bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrative -omics and HLA-ligandomics analysis to identify novel drug targets for ccRCC immunotherapy
Authors: Reustle Anna , Di Marco Moreno , Meyerhoff Carolin , Nelde Annika , Walz Juliane S. , Winter Stefan , Kandabarau Siahei , Büttner Florian , Haag Mathias , Backert Linus , Kowalewski Daniel J. , Rausch Steffen , Hennenlotter Jörg , Stühler Viktoria , Scharpf Marcus , Fend Falko , Stenzl Arnulf , Rammensee Hans-Georg , Bedke Jens , Stevanović Stefan , Schwab Matthias , Schaeffeler Elke 
Published: March 2020

Abstract
Background
Clear cell renal cell carcinoma (ccRCC) is the dominant subtype of renal cancer. With currently available therapies, cure of advanced and metastatic ccRCC is achieved only in rare cases. Here, we developed a workflow integrating different -omics technologies to identify ccRCC-specific HLA-presented peptides as potential drug targets for ccRCC immunotherapy.

Methods
We analyzed HLA-presented peptides by MS-based ligandomics of 55 ccRCC tumors (cohort 1), paired non-tumor renal tissues, and 158 benign tissues from other organs. Pathways enriched in ccRCC compared to its cell type of origin were identified by transcriptome and gene set enrichment analyses in 51 tumor tissues of the same cohort. To retrieve a list of candidate targets with involvement in ccRCC pathogenesis, ccRCC-specific pathway genes were intersected with the source genes of tumor-exclusive peptides. The candidates were validated in an independent cohort from The Cancer Genome Atlas (TCGA KIRC, n = 452). DNA methylation (TCGA KIRC, n = 273), somatic mutations (TCGA KIRC, n = 392), and gene ontology (GO) and correlations with tumor metabolites (cohort 1, n = 30) and immune-oncological markers (cohort 1, n = 37) were analyzed to characterize regulatory and functional involvements. CD8+ T cell priming assays were used to identify immunogenic peptides. The candidate gene EGLN3 was functionally investigated in cell culture.

Results
A total of 34,226 HLA class I- and 19,325 class II-presented peptides were identified in ccRCC tissue, of which 443 class I and 203 class II peptides were ccRCC-specific and presented in ≥ 3 tumors. One hundred eighty-five of the 499 corresponding source genes were involved in pathways activated by ccRCC tumors. After validation in the independent cohort from TCGA, 113 final candidate genes remained. Candidates were involved in extracellular matrix organization, hypoxic signaling, immune processes, and others. Nine of the 12 peptides assessed by immunogenicity analysis were able to activate naïve CD8+ T cells, including peptides derived from EGLN3. Functional analysis of EGLN3 revealed possible tumor-promoting functions.

Conclusions
Integration of HLA ligandomics, transcriptomics, genetic, and epigenetic data leads to the identification of novel functionally relevant therapeutic targets for ccRCC immunotherapy. Validation of the identified targets is recommended to expand the treatment landscape of ccRCC.
Iguratimod as an alternative induction therapy for refractory lupus nephritis: a preliminary investigational study
Authors: Kang Yuening , Yan Qingran , Fu Qiong , Wang Ran , Dai Min , Du Fang , Dai Qing , Ye Ping , Wu Chunmei , Lu Liangjing , Bao Chunde 
Published: March 2020

Abstract
Objectives
Iguratimod, a novel immunomodulatory agent for rheumatoid arthritis, has been shown to be effective against murine lupus. The aim of this study was to make a preliminary evaluation of the efficacy and safety of iguratimod as salvage therapy in patients with refractory lupus nephritis (LN).

Methods
We enrolled eligible patients with refractory LN, which we defined as having failed or relapsed on at least two immunosuppressant agents. After enrollment, we substituted iguratimod (25 mg twice daily) for their previous immunosuppressant agents without increasing the dose of steroids. The primary outcome was complete/partial remission (PR/CR) at week 24. Patients who achieved remission continued iguratimod as maintenance therapy over an extended follow-up.

Results
The study cohort comprised 14 patients with refractory LN, 10 of whom had recent treatment failure and 4 repeated relapses with inadequate initial responses. At enrollment, none of the patients had detectable evidence of extra-renal involvement. The median prednisone dosage was 10 mg/d (IQR 0–10 mg/day). Thirteen patients were eligible for response evaluation, with one patient missed. The renal response rate was 92.3% (12/13) at week 24, with 38.5% (5/13) achieving CR and 53.8% (7/13) achieving PR. We then continued to follow up the responding patients for up to 144 weeks. Twenty-five percent of the patients (3/12) had renal relapse after initial PR. The estimated glomerular filtration rate of all patients maintained stable during follow-up. One patient had a severe adverse reaction (anemia) but recovered fully after stopping iguratimod.

Conclusions
Our study supports the potential of iguratimod for treatment of refractory LN. Iguratimod could be a promising candidate drug for this condition.
Effects of high intensity interval training on exercise capacity in people with chronic pulmonary conditions: a narrative review
Authors: Sawyer Abbey , Cavalheri Vinicius , Hill Kylie 
Published: March 2020

AbstractBackgroundExercise training is important in the management of adults with chronic pulmonary conditions. However, achieving high intensity exercise may be challenging for this clinical population. There has been clinical interest in applying interval-based training as a strategy to optimise the load that can be tolerated during exercise training. Evidence for such an approach is limited in most chronic pulmonary populations.Main bodyIn this narrative review, we provide an appraisal of studies investigating whole-body high intensity interval training (HIIT) in adults with chronic obstructive pulmonary disease (COPD). This is the first review to also include studies investigating HIIT in people with conditions other than COPD. Studies undertaken in adults with a chronic pulmonary condition were reviewed when participants were randomised to receive; (i) HIIT or no exercise or, (ii) HIIT or moderate intensity continuous exercise. Data were extracted on peak rate of oxygen uptake (VO2peak; ‘cardiorespiratory fitness’) and maximal work rate (Wmax; ‘exercise capacity’).In people with COPD, two studies demonstrated between-group differences favouring HIIT compared with no exercise. There appears to be no advantage for HIIT compared to continuous exercise on these outcomes. In people with cystic fibrosis (CF), no studies have compared HIIT to no exercise and the two studies that compared HIIT to continuous exercise reported similar benefits. In people prior to resection for non-small cell lung cancer, one study demonstrated a between-group difference in favour of HIIT compared with no exercise on VO2peak. In people with asthma, one study demonstrated a between-group difference in favour of HIIT compared with no exercise on VO2peakand one that compared HIIT to continuous exercise reported similar benefits. No studies were identified non-CF bronchiectasis or interstitial lung diseases.ConclusionsHigh intensity interval training increases cardiorespiratory fitness and exercise capacity when compared with no exercise and produces a similar magnitude of change as continuous exercise in people with COPD. There is a paucity of studies exploring the effects of HIIT in other chronic pulmonary conditions.
Study determinants of increased Z-Score of Body Mass Index in preschool-age children
Authors: El-Gamal Fathi M. , Babader Rawan , Al-Shaikh Maha , Al-Harbi Amani , Al-Kaf Jumana , Al-Kaf Wafa 
Published: March 2020

Abstract
Objective
To determine the association between socioeconomic level, gender, stunting and other characteristics with the presence of overweight/obesity in the preschool children.

Result
BMI/Age Z score > + 2 SD was found in 19.5% of the children. It was more common among the children from areas with high socio-economic level (OR: 2.43; 95% CI 1.54, 3.84, and p < .000). Obesity was higher among the males (OR 1.76; 95% CI 1.09, 2.8, and p < .02) compared to females. The increased duration of breast feeding, was significantly associated with increased BMI/Age Z-score (b = .027, p < .004). Decreased age of the child was significantly associated with increased BMI/Age Z-score (b = −  .013, p < .004). The children with stunted growth were 6.7 times fold likely to have BMI/Age Z Score > + 2 SD compared to the normal children (OR 6.73; 95% CI 3.79, 10.80, and p < .000), after allowing for other factors. No significant association was found between allergic disorders and BMI/Age Z score > + 2 SD. Thus male gender, high socioeconomic condition, increased duration of breast feeding and stunting were significantly associated with overweight/obesity in preschool children.
Loss of the neurodevelopmental disease-associated gene miR-146a impairs neural progenitor differentiation and causes learning and memory deficits
Authors: Fregeac Julien , Moriceau Stéphanie , Poli Antoine , Nguyen Lam Son , Oury Franck , Colleaux Laurence 
Published: March 2020

AbstractBackgroundFormation and maintenance of appropriate neural networks require tight regulation of neural stem cell proliferation, differentiation, and neurogenesis. microRNAs (miRNAs) play an important role in brain development and plasticity, and dysregulated miRNA profiles have been linked to neurodevelopmental disorders including autism, schizophrenia, or intellectual disability. Yet, the functional role of miRNAs in neural development and postnatal brain functions remains unclear.MethodsUsing a combination of cell biology techniques as well as behavioral studies and brain imaging, we characterize mouse models with either constitutive inactivation or selectively hippocampal knockdown of the neurodevelopmental disease-associated gene Mir146a, the most commonly deregulated miRNA in developmental brain disorders (DBD).ResultsWe first show that during development, loss ofmiR-146aimpairs the differentiation of radial glial cells, neurogenesis process, and neurite extension. In the mouse adult brain, loss ofmiR-146acorrelates with an increased hippocampal asymmetry coupled with defects in spatial learning and memory performances. Moreover, selective hippocampal downregulation ofmiR-146ain adult mice causes severe hippocampal-dependent memory impairments indicating for the first time a role for this miRNA in postnatal brain functions.ConclusionOur results show thatmiR-146aexpression is critical for correct differentiation of neural stem cell during brain development and provide for the first time a strong argument for a postnatal role ofmiR-146ain regulating hippocampal-dependent memory. Furthermore, the demonstration that theMir146a−/−mouse recapitulates several aspects reported in DBD patients, including impaired neurogenesis, abnormal brain anatomy, and working and spatial memories deficits, provides convincing evidence that the dysregulation ofmiR146acontributes to the pathogenesis of DBDs.
CCR5-Δ32 biology, gene editing, and warnings for the future of CRISPR-Cas9 as a human and humane gene editing tool
Authors: Xu MengMeng 
Published: March 2020

Abstract
Background
Biomedical technologies have not just improved human health but also assisted in the creation of human life. Since the first birth of a healthy baby by in vitro fertilization (IVF) 40 years ago, IVF has been the mainstay treatment for couples struggling with infertility. This technology, in addition to increasingly accessible genetic testing, has made it possible for countless couples to have children. Since CRISPR-Cas9 gene editing was described in 2015, its potential for targeting genetic diseases has been much anticipated. However, the potential of using CRISPR-Cas9 for human germline modification has led to many fears of “designer babies” and widespread concerns for the impact of this technology on human evolution and its implications in Social Darwinism. In addition to these ethical/moral concerns, there remain many unknowns about CRISPR-Cas9 technology and endless unanticipated consequence to gene editing.

Methods
In this paper, we analyze the current progresses of CRISPR-Cas9 technology and discuss the theoretical advantages of certain allelic variances in the C-C chemokine receptor 5 gene (CCR5) in the setting of recent ethical/moral concerns regarding gene editing using the CRISPR-Cas9 system.

Results
These uncertainties have been highlighted recently by the birth of Chinese twins whose C-C chemokine receptor 5 (CCR5) gene had been inactivated via CRISPR-Cas9 to be theoretically protective against HIV infection. CCR5 signaling is critical for the successful infection of human immunodeficiency virus (HIV) and people with homozygous inactivating CCR5-Δ32 mutations have been shown to be protected against HIV infection. Those with the CCR5-Δ32/Δ32 mutation also have greater neuroplasticity, allowing for improved recovery from neurological trauma, and decreased Chagas cardiomyopathy. However, the CCR5-Δ32/Δ32 mutation has also been associated with earlier clinical manifestations for West Nile infection, ambiguous effects on osteoclast function, and a four-fold increased mortality from influenza infection. These detrimental health impacts, in addition to the confounding factor that these CRISPR babies do not carry this exact CCR5-Δ32/Δ32 mutation, lead to many questions regarding the children’s future health and the moral conundrum of their birth. The creation and birth of these babies was not completed with any scientific, ethical, or governmental oversight, which has spurned the acceleration of talks regarding global regulations for human genetic editing.

Conclusions
Although we can try to regulate for ethical, health-related only use of this technology, moral and governmental oversights need to be supplemented by technical regulations. For instance, whole genome sequencing needs to be used to eliminate off-target mutations that could affect the health and safety of infants born to this process. Like Pandora’s Box, we cannot pretend to forget CRISPR-Cas9 technology, all we can do is ensure a safe, moral, and equitable used of this technology.
BRCA1 and homologous recombination: implications from mouse embryonic development
Authors: Liu Yidan , Lu Lin-Yu 
Published: March 2020

AbstractAs an important player in DNA damage response, BRCA1 maintains genomic stability and suppresses tumorigenesis by promoting DNA double-strand break (DSB) repair through homologous recombination (HR). Since the cloning of BRCA1 gene, many Brca1 mutant alleles have been generated in mice. Mice carrying homozygous Brca1 mutant alleles are embryonic lethal, suggesting that BRCA1’s functions are important for embryonic development. Studies of embryonic development in Brca1 mutant mice not only reveal the physiological significance of BRCA1’s known function in HR, but also lead to the discovery of BRCA1’s new function in HR: regulation of DSB repair pathway choice.
New insights into the cellular activities of Fndc5/Irisin and its signaling pathways
Authors: Rabiee Farzaneh , Lachinani Liana , Ghaedi Sarvenaz , Nasr-Esfahani Mohammad Hossein , Megraw Timothy L. , Ghaedi Kamran 
Published: March 2020

AbstractFndc5, a well-defined myokine and also identified as an adipokine, has a critical role in modulation of metabolism and protection against obesity. These important functions are mediated by irisin, a secretory peptide produced from proteolytic processing of Fndc5. The other beneficial physiological effects of irisin are alleviation of oxidative stress, neuroprotective effects, and anti-inflammatory properties and associated anti-metastatic effects. Fndc5/irisin exerts its biological effects through several intracellular signaling pathways. The major signaling pathway is thought to be MAPK signaling pathways which are involved in neural differentiation, browning of white adipocytes, as well as osteoblast proliferation and differentiation. Other essential functions of Fndc5/irisin are mediated through additional pathways including AMPK pathway, PI3K/AKT, and STAT3/Snail. Thorough understanding of the mechanisms of irisin actions are essential in order to develop Fndc5/irisin for therapeutic purposes. In the present review, we focus on the current knowledge of the signaling pathways that elicit irisin actions.
The experience of high-flow nasal cannula in hospitalized patients with 2019 novel coronavirus-infected pneumonia in two hospitals of Chongqing, China
Authors: Wang Ke , Zhao Wei , Li Ji , Shu Weiwei , Duan Jun 
Published: March 2020

Abstract
Background
The outbreak of a novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) is currently ongoing in China. Most of the critically ill patients received high-flow nasal cannula (HFNC) oxygen therapy. However, the experience of HFNC in this population is lacking.

Methods
We retrospectively screened 318 confirmed patients with NCIP in two hospitals of Chongqing, China, from January 1st to March 4th, 2020. Among them, 27 (8.4%) patients experienced severe acute respiratory failure including 17 patients (63%) treated with HFNC as first-line therapy, 9 patients (33%) treated with noninvasive ventilation (NIV) and one patient (4%) treated with invasive ventilation. HFNC failure was defined by the need of NIV or intubation as rescue therapy.

Results
Of the 17 HFNC patients, 7 (41%) experienced HFNC failure. The HFNC failure rate was 0% (0/6) in patients with PaO2/FiO2 > 200 mm Hg vs. 63% (7/11) in those with PaO2/FiO2 ≤ 200 mm Hg (p = 0.04). Compared with baseline data, the respiratory rate significantly decreased after 1–2 h of HFNC in successful group [median 26 (IQR: 25–29) vs. 23 (22–25), p = 0.03]. However, it did not in the unsuccessful group. After initiation of NIV as rescue therapy among the 7 patients with HFNC failure, PaO2/FiO2 significantly improved after 1–2 h of NIV [median 172 (150–208) mmHg vs. 114 (IQR: 79–130) under HFNC, p = 0.04]. However, two out of seven (29%) patients with NIV as rescue therapy ultimately received intubation. Among the 27 patients with severe acute respiratory failure, four patients were eventually intubated (15%).

Conclusions
Our study indicated that HFNC was the most common ventilation support for patients with NCIP. Patients with lower PaO2/FiO2 were more likely to experience HFNC failure.
Movement-assisted localization from acoustic telemetry data
Authors: Hostetter Nathan J. , Royle J. Andrew 
Published: March 2020

AbstractBackgroundAcoustic telemetry technologies are being increasingly deployed to study a variety of aquatic taxa including fishes, reptiles, and marine mammals. Large cooperative telemetry networks produce vast quantities of data useful in the study of movement, resource selection and species distribution. Efficient use of acoustic telemetry data requires estimation of acoustic source locations from detections at receivers (i.e., “localization”). Multiple processes provide information for localization estimation including detection/non-detection data at receivers, information on signal rate, and an underlying movement model describing how individuals move and utilize space. Frequently, however, localization methods only integrate a subset of these processes and do not utilize the full spatial encounter history information available from receiver arrays.MethodsIn this paper we draw analogies between the challenges of acoustic telemetry localization and newly developed methods of spatial capture-recapture (SCR). We develop a framework for localization that integrates explicit sub-models for movement, signal (or cue) rate, and detection probability, based on acoustic telemetry spatial encounter history data. This method, which we call movement-assisted localization, makes efficient use of the full encounter history data available from acoustic receiver arrays, provides localizations with fewer than three detections, and even allows for predictions to be made of the position of an individual when it wasnotdetected at all. We demonstrate these concepts by developing generalizable Bayesian formulations of the SCR movement-assisted localization model to address study-specific challenges common in acoustic telemetry studies.ResultsSimulation studies show that movement-assisted localization models improve point-wise RMSE of localization estimates by >50%and greatly increased the precision of estimated trajectories compared to localization using only the detection history of a given signal. Additionally, integrating a signal rate sub-model reduced biases in the estimation of movement, signal rate, and detection parameters observed in independent localization models.ConclusionsMovement-assisted localization provides a flexible framework to maximize the use of acoustic telemetry data. Conceptualizing localization within an SCR framework allows extensions to a variety of data collection protocols, improves the efficiency of studies interested in movement, resource selection, and space-use, and provides a unifying framework for modeling acoustic data.
A full-polarization GNSS-R Delay-Doppler-Map (DDM) simulator for bare soil freeze/thaw process detection
Authors: Wu Xuerui , Jin Shuanggen , Ouyang Xinqiu 
Published: March 2020

AbstractThe soil freeze/thaw processes have a significant impact on the surface energy and moisture balance, which play a key role in ecosystem diversity and productivity. The air-/space-borne Global Navigation Satellite System (GNSS)-Reflectometry (GNSS-R) is a bistatic radar with receiving power as the Delay Doppler Map (DDM), which may monitor soil freeze/thaw processes. However, the scattering mechanism of monitoring soil freeze/thaw processes by GNSS-R DDM is not clear. In this paper, it is the first time to simulate full-polarization GNSS-R Delay-Doppler-Map (DDM) for bare soil freeze/thaw process, not only the linear polarization but also the circular polarizations. As the bare soil freeze/thaw process occurs, the corresponding DDM variations are able to present by this simulator. Other geophysical parameters, such as soil moisture and surface roughness, are also two important parameters affecting the final GNSS-R receiver power and their effects on DDM are also presented by the simulator. This simulator can be a potentially efficient tool for data analysis and interoperation of GNSS-R received power as well as the in situ experimental design.
Post-hepatectomy tolvaptan-induced hypernatremia in a hepatocellular carcinoma patient with cirrhosis: a case report
Authors: Iida Hiroya , Maehira Hiromitsu , Mori Haruki , Maekawa Tsuyoshi , Tani Masaji 
Published: March 2020

AbstractBackgroundTolvaptan is used in Japan to reduce fluid retention caused by cirrhosis. However, hypernatremia is one of the most important side effects. This report is the first case report of a patient who developed hypernatremia after tolvaptan administration in the early stages following hepatectomy.Case presentationA female patient in her 60s, who was admitted to the psychiatric department of a different hospital for bipolar disorder, developed hepatocellular carcinoma with cirrhosis. She was transferred to our hospital, and hepatectomy was performed in October 2019, after which pleural effusion and severe edema due to fluid retention were evident. Thus, the patient was started on tolvaptan (7.5 mg/day) from postoperative day (POD) 1. The patient began to experience disturbance of consciousness after POD 4. On the fifth day, the serum sodium (Na) level increased to 174 mEq/L, and hypernatremia was diagnosed. The Na level gradually improved with fluid infusion therapy, dropping to preoperative levels on the ninth day; her consciousness also gradually improved.ConclusionsTolvaptan administration must be performed under strictly controlled conditions, followed by careful observation during the early postoperative period, when the patient’s physical status is unstable.