bluuebunny/crossref_metadata_2025_split huggingface dataset:
Severity of radiation pneumonitis, from clinical, dosimetric and biological features: a pilot study
Authors: Aso Samantha , Navarro-Martin Arturo , Castillo Richard , Padrones Susana , Castillo Edward , Montes Ana , Martínez José Ignacio , Cubero Noelia , López Rosa , Rodríguez Laura , Palmero Ramon , Manresa Federico , Guerrero Thomas , Molina María 
Published: October 2020

Abstract
Background and objective
Radiation pneumonitis (RP) could be a lethal complication of lung cancer treatment. No reliable predictors of RP severity have been recognized. This prospective pilot study was performed to identify early predictors of high grade lung toxicity and to evaluate clinical, biological or dosimetric features associated with different grades of toxicity.

Method
Sixteen patients with non-small cell lung cancer with indication of concurrent chemoradiotherapy using 60 Gy/2 Gy/fraction starting at cycle one of platinum based chemotherapy were included. Bronchoalveolar lavage (BAL), pulmonary function testing (PFT), and 18F-2-fluoro-2-deoxy-D-glucose positron-emission tomography was performed before radiotherapy (RT), after three weeks of treatment, and two months post-RT. For analysis, patients were grouped by grade (low [G1-G2] vs. high [G3-G5]). The two groups were compared to identify predictors of RP. Protein expression BAL and lung tissue metabolism was evaluated in two patients (RP-G1 vs. RP-G3). Categorical variables such as comorbidities, stages and locations were summarized as percentages. Radiation doses, pulmonary function values and time to RP were summarized by medians with ranges or as means with standard deviation. Longitudinal analysis PFT was performed by a T-test.

Results
All 16 patients developed RP, as follows: G1 (5 pts; 31.3%); G2 (5 pts; 31.3%); G3 (5 pts; 31.3%); and G5 (1 pts; 6.1%). Patients with high grade RP presented significant decrease (p = 0.02) in diffusing lung capacity for carbon monoxide (DLCO) after three weeks of RT. No correlation between dosimetric values and RP grades was observed. BAL analysis of the selected patients showed that CXCL-1, CD154, IL-1ra, IL-23, MIF, PAI-1 and IFN-γ were overexpressed in the lungs of the RP-G3 patient, even before treatment. The pre-RT SUVmax value in the RP-G3 patient was non-significantly higher than in the patient with RP-G1.

Conclusions
RT induces some degree of RP. Our data suggest that decrease in DLCO% is the most sensitive parameter for the early detection of RP. Moreover, we detect biological differences between the two grades of pneumonitis, highlighting the potential value of some cytokines as a prognostic marker for developing high grade lung toxicity. Further multicenter studies with larger sample size are essential to validate these findings.
Heart transplantation of patients with ventricular assist devices: impact of normothermic ex-vivo preservation using organ care system compared with cold storage
Authors: Kaliyev Rymbay , Lesbekov Timur , Bekbossynov Serik , Nurmykhametova Zhuldyz , Bekbossynova Makhabbat , Novikova Svetlana , Medressova Assel , Smagulov Nurlan , Faizov Linar , Samalavicius Robertas , Pya Yuriy 
Published: October 2020

Abstract
Background
Organ Care System (OCS) minimizes the cold ischemic time and allows for optimization of logistics and meticulous recipient preparation. Impact of normothermic ex-vivo preservation using OCS compared with cold storage (CS) for prolonged heart preservation especially beneficial for high-risk recipients bridged to transplantation with Mechanical Circulatory Support (MCS).

Methods
Between 2012 and 2018, we performed a retrospective single-center review of prospectively collected data. All patients who underwent heart transplantation with MCS using the OCS Heart (n = 25) versus standard cold storage (n = 10) were included in this study.

Results
During this period, 353 patients were implanted with left ventricular assisted device (LVAD) and 35 (10%) were bridged to heart transplantation. There was no significant difference in donor and recipient characteristics and risk factors. The Index for Mortality Prediction after Cardiac Transplantation (IMPACT) score was a trend towards higher estimated risk of death at 1y in the OCS group (14.2 vs. 10.8% p = 0.083). Mean total ischemic time during preservation was statistically significantly longer in CS vs OCS group (210 (23) Vs 74.6 (13) min p = 0.001). Median ex vivo normothermic heart perfusion time in OCS was 348.4(132; 955) min. There was significant difference in total out of body time between OCS group 423(67) Vs CS group 210(23) min p = 0.002). All patients were alive on the 30th days post implant in CS groups and 96% in OCS group (p = 0.5).

Conclusion
Normothermic ex-vivo preservation of the allograft during transportation with the organ care system might be beneficial for long-time out of body organ preservation in comparison of cold storage especially for recipients on mechanical circulatory support.
The effect of the glucosylceramide synthase inhibitor lucerastat on cardiac repolarization: results from a thorough QT study in healthy subjects
Authors: Mueller Markus S. , Sidharta Patricia N. , Voors-Pette Christine , Darpo Borje , Xue Hongqi , Dingemanse Jasper 
Published: October 2020

Abstract
Background
Fabry disease is a rare inherited glycosphingolipid storage disorder caused by deleterious mutations in the GLA gene coding for the lysosomal enzyme α-galactosidase A. The glucosylceramide synthase inhibitor lucerastat is an iminosugar with potential to provide oral substrate reduction therapy in Fabry disease, regardless of the patient´s underlying mutation. Since lucerastat exhibits systemic exposure and many patients with Fabry disease suffer from rhythm and conduction abnormalities its effects on cardiac repolarization were evaluated in a thorough QT study.

Methods
In Part A of this randomized, double-blind, placebo-controlled phase 1 study, single oral doses of 2000 and 4000 mg lucerastat were investigated to determine the supratherapeutic dose for Part B. The latter was a four-way crossover study to demonstrate that lucerastat at single oral therapeutic and supratherapeutic doses had no effect on the QTc interval > 10 ms using concentration-QTc modeling as primary analysis. The primary ECG endpoint was placebo-corrected change-from-baseline (ΔΔ) in Fridericia-corrected QTc (ΔΔQTcF). Open-label moxifloxacin served as positive control.

Results
The effect of lucerastat on ΔΔQTcF was predicted as 0.39 ms (90% confidence interval [CI] − 0.13 to 0.90) and 1.69 ms (90% CI 0.33–3.05) at lucerastat peak plasma concentration after dosing with 1000 mg (5.2 µg/mL) and 4000 mg (24.3 µg/mL), respectively. A QTcF effect > 10 ms was excluded up to lucerastat plasma concentrations of approximately 34.0 µg/mL. Lucerastat did not exert an effect on other ECG parameters. Across doses, absorption of lucerastat was rapid, its elimination half-life ranged from 8.0 to 10.0 h, and the pharmacokinetics (PK) of lucerastat were dose-proportional. Moxifloxacin PK were in line with published data and assay sensitivity was demonstrated by the moxifloxacin QTc response. Lucerastat was safe and well tolerated.

Conclusions
Lucerastat up to a dose of 4000 mg has no clinically relevant liability to prolong the QT interval or any clinically relevant effect on other ECG parameters. This will be an important factor in the overall benefit-risk assessment of lucerastat in the potential treatment of Fabry disease.

Trial registration The study was registered with the ClinicalTrials.gov identifier NCT03832452 (February 6th, 2019, https://clinicaltrials.gov/ct2/show/NCT03832452) and the EudraCT number 2018-004546-42 (December 17th, 2018).
Design, development and deployment of a web-based interoperable registry for inherited retinal dystrophies in Portugal: the IRD-PT
Authors: Marques João Pedro , Carvalho Ana Luísa , Henriques José , Murta Joaquim Neto , Saraiva Jorge , Silva Rufino 
Published: October 2020

Abstract
Background
The development of multicenter patient registries promotes the generation of scientific knowledge by using real-world data. A country-wide, web-based registry for inherited retinal dystrophies (IRDs) empowers patients and community organizations, while supporting formal partnerships research. We aim to describe the design, development and deployment of a country-wide, with investigators and stakeholders in the global aim to develop high-value, high-utility web-based, user-friendly and interoperable registry for IRDs—the IRD-PT.

Results
The IRD-PT is a clinical/genetic research registry included in the retina.pt platform (https://www.retina.com.pt), which was developed by the Portuguese Retina Study Group. The retina.pt platform collects data on individuals diagnosed with retinal diseases, from several sites across Portugal, with over 1800 participants and over 30,000 consultations to date. The IRD-PT module interacts with the retina.pt core system which provides a range of basic functions for patient data management, while the IRD-PT module allows data capture for the specific purpose of IRDs. All IRDs are coded accordingly to the International Statistical Classification of Diseases and Related Health Problems (ICD) 9, ICD 10, ICD 11, and Orphanet Rare Disease Ontology (ORPHA codes) to make the IRD-PT interoperable with other IRD registries across the world. Furthermore, the genes are coded according to the Ontology of Genes and Genomes and Online Mendelian Inheritance in Man, whereas signs and symptoms are coded according to the Human Phenotype Ontology. The IRD-PT module pre-launched at Centro Hospitalar e Universitário de Coimbra, the largest reference center for IRDs in Portugal. As of April 1st 2020, finalized data from 537 participants were available for this preliminary analysis.

Conclusions
In the specific field of rare diseases, the use of registries increases research accessibility for individuals, while providing clinicians/investigators with a coherent data ecosystem necessary to boost research. Appropriate design and implementation of patient registries enables rapid decision making and ongoing data mining, ultimately leading to improved patient outcomes. We have described here the principles behind the design, development and deployment of a web-based, user-friendly and interoperable software tool aimed to generate important knowledge and collecting high-quality data on the epidemiology, genomic landscape and natural history of IRDs in Portugal.
Ovarian metastasis from nongynecologic primary sites: a retrospective analysis of 177 cases and 13-year experience
Authors: Zhang Jing-Jing , Cao Dong-Yan , Yang Jia-Xin , Shen Keng 
Published: October 2020

Abstract
Background
Metastasis to the ovary from nongynecologic organs accounts for 9% of all ovarian malignancies. Although the most common nongynecologic primary site of ovarian metastasis is the gastrointestinal tract, metastasis from other sites to the ovary is not uncommon. Differential diagnosis of primary and metastatic ovarian tumors is important; otherwise, appropriate treatment cannot be determined. Furthermore, an optimal treatment strategy for ovarian metastasis from nongynecologic primary sites still needs to be explored.

Methods
One hundred seventy-seven patients with ovarian metastasis from nongynecologic primary sites admitted to Peking Union Medical College Hospital between May 2005 and May 2018 were retrospectively evaluated.

Results
The mean age was 48 years (range, 18–83). Approximately 60% of patients were premenopausal women. The two most common nongynecologic primary sites of ovarian metastasis were the colorectum (68 cases) and stomach (61 cases). In addition to the most common symptoms of abdominal distension (39.0%), abdominal pain (37.9%), and ascites (27.7%), 18.1% of patients presented with abnormal uterine bleeding. Half of the patients who tested serum CA-125 preoperatively had elevated CA-125 levels within the range of 35 U/ml to 200 U/ml. More than 70% of synchronous ovarian metastases were preoperatively misdiagnosed as primary ovarian cancer. Of all included cases, 56.5% achieved optimal cytoreductive surgery (the diameter of the largest residual lesion < 2 cm). The overall 5-year survival rate and median survival time were 10% and 20 months, respectively. The primary site, optimal cytoreductive surgery, tumor differentiation, and postoperative adjuvant treatment were identified as prognostic indicators.

Conclusions
The colorectum and stomach are the most common nongynecologic primary sites of ovarian metastasis. Synchronous ovarian metastasis is easily misdiagnosed as primary ovarian cancer. Optimal cytoreductive surgery and postoperative adjuvant treatment can be performed to confer survival benefit in selected patients.
Differential kynurenine pathway metabolism in highly metastatic aggressive breast cancer subtypes: beyond IDO1-induced immunosuppression
Authors: Heng Benjamin , Bilgin Ayse A. , Lovejoy David B. , Tan Vanessa X. , Milioli Heloisa H. , Gluch Laurence , Bustamante Sonia , Sabaretnam Tharani , Moscato Pablo , Lim Chai K. , Guillemin Gilles J. 
Published: October 2020

Abstract
Background
Immunotherapy has recently been proposed as a promising treatment to stop breast cancer (BrCa) progression and metastasis. However, there has been limited success in the treatment of BrCa with immune checkpoint inhibitors. This implies that BrCa tumors have other mechanisms to escape immune surveillance. While the kynurenine pathway (KP) is known to be a key player mediating tumor immune evasion and while there are several studies on the roles of the KP in cancer, little is known about KP involvement in BrCa.

Methods
To understand how KP is regulated in BrCa, we examined the KP profile in BrCa cell lines and clinical samples (n = 1997) that represent major subtypes of BrCa (luminal, HER2-enriched, and triple-negative (TN)). We carried out qPCR, western blot/immunohistochemistry, and ultra-high pressure liquid chromatography on these samples to quantify the KP enzyme gene, protein, and activity, respectively.

Results
We revealed that the KP is highly dysregulated in the HER2-enriched and TN BrCa subtype. Gene, protein expression, and KP metabolomic profiling have shown that the downstream KP enzymes KMO and KYNU are highly upregulated in the HER2-enriched and TN BrCa subtypes, leading to increased production of the potent immunosuppressive metabolites anthranilic acid (AA) and 3-hydroxylanthranilic acid (3HAA).

Conclusions
Our findings suggest that KMO and KYNU inhibitors may represent new promising therapeutic targets for BrCa. We also showed that KP metabolite profiling can be used as an accurate biomarker for BrCa subtyping, as we successfully discriminated TN BrCa from other BrCa subtypes.
The effects of exercise training on hypothalamic-pituitary-adrenal axis reactivity and autonomic response to acute stress—a randomized controlled study
Authors: Arvidson Elin , Dahlman Anna Sjörs , Börjesson Mats , Gullstrand Lennart , Jonsdottir Ingibjörg H. 
Published: October 2020

Abstract
Background
Exercise training is suggested to have a stress-buffering effect on physiological reactions to acute stress. The so-called cross-stressor adaptation hypothesis is one of many theories behind the plausible effects, proposing that the attenuated physiological reaction seen in trained individuals in response to acute exercise is also seen when the individual is exposed to acute psychosocial stress. However, few randomized controlled trials (RCT) are available in this field. Therefore, the aim of the present trial was to study the effects of a 6-month aerobic exercise intervention on the physiological response to acute laboratory stress.

Methods
A two-armed RCT including untrained but healthy individuals aged 20–50 years was conducted. Assessments included a peak oxygen uptake test and a psychosocial stress test (the Trier Social Stress Test). A total of 88 participants went through both baseline and follow-up measures (48 in the intervention group and 40 in the control group) with a similar proportion of women and men (20 women and 28 men in the intervention group and 18 women and 22 men in the control group). Outcome measures were adrenocorticotrophic hormone, cortisol, systolic and diastolic blood pressure, and heart rate responses to acute psychosocial stress.

Results
Oxygen uptake and time-to-exhaustion increased significantly following the intervention, while a decrease was seen in the control group. The analyses showed attenuated responses to acute psychosocial stress for all variables in both groups at follow-up, with no differences between the groups. No correlation was seen between amount of exercise training and reactivity to the stress test. Despite the increased oxygen uptake in the intervention group, no differences were seen between the groups for any of the outcome variables at follow-up.

Conclusions
In this study, the cross-stressor adaptation hypothesis could not be confirmed. Both groups showed decreased reactions indicating a habituation to the stress test.

Trial registration
ClinicalTrials.gov NCT02051127. Registered on 31 January 2014—retrospectively registered.
Assessment of the susceptibility status of Aedes aegypti (Diptera: Culicidae) populations to pyriproxyfen and malathion in a nation-wide monitoring of insecticide resistance performed in Brazil from 2017 to 2018
Authors: Campos Kauara Brito , Martins Ademir Jesus , Rodovalho Cynara de Melo , Bellinato Diogo Fernandes , Dias Luciana dos Santos , Macoris Maria de Lourdes da Graça , Andrighetti Maria Teresa Macoris , Lima José Bento Pereira , Obara Marcos Takashi 
Published: October 2020

Abstract
Background
Chemical mosquito control using malathion has been applied in Brazil since 1985. To obtain chemical control effectiveness, vector susceptibility insecticide monitoring is required. This study aimed to describe bioassay standardizations and determine the susceptibility profile of Ae. aegypti populations to malathion and pyriproxyfen, used on a national scale in Brazil between 2017 and 2018, and discuss the observed impacts in arbovirus control.

Methods
The diagnostic-doses (DD) of pyriproxyfen and malathion were determined as the double of adult emergence inhibition (EI) and lethal doses for 99% of the Rockefeller reference strain, respectively. To monitor natural populations, sampling was performed in 132 Brazilian cities, using egg traps. Colonies were raised in the laboratory for one or two generations (F1 or F2) and submitted to susceptibility tests, where larvae were exposed to the pyriproxyfen DD (0.03 µg/l) and adults, to the malathion DD determined in the present study (20 µg), in addition to the one established by the World Health Organization (WHO) DD (50 µg) in a bottle assay. Dose-response (DR) bioassays with pyriproxyfen were performed on populations that did not achieve 98% EI in the DD assays.

Results
Susceptibility alterations to pyriproxyfen were recorded in six (4.5%) Ae. aegypti populations from the states of Bahia and Ceará, with Resistance Ratios (RR95) ranging from 1.51 to 3.58. Concerning malathion, 73 (55.3%) populations distributed throughout the country were resistant when exposed to the local DD 20 µg/bottle. On the other hand, no population was resistant, and only 10 (7.6%) populations in eight states were considered as exhibiting decreased susceptibility (mortality ratios between 90 and 98%) when exposed to the WHO DD (50 µg/bottle).

Conclusions
The feasibility of conducting an insecticide resistance monitoring action on a nation-wide scale was confirmed herein, employing standardized and strongly coordinated sampling methods and laboratory bioassays. Brazilian Ae. aegypti populations exhibiting decreased susceptibility to pyriproxyfen were identified. The local DD for malathion was more sensitive than the WHO DD for early decreased susceptibility detection.
Culex pipiens and Culex restuans egg rafts harbor diverse bacterial communities compared to their midgut tissues
Authors: Juma Elijah O. , Kim Chang-Hyun , Dunlap Christopher , Allan Brian F. , Stone Chris M. 
Published: October 2020

Abstract
Background
The bacterial communities associated with mosquito eggs are an essential component of the mosquito microbiota, yet there are few studies characterizing and comparing the microbiota of mosquito eggs to other host tissues.

Methods
We sampled gravid female Culex pipiens L. and Culex restuans Theobald from the field, allowed them to oviposit in the laboratory, and characterized the bacterial communities associated with their egg rafts and midguts for comparison through MiSeq sequencing of the 16S rRNA gene.

Results
Bacterial richness was higher in egg rafts than in midguts for both species, and higher in Cx pipiens than Cx. restuans. The midgut samples of Cx. pipiens and Cx. restuans were dominated by Providencia. Culex pipiens and Cx. restuans egg rafts samples were dominated by Ralstonia and Novosphingobium, respectively. NMDS ordination based on Bray-Curtis distance matrix revealed that egg-raft samples, or midgut tissues harbored similar bacterial communities regardless of the mosquito species. Within each mosquito species, there was a distinct clustering of bacterial communities between egg raft and midgut tissues.

Conclusion
These findings expand the list of described bacterial communities associated with Cx. pipiens and Cx. restuans and the additional characterization of the egg raft bacterial communities facilitates comparative analysis of mosquito host tissues, providing a basis for future studies seeking to understand any functional role of the bacterial communities in mosquito biology.
Inguinal ureter herniation evaluated with magnetic resonance imaging: a case report
Authors: Renzulli Matteo , Marzocchi Guido , Vara Giulio , Corcioni Beniamino , Ierardi Anna Maria , Gaudiano Caterina , Golfieri Rita 
Published: October 2020

Abstract
Background
The herniation of the ureter into the inguinal canal is a rare condition, but probably underreported. Acquired nephroptosis could cause herniation of the ureter and, therefore, when diagnosed, a full study of the urinary tract should be performed especially in patients with inguinal hernia.

Case presentation
We present the case of an 86-year-old white man with a herniated ureter likely caused by acquired nephroptosis presenting with acute urinary retention, documented with magnetic resonance imaging for the first time.

Conclusions
The Fast Imaging Employing Steady State Acquisition sequence on magnetic resonance imaging, for many reasons, could allow correct evaluation of the urinary tract, especially in cases of renal dysfunction that contraindicate the use of intravenous contrast agents.