anny Waloski , Pinheiro Carlos Bruno Reis , Aguiar Marcelo de Freitas , Blanco Pablo Javier , Zilves Eduardo Guerreiro , Brofman Paulo Roberto Slud , Borojevic Radovan 
Published: April 2024

Abstract
Condylar resorption is an aggressive and disability form of temporomandibular joint (TMJ) degenerative disease, usually non-respondent to conservative or minimally invasive therapies and often leading to surgical intervention and prostheses implantation. This condition is also one of the most dreaded postoperative complications of orthognathic surgery, with severe cartilage erosion and loss of subchondral bone volume and mineral density, associated with a painful or not inflammatory processes. Because regenerative medicine has emerged as an alternative for orthopedic cases with advanced degenerative joint disease, we conducted a phase I/IIa clinical trial (U1111-1194-6997) to evaluate the safety and efficacy of autologous nasal septal chondroprogenitor cells. Ten participants underwent biopsy of the nasal septum cartilage during their orthognathic surgery. The harvested cells were cultured in vitro and analyzed for viability, presence of phenotype markers for mesenchymal stem and/or chondroprogenitor cells, and the potential to differentiate into chondrocytes, adipocytes, and osteoblasts. After the intra-articular injection of the cell therapy, clinical follow-up was performed using the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) and computed tomography (CT) images. No serious adverse events related to the cell therapy injection were observed during the 12-month follow-up period. It was found that autologous chondroprogenitors reduced arthralgia, promoted stabilization of mandibular function and condylar volume, and regeneration of condylar tissues. This study demonstrates that chondroprogenitor cells from the nasal septum may be a promise strategy for the treatment of temporomandibular degenerative joint disease that do not respond to other conservative therapies.
Automating Patient-reported Data Collection: Does it Work?
Authors: Bogor Sayah , Niknam Kian , Less Justin , Andaya Veronica , Swarup Ishaan 
Published: April 2024

Objective:
There are several electronic patient-reported outcomes (ePROs) vendors that are being used at institutions to automate data collection. However, there is little known about their success in collecting patient-reported outcomes (PROs) and it is unknown which patients are more likely to complete these surveys. In this study, we assessed rates of PRO completion, as well as determined factors that contributed to the completion of baseline and follow-up surveys.

Methods:
We queried our ePRO platform to assess rates of completion for baseline and follow-up surveys for patients from October 2019 to June 2022. All baseline surveys were administered before pediatric orthopaedic procedures, and follow-up surveys were sent at 3 months, 6 months, 1 year, and 2 years after surgery to patients with baseline data. Descriptive statistics were used to summarize the data. Univariate and multivariate analyses were performed to assess differences in patients who did and did not complete surveys.

Results:
This study included 1313 patients during the study period. Baseline surveys were completed by 66% of the cohort (n = 873 patients). There was a significant difference in race/ethnicity and language spoken in the patients who did and did not complete baseline surveys (P < 0.01) with lower rates of completion in African American, Hispanic, and Spanish-speaking patients. At least one follow-up was obtained for 68% of patients with baseline surveys (n = 597 patients). There were significant differences in completion rates based on race/ethnicity (P = 0.03) and language spoken (P = 0.01). There were lower rates of baseline completion for patients with government insurance in our multivariate analysis (odds ratio: 0.6, P < 0.01).

Conclusion:
Baseline and follow-up PRO data can be obtained from the majority of patients using automated ePRO platforms. However, additional focus is needed on collecting data from traditionally underrepresented patient groups to better understand outcomes in these patient populations.

Level of Evidence:
Level III—retrospective cohort study.
The Combined Influence of Sleep Disturbance and Depression on 12-month Outcomes After Lumbar Spine Surgery
Authors: Coronado Rogelio A. , Pennings Jacquelyn S. , Master Hiral , Brintz Carrie E. , Cole Keith R. , Helmy Joseph , Oleisky Emily R. , Davidson Claudia , Abtahi Amir M. , Stephens Byron F. , Archer Kristin R. 
Published: April 2024

Study Design.
Retrospective analysis of prospectively collected data.

Objective.
To examine the combined influence of preoperative sleep disturbance and depression on 12-month patient-reported outcomes after lumbar spine surgery (LSS).

Summary of Background Data.
Psychological and behavioral factors are considered major risk factors for poor outcomes after LSS. However, there is a need to explore the combined effects of preoperative factors such as sleep disturbance and depression. Understanding the influence of sleep disturbance and depression can inform evidence-based preoperative assessment and shared-decision making of preoperative and postoperative treatment.

Methods.
Data from 700 patients undergoing LSS were analyzed. Preoperative sleep disturbance and depression were assessed with PROMIS subscales. Established thresholds defined patients with moderate/severe symptoms. Outcomes for disability (Oswestry Disability Index) and back and leg pain (Numeric Rating Scales) were assessed preoperatively and at 12 months. Separate multivariable linear regressions examined the influence of each factor on 12-month outcomes with and without accounting for the other and in combination as a 4-level variable: (1) moderate/severe sleep disturbance alone, (2) moderate/severe depression alone, (3) both moderate/severe sleep disturbance and depression, (4) no moderate/severe sleep disturbance or depression.

Results.
Preoperative sleep disturbance and depression were associated with 12-month disability and pain (P<0.05). After accounting for depression, preoperative sleep disturbance remained associated with disability, while preoperative depression adjusting for sleep disturbance remained associated with all outcomes (P<0.05). Patients reporting both moderate/severe sleep disturbance and moderate/severe depression had 12.6 points higher disability and 1.5 points higher back and leg pain compared with patients without moderate/severe sleep disturbance or depression.

Conclusions.
The combination of sleep disturbance and depression impacts postoperative outcomes considerably. The high-risk group of patients with moderate/severe sleep disturbance and depression could benefit from targeted treatment strategies.

Level of Evidence.
Level II.
“Bubble Behind Iris” Technique in Descemet Membrane Endothelial Keratoplasty for Vitrectomized Eyes
Authors: Igarashi Ami , Shimizu Toshiki , Yokogawa Hideaki , Kobayashi Akira , Yamagami Satoru , Hayashi Takahiko 
Published: April 2024

Purpose:
Performing Descemet membrane keratoplasty (DMEK) in vitrectomized eyes can be challenging, owing to the compromised stability of the iris–lens diaphragm. This study presents a “bubble behind iris” technique in DMEK to achieve a shallower anterior chamber in vitrectomized and pseudophakic eyes.

Methods:
The patients with vitrectomized eyes who underwent DMEK between October 2022 and March 2023 were enrolled in this study. Following the insertion of the donor tissue into the anterior chamber, a 30-gauge blunt cannula was used to introduce an air bubble posterior to the iris. The depth of the anterior chamber was confirmed before unfolding the graft. Subsequently, the air bubble was carefully replaced with balanced salt solution insertion using the blunt cannula, and the anterior chamber was filled with gas for graft attachment.

Results:
This study included 3 eyes of 3 patients (3 men; mean age 62.3 ± 8.5 years). The best spectacle corrected visual acuity and central corneal thickness improved in all eyes with no notable complications.

Conclusions:
The “bubble behind iris” technique is a straightforward and minimally invasive approach for maintaining an optimal anterior chamber depth during DMEK in vitrectomized and pseudophakic eyes.
Influencing factors, surgical management, and predictors of posterior fossa tumors with hydrocephalus in children
Authors: Feng Jiaqi , Zhang Tianyi , He Dake , Mao Weiwei , Wang Weiping , Zhou Yabing , Wang Xiaoqiang 
Published: April 2024

Background:
Hydrocephalus is a common disease in neurosurgery. In pediatric central nervous system tumors, the proportion of posterior fossa tumors (PFTs) in children is high, hydrocephalus is often the first manifestation, and some cases have de novo or aggravated hydrocephalus after surgery.

Objective:
To conclude some controversies about the treatment methods and timeline of PFT with hydrocephalus.

Methods:
This article reviews the latest progress in the literature and practical problems encountered in clinical practices.

Results:
For most children, surgical drainage is the most effective treatment; however, medical treatment can be performed before surgery or a definite diagnosis is made. In children with PFT, the risk of hydrocephalus can be initially predicted according to the condition of the child, which has clear clinical significance for the selection of treatment methods and the evaluation of related prognosis.

Conclusion:
PFT is a common site for CNS tumors in children, and its clinical manifestations are often hydrocephalus-related. According to the condition of pediatric patients, early prediction of the risk of hydrocephalus has clear clinical significance for the selection of treatment methods and the evaluation of related prognoses.
Effectiveness and safety of Buzzy device in needle-related procedures for children under twelve years of age: A systematic review and meta-analysis
Authors: Jin Faguang , Wang Xiaofang , Qi Maomao , Zhang Wenhua , Zhang Yongfeng 
Published: April 2024

Background:
Pain transcends simple physiology, encompassing biological, emotional, psychological, and social facets. Children show pronounced immediate and enduring responses to pain-related procedures. The aim of this meta-analysis is to investigate the efficacy and safety of the Buzzy device for needle-related procedures in children aged twelve years or younger.

Methods:
PubMed, Web of Science, and Embase were searched from inception to July 2023. Only randomized controlled trials utilizing the Buzzy device for needle-related procedures in children under twelve years old were included. Two reviewers independently conducted study selection, data extraction, and risk of bias assessment. Random-effects models were utilized, and analyses were performed using mean differences or standardized mean differences as well as risk ratios.

Results:
A total of 19 studies were included, involving 2846 participants (Buzzy = 1095, Control = 1751). Compared to no intervention, the Buzzy device significantly reduced pain response [self-report SMD = −1.90 (−2.45, −1.36), parental SMD = −3.04 (−4.09, −1.99), observer SMD = −2.88 (−3.75, −2.02)] and anxiety scores [self-report SMD = −1.97 (−3.05, −0.88), parental SMD = −2.01 (−2.93, −1.08), observer SMD = −1.92 (−2.64, −1.19)]. Compared to virtual reality (VR), the Buzzy device reduced self-reported anxiety levels SMD = −0.47 (−0.77, −0.17), and compared to distraction cards, the Buzzy device reduced parental and observer-reported pain [parental SMD = −0.85 (−1.22, −0.48), observer SMD = −0.70 (−1.00, −0.40)] and anxiety [parental SMD = −0.96 (−1.46, −0.47), observer SMD = −0.91 (−1.40, −0.42)]. Subgroup analysis results showed that procedure type, patient age, measurement scales used, and distance of operation were not the reason of heterogeneity. The summarized first puncture attempt success rate did not differ from other interventions. There were no significant adverse events in the included studies.

Conclusion:
The Buzzy device reduces pain and anxiety in children during needle procedures, ensuring success and safety. Additionally, the effectiveness of the Buzzy device in reducing pain during venipuncture is superior when compared to its effectiveness during intramuscular injections.
Electrocardiogram prediction of atrial fibrillation risk after stroke: A protocol for systematic review and meta-analysis
Authors: Cheng Xiaoli , Wang Xiaoli 
Published: April 2024

Background:
Atrial fibrillation (AF) is one of the most common clinical arrhythmias. This study aims to predict the risk of post-stroke AF through electrocardiographic changes in sinus rhythm.

Methods:
We searched the MEDLINE (PubMed) and EMBASE databases to identify relevant research articles published until August 2023. Prioritized items from systematic reviews and meta-analyses were screened, and data related to AF detection rate were extracted. A meta-analysis using a random-effects model was conducted for data synthesis and analysis.

Results:
A total of 32 studies involving electrocardiograms (ECG) were included, with a total analysis population of 330,284 individuals. Among them, 16,662 individuals (ECG abnormal group) developed AF, while 313,622 individuals (ECG normal group) did not. ECG patterns included terminal P-wave terminal force V1, interatrial block (IAB), advanced interatrial block, abnormal P-wave axis, pulse rate prolongation, and atrial premature complexes. Overall, 15,762 patients experienced AF during the study period (4.77%). In the ECG abnormal group, the proportion was 14.21% (2367/16,662), while in the control group (ECG normal group), the proportion was 4.27% (13,395/313,622). The pooled risk ratio for developing AF was 2.45 (95% confidence interval [CI]: 2.02–2.98, P < .001), with heterogeneity (I
2) of 95%. The risk ratio values of alAB, P-wave terminal force V1, interatrial block, abnormal P-wave axis, pulse rate prolongation and atrial premature complexes were 4.12 (95% CI, 2.99–5.66), 1.47 (95% CI, 1.19–1.82), 2.54 (95% CI, 1.83–3.52), 1.70 (95% CI, 0.98–2.97), 2.65 (95% CI, 1.88–3.72), 3.79 (95% CI, 2.12–6.76), respectively.

Conclusion:
There is a significant correlation between ECG patterns and the occurrence of AF. The alAB exhibited the highest level of predictability for the occurrence of AF. These indicators support their use as screening tools to identify high-risk individuals who may benefit from further examinations or empirical anticoagulation therapy following stroke.
Direct gastric invasion from the liver metastasis of colorectal origin: A case report
Authors: Nam Jun Yeb , Lee Jung Wook , Kim Jae Hyun , Jung Minjung , Park Moo In , Moon Won , Kim Sung Eun , Jung Kyoungwon , Park Seun Ja 
Published: April 2024

Rationale:
Colorectal cancer is the third most common cancer diagnosed worldwide. At the time of diagnosis of colorectal cancer, one of the most common metastatic sites is liver. Gastric metastasis from colorectal origin is rare. Moreover, a direct invasion of the stomach, by hepatic metastasis from colorectal cancer, is particularly uncommon.

Patient concerns:
A 56-year-old male patient with hematochezia was referred to our hospital.

Diagnosis:
The patient was diagnosed with unresectable colorectal cancer because of the presence of >10 metastases involving both lobes of the liver.

Interventions and Outcomes:
After chemotherapy, the metastatic nodules in the liver nearly disappeared, except for a small nodule in segment VI. The patient underwent a radiofrequency ablation for the single lesion in the liver and laparoscopic low-anterior-resection for the primary tumor. Despite receiving various chemotherapy regimens, he experienced 6 recurrences, leading to 5 hepatectomies including a right hemi-hepatectomy, 1 pulmonary wedge resection, and 2 courses of radiation treatments. Lastly, a metastatic lesion in the liver was observed with invasion into the stomach. Subsequently, gastric wedge resection with resection of segments III and IV of the liver was performed. Direct invasion of the liver metastases into the stomach was confirmed histologically.

Lessons:
The patient is still alive, with a good quality of life, even after more than 8 years since the initial diagnosis. In the last instance of metastatic recurrence, direct invasion from the liver metastases into the stomach was observed, which is rare, and there are currently no reported cases.
Prognostic role of lymph node micrometastasis in pN0 esophageal cancer: A meta-analysis
Authors: Yang Yanhui , Wang Yi , Li Xiaoliang , Xie Xiaoyang 
Published: April 2024

Background:
To further identify the association between the lymph node micrometastasis (LNM) and long-term survival among pN0 esophageal cancer patients receiving the surgery.

Methods:
Several databases were searched for relevant studies up to June 22, 2023. The primary and secondary outcomes were separately overall survival (OS) and relapse-free survival (RFS) and hazard ratios (HRs) with 95% confidence intervals (CIs) were combined. Subgroup analysis based on pathological type and source of HR was further performed. All statistical analyses were conducted by STATA 15.0 software.

Results:
A total of 20 studies involving 1830 pN0 patients were included in this meta-analysis. The pooled results demonstrated that the presence of LNM indicated significantly worse OS (HR = 2.19, 95% CI = 1.77–2.70, P < .001) and RFS (HR = 2.15, 95% CI = 1.65–2.80, P < .001). Besides, subgroup analysis for the OS and RFS stratified by the pathological type (squamous cell carcinoma vs mixed esophageal cancer) and source of HR (reported vs estimated) further identified the significant relationship of LNM with prognosis in surgical esophageal cancer.

Conclusion:
The presence of LNM indicated significantly poorer long-term survival among operated pN0 esophageal cancer patients. LNM could serve as a novel and reliable prognostic indicator in surgical esophageal cancer.
Smokeless tobacco keratosis in oral mucosa with epithelial dysplasia: A case report
Authors: Kaabi Hassan Hamed 
Published: April 2024

Rationale:
Smokeless tobacco use is a risk factor for the development of various oral lesions, among which is smokeless tobacco keratosis (STK). This condition is caused by constant frictional irritation of smokeless tobacco products against the oral mucosa and appears as a White-to-gray plaque with wrinkling.

Patient concerns:
A 50-year-old man who had been using smokeless tobacco for 24 years visited our clinic complaining of changes in the lower right sulcus of the oral cavity for 10 days. Clinical examination revealed a unilateral, nonhomogeneous White lesion in the area of the complaint. Histopathological examination showed hyperkeratosis, areas of keratin plugging, and mild dysplastic epithelial changes.

Diagnosis:
The clinico-histopathological correlation suggested a diagnosis of STK with focal mild epithelial dysplasia.

Intervention and outcome:
A comprehensive management plan included maintaining oral hygiene, education on the detrimental effects of smokeless tobacco, advice to cease smoking, and regular follow-up to monitor the potential for malignant transformation. The patient was referred to a tobacco cessation society for tailored advice and counseling. On follow-up visits, there was an improvement in the lesion after habitual cessation.

Lessons:
The diagnosis of tobacco-related oral lesions is often delayed, which may result in malignant transformation. This illustrates the need to train healthcare professionals to identify tobacco-related conditions at an early stage and to educate patients regarding the harmful effects of tobacco use.