bluuebunny/crossref_metadata_2025 huggingface dataset:
Wendan decoction for dyslipidemia
Authors: Feng Wenwei , Ye Xiaohan , Lv Hongxue , Hou Chijun , Chen Yingjun
Published: January 2019

Background:

Dyslipidemia is one of the most popular metabolic diseases and an important risk factor for arteriosclerotic cardiovascular diseases. In China, Wendan decoction (WDD) has been widely used to treat hyperlipidemia. However, no systematic review has been found. In order to evaluate the efficacy and safety of WDD in the treatment of dyslipidemia, a meta-analysis and systematic evaluation are conducted.

Methods:

The randomized controlled trials (RCTs) evaluating the effectiveness and safety of WDD in the treatment of dyslipidemia will be enrolled. Data are mainly from 4 English databases (Pubmed, Embase, Cochrane Library, and Web of science) and 4 Chinese databases (Wanfang, CBM, CNKI, and VIP Database). The enrollment of RCTs is from the starting date of database establishment till December 15, 2018. Low density lipoprotein cholesterol is considered as the main outcome, while the serum concentrations of total cholesterol, triglyceride, high density lipoprotein cholesterol, apolipoprotein A, and apolipoprotein B are regarded as the secondary outcome. Safety indicators include liver enzyme, fasting blood glucose, and kidney function. The work such as selection of literature, data collection, quality evaluation of included literature, and assessment of publication bias will be conducted by 2 independent researchers. Meta-analysis will be performed by RevMan 5.0 software.

Results:

This study will provide high-quality evidence for the treatment of dyslipidemia with WDD in terms of effectiveness and safety.

Conclusion:

The results of the study will help us determine whether WDD can effectively treat hyperlipidemia.

PROSPERO registration number:

PROSPERO CRD 42018114957.
What is the appropriate duration of adjuvant imatinib mesylate treatment for primary gastrointestinal stromal tumors classified according to the strict definition of tumor rupture?
Authors: Lu Jun , Dai Yun , Zheng Hua-Long , Xie Jian-Wei , Wang Jia-Bin , Lin Jian-Xian , Chen Qi-Yue , Cao Long-Long , Lin Mi , Tu Ru-Hong , Huang Ze-Ning , Lin Ju-Li , Li Ping , Huang Chang-Ming , Zheng Chao-Hui
Published: January 2019

In gastrointestinal stromal tumors (GISTs), rupture is a high-risk feature; however, “tumor rupture” is inconsistently defined, and its prognostic value remains controversial.

Six hundred ninety-one patients undergoing surgery for primary nonmetastatic GISTs from 2003 to 2015 at our institution were enrolled. The strict definitions of “tumor rupture” according to the Kinki GIST Study Group (KGSG) were used.

The median follow-up time was 64 months. The 5-year recurrence-free survival (RFS) and overall survival (OS) rates in the entire group were 79.3% and 84.1%, respectively. According to the KGSG's definition, tumor rupture occurred only in 24 (3.5%) of 691 patients. For all 691 patients, multivariable analysis showed that tumor rupture, according to KGSG's definition, is one of the independently prognostic factors for both RFS and OS. Twenty-four patients with tumor rupture were further analyzed. Receiving IM for more than 3 years was significantly associated with improved RFS and OS in GISTs patients with tumor rupture.

Tumor rupture according to KGSG's definition was an independent predictive factor associated with GIST patient prognosis. More importantly, for GISTs with tumor rupture according to the KGSG's strict definition, receiving IM treatment for ≥3 years should be considered.
Simultaneous Hodgkin lymphoma and BRAF V600E -positive papillary thyroid carcinoma
Authors: Liu Shu , Zhao Yanru , Li Miaojing , Xi Jieying , Shi Bingyin , Zhu Huachao
Published: January 2019

Rationale:

Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. However, the simultaneous occurrence of PTC and Hodgkin Lymphoma (HL) was rarely reported.

Patient concerns:

We present a case of simultaneous BRAF

V600E

-positive PTC and HL in a 17-year-old female.

Diagnosis:

She was referred to our clinic with a painless lump in her left neck. A highly suspicious thyroid nodule and multiple enlarged lymph nodes in the neck were found by ultrasonography examination. The suspicious nodule was diagnosed as PTC by fine needle aspiration cytology.

Interventions:

A total thyroidectomy with bilateral lymph node dissection was performed and the microscopic examination revealed a 2-cm PTC with BRAF

V600E
mutation and HL (mixed cellularity) in the bilateral lymph nodes. PTC was postoperatively considered as T1bN0M0. Levothyroxine (125 μg/d) was administered to the patient for thyrotropin suppression therapy. Then the patient was referred to the Department of Hematology to receive 4 cycles of ABVD followed by 30 Gy involved-site radiotherapy and radioactive iodine (RAI) therapy for thyroid cancer.

Outcomes:

After two cycles of ABVD, multiple enlarged lymph nodes showed a significant response to the chemotherapy in the patient.

Lessons:

Simultaneous HL and BRAF

V600E
-positive PTC is extremely rare. Biopsy of the suspicious lymph nodes should be performed to confirm malignancy metastasizing from PTC or other lesions. Similarly, in HL patients with suspicious thyroid nodule, ultrasound-guided fine needle aspiration of thyroid nodule should be performed to exclude thyroid malignancy.
Surgical management of spinal metastases of thymic carcinoma
Authors: Liu Shuzhong , Zhou Xi , Song An , Huo Zhen , Li William A. , Rastogi Radhika , Wang Yipeng , Liu Yong
Published: January 2019

Rationale:

Metastatic thymic carcinoma in the spine is a rare disease with no standard curative managements yet. The objective of this study is to report a very rare case of spinal metastases of thymic carcinoma successfully operated by combination of instrumentation and cement augmentation together with adjuvant treatment. The management of these unique cases has yet to be well-documented.

Patient concerns:

A 57-year-old man presented with a 6-month history of continuous and progressive back pain. The patient, who had been diagnosed of thymic carcinoma (stage IV B) for 3 years, received surgical treatment of median sternotomy thymectomy, followed by 3 cycles of chemotherapy and 12 cycles of radiotherapy.

Diagnosis:

Magnetic resonance imaging (MRI) of spine showed spinal cord compression secondary to the epidural component of the T4 mass, with increased metastatic marrow infiltration of the left T4 vetebral body, which presented as a solid tumor. Post-operative pathology confirmed the diagnosis of spinal metastases of thymic carcinoma.

Interventions:

The patient underwent exploratory surgery, circumferential spinal cord decompression, cement augmentation and a stabilization procedure via a posterior approach.

Outcomes:

The patient's neurological deficits improved significantly after the surgery, and the postoperative period was uneventful at the 3-month follow-up visit. There were no other complications associated with the operation during the follow-up period.

Lessons:

Taken together, the lesion's clinical features, imaging results, and pathological characteristics are unique. Combined efforts of specialists from orthopedics, neurosurgery, thoracic surgery, and medical oncology led to the successful diagnosis and management of this patient. Metastatic thymic carcinoma of the spine, although rare, should be part of the differential diagnosis when the patient has a history of thymic carcinoma and presents with back pain and radiculopathy. We recommend the posterior approach for spinal decompression of the metastatic thymic carcinoma when the tumor has caused neurological deficits. Osteoplasty by cement augmentation is also a good choice for surgical treatment.
Effect of preoperative smoking cessation on postoperative pain outcomes in elderly patients with high nicotine dependence
Authors: Zhao Shuai , Chen Fan , Wang Dunwei , Wang Hongdan , Han Wei , Zhang Yuan
Published: January 2019

Objective:

To investigate the effect of smoking cessation before surgery on postoperative pain and analgesic consumption after thoracoscopic radical resection of lung cancer in elderly patients with high nicotine dependence.

Methods:

A total of 107 male patients, ages 60 to 70 years, undergoing elective thoracoscopic radical lung cancer surgery from July 2017 to July 2018 were enrolled into 3 groups: group A (highly nicotine-dependent and discontinued smoking <3 weeks before surgery, n = 36), group B (highly nicotine-dependent and discontinued smoking >3 weeks before surgery, n = 38), and group C (nonsmokers, n = 33). Postoperative sufentanil consumption, visual analog scale (VAS) pain scores at rest and during cough, rescue analgesia, opioid-related adverse events, and patient satisfaction were assessed from 0 to 48 h postoperatively.

Results:

Patient characteristics were comparable among the 3 groups. Sufentanil consumption and VAS pain scores from postoperative 0 to 48 h were significantly higher in groups A and B than in group C. In addition, group B had lower sufentanil consumption and pain scores than group A. No differences in the need for rescue analgesia, patient satisfaction, or occurrence of postoperative adverse events, including nausea, vomiting, respiratory depression, and oversedation, were observed among the 3 groups.

Conclusion:

Compared with nonsmokers, highly nicotine-dependent male patients who were deprived of cigarettes experienced more severe pain and required treatment with more sufentanil after thoracoscopic radical lung cancer surgery. Moreover, preoperative smoking cessation at least 3 weeks before surgery led to better postoperative pain outcomes than smoking cessation within 3 weeks of surgery.
Progress in the problem of relapsed or refractory acute myeloid leukemia
Authors: Mims Alice S. , Blum William
Published: January 2019

Purpose of review

The majority of patients with acute myeloid leukemia (AML) die from disease recurrence and historically, treatment options in both the relapsed and refractory settings of this disease have been limited. However, new insights into the molecular characterization and biology of relapsed and refractory AML have led to novel therapeutics and improvement in outcomes in these settings. The current understanding of mechanisms of disease resistance and status of treatment options both currently available and under exploration in relapsed and refractory AML are summarized in this review.

Recent findings

The rapid approval of multiple therapeutic agents since 2017 has led to improvement in selected populations such as isocitrate dehydrogenase and fms-like tyrosine kinase 3-mutated relapsed and refractory AML with agents such as enasidenib, ivosidenib, and gilteritinib. Despite these advancements, the only current curative approach remains allogeneic transplantation and only for those minority of patients that are candidates. However, encouraging results are being seen with a multitude of novel small molecular inhibitors and immunotherapeutic approaches currently in clinical trials both as single agents and combination strategies in both upfront and relapsed/refractory AML.

Continued advancements in the knowledge of various mechanisms of relapse and resistance in AML are ongoing, leading to the realization that diverse treatment strategies are needed to both prevent and manage relapsed and refractory disease.
Evaluating Longitudinal Associations Between Depressive Symptoms, Smoking, and Biomarkers of Cardiovascular Disease in the CARDIA Study
Authors: Carroll Allison J. , Huffman Mark D. , Zhao Lihui , Jacobs David R. , Stewart Jesse C. , Kiefe Catarina I. , Liu Kiang , Hitsman Brian
Published: January 2019

Objective

The aim of the study was to evaluate associations between 15-year trajectories of co-occurring depressive symptoms and smoking with biomarkers of cardiovascular disease at year 15.

Methods

In the Coronary Artery Risk Development in Young Adults study, we modeled trajectories of depressive symptoms (Center for Epidemiologic Studies-Depression scale [CES-D]) and smoking (cigarettes per day [CPD]) among 3614 adults followed from year 0 (ages 18–30 years) through year 15 (ages 33–45 years). Biomarkers of inflammation (high-sensitivity C-reactive protein), oxidative stress (superoxide dismutase, F2-isoprostanes), and endothelial dysfunction (soluble intercellular adhesion molecule 1, soluble P-selectin) were assessed at year 15. We conducted separate linear regression analyses with CES-D trajectory, CPD trajectory, and their interaction with each of the five biomarkers.

Results

The sample was 56% women, 47% black, and 40 years old on average at year 15. The CES-D trajectory by CPD trajectory interaction was not associated with any of the biomarkers (allp's > .01). Removing the interaction term, CES-D trajectory was associated with inflammation: higher levels of high-sensitivity C-reactive protein were observed in the subthreshold (β = 0.57,p= .004) and increasing depressive symptoms (β = 1.36,p< .001) trajectories compared with the no depression trajectory. CPD trajectory was associated with oxidative stress and endothelial dysfunction: compared with never smokers, heavy smokers had significantly higher levels of F2-isoprostanes (β = 6.20,p= .001), soluble intercellular adhesion molecule 1 (β = 24.98,p< .001), and soluble P-selectin (β = 2.91,p< .001).

Conclusions

Co-occurring depressive symptoms and smoking do not seem to synergistically convey risk for cardiovascular disease via processes of inflammation, oxidative stress, or endothelial dysfunction. Nonetheless, these results advance our understanding of the complex relationships between modifiable risk factors and chronic disease.
Socioeconomic Adversity, Social Resources, and Allostatic Load Among Hispanic/Latino Youth: The Study of Latino Youth
Authors: Gallo Linda C. , Roesch Scott C. , Bravin Julia I. , Savin Kimberly L. , Perreira Krista M. , Carnethon Mercedes R. , Delamater Alan M. , Salazar Christian R. , Lopez-Gurrola Maria , Isasi Carmen R.
Published: January 2019

Objective

We examined associations among socioeconomic adversity, social resources, and allostatic load in Hispanic/Latino youth, who are at high risk for obesity and related cardiometabolic risks.

Methods

Participants were 1343 Hispanic/Latino youth (51% male; ages 8–16 years) offspring of Hispanic Community Health Study/Study of Latinos participants. Between 2012 and 2014, youth underwent a fasting blood draw and anthropometric assessment, and youth and their enrolled caregivers provided social and demographic information. A composite indicator of allostatic load represented dysregulation across general metabolism, cardiovascular, glucose metabolism, lipid, and inflammation/hemostatic systems. Socioeconomic adversity was a composite of caregiver education, employment status, economic hardship, family income relative to poverty, family structure, and receipt of food assistance. Social resources were a composite of family functioning, parental closeness, peer support, and parenting style variables.

Results

Multivariable regression models that adjusted for sociodemographic factors, design effects (strata and clustering), and sample weights revealed a significant, positive, association between socioeconomic adversity and allostatic load (β = .10, p = .035), and a significant, inverse association between socioeconomic adversity and social resources (β = −.10, p = .013). Social resources did not relate to allostatic load and did not moderate or help explain the association of adversity with allostatic load (all p values > .05).

Conclusions

Statistically significant, but small associations of socioeconomic adversity with both allostatic load and social resources were identified. The small effects may partially reflect range restriction given overall high socioeconomic adversity and high social resources in the cohort.
Quantitative Multiparametric Breast Ultrasound
Authors: Kapetas Panagiotis , Clauser Paola , Woitek Ramona , Wengert Georg J. , Lazar Mathias , Pinker Katja , Helbich Thomas H. , Baltzer Pascal A.T.
Published: January 2019

Objectives

The aim of this study was to evaluate breast multiparametric ultrasound (mpUS) and its potential to reduce unnecessary breast biopsies with 1, 2, or 3 additional quantitative parameters (Doppler, elastography, and contrast-enhanced ultrasound [CEUS]) to B-mode and investigate possible variations with different reader experience.

Materials and Methods

This prospective study included 124 women (age range, 18–82 years; mean, 52 years), each with 1 new breast lesion, scheduled for ultrasound-guided biopsy between October 2015 and September 2016. Each lesion was examined with B-mode, elastography (Virtual Touch IQ [VTIQ]), Doppler, and CEUS, and different quantitative parameters were recorded for each modality. Four readers (2 experienced breast radiologists and 2 in-training) independently evaluated B-mode images of each lesion and assigned a BI-RADS (Breast Imaging Reporting and Data System) score. Using the area under the receiver operating characteristic curve (AUC), the most accurate quantitative parameter for each modality was chosen. These were then combined with the BI-RADS scores of all readers. Descriptive statistics and AUC were used to evaluate the diagnostic performance of mpUS.

Results

Sixty-five lesions were malignant. MpUS with B-mode and 2 additional quantitative parameters (VTIQ and CEUS or Doppler) showed the highest diagnostic performance for all readers (averaged AUCs, 0.812–0.789 respectively vs 0.683 for B-mode, P = 0.0001). Both combinations significantly reduced the number of false-positive findings up to 46.9% (P < 0.0001).

Conclusions

Quantitative mpUS with 2 different triple assessment modalities (B-mode, VTIQ elastography, CEUS, or Doppler) shows the best diagnostic performance for breast cancer diagnosis and leads to a significant reduction of false-positive biopsy recommendations, for both experienced and inexperienced readers.
Preferential Associated Malformation in Patients With Anotia and Microtia
Authors: Shibazaki-Yorozuya Reiko , Nagata Satoru
Published: January 2019

Objective:

Few epidemiological studies have investigated the external ear malformations anotia and microtia. The authors’ study aimed to investigate the relationships between age, sex, type of microtia, and birth place and associated malformation as seen in 1 private Japanese clinic.

Methods:

Cases of anotia/microtia that presented in Nagata Microtia and Reconstructive Plastic Surgery Clinic (Saitama, Japan) between 2005 and 2018 were included in the study. The authors identified 1896 patients with anotia/microtia with or without associated malformation. Most were primary cases, with some secondary reconstruction cases wherein the primary surgery was performed at another hospital. Cases were classified with Nagata classification; lobule type, small concha type, concha type, and anotia. Cryptotia was also observed in this study.

Results:

Among the patients, 61.1% were male, 85.4% had unilateral defects (69.0% LB), and 59.1% had a right-sided defect. Most patients were less than 1 year old (15.0%) or 8 to 10 years old (5.5%–6.3%) on first examination, while 58% were from the Kanto region, including Tokyo. Regarding concomitant disorders, 32.7% had an accompanying malformation, while 13.3% had associated syndromes (eg, craniofacial microsomia, Treacher Collins syndrome). To conclude, in the authors’ clinic, most cases of anotia/microtia were LB, unilateral, and seen in male patients. Information regarding several characteristic clinical features was obtained, especially that clefts and musculoskeletal deformities of the skull/face and jaw were the main accompanying malformations.
Anatomical Study and Clinical Application of Free Thoracoacromial Artery True-Perforator Flap for Reconstruction of the Face
Authors: Iida Takuya , Yoshimatsu Hidehiko
Published: January 2019

Introduction:

The clavicular region is acknowledged as one of the most suitable donor sites for reconstruction of the face or neck. Recently, a free thoracoacromial artery (TAA) perforator (TAAP) flap was reported as a new option for reconstruction of the face. However, the TAAP flap has several drawbacks including tedious intramuscular dissection of the pedicle and loss of availability of a pectoralis major flap as a bailout option in case of cancer recurrence. We performed an anatomical study of the TAAP and developed a novel TAA “true-perforator” flap, in which we can preserve the main trunk of the TAA.

Patients and Methods:

Anatomical study of the TAAPs was performed in 6 patients while elevating a deltopectoral flap or a pedicled TAAP flap. Location and diameter of the perforators were recorded. Based on these anatomical findings, we developed a novel free TAA true-perforator flap, which we used for the reconstruction of a facial defect after cancer resection.

Results:

The most dominant TAAP was identified 4.8-cm (4 to 7-cm) caudally from the upper border of the deltopectoral triangle along the cephalic vein and 1.7-cm (0.5 to 2-cm) medially from the cephalic vein. The diameter of the TAAPs at the level of fascial penetration was 0.78-mm (0.6 to 1.0-mm). The pedicle could be elongated up to 3-cm with proximal dissection. Clinical case showed a satisfactory aesthetic result with minimal donor-site morbidity.

Conclusions:

A free TAA true-perforator flap can be a new option for the reconstruction of the face with many advantages including reduced donor-site morbidity and satisfactory aesthetic outcome.
Biological Response to Recombinant Human Bone Morphogenetic Protein-2 on Bone-Implant Osseointegration in Ovariectomized Experimental Design
Authors: Song Yanbin , Wan Linzhong , Zhang Shuangyue , Du Yifei
Published: January 2019

Objective:

The aim of this study is to investigate the effects of recombinant human bone morphogenetic protein-2 (rhBMP-2) on bone-implant osteointegration in osteoporotic rats.

Materials and Methods:

Thirty-six female Wistar rats were randomly divided into 3 groups: sham-operation (SHAM), ovariectomized (OVX), and ovariectomized with rhBMP-2 (OVX + rhBMP-2). The bone density of right tibia was observed with x-ray and the serum alkaline phosphatase (ALP) activity was measured preovariectomy and postovariectomy using an ALP-kit. In OVX + rhBMP-2 group, rhBMP-2 was embedded in the peri-implant area, while SHAM and OVX groups did not contain rhBMP-2. Four and eight weeks after implantation, the rats were killed and the right tibia with implants was taken by x-ray. Histologic changes were investigated by hematoxylin and eosin staining, scanning electron microscope (SEM), and energy dispersive spectrometer examinations.

Results:

The serum ALP level was significantly higher in ovariectomized rats compared with that before ovariectomy (P < 0.05), while no difference was found in SHAM rats. At 12 weeks after ovariectomy, radiographic and histologic findings showed significant osteoporotic changes in proximal tibial metaphyses of OVX rats, including reduced cortical bone density and enlargement of bone marrow cavity compared with SHAM ones. The results of implantation verified new bone formation around implants in OVX + rhBMP-2 and SHAM groups, indicating favorable bone healing and osseointegration. No bone resorption was found in OVX + rhBMP-2 group, while some soft tissue was observed in bone-implant interface in SHAM group. In OVX group, there was no effective bone-implant osseointegration and mature bone formed around implants, and some implants were even lost due to chronic inflammation. The percentage of calcium and phosphorous atoms was significantly higher and the percentage of sulfur element was significantly lower in peri-implant area in OVX + rhBMP-2 and SHAM groups than that in OVX group.

Conclusion:

rhBMP-2 could enhance the osseous healing and restore bone-implant osseointegration in osteoporotic rats.
Management of Mandibular Fractures Using Locking and Nonlocking Miniplates
Authors: Wusiman Patiguli , Tayie Alifu , Ling Wang , Moming Adili
Published: January 2019

Purpose:

The study proposed to determine the superiority between locking plate and nonlocking miniplate for mandibular fractures (MFs) treatment.

Methods:

A comprehensive electronic search examining Medline-Ovid, Embase, and PubMed databases language without date was performed in February 2018. Inclusion criteria were studies in humans, including randomized controlled trials, controlled clinical trials, with the aim of comparing the 2 techniques. The quality of studies was assessed, and the relative risk (RR) with its corresponding 95% confidence interval (CI) was assessed to measure the effect size.

Results:

Thirteen publications were enrolled into the analysis. The results showed that there were significant differences in overall complications (RR, 0.62; 95% CI, 0.351–1.094; P = 0.06), postoperative infection (RR, 0.503, 95% CI, 0.223–1.136) when comparing locking miniplates with nonlocking miniplates in treating mandible fractures. The incidence of malocclusion showed a statistically significant difference in the outcome favoring locking miniplates (fixed: RR, 0.503; 95% CI, 0.125–2.030; P = 0.06). In addition, the use of locking miniplates had a lower postoperative maxillomandibular fixation rate than the use of nonlocking miniplates (RR, 0.414; 95% CI, 0.196–0.872; P = 0.002).

Conclusion:

The result of meta-analysis revealed that use of locking plate is superior to the nonlocking plate in the reducing of postoperative complication rates in the management of MFs.
Short- and Long-Term Outcomes by Procedure Type for Nonsagittal Single-Suture Craniosynostosis
Authors: Bennett Katelyn G. , Hespe Geoffrey E. , Vercler Christian J. , Buchman Steven R.
Published: January 2019

Background:

Minimally invasive approaches for the treatment of single-suture craniosynostosis are sometimes touted as equivalent to cranial vault reconstruction. While techniques for sagittal synostosis have been reviewed previously, evidence regarding open and less invasive surgical techniques for metopic, coronal, and lambdoid synostosis has yet to be reviewed.

Methods:

Systematic searches were performed using Embase.com and PubMed. Included studies reported short- or long-term outcomes, compared at least 2 standard techniques, discussed single-suture coronal, metopic, or lambdoid craniosynostosis, and enrolled at least 20 study participants. Two authors screened titles and abstracts, and also performed full text review and data extraction. Given heterogeneous outcomes, qualitative synthesis was performed after data extraction.

Results:

The search strategy yielded 2348 articles. Of these, 313 were removed as duplicates, and 1935 were excluded during title/abstract review. After full text review of 100 articles, 19 were selected for data extraction. The heterogeneity of outcomes precluded meta-analysis and required qualitative synthesis. While short-term outcomes indicated decreased morbidity of minimally invasive techniques, only 2 articles presented long-term reoperation rates. One study reported higher reoperation rates in the less invasive technique, and the second reported no reoperations in the median follow-up period of 33 months.

Conclusion:

Studies comparing long-term outcomes between different surgical techniques for single-suture craniosynostosis remain deficient. The development of standardized outcome measures is essential, and prospective, multicenter studies are necessary to assess the long-term efficacy of these procedures.
Intraoperative Image-Guided Navigation in Craniofacial Surgery: Review and Grading of the Current Literature
Authors: DeLong Michael R. , Gandolfi Brad M. , Barr Meaghan L. , Datta Neha , Willson Thomas D. , Jarrahy Reza
Published: January 2019

Introduction:

Image-guided navigation has existed for nearly 3 decades, but its adoption to craniofacial surgery has been slow. A systematic review of the literature was performed to assess the current status of navigation in craniofacial surgery.

Methods:

A Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) systematic review of the Medline and Web of Science databases was performed using a series of search terms related to Image-Guided Navigation and Craniofacial Surgery. Titles were then filtered for relevance and abstracts were reviewed for content. Single case reports were excluded as were animal, cadaver, and virtual data. Studies were categorized based on the type of study performed and graded using the Jadad scale and the Newcastle-Ottawa scales, when appropriate.

Results:

A total of 2030 titles were returned by our search criteria. Of these, 518 abstracts were reviewed, 208 full papers were evaluated, and 104 manuscripts were ultimately included in the study. A single randomized controlled trial was identified (Jadad score 3), and 12 studies were identified as being case control or case cohort studies (Average Newcastle-Ottawa score 6.8) The most common application of intraoperative surgical navigation cited was orbital surgery (n = 36), followed by maxillary surgery (n = 19). Higher quality studies more commonly pertained to the orbit (6/13), and consistently show improved results.

Conclusion:

Image guided surgical navigation improves outcomes in orbital reconstruction. Although image guided navigation has promise in many aspects of craniofacial surgery, current literature is lacking and future studies addressing this paucity of data are needed before universal adoption can be recommended.
Anatomical Characteristics of the Perpendicular Plate of the Ethmoid: An Analysis of Paranasal Sinus Computed Tomography via Three-Dimensional Reconstruction
Authors: Yang Xiao , Li Dong , Xue Hongyu , Du Shanshan , Yang Xin , Wang Jing , An Yang , Duscher Dominik
Published: January 2019

In recent years, the perpendicular plate of the ethmoid (PPE) has emerged as a new autogenous grafting material in rhinoplasty and septoplasty of nasal deviation. However, no studies have outlined the precise size, shape, and morphologic features of the PPE. Therefore, this study aimed to provide detailed information on the anatomical and morphologic characteristics of the PPE to assist surgeons in performing surgeries that are more precise. About 104 Chinese patients who underwent paranasal computed tomography were assessed in this study. By analyzing the features of the PPE reconstructed with 3-dimensional models, the characteristics of the PPE at different stages of development and according to sex were observed. The PPE had a flat shape, and its lower part was relatively thin. It usually developed horizontally with age, which contributed to expansion of the PPE area. The dimensions of the PPE were significantly larger in male patients than in female patients. Through the reconstruction and measurement of Chinese patients’ PPE, the authors have established precise information about the PPE's anatomical and morphologic features. The flat shape and proper size, which are similar to those of nasal septum cartilage, make the PPE an ideal alternative to conventional autogenous grafting materials. The findings might be useful to surgeons in helping them perform surgeries that are more precise.
Molecular design, optimization and genomic integration of chimeric B cell receptors in murine B cells
Authors: Pesch Theresa , Bonati Lucia , Kelton William , Parola Cristina , Ehling Roy A , Csepregi Lucia , Kitamura Daisuke , Reddy Sai T
Published: January 2019

Immune cell therapies based on the integration of synthetic antigen receptors provide a powerful strategy for the treatment of diverse diseases, most notably retargeting T cells engineered to express chimeric antigen receptors (CAR) for cancer therapy. In addition to T lymphocytes, B lymphocytes may also represent valuable immune cells that can be engineered for therapeutic purposes such as protein replacement therapy or recombinant antibody production. In this article, we report a promising concept for the molecular design, optimization and genomic integration of a novel class of synthetic antigen receptors, chimeric B cell receptors (CBCR). We initially optimized CBCR expression and detection by modifying the extracellular surface tag, the transmembrane regions and intracellular signaling domains. For this purpose, we stably integrated a series of CBCR variants into immortalized B cell hybridomas using CRISPR-Cas9. Subsequently, we developed a reliable and consistent pipeline to precisely introduce cassettes of several kilobases size into the genome of primary murine B cells, again via CRISPR-Cas9 induced HDR. Finally, we were able to show the robust surface expression and antigen recognition of a synthetic CBCR in primary B cells. We anticipate that CBCRs and our approach for engineering primary B cells will be a valuable tool for the advancement of future B cell-based immune therapies.
A 3D-printed hand-powered centrifuge for molecular biology
Authors: Byagathvalli Gaurav , Pomerantz Aaron F. , Sinha Soham , Standeven Janet , Bhamla M. Saad
Published: January 2019

The centrifuge is an essential tool for many aspects of research and medical diagnostics. However, conventional centrifuges are often inaccessible outside of conventional laboratory settings, such as remote field sites, require a constant external power source, and can be prohibitively costly in resource-limited settings and STEM-focused programs. Here we present the 3D-Fuge, a 3D-printed hand-powered centrifuge, as a novel alternative to standard benchtop centrifuges. Based on the design principles of a paper-based centrifuge, this 3D-printed instrument increases the volume capacity to 2 mL and can reach hand-powered centrifugation speeds up to 6,000 rpm. The 3D-Fuge devices presented here are capable of centrifugation of a wide variety of different solutions such as spinning down samples for biomarker applications and performing nucleotide extractions as part of a portable molecular lab setup. We introduce the design and proof-of-principle trials that demonstrate the utility of low-cost 3D printed centrifuges for use in remote and educational settings.
A natural, conditional gene drive in plants
Authors: Conner Anthony J. , Jacobs Jeanne M.E.
Published: January 2019

A new class of gene drive in plant populations with herbicide resistance is described; a conditional gene drive that operates following herbicide application. Screening progeny from controlled crosses of Brassica napus heterozygous for a dominant allele conferring chlorsulfuron resistance, demonstrated that the herbicide imposes in planta gametic selection against pollen and ovules with the recessive allele for herbicide susceptibility, as well as embryonic selection against embryos homozygous for the susceptible allele. We postulate that natural gene drives are common in plant populations and can operate in a conditional manner resulting in non-Mendelian inheritance in response to abiotic and biotic stresses.
Better ears with eyes open: effects of multisensory stimulation with nonconscious visual stimuli on auditory learning
Authors: Ávila Milton A. V. , Ruggiero Rafael N. , Leite João P. , Bueno-Junior Lezio S. , Del-Ben Cristina M.
Published: January 2019

Audiovisual integration may improve unisensory perceptual performance and learning. Interestingly, this integration may occur even when one of the sensory modalities is not conscious to the subject, e.g., semantic auditory information may impact nonconscious visual perception. Studies have shown that the flow of nonconscious visual information is mostly restricted to early cortical processing, without reaching higher-order areas such as the parieto-frontal network. Thus, because multisensory cortical interactions may already occur in early stages of processing, we hypothesized that nonconscious visual stimulation might facilitate auditory pitch learning. In this study we used a pitch learning paradigm, in which individuals had to identify six pitches in a scale with constant intervals of 50 cents. Subjects were assigned to one of three training groups: the test group (Auditory + congruent unconscious visual, AV), and two control groups (Auditory only, A, and Auditory + incongruent unconscious visual, AVi). Auditory-only tests were done before and after training in all groups. Electroencephalography (EEG) was recorded throughout the experiment. Results show that the test group (AV, with congruent nonconscious visual stimuli) performed better during the training, and showed a greater improvement from pre-to post-test. Control groups did not differ from one another. Changes in the AV group were mainly due to performances in the first and last pitches of the scale. We also observed consistent EEG patterns associated with this performance improvement in the AV group, especially maintenance of higher theta-band power after training in central and temporal areas, and stronger theta-band synchrony between visual and auditory cortices. Therefore, we show that nonconscious multisensory interactions are powerful enough to boost auditory perceptual learning, and that increased functional connectivity between early visual and auditory cortices after training might play a role in this effect. Moreover, we provide a methodological contribution for future studies on auditory perceptual learning, particularly those applied to relative and absolute pitch training.
Cyto-architecture constrains a photoactivation induced tubulin gradient in the syncytialDrosophilaembryo
Authors: Thukral Sameer , Kaity Bivash , Dey Bipasha , Sharma Swati , Nandi Amitabha , Mitra Mithun K. , Rikhy Richa
Published: January 2019

Drosophilaembryogenesis begins with nuclear division in a common cytoplasm forming a syncytial cell. Morphogen gradient molecules spread across nucleo-cytoplasmic domains to pattern the body axis of the syncytial embryo. The diffusion of molecules across the syncytial nucleo-cytoplasmic domains is potentially constrained by association with the components of cellular architecture, however the extent of restriction has not been examined so far. Here we use photoactivation (PA) to generate a source of cytoplasmic or cytoskeletal molecules in order to monitor the kinetics of their spread in the syncytialDrosophilaembryo. Photoactivated PA-GFP and PA-GFP-Tubulin within a fixed anterior area diffused along the antero-posterior axis. These molecules were enriched in cortical cytoplasm above the yolk-filled center suggesting that the cortical cytoplasm is phase separated from the yolk-filled center. The length scales of diffusion were extracted using exponential fits under steady state assumptions. PA-GFP spread to greater distance as compared to PA-GFP-Tubulin. Both gradients were steeper and more restricted when generated in the center of the embryo probably due to a higher density of nucleo-cytoplasmic domains. The length scale of diffusion for PA-GFP-Tubulin gradient increased in mutant embryos containing short plasma membrane furrows and disrupted tubulin cytoskeleton. The PA-GFP gradient shape was unaffected by cyto-architecture perturbation. Taken together, these data show that PA-GFP-Tubulin gradient is largely restricted by its incorporation in the microtubule network and intact plasma membrane furrows. This photoactivation based analysis of protein spread across allows for interpretation of the dependence of gradient formation on the syncytial cyto-architecture.
Identification of compounds that rescue otic and myelination defects in the zebrafish adgrg6 (gpr126) mutant
Authors: Diamantopoulou Elvira , Baxendale Sarah , de la Vega de León Antonio , Asad Anzar , Holdsworth Celia J. , Abbas Leila , Gillet Valerie J. , Wiggin Giselle R. , Whitfield Tanya T.
Published: January 2019

Adgrg6 (Gpr126) is an adhesion class G protein-coupled receptor with a conserved role in myelination of the peripheral nervous system. In the zebrafish, mutation of adgrg6 also results in defects in the inner ear: otic tissue fails to down-regulate versican gene expression and morphogenesis is disrupted. We have designed a whole-animal screen that tests for rescue of both up- and down-regulated gene expression in mutant embryos, together with analysis of weak and strong alleles. From a screen of 3120 structurally diverse compounds, we have identified 68 that reduce versican b expression in the adgrg6 mutant ear, 41 of which also restore myelin basic protein gene expression in Schwann cells of mutant embryos. Nineteen compounds unable to rescue a strong adgrg6 allele provide candidates for molecules that interact directly with the Adgrg6 receptor. Our pipeline provides a powerful approach for identifying compounds that modulate GPCR activity, with potential impact for future drug design.
Measuring vision using innate behaviours in mice with intact and impaired retina function
Authors: Storchi R. , Rodgers J. , Gracey M. , Martial F.P. , Wynne J. , Ryan S. , Twining C.J. , Cootes T.F. , Killick R. , Lucas R.J.
Published: January 2019

Measuring vision in rodents is a critical step for understanding vision, improving models of human disease, and developing therapies. Established behavioural tests for perceptual vision, such as the visual water task, rely on learning. The learning process, while effective for sighted animals, can be laborious and stressful in animals with impaired vision, requiring long periods of training. Current tests that that do not require training are based on sub-conscious, reflex responses (e.g. optokinetic nystagmus) that don’t require involvement of visual cortex and higher order thalamic nuclei. A potential alternative for measuring vision relies on using visually guided innate defensive responses, such as escape or freeze, that involve cortical and thalamic circuits. In this study we address this possibility in mice with intact and degenerate retinas. We first develop automatic methods to detect behavioural responses based on high dimensional tracking and changepoint detection of behavioural time series. Using those methods, we show that visually guided innate responses can be elicited using parametisable stimuli, and applied to describing the limits of visual acuity in healthy animals and discriminating degrees of visual dysfunction in mouse models of retinal degeneration.
Conflicting Bottom-up and Top-down Signals during Misrecognition of Visual Objects
Authors: Abdelhack Mohamed , Kamitani Yukiyasu
Published: January 2019

Visual recognition involves integrating visual information with other sensory information and prior knowledge. In accord with Bayesian inference under conditions of unreliable visual input, the brain relies on the prior as a source of information to achieve the inference process. This drives a top-down process to improve the neural representation of visual input. However, the extent to which non-stimulus-driven top-down information affects processing in the ventral stream is still unclear. We conducted a perceptual decision-making task using blurred images, while conducting functional magnetic resonance imaging. We then transformed brain activity into deep neural network features to distinguish bottom-up and top-down signals. We found that top-down information unrelated to the stimulus had a minimal effect on lower-level visual processes. The neural representations of degraded stimuli that were misrecognized were still correlated with the correct object category in the lower levels of processing. In contrast, activity in the higher cognitive areas was more strongly correlated with recognition reported by the subjects. The results indicated a discrepancy between the results of processing at the lower and higher levels, indicating the existence of a stimulus-independent top-down signal flowing back down the hierarchy. These findings suggest that integration between bottom-up and top-down information takes the form of competing evidence in higher visual areas between prior-driven top-down and stimulus-driven bottom-up signals. These findings could provide important insight into the different modes of integration of neural signals in the visual cortex that contribute to the visual inference process.
Rethinking pain threshold as a zone of uncertainty
Authors: Madden Victoria J , Kamerman Peter R , Catley Mark J , Bellan Valeria , Russek Leslie N , Camfferman Danny , Moseley G Lorimer
Published: January 2019

Background

The pain threshold is traditionally conceptualised as a boundary that lies between painful and non-painful events, suggesting a reasonably stable relationship between stimulus and response. In two previous experiments, participants received laser stimuli of various intensities and rated each stimulus on the Sensation and Pain Rating Scale (SPARS), which includes ranges for rating painful and non-painful events and clearly defines the presumed boundary between them. In the second experiment, participants also provided ratings on the conventional 0-100 Numerical Rating Scale for pain (NRS) and a new rating scale for non-painful events. Those data showed the SPARS to have a curvilinear stimulus-response relationship, reflecting that several different intensities may be rated as painful and non-painful in different trials. This suggests that participants were uncertain about painfulness over a range of intensities and calls into question the idea of a boundary between non-painful and painful events. The current study aimed to determine the number of different stimulus intensities across which each participant provided ‘painful’ and ‘non-painful’ reports in different trials.

Methods

We undertook novel exploratory analyses on data from the aforementioned two experiments (n = 19, 11 female, 18-31 years old; n = 7, 5 female, 21-30 years old). We used the binomial test to formally determine the width of this ‘zone of uncertainty’ about painfulness, using ratings on the SPARS and the comparator scales, and data visualisation to assess whether trial-to-trial change in stimulus intensity influences ratings.

Results

We found that the width of the zone of uncertainty varied notably between individuals and that the zone was non-continuous for most participants. Plots of group-level data concealed the inter-individual variability apparent in the individual plots, but still showed a wide zone of uncertainty on both the SPARS and the NRS, but a narrow zone on the scale for non-painful events. There was no evidence that trial-to-trial change in stimulus intensity influenced ratings.

Conclusions

The variability revealed by this study has important design implications for experiments that include initial calibration of repeatedly delivered stimuli. The variability also stands to inflate the size of sample that is required for adequate statistical powering of experiments, and provides rationale for the use of statistical approaches that account for individual variability in studies of pain. Finally, the high variability implies that, if experimental stimuli are to be used in clinical phenotyping, many trials may be required to obtain results that represent a single patient’s actual response profile.