bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parental information about the option to apply for pregnancy termination after the detection of a congenital abnormality and factors influencing parental decision-making: a cohort study
Authors: Hjort-Pedersen Karina , Olesen Annette Wind , Garne Ester , Toerring Pernille Mathiesen , Wu Chunsen , Sperling Lene 
Published: December 2022

AbstractBackgroundThe detection of an abnormality during prenatal screening implies that the parents are informed about possible treatment and management of the pregnancy, birth, and postnatal course. This information should enable the parents to make decisions regarding the pregnancy, especially in cases where termination of pregnancy may be an option. The objectives of this study were to investigate how often doctors informed parents about pregnancy termination when the fetus had an anomaly and which demographic factors were related to parental decision-making.MethodsThis was a retrospective cohort study with prospectively collected data of fetuses diagnosed with an abnormality during prenatal screening between 2014 and 2016 in Denmark. We categorized the abnormalities into five long-term prognosis groups and analyzed their association with the doctor provided information about termination. We tested the association between demographic variables and parental decisions using univariate and multivariate statistical analyses.ResultsThree hundred and twenty fetuses were diagnosed with an abnormality. In 67% of these cases, the parents were informed about termination. All parents whose fetus had a lethal prognosis were informed about termination. By comparison, the parents of 98% of fetuses with genetic disorders, 96% of fetuses with poor prognosis, 69% of fetuses with uncertain prognosis, and 12% of fetuses with good prognosis were informed about termination. Of these parents, 92% chose to terminate. A lethal long-term prognosis was the only factor related to parental decision to terminate a pregnancy.ConclusionsDoctors mainly informed parents about the option of pregnancy termination for conditions with a poor or lethal long-term prognosis or for genetic disorders. Only conditions with a lethal prognosis were significantly related to the parental decision to terminate the pregnancy.
Effect of EGFR amplification on the prognosis of EGFR-mutated advanced non–small-cell lung cancer patients: a prospective observational study
Authors: Peng Duanyang , Liang Pingan , Zhong Congying , Xu Peng , He Yanqing , Luo Yuxi , Wang Xia , Liu Anwen , Zeng Zhimin 
Published: December 2022

Abstract
Background
Epidermal growth factor receptor (EGFR) amplification refers to the copy number increase of EGFR gene, and is often identified as a “bypass” way of Epidermal growth factor receptor Tyrosine kinase inhibitors (EGFR-TKI) resistance. We aimed to explore the effect of EGFR amplification on EGFR mutation treatment-naive advanced non-squamous non-small cell lung cancer (NSCLC) patients.

Methods
We conducted a prospective observational study in single center, enrolling advanced non-squamous NSCLC patients receiving Tyrosine kinase inhibitors (TKIs) between March 3, 2019, and February 1, 2022. Next-generation sequencing (NGS) was used to detect genetic alterations in tumor tissue samples. Progression-free survival (PFS) curves were performed using the Kaplan-Meier method. Univariate and multivariate analyses were used to evaluate factors affecting the efficacy of TKIs.

Results
A total of 117 treatment-naive advanced NSCLC patients were identified in this study. EGFR amplification was found in 22 of 117 (18.8%) patients with EGFR mutations. Of 22 patients with EGFR amplification, 10 patients harbored EGFR 19 del, 11 patients with 21-L858R. The median follow-up time was 22.47 months. The median PFS of the patients with or without EGFR amplification was 8.25 months and 10.67 months, respectively (log-rank test, P = 0.63). In multivariate analysis, EGFR amplification was not an independent prognosis factor for the patients receiving first-line TKIs [HR = 1.38, 95%CI (0.73–2.58), P = 0.321]. Subgroup analysis revealed that EGFR amplification is a risk factor for progression in the brain metastasis population. [HR = 2.28, 95%CI (1.01, 5.14), P = 0.047].

Conclusion
EGFR amplification is not an independent prognosis factor for PFS in advanced non-squamous NSCLC patients receiving first-line TKIs. However, it is an independent risk factor for PFS in the brain metastasis population.
Feasibility of edoxaban for asymptomatic cancer-associated thrombosis in Japanese patients with gastrointestinal cancer: ExCAVE study
Authors: Nakamura Michio , Ishiguro Atsushi , Dazai Masayoshi , Kawamoto Yasuyuki , Yuki Satoshi , Sogabe Susumu , Hosokawa Ayumu , Sawada Kentaro , Muto Osamu , Izawa Naoki , Nakashima Koji , Horie Yoshiki , Yagisawa Masataka , Kajiura Shinya , Ando Takayuki , Mitsuhashi Yosuke , Sunakawa Yu , Kikuchi Yasuka , Komatsu Yoshito 
Published: December 2022

Abstract
Background
Although initial therapy with a parenteral anticoagulant is required before edoxaban, this strategy is frequently avoided in actual clinical practice because of its complexity. This study assessed the feasibility of edoxaban without initial heparin usage for asymptomatic cancer-associated thrombosis (CAT) in Japanese patients with gastrointestinal cancer (GIC) at high risk of bleeding.

Methods
In this multicenter prospective feasibility study conducted at 10 Japanese institutions, patients with active GIC who developed accidental asymptomatic CAT during chemotherapy were recruited. Edoxaban was orally administered once daily without initial parenteral anticoagulant therapy within 3 days after detecting asymptomatic CAT. The primary outcome was the incidence of major bleeding (MB) or clinically relevant non-major bleeding (CRNMB) during the first 3 months of edoxaban administration.

Results
Of the 54 patients enrolled from October 2017 to September 2020, one was excluded because of a misdiagnosis of CAT. In the remaining 53 patients, the primary outcome occurred in six patients (11.3%). MB occurred in four patients (7.5%), including gastrointestinal bleeding in three patients and intracranial hemorrhage in one patient. CRNMB occurred in two patients (3.8%), including bleeding from the stoma site and genital bleeding in one patient each. There were no deaths attributable to bleeding, and all patients who experienced MB or CRNMB recovered.

Conclusions
The risk of bleeding after edoxaban without heparin pretreatment was acceptable, demonstrating new treatment options for asymptomatic CAT in patients with GIC.
A phase II study of daily encorafenib in combination with biweekly cetuximab in patients with BRAF V600E mutated metastatic colorectal cancer: the NEW BEACON study
Authors: Eriksen Martina , Pfeiffer Per , Rohrberg Kristoffer Staal , Yde Christina Westmose , Petersen Lone Nørgård , Poulsen Laurids Østergaard , Qvortrup Camilla 
Published: December 2022

Abstract
Background
Patients with BRAF V600E mutated metastatic colorectal cancer (mCRC) have a poor prognosis. The introduction of BRAF targeted therapy with encorafenib and weekly administered cetuximab have shown improved survival with a median progression free survival (PFS) of 4.3 months. However, a regimen with cetuximab given every second week may have comparable efficacy and is more convenient for patients. While BRAF targeted therapy is a new standard therapy in pre-treated patients with BRAF V600E mutated mCRC, resistance invariably occurs and is an emerging challenge. The aim of this study is to investigate the efficacy and tolerability of cetuximab given every second week in combination with daily encorafenib and to explore the correlation between markers of resistance and outcome.

Methods
The study is an open label, single arm, phase II study, investigating the efficacy and tolerability of cetuximab given every second week in combination with encorafenib in patients with BRAF V600E mutated mCRC. Furthermore, we will be investigating mechanisms of response and resistance against BRAF targeted therapy though comprehensive genomic profiling on tumor tissue and blood for circulating tumor DNA analysis. A total of 53 patients (19 + 34 in two steps) will be included according to Simon’s optimal two stage design. The primary end point of the study is 2 months PFS rate.

Discussion
By combining BRAF inhibitor with cetuximab given every second week we can halve the number of visits in the hospital compared to the currently approved regimen with weekly cetuximab. This seems particularly relevant in a group of patients with a median overall survival of 9.3 months. Resistance after initial response to targeted therapy can be either adaptive (e.g., epigenetic, or transcriptomic alterations) or acquired (selective genetic alterations - e.g., activating de novo mutations) resistance. It is of great importance to untangle these complex mechanisms of resistance in patients with BRAF V600E mutated mCRC to improve treatment strategies in the future potentially even further.

Trial registration
EU Clinical Trial Register, Eudract no. 2020-003283-10. Registered on 11 November 2020.
Clinical and economic burden of physician-diagnosed influenza in adults during the 2017/2018 epidemic season in Spain
Authors: Gil-de-Miguel Ángel , Martinón-Torres Federico , Díez-Domingo Javier , de Lejarazu Leonardo Raúl Ortiz , Pumarola Tomàs , Carmo Mafalda , Drago Georgina , López-Belmonte Juan Luis , Bricout Hélène , de Courville Caroline , Margüello Esther Redondo 
Published: December 2022

Abstract
Background
Influenza is an acutely debilitating respiratory infection, contributing significantly to outpatient visits and hospitalizations. Spain lacks comprehensive and updated data on the burden of influenza, particularly in the outpatient setting. Our study aimed to fill this gap by estimating the clinical and economic burden of physician-diagnosed influenza cases in adults from four Spanish regions, stratified by age groups and presence of comorbidities.

Methods
A retrospective cost-of-illness study was conducted using data from an electronic medical records database from the National Healthcare Service (NHS) of four Spanish regions for individuals aged ≥ 18 years diagnosed for influenza during the 2017/2018 epidemic season. Health resource utilization and related cost data were collected, including primary care visits, referrals to other specialists, visits to the emergency department, hospitalizations, and prescribed medicines.

Results
The study reported a total of 28,381 patients aged ≥ 18 years diagnosed with influenza, corresponding to 1,804 cases per 100,000 population. Most patients were aged < 65 years: 60.5% (n = 17,166) aged 18–49 and 26.3% (n = 7,451) 50–64 years. A total of 39.2% (n = 11,132) of patients presented a comorbidity. Cardiovascular diseases were the most common comorbidity reported along with influenza. The mean healthcare cost per case was estimated at €235.1 in population aged 18–49 years, increasing by 1.7 and 4.9 times in those aged 50–64 (€402.0) and ≥ 65 (€1,149.0), respectively. The mean healthcare cost per case was 3.2 times higher in patients with comorbidities. The total healthcare cost of medically attended influenza cases was mainly driven by primary care (45.1%) and hospitalization (42.0%). Patients aged 18–64 years old accounted for 61.9% of the costs of medically attended influenza. Irrespective of age, patients with comorbidities accounted for 67.1% of costs.

Conclusions
Season 2017/2018 was associated with a considerable burden of influenza in Spain, which increased with age and presence of comorbidities. Individuals with comorbidities accounted for most of the costs of influenza. Results suggest that population aged 18–64 years old is generating the highest share of costs to the NHS when all healthcare costs are considered. Preventive strategies targeting subjects with comorbidities, regardless of age, should be warranted.
Perceived controllability of a SARS-CoV-2 infection: an investigation of intersectional differences
Authors: Neugebauer Till , Wahidie Diana , Erdsiek Fabian , Yilmaz-Aslan Yüce , Brzoska Patrick 
Published: December 2022

AbstractBackgroundThe perceived ability to influence an infection with SARS-CoV-2 has an impact on compliance with protective measures. Factors influencing perceived controllability are not yet fully known. The aim of this study was to identify intersectional differences in perceived controllability. Insights into these intersectional differences could help to develop user-centered strategies to improve the acceptance of protective measures.MethodsData from the seventh wave of the German Ageing Survey (DEAS) was used to investigate differences in the population regarding the perceived controllability. The role of socio-demographic and socio-economic predictors was investigated using multivariable linear regression modeling. Intersectional differences were examined using interaction terms.ResultsInformation on 4,823 respondents aged 46 to 100 years were available, of which 50.9% were female. Migration status (yes vs. no: β = -0.27; 95%-CI = -0.48,-0.06), education level (high vs. low: β = 0.31; 95%-CI: 0.08, 0.55) and employment status (retired vs. employed: β = 0.33; 95%-CI: 0.19, 0.48) were found to be significantly influencing perceived controllability. Interaction effects were found with respect to sex and migration status, with migrant women rating their perceived controllability lower than non-migrant women (β = -0.51; 95%-CI = -0.80, -0.21), while no differences were evident between migrant and non-migrant men (β = -0.02; 95%-CI = -0.32, 0.28). Further intersectional differences were not observed.ConclusionsThe results show that intersectional differences in perceived controllability occur especially between migrant and non-migrant women. Possible causes may lie in language barriers, which in connection with lower health literacy may affect perceived controllability. Dedicated efforts to improve controllability among older adults, those with lower educational attainment and migrant women are warranted.
Alveolus analysis: a web browser-based tool to analyze lung intravital microscopy
Authors: Politowicz Alexander L. , Burks Andrew T. , Dong Yushen , Htwe Yu Maw , Dudek Steven M. , Elisabeta Marai G. , Belvitch Patrick 
Published: December 2022

Abstract
Background
Acute lung injury and the acute respiratory distress syndrome are characterized by pulmonary inflammation, reduced endothelial barrier integrity and filling of the alveolar space with protein rich edema fluid and infiltrating leukocytes. Animal models are critical to uncovering the pathologic mechanisms of this devastating syndrome. Intravital imaging of the intact lung via two-photon intravital microscopy has proven a valuable method to investigate lung injury in small rodent models through characterization of inflammatory cells and vascular changes in real time. However, respiratory motion complicates the analysis of these time series images and requires selective data extraction to stabilize the image. Consequently, analysis of individual alveoli may not provide a complete picture of the integrated mechanical, vascular and inflammatory processes occurring simultaneously in the intact lung. To address these challenges, we developed a web browser-based visualization application named Alveolus Analysis to process, analyze and graphically display intravital lung microscopy data.

Results
The designed tool takes raw temporal image data as input, performs image preprocessing and feature extraction offline, and visualizes the extracted information in a web browser-based interface. The interface allows users to explore multiple experiments in three panels corresponding to different levels of detail: summary statistics of alveolar/neutrophil behavior, characterization of alveolar dynamics including lung edema and inflammatory cells at specific time points, and cross-experiment analysis. We performed a case study on the utility of the visualization with two members or our research team and they found the tool useful because of its ability to preprocess data consistently and visualize information in a digestible and informative format.

Conclusions
Application of our software tool, Alveolus Analysis, to intravital lung microscopy data has the potential to enhance the information gained from these experiments and provide new insights into the pathologic mechanisms of inflammatory lung injury.
Predictors and tactics for revision surgery in lateral lumbar interbody fusion
Authors: Wang Weijian , Li Jiaqi , Xu Yafei , Luo Yun , Ding Wenyuan , Zhang Wei 
Published: December 2022

Abstract
Background
The purpose of this study is to analyze the factors affecting the revision of lateral lumbar interbody fusion (LLIF), and to summarize the complications and decision-making strategies for revision surgery after LLIF.

Methods
We retrospectively reviewed 21 cases suffered from a revision surgery after LLIF in our department from May 2017 to June 2020, with a mean follow-up of 14 months (12-25months). We collected X-ray plain films, CT (computed tomography), MRI (magnetic resonance imaging) and medical records of all patients undergoing LLIF surgery, then analyzed the reasons for revision and summarized the revision strategies in different situations. We analysed correlations between revision surgery and several factors, including age, body mass index (BMI), sex, bone quality, mode of internal fixation, spinal stenosis, postperative foraminal stenosis, disc height. Then we brought the different indicators into logistic regression to find out the risk factors of revision after LLIF. All these patients were evaluated by Quality-of-life outcomes. Univariate statistical analysis was performed using T-tests, Mann-Whitney U tests and Chi square tests.

Results
Of the 209 cases of LLIF, 21 patients underwent postoperative revision. All revision surgeries were successfully completed. The reasons for revision included vascular injury, unsatistactory implant placement, internal spinal instrumentation failure, cage migration, indirect decompression failure and infection. Indirect decompression failure was the most common indications for revision. Clinical status was apparently improved in ODI scores and VAS scores. Revision surgery did not impact long-term effect and satisfaction. Postoperative foraminal stenosis is a positive predictor for a revision surgical procedure.

Conclusion
Patients with postoperative foraminal stenosis are at higher risk of undergoing revision surgery after lateral lumbar interbody fusion. The correct choice of revision surgery can achieve satisfactory clinical results.
Combined arthroscopic release with corticosteroid hydrodilatation versus corticosteroid hydrodilatation only in treating freezing-phase primary frozen shoulder: a randomized clinical trial
Authors: Dai Zhu , Liu Quanhui , Liu Bo , Long Ke , Liao Ying , Wu Biao , Huang Wen , Liu Chao 
Published: December 2022

Abstract
Background
There has been no ideal treatment for freezing-phase frozen shoulder to rapidly relieve pain and improve joint mobility. No any other team directly compared the effectiveness of combination of arthroscopic release and corticosteroid hydrodilatation with corticosteroid hydrodilatation only in treatment of freezing-phase frozen shoulder.

Methods
Seventy-two patients with freezing-phase frozen shoulder were randomly assigned to combined arthroscopic release with corticosteroid hydrodilatation (group A) or corticosteroid hydrodilatation only (group B). Clinical states were examined at baseline and periodically (Weeks 1, 4, 12, 24 and 1 year) after intervention by passive ROM; visual analog scale (VAS); UCLA and Disabilities of the Arm, Shoulder, and Hand (DASH) score.

Results
The passive ROM, VAS, UCLA and DASH scores always improved along the time points (all p < 0.01). The passive abduction (pAB), passive forward flexion (pFL), passive external rotation (pER), passive internal rotation (pIR) were better in group A than in group B at Week 1, 4, 12, 24 (all p < 0.01). At 1 year post-operation, the pFL and pIR were better in group A than in group B (all p < 0.01). VAS scores of group A were similar with those of group B (all p > 0.01), the differences between group A and group B were all lower than minimal clinically important difference (MCID). At Week 12, the UCLA sores and DASH scores were 26.8 ± 3.8, 14.2 ± 2.0 in group A versus 22.3 ± 3.4, 22.5 ± 3.1 in group B (all p < 0.01). At Week 24 post-operation, there were 32.7 ± 2.0, 9.8 ± 1.5 in group A versus 26.3 ± 3.6, 17.5 ± 3.5 in group B (all p < 0.01). At 1 year post-operation, there were 34.5 ± 0.8, 1.7 ± 1.5 in group A versus 32.1 ± 2.3, 8.8 ± 2.8 in group B (all p < 0.01), the differences of UCLA scores between group A and group B at Week 24 was higher than the MCID. There were no complications such as infection, nerve or vascular injury.

Conclusions
Combined arthroscopic release with corticosteroid hydrodilatation would yield better results in passive ROM and function than corticosteroid hydrodilatation only.

Trial registration
ChiCTR1900024235, July 2, 2019 (Retrospectively registered).
Familial hypocalciuric hypercalcaemia type 1 caused by a novel heterozygous missense variant in the CaSR gene, p(His41Arg): two case reports
Authors: Courtney Aoife , Hill Arnold , Smith Diarmuid , Agha Amar 
Published: December 2022

Abstract
Background
Familial hypocalciuric hypercalcaemia (FHH) is a rare, inherited disorder of extracellular calcium sensing. It is clinically characterised by mild to moderate parathyroid hormone dependent hypercalcaemia, an autosomal dominant pattern of inheritance, and a normal to reduced urinary calcium excretion in spite of high serum calcium.

Case presentation
We report two cases of FHH in a family caused by a novel pathogenic missense variant in the CaSR gene, p. His41Arg. Case 1, describes a 17 year old female with no significant past medical history, admitted with acute appendicitis requiring laparoscopic appendectomy and reporting a six month history of polydipsia. Routine investigations were significant for hypercalcaemia, corrected calcium 3.19 mmol/L (2.21-2.52mmol/L), elevated parathyroid hormone of 84pg/ml (15-65pg/ml) and a low 24-hour urine calcium of 0.75mmol/24 (2.50-7.50mmol/24). She was initially managed with intravenous fluids and Zolendronic acid with temporary normalisation of calcium though ultimately required commencement of Cinacalcet 30 mg daily for persistent symptomatic hypercalcaemia. Genetic analysis was subsequently positive for the above variant. Case 2, a 50-year-old female, was referred to the endocrine outpatient clinic for the management of type 2 diabetes and reported a longstanding history of asymptomatic hypercalcaemia which had not been investigated previously. Investigation revealed hypercalcaemia; corrected calcium of 2.6 mmol/L (reference range: 2.21–2.52 mmol/L); PTH of 53.7ng/L (reference range: 15–65 ng/L) and an elevated 24-hour urine calcium of 10 mmol/24 (2.50–7.50 mmol/24hr) with positive genetic analysis and is managed conservatively. Despite sharing this novel mutation, these cases have different phenotypes and their natural history is yet to be determined. Two further relatives are currently undergoing investigation for hypercalcaemia and the family have been referred for genetic counselling.

Conclusion
Accurate diagnosis of FHH and differentiation from classic primary hyperparathyroidism can be challenging, however it is essential to avoid unnecessary investigations and parathyroid surgery. Genetic analysis may be helpful in establishing a diagnosis of FHH in light of the biochemical heterogeneity in this population and overlap with other causes of hypercalcaemia.