bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gabapentin and intrathecal morphine combination therapy results in decreased oral narcotic use and more consistent pain scores after posterior spinal fusion for adolescent idiopathic scoliosis
Authors: Li Ying , Swallow Jennylee , Robbins Christopher , Caird Michelle S. , Leis Aleda , Hong Rebecca A. 
Published: November 2021

Abstract
Background
Gabapentin and intravenous patient-controlled analgesia (PCA) can reduce postoperative pain scores, postoperative opioid use, and time to completing physical therapy compared to PCA alone after posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS). Gabapentin combined with intrathecal morphine has not been studied. The primary purpose of this retrospective study was to evaluate whether perioperative gabapentin and intrathecal morphine provide more effective pain control than intrathecal morphine alone after PSF for AIS.

Methods
Patients aged 11 to 18 years who underwent PSF for AIS were identified. Patients who received intrathecal morphine only (ITM group) were matched by age and sex to patients who received intrathecal morphine and perioperative gabapentin (ITM+GABA group). The ITM+GABA group received gabapentin preoperatively and for up to 2 days postoperatively. Both groups received oxycodone and the same non-narcotic adjuvant medications.

Results
Our final study group consisted of 50 patients (25 ITM, 25 ITM+GABA). The ITM+GABA group had significantly lower mean total oxycodone consumption during the hospitalization (0.798 vs 1.036 mg/kg, P<0.015). While the ITM group had a lower mean pain score between midnight and 8 am on POD 1 (2.4 vs 3.7, P=0.026), pain scores were significantly more consistent throughout the postoperative period in ITM+GABA group. The ITM+GABA group experienced less nausea/vomiting (52% vs 84%, P=0.032) and pruritus (44% vs 72%, P=0.045). Time to physical therapy discharge and length of hospital stay were similar.

Conclusion
Addition of gabapentin resulted in reduced oral opioid consumption and more consistent postoperative pain scores after PSF for AIS. The patients who received intrathecal morphine and gabapentin also experienced a lower rate of nausea/vomiting and pruritus.

Trial registration
All data was collected retrospectively from chart review, with institutional IRB approval. Trial registration is not applicable.
Circular RNA circHERC4 as a novel oncogenic driver to promote tumor metastasis via the miR-556-5p/CTBP2/E-cadherin axis in colorectal cancer
Authors: He Jiehua , Chu Ziqiang , Lai Wei , Lan Qiusheng , Zeng Yujie , Lu Daning , Jin Shaowen , Xu Heyang , Su Pengwei , Yin Dong , Chu Zhonghua , Liu Lu 
Published: November 2021

Abstract
Background
The main cause of death in colorectal cancer patients is metastasis. Accumulating evidences suggest that circRNA plays pivotal roles in cancer initiation and development. However, the underlying molecular mechanisms of circRNAs that orchestrate cancer metastasis remain vague and need further clarification.

Methods
Two paired CRC and adjacent normal tissues were used to screen the upregulated circRNAs by circRNA-seq; then, cell invasion assay was applied to confirm the functional invasion-related circRNAs. According to the above methods, circHERC4 (hsa_circ_0007113) was selected for further research. Next, we investigated the clinical significance of circHERC4 in a large cohort of patients with CRC. The oncogenic activity of circHERC4 was investigated in both CRC cell lines and animal xenograft studies. Finally, we explored the molecular mechanisms underlying circHERC4 as a malignant driver.

Results
We demonstrated that circHERC4 was aberrantly elevated in CRC tissues (P < 0.001), and was positively associated with lymph node metastasis and advanced tumor grade (P < 0.01). Notably, the expression of circHERC4 was associated with worse survival in patients with CRC. Silencing of circHERC4 significantly inhibited the proliferation and migration of two highly aggressive CRC cell lines and reduced liver and lung metastasis in vivo. Mechanistically, we revealed that circHERC4 inactivated the tumor suppressor, miR-556-5p, leading to the activation of CTBP2/E-cadherin pathway which promotes tumor metastasis in CRC.

Conclusions
CircHERC4 exerts critical roles in promoting tumor aggressiveness through miR-556-5p/CTBP2/E-cadherin pathway and is a prognostic biomarker of the disease, suggesting that circHERC4 may serve as an exploitable therapeutic target for patients with CRC.
STOML2 interacts with PHB through activating MAPK signaling pathway to promote colorectal Cancer proliferation
Authors: Ma Wenhui , Chen Yuehong , Xiong Wenjun , Li Wenyi , Xu Zhuoluo , Wang Ying , Wei Zhigang , Mou Tingyu , Wu Zhaokun , Cheng Mingzhen , Zou Yini , Zhu Yu , Zhou Weijie , Liu Feng , Geng Yan 
Published: November 2021

Abstract
Background
Highly expressed STOML2 has been reported in a variety of cancers, yet few have detailed its function and regulatory mechanism. This research aims to reveal regulatory mechanism of STOML2 and to provide evidence for clinical therapeutics, via exploration of its role in colorectal cancer, and identification of its interacting protein.

Methods
Expression level of STOML2 in normal colon and CRC tissue from biobank in Nanfang Hospital was detected by pathologic methods. The malignant proliferation of CRC induced by STOML2 was validated via gain-of-function and loss-of-function experiments, with novel techniques applied, such as organoid culture, orthotopic model and endoscopy monitoring. Yeast two-hybrid assay screened interacting proteins of STOML2, followed by bioinformatics analysis to predict biological function and signaling pathway of candidate proteins. Target protein with most functional similarity to STOML2 was validated with co-immunoprecipitation, and immunofluorescence were conducted to co-localize STOML2 and PHB. Pathway regulated by STOML2 was detected with immunoblotting, and subsequent experimental therapy was conducted with RAF inhibitor Sorafenib.

Results
STOML2 was significantly overexpressed in colorectal cancer and its elevation was associated with unfavorable prognosis. Knockdown of STOML2 suppressed proliferation of colorectal cancer, thus attenuated subcutaneous and orthotopic tumor growth, while overexpressed STOML2 promoted proliferation in cell lines and organoids. A list of 13 interacting proteins was screened out by yeast two-hybrid assay. DTYMK and PHB were identified to be most similar to STOML2 according to bioinformatics in terms of biological process and signaling pathways; however, co-immunoprecipitation confirmed interaction between STOML2 and PHB, rather than DTYMK, despite its highest rank in previous analysis. Co-localization between STOML2 and PHB was confirmed in cell lines and tissue level. Furthermore, knockdown of STOML2 downregulated phosphorylation of RAF1, MEK1/2, and ERK1/2 on the MAPK signaling pathway, indicating common pathway activated by STOML2 and PHB in colorectal cancer proliferation.

Conclusions
This study demonstrated that in colorectal cancer, STOML2 expression is elevated and interacts with PHB through activating MAPK signaling pathway, to promote proliferation both in vitro and in vivo. In addition, combination of screening assay and bioinformatics marks great significance in methodology to explore regulatory mechanism of protein of interest.
SNHG17 promotes colorectal tumorigenesis and metastasis via regulating Trim23-PES1 axis and miR-339-5p-FOSL2-SNHG17 positive feedback loop
Authors: Bian Zehua , Zhou Mingyue , Cui Kaisa , Yang Fan , Cao Yulin , Sun Shengbai , Liu Bingxin , Gong Liang , Li Jiuming , Wang Xue , Li Chaoqun , Yao Surui , Yin Yuan , Huang Shenglin , Fei Bojian , Huang Zhaohui 
Published: November 2021

Abstract
Background
Small nucleolar RNA host gene (SNHG) long noncoding RNAs (lncRNAs) are frequently dysregulated in human cancers and involved in tumorigenesis and progression. SNHG17 has been reported as a candidate oncogene in several cancer types, however, its regulatory role in colorectal cancer (CRC) is unclear.

Methods
SNHG17 expression in multiple CRC cohorts was assessed by RT-qPCR or bioinformatic analyses. Cell viability was evaluated using Cell Counting Kit-8 (CCK-8) and colony formation assays. Cell mobility and invasiveness were assessed by Transwell assays. Tumor xenograft and metastasis models were applied to confirm the effects of SNHG17 on CRC tumorigenesis and metastasis in vivo. Immunohistochemistry staining was used to measure protein expression in cancer tissues. RNA pull-down, RNA immunoprecipitation, chromatin immunoprecipitation, and dual luciferase assays were used to investigate the molecular mechanism of SNHG17 in CRC.

Results
Using multiple cohorts, we confirmed that SNHG17 is aberrantly upregulated in CRC and correlated with poor survival. In vitro and in vivo functional assays indicated that SNHG17 facilitates CRC proliferation and metastasis. SNHG17 impedes PES1 degradation by inhibiting Trim23-mediated ubiquitination of PES1. SNHG17 upregulates FOSL2 by sponging miR-339-5p, and FOSL2 transcription activates SNHG17 expression, uncovering a SNHG17-miR-339-5p-FOSL2-SNHG17 positive feedback loop.

Conclusions
We identified SNHG17 as an oncogenic lncRNA in CRC and identified abnormal upregulation of SNHG17 as a prognostic risk factor for CRC. Our mechanistic investigations demonstrated, for the first time, that SNHG17 promotes tumor growth and metastasis through two different regulatory mechanisms, SNHG17-Trim23-PES1 axis and SNHG17-miR-339-5p-FOSL2-SNHG17 positive feedback loop, which may be exploited for CRC therapy.
A systematic review and meta-analysis of enrollment into ARDS and sepsis trials published between 2009 and 2019 in major journals
Authors: Krutsinger Dustin C. , Yadav Kuldeep N. , Harhay Michael O. , Bartels Karsten , Courtright Katherine R. 
Published: November 2021

AbstractBackgroundEnrollment problems are common among randomized controlled trials conducted in the ICU. However, little is known about actual trial enrollment rates and influential factors. We set out to determine the overall enrollment rate in recent randomized controlled trials (RCTs) of patients with acute respiratory distress syndrome (ARDS), acute lung injury (ALI), or sepsis, and which factors influenced enrollment rate.MethodsWe conducted a systematic review by searching Pubmed using predefined terms for ARDS/ALI and sepsis to identify individually RCTs published among the seven highest impact general medicine and seven highest impact critical care journals between 2009 and 2019. Cluster randomized trials were excluded. Data were extracted by two independent reviewers using an electronic database management system. We conducted a random-effects meta-analysis of the eligible trials for the primary outcome of enrollment rate by time and site.ResultsOut of 457 articles identified, 94 trials met inclusion criteria. Trials most commonly evaluated pharmaceutical interventions (53%), were non-industry funded (78%), and required prospective informed consent (81%). The overall mean enrollment rate was 0.83 (95% confidence interval: 0.57–1.21) participants per month per site. Enrollment in ARDS/ALI and sepsis trials were 0.48 (95% CI 0.32–0.70) and 0.98 (95% CI 0.62–1.56) respectively. The enrollment rate was significantly higher for single-center trials (4.86; 95% CI 2.49–9.51) than multicenter trials (0.52; 95% CI 0.41–0.66). Of the 36 trials that enrolled < 95% of the target sample size, 8 (22%) reported slow enrollment as the reason.ConclusionsIn this systematic review and meta-analysis, recent ARDS/ALI and sepsis clinical trials had an overall enrollment rate of less than 1 participant per site per month. Novel approaches to improve critical care trial enrollment efficiency are needed to facilitate the translation of best evidence into practice.
Cone beam computed tomography for detecting residual stones in percutaneous nephrolithotomy, a randomized controlled trial (CAPTURE) protocol
Authors: Kingma R. A. , de Jong I. J. , Greuter M. J. W. , Roemeling S. 
Published: November 2021

Abstract
Introduction
Percutaneous nephrolithotomy (PCNL) is the standard surgical treatment method for large kidney stones. Its aim is to achieve a stone-free status, since any residual fragments (RFs) after PCNL are likely to cause additional morbidity or stone growth. Enhancing intraoperative detectability of RFs could lead to increased stone-free rates and decreased re-intervention rates. Cone beam computed tomography (CBCT) has recently been introduced in urology as a feasible method for intraoperatively imaging RFs. The aim of this trial is to determine the added value of CBCT in percutaneous nephrolithotomy, by measuring differences in stone-related morbidity for patients with procedures in which a CBCT is used versus patients with procedures without the use of CBCT.

Methods
The CAPTURE trial is an investigator-initiated single-center, randomized controlled trial (RCT) in adult patients who have an indication for percutaneous nephrolithotomy. A contemporary percutaneous nephrolithotomy is performed. Once the surgeon is convinced of a stone-free status by means of fluoroscopy and nephroscopy, randomization allocates patients to either the study group in whom an intraoperative CBCT scan is performed or to the control group in whom no intraoperative CBCT scan is performed. The main endpoint is the stone-free status as assessed four weeks postoperatively by low-dose non-contrast abdominal CT, as a standard follow-up procedure. Secondary endpoints include the number of PCNL procedures required and the number of stone-related events (SREs) registered. The total study population will consist of 320 patients that undergo PCNL and are eligible for randomization for an intraoperative CBCT scan.

Discussion
We deem a randomized controlled trial to be the most effective and reliable method to assess the efficacy of CBCT in PCNL. Though some bias may occur due to the impossibility of blinding the urologist at randomization, we estimate that the pragmatic nature of the study, standardized circumstances, and follow-up methods with pre-defined outcome measures will result in a high level of evidence.

Trial registration
Netherlands Trial Register (NTR) NL8168, ABR NL70728.042.19. Registered on 15 October 2019. Prospectively registered.
Efficient iterative methods for finding simultaneously all the multiple roots of polynomial equation
Authors: Shams Mudassir , Rafiq Naila , Kausar Nasreen , Agarwal Praveen , Park Choonkil , Momani Shaher 
Published: November 2021

AbstractTwo new iterative methods for the simultaneous determination of all multiple as well as distinct roots of nonlinear polynomial equation are established, using two suitable corrections to achieve a very high computational efficiency as compared to the existing methods in the literature. Convergence analysis shows that the orders of convergence of the newly constructed simultaneous methods are 10 and 12. At the end, numerical test examples are given to check the efficiency and numerical performance of these simultaneous methods.
Long-term evaluation of factors affecting removal torque of microimplants
Authors: Kim Ho-Jin , Park Hyo-Sang 
Published: November 2021

Abstract
Background
The current study aimed to evaluate factors affecting the long-term stability of microimplants using removal torque and the correlation between removal torque and clinical variables.

Materials and methods
This research evaluated 703 microimplants placed in 354 patients (mean age: 30.4 ± 12.1 years). The removal torque was evaluated according to various clinical variables including sex, age, placement site, microimplant size, and placement method (self-drilling versus pre-drilling). Pearson correlation and stepwise multiple linear regression analyses were performed to investigate different variables and their association with removal torque.

Results
The mean removal torque was significantly higher in the mandible (4.46 N cm) than in the maxilla (3.73 N cm). The values in the posterior teeth/retromolar areas were significantly higher than those in the anterior teeth area. There were no significant difference in terms of sex. Teenagers had a lower removal torque than older adults in the mandible, but not in the maxilla. Microimplants with a greater length and diameter, except for those with a greater diameter in the maxilla, was associated with a higher removal torque. Regardless of placement torque, the removal torque convergently reached approximately 4 N cm in both placement methods. The removal torque was significantly correlated with screw length in the self-drilling group and with diameter in the pre-drilling group.

Conclusions
Removal torque was related with placement site, age, placement method, and length and diameter of microimplants.
Crustal deformation detection capability of the GNSS-A seafloor geodetic observation array (SGO-A), provided by Japan Coast Guard
Authors: Yokota Yusuke , Ishikawa Tadashi , Watanabe Shun-ichi , Nakamura Yuto 
Published: November 2021

AbstractThe GNSS-A technique is an observation method that can detect seafloor crustal deformations with centimeter-level positioning accuracy. The GNSS-A seafloor geodetic observation array operated by the Japan Coast Guard (SGO-A) has been constructed near the Japanese Islands along the Nankai Trough and the Japan Trench. This observation array has detected several earthquakes’ displacements and episodic slow crustal deformation. To compare the detection results of SGO-A with other observation networks and expand the SGO-A coverage area, it is necessary to correctly understand its detection capability. In this paper, numerical simulations and statistical verifications were used to assess the capabilities of the present GNSS-A system using a manned vessel (observation frequency: 4–6 times/year, positioning accuracy: standard deviation = 1.5 cm) to detect (1) secular deformation only, (2) a transient slip event only and (3) secular deformation and a transient event together. We verified these results with appropriate thresholds and found the following features: When it is known that there is no transient event, the 95% confidence level (CL) for the estimation of secular crustal deformation rate with 4-year observation is about 0.5–0.8 cm/year; when the deformation rate is known, a signal of about 3.0 cm can be detected by observations of about 4 times before and after the transient event. When the deformation rate and the transient event are detected together, to keep the false positive low (about 0.05), the false negative becomes high (about 0.7–0.2 for detecting a signal of 4.5–6.0 cm). The determined rate and event variations are approximately 1.8 cm/year (95%CL) and 1.5 cm (standard deviation), respectively. We also examined the detection capability for higher observation frequency and positioning accuracy, to examine how the detection capability improves by technological advancements in the future. Additionally, we calculated the spatial range of event detectability using the determined values of detection sensitivity. Obtained results show that each seafloor site can detect a slip event of < 1.0 m scale within about 30 km radius, and approximately one-third of the subseafloor slip event over 100 km from land along the Nankai Trough can only be detected by SGO-A.
A case of Epstein Barr virus-associated primary squamous cell carcinoma of stomach
Authors: Katsura Yuki , Okabayashi Takehiro , Ozaki Kazuhiro , Shibuya Yuichi , Iwata Jun 
Published: November 2021

Abstract
Background
Primary squamous cell carcinoma (SCC) of stomach is extremely rare. The pathogenesis of SCC of stomach remains unclear. There is only one report that Epstein Barr virus (EBV) infection may be involved in the pathogenesis of SCC arising in the stomach ever before. Here, we report a case of Epstein Barr virus infection-associated primary SCC of stomach in a 70-year-old woman. She was presented to the referring hospital with hematemesis. Initial endoscopy revealed a bleeding gastric ulcer in the upper part of gastric corpus and the coagulation therapy was followed. After a 3-month follow-up, endoscopy revealed a submucosal tumor-like protrusion instead of an ulcer. Computed tomography revealed a mass in the upper part of stomach and swollen lymph nodes along with the lesser curvature and para-aortic lymph node. Biopsy could not confirm the definitive diagnosis. We performed total gastrectomy with para-aortic lymph node sampling. Histological analysis revealed squamous cell carcinoma with EBV infection with lymph node metastases. Tumor cells were positive for EBV-encoded small RNA (EBER) by in situ hybridization. The postoperative course was uneventful and the patient was discharged on day 11 after the operation. CapeOX was started as adjuvant chemotherapy, and the patient remains alive without recurrence 7 months after surgery.

Conclusion
This is the first case report of EBV infection-associated primary SCC of the stomach diagnosed by in situ hybridization of EBER. EBV infection may be related to the pathogenesis of primary SCC. Further evidence and studies are required to establish optimal strategy for this rare disease.
Laparoscopic and endoscopic cooperative surgery for advanced gastric cancer as palliative surgery in elderly patients: a case report
Authors: Washio Marie , Hiki Naoki , Hosoda Kei , Niihara Masahiro , Chuman Motohiro , Sakuraya Mikiko , Wada Takuya , Harada Hiroki , Sato Takeo , Tanaka Kiyoshi , Naitoh Takeshi , Kumamoto Yusuke , Sangai Takafumi , Tanabe Satoshi , Yamashita Keishi 
Published: November 2021

Abstract
Background
The number of elderly patients with gastric cancer is increasing, with the very elderly often refusing radical gastrectomy with lymph node dissection. Such a patient presented to us and we proposed a palliative surgery involving gastric local resection using laparoscopy endoscopy cooperative surgery (LECS).

Case presentation
An 89-year-old woman presented to our hospital with progressing anemia. She had an aortic arch replacement for aortic dissection 6 months previously and was taking antithrombotic drugs for atrial fibrillation. She was diagnosed with advanced gastric cancer, and we presented a radical resection treatment plan involving distal gastrectomy with lymph node dissection. However, she strongly refused undergoing radical gastric cancer resection. We believed that at least local control of the tumor could be effective in preventing future bleeding or stenosis due to tumor progression. Therefore, we proposed a local gastrectomy with LECS as an optional treatment, and she agreed to this treatment. The surgery was performed with minimal blood loss, and no postoperative complications were observed. Histopathological examination revealed a 45 × 31-mm, Type 2, poorly differentiated adenocarcinoma (pT4a, ly0, v1a), and the resected margin was negative. The patient was alive 2 years after surgery without apparent recurrence or other illness. In addition, her weight was maintained, together with her daily activity.

Conclusion
Local resection of gastric cancer with LECS might be an option for the palliative treatment of patients who refuse radical resection of gastric cancer.