bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reference range of fetal thorax using two-dimensional and three-dimensional ultrasound VOCAL technique and application in fetal thoracic malformations
Authors: Lian Xihua , Xu Zhenhong , Zheng Liping , Zhu Zhixing , Ejiwale Tofunmi , Kumar Ayush , Cai Peiya , He Shaozheng , Liu Shunlan , Zhang Ying , Lyu Guorong 
Published: February 2021

Abstract
Background
To establish the normal reference range of fetal thorax by two-dimensional (2D) and three-dimensional (3D) ultrasound VOCAL technique and evaluate the application in diagnosing fetal thoracic malformations.

Methods
A prospective cross-sectional study was undertaken involving 1077 women who have a normal singleton pregnancy at 13–40 weeks gestational age (GA). 2D ultrasound and 3D ultrasound VOCAL technique were utilized to assess fetal thoracic transverse diameter, thoracic anteroposterior diameter, thoracic circumference, thoracic area, lung volume, thoracic volume and lung-to-thoracic volume ratio. The nomograms of 2D and 3D fetal thoracic measurements were created to GA. 50 cases were randomly selected to calculate intra- and inter-observer reliability and agreement. In addition, the case groups including congenital skeletal dysplasia (SD) (15), congenital diaphragmatic hernia (CDH) (30), pulmonary sequestration (PS) (25) and congenital cystic adenomatoid malformation (CCAM) (36) were assessed by the nomograms and followed up subsequently.

Results
Both 2D and 3D fetal thoracic parameters increased with GA using a quadratic regression equation. The intra- and inter-observer reliability and agreement of each thoracic parameter were excellent. 2D fetal thoracic parameters could initially evaluate the fetal thoracic development and diagnose the skeletal thoracic deformity, and lung volume, thoracic volume and lung-to-thorax volume ratio were practical to diagnose and differentiate CDH, PS and CCAM.

Conclusion
We have established the normal fetal thoracic reference range at 13–40 weeks, which has a high value in diagnosing congenital thoracic malformations.
Assessment of acute kidney injury risk using a machine-learning guided generalized structural equation model: a cohort study
Authors: Wong Wen En Joseph , Chan Siew Pang , Yong Juin Keith , Tham Yen Yu Sherlyn , Lim Jie Rui Gerald , Sim Ming Ann , Soh Chai Rick , Ti Lian Kah , Chew Tsong Huey Sophia 
Published: February 2021

AbstractBackgroundAcute kidney injury is common in the surgical intensive care unit (ICU). It is associated with poor patient outcomes and high healthcare resource usage. This study’s primary objective is to help identify which ICU patients are at high risk for acute kidney injury. Its secondary objective is to examine the effect of acute kidney injury on a patient’s prognosis during and after the ICU admission.MethodsA retrospective cohort of patients admitted to a Singaporean surgical ICU between 2015 to 2017 was collated. Patients undergoing chronic dialysis were excluded. The outcomes were occurrence of ICU acute kidney injury, hospital mortality and one-year mortality. Predictors were identified using decision tree algorithms. Confirmatory analysis was performed using a generalized structural equation model.ResultsA total of 201/940 (21.4%) patients suffered acute kidney injury in the ICU. Low ICU haemoglobin levels, low ICU bicarbonate levels, ICU sepsis, low pre-ICU estimated glomerular filtration rate (eGFR) and congestive heart failure was associated with the occurrence of ICU acute kidney injury. Acute kidney injury, together with old age (> 70 years), and low pre-ICU eGFR, was associated with hospital mortality, and one-year mortality. ICU haemoglobin level was discretized into 3 risk categories for acute kidney injury: high risk (haemoglobin ≤9.7 g/dL), moderate risk (haemoglobin between 9.8–12 g/dL), and low risk (haemoglobin > 12 g/dL).ConclusionThe occurrence of acute kidney injury is common in the surgical ICU. It is associated with a higher risk for hospital and one-year mortality. These results, in particular the identified haemoglobin thresholds, are relevant for stratifying a patient’s acute kidney injury risk.
Intravenous methadone causes acute toxic and delayed inflammatory encephalopathy with persistent neurocognitive impairments
Authors: Repple Jonathan , Haessner Svea , Johnen Andreas , Landmeyer Nils C. , Schulte-Mecklenbeck Andreas , Pawlitzki Marc , Wiendl Heinz , Meyer zu Hörste Gerd 
Published: February 2021

Abstract
Background
The mu-opioid agonist methadone is administered orally and used in opioid detoxification and in the treatment of moderate-to-severe pain. Acute oral methadone–use and –abuse have been associated with inflammatory and toxic central nervous system (CNS) damage in some cases and cognitive deficits can develop in long-term methadone users. In contrast, reports of intravenous methadone adverse effects are rare.

Case presentation
Here, we report a patient who developed acute bilateral hearing loss, ataxia and paraparesis subsequently to intravenous methadone-abuse. While the patient gradually recovered from these deficits, widespread magnetic resonance imaging changes progressed and delayed-onset encephalopathy with signs of cortical dysfunction persisted. This was associated with changes in the composition of monocyte and natural killer cell subsets in the cerebrospinal fluid.

Conclusion
This case suggests a potential bi-phasic primary toxic and secondary inflammatory CNS damage induced by intravenous methadone.
Tumor co-expression of progranulin and sortilin as a prognostic biomarker in breast cancer
Authors: Berger Karoline , Rhost Sara , Rafnsdóttir Svanheiður , Hughes Éamon , Magnusson Ylva , Ekholm Maria , Stål Olle , Rydén Lisa , Landberg Göran 
Published: February 2021

Abstract
Background
The growth factor progranulin has been implicated in numerous biological processes such as wound healing, inflammation and progressive tumorigenesis. Both progranulin and its receptor sortilin are known to be highly expressed in subgroups of breast cancer and have been associated with various clinical properties including tamoxifen resistance. Recent data further suggest that progranulin, via its receptor sortilin, drives breast cancer stem cell propagation in vitro and increases metastasis formation in an in vivo breast cancer xenograft model. In this retrospective biomarker analysis, we aimed to determine whether tumor co-expression of progranulin and sortilin has prognostic and treatment predictive values for breast cancer patients.

Methods
We explored how co-expression of progranulin and sortilin was associated with established clinical markers by analyzing a tissue microarray including 560 randomized premenopausal breast cancer patients receiving either 2 years of tamoxifen treatment or no adjuvant treatment, with a median follow-up time of 28 years. Breast cancer-specific survival was analyzed using Kaplan-Meier and Cox Proportional Hazards regression models to assess the prognostic and predictive value of progranulin and sortilin in relation to known clinical markers.

Results
Co-expression of progranulin and sortilin was observed in 20% of the breast cancer samples. In untreated patients, prognostic considerations could be detailed separately from treatment prediction and the high progranulin and sortilin expressing subgroup was significantly associated with breast cancer-specific death in multivariable analyses (HR=2.188, CI: 1.317–3.637, p=0.003) along with tumor size, high tumor grade and lymph node positivity. When comparing the untreated patients with tamoxifen treated patients in the ERα positive subgroup, co-expression of progranulin and sortilin was not linked to tamoxifen resistance.

Conclusion
Data suggest that co-expression of progranulin and its receptor sortilin is a novel prognostic biomarker combination identifying a highly malignant subgroup of breast cancer. Importantly, this subpopulation could potentially be targeted with anti-sortilin based therapies.
Bowel necrosis in patient with severe case of COVID-19: a case report
Authors: Soeselo Daniel Ardian , Hambali Wirawan , Theresia Sandy 
Published: February 2021

Abstract
Background
In patients who are critically ill with COVID-19, multiple extrapulmonary manifestations of the disease have been observed, including gastrointestinal manifestations.

Case presentation
We present a case of a 65 year old man with severe COVID-19 pneumonia that developed hypercoagulation and peritonitis. Emergent laparotomy was performed and we found bowel necrosis in two sites.

Conclusions
Although rare, the presentation of COVID-19 with bowel necrosis requires emergency treatments, and it has high mortality rate.
Management of high-energy tibial shaft fractures using the hexapod circular external fixator
Authors: Liu Yanshi , Liu Jialin , Yushan Maimaiaili , Liu Zhenhui , Zhang Tao , Ma He , Ma Chuang , Yusufu Aihemaitijiang 
Published: February 2021

Abstract
Background
The hexapod external fixator (HEF) is increasingly used for high-energy tibial shaft fracture care as more general orthopedic surgeons are gaining expertise of this versatile device. The purpose of this study was to evaluate the clinical effectiveness of the HEF for definitive management in patients with high-energy tibial shaft fractures.

Methods
The study was conducted on 34 patients with tibial shaft fractures who were admitted or referred to our institution and consented to HEF treatment from Jan 2016 to June 2019, including 27 males and 7 females with a mean age of 39 years (range 18 to 65 years). Patients' clinical and radiological data, and the final clinical outcomes at a minimum of 12 months follow-up were collected and retrospectively analyzed. All complications were documented according to Paley’s classification. The clinical outcomes were evaluated using the Association for the Study and Application of the Method of Ilizarov criteria (ASAMI) at the last clinical visit.

Results
All patients remained in the HEF for a mean of 26 weeks (range 15 to 52 weeks) and acquired complete bone union. The satisfactory alignment was achieved in all patients, and all the patients were able to perform daily activities with no difficulty at the last clinical visit. Complications included pin tract infection (44%), delayed union (6%), nonunion (3%), and joint stiffness (3%). The ASAMI bony result was excellent in 31 patients and good in 3. The ASAMI functional result was excellent in 27 patients, good in 6, and fair in 1.

Conclusions
Definitive management using the hexapod external fixator is an alternative and effective method for high-energy tibial shaft fractures, including technical advantages of early trauma-control, the versatility of achieving excellent alignment, and the continuity of device until bone union.
FESEM evaluation of smear layer removal from conservatively shaped canals: laser activated irrigation (PIPS and SWEEPS) compared to sonic and passive ultrasonic activation—an ex vivo study
Authors: Mancini Manuele , Cerroni Loredana , Palopoli Pietro , Olivi Giovanni , Olivi Matteo , Buoni Cristiano , Cianconi Luigi 
Published: February 2021

AbstractBackgroundIrrigation of the pulp space is a mandatory step to get rid of all its organic and inorganic content. Activation of the irrigants play a key role in the era of minimally invasive endodontics. The aim of this study was to assess the effectiveness of different irrigants activation methods in removing the smear layer at 1, 3, 5 and 8 mm from the apex from conservatively shaped canals.MethodsEighty-five human mandibular premolars were selected. Specimens were shaped to TruShape 25/.06 and divided into 5 groups (1 control and 4 test groups) according to the final activation technique (EndoActivator, EA), Ultrasonic (EndoUltra, PUI) and Laser (PIPS and SWEEPS). EDTA (Ethylenediaminetetraacetic acid) followed by NaOCl (Sodium Hypochlorite) and again EDTA were activated for each test group. Specimens were then split longitudinally and observed by Field Emission Scanning Electron Microscopy (FESEM). Blinded evaluation of the presence of smear layer was performed at 1000X magnification, according to a 5-score index system. Comparison between groups were analysed statistically using the Kruskal–Wallis non-parametric analysis of variance. Bonferroni multiple comparison tests were used.ResultsAt 1 mm only PIPS and SWEEPS performed better than the control group. At 3, 5 and 8 mm from the apex, every activation technique showed statistically significant reduction of smear layer when compared to the control group. PIPS and SWEEPS obtained better cleanliness result compared to EA, while only PIPS was superior to PUI in terms of cleanliness.ConclusionsPIPS and SWEEPS showed the best results in conservative canal preparations. Nowadays, contemporary rotary instruments allow fast and minimally invasive shaping of the endodontic space. In this scenario irrigants’ activation may be regarded as a mandatory step to a favourable clinical outcome.
Man or machine? Impact of tutor-guided versus simulator-guided short-time bronchoscopy training on students learning outcomes
Authors: Schertel Anke , Geiser Thomas , Hautz Wolf E. 
Published: February 2021

Abstract
Background
Simulation based medical education is efficient for the acquisition of flexible bronchoscopy navigational skills and the knowledge of the tracheobronchial anatomy. However, bronchoscopy simulator training is not routinely integrated into pneumologic fellowship programs or undergraduate medical education for time and/or cost reasons. Our study compares the effect of self-guided bronchoscopy simulator training versus tutor guided training on the acquisition of navigational skills and knowledge of the bronchial anatomy.

Methods
Third-year undergraduate medical students were randomized to either a tutor- or simulator guided bronchoscopy simulator training focusing on the acquisition of navigational skills and the knowledge of the tracheobronchial anatomy. Every student performed a baseline bronchoscopy followed by a structured bronchoscopy simulator training and finally an assessment bronchoscopy at the end of the training program. Groups were compared by means of a repeated measurement ANOVA and effect sizes calculated as Cohens’ d.

Results
Fifty-four eligible students participated in the study. Knowledge of the tracheobronchial anatomy significantly increased from pre- to post training (all p < 0.001; all d > 2), navigational skills significantly decreased (all p < 0.005; all d < 1). There were no significant differences between groups. Instruction by the simulator as well as by the tutor was rated as helpful by the students. Twenty-two (84.6%) of the participants of the simulator guided group would have appreciated an additional instruction by a tutor.

Conclusion
Short-time simulator guided bronchoscopy training improves knowledge of the tracheobronchial anatomy in novice bronchoscopists as much as tutor guided training, but navigational skills seem to worsen in both groups. Further studies assessing transfer to clinical practice are needed to find the optimal teaching method for basic flexible bronchoscopy.
A clinical trials corpus annotated with UMLS entities to enhance the access to evidence-based medicine
Authors: Campillos-Llanos Leonardo , Valverde-Mateos Ana , Capllonch-Carrión Adrián , Moreno-Sandoval Antonio 
Published: February 2021

AbstractBackgroundThe large volume of medical literature makes it difficult for healthcare professionals to keep abreast of the latest studies that support Evidence-Based Medicine. Natural language processing enhances the access to relevant information, and gold standard corpora are required to improve systems. To contribute with a new dataset for this domain, we collected the Clinical Trials for Evidence-Based Medicine in Spanish (CT-EBM-SP) corpus.MethodsWe annotated 1200 texts about clinical trials with entities from the Unified Medical Language System semantic groups: anatomy (ANAT), pharmacological and chemical substances (CHEM), pathologies (DISO), and lab tests, diagnostic or therapeutic procedures (PROC). We doubly annotated 10% of the corpus and measured inter-annotator agreement (IAA) using F-measure. As use case, we run medical entity recognition experiments with neural network models.ResultsThis resource contains 500 abstracts of journal articles about clinical trials and 700 announcements of trial protocols (292 173 tokens). We annotated 46 699 entities (13.98% are nested entities). Regarding IAA agreement, we obtained an average F-measure of 85.65% (±4.79, strict match) and 93.94% (±3.31, relaxed match). In the use case experiments, we achieved recognition results ranging from 80.28% (±00.99) to 86.74% (±00.19) of average F-measure.ConclusionsOur results show that this resource is adequate for experiments with state-of-the-art approaches to biomedical named entity recognition. It is freely distributed at:http://www.lllf.uam.es/ESP/nlpmedterm_en.html. The methods are generalizable to other languages with similar available sources.
Mycosis fungoides and Sézary syndrome: a population-wide study on prevalence and health care use in Finland in 1998–2016
Authors: Keto Jaana , Hahtola Sonja , Linna Miika , Väkevä Liisa 
Published: February 2021

Abstract
Background
Information about health care use and costs of cutaneous T-cell lymphoma (CTCL) patients is limited, particularly in a European setting.

Methods
In this population-wide study we set out to investigate prevalence, and trends in health care use in two CTCL subtypes, mycosis fungoides (MF) and Sézary syndrome (SS) over a time period of 19 years in 1998–2016 by using a nation-wide patient register containing data on all diagnosed MF and SS cases in Finland.

Results
The prevalence of diagnosed MF and SS rose from 2.04 to 5.38/100000, and from 0.16 to 0.36/100000 for MF and SS respectively during 1998–2016. We found a substantial decrease in inpatient treatment of MF/SS in the past two decades with a mean of 2 inpatient days/patient/year due to MF/SS in 2016, while the mean numbers of MF/SS related outpatient visits remained stable at 8 visits/year/patient. Most MF/SS-related outpatient visits occurred in the medical specialty of dermatology. In a ten-year follow-up after MF/SS diagnosis, the main causes for outpatient visits and inpatient stays were MF/SS itself, other cancers, and other skin conditions. Also cardiovascular disease and infections contributed to the number of inpatient days. Mean total hospital costs decreased from 11,600 eur/patient/year to 3600 eur/patient/year by year 4 of the follow-up, and remained at that level for the remainder of the 10-year follow-up. MF/SS accounted for approximately half of the hospital costs of these patients throughout the follow-up.

Conclusions
The nearly 3-fold increase in prevalence of diagnosed MF/SS during 1998–2016 puts pressure on the health care system, as this is a high-cost patient group with a heavy burden of comorbidities. The challenge can be in part answered by shifting the treatment of MF/SS to a more outpatient-based practice, and by adapting new pharmacotherapy, as has been done in Finland.
Systemic administration of β-glucan induces immune training in microglia
Authors: Heng Yang , Zhang Xiaoming , Borggrewe Malte , van Weering Hilmar R. J. , Brummer Maaike L. , Nijboer Tjalling W. , Joosten Leo A. B. , Netea Mihai G. , Boddeke Erik W. G. M. , Laman Jon D. , Eggen Bart J. L. 
Published: February 2021

Abstract
Background
An innate immune memory response can manifest in two ways: immune training and immune tolerance, which refers to an enhanced or suppressed immune response to a second challenge, respectively. Exposing monocytes to moderate-to-high amounts of bacterial lipopolysaccharide (LPS) induces immune tolerance, whereas fungal β-glucan (BG) induces immune training. In microglia, it has been shown that different LPS inocula in vivo can induce either immune training or tolerance. Few studies focused on impact of BG on microglia and were only performed in vitro. The aim of the current study was to determine whether BG activates and induces immune memory in microglia upon peripheral administration in vivo.

Methods
Two experimental designs were used. In the acute design, mice received an intraperitoneal (i.p.) injection with PBS, 1 mg/kg LPS or 20 mg/kg BG and were terminated after 3 h, 1 or 2 days. In the preconditioning design, animals were first challenged i.p. with PBS, 1 mg/kg LPS or 20 mg/kg BG. After 2, 7 or 14 days, mice received a second injection with PBS or 1 mg/kg LPS and were sacrificed 3 h later. Microglia were isolated by fluorescence-activated cell sorting, and cytokine gene expression levels were determined. In addition, a self-developed program was used to analyze microglia morphological changes. Cytokine concentrations in serum were determined by a cytokine array.

Results
Microglia exhibited a classical inflammatory response to LPS, showing significant upregulation of Tnf, Il6, Il1β, Ccl2, Ccl3 and Csf1 expression, three h after injection, and obvious morphological changes 1 and 2 days after injection. With an interval of 2 days between two challenges, both BG and LPS induced immune training in microglia. The training effect of LPS changed into immune tolerance after a 7-day interval between 2 LPS challenges. Preconditioning with BG and LPS resulted in increased morphological changes in microglia in response to a systemic LPS challenge compared to naïve microglia.

Conclusions
Our results demonstrate that preconditioning with BG and LPS both induced immune training of microglia at two days after the first challenge. However, with an interval of 7 days between the first and second challenge, LPS-preconditioning resulted in immune tolerance in microglia.
Leadership and capacity building in chiropractic research: report from the first CARL cohort
Authors: Hartvigsen Jan , Kawchuk Greg , Breen Alexander , De Carvalho Diana , Eklund Andreas , Fernandez Matthew , Funabashi Martha , Holmes Michelle M. , Johansson Melker S. , de Luca Katie , Moore Craig , Pagé Isabelle , Pohlman Katherine A. , Swain Michael S. , Wong Arnold Y. L. , Adams Jon 
Published: February 2021

AbstractThe Chiropractic Academy for Research Leadership (CARL) was formed in 2016 in response to a need for a global network of early career researchers and leaders in the chiropractic profession. Thirteen fellows were accepted competitively and have since worked together at residentials and virtually on many research and leadership projects. In 2020, the CARL program ended for this first cohort, and it is now timely to take stock and reflect on the achievements and benefits of the program. In this paper we present the structure of CARL, the scientific and leadership outputs as well as the personal value of CARL for the participating fellows. As a result of the success of the first CARL cohort, organizations from Europe, North America, and Australia have supported a second cohort of 14 CARL fellows, who were competitively accepted into the program in early 2020.