bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeted next-generation sequencing of circulating cell-free DNA vs bone marrow in patients with acute myeloid leukemia
Authors: Short Nicholas J. , Patel Keyur P. , Albitar Maher , Franquiz Miguel , Luthra Rajyalakshmi , Kanagal-Shamanna Rashmi , Wang Feng , Assi Rita , Montalban-Bravo Guillermo , Matthews Jairo , Ma Wanlong , Loghavi Sanam , Takahashi Koichi , Issa Ghayas C. , Kornblau Steven M. , Jabbour Elias , Garcia-Manero Guillermo , Kantarjian Hagop M. , Estrov Zeev , Ravandi Farhad 
Published: April 2020

AbstractCirculating cell-free DNA (ccfDNA) allows for noninvasive peripheral blood sampling of cancer-associated mutations and has established clinical utility in several solid tumors. We performed targeted next-generation sequencing of ccfDNA and bone marrow at the time of diagnosis and after achieving remission in 22 patients with acute myeloid leukemia (AML). Among 28 genes sequenced by both platforms, a total of 39 unique somatic mutations were detected. Five mutations (13%) were detected only in ccfDNA, and 15 (38%) were detected only in bone marrow. Among the 19 mutations detected in both sources, the concordance of variant allelic frequency (VAF) assessment by both methods was high (R2 = 0.849). Mutations detected in only 1 source generally had lower VAF than those detected in both sources, suggesting that either method may miss small subclonal populations. In 3 patients, sequencing of ccfDNA detected new or persistent leukemia-associated mutations during remission that appeared to herald overt relapse. Overall, this study demonstrates that sequencing of ccfDNA in patients with AML can identify clinically relevant mutations not detected in the bone marrow and may play a role in the assessment of measurable residual disease. However, mutations were missed by both ccfDNA and bone marrow analyses, particularly when the VAF was &lt;10%, suggesting that ccfDNA and bone marrow may be complementary in the assessment and monitoring of patients with AML.
TooT-T: discrimination of transport proteins from non-transport proteins
Authors: Alballa Munira , Butler Gregory 
Published: April 2020

Abstract
Background
Membrane transport proteins (transporters) play an essential role in every living cell by transporting hydrophilic molecules across the hydrophobic membranes. While the sequences of many membrane proteins are known, their structure and function is still not well characterized and understood, owing to the immense effort needed to characterize them. Therefore, there is a need for advanced computational techniques takes sequence information alone to distinguish membrane transporter proteins; this can then be used to direct new experiments and give a hint about the function of a protein.

Results
This work proposes an ensemble classifier TooT-T that is trained to optimally combine the predictions from homology annotation transfer and machine-learning methods to determine the final prediction. Experimental results obtained by cross-validation and independent testing show that combining the two approaches is more beneficial than employing only one.

Conclusion
The proposed model outperforms all of the state-of-the-art methods that rely on the protein sequence alone, with respect to accuracy and MCC. TooT-T achieved an overall accuracy of 90.07% and 92.22% and an MCC 0.80 and 0.82 with the training and independent datasets, respectively.
Heterogeneous multiple kernel learning for breast cancer outcome evaluation
Authors: Yu Xingheng , Gong Xinqi , Jiang Hao 
Published: April 2020

Abstract
Background
Breast cancer is one of the common kinds of cancer among women, and it ranks second among all cancers in terms of incidence, after lung cancer. Therefore, it is of great necessity to study the detection methods of breast cancer. Recent research has focused on using gene expression data to predict outcomes, and kernel methods have received a lot of attention regarding the cancer outcome evaluation. However, selecting the appropriate kernels and their parameters still needs further investigation.

Results
We utilized heterogeneous kernels from a specific kernel set including the Hadamard, RBF and linear kernels. The mixed coefficients of the heterogeneous kernel were computed by solving the standard convex quadratic programming problem of the quadratic constraints. The algorithm is named the heterogeneous multiple kernel learning (HMKL). Using the particle swarm optimization (PSO) in HMKL, we selected the kernel parameters, then we employed HMKL to perform the breast cancer outcome evaluation. By testing real-world microarray datasets, the HMKL method outperforms the methods of the random forest, decision tree, GA with Rotation Forest, BFA + RF, SVM and MKL.

Conclusions
On one hand, HMKL is effective for the breast cancer evaluation and can be utilized by physicians to better understand the patient’s condition. On the other hand, HMKL can choose the function and parameters of the kernel. At the same time, this study proves that the Hadamard kernel is effective in HMKL. We hope that HMKL could be applied as a new method to more actual problems.
Transcriptome analysis reveals differential immune related genes expression in Ruditapes philippinarum under hypoxia stress: potential HIF and NF-κB crosstalk in immune responses in clam
Authors: Nie Hongtao , Wang Huamin , Jiang Kunyin , Yan Xiwu 
Published: April 2020

Abstract
Background
Hypoxia is an important environmental stressor in aquatic ecosystems, with increasingly impacts on global biodiversity. Benthic communities are the most sensitive parts of the coastal ecosystem to eutrophication and resulting hypoxia. As a filter-feeding organism living in the seafloor sediment, Ruditapes philippinarum represents an excellent “sentinel” species to assess the quality of marine environment. In order to gain insight into the molecular response and acclimatization mechanisms to hypoxia stress in marine invertebrates, we examined hypoxia-induced changes in immune-related gene expression and gene pathways involved in hypoxia regulation of R. philippinarum.

Results
We investigated the response of the Manila clam R. philippinarum to hypoxia under experimental conditions and focused on the analysis of the differential expression patterns of specific genes associated with hypoxia response by RNA-seq and time course qPCR analysis. A total of 75 genes were captured significantly differentially expressed, and were categorized into antioxidant/oxidative stress response, chaperones/heat shock proteins, immune alteration, and cell proliferation/apoptosis. Fourteen hypoxia responsive genes were validated significantly up/down regulated at different time 0, 2, 5, and 8 d in gills of R. philippinarum in hypoxia challenged group. Functional enrichment analysis revealed the HIF signaling pathway and NF-κB signaling pathway play pivotal roles in hypoxia tolerance and resistance in R. philippinarum.

Conclusion
The HIF signaling pathway and NF-κB signaling pathway play a critical role in hypoxia tolerance and resistance in Manila clam. The immune and defense related genes and pathways obtained here gain a fundamental understanding of the hypoxia stress in marine bivalves and provide important insights into the physiological acclimation, immune response and defense activity under hypoxia challenge. The reduced metabolism is a consequence of counterbalancing investments in immune defense against other physiological processes.
Clinicopathological characteristics of light chain proximal tubulopathy in Korean patients and the diagnostic usefulness of immunohistochemical staining for immunoglobulin light chain
Authors: Jung Minsun , Lee Youngeun , Lee Hajeong , Moon Kyung Chul 
Published: April 2020

Abstract
Background
Light chain proximal tubulopathy (LCPT) is a rare paraproteinemic renal disease that has been mostly reported in Western patients. LCPT is characterized by the accumulation of immunoglobulin (Ig)-light chain (LC) in the proximal tubule. Immunohistochemical staining for Ig-LC has not been investigated in the context of LCPT. We reported the clinicopathological characteristics and Ig-LC immunoexpression of patients with LCPT for the first time in Korea.

Methods
We reviewed the clinicopathological findings of 5 Korean patients diagnosed with LCPT between 2016 and 2018. In addition, immunohistochemical staining for κ-LC and λ-LC was conducted on paraffin-embedded tissues.

Results
The median age was 63 years, and the male-to-female ratio was 3:2. The primary renal manifestations were either azotemia or tubular proteinuria. All patients were diagnosed with multiple myeloma with monoclonal κ-LC (#1–2) or λ-LC (#3–5) in the serum and urine. Kidney biopsies revealed diverse and subtle alterations of the proximal tubule, including crystallization, vacuolization, and/or swelling. Electron microscopy revealed crystals in patients #1–2 and non-crystalline particles within numerous/large/dysmorphic lysosomes in patients #3–5. Ig-LC restriction was demonstrated in the proximal tubule as κ-type in patients #1–2 and as λ-type in patients #3–5 by immunohistochemistry and immunofluorescence. Immunohistochemical staining showed diffuse positivity to κ- and λ-LC, although immunofluorescent staining for κ-LC was focal and weak. LCPT has diverse clinicopathological characteristics and subtle morphological alterations, which necessitate ancillary tests for diagnosis.

Conclusions
We introduced immunohistochemical staining for Ig-LC as a useful tool for the diagnosis of LCPT, especially in the case of κ-type crystals.
Prognostic factors for ARDS: clinical, physiological and atypical immunodeficiency
Authors: Song Min , Liu Yijie , Lu Zhiwen , Luo Hong , Peng Hong , Chen Ping 
Published: April 2020

AbstractBackgroundRisk factors affecting the prognosis of acute respiratory distress syndrome (ARDS) in adults were investigated. The aim was to identify new predictors for ARDS patient prognosis, including those with clinical, pathophysiological, and atypical immunodeficiency.MethodsARDS patients were retrospectively included. The patients were grouped and analysed according to different oxygenation index grades and prognosis, and factors influencing prognosis and survival were examined. Adolescent patients, patients with typical immunodeficiency and patients who died within 24 h after being diagnosed with ARDS were excluded. The predictive value for mortality was determined by Cox proportional hazard analysis.ResultsIn total, 201 patients who fulfilled the Berlin definition of ARDS were included. The severity of critical illness on the day of enrolment, as measured by the Acute Physiology and Chronic Health Evaluation (APACHE) II score (P = 0.016), Sequential Organ Failure Assessment (SOFA) score (P = 0.027), and PaO2/FiO2(P = 0.000), worsened from mild to severe ARDS cases. Compared with survivors, non-survivors were significantly older and had higher APACHE II and SOFA scores. Moreover, significantly lower lymphocyte/neutrophil ratios and leukocyte counts were found among non-survivors than survivors (P = 0.008,P = 0.012). A moderate positive correlation between the lymphocyte/neutrophil and PaO2/FiO2ratios (P = 0.023) was observed. In predicting 100-day survival in patients with ARDS, the area under the curve (AUC) for the lymphocyte/neutrophil ratio was significantly higher than those for the PaO2/FiO2ratio alone, body mass index (BMI) alone, and the lymphocyte count alone (P = 0.0062, 0.0001, and 0.0154). Age (per log10years), BMI < 24, SOFA score, leukocyte count, and the lymphocyte/neutrophil ratio were independent predictors of 28-day mortality in ARDS patients. Additionally, ARDS patients with a lymphocyte/neutrophil ratio < 0.0537 had increased 28-day mortality rates (P = 0.0283). Old age affected both 28-day and 100-day mortality rates (P = 0.0064,0.0057).ConclusionsAge (per log10years), BMI < 24, SOFA score, lymphocytes, and the lymphocyte/neutrophil ratio were independent predictors of 100-day mortality in patients with ARDS. The lymphocyte/neutrophil ratio may represent a potential molecular marker to evaluate atypical immunosuppression or impairment in patients with ARDS.
Patellar sleeve avulsion fracture in a patient with Sinding-Larsen-Johansson syndrome: a case report
Authors: Schmidt-Hebbel Andrés , Eggers Felipe , Schütte Vincent , Achtnich Andrea , Imhoff Andreas B. 
Published: April 2020

Abstract
Background
Patellar sleeve avulsion (PSA) fractures are rare injuries that occur in in skeletally immature patients. Initial diagnosis is key to a successful outcome, as these injuries are easily overlooked on plain radiographs with poor results well documented from delayed management. High index of suspicion from the mechanism of injury, thorough clinical examination and Magnetic Resonance Imaging (MRI) help to avoid misdiagnosis.

Case presentation
The case of a 12-year-old male athlete with an acute PSA after a conservative treatment of a SLJ syndrome is described. The patient was referred to our clinic due to severe pain and loss of function after performing a high jump. Plain radiographs (X-ray) and MRI confirmed an inferior pole PSA which was fixed with double trans osseous ultra-high strength tapes. At the 3-month follow- up visit the patient was able to ambulate brace free. At 2-years follow up the patient was able to play soccer and ice hockey. To our knowledge, there are no case reports of inferior pole PSA with prior SLJ syndrome described in literature.

Conclusions
Early clinical suspicion and distinguishing this PSA from other enchondral ossification disorders around the knee is critical to avoid misdiagnosis. Whether SLJ syndrome increases the risk of sustaining a PSA is still not clear. Trans osseous fixation with suture tapes leads to good functional results in a young athlete with inferior pole PSA.
Non-health outcomes affecting self-care behaviors and medical decision-making preference in patients with type 2 diabetes: a cross-sectional study
Authors: Wang Ming-Jye , Lin Hung-Ming , Hung Li-Chen , Lo Yi-Ting 
Published: April 2020

AbstractBackgroundThe effects of patient sustained self-care behaviors on glycemic control are even greater than the effects of medical treatment, indicating the value of identifying the factors that influence self-care behaviors. To date, these factors have not been placed in a single model to clarify the critical path affecting self-care behaviors. The aims of this study were to explore the relationships of these factors and the differences in patient preference for medical decision-making.MethodsA cross-sectional study was conducted among outpatients with type 2 diabetes at a regional teaching hospital. Purposive sampling was adopted to recruit 316 eligible patients via self-administered questionnaires. Partial least squares structural equation modeling was used for analysis.ResultsSignificant direct pathways were identified from health literacy to self-efficacy, patient empowerment, and self-care behaviors; from self-efficacy to self-care behaviors; and from patient empowerment to self-care behaviors. Indirect pathways were from health literacy to self-care behaviors via self-efficacy or patient empowerment. The pathway from health literacy to self-efficacy was significantly stronger in those preferring shared decision-making than in those who preferred physician decision-making.ConclusionsHealth literacy is a critical factor in improving self-care behaviors in patients with type 2 diabetes, and the effect of health literacy on self-efficacy was more significant in the shared decision-making than in the physician decision-making. Therefore, developing an effective health strategy to strengthen health literacy awareness and designing friendly, diverse health literacy materials, and application tools is the most important factor to facilitate self-care behaviors in this population.
Assessing the youth-friendliness of youth clinics in northern Sweden: a survey analyzing the perspective of the youth
Authors: Waenerlund Anna-Karin , San Sebastian Miguel , Hurtig Anna-Karin , Wiklund Maria , Christianson Monica , Goicolea Isabel 
Published: April 2020

Abstract
Background
Sweden has nearly 300 youth clinics that have been offering services since the 1970s. However, no evaluation has been done to assess their youth-friendliness. This study aims to assess: i) to what extent youth clinics are perceived as youth-friendly by the young people using them; and ii) if the level of youth friendliness is equally perceived across different sociodemographic groups of users.

Methods
The four northernmost counties of Sweden were included in the study. Of the total identified 22 youth clinics, 20 participated by giving out questionnaires to the youth after their visits to the respective youth clinics. In total 1110 youth participated in the study and answered questions according to the World Health Organization’s criteria of accessibility, equity, respect, privacy and confidentiality, no judgement, and quality. Means and frequencies were calculated, and t-test and ANOVA were used to compare means by sociodemographic variables.

Results
Participants perceived the youth clinics as very youth friendly across the measured domains, with scores as high as 4.8 and 4.9 (of a maximum of 5). Youth clinics were perceived in a similar way regardless of gender, but other sociodemographic factors influenced some of the domains, especially ethnic background.

Conclusions
The perception of youth friendliness in youth clinics was very high. Nonetheless, younger users; users who did not categorize themselves as either heterosexual, homosexual, or bisexual; users with trans-experiences; and users with non-Swedish backgrounds gave youth clinics lower scores for certain domains.
‘Wait and wait, that is the only thing they can say’: a qualitative study exploring experiences of immigrated Syrian doctors applying for medical license in Germany
Authors: Loss Julika , Aldoughle Yamen , Sauter Alexandra , von Sommoggy Julia 
Published: April 2020

Abstract
Background
Due to the civil war in Syria, many Syrian citizens have had to flee their country during recent years, among them many physicians. Germany is among the preferred immigration countries. Immigrant Syrian physicians could help overcome the prevailing shortage of medical specialists in Germany. This study explores the experiences and perceptions of Syrian physicians of the licensure process and job application. The study aims at understanding barriers in integrating Syrian doctors into the German health care system.

Methods
We conducted 20 semi standardized interviews with Syrian doctors (n = 17 m; n = 3 f) living in different federal states in Germany. The interviews dealt with the procedure of the accreditation process, its speed and challenges, the interactions with authorities, and the job application process; they were transcribed verbatim. A detailed content analysis was performed.

Results
All interviewees described the licensure process as a complex, lengthy, ever-changing and non-transparent procedure, which is perceived as a partly unfair, sometimes arbitrary bureaucracy. They often feel at mercy of Government employees and report experiences with reviewers who ask for absurd and impossible accomplishments, refuse to give information, and act at random. As a consequence, the interviewees describe themselves as depressed, irritated and/or in despair. According to the interviews, informational and practical support from official institutions was scarce. Instead, the Syrian doctors relied on peers or, in some cases, German friends to understand the requirements and seek information about the licensure process. To find a job placement, it was very helpful, if not essential, to have a German acquaintance establishing contact with possible employers. All three interviewed female doctors reported that their wearing a Hijab led to episodes of discrimination in their job search.

Conclusions
The study points towards the necessity to establish an official information source which provides immigrant doctors with accurate and detailed information about the licensure process, e.g. required documents, estimated waiting times, regulation for courses and exams, criteria regarding credentials, sources of help, etc. Additionally, it seems advisable to consider providing help with regard to the job search and sensitize hospital management for cultural and religious diversity to avoid discrimination.
A case series of CHARGE syndrome: identification of key features for a neonatal diagnosis
Authors: Bedeschi Maria Francesca , Crippa Beatrice Letizia , Colombo Lorenzo , Buscemi Martina , Rossi Cesare , Villa Roberta , Gangi Silvana , Picciolini Odoardo , Cinnante Claudia , Fergnani Viola Giulia Carlina , Ajmone Paola Francesca , Scola Elisa , Triulzi Fabio , Mosca Fabio 
Published: April 2020

Abstract
Background
An early diagnosis of CHARGE syndrome is challenging, especially for the primary care physicians who often take care of neonates with multiple congenital anomalies. Here we report eight cases of CHARGE syndrome whose diagnosis was made early in life with the intent to identify the most helpful features allowing a prompt clinical diagnosis.

Methods
Medical records of patients with CHARGE syndrome whose diagnosis was made at the Fondazione IRCCS Ca′ Granda Ospedale Maggiore Policlinico in Milan, Italy were retrospectively reviewed.

Results
Taken together, these patients reflect the considerable phenotypic variability of the syndrome; in one patient, the diagnosis was made immediately after birth because all the major criteria were met. In six patients, presenting with relatively nonspecific defects, a temporal bone computerized tomography scan was essential to achieve the correct diagnosis. In one patient, the diagnosis was made later than the others were. A careful examination revealed the presence of outer, middle, and inner ear anomalies: these elements, in the absence of any additional major criteria, represented for us an important diagnostic clue.

Conclusions
This article suggests that an accurate evaluation of the ear should be made every time CHARGE syndrome is considered as a likely diagnosis even when the standard criteria are not fulfilled.
RETRACTED ARTICLE: EV71 virus reduces Nrf2 activation to promote production of reactive oxygen species in infected cells
Authors: Bai Zhenzi , Zhao Xiaonan , Li Chenghua , Sheng Chuanlun , Li Hongyan 
Published: April 2020

Abstract
Background
Emerging evidence closely links Enterovirus 71 (EV71) infection with the generation of reactive oxygen species (ROS). Excess ROS results in apoptosis and exacerbates inflammatory reactions. The Keap1–Nrf2 axis serves as an essential oxidant counteracting pathway.

Methods
The present study aimed to elucidate the role of the Keap1–Nrf2 pathway in modulating apoptosis and inflammatory reactions triggered by oxidative stress in Vero and RD cells upon EV71 infection.

Results
Elevated ROS production was identified in EV71 infected Vero and RD cells. The percentage of dead cells and expression of inflammation-promoting cytokines were increased in these cells. EV71 infected cells also displayed reinforced Keap1 expression and abrogated Nrf2 expression. Keap1 silencing resulted in the downstream aggregation of the Nrf2 protein and heme oxygenase-1 HO-1. Keap1 silencing repressed ubiquitination and reinforced Nrf2 nuclear trafficking. Furthermore, silencing Keap1 expression repressed ROS production, cell death, and inflammatory reactions in EV71 infected RD and Vero cells. In contrast, silencing of both Keap1 and Nrf2 restored ROS production, cell death, and inflammatory reactions. Nrf2 and Keap1 modulated the stimulation of the Akt sensor and extrinsic as well as intrinsic cell death pathways, resulting in EV71-triggered cell death and inflammatory reactions.

Conclusions
EV71 infection can trigger ROS production, cell death, and inflammatory reactions by modulating the Nrf2 and Keap1 levels of infected cells.