bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel nomogram to predict mortality in patients with stroke: a survival analysis based on the MIMIC-III clinical database
Authors: Li Xiao-Dan , Li Min-Min 
Published: April 2022

Abstract
Background
Stroke is a disease characterized by sudden cerebral ischemia and is the second leading cause of death worldwide. We aimed to develop and validate a nomogram model to predict mortality in intensive care unit patients with stroke.

Methods
All data involved in this study were extracted from the Medical Information Mart for Intensive Care III database (MIMIC-III). The data were analyzed using multivariate Cox regression, and the performance of the novel nomogram, which assessed the patient’s overall survival at 30, 180, and 360 days after stroke, was evaluated using Harrell’s concordance index (C-index) and the area under the receiver operating characteristic curve. A calibration curve and decision curve were introduced to test the clinical value and effectiveness of our prediction model.

Results
A total of 767 patients with stroke were randomly divided into derivation (n = 536) and validation (n = 231) cohorts at a 7:3 ratio. Multivariate Cox regression showed that 12 independent predictors, including age, weight, ventilation, cardiac arrhythmia, metastatic cancer, explicit sepsis, Oxford Acute Severity of Illness Score or OASIS score, diastolic blood pressure, bicarbonate, chloride, red blood cell and white blood cell counts, played a significant role in the survival of individuals with stroke. The nomogram model was validated based on the C-indices, calibration plots, and decision curve analysis results.

Conclusions
The plotted nomogram accurately predicted stroke outcomes and, thus may contribute to clinical decision-making and treatment as well as consultation services for patients.
Neoadjuvant apatinib combined with oxaliplatin and capecitabine in patients with locally advanced adenocarcinoma of stomach or gastroesophageal junction: a single-arm, open-label, phase 2 trial
Authors: Tang Zhaoqing , Wang Yan , Yu Yiyi , Cui Yuehong , Liang Liang , Xu Chen , Shen Zhenbin , Shen Kuntang , Wang Xuefei , Liu Tianshu , Sun Yihong 
Published: April 2022

Abstract
Background
Adding anti-angiogenics to neoadjuvant chemotherapy for localized gastric cancer is recognized as a promising strategy, but its clinical value remains to be defined.

Methods
This single-center, single-arm, phase 2 trial included patients with locally advanced (cT3/4aN+M0) adenocarcinoma of the stomach or gastroesophageal junction (GEJ) who received three cycles of intravenous oxaliplatin (135 mg/m2 on day 1), oral capecitabine (1000 mg/m2 twice daily on days 1 to 14), and oral apatinib for 21 days (250 mg once daily in the first two cycles, and further increased to 500 mg daily in the third cycle based on whether any adverse event of grade 3 or worse occurred), and an additional cycle of oxaliplatin plus capecitabine, followed by gastrectomy with D2 lymphadenectomy. The primary endpoint was the proportion of patients who achieved an objective response according to RECIST version 1.1.

Results
Between April 28, 2017, and October 23, 2019, 37 patients were screened and 35 participants were included. Of the 32 patients assessable for efficacy and safety, objective responses were achieved in 25 (78.1%; 95% confidence interval [CI], 60.0% to 90.7%) patients. Thirty-one (96.9%) patients received R0 resection, two (6.3%) patients achieved pathological complete response, and 11 (34.4%) patients achieved pathological response. At the data cutoff date (September 30, 2021), the median event-free survival was 42.6 (95% CI, 16.2 to not reached) months, and the median overall survival was not reached. The most common grade 3 or 4 treatment-emergent adverse events were hypertension (9/32, 28.1%), thrombocytopenia (7/32, 21.9%), and neutropenia (5/32, 15.6%). Seven (21.9%) patients developed surgical complications, and the most common one was intra-abdominal abscess (4/32, 12.5%).

Conclusions
The concomitant use of apatinib, oxaliplatin, and capecitabine as neoadjuvant therapy showed promising efficacy and manageable safety profile in patients with locally advanced adenocarcinoma of the stomach or GEJ, and further phase 3 study is warranted.

Trial registration
This study was registered with ClinicalTrial.gov (NCT03229096).
Myogenesis controlled by a long non-coding RNA 1700113A16RIK and post-transcriptional regulation
Authors: Fu Xin , Li Sheng , Jia Minzhi , Xu Bo , Yang Lele , Ma Ruimiao , Cheng Hong , Yang Wenjun , Hu Ping 
Published: April 2022

AbstractLong non-coding (lnc) RNA plays important roles in many cellular processes. The function of the vast majority of lncRNAs remains unknown. Here we identified that lncRNA-1700113A16RIK existed in skeletal muscle stem cells (MuSCs) and was significantly elevated during MuSC differentiation. Knockdown of 1700113A16RIK inhibits the differentiation of muscle stem cells. In contrast, overexpression of 1700113A16RIK promotes the differentiation of muscle stem cells. Further study shows the muscle specific transcription factor Myogenin (MyoG) positively regulates the expression of 1700113A16RIK by binding to the promoter region of 1700113A16RIK. Mechanistically, 1700113A16RIK may regulate the expression of myogenic genes by directly binding to 3’UTR of an important myogenic transcription factor MEF2D, which in turn promotes the translation of MEF2D. Taken together, our results defined 1700113A16RIK as a positive regulator of MuSC differentiation and elucidated a mechanism as to how 1700113A16RIK regulated MuSC differentiation.
Anatomical differences in nociceptor neurons sensitivity
Authors: Crosson Theo , Talbot Sebastien 
Published: April 2022

Abstract
Background
Dorsal Root Ganglia (DRG) neurons are derived from the neural crest and mainly innervate the skin, while Jugular Nodose Complex (JNC) neurons originate from the placode and innervate internal organs. These ganglia are composed of highly heterogeneous groups of neurons aimed at assessing and preserving homeostasis. Among other subtypes, nociceptor neurons are specialized in sensing and responding to environmental dangers. As form typically follows function, we hypothesized that JNC and DRG neurons would be phenotypically and transcriptomically different.

Methods
Mouse JNC and DRG neurons were cultured ex vivo. Using calcium imaging, qPCR and neurite outgrowth assay, we compared the sensitivity of JNC and DRG neurons. Using in-silico analysis of existing RNA sequencing datasets, we confronted our results to transcriptomic differences found between both ganglia.

Results
We found drastically different expression levels of Transient Receptor Potential (TRP) channels, growth factor receptors and neuropeptides in JNC and DRG neurons. Functionally, naïve JNC neurons’ TRP channels are more sensitive to thermal cues than the ones from DRG neurons. However, DRG neurons showed increased TRP channel responsiveness, neuropeptide release and neurite outgrowth when exposed to Nerve Growth Factor (NGF). In contrast, JNC neurons preferentially responded to Brain-derived neurotrophic factor (BDNF).

Conclusion
Our data show that JNC and DRG neurons are transcriptomically and functionally unique and that pain sensitivity is different across anatomical sites. Drugs targeting NGF signaling may have limited efficacy to treat visceral pain. Bioelectronics nerve stimulation should also be adjusted to the ganglia being targeted and their different expression profile.
Factors that shape pregnant women’s perceptions regarding the safety of cannabis use during pregnancy
Authors: Satti Mohamed A. , Reed Eda G. , Wenker Elizabeth S. , Mitchell Stephanie L. , Schulkin Jay , Power Michael L. , Mackeen A. Dhanya 
Published: April 2022

Abstract
Background
Cannabis use among pregnant women has increased. We surveyed pregnant women in rural Pennsylvania to examine cannabis use and opinions regarding its safety during pregnancy. We examined associations between challenges of pregnancy (e.g., exhaustion, pain, nausea) and cannabis use.

Methods
A cross-sectional survey was administered to a convenience sample of English-speaking pregnant women receiving prenatal care at Geisinger, May–June 2019. Principal component analysis (PCA) was used to construct three scores (overwhelmed/exhausted, happy/optimistic, and health worries) based on 10 questions regarding common experiences during pregnancy (e.g., nausea/vomiting, pain, exhaustion, mood). A score based on four questions regarding cannabis safety during pregnancy was also constructed.

Results
From a maximum of 300 surveys distributed, 284 were completed (95%). Most participants were white (87%), married (49%) or living with a partner (38%), and had private health insurance (62%). Most women indicated it was unsafe to use alcohol and tobacco products during pregnancy (> 90%), but that proportion dropped to 82% and 63% regarding recreational cannabis and medical cannabis, respectively. Only women with prior cannabis use (23% of sample) continued to do so during pregnancy: 57% of women reporting daily cannabis use prior to pregnancy continued to use cannabis during pregnancy with 33% reporting daily use. Two thirds of users during pregnancy indicated they were self-medicating for: nausea (90%), anxiety (70%), insomnia (30%), and pain management (30%). Many (56%) of the women who used cannabis during pregnancy believed it is safe. Younger women and women who were overwhelmed/exhausted or less happy/optimistic were more likely to believe cannabis use is safe. Women valued healthcare provider advice more than advice from family and friends. Study strengths include a high response rate. Weaknesses include self-report and that is was a convenience sample; however, the demographics of the sample were similar to past studies.

Conclusion
Women with a history of cannabis use, especially daily use, are at risk of continuing during pregnancy and should receive counseling. Younger women and women with greater stressors during pregnancy also are at greater risk. Screening for prior use and for stressors may identify patients that would benefit from enhanced counseling.
Optimal Sequential Predictive Probability Designs for Early-Phase Oncology Expansion Cohorts
Authors: Zabor Emily C. , Kaizer Alexander M. , Garrett-Mayer Elizabeth , Hobbs Brian P. 
Published: April 2022

PURPOSE The customary approach to early-phase clinical trial design, where the focus is on identification of the maximum tolerated dose, is not always suitable for noncytotoxic or other targeted therapies. Many trials have continued to follow the 3 + 3 dose-escalation design, but with the addition of phase I dose-expansion cohorts to further characterize safety and assess efficacy. Dose-expansion cohorts are not always planned in advance nor rigorously designed. We introduce an approach to the design of phase I expansion cohorts on the basis of sequential predictive probability monitoring. METHODS Two optimization criteria are proposed that allow investigators to stop for futility to preserve limited resources while maintaining traditional control of type I and type II errors. We demonstrate the use of these designs through simulation, and we elucidate their implementation with a redesign of the phase I expansion cohort for atezolizumab in metastatic urothelial carcinoma. RESULTS A sequential predictive probability design outperforms Simon's two-stage designs and posterior probability monitoring with respect to both proposed optimization criteria. The Bayesian sequential predictive probability design yields increased power while significantly reducing the average sample size under the null hypothesis in the context of the case study, whereas the original study design yields too low type I error and power. The optimal efficiency design tended to have more desirable properties, subject to constraints on type I error and power, compared with the optimal accuracy design. CONCLUSION The optimal efficiency design allows investigators to preserve limited financial resources and to maintain ethical standards by halting potentially large dose-expansion cohorts early in the absence of promising efficacy results, while maintaining traditional control of type I and II error rates.
Effect of superconductivity on the shape of flat bands
Authors: Shaginyan V. R. , Msezane A. Z. , Amusia M. Ya. , Japaridze G. S. 
Published: April 2022

Abstract
For the first time, basing both on experimental facts and our theoretical consideration, we show that Fermi systems with flat bands should be tuned with the superconducting state. Experimental measurements on magic-angle twisted bilayer graphene of the Fermi velocity V

F
as a function of the temperature T

c
of superconduction phase transition have revealed

, where N

s
(0) is the density of states at the Fermi level. We show that the high-T

c
compounds

exhibit the same behavior. Such observation is a challenge to theories of high-T

c
superconductivity, since V

F
is negatively correlated with T

c
, for

. We show that the theoretical idea of forming flat bands in strongly correlated Fermi systems can explain this behavior and other experimental data collected on both

and twisted bilayer graphene. Our findings place stringent constraints on theories describing the nature of high-T

c
superconductivity and the deformation of flat band by the superconducting phase transition.
GH Action in Prostate Cancer Cells Promotes Proliferation, Limits Apoptosis, and Regulates Cancer-related Gene Expression
Authors: Unterberger Christopher J , Maklakova Vilena I , Lazar Michelle , Arneson Paige D , Mcilwain Sean J , Tsourkas Philippos K , Hu Rong , Kopchick John J , Swanson Steven M , Marker Paul C 
Published: April 2022

Abstract
Previous studies investigating the effects of blocking the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis in prostate cancer found no effects of the growth hormone receptor (GHR) antagonist, pegvisomant, on the growth of grafted human prostate cancer cells in vivo. However, human GHR is not activated by mouse GH, so direct actions of GH on prostate cancer cells were not evaluated in this context. The present study addresses the species specificity of GH-GHR activity by investigating GH actions in prostate cancer cell lines derived from a mouse Pten-deletion model. In vitro cell growth was stimulated by GH and reduced by pegvisomant. These in vitro GH effects were mediated at least in part by the activation of JAK2 and STAT5. When Pten-mutant cells were grown as xenografts in mice, pegvisomant treatment dramatically reduced xenograft size, and this was accompanied by decreased proliferation and increased apoptosis. RNA sequencing of xenografts identified 1765 genes upregulated and 953 genes downregulated in response to pegvisomant, including many genes previously implicated as cancer drivers. Further evaluation of a selected subset of these genes via quantitative reverse transcription–polymerase chain reaction determined that some genes exhibited similar regulation by pegvisomant in prostate cancer cells whether treatment was in vivo or in vitro, indicating direct regulation by GH via GHR activation in prostate cancer cells, whereas other genes responded to pegvisomant only in vivo, suggesting indirect regulation by pegvisomant effects on the host endocrine environment. Similar results were observed for a prostate cancer cell line derived from the mouse transgenic adenocarcinoma of the mouse prostate (TRAMP) model.
Machine Learning to Predict Successful Opioid Dose Reduction or Stabilization After Spinal Cord Stimulation
Authors: Adil Syed M. , Charalambous Lefko T. , Rajkumar Shashank , Seas Andreas , Warman Pranav I. , Murphy Kelly R. , Rahimpour Shervin , Parente Beth , Dharmapurikar Rajeev , Dunn Timothy W. , Lad Shivanand P. 
Published: April 2022

BACKGROUND:
Spinal cord stimulation (SCS) effectively reduces opioid usage in some patients, but preoperatively, there is no objective measure to predict who will most benefit.

OBJECTIVE:
To predict successful reduction or stabilization of opioid usage after SCS using machine learning models we developed and to assess if deep learning provides a significant benefit over logistic regression (LR).

METHODS:
We used the IBM MarketScan national databases to identify patients undergoing SCS from 2010 to 2015. Our models predict surgical success as defined by opioid dose stability or reduction 1 year after SCS. We incorporated 30 predictors, primarily regarding medication patterns and comorbidities. Two machine learning algorithms were applied: LR with recursive feature elimination and deep neural networks (DNNs). To compare model performances, we used nested 5-fold cross-validation to calculate area under the receiver operating characteristic curve (AUROC).

RESULTS:
The final cohort included 7022 patients, of whom 66.9% had successful surgery. Our 5-variable LR performed comparably with the full 30-variable version (AUROC difference <0.01). The DNN and 5-variable LR models demonstrated similar AUROCs of 0.740 (95% CI, 0.727-0.753) and 0.737 (95% CI, 0.728-0.746) (P = .25), respectively. The simplified model can be accessed at SurgicalML.com.

CONCLUSION:
We present the first machine learning–based models for predicting reduction or stabilization of opioid usage after SCS. The DNN and 5-variable LR models demonstrated comparable performances, with the latter revealing significant associations with patients' pre-SCS pharmacologic patterns. This simplified, interpretable LR model may augment patient and surgeon decision making regarding SCS.
Comparative Clinical and Radiographic Cohort Study: Uniportal Thoracic Endoscopic Laminotomy With Bilateral Decompression by Using the 1-Block Resection Technique and Thoracic Open Laminotomy With Bilateral Decompression for Thoracic Ossified Ligamentum Flavum
Authors: Kim Hyeun Sung , Wu Pang Hung , Kim Ji-Yeon , Lee Yeon Jin , Kim Dae Hwan , Lee Jun Hyung , Jeon Jun Bok , Jang Il-Tae 
Published: April 2022

BACKGROUND:
Symptomatic thoracic myelopathy secondary to thoracic ossified ligamentum flavum (OLF) often requires decompression spinal surgery.

OBJECTIVE:
To compare clinical and radiological outcomes in uniportal endoscopic vs open thoracic decompression for thoracic OLF.

METHODS:
Retrospective evaluation of patients who underwent uniportal thoracic endoscopic unilateral laminotomy with bilateral decompression (TE-ULBD) by using the one-block resection technique compared with thoracic open laminotomy (TOL) with bilateral decompression. Radiological outcomes in MRI scan and clinical charts were evaluated.

RESULTS:
Thirty-five levels of TE-ULBD were compared with 24 levels of TOL. The overall complication rate of TOL was 15% while TE-ULBD was 6.5%. Both TOL and TE-ULBD cohort had significantly improved their visual analog scale (VAS), Oswestry Disability Index, and Japanese Orthopaedic Association (JOA) myelopathy score after operation. Comparative analysis of TE-ULBD performed statistically and significantly better than TOL in improvement of final VAS and JOA scores. The mean difference ± standard deviation of VAS and JOA improvement in final follow-up when compared with preoperative state of TE-ULBD and TOL was 0.717 ± 0.131 and 1.03 ± 0.2, respectively, P < .05. The mean Hirabayashi recovery rates were 94.5% (TE-ULBD) and 56.8% (TOL). There was no statistical difference in change in preoperative and final Oswestry Disability Index and MRI volume at upper endplate, middisk, and lower endplate canal cross-sectional area.

CONCLUSION:
Uniportal TE-ULBD achieved significantly improved pain and neurological recovery with sufficient spinal canal decompression, as compared with thoracic open laminectomy for patients with myelopathy secondary to OLF in our cohort.
Single-Center Experience Using a 3D4K Digital Operating Scope System for Aneurysm Surgery
Authors: Pantel Tobias , Drexler Richard , Göttsche Jennifer , Piffko Andras , Westphal Manfred , Regelsberger Jan , Dührsen Lasse 
Published: April 2022

BACKGROUND:
In recent years, 3D4K exoscope systems (EXs) have been introduced to microneurosurgery and reported to be an alternative to conventional operating microscopes (OMs). This study reviews our single-center experience using an 3D4K EX in intracranial aneurysm surgery.

OBJECTIVE:
To investigate the applicability of a novel 3D4K EX for intracranial aneurysm surgery.

METHODS:
A retrospective analysis of patients who underwent microsurgical repair of incidentally or ruptured cerebral aneurysms between August 2018 and August 2020 was performed. Patient and aneurysm characteristics and technical features, including 3-dimensional indocyanine green fluorescence, were evaluated. Data on surgery duration were statically assessed for a time trend and comparability with the OM cohort.

RESULTS:
Overall, we collected 185 aneurysm cases in which the exoscope was used in 44 cases. The mean duration of surgery using the EX was in similar range to those using the OM (165.5 ± 45.8 minutes vs 160.5 ± 39.2 minutes, P > .05). Routine postoperative computed tomography angiography showed comparable rates of complete aneurysm occlusion (95.5% vs 92.2%, P > .05) and postoperative complications (9.1% vs 9.7%, P > .05). There was no necessity to revert to the OM from the EX. Three-dimensional indocyanine green fluorescence was used in all procedures without any malfunction.

CONCLUSION:
The 3D4K EX for vascular microsurgical cases proved to be as useful as the OM. Because of the ease of use and comparable surgical results, the EX has the potential to become an accepted and additional visualization tool in vascular microsurgery next to the OM.
Three-Dimensional Assessment of Vertebral Derotation in Adolescent Idiopathic Scoliosis: Review of a Surgical Technique and Its Success in Achieving Derotation in the Instrumented and Uninstrumented Spine
Authors: Zuckerman Scott L. , Segar Anand H. , Cerpa Meghan , Chanbour Hani , Sardar Zeeshan M. , Lenke Lawrence G. 
Published: April 2022

BACKGROUND:
Three-dimensional (3D) imaging represents a novel way to assess surgical derotation maneuvers in adolescent idiopathic scoliosis (AIS).

OBJECTIVE:
To assess the following in patients with AIS undergoing derotation surgery with Lenke type 1/2 curves using 3D imaging: (1) the primary outcome of thoracic apical vertebral rotation (T-AVR) and (2) secondary outcomes of thoracic kyphosis (TK), lumbar AVR (L-AVR), and rotation of each thoracic/lumbar vertebrae.

METHODS:
A retrospective, pilot study of type 1/2 AIS patients from 2017 to 2018 was performed. All patients received posterior pedicle screw/rod constructs with consistent direct vertebral derotational maneuvers and received full length SterEOS imaging with 3D reconstruction. The primary outcome of interest was T-AVR. Secondary outcomes included TK, L-AVR, and rotation at each thoracic/lumbar vertebrae.

RESULTS:
Fifteen patients (mean age 15.7 ± 1.2 years, 67.0% female) were studied. The mean preoperative/postoperative Cobb angle of the major curve was 51.8° ± 14.9° (range 39.8-62.0) and 11.0° ± 5.1° (range 3.7-20.7). Mean level fused was 10.5 ± 1.2. The primary outcome of T-AVR showed significant improvement (13.8° ± 12.5° vs 9.2° ± 8.6°, P = .015) after surgery, along with secondary outcome of TK (T1-12/T4-12, P = .008/.027). Significant spontaneous rotational improvement was seen in L-AVR (P = .016). Significant improvement was also seen in 11 of 17 (64.7%) individual vertebrae (T3-8/T11-L3) (P < .05).

CONCLUSION:
In Lenke Type 1/2 AIS patients undergoing surgical derotation and fusion, 3D imaging techniques captured improvements in rotation. Significant postoperative improvement was seen in T-AVR, TK, L-AVR, and rotation of the individual vertebrae T3-8/T11-L3. These pilot results warrant the study of 3D imaging in all patients with AIS and other scoliosis populations.