bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel dual-targeting c-Myc inhibitor D347-2761 represses myeloma growth via blocking c-Myc/Max heterodimerization and disturbing its stability
Authors: Yao Ruosi , Zhang Menghui , Zhou Jian , Liu Linlin , Zhang Yan , Gao Jian , Xu Kailin 
Published: May 2022

Abstract
Background
Transcription factor c-Myc plays a critical role in various physiological and pathological events. c-Myc gene rearrangement is closely associated with multiple myeloma (MM) progression and drug resistance. Thereby, targeting c-Myc is expected to be a useful therapeutic strategy for hematological disease, especially in MM.

Methods
Molecular docking-based virtual screening and dual-luciferase reporter gene assay were used to identify novel c-Myc inhibitors. Cell viability and flow cytometry were performed for evaluating myeloma cytotoxicity. Western blot, immunofluorescence, immunoprecipitation, GST pull down and Electrophoretic Mobility Shift Assay were performed for protein expression and interaction between c-Myc and Max. c-Myc downstream targets were measured by Q-PCR and Chromatin immunoprecipitation methods. Animal experiments were used to detect myeloma xenograft and infiltration in vivo.

Results
We successfully identified a novel c-Myc inhibitor D347-2761, which hindered the formation of c-Myc/Max heterodimer and disturbed c-Myc protein stability simultaneously. Compound D347-2761 dose-and time-dependently inhibited myeloma cell proliferation and induced apoptosis. Dual knockout Bak/Bax partially restored D347-2761-mediated cell death. Additionally, compound D347-2761 could, in combination with bortezomib (BTZ), enhance MM cell DNA damage and overcome BTZ drug resistance. Our in vivo studies also showed that compound D347-2761 repressed myeloma growth and distal infiltration by downregulating c-Myc expression. Mechanistically, novel dual-targeting c-Myc inhibitor D347-2761 promoted c-Myc protein degradation via stimulating c-Myc Thr58 phosphorylation levels, which ultimately led to transcriptional repression of CDK4 promoter activity.

Conclusions
We identified a novel dual-targeting c-Myc small molecular inhibitor D347-2761. And this study may provide a solid foundation for developing a novel therapeutic agent targeting c-Myc.
The feasibility and safety of cocktail treatment of triple anti-inflammatory agents loaded with gelatin sponge promotes early recovery after posterior percutaneous endoscopic cervical discectomy
Authors: Zou Peng , Zhang Xiaoping , Zhang Rui , Yang Jun-Song , Chu Lei , Wang Xiang-Fu , Wei Jian-Min , Chai Xin , Zhao Yuan-Ting , Liao Bo 
Published: May 2022

Abstract
Purpose
To investigate whether a cocktail therapy of dexamethasone, ropivacaine, dexmedetomidine, and vitamin B12 can achieve satisfactory pain relief and promote early functional recovery after PPECD.

Methods
Eighty single-level patients with CDH who received PPECD were retrospectively divided into two groups: the cocktail and control groups. Clinical data were recorded and evaluated by a dedicated physician who was not involved in the patient’s treatment. The primary clinical outcomes included visual analog scores (VASs) for upper limber pain and neck disability index (NDI) scores. The follow-up time points were preoperatively and postoperative 1 week, 1 month, 3 months, 6 months, and 12 months. The modified MacNab criteria was used to evaluate the surgical effect of the last follow-up.

Results
The follow-up data of 74 cases were complete, except 6 cases lost to follow-up. There was no significant difference between the two groups in demographics, duration of symptoms, operation stage (p > 0.05), and operation time (80.5 ± 5.5 vs. 81.5 ± 3.5 min). The VAS in the upper limbs pain was significantly higher postoperatively than preoperatively in both groups (p < 0.05). The cocktail group had a lower VAS than the control group 1 week postoperatively (p < 0.05); however, VAS not different between groups at the remaining time points. The NDI scores were significantly better postoperatively than preoperatively, and no significant differences were seen when comparing nodes at postoperative follow-up (p > 0.05). In the control group, two cases with foraminal stenosis were found to have unrelieved pain in the early postoperative period, but the pain was relieved at the final follow-up and did not convert to open decompression surgery.

Conclusions
Cocktail treatment, in which a drug sustained-release material made of gelatin sponge was impregnated with dexamethasone, ropivacaine, dexmedetomidine and vitamin B12, facilitates pain relief and early postoperative recovery after PPECD.
Can fat infiltration in the multifidus muscle be a predictor of postoperative symptoms and complications in patients undergoing lumbar fusion for degenerative lumbar spinal stenosis? A case–control study
Authors: Han Gengyu , Zou Da , Li Xinhang , Zhang Shuquan , Li Zhenxu , Zhou Siyu , Li Wei , Sun Zhuoran , Li Weishi 
Published: May 2022

Abstract
Purpose
This study aimed to explore whether 25% as the cutoff value of fat infiltration (FI) in multifidus (MF) could be a predictor of clinical outcomes of lumbar spinal stenosis (LSS) patients.

Methods
A total of 461 patients undergoing posterior lumbar interbody fusion for LSS with 1-year follow-up were identified. After sex- and age-match, 160 pairs of patients were divided into a FI < 25% group and a FI ≥ 25% group according to FI of MF at L4 on preoperative magnetic resonance imaging. Patient-reported outcomes including the visual analog scale scores (VAS) for back pain and leg pain and the Oswestry disability index (ODI) scores were evaluated. Bone nonunion and screw loosening were evaluated by dynamic X-ray.

Results
After matching, there was no significant difference in age, sex, body mass index, fusion to S1, number of fusion levels, osteoporosis, spondylolisthesis, smoking and diabetes. FI ≥ 25% group had significantly higher VAS for back pain, VAS for leg pain and ODI than FI < 25% group at 1-year follow-up. However, there was no significant difference in the change of them from baseline to 1-year follow-up between the two groups. In light of complications, FI ≥ 25% group had a significantly higher rate of bone nonunion than FI < 25% group, whereas there was no significant difference of screw loosening rates between the two groups.

Conclusion
MF FI might be a pragmatic cutoff value to predict bone nonunion in LSS patients, but it has little predictive value on screw loosening and postoperative improvement of symptoms.
Histologic evidence of tracheal stenosis directly resulting from SARS-CoV-2 tissue infiltration, a case series
Authors: Draeger Tyler B. , Tedesco Sarah , Andaz Shahriyour K. , Gibson Vanessa R. 
Published: May 2022

Abstract
Background
There has been an anecdotal increase in the incidence of tracheal stenosis that has coincided with the SARS-CoV-2 pandemic.

Case presentation
This is a case series in which we report clinical and pathologic findings of two patients who subsequently developed subglottic tracheal stenosis after having been hospitalized with COVID-19 pneumonia. Histopathologic analysis of tissue from these patients shows features consistent with tissue infiltrated with SARS-CoV-2 virus, namely multinucleated syncytial cells with prominent nucleoli.

Conclusion
Our findings directly implicate SARS-CoV-2 in the pathogenesis of tracheal stenosis.
VATS surgical anatomical resection of bronchopulmonary sequestration presenting as chest sepsis
Authors: Patel Akshay J. , Mangel Tobin , Perris Rebecca , El-Gamal Islam , Shatila Mohamed , Farooq Muhammad Omar , Kalkat Maninder S. 
Published: May 2022

Abstract
Background
Bronchopulmonary sequestration (BPS) is a malformation of the lungs resulting in lung tissue lacking direct communication to the tracheobronchial tree. Most cases demonstrate systemic arterial blood supply from the descending thoracic aorta, the abdominal aorta, celiac axis or splenic artery and venous drainage via the pulmonary veins with occasional drainage into azygos vein. BPS is considered a childhood disease and accounts for 0.15–6.40% of congenital pulmonary malformations. BPS is divided into intralobar sequestrations (ILS) and extralobar sequestrations (ELS) with ILS accounting for 75% of all cases.

Methods
Here we present our 11-year experience of dealing with BPS; all cases presented with recurrent chest sepsis in young-late adulthood regardless of the type of pathological sequestration. The surgical technique employed was a minimally invasive video-assisted thoracoscopic anterior approach (VATS).

Results
Between May 2010 and September 2021, we have operated on nine adult patients with bronchopulmonary sequestration who presented late with symptoms of recurrent chest sepsis. Most patients in the cohort had lower lobe pathology, with a roughly even split between right and left sided pathology. Moreover, the majority were life-long never smokers and an equal preponderance in males and females. The majority were extralobar sequestrations (56%) with pathological features in keeping with extensive bronchopneumonia and bronchiectasis. There were no major intra-operative or indeed post-operative complications. Median length of stay was 3 days.

Conclusions
Dissection and division of the systemic feeding vessel was readily achievable through a successful anterior VATS approach, regardless of the type of sequestration and without the use of pre-operative coiling of embolization techniques. This approach gave excellent access to the hilar structures yet in this pathology, judicious and perhaps a lower threshold for open approach should be considered.
Health Information and Monitoring of Sexually Transmitted Infections (SIM study): a single-center, parallel, three-arm randomized controlled trial protocol for enhancing adherence to syphilis treatment and follow-up
Authors: Wendland Eliana M. , de Oliveira Vanessa M. , Pedrotti Luana Giongo , Souza Flavia M. A. , Pereira Gerson F. M. , Gerbase Antonio 
Published: May 2022

Abstract
Background
Syphilis has recently resurfaced as a significant public health problem. Since the 2000s, isolated syphilis outbreaks have increasingly occurred in North America, Europe, and Australia; in Brazil, there have been progressive increases in both congenital and acquired syphilis. There are several possible explanations, such as misdiagnosis of acquired syphilis, which could increase the number of untreated transmitters in the population; failure to initiate or complete treatment; and nontreatment of sexual partners (leading to reinfection). Mobile technologies have been successfully used to promote behavior changes and can positively impact treatment and follow-up adherence in patients with infectious diseases. The purpose of this clinical trial is to evaluate treatment and monitoring methods in patients with syphilis, including follow-up by telephone, via a game in a smartphone app, and at public health centers.

Methods
The SIM study is a single-center, randomized controlled trial with a 12-month follow-up period. The aim is to identify the most effective method of follow-up regarding patient compliance with treatment. The tests will be performed in a mobile unit in easily accessible locations. The goal is to perform 10,000 rapid tests for syphilis. Patients with a confirmed diagnosis according to VDRL tests will be randomized to one of three arms: telephone, smartphone game, or conventional in-person follow-up. All analyses will follow the intention-to-treat principle.

Conclusion
If we find differences in effectiveness, a major change in the conventional approach for this patient population may be needed, potentially affecting current Brazilian health policy strategies.

Trial registration
NTC04753125. Version 1 of protocol 1/09/2020.
Knockdown of the stem cell marker Musashi-1 inhibits endometrial cancer growth and sensitizes cells to radiation
Authors: Falke Isabel , Troschel Fabian M. , Palenta Heike , Löblein Maria T. , Brüggemann Kathrin , Borrmann Katrin , Eich Hans Theodor , Götte Martin , Greve Burkhard 
Published: May 2022

Abstract
Background
Endometrial carcinoma is the most common gynecological cancer in Europe. Musashi-1 is known to be a key regulator of endometrial cancer stem cells and a negative prognostic marker. In the present study, we aimed to understand growth and gene expression patterns in endometrial carcinoma after Musashi-1 knockdown in vitro and in vivo. Changes in therapeutic resistance were also assessed.

Methods
First, we performed analyses to understand Musashi-1 expression patterns using The Cancer Genome Atlas database. We then proceeded to assess effects of small interfering RNA-based Musashi-1 targeting in two endometrial carcinoma cell lines, Ishikawa and KLE. After quantifying baseline changes in cell metabolism, we used MTT tests to assess chemotherapy effects and colony formation assays to understand changes in radioresistance. For mechanistic study, we used quantitative polymerase chain reaction (qPCR) and western blotting of key Musashi-1 target genes and compared results to primary tissue database studies. Finally, xenograft experiments in a mouse model helped understand in vivo effects of Musashi-1 knockdown.

Results
Musashi-1 is aberrantly expressed in primary tumor tissues. In vitro, silencing of Musashi-1 resulted in a strong decline in cell proliferation and radioresistance, while chemoresistance remained unchanged. Loss of Musashi-1 led to downregulation of telomerase, DNA-dependent protein kinase, the Notch pathway and overexpression of cyclin-dependent kinase inhibitor p21, the latter of which we identified as a key mediator of Msi-1 knockdown-related anti-proliferative signaling. In vivo, the anti-proliferative effect was confirmed, with Msi-1 knockdown tumors being about 40% reduced in size.

Conclusions
Musashi-1 knockdown resulted in a strong decrease in endometrial cancer proliferation and a loss of radioresistance, suggesting therapeutic potential.
Fibronectin extra domain A (FN-EDA) causes glaucomatous trabecular meshwork, retina, and optic nerve damage in mice
Authors: Mavlyutov Timur A. , Myrah Justin J. , Chauhan Anil K. , Liu Yang , McDowell Colleen M. 
Published: May 2022

Abstract
Background
Elevated intraocular pressure (IOP) is a major risk factor for the development and progression of primary open angle glaucoma and is due to trabecular meshwork (TM) damage. Here, we investigate the role of an endogenous Toll-like receptor 4 (TLR4) ligand, FN-EDA, in the development of glaucoma utilizing a transgenic mouse strain (B6.EDA+/+) that constitutively expresses only FN containing the EDA isoform.

Methods
Eyes from C57BL6/J (wild-type), B6.EDA+/+ (constitutively active EDA), B6.EDA-/- (EDA null) mice were processed for electron microscopy and consecutive images of the entire length of the TM and Schlemm’s canal (SC) from anterior to posterior were collected and montaged into a single image. ECM accumulation, basement membrane length, and size and number of giant vacuoles were quantified by ImageJ analysis. Tlr4 and Iba1 expression in the TM and ONH cells was conducted using RNAscope in situ hybridization and immunohistochemistry protocols. IOP was measured using a rebound tonometer, ON damage assessed by PPD stain, and RGC loss quantified in RBPMS labeled retina flat mounts.

Results
Ultrastructure analyses show the TM of B6.EDA+/+ mice have significantly increased accumulation of ECM between TM beams with few empty spaces compared to C57BL/6 J mice (p < 0.05). SC basement membrane is thicker and more continuous in B6.EDA+/+ mice compared to C57BL/6 J. No significant structural differences are detected in the TM of EDA null mice. Tlr4 and Iba1 expression is increased in the TM of B6.EDA+/+ mice compared to C57BL/6 J eyes (p < 0.05). IOP is significantly higher in B6.EDA+/+ mice compared to C57BL/6 J eyes (p < 0.001), and significant ON damage (p < 0.001) and RGC loss (p < 0.05) detected at 1 year of age. Tlr4 mRNA is expressed in mouse ONH cells, and is present in ganglion cell axons, microglia, and astrocytes. There is a significant increase in the area occupied by Iba-1 positive microglia cells in the ONH of B6.EDA+/+ mice compared to C57BL/6 J control eyes (p < 0.01).

Conclusions
B6.EDA+/+ mice have increased ECM accumulation in the TM, elevated IOP, enhanced proinflammatory changes in the ONH, loss of RGCs, and ONH damage. These data suggest B6.EDA+/+ mice recapitulate many aspects of glaucomatous damage.
Assessment of echinococcosis control in Tibet Autonomous Region, China
Authors: Wang Liying , Gongsang Quzhen , Pang Huasheng , Qin Min , Wang Ying , Li Jingzhong , Frutos Roger , Gavotte Laurent 
Published: May 2022

Abstract
Background
In China the highest prevalence of echinococcosis is in Tibet Autonomous Region (TAR). The government has issued documents and implemented comprehensive prevention and control measures focusing on controlling the source of infection of echinococcosis. It was very important to understand the implementation and effect of infectious source control measures. The purpose of this study was to examine the implementation of measures to control infectious source (domestic and stray dogs) in TAR and to assess their effectiveness.

Methods
We collected data on domestic dog registration and deworming and stray dog sheltering in 74 counties/districts in the TAR from 2017 to 2019. Fecal samples from domestic dogs were collected from randomly selected towns to determine Echinococcus infection in dogs using coproantigen ELISA. We analyzed the data to compare the canine rate of infection between 2016 and 2019. The data analysis was performed by SPSS statistical to compare dog infection rate in 2016 and 2019 by chi-square test, and ArcGIS was used for mapping.

Results
From 2017 to 2019, 84 stray dog shelters were built in TAR, and accumulatively 446,660 stray or infected dogs were arrested, sheltered, or disposed of. The number of domestic dogs went downward, with an increased registration management rate of 78.4% (2017), 88.8% (2018), and 99.0% (2019). Dogs were dewormed 5 times in 2017, 12 times in 2018, and 12 times in 2019. The dog infection rate was 1.7% (252/14,584) in 2019, significantly lower than 7.3% (552/7564) from the survey of echinococcosis prevalence in Tibet in 2016 (P < 0.05).

Conclusion
Between 2017 and 2019, the number of stray dogs and infection rate of Echinococcus spp. in domestic dogs decreased significantly, indicating that dogs were effectively controlled as a source of infection in TAR and reflecting a significant decrease in the risk of echinococcosis transmission.

Graphical Abstract
Methylprednisolone in the treatment of lymphangioleiomyomatosis
Authors: Dale Ventour , Thannoo Geosanne , Ramlakhan Shammi 
Published: May 2022

AbstractThis case report proposes the use of pulsed methylprednisolone in a patient with lymphangioleiomyomatosis (LAM) who was invasively ventilated. A 38-year-old, East Indian gravida 4, para 1+2, patient with worsening respiratory function with spontaneous pneumothoraxes and hypoxemia was pulsed with methylprednisolone leading to rapid resolution of respiratory failure.The author proposes pulsed methylprednisolone in ventilated LAM patients, which gives another option to patients which resulted in alleviation of hypoxemia and maintaining foetal viability.
Economic Cost and Sustainability of Oral Therapies in Precision Oncology
Authors: Desai Aakash P. , Scheckel Caleb J. , Soderberg Leah C. , Jensen Chelsee J. , Orme Jacob J. , Tella Sri H. , Kommalapati Anuhya , Pritchett Joshua C. , Khera Nandita , Mahipal Amit , Go Ronald S. ,   on behalf of the Mayo Clinic Hematology and ONcology Outcomes Research (HONOR) Group
Published: May 2022

PURPOSE: Precision oncology promises improved outcomes but the cost-effectiveness and accessibility of targeted therapies is debatable. We report price change patterns from 2015 to 2019 for several oral anticancer medications for common solid tumor malignancies. METHODS: We collected provider utilization and payment data from the public Medicare Part D database and extracted drug price information for commonly prescribed targeted oral anticancer agents for lung, breast, and prostate cancer. We then calculated median Pearson correlation coefficient values for various drugs (containing more than two data points) within each therapeutic class. We also calculated compound annual growth rates (CAGRs) for medication costs within each class and compared them with the consumer price index (CPI). RESULTS: Our study included six epidermal growth factor receptor inhibitors (EGFRi; one generic), five anaplastic lymphoma kinase inhibitors (ALKi), two B-Raf inhibitors (BRAFi), three hormonal agents (one generic), three cyclin-dependent kinases 4 and 6 inhibitors (CDK4/6i), two poly-ADP-ribose inhibitors (PARPi), and seven antiandrogen agents (two generic). The median (range) Pearson correlation coefficient values for cost of drugs within each therapeutic class were 0.967 (0.915-0.978) for EGFRi, 0.981 (0.966-0.989) for ALKi, 0.996 for BRAFi, 0.994 (0.992-0.999) for CDK4/6i, 0.855 for PARPi, and 0.442 (–0.522 to 0.962) for antiandrogens. Therapies with two or fewer data points (generic erlotinib, dacomitinib, abiraterone, apalutamide, and darolutamide) were excluded. The median CAGRs in costs over the 5-year period were 4.56% (EGFRi), 6.40% (ALKi), 2.58% (BRAFi), 5.48% (hormonal agents), 5.21% (CDK4/6i), 27.29% (PARPi), and 34.8% (antiandrogens). The CPI over 5 years was 2.26%/year, and the average inflation rate was 1.90%/year. CONCLUSION: The median CAGR in costs for modern oral precision-driven cancer therapeutic classes mostly outpaced CPI and the average inflation. Increase in cost within the same class should be weighed against incremental clinical benefit for the patients to ensure that rising costs do not limit access to targeted therapies.
Pinch2 regulates myelination in the mouse central nervous system
Authors: Paes de Faria Joana , Vale-Silva Raquel S. , Fässler Reinhard , Werner Hauke B. , Relvas João B. 
Published: May 2022

ABSTRACT
The extensive morphological changes of oligodendrocytes during axon ensheathment and myelination involve assembly of the Ilk-Parvin-Pinch (IPP) heterotrimeric complex of proteins to relay essential mechanical and biochemical signals between integrins and the actin cytoskeleton. Binding of Pinch1 and Pinch2 isoforms to Ilk is mutually exclusive and allows the formation of distinct IPP complexes with specific signaling properties. Using tissue-specific conditional gene ablation in mice, we reveal an essential role for Pinch2 during central nervous system myelination. Unlike Pinch1 gene ablation, loss of Pinch2 in oligodendrocytes results in hypermyelination and in the formation of pathological myelin outfoldings in white matter regions. These structural changes concur with inhibition of Rho GTPase RhoA and Cdc42 activities and phenocopy aspects of myelin pathology observed in corresponding mouse mutants. We propose a dual role for Pinch2 in preventing an excess of myelin wraps through RhoA-dependent control of membrane growth and in fostering myelin stability via Cdc42-dependent organization of cytoskeletal septins. Together, these findings indicate that IPP complexes containing Pinch2 act as a crucial cell-autonomous molecular hub ensuring synchronous control of key signaling networks during developmental myelination.