bluuebunny/crossref_metadata_2025_split huggingface dataset:
Upregulated Plant Homeodomain Finger Protein 6 Promotes Extracellular Matrix Degradation in Intervertebral Disc Degeneration Based on Microarray Analysis
Authors: Rui Gang , Sun Naikun , Hu Baoshan , Lin Shengrong , Wang Zhongtang , Lin Qingfu 
Published: May 2020

Study Design.
mRNA analysis.

Objective.
The aim of this study was to identify differentially expressed genes (DEGs) in disc degeneration, analyze the potential biological functions of DEGs, and screen for a new target to prevent the degeneration.

Summary of Background Data.
Intervertebral disc degeneration (IDD) is an irreversible process and causes long-term heavy socioeconomic burdens. Existing and therapies under development are unable to prevent disc degeneration in a safe and effective manner. Therefore, elucidating the potential mechanism underlying degeneration and the development of new targets for IDD therapy are urgently required.

Methods.
Nucleus pulposus (NP) cells from mild and severe IDD (Ctrl and IDD groups) were separated, and DEGs of the two groups were identified with mRNA microarray analysis, followed by bioinformatics analysis.
Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was performed to verify the microarray results. Gene over-expression and silencing technologies were used to study the role of plant homeodomain finger protein 6 (PHF6). qRT-PCR and western blot analyses were used to detect the expressions of collagen II (COL2), matrix metalloproteinases 13 (MMP13), and ADAM metallopeptidase with thrombospondin type 1 motif 4 (ADAMTS4).

Results.
The study identified 377 up- and 116 downregulated DEGs in NP cells from two groups. These DEGs were mainly involved in cellular and metabolic processes and enriched in immune system and nucleotide metabolism pathways. Upregulated PHF6, with the highest verified fold change, was significantly increased in the IDD group. Over-expressing PHF6 in Ctrl NP cells significantly inhibited the expression of COL2 and enhanced the expressions of MMP13 and ADAMTS4, whereas silencing PHF6 in IDD NP cells reversed such expression alterations.

Conclusion.
Upregulated PHF6 caused IDD by promoting extracellular matrix degradation; therefore, PHF6 could be developed as a potential novel target to prevent the degeneration. Our DEG profiling of NP cells from IDD patients provided a database to identify the key genes involved in IDD.

Level of Evidence.
N/A
Surgical Treatment for Severe Fixed Hyperkyphosis in an Adult Patient Suffering From Ankylosing Spondylitis and Hereditary Hypophosphatemia With Vertebral Osteopetrosis
Authors: Wolfram Julia M. , Zitt Emanuel , Bach Christian M. 
Published: May 2020

Purpose:
Ankylosing spondylitis and hereditary hypophosphatemia with long-term high dose supplementation of phosphorous and calcitriol can both lead to severe structural abnormalities of the vertebrae. Impairment of spinal mobility and spinal deformity may ultimately necessitate surgical treatment. A severe fixed hyperkyphosis in a patient with ankylosing spondylitis is a surgically demanding condition, therefore, the indication for surgical treatment should be thoroughly considered and chosen individually.

Methods:
This is an uncommon case with a combination of a severe fixed hyperkyphosis with a Cobb-angle of 105 degrees between Th2 and L4 in an adult male patient suffering from ankylosing spondylitis and X-linked hypophosphatemia with surprisingly massive osteopetrosis. In this paper, the coexisting conditions of late-stage ankylosing spondylitis and long-term treated hereditary hypophosphatemia are highlighted. The surgical treatment with different techniques, complications, and results are well explained.

Results:
A normal gait and stand were achieved by a long posterior fusion with 3 pedicle subtraction osteotomies on L1, L3, and L5. The surgical correction was performed in 3 stages. Postoperative the patient was administered to a rehabilitation center for 3 months. The hyperkyphosis, the C7 plumbline, and the pelvic retroversion were corrected.

Conclusions:
Surgical treatment of a severe fixed hyperkyphosis due to ankylosing spondylitis is technically demanding but can be successfully achieved if all surgical challenges and comorbidities are adequately addressed including intraoperative surprising findings like osteopetrotic bone in a patient with hereditary hypophosphatemia as in our case.
Current concepts in the treatment of giant cell tumour of bone
Authors: van der Heijden Lizz , Dijkstra Sander , van de Sande Michiel , Gelderblom Hans 
Published: May 2020

Purpose of review
Giant cell tumour of bone (GCTB) is an intermediate, locally aggressive primary bone tumour. In addition to local therapy, new drugs became available for this disease. Denosumab, a receptor activator of nuclear factor κ-B-ligand inhibitor, was introduced as systemic targeted therapy for advanced or inoperable and metastatic GCTB. Also, the bisphosphonate zoledronic acid has activity in GCTB by directly targeting the neoplastic stromal cells.

Recent findings
In a small RCT, bisphosphonates were successful in controlling tumour growth and a higher apoptotic index of tumour cells was seen after zoledronic acid versus controls. Although bisphosphonate-loaded bone cement has not been studied to a large extent, it does not seem harmful and may constitute a logical local adjuvant. From the largest clinical trial to date, the risk-to-benefit ratio for denosumab in patients with advanced GCTB remains favourable, also in facilitating less morbid surgery. Concerns have arisen that recurrence rates would be higher than after conventional treatment, ranging from 20 to 100% in a systematic review, although this may be because of bias. H3F3A (G34W) driver mutations are helpful in the differentiation between GCTB and other giant cell-containing malignancies. H3.3-G34W proved sufficient to drive tumourigenesis. The cumulative incidence of malignancy in GCTB is estimated at 4%, of which primary malignancy 1.6% and secondary malignancy 2.4%, the latter mainly after radiation. To date, a potential causal relationship between denosumab and pulmonary metastases has not been confirmed; if they do not behave indolently, it would be advised to reassess diagnosis and consider malignancy.

Summary
Denosumab remains a highly effective treatment option for patients with advanced GCTB. A short duration of 2–4 months neoadjuvant denosumab is advised to facilitate less morbid surgery and prevent incomplete curettage by macroscopic tumour alterations. Reduced dose intensity is being studied to reduce long term side-effects. Further research on bisphosphonates and other targets including H3.3-G34W remains warranted.
Atrial Fibrillation in COVID-19: From Epidemiological Association to Pharmacological Implications
Authors: Russo Vincenzo , Rago Anna , Carbone Andreina , Bottino Roberta , Ammendola Ernesto , Della Cioppa Nadia , Galante Dario , Golino Paolo , Nigro Gerardo 
Published: May 2020

Abstract:
Coronavirus disease 2019 (COVID-19) outbreak is a public health emergency of international concerns because of a highly pathogenic human coronavirus (HCoV), actually named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite much emerging data about the epidemiological association between cardiovascular diseases and COVID-19, little is still known about atrial fibrillation and its optimal management in this clinical contest. The aim of our review is to describe the pharmacological interactions between cardiovascular drugs more commonly used in atrial fibrillation management and experimental COVID-19 therapies, based on EU and US summaries of product characteristics.
Baseline estrogen levels in postmenopausal women participating in the MAP.3 breast cancer chemoprevention trial
Authors: Richardson Harriet , Ho Vikki , Pasquet Romain , Singh Ravinder J. , Goetz Matthew P. , Tu Dongsheng , Goss Paul E. , Ingle James N. 
Published: May 2020

Abstract

Objective:
The aim of the study was to quantify baseline estradiol (E2) and estrone (E1) concentrations according to selected patient characteristics in a substudy nested within the MAP.3 chemoprevention trial.

Methods:
E2 and E1 levels were measured in 4,068 postmenopausal women using liquid chromatography-tandem mass spectrometry. Distributions were described by age, years since menopause, race, body mass index (BMI), smoking status, and use and duration of hormone therapy using the Kruskal-Wallis test. Multivariable linear regression was also used to identify characteristics associated with estrogen levels.

Results:
After truncation at the 97.5th percentile, the mean (SD)/median (IQR) values for E2 and E1 were 5.41 (4.67)/4.0 (2.4-6.7) pg/mL and 24.7 (14.1)/21 (15-31) pg/mL, respectively. E2 and E1 were strongly correlated (Pearson correlation [r] = 0.8, P < 0.01). The largest variation in E2 and E1 levels was by BMI; mean E2 and E1 levels were 3.5 and 19.1 pg/mL, respectively for women with BMI less than 25 and 7.5 and 30.6 pg/mL, respectively, for women with BMI greater than 30. E2 and E1 varied by age, BMI, smoking status, and prior hormone therapy in multivariable models (P < 0.01).

Conclusions:
There was large interindividual variability observed for E2 and E1 that varied significantly by participant characteristics, but with small absolute differences except in the case of BMI. Although the majority of participant characteristics were independently associated with E1 and E2, together, these factors only explained about 20% of the variation in E1 and E2 levels.
Computer-aided Design and Syringe-aided Manufacturing for Mandibular Reconstruction Using a Vascularized Fibula Flap
Authors: Karakawa Ryo , Yano Tomoyuki , Yoshimatsu Hidehiko , Katsuta Hideyuki , Kushihashi Yukiomi , Shimane Toshikazu 
Published: May 2020

Summary:
Thanks to the introduction of virtual surgical planning (VSP), mandibular reconstruction using a fibula flap has become simplified, and patient-specific reconstruction is now possible. With a VSP software, surgical “cutting guides” and custom-made titanium plates can be designed to help surgeons. However, they are expensive and require extended periods of time either for prototyping or to acquire the advanced knowledge necessary for operating the VSP software. The aim of this article is to introduce a new easy and low-cost method of surgical planning for mandible reconstruction using a computer-aided design and the syringe-aided manufacturing technique. Simulations of fibula osteotomy are performed using regular and commercially available 10-ml syringes. The syringes are cut into separate segments to fit the defect of the 3-dimensional mandible model and to match the prebent titanium plate. The syringe segments are then connected together 3-dimensionally to confirm that the shape matched both the contour of the defect and the angles of the mandible. The simulated syringe segments are used as cutting guides. Then osteotomies are performed according to the cutting guide to obtain the exact lengths and angles required to achieve precise bony reconstruction. The mandibular reconstruction procedures are successful, with a good match between the preoperative planned syringe models and the final results of the surgery. Although further clinical investigation will be required to confirm its efficacy, the computer-aided design and the syringe-aided manufacturing method has the potential to be a useful technique for mandible reconstruction using a vascularized fibula flap.
New Surgical Technique: Bidirectional Forehead Narrowing and Eyebrow Lifting Using Regional Flap Mobility
Authors: Kim Jae B. , Kim Sang W. , Chung Jae Y. 
Published: May 2020

Background:
We describe our experience with bidirectional forehead narrowing and eyebrow lifting (BiNaLi), a surgical technique we have been practicing for several years to correct facial esthetic issues of patients such as long forehead, high hairline, and low eyebrow level, which helps us achieve forehead height reduction with eyebrow lifting, using 1 incision line in a one-stage procedure.

Methods:
We divided 576 patients who visited our institution between March 2014 and February 2019 into 4 groups: long forehead only (group I), low eyebrow level (groups II and IV), and M-shaped hairline (groups III and IV); BiNaLi operation was performed as appropriate for each group.

Results:
The preoperative length of the median area of the forehead was 7.3 cm, and the mean postoperative change in the length of the same was 1.4 cm. The lateral forehead length was also measured for groups III and IV. The mean preoperative length was 7.7 cm, and the mean postoperative change in the length was 1.7 cm. Eyelid length was also measured for groups II and IV. The mean preoperative length was 0.7 cm, and the mean postoperative change in the length was 0.3 cm. More than 90% of the patients gave a score of 4.0 or higher for esthetic satisfaction.

Conclusions:
We designed a BiNaLi technique to satisfy patients’ facial esthetic needs using changes in flap movement direction, adjustment in the range of skin excision, and differences in flap dissection. A single operation can have various effects, including achieving forehead shortening, clear double-fold line through eyebrow lifting, and correction of a mild M-shaped hairline.
Usefulness of a Novel Pinwheel-shaped Incision Technique for Skin Tumor Excision
Authors: Watanabe Ayako , Miyamoto Towa 
Published: May 2020

Summary:
Use of the fusiform ellipse excision technique is the most common method for direct closure of circular and elliptical defects. To prevent dog-ear formation after suturing, the long-axis length of the fusiform ellipse should be ≥3 times the transverse dimension and the angle formed by the 2 lines at both ends should be <30°. We devised a pinwheel-shaped incision technique for skin tumor excision that could reduce the scar size. We aim to present this technique and report its results and usefulness. We included 50 patients (55 cases; 54% women; mean age, 39.8 years) who underwent surgery using our pinwheel-shaped incision technique between January 2016 and December 2018. The incision line was designed like a pinwheel around the tumor, and the excess skin was trimmed after suturing at the center. The length-to-width ratio was calculated using the width before the operation and the suture length at the end of the operation. The operation site was primarily the face, and the maximum tumor width was 48 mm. The postoperative suture line length was 2.1 ± 0.2 (mean ± SD) times the width of the excision area. There were no complications such as skin necrosis, and no patient required reoperation because of dog-ear formation. Our new pinwheel-shaped incision technique allows shortening of the length-to-width ratio compared with that required in the conventional method and helps avoid dog-ear formation. We successfully used this technique in 55 cases and confirmed its usefulness.
Postmastectomy Breast Reconstruction in the Time of the Novel Coronavirus Disease 2019 (COVID-19) Pandemic
Authors: Chetta Matthew D. , Schoenbrunner Anna R. , Lee Clara N. 
Published: May 2020

Background:
Breast reconstruction has a well-documented positive impact on the psychosocial well-being of women recovering from breast cancer. Rates of breast cancer diagnoses are rising, and more women are seeking mastectomy as treatment and as prophylaxis.

Methods:
Postmastectomy breast reconstruction often begins at the time of mastectomy in coordination with the oncologic breast surgeons. Immediate breast reconstruction increases complication rate (11% vs 4%) and unplanned reoperation rate (7% vs 4%), requiring more personnel and resources used during the preoperative, intraoperative, and postoperative phases of patient care.

Discussion:
In the setting of global pandemics such as coronavirus disease 2019 (COVID-19), breast reconstruction demands a unique and nuanced approach, as most forms of breast reconstruction can occur successfully in a delayed fashion. While this may prolong the overall time until completion of reconstruction, other factors come into play in the setting of a communicable (potentially deadly) illness. Factors that must be considered include allocation of essential resources and protection of patients and families from disease transmission.

Conclusions:
Plastic surgeons performing breast reconstruction must take these factors into account when counseling their patients, colleagues, and institutions and be proactive in determining which procedures are time-critical and which should be postponed until the disaster situation has relieved.
Low cholesterol syndrome and drug development
Authors: Handhle Ahmed , Viljoen Adie , Ramachandran Radha , Wierzbicki Anthony S. 
Published: May 2020

Purpose of review
Low cholesterol syndromes were considered curiosities. The present article reviews some hypolipidaemic disorders and the drugs developed from the insights they provided.

Recent findings
Abetalipopoproteinaemia and hypobetalipoproteinaemia are associated with low cholesterol concentrations and caused by mutations in apolipoprotein (apo) B or microsomal transfer protein. This led to the development of mipomersen and lomitapide which are used to treat homozygous familial hypercholesterolaemia. Mutations in proprotein convertase subtilisin kexin-9 (PCSK9) can cause either high or low cholesterol. Loss of function PCSK9 mutations prompted the development of antibody therapies to PCSK9 which are now widely used to treat hypercholesterolaemia. Mutations in apolipoprotein C-3 and angiopoietin-like protein 3 (ANGPTL3) cause hypolipoproteinaemia and reduced triglycerides. Antisense therapies to apolipoprotein C-3 and antibodies to ANGPTL3 are in development to treat familial chylomicronaemia syndrome. Activating mutations in apoA-1 result in hyper-functioning high-density lipoprotein (HDL) and suggest that modifying HDL turnover may reduce cardiovascular disease (CVD) risk.

Summary
Orphan lipid disorders have provided insights into mechanisms involved in lowering cholesterol levels and the potential safety and efficacy of interventional processes. They have been not only enabled development of drugs to treat rare lipid disorders but also those finding wider use in general lowering of CVD risk.
Evaluation of liver fibrosis in patients with Wilson’s disease
Authors: Przybyłkowski Adam , Szeligowska Jowita , Januszewicz Magdalena , Raszeja-Wyszomirska Joanna , Szczepankiewicz Benedykt , Nehring Piotr , Górnicka Barbara , Litwin Tomasz , Członkowska Anna 
Published: May 2020

Objectives
Staging of fibrosis in chronic liver disease is important for prognosis and treatment planning. Liver biopsy is the gold standard in fibrosis assessment; however, new methods for fibrosis and stiffness measurement exist which have not been evaluated in patients with Wilson’s disease. To evaluate the accuracy of collagen proportionate area (CPA), transient elastography and shear wave elastography (SWE) in the assessment of liver fibrosis in adult patients with Wilson’s disease.

Methods
In this retrospective study of 60 patients with Wilson’s disease, results of percutaneous cutting liver biopsy assessed using the Ishak fibrosis score and CPA were compared with liver stiffness measured with transient elastography and SWE.

Results
CPA correlated with the Ishak score (r = 0.45; P = 0.001) and transient elastography results correlated with SWE measurements (r = 0.80; P = 0.0001). In contrast, transient elastography or SWE did not significantly correlate with the Ishak score or CPA.

Conclusion
Collagen content assessment may be useful for estimation of liver fibrosis in patients with Wilson’s disease. However, single time-point elastographic liver stiffness measurements have a limited diagnostic value in Wilson’s disease.
Whole-body 75SeHCAT retention is determined by entero-hepatic bile acid recycling rate
Authors: Soares Sara , Vadrucci Manuela , Peters A. Michael 
Published: May 2020

Aim
It has previously been proposed that entero-hepatic bile acid recycling frequency is a major determinant of whole-body retention (WBR) of 75SeHCAT. Hepatocyte to terminal ileum accounts for almost the entire cycle. The study aim was to test this hypothesis by comparing WBR with an estimate of speed of transit of bile acids using 99mTc-HIDA scintigraphy performed on a separate occasion.

Methods
Using an un-collimated gamma camera and patient-to-camera distance of 1.5 m, WBR at 7 days after oral 75SeHCAT administration was measured in 14 patients with chronic diarrhoea, of whom 10 had previous cholecystectomy. The distance reached within the intestine of 99mTc-HIDA at 1 h (n = 14) and 2 h (n = 7) following iv injection was graded as follows: grades 1 and 2: small bowel on left and right sides of abdomen, respectively; and grade 3: colon. Relationships between WBR and grade were assessed using Spearman rank correlation.

Results
Interval between studies ranged from 3 to 1219 (median 330) days. Grading correlated with WBR at 1 h (rs = −0.63; P = 0.02) and weakly at 2 h (rs = −0.68; P = 0.09) post-injection of 99mTc-HIDA. In nine patients in whom 99mTc-HIDA and 75SeHCAT scans were performed within 1 year of each other, the correlation remained significant at 1 h (rs = −0.73; P = 0.03). There was no difference in WBR or grading between patients with or without a gall bladder.

Conclusion
Entero-hepatic bile acid recycling frequency is a major determinant of whole-body 75SeHCAT retention.
Dynamic 18F-fluorocholine PET/CT for parathyroid imaging in patients with primary hyperparathyroidism
Authors: Broos Wouter A.M. , Wondergem Maurits , van der Zant Friso M. , Schaper Nicolaas C. , Knol Remco J.J. 
Published: May 2020

Objective
In the past few years, 18F-fluorocholine PET/CT has been established as a promising imaging technique for preoperative localization of parathyroid adenomas, but the optimal time point to start PET/CT acquisition after tracer injection is yet unknown. The aim of the present study was to assess the optimal time frame to acquire the PET/CT images and to evaluate the ability of dynamic imaging to differentiate parathyroid adenomas from active lymph nodes, a common cause for false-positive scan results.

Patients and methods
Patients with primary hyperparathyroidism who had undergone a dynamic 18F-fluorocholine PET/CT positive for parathyroid disease and who subsequently underwent successful parathyroidectomy were retrospectively included in this study. On the 20 minutes dynamic images, standardized uptake value measurements were acquired per 1 minute frame for the parathyroid adenoma, the thyroid gland, blood pool activity, and, if present, lymph node activity.

Results
A total of 101 patients were included in this study. Time-activity curves showed a decrease of activity in parathyroid and thyroid glands, with faster wash-out from the thyroid gland and on average a stable, lower activity in lymph nodes. Blood pool activity was particularly present in the first 2 minutes. Differentiation of a parathyroid adenoma from active lymph nodes was best before 5 minutes, but no definitive cutoff value could be determined. Differentiation of a parathyroid adenoma from the thyroid gland was best after 10 minutes.

Conclusion
Dynamic imaging starting at the early time point of 2 minutes after injection of 18F-fluorocholine is useful for characterization of hyperfunctioning parathyroid glands.