bluuebunny/crossref_metadata_2025_split huggingface dataset:
17β-Estradiol Prevents Extracellular Matrix Degradation by Downregulating MMP3 Expression via PI3K/Akt/FOXO3 Pathway
Authors: Gao Xiao-Wen , Su Xiao-Tao , Lu Zheng-Hao , Ou Jun 
Published: December 2019

Study Design.

In vitro studies of the role of 17β-estradiol (E2) and its possible targets in intervertebral disc degeneration (IDD).

Objective.
To define the regulatory role of E2 in IDD and the potential mechanisms.

Summary of Background Data.
IDD has intricate etiology that is influenced by multiple risk factors. However, the underlying molecular mechanisms of occurrence and progression of IDD are not well elucidated. The degradation of extracellular matrix (ECM) has been extensively observed in IDD. E2 was found to inhibit ECM degradation in human nuleus pulposus cells (HNPCs), but the molecular mechanism remained to be determined.

Methods.
Western blot and qPCR was performed to quantify the expression of target proteins in HNPCs. Luciferase reporter gene assay was applied to detect the effects of E2 and forkhead box O-3 (FOXO3) on matrix metalloproteinases (MMP)-3 promoter activity. Chromatin immunoprecipitation assay analyzed the binding of FOXO3 to MMP-3 and the effect of E2 on this process.

Results.
We identified the upregulation of collagen II and aggrecan by E2 independent of time and concentration. And E2 downregulated MMP-3 expression in human nucleus pulposus cells. The phosphorylation of FOXO3 led to the reduction of MMP-3 promoter activity. Furthermore, 17β-estradiol-induced the activation of PI3K/Akt pathway is required for FOXO3 phosphorylated.

Conclusion.
E2 prevents the degradation of ECM by upregulating collagen II and aggrecan expression via reducing MMP-3 expression in HNPCs, and PI3K/Akt/FOXO3 pathway is dispensable for MMP-3 downregulated. Therefore, E2 protects against IDD by preventing ECM degradation.

Level of Evidence: 3
A Deep Convolutional Neural Network With Performance Comparable to Radiologists for Differentiating Between Spinal Schwannoma and Meningioma
Authors: Maki Satoshi , Furuya Takeo , Horikoshi Takuro , Yokota Hajime , Mori Yasukuni , Ota Joji , Kawasaki Yohei , Miyamoto Takuya , Norimoto Masaki , Okimatsu Sho , Shiga Yasuhiro , Inage Kazuhide , Orita Sumihisa , Takahashi Hiroshi , Suyari Hiroki , Uno Takashi , Ohtori Seiji 
Published: December 2019

Study Design.
Retrospective analysis of magnetic resonance imaging (MRI).

Objective.
The aim of this study was to evaluate the performance of our convolutional neural network (CNN) in differentiating between spinal schwannoma and meningioma on MRI. We compared the performance of the CNN and that of two expert radiologists.

Summary of Background Data.
Preoperative discrimination between spinal schwannomas and meningiomas is crucial because different surgical procedures are required for their treatment. A deep-learning approach based on CNNs is gaining interest in the medical imaging field.

Methods.
We retrospectively reviewed data from patients with spinal schwannoma and meningioma who had undergone MRI and tumor resection. There were 50 patients with schwannoma and 34 patients with meningioma. Sagittal T2-weighted magnetic resonance imaging (T2WI) and sagittal contrast-enhanced T1-weighted magnetic resonance imaging (T1WI) were used for the CNN training and validation. The deep learning framework Tensorflow was used to construct the CNN architecture. To evaluate the performance of the CNN, we plotted the receiver-operating characteristic (ROC) curve and calculated the area under the curve (AUC). We calculated and compared the sensitivity, specificity, and accuracy of the diagnosis by the CNN and two board-certified radiologists.

Results.
. The AUC of ROC curves of the CNN based on T2WI and contrast-enhanced T1WI were 0.876 and 0.870, respectively. The sensitivity of the CNN based on T2WI was 78%; 100% for radiologist 1; and 95% for radiologist 2. The specificity was 82%, 26%, and 42%, respectively. The accuracy was 80%, 69%, and 73%, respectively. By contrast, the sensitivity of the CNN based on contrast-enhanced T1WI was 85%; 100% for radiologist 1; and 96% for radiologist 2. The specificity was 75%, 56, and 58%, respectively. The accuracy was 81%, 82%, and 81%, respectively.

Conclusion.
We have successfully differentiated spinal schwannomas and meningiomas using the CNN with high diagnostic accuracy comparable to that of experienced radiologists.

Level of Evidence: 4
Effectiveness of Surgical Treatment for Degenerative Cervical Myelopathy in Preventing Falls and Fall-related Neurological Deterioration
Authors: Kimura Atsushi , Takeshita Katsushi , Shiraishi Yasuyuki , Inose Hiroyuki , Yoshii Toshitaka , Maekawa Asato , Endo Kenji , Miyamoto Takuya , Furuya Takeo , Nakamura Akira , Mori Kanji , Seki Shoji , Kanbara Shunsuke , Imagama Shiro , Matsunaga Shunji , Okawa Atsushi 
Published: December 2019

Study Design.
Prospective multi-center study.

Objective.
The aim of this study was to evaluate the effectiveness of surgical treatment in reducing falls and fall-related neurological deterioration in a prospective cohort of patients undergoing surgery for degenerative cervical myelopathy (DCM).

Summary of Background Data.
Current evidence is limited for the effectiveness of surgical interventions for DCM in reducing the risk of fall-related neurological deterioration.

Methods.
Patients with DCM scheduled for surgical treatment were enrolled prospectively at eight participating institutes. At the time of enrollment, participants were given diaries to record details of their falls, to be returned at the 1-year postoperative follow-up. In the fall diary, patients were asked whether they had experienced any deterioration in neurological symptoms at each fall episode. Deterioration of neurological symptoms was categorized as follows: only deterioration of sensory function in the limbs; or deterioration of motor deficits. The incidence rate of falls was calculated separately for the preoperative and postoperative periods, as the total number of falls divided by the time over which falls were monitored (100 person-years). Functional outcome was assessed with the Japanese Orthopaedic Association (JOA) score and Neck Disability Index.

Results.
Of the initial 168 participants, 159 completed the 1-year follow-up, and 132 fall diaries were retrieved and analyzed. Of these 132 patients, 65 (49%) reported at least one fall during the survey period. The incidence rate of falls decreased significantly from 497.4 to 90.3 falls per 100 person-years after surgery. The incidence of motor deterioration per fall decreased significantly from 34% to 8% after surgery. Patients who experienced preoperative fall-related motor deterioration had a significantly lower JOA score compared with patients without fall-related motor deterioration at 1-year follow-up.

Conclusion.
Surgical intervention for DCM is effective not only in reducing the frequency of falls, but also in reducing the risk of fall-related deterioration of motor deficits.

Level of Evidence: 2
The Practice of Continuation of Anti-platelet Therapy During the Perioperative Period in Lumbar Minimally Invasive Spine Surgery (MISS)
Authors: Kulkarni Arvind G. , Patel Jwalant , Khandge Ashwin , Mewara Navin 
Published: December 2019

Study Design.
Cohort.

Objective.
To evaluate perioperative morbidity in patients undergoing minimally invasive spine surgery of the lumbar spine while continuing the antiplatelet drug (APD) perioperatively as compared with those not continuing these drugs and those not on these drugs.

Summary of Background Data.
While discontinuation of antiplatelet drugs carries with it the risk of thrombosis of the cardiac stents, myocardial infarction, peripheral vascular occlusion, cerebro-vascular events and other thrombotic complications, continuation of these drugs has the risk of intra spinal bleeding and the serious consequences of subsequent epidural hematoma with associated spinal cord compression.

Methods.
This institutional review board approved study included 1587 patients from 2011 to 2018. Perioperative parameters were analyzed for 216 patients who underwent spinal surgery after the discontinuation of anticoagulation therapy, 240 patients who continued to take APD daily through the perioperative period and 1131 patients who were never exposed to APD therapy. The operative time, intraoperative estimated blood loss, length of hospital stay, incidence of clinically evident hematoma, and transfusion of blood products were also recorded and compared in three cohorts.

Results.
The patients who continued taking APD in the perioperative period had a longer length of hospital stay on average (2.5 ± 0.67 vs. 1.59 ± 0.76 and 1.67 ± 0.83, P < 0.05), whereas there was no significant difference in the operative time, estimated blood loss, the amount of blood products transfused, and overall intra and postoperative complication rate. There were no instances of postoperative wound soakage or neurological deficit suggestive of possible spinal epidural hematomas in either of the study groups.

Conclusion.
The current study has observed no appreciable increase in perioperative morbidities including bleeding related complication rates in patients undergoing lumbar minimally invasive spine surgery while continuing to take APD compared with patients who either discontinued APD prior to surgery or those not taking APD.

Level of Evidence: 4
Black Patients Experience Highest Rates of Cancer-associated Venous Thromboembolism
Authors: Addo-Tabiri Nana Oduraa , Chudasama Rani , Vasudeva Rhythm , Leiva Orly , Garcia Brenda , Ravid Jonathan D. , Bunze Tamala , Rosen Linda , Belghasem Mostafa , Francis Jean , Brophy Mary , Johnson Brett , Ferguson Ryan , Weinberg Janice , Chitalia Vipul C. 
Published: December 2019

Purpose:
Cancer patients are at a higher risk of venous thromboembolism (VTE) than the general population. In the general population, blacks are at a higher risk of VTE compared with whites. The influence of race on cancer-associated VTE remains unexplored. We examined whether black cancer patients are at a higher risk of VTE and whether these differences are present in specific cancer types.

Design:
A retrospective study was performed in the largest safety net hospital of New England using a cohort of cancer patients characterized by a substantial number of nonwhites.

Results:
We identified 16,498 subjects with solid organ and hematologic malignancies from 2004 to 2018. Among them, we found 186 unique incident VTE events, of which the majority of the events accrued within the first 2 years of cancer diagnosis. Overall, blacks showed a 3-fold higher incidence of VTE (1.8%) compared with whites (0.6%; P<0.001). This difference was observed in certain cancer types such as lung, gastric and colorectal. In lung cancer, the odds of developing VTE in blacks was 2.77-times greater than those in white patients (confidence interval, 1.33-5.91; P=0.007). Despite the greater incidence of cancer-associated VTE in blacks, their Khorana risk score of VTE was not higher.

Conclusions:
In a diverse cancer cohort, we observed a higher incidence of cancer-associated VTE in blacks compared with patients from other races. This study indicates the consideration of race in the risk assessment of cancer-associated VTE. It could also lead to future mechanistic studies aiming at identifying reasons for differential VTE risk depending on cancer type.
Retiform Purpura as a Complication of Microsphere Emboli Following Transarterial Chemoembolization for Primary Hepatocellular Carcinoma: A Case Report and Literature Review
Authors: Kuan Amanda , Khoo Lawrence , Yang Sam S. , Chia Hui Yi , Lee Joyce S. S. 
Published: December 2019

Abstract:
We report an elderly man with hepatocellular carcinoma who developed a rash after undergoing transarterial chemoembolization (TACE). On examination, there was a reticulated macular pigmentation over the chest and upper abdomen. Skin biopsy revealed foreign material that occluded the small dermal cutaneous vessels. These structures were perfectly spherical, homogeneously eosinophilic, and were also nonrefractile. They had a maximum diameter of 40 μm, consistent with the size of the microspheres used in TACE. TACE is a palliative measure used to treat hepatocellular carcinoma in patients who are not surgical candidates. Vaso-occlusive manifestations of the skin are rare occurrences, with only 8 reported cases. Seven cases attributed this to nontarget embolization of the hepatic falciform artery and 1 case postulated that collateral supply of the targeted area allowed for hematogenous migration of the occluding beads via the microcirculation. Pertaining to treatment, all patients were treated with oral nonsteroidal anti-inflammatory agents to good effect, with 1 patient receiving additional laser treatment and another having local steroid injections. Prognosis is excellent, because the skin lesions tend to resolve within a year. Several methods have been suggested to prevent these vaso-occlusive skin complications, including prophylactic application of ice or placing the tip of the microcatheter distal to the origin of the hepatic falciform artery and falciform artery.
Expression of Connexin 43 in 32 Cases of Merkel Cell Carcinoma
Authors: Fernandez-Flores Angel , Varela-Vazquez Adrian , Suárez Peñaranda Jose Manuel , Mayan Maria D. , Fonseca Eduardo 
Published: December 2019

Introduction:
Connexins (Cxs) are channel proteins that allow direct connection among cells and between cells and the extracellular space. There is very little information in the literature on the expression of Cxs by Merkel cell carcinoma (MCC).

Materials and Methods:
Thirty-two cases of MCC were recovered from our archives and studied immunohistochemically for Cx43.

Results:
All our cases expressed several neuroendocrine markers. Most cases showed nonimmunohistochemically perceptible staining for Cx43. There was no difference between Merkel cell polyomavirus (MCPyV)-positive and MCPyV-negative cases. One case could not be evaluated. Only 2 cases showed a focal (10% of the tumor) membranous staining of Cx43. One of these cases was MCPyV-negative and, in the other, CM2B4 could not be evaluated. CM2B4 was positive in 18 cases and negative in 13 cases, and it could not be evaluated in 1 case.

Conclusions:
MCC shows a low Cx43 level, with no differences between MCPyV-positive and MCPyV-negative cases. Therefore, this opens the door for Cx43 targeting in therapeutic approaches to MCC.
Child-Adult Relationship Enhancement in Primary Care: A Randomized Trial of a Skill-Based Parent Training with Parent Mentor Adaptation
Authors: Schilling Samantha , Ritter Victor , Wood Joanne N. , Fine Jason , Zolotor Adam J. 
Published: December 2019

ABSTRACT:

Introduction:
Child-Adult Relationship Enhancement in Primary Care (PriCARE) is a 6-session group training designed to teach positive parenting skills. Parent engagement in such programs is a common implementation barrier. Our objectives were to (1) examine the impact of a peer mentor on attendance and stigma and (2) replicate a previous study by measuring PriCARE's impact on child behavior and parenting practices.

Method:
Parents of 2- to -6-year-old children without specific behavior problems were randomized to mentored PriCARE (n = 50), PriCARE (n = 50), or control (n = 50). Stigma was measured at 10 weeks. Child behavior and parenting practices were measured at baseline and 10 weeks using the Eyberg Child Behavior Inventory (ECBI) and Parenting Scale (PS). Analysis of variance models were used to examine differences across groups.

Results:
There was no significant difference in attendance between mentored PriCARE and PriCARE arms (mean 3.80 vs 3.36 sessions, p = 0.35). Parents randomized to the mentor reported lower stigma (3.75 vs 5.04, p = 0.02). Decreases in the mean ECBI scores between 0 and 10 weeks were greater in the PriCARE arms (n = 100) compared with the control arm (n = 50), reflecting larger improvements in behavior [intensity: −7 (−2 to −13) vs 4 (−3 to 12) to p = 0.014; problem: −3 (−1 to −4) vs 1 (−1 to 3) to p = 0.007]. Scores on all PS subscales reflected greater improvements in parenting behaviors in PriCARE arms compared with control (all p < 0.04).

Conclusion:
Adapting PriCARE with a peer mentor may decrease stigma but does not improve program attendance. PriCARE shows promise in improving behavior in preschool-aged children and increasing positive parenting practices.
Testing Unconventional Matrices to Monitor for Prenatal Exposure to Heroin, Cocaine, Amphetamines, Synthetic Cathinones, and Synthetic Opioids
Authors: Carlier Jeremy , La Maida Nunzia , Di Trana Annagiulia , Huestis Marilyn A. , Pichini Simona , Busardò Francesco P. 
Published: December 2019

Background:
The prevalence of drug use during pregnancy continues to increase despite the associated serious adverse obstetrical outcomes, including increased risk of miscarriage, fetal growth restriction, brain development impairment, neonatal abstinence syndrome, preterm delivery, and stillbirths. Monitoring drug use during pregnancy is crucial to limit prenatal exposure and provide suitable obstetrical health care. The authors reviewed published literature reporting the concentrations of common drugs of abuse and new psychoactive substances (NPS), such as synthetic cathinones and synthetic opioids, NPS, and their metabolites using unconventional matrices to identify drug use during pregnancy and improve data interpretation.

Methods:
A literature search was performed from 2010 to July 2019 using PubMed, Scopus, Web of Science scientific databases, and reports from international institutions to review recently published articles on heroin, cocaine, amphetamine, methamphetamine, synthetic cathinone, and synthetic opioid monitoring during pregnancy.

Results:
Meconium has been tested for decades to document prenatal exposure to drugs, but data regarding drug concentrations in amniotic fluid, the placenta, the umbilical cord, and neonatal hair are still lacking. Data on prenatal exposure to NPS are limited.

Conclusions:
Maternal hair testing is the most sensitive alternative matrix for identifying drug use during pregnancy, while drug concentrations in the meconium, placenta, and umbilical cord offer the identification of prenatal drug exposure at birth. Adverse developmental outcomes for the infant make it critical to promptly identify maternal drug use to limit fetal exposure or, if determined at birth, to provide resources to the exposed child and family. Alternative matrices offer choices for monitoring and challenge laboratories to deliver highly sensitive and specific analytical methods for detection.
The Clinical Application of Medial Sural Vessels as Recipient Vessels in Repairing Traumatic Tissue Defects in the Lower Limbs
Authors: Fu Jile , Gao Junqing , Yi Yanhua , Jia James , Miao Yong , Chen Yuxin , Hu Zhiqi , Gao Jianhua 
Published: December 2019

Background
The use of medial sural vessels (MSVs) as recipient vessels to repair wounds in the lower limbs has been previously reported. However, there is controversy regarding the methods used to expose MSVs and the repairable area of the wound.

Methods
Eight fresh cadavers were used to determine the shape, outer diameter, and length of the MSVs arising from the popliteal vessels. Lower extremity wounds were repaired in 7 patients using free latissimus dorsi flaps with the MSVs as recipient vessels. The flap area ranged from 18 × 11 cm to 24 × 17 cm, and the postoperative follow-up time ranged from 7 to 60 months.

Results
The outer diameter of the medial sural artery from the starting point of the popliteal artery was 2.48 ± 0.24 mm. After descending 29.98 ± 4.62 mm, the vessels entered the muscle; the outer diameter of the blood vessel upon entry was 2.24 ± 0.17 mm. Notably, the outer diameter of the vessel was 1.88 ± 0.09 mm only 2 cm after entering the muscle. Seven cases were treated clinically. In 6 cases, we used an approach between the medial head of the gastrocnemius muscle and the tibia to expose and anastomose the MSVs. In 1 case, the vascular diameter was mismatched. After surgery, the flap survived completely in 6 cases. The remaining case experienced epidermal necrosis in the distal part of the flap, which resolved spontaneously. There were no obvious complications.

Conclusions
An approach between the medial head of the gastrocnemius muscle and the tibia can easily expose and anastomose the MSVs in a lateral position. Latissimus dorsi flaps were useful in repairing limb wounds as far as the talocrural region with the MSVs as the recipient vessels.
The Trk fused gene-product (Tfg) is part of a 600-700kDa CARMA1 complex
Authors: Grohmann Markus , Steinmetz Tobit , Jäck Hans-Martin , Mielenz Dirk 
Published: December 2019

AbstractB cell receptor (BCR) mediated activation of nuclear factor κB (NF-κB) is key to humoral immunity. CARMA1 (CARD11) is essential for BCR mediated NF-κB activation by interacting with Bcl10 and MALT1. Besides these two main players, few interaction partners of the CARMA1 complex are known. Here we identified new interaction partners of CARMA1. We generated two rabbit antisera against mouse CARMA1 to immunopurify endogenous CARMA1 from lysates of mouse B cells. Nik-binding protein (NIBP), Ras-GAP SH3 binding protein 2 (G3BP1) and Trk-fused gene (Tfg) were identified by peptide mass fingerprinting in immunopurified CARMA1 complexes. The interaction of Tfg and CARMA1 was confirmed by co-immunoprecipitation and Blue native polyacrylamide gel electrophoresis using the anti CARMA1 and newly generated anti Tfg antibodies. This analysis revealed that CARMA1 formed complexes of 600-1000 kDa. Additionally, Tfg was found in complexes of 500-600 kDa which increased in size to ∼740 kDa upon overexpresssion.