bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term outcome of stereotactic brachytherapy with temporary Iodine-125 seeds in patients with WHO grade II gliomas
Authors: Watson Juliana , Romagna Alexander , Ballhausen Hendrik , Niyazi Maximilian , Lietke Stefanie , Siller Sebastian , Belka Claus , Thon Niklas , Nachbichler Silke Birgit 
Published: December 2020

Abstract
Background
This long-term retrospective analysis aimed to investigate the outcome and toxicity profile of stereotactic brachytherapy (SBT) in selected low-grade gliomas WHO grade II (LGGII) in a large patient series.

Methods
This analysis comprised 106 consecutive patients who received SBT with temporary Iodine-125 seeds for histologically verified LGGII at the University of Munich between March 1997 and July 2011. Investigation included clinical characteristics, technical aspects of SBT, the application of other treatments, outcome analyses including malignization rates, and prognostic factors with special focus on molecular biomarkers.

Results
For the entire study population, the 5- and 10-years overall survival (OS) rates were 79% and 62%, respectively, with a median follow-up of 115.9 months. No prognostic factors could be identified. Interstitial radiotherapy was applied in 51 cases as first-line treatment with a median number of two seeds (range 1–5), and a median total implanted activity of 21.8 mCi (range 4.2–43.4). The reference dose average was 54.0 Gy. Five- and ten-years OS and progression-free survival rates after SBT were 72% and 43%, and 40% and 23%, respectively, with a median follow-up of 86.7 months. The procedure-related mortality rate was zero, although an overall complication rate of 16% was registered. Patients with complications had a significantly larger tumor volume (p = 0.029).

Conclusion
SBT is a minimally invasive treatment modality with a favorable outcome and toxicity profile. It is both an alternative primary treatment method as well as an adjunct to open tumor resection in selected low-grade gliomas.
Impact of the SARS-CoV-2 pandemic on emergency surgery services—a multi-national survey among WSES members
Authors:   The WSES COVID-19 emergency surgery survey collaboration group, Reichert Martin , Sartelli Massimo , Weigand Markus A. , Doppstadt Christoph , Hecker Matthias , Reinisch-Liese Alexander , Bender Fabienne , Askevold Ingolf , Padberg Winfried , Coccolini Federico , Catena Fausto , Hecker Andreas 
Published: December 2020

Abstract
Background
The SARS-CoV-2 pandemic is a major challenge for health care services worldwide. It’s impact on oncologic therapies and elective surgery has been described recently, and the literature provides guidelines regarding appropriate elective patient treatment during the pandemic. However, the impact of SARS-CoV-2 pandemic on emergency surgery services has been poorly investigated up to now.

Methods
A 17-item web survey had been distributed to emergency surgeons in June 2020 around the world, investigating the impact of SARS-CoV-2 pandemic on patients and septic diseases both requiring emergency surgery and the time-to-intervention in emergency surgery routine, as well as experiences with surgery in COVID-19 patients.

Results
Ninety-eight collaborators from 31 countries responded to the survey. The majority (65.3%) estimated the impact of the SARS-CoV-2 pandemic on emergency surgical patient care as being strong or very strong. Due to the pandemic, 87.8% reported a decrease in the total number of patients undergoing emergency surgery and approximately 25% estimated a delay of more than 2 h in the time-to-diagnosis and another 2 h in the time-to-intervention. Fifty percent make structural problems with in-hospital logistics (e.g. transport of patients, closed normal wards etc.) mainly responsible for delayed emergency surgery and the frequent need (56.1%) for a triage of emergency surgical patients. 56.1% of the collaborators observed more severe septic abdominal diseases during the pandemic, especially for perforated appendicitis and severe septic cholecystitis (41.8% and 40.2%, respectively). 62.2% had experiences with surgery in COVID-19-infected patients.

Conclusions
The results of The WSES COVID-19 emergency surgery survey are alarming. The combination of an estimated decrease in numbers of emergency surgical patients and an observed increase in more severe septic diseases may be a result of the fear of patients from infection with COVID-19 and a consecutive delayed hospital admission and diagnosis. A critical delay in time-to-diagnosis and time-to-intervention may be a result of changes in in-hospital logistics and operating room as well as intensive care capacities. Both reflect the potentially harmful impact of SARS-CoV-2 pandemic on emergency surgery services.
Clinical value of CT-based patient-specific 3D preoperative design combined with conventional instruments in primary total knee arthroplasty: a propensity score-matched analysis
Authors: Lei Kai , Liu Li Ming , Xiang Yi , Chen Xin , Fan Hua Quan , Peng Yang , Luo Jiang Ming , Guo Lin 
Published: December 2020

AbstractPurposeTo evaluate the operation and early clinical effect in primary total knee arthroplasty (TKA) about the novel combination of CT-based patient-specific three-dimensional (3D) preoperative design and conventional osteotomy instruments, compared with the conventional method.MethodsAfter a 1:1 propensity score-matching (PSM), patients were matched to the novel technique group and the conventional group, 109 cases in each group. The conventional group adopted a preoperative design based on a full-length radiograph (FLX) and received TKA with conventional osteotomy instruments. The novel technique group used a CT-based patient-specific 3D preoperative design combined with conventional osteotomy instruments; during the surgery, the femoral entry point, femoral valgus osteotomy angle, the fix point of tibial plateau extramedullary guide pin, and the position of tibial extramedullary positioning rod were accurately selected according to the preoperative 3D design to ensure accurate intraoperative implementation. The lower limb alignment, component position, operation time, tourniquet time, hospital stay, blood loss volume, incidence of postoperative complications, visual analog scale (Vas) score, and New Knee Society Score System (NEW-KSS) at 1 day before operation and 1, 6, and 12 months after operation were recorded and compared.ResultsThe novel technique group was significantly better than the conventional group in controlling lateral tibial component angle (LTC) (P< 0.001), and the novel technique group had lower percentages of hip-knee-ankle angle (HKA) outliers (P< 0.001) and overcorrection (P= 0.003). The operation time, tourniquet time, and hospital stay of the novel technique group was shorter (P< 0.05). In 1 month after the operation, the novel technique group achieved a significantly better VAS score (P< 0.05), but a similar NEW-KSS score (P> 0.05) when compared with the conventional group. But in 6 and 12 months after surgery, no statistical differences were seen in the above two scores (P> 0.05).ConclusionThe novel technique of CT-based patient-specific 3D preoperative design combined with conventional instruments can improve the accuracy of osteotomy in primary total knee arthroplasty, with benefits of significantly reducing pain and rapid recovery during the early postoperative period, but having no obvious effect on outcome after a 1-year follow-up.
Gradual ulnar lengthening in Masada type I/IIb deformity in patients with hereditary multiple osteochondromas: a retrospective study with a mean follow-up of 4.2 years
Authors: Li Yuchan , Wang Zhigang , Chen Mu , Cai Haoqi 
Published: December 2020

Abstract
Background
Gradual ulnar lengthening is the most commonly used procedure in the treatment of Masada type I/II deformity in patients with hereditary multiple osteochondromas. However, the treatment remains controversial for the recurrence of deformity in growing children. This study aims to evaluate the clinical and radiological outcomes of ulnar gradual lengthening in our clinic.

Methods
We retrospectively reviewed patients who underwent ulnar lengthening by distraction osteogenesis from June 2008 to October 2017. The carrying angle (CA) and range of motion (ROM) of the forearm and elbow were clinically assessed, and the radial articular angle (RAA) and ulnar shortening (US) were radiologically assessed before lengthening, 2 months after external frame removal, and at the last follow-up.

Results
The current study included 15 patients (17 forearms) with a mean age of 9.4 ± 2.3 years at the index surgery. The mean follow-up period was 4.2 ± 2.4 years. There were 9 patients (10 forearms) with Masada type I deformity and 6 patients (7 forearms) with Masada type IIb deformity. The mean amount of ulnar lengthening was 4.2 ± 1.2 cm. The mean RAA improved from 37 ± 8 to 30 ± 7° initially (p = 0.005) and relapsed to 34 ± 8° at the last follow-up (p = 0.255). There was a minimal deterioration of US yet significant improvement at the last follow-up compared to pre-op (p < 0.001). At the last follow-up, the mean forearm pronation and elbow flexion increased significantly (p < 0.001 and p = 0.013, respectively), and the mean carrying angle also improved significantly (p < 0.001). No patient with type IIb deformity achieved a concentric radial head reduction.

Conclusions
Gradual ulnar lengthening significantly reduces cosmetic deformity and improves function in patients with Masada type I/IIb deformity. Our results supported early ulnar lengthening for patients with a tendency of dislocation of the radial head.
The drug likeness analysis of anti-inflammatory clerodane diterpenoids
Authors: Feng Zheling , Cao Jun , Zhang Qingwen , Lin Ligen 
Published: December 2020

AbstractInflammation is an active defense response of the body against external stimuli. Long term low-grade inflammation has been considered as a deteriorated factor for aging, cancer, neurodegeneration and metabolic disorders. The clinically used glucocorticoids and non-steroidal anti-inflammatory drugs are not suitable for chronic inflammation. Therefore, it’s urgent to discover and develop new effective and safe drugs to attenuate inflammation. Clerodane diterpenoids, a class of bicyclic diterpenoids, are widely distributed in plants of the Labiatae, Euphorbiaceae and Verbenaceae families, as well as fungi, bacteria, and marine sponges. Dozens of anti-inflammatory clerodane diterpenoids have been identified on different assays, both in vitro and in vivo. In the current review, the up-to-date research progresses of anti-inflammatory clerodane diterpenoids were summarized, and their druglikeness was analyzed, which provided the possibility for further development of anti-inflammatory drugs.
Root causes of elective surgical case cancellation in Ethiopia: a systematic review and meta-analysis
Authors: Birhanu Yeneabat , Endalamaw Aklilu , Adu Aynalem 
Published: December 2020

Abstract
Background
Cancellation of elective surgical operation recognized as a major cause of emotional trauma to patients as well as their families. In Ethiopia, prevalence and root causes for elective surgical case cancellation varies from time to time in different settings. This systematic review and meta-analysis aimed to find the pooled prevalence and root causes for elective surgical case cancellation in Ethiopia.

Methods
The databases for the search were Web of Science, PubMed, and Google Scholar. The last literature search was performed on February 8, 2020. To assess publication bias Egger’s regression analysis was applied. The pooled estimation was estimated using random-effects model meta-analysis. Subgroup analysis was also done based on the root causes of surgical case cancellation.

Results
This meta-analysis included a total of 5 studies with 5591 study participants. The pooled prevalence of elective surgical case cancellation was 21.41% (95% CI: 12.75 to 30.06%).
Administration-related reason (34.50%) was the most common identified root cause, followed by surgeon (25.29%), medical (13.90%), and patient-related reasons (13.34%).

Conclusion
The prevalence of elective surgical case cancellation was considerable. The most common root cause for elective surgical case cancellation was administration-related reasons, followed by the surgeon, medical and patient-related reasons. The causes for the surgical cancellations are potentially preventable. Thus, efforts should be made to prevent unnecessary cancellations through careful planning.
Chidamide increases the sensitivity of refractory or relapsed acute myeloid leukemia cells to anthracyclines via regulation of the HDAC3 -AKT-P21-CDK2 signaling pathway
Authors: Wang Hao , Liu Yu-chen , Zhu Cheng-ying , Yan Fei , Wang Meng-zhen , Chen Xiao-su , Wang Xiao-kai , Pang Bao-xu , Li Yong-hui , Liu Dai-hong , Gao Chun-ji , Liu Shu-jun , Dou Li-ping 
Published: December 2020

Abstract
Background
Induction therapy for acute myeloid leukemia (AML) is an anthracycline-based chemotherapy regimen. However, many patients experience a relapse or exhibit refractory disease (R/R). There is an urgent need for more effective regimens to reverse anthracycline resistance in these patients.

Methods
In this paper, Twenty-seven R/R AML patients with anthracycline resistance consecutively received chidamide in combination with anthracycline-based regimen as salvage therapy at the Chinese PLA General Hospital.

Results
Of the 27 patients who had received one course of salvage therapy, 13 achieved a complete response and 1 achieved a partial response. We found that the HDAC3-AKT-P21-CDK2 signaling pathway was significantly upregulated in anthracycline-resistant AML cells compared to non-resistant cells. AML patients with higher levels of HDAC3 had lower event-free survival (EFS) and overall survival (OS) rates. Moreover, anthracycline-resistant AML cells are susceptible to chidamide, a histone deacetylase inhibitor which can inhibit cell proliferation, increase cell apoptosis and induce cell-cycle arrest in a time- and dose-dependent manner. Chidamide increases the sensitivity of anthracycline-resistant cells to anthracycline drugs, and these effects are associated with the inhibition of the HDAC3-AKT-P21-CDK2 signaling pathway.

Conclusion
Chidamide can increase anthracycline drug sensitivity by inhibiting HDAC3-AKT-P21-CDK2 signaling pathway, thus demonstrating the potential for application.
Cathepsin V suppresses GATA3 protein expression in luminal A breast cancer
Authors: Sereesongsaeng Naphannop , McDowell Sara H. , Burrows James F. , Scott Christopher J. , Burden Roberta E. 
Published: December 2020

Abstract
Background
Lysosomal cysteine protease cathepsin V has previously been shown to exhibit elevated expression in breast cancer tissue and be associated with distant metastasis. Research has also identified that cathepsin V expression is elevated in tumour tissues from numerous other malignancies, but despite this, there has been limited examination of the function of this protease in cancer. Here we investigate the role of cathepsin V in breast cancer in order to delineate the molecular mechanisms by which this protease contributes to tumourigenesis.

Methods
Lentiviral transductions were used to generate shRNA cell line models, with cell line validation undertaken using RQ-PCR and Western blotting. Phenotypic changes of tumour cell biology were examined using clonogenic and invasion assays. The relationship between GATA3 expression and cathepsin V was primarily analysed using Western blotting. Site-directed mutagenesis was used to generate catalytic mutant and shRNA-resistant constructs to confirm the role of cathepsin V in regulating GATA3 expression.

Results
We have identified that elevated cathepsin V expression is associated with reduced survival in ER-positive breast cancers. Cathepsin V regulates the expression of GATA3 in ER-positive breast cancers, through promoting its degradation via the proteasome. We have determined that depletion of cathepsin V results in elevated pAkt-1 and reduced GSK-3β expression, which rescues GATA3 from proteasomal degradation.

Conclusions
In this study, we have identified that cysteine protease cathepsin V can suppress GATA3 expression in ER-positive breast cancers by facilitating its turnover via the proteasome. Therefore, targeting cathepsin V may represent a potential therapeutic strategy in ER-positive breast cancers, by restoring GATA3 protein expression, which is associated with a more favourable clinical outcome.
Effects of football versus aerobic exercise training on muscle architecture in healthy men adults: a study protocol of a two-armed randomized controlled trial
Authors: Alkhateeb Guevar , Donath Lars 
Published: December 2020

Abstract
Background
Sports and exercise training can attenuate age-related declines in physical function. As people age, they suffer a progressive deterioration of overall muscle structure and function, such as muscle diameter, strength, mass, and power. Therefore, supporting older adults—aged 50 years and above—to continue being physically active is a very important factor. Several forms of exercise (strength, agility, endurance, balance, and flexibility) are recommended. In this regard, football has been repeatedly shown to be an integrative approach to promote measures of strength, endurance, and agility. However, there has been no previous randomized controlled trial that comparatively investigates the effects of football training versus traditional aerobic exercise training on muscle architecture and patella tendon properties in healthy community dwellers. The study protocol is designed to examine whether football differentially affects muscle thickness, muscle length, fascicle length, pennation angle, patella tendon length, and thickness compared to a workload matched traditional aerobic exercise training regimen.

Methods
The study sample consists of 60 untrained but healthy men (50–60 years old), who will be randomly assigned (strata: age, activate) to two groups: football group (n = 30) and aerobic group (n = 30). The intervention will take place within 12 consecutive weeks, two times a week for 60 min each session. The football group will perform recreational football training as a large-sided game, whereas the aerobic group undergoes a running exercise. Both groups have the same external workload ranging between moderate and high exercise intensity. The outcome measure will be collected before and after the intervention period.

Discussion
Findings of this study will provide insight into the effects of 24 sessions of both football and aerobic training program on the selected groups of men adults, including detecting their effects on the thigh muscle architecture.

Trial registration
DRKS—German Clinical Trials Register, DRKS00020536. Registered on 30 January 2020.
A randomized, open-label, adaptive, proof-of-concept clinical trial of modulation of host thromboinflammatory response in patients with COVID-19: the DAWn-Antico study
Authors: Vanassche T. , Engelen M. M. , Van Thillo Q. , Wauters J. , Gunst J. , Wouters C. , Vandenbriele C. , Rex S. , Liesenborghs L. , Wilmer A. , Meersseman P. , Van den Berghe G. , Dauwe D. , Verbeke G. , Thomeer M. , Fivez T. , Mesotten D. , Ruttens D. , Heytens L. , Dapper I. , Tuyls S. , De Tavernier B. , Verhamme P. ,   DAWn consortium members, Gyselinck Iwein , Teuwen Laure-Anne , Geldhof Vincent , Landeloos Ewout , Geukens Tatjana , Ceunen Helga , Debaveye Barbara , Devooght Caroline , Ockerman Anna , Servaes Veerle , Belmans Ann 
Published: December 2020

Abstract
Background
The peak of the global COVID-19 pandemic has not yet been reached, and many countries face the prospect of a second wave of infections before effective vaccinations will be available. After an initial phase of viral replication, some patients develop a second illness phase in which the host thrombotic and inflammatory responses seem to drive complications. Severe COVID-19 disease is linked to high mortality, hyperinflammation, and a remarkably high incidence of thrombotic events. We hypothesize a crucial pathophysiological role for the contact pathway of coagulation and the kallikrein-bradykinin pathway. Therefore, drugs that modulate this excessive thromboinflammatory response should be investigated in severe COVID-19.

Methods
In this adaptive, open-label multicenter randomized clinical trial, we compare low molecular weight heparins at 50 IU anti-Xa/kg twice daily—or 75 IU anti-Xa twice daily for intensive care (ICU) patients—in combination with aprotinin to standard thromboprophylaxis in hospitalized COVID-19 patients. In the case of hyperinflammation, the interleukin-1 receptor antagonist anakinra will be added on top of the drugs in the interventional arm. In a pilot phase, the effect of the intervention on thrombotic markers (D-dimer) will be assessed. In the full trial, the primary outcome is defined as the effect of the interventional drugs on clinical status as defined by the WHO ordinal scale for clinical improvement.

Discussion
In this trial, we target the thromboinflammatory response at multiple levels. We intensify the dose of low molecular weight heparins to reduce thrombotic complications. Aprotinin is a potent kallikrein pathway inhibitor that reduces fibrinolysis, activation of the contact pathway of coagulation, and local inflammatory response. Additionally, aprotinin has shown in vitro inhibitory effects on SARS-CoV-2 cellular entry. Because the excessive thromboinflammatory response is one of the most adverse prognostic factors in COVID-19, we will add anakinra, a recombinant interleukin-1 receptor antagonist, to the regimen in case of severely increased inflammatory parameters. This way, we hope to modulate the systemic response to SARS-CoV-2 and avoid disease progressions with a potentially fatal outcome.

Trial registration
The EU Clinical Trials Register 2020-001739-28. Registered on April 10, 2020.
Clinical trial protocol to evaluate the efficacy of cefixime in the treatment of early syphilis
Authors: Mehta Shivani N. , Stafylis Chrysovalantis , Tellalian David M. , Burian Pamela L. , Okada Cliff M. , Millner Carl E. , Mejia Christopher M. , Klausner Jeffrey D. 
Published: December 2020

AbstractBackgroundSyphilis rates have been increasing both in the USA and internationally with incidence higher among men-who-have-sex-with-men and people living with human immunodeficiency virus (HIV) infection. Currently, benzathine penicillin is the recommended treatment for syphilis in all patients. Global shortages and cost increases in benzathine penicillin call for alternative treatment options. This study evaluates the efficacy of oral cefixime for the treatment of early syphilis.MethodsWe are conducting a randomized, multisite, open-label, non-comparative clinical trial in Los Angeles and Oakland, CA. Eligible participants are ≥ 18 years old, with primary, secondary, or early latent syphilis (rapid plasma reagin [RPR] titer ≥ 1:8). Patients with HIV infection must have a viral load≤ 200 copies/mL and CD4+ T cell count ≥ 350 cells/μL during the past 6 months. Participants are randomized to receive either 2.4 M IU benzathine penicillin G intramuscularly once or cefixime 400 mg orally twice a day for 10 days. Participants return at 3, 6, and 12 months post-treatment for follow-up RPR serological testing. The primary outcome is the proportion of participants who achieve ≥ 4-fold RPR titer decrease at 3 or 6 months post-treatment.DiscussionClinical trials evaluating the efficacy of alternative antibiotics to penicillin are urgently needed.Trial registrationClinicaltrials.govNCT03660488. Registered on 4 September 2018.