bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dose reduction and discontinuation of standard-dose regorafenib associated with adverse drug events in cancer patients: a systematic review and meta-analysis
Authors: Rizzo Alessandro , Nannini Margherita , Novelli Marco , Dalia Ricci Angela , Scioscio Valerio Di , Pantaleo Maria Abbondanza 
Published: July 2020

Background: Regorafenib (REG) is an oral multikinase inhibitor used in colorectal cancer, gastrointestinal stromal tumour and hepatocellular carcinoma. Several adverse events (AEs) are commonly reported during REG administration, and strategies for managing AEs in everyday clinical practice include supportive care, dose modifications and, when necessary, treatment withdrawal. We performed a systematic review and meta-analysis to assess the schedule treatment modifications of REG associated with AEs across randomized controlled clinical trials (RCTs). Methods: Eligible studies included RCTs assessing standard dose REG versus placebo. Outcomes of interest included: AE-related permanent discontinuation, dose interruptions and dose reductions. Results: We retrieved all the relevant RCTs through PubMed/Med, Cochrane library and EMBASE: 7 eligible studies involving a total of 2099 patients (Regorafenib: 1362; placebo: 737) were included in our analysis. The use of REG was associated with higher incidence and risk of all outcomes of interest when compared with placebo. The incidences of permanent discontinuation, dose interruptions and dose reductions in patients receiving REG were 9.7%, 57.2% and 47%, respectively, versus 3.3%, 16.7% and 7.7% of placebo group; compared with placebo, the summary relative risks (RRs) of permanent discontinuation, dose interruptions and dose reductions in REG arm were 2.80 (95% CI 1.85–4.22), 3.21 (95% CI 2.59–3.99) and 6.02 (95% CI 3.28–11.03), respectively. Conclusions: Treatment with REG at the standard dose of 160 mg is associated with a significant increase in AE-related permanent discontinuation, dose interruptions and dose reductions. Prompt identification and management of AEs seem mandatory to obtain maximal benefit from REG treatment. In the current landscape, dose personalization of REG may have the potential to improve quality of life, minimize treatment discontinuation and maximize patient outcomes.
Deep learning based detection of intracranial aneurysms on digital subtraction angiography: A feasibility study
Authors: Hainc Nicolin , Mannil Manoj , Anagnostakou Vaia , Alkadhi Hatem , Blüthgen Christian , Wacht Lorenz , Bink Andrea , Husain Shakir , Kulcsár Zsolt , Winklhofer Sebastian 
Published: July 2020

Background Digital subtraction angiography is the gold standard for detecting and characterising aneurysms. Here, we assess the feasibility of commercial-grade deep learning software for the detection of intracranial aneurysms on whole-brain anteroposterior and lateral 2D digital subtraction angiography images. Material and methods Seven hundred and six digital subtraction angiography images were included from a cohort of 240 patients (157 female, mean age 59 years, range 20–92; 83 male, mean age 55 years, range 19–83). Three hundred and thirty-five (47%) single frame anteroposterior and lateral images of a digital subtraction angiography series of 187 aneurysms (41 ruptured, 146 unruptured; average size 7±5.3 mm, range 1–5 mm; total 372 depicted aneurysms) and 371 (53%) aneurysm-negative study images were retrospectively analysed regarding the presence of intracranial aneurysms. The 2D data was split into testing and training sets in a ratio of 4:1 with 3D rotational digital subtraction angiography as gold standard. Supervised deep learning was performed using commercial-grade machine learning software (Cognex, ViDi Suite 2.0). Monte Carlo cross validation was performed. Results Intracranial aneurysms were detected with a sensitivity of 79%, a specificity of 79%, a precision of 0.75, a F1 score of 0.77, and a mean area-under-the-curve of 0.76 (range 0.68–0.86) after Monte Carlo cross-validation, run 45 times. Conclusion The commercial-grade deep learning software allows for detection of intracranial aneurysms on whole-brain, 2D anteroposterior and lateral digital subtraction angiography images, with results being comparable to more specifically engineered deep learning techniques.
Most High-Intensity Transient Signals Are Not Associated With Specific Surgical Maneuvers
Authors: Twedt Max H. , Hage Benjamin D. , Hammel James M. , Ibrahimye Ali N. , Shukry Mohanad , Qadeer Ahsan , Eskridge Kent M. , Truemper Edward J. , Bashford Gregory R. 
Published: July 2020

Background: Mortality after congenital heart defect surgery has dropped dramatically in the last few decades. Current research on long-term outcomes has focused on preventing secondary neurological sequelae, for which embolic burden is suspected. In children, little is known of the correlation between specific surgical maneuvers and embolic burden. Transcranial Doppler ultrasound is highly useful for detecting emboli but has not been widely used with infants and children. Methods: Bilateral middle cerebral artery blood flow was continuously monitored from sternal incision to chest closure in 20 infants undergoing congenital heart defect repair or palliative surgery. Embolus counts for specific maneuvers were recorded using widely accepted criteria for identifying emboli via high-intensity transient signals (HITS). Results: An average of only 13% of all HITS detected during an operation were correlated with any of the surgical maneuvers of interest. The highest mean number of HITS associated with a specific maneuver occurred during cross-clamp removal. Cross-clamp placement also had elevated HITS counts that significantly differed from other maneuvers. Conclusions: In this study of infants undergoing cardiac surgery with cardiopulmonary bypass, the great majority of HITS detected are not definitively associated with a specific subset of surgical maneuvers. Among the measured maneuvers, removal of the aortic cross-clamp was associated with the greatest occurrence of HITS. Future recommended research efforts include identifying and confirming other sources for emboli and longitudinal outcome studies to determine if limiting embolic burden affects long-term neurological outcomes.
The Destiny of Postoperative Residual Ventricular Septal Defects After Surgical Repair in Infants and Children
Authors: Bibevski Steve , Ruzmetov Mark , Mendoza Laura , Decker Jonathan , Vandale Breanna , Jayakumar Kaimal A. , Chan Kak Chen , Bove Edward , Scholl Frank G. 
Published: July 2020

Purpose: Residual ventricular septal defects (rVSDs) of small size are commonly seen on transesophageal echocardiography after surgical repair. This study aimed to determine the destiny of rVSD found on intraoperative echocardiogram. Methods: Patients undergoing surgical repair of VSD as the primary procedure with available intraoperative and discharge echocardiograms between 2007 and 2017 were reviewed. Presence of an rVSD on intraoperative echo triggered review of discharge echo and of subsequent follow-up echocardiograms. Results: One hundred four patients were analyzed. The mean age and weight for the entire cohort were 1.4 ± 2.9 years (median, 5.4 months; range, 29 days to 14 years) and 8.8 ± 9.9 kg (median, 5.1 kg; range, 2.7-58 kg), respectively. Sixty (57%) patients had rVSD at discharge, with mean size of residual VSD of 1.38 ± 0.92 mm (mode, 0.6; median, 2.2 mm; range, 0.5-3.9 mm). The mean follow-up time was 3.7 ± 3.1 years (range, 1 month to 9.3 years). Among those with rVSD at discharge, a residual shunt persisted in 73% at one-month follow-up. On follow-up at three years postdischarge, of the 60 patients with early rVSD, 6 had a persistent rVSD (10%) with a mean diameter of 3.0 ± 0.8 mm (range, 2.4-3.9 mm). Conclusions: Residual VSD after surgical repair is detected frequently on postoperative echocardiogram. The presence of rVSD was not associated with any preoperative, intraoperative, or postoperative factors. By three years of follow-up, only six patients continued to demonstrate rVSD with a mean diameter of 3 mm, suggesting that defects 3 mm or greater may be less likely to close spontaneously after three years.
Posterior Minimally Invasive Transpedicular Approach for Giant Calcified Thoracic Disc Herniation
Authors: Shedid Daniel , Wang Zhi , Najjar Ahmad , Yuh Sung-Joo , Boubez Ghassan , Sebaaly Amer 
Published: July 2020

Study Design: Retrospective case series. Objective: Posterior surgery for thoracic disc herniation was associated with increased morbidity and mortality and new minimally invasive approaches have been recommended for soft disc herniation but not for calcified central disc. The objective of this study is to describe a posterolateral microscopic transpedicular approach for central thoracic disc herniation. Methods: This is a single center retrospective review of all the cases of giant thoracic calcified disc herniation as defined by Hott et al. Presence of myelopathy, percentage of canal compromise, T2 hypersignal, ASIA score, and ambulatory status were recorded. This posterolateral technique using a tubular retractor was thoroughly described. Results: Eight patients were operated upon with a mean follow-up of 16 months. Mean canal compromise was 61%. Mean operative time was 228 minutes and mean operative bleeding was 250 mL. There were no cases of dural tear or neurologic degradation. Conclusion: This is the first report of posterior minimally invasive transpedicular approach for giant calcified disc herniation. There were neither cases of neurological deterioration nor increased rate of dural tears. This technique is thus safe and could be recommended for treatment of this rare disease.
Incidence, prevalence, and outcomes of systemic malignancy with bone metastases
Authors: Jiang Wenli , Rixiati Youlutuziayi , Zhao Bingqing , Li Yongcheng , Tang Chuangang , Liu Jun 
Published: July 2020

Purpose: Evidence on the incidence, prevalence, and outcomes of bone metastases among patients with systemic malignancy is limited. This study aimed to evaluate it using the Surveillance, Epidemiology, and End Results (SEER) database. Methods: We collected patients diagnosed with solid malignant tumors deriving outside of the bone, hematologic malignancies, Kaposi sarcoma, lymphoma, and myeloma from the SEER database (from 2010 to 2013). The incidence, prevalence, and outcomes of these systemic malignancies with bone metastases were then analyzed. Results: A total of 67,605 patients with bone metastases at cancer diagnosis were included. The highest rate of bone metastases was observed in patients with small-cell lung cancer at the time of alternative primary site cancer diagnosis. Among 226,816 cases with metastatic disease, cases with breast cancer (65.58%), and prostate cancer (89.60%) had a high incidence proportion (>10%) of identified bone metastases. Patients with additional bone metastases resulting from prostate cancer, breast cancer, and testis cancer presented the best survival time. Conclusions: Incidence and prognosis differ considerably among bone metastases with different primary malignancy sites. These results may encourage appropriate application of bone imaging.
Regulating Australia’s Participation in the Orphanage Industry
Authors: Doore Kathryn E. van 
Published: July 2020

Orphanages harness the goodwill of volunteers, visitors and donors to generate funding. However, in recent years, evidence has emerged that in some cases children are being recruited or trafficked into orphanages in order to generate profit from this goodwill. This is known as the ‘orphanage industry’, and the recruitment of children into orphanages for the purpose of profit and exploitation is ‘orphanage trafficking’. Australia is reported to be the largest funder of residential care for children in South East Asia. In 2017, Australia became the first government in the world to consider orphanage trafficking as a form of modern slavery. This article traces the evolution of the recognition of orphanage trafficking broadly, and then focusses on recommendations made by the Australian government following the release of its 2017 Hidden in Plain Sight Report. This article analyses the emerging policy and legislative reforms that are being undertaken by the Australian government and recommends further development to ensure that funding and finances are appropriately directed to divest from orphanages and instead support burgeoning care reform in the South Asian region. Finally, the article responds to critiques of the Australian government’s standpoint on orphanage trafficking as it relates to the over-reliance on institutional care and provides clarification on why a criminal justice response to orphanage trafficking is appropriate.
A Prospective, Randomized Investigation of Syndesmosis Injury Fixation
Authors: Giza Eric , Oliver Todd , Barousse Patrick S. , Allen Tyler , Shelton Trevor , Sarcon Aida K. , Sathy Ashoke , Faerber Wade , Lin Johnny L. , Stannard James P. , Crist Brett , Rocca Gregory J. Della , Ronan James , Kreulen Christopher D. 
Published: July 2020

Category: Ankle; Trauma Introduction/Purpose: Syndesmotic disruption occurs in 10 to 13% of all ankle fractures. It is present in 15 cases per 100,000 of the general population. There has been debate on the best treatment for syndesmotic injuries. The typical surgical treatments include fixation with either screws or suture button devices. The purpose of this study is to compare clinical outcomes of syndesmotic injuries treated surgically with either screws or suture button devices. It was hypothesized that suture button fixation would provide equal clinical results with less need for hardware removal. Methods: This was a multi-center, randomized, prospective clinical trial comparing two surgical interventions for treatment of acute syndesmotic injury. Subjects were placed into either screw fixation or the Suture-button device group. Subjects with clinical signs or radiographic evidence of syndesmotic injury were asked to participate in this study. Inclusion criteria was ages 18 to 65 years old with confirmed syndesmotic instability. The primary outcomes of the study were VAS scores (activity, pain, satisfaction) and FFI scores (pain, disability, activity) which were collected at preoperative state, 6 weeks, and 12 months postoperatively. Results: Sixty-five subjects were enrolled in this study. Thirty-two subjects received Suture-button fixation (49%) and 33 received screw fixation (51%). VAS scores and FFI scores for subjects treated with the Suture-button device or screw fixation comparing preoperative, six-week, and 12-month scores all showed clinical improvement. There was no significant difference between the two treatment groups (p >0.05).Nine subjects (27%) in the syndesmotic screw fixation group experienced adverse events, and only one subject (3%) in the suture-button group had adverse event. Conclusion: The short-term clinical outcomes suggest that both syndesmotic screws and suture-button devices are effective treatment options to address acute syndesmotic injuries. In the short-term (12-months), suture-button fixation resulted in significantly less adverse events compared to syndesmotic screw fixation group.
Meta-analysis for milk fat and protein percentage using imputed sequence variant genotypes in 94,321 cattle from eight cattle breeds
Authors: van den Berg Irene , Xiang Ruidong , Jenko Janez , Pausch Hubert , Boussaha Mekki , Schrooten Chris , Tribout Thierry , Gjuvsland Arne B. , Boichard Didier , Nordbø Øyvind , Sanchez Marie-Pierre , Goddard Mike E. 
Published: July 2020

AbstractBackgroundSequence-based genome-wide association studies (GWAS) provide high statistical power to identify candidate causal mutations when a large number of individuals with both sequence variant genotypes and phenotypes is available. A meta-analysis combines summary statistics from multiple GWAS and increases the power to detect trait-associated variants without requiring access to data at the individual level of the GWAS mapping cohorts. Because linkage disequilibrium between adjacent markers is conserved only over short distances across breeds, a multi-breed meta-analysis can improve mapping precision.ResultsTo maximise the power to identify quantitative trait loci (QTL), we combined the results of nine within-population GWAS that used imputed sequence variant genotypes of 94,321 cattle from eight breeds, to perform a large-scale meta-analysis for fat and protein percentage in cattle. The meta-analysis detected (p ≤ 10−8) 138 QTL for fat percentage and 176 QTL for protein percentage. This was more than the number of QTL detected in all within-population GWAS together (124 QTL for fat percentage and 104 QTL for protein percentage). Among all the lead variants, 100 QTL for fat percentage and 114 QTL for protein percentage had the same direction of effect in all within-population GWAS. This indicates either persistence of the linkage phase between the causal variant and the lead variant across breeds or that some of the lead variants might indeed be causal or tightly linked with causal variants. The percentage of intergenic variants was substantially lower for significant variants than for non-significant variants, and significant variants had mostly moderate to high minor allele frequencies. Significant variants were also clustered in genes that are known to be relevant for fat and protein percentages in milk.ConclusionsOur study identified a large number of QTL associated with fat and protein percentage in dairy cattle. We demonstrated that large-scale multi-breed meta-analysis reveals more QTL at the nucleotide resolution than within-population GWAS. Significant variants were more often located in genic regions than non-significant variants and a large part of them was located in potentially regulatory regions.
Identification of tRFs and phasiRNAs in tomato (Solanum lycopersicum) and their responses to exogenous abscisic acid
Authors: Luan Wei , Dai Ya , Li Xin-Yu , Wang Yan , Tao Xiang , Li Cai-Xia , Mao Ping , Ma Xin-Rong 
Published: July 2020

Abstract
Background
The non-coding small RNA tRFs (tRNA-derived fragments) and phasiRNAs (plant-specific) exert important roles in plant growth, development and stress resistances. However, whether the tRFs and phasiRNAs respond to the plant important stress hormone abscisic acid (ABA) remain enigma.

Results
Here, the RNA-sequencing was implemented to decipher the landscape of tRFs and phasiRNAs in tomato (Solanum lycopersicum) leaves and their responses when foliar spraying exogenous ABA after 24 h. In total, 733 tRFs and 137 phasiRNAs were detected. The tRFs were mainly derived from the tRNAAla transporting alanine, which tended to be cleaved at the 5’terminal guanine site and D loop uracil site to produce tRFAla with length of 20 nt. Most of phasiRNAs originated from NBS-LRR resistance genes. Expression analysis revealed that 156 tRFs and 68 phasiRNAs expressed differentially, respectively. Generally, exogenous ABA mainly inhibited the expression of tRFs and phasiRNAs. Furthermore, integrating analysis of target gene prediction and transcriptome data presented that ABA significantly downregulated the abundance of phsaiRNAs associated with biological and abiotic resistances. Correspondingly, their target genes such as AP2/ERF, WRKY and NBS-LRR, STK and RLK, were mainly up-regulated.

Conclusions
Combined with the previous analysis of ABA-response miRNAs, it was speculated that ABA can improve the plant resistances to various stresses by regulating the expression and interaction of small RNAs (such as miRNAs, tRFs, phasiRNAs) and their target genes. This study enriches the plant tRFs and phasiRNAs, providing a vital basis for further investigating ABA response-tRFs and phasiRNAs and their functions in biotic and abiotic stresses.
Prehospital administration of blood products: experiences from a Finnish physician-staffed helicopter emergency medical service
Authors: Vuorinen Pauli , Kiili Joonas-Eemeli , Setälä Piritta , Kämäräinen Antti , Hoppu Sanna 
Published: July 2020

Abstract
Background
Massive infusions of crystalloids into bleeding hypotensive patients can worsen the outcome. Military experience suggests avoiding crystalloids using early damage control resuscitation with blood components in out of hospital setting. Civilian emergency medical services have since followed this idea. We describe our red blood cell protocol in helicopter emergency medical services (HEMS) and initial experience with prehospital blood products from the first 3 years after implementation.

Methods
We performed an observational study of patients attended by the HEMS unit between 2015 and 2018 to whom packed red blood cells, freeze-dried plasma, or both were transfused. The Student’s two-sided T-test was used to compare vitals in prehospital phase with those at the hospital’s emergency department. A p-value < 0.05 was considered significant.

Results
Altogether, 62 patients received prehospital transfusions. Of those, 48 (77%) were trauma patients and most (n = 39, 81%) suffered blunt trauma. The transfusion began at a median of 33 (IQR 21–47) minutes before hospital arrival. Median systolic blood pressure showed an increase from 90 mmHg (IQR 75–111 mmHg) to 107 mmHg (IQR 80–124 mmHg; P < 0.026) during the prehospital phase. Four units of red blood cells were handled incorrectly when unused red blood cells were returned and required disposal during a three-year period. There were no reported adverse effects from prehospital transfusions.

Conclusion
We treated two patients per month with prehospital blood products. A prehospital physician-staffed HEMS unit carrying blood products is a feasible and safe method to start transfusion roughly 30 min before arrival to the hospital.

Trial registration
The study was retrospectively registered by the Tampere University Hospital’s Medical Director (R19603) 5.11.2019.
Comparison of clinical features and outcomes between patients with early and delayed lupus nephritis
Authors: Ahn Sung Soo , Yoo Juyoung , Jung Seung Min , Song Jason Jungsik , Park Yong-Beom , Lee Sang-Won 
Published: July 2020

Abstract
Background
Lupus nephritis is associated with increased risk of end-stage renal disease (ESRD) and all-cause mortality. We evaluated the clinical features and outcomes of patients with early and delayed lupus nephritis.

Methods
The medical records of 171 patients who met the 1997 revised classification criteria for systemic lupus erythematosus (SLE) with pathologic confirmation of lupus nephritis were reviewed. Early lupus nephritis was defined when lupus nephritis was histopathologically confirmed as the first clinical manifestation of SLE, whereas delayed lupus nephritis was defined as lupus nephritis that was identified after the diagnosis of SLE. Clinical and laboratory data, as well as kidney histopathology and medication usage were investigated. Kaplan-Meier and Cox-proportional hazard analysis was performed to compare the outcomes of early and delayed lupus nephritis and evaluate factors associated with ESRD and all-cause mortality.

Results
Patients with early lupus nephritis had higher disease activity (median non-renal SLE disease activity index-2000, 6.0 vs. 4.0; p < 0.001) and more frequent skin rash, oral ulcer and serositis; however, the proportion of patients with higher renal chronicity index was greater in the delayed lupus nephritis group (p = 0.007). Nevertheless, no difference was found regarding ESRD and all-cause mortality between the groups. In Cox-proportional hazard analysis, C-reactive protein level, creatinine level and chronicity index were factors associated with ESRD, while age and haemoglobin level were associated with all-cause mortality.

Conclusions
In conclusion, clinical outcomes of early and delayed lupus nephritis are not significantly different. Rigorous adherence to current treatment recommendations is essential for the treatment of lupus nephritis.