bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lymphadenitis “As Rosary beads” - a diagnostic challenge
Authors: Dos Santos Vitorino Modesto , De Azevedo Micheline Silva Abreu , Brito Katia Rejane Marques , Da Luz Larissa Almondes , Ribeiro Kayursula Dantas 
Published: October 2019

Introduction: nodular lymphangitis (NL) may be a manifestation of various infectious and non-infectious conditions, characterised by subcutaneous inflammatory nodules that extend from the site of the primary focus to the regional lymph nodes. NL usually constitutes a challenge in primary health care, and histopathological and microbiological evaluations are necessary to establish the definitive diagnosis. Methods: We report a classic case of NL that developed in the upper limb of a middle-aged man after trauma on the right thumb. The objective: was to emphasise some aspects of the differential diagnosis in a patient with NL and to reduce the rate of misdiagnosis in the scenery of initial medical attention. Results: the clinical manifestations were non-specific, but the microbiological study revealed typical characteristics of sporotrichosis. The treatment with itraconazole (200 mg daily) for six months was successful. Conclusion: NL constitutes a challenging condition and the early diagnosis depends on a high index of suspicion. Case reports may reduce late diagnoses with unfavourable results.
Histone-Related Genes Are Hypermethylated in Lung Cancer and Hypermethylated HIST1H4F Could Serve as a Pan-Cancer Biomarker
Authors: Dong Shihua , Li Wei , Wang Lin , Hu Jie , Song Yuanlin , Zhang Baolong , Ren Xiaoguang , Ji Shimeng , Li Jin , Xu Peng , Liang Ying , Chen Gang , Lou Jia-Tao , Yu Wenqiang 
Published: October 2019

Abstract

Lung cancer is the leading cause of cancer-related deaths worldwide. Cytologic examination is the current “gold standard” for lung cancer diagnosis, however, this has low sensitivity. Here, we identified a typical methylation signature of histone genes in lung cancer by whole-genome DNA methylation analysis, which was validated by The Cancer Genome Atlas (TCGA) lung cancer cohort (n = 907) and was further confirmed in 265 bronchoalveolar lavage fluid samples with specificity and sensitivity of 96.7% and 87.0%, respectively. More importantly, HIST1H4F was universally hypermethylated in all 17 tumor types from TCGA datasets (n = 7,344), which was further validated in nine different types of cancer (n = 243). These results demonstrate that HIST1H4F can function as a universal-cancer-only methylation (UCOM) marker, which may aid in understanding general tumorigenesis and improve screening for early cancer diagnosis.

Significance:
These findings identify a new biomarker for cancer detection and show that hypermethylation of histone-related genes seems to persist across cancers.
Tumor-Derived Thymic Stromal Lymphopoietin Expands Bone Marrow B-cell Precursors in Circulation to Support Metastasis
Authors: Ragonnaud Emeline , Moritoh Kanako , Bodogai Monica , Gusev Fedor , Garaud Soizic , Chen Chen , Wang Xin , Baljinnyam Tuvshintugs , Becker Kevin G. , Maul Robert W. , Willard-Gallo Karen , Rogaev Evgeny , Biragyn Arya 
Published: October 2019

Abstract

Immature B cells in the bone marrow emigrate into the spleen during adult lymphopoiesis. Here, we report that emigration is shifted to earlier B-cell stages in mice with orthotopic breast cancer, spontaneous ovarian cancer, and possibly in human breast carcinoma. Using mouse and human bone marrow aspirates and mouse models challenged with highly metastatic 4T1 breast cancer cells, we demonstrated that this was the result of secretion of thymic stromal lymphopoietin (TSLP) by cancer cells. First, TSLP downregulated surface expression of bone marrow (BM) retention receptors CXCR4 and VLA4 in B-cell precursors, increasing their motility and, presumably, emigration. Then, TSLP supported peripheral survival and proliferation of BM B-cell precursors such as pre-B–like cells. 4T1 cancer cells used the increased pool of circulating pre-B–like cells to generate metastasis-supporting regulatory B cells. As such, the loss of TSLP expression in cancer cells alone or TSLPR deficiency in B cells blocked both accumulation of pre-B–like cells in circulation and cancer metastasis, implying that the pre-B cell–TSLP axis can be an attractive therapeutic target.

Significance:
Cancer cells induce premature emigration of B-cell precursors from the bone marrow to generate regulatory B cells.
ARID5B Influences Antimetabolite Drug Sensitivity and Prognosis of Acute Lymphoblastic Leukemia
Authors: Xu Heng , Zhao Xujie , Bhojwani Deepa , E Shuyu , Goodings Charnise , Zhang Hui , Seibel Nita L. , Yang Wentao , Li Chunliang , Carroll William L. , Evans William E. , Yang Jun J. 
Published: October 2019

Abstract

Purpose:
Treatment outcomes for childhood acute lymphoblastic leukemia (ALL) have improved steadily, but a significant proportion of patients still experience relapse due to drug resistance, which is partly explained by inherited and/or somatic genetic alternations. Recently, we and others have identified genetic variants in the ARID5B gene associated with susceptibility to ALL and also with relapse. In this study, we sought to characterize the molecular pathway by which ARID5B affects antileukemic drug response in patients with ALL.

Experimental Design:
We analyzed association of ARID5B expression in primary human ALL blasts with molecular subtypes and treatment outcome. Subsequent mechanistic studies were performed in ALL cell lines by manipulating ARID5B expression isogenically, in which we evaluated drug sensitivity, metabolism, and molecular signaling events.

Results:
ARID5B expression varied substantially by ALL subtype, with the highest level being observed in hyperdiploid ALL. Lower ARID5B expression at diagnosis was associated with the risk of ALL relapse, and further reduction was noted at ALL relapse. In isogenic ALL cell models in vitro, ARID5B knockdown led to resistance specific to antimetabolite drugs (i.e., 6-mercaptopurine and methotrexate), without significantly affecting sensitivity to other antileukemic agents. ARID5B downregulation significantly inhibited ALL cell proliferation and caused partial cell-cycle arrest. At the molecular level, the cell-cycle checkpoint regulator p21 (encoded by CDKN1A) was most consistently modulated by ARID5B, plausibly as its direct transcription regulation target.

Conclusions:
Our data indicate that ARID5B is an important molecular determinant of antimetabolite drug sensitivity in ALL, in part, through p21-mediated effects on cell-cycle progression.
An Unbiased Proteomics Method to Assess the Maturation of Human Pluripotent Stem Cell–Derived Cardiomyocytes
Authors: Cai Wenxuan , Zhang Jianhua , de Lange Willem J. , Gregorich Zachery R. , Karp Hannah , Farrell Emily T. , Mitchell Stanford D. , Tucholski Trisha , Lin Ziqing , Biermann Mitch , McIlwain Sean J. , Ralphe J. Carter , Kamp Timothy J. , Ge Ying 
Published: October 2019

Rationale:
Human pluripotent stem cell (hPSC)–derived cardiomyocytes exhibit the properties of fetal cardiomyocytes, which limits their applications. Various methods have been used to promote maturation of hPSC-cardiomyocytes; however, there is a lack of an unbiased and comprehensive method for accurate assessment of the maturity of hPSC-cardiomyocytes.

Objective:
We aim to develop an unbiased proteomics strategy integrating high-throughput top-down targeted proteomics and bottom-up global proteomics for the accurate and comprehensive assessment of hPSC-cardiomyocyte maturation.

Methods and Results:

Utilizing hPSC-cardiomyocytes from early- and late-stage 2-dimensional monolayer culture and 3-dimensional engineered cardiac tissue, we demonstrated the high reproducibility and reliability of a top-down proteomics method, which enabled simultaneous quantification of contractile protein isoform expression and associated post-translational modifications. This method allowed for the detection of known maturation-associated contractile protein alterations and, for the first time, identified contractile protein post-translational modifications as promising new markers of hPSC-cardiomyocytes maturation. Most notably, decreased phosphorylation of α-tropomyosin was found to be associated with hPSC-cardiomyocyte maturation. By employing a bottom-up global proteomics strategy, we identified candidate maturation-associated markers important for sarcomere organization, cardiac excitability, and Ca
2+
homeostasis. In particular, upregulation of myomesin 1 and transmembrane 65 was associated with hPSC-cardiomyocyte maturation and validated in cardiac development, making these promising markers for assessing maturity of hPSC-cardiomyocytes. We have further validated α-actinin isoforms, phospholamban, dystrophin, αB-crystallin, and calsequestrin 2 as novel maturation-associated markers, in the developing mouse cardiac ventricles.

Conclusions:
We established an unbiased proteomics method that can provide accurate and specific assessment of the maturity of hPSC-cardiomyocytes and identified new markers of maturation. Furthermore, this integrated proteomics strategy laid a strong foundation for uncovering the molecular pathways involved in cardiac development and disease using hPSC-cardiomyocytes.
100 Years of Progress in Cloud Physics, Aerosols, and Aerosol Chemistry Research
Authors: Kreidenweis Sonia M. , Petters Markus , Lohmann Ulrike 
Published: October 2019

AbstractThis chapter reviews the history of the discovery of cloud nuclei and their impacts on cloud microphysics and the climate system. Pioneers including John Aitken, Sir John Mason, Hilding Köhler, Christian Junge, Sean Twomey, and Kenneth Whitby laid the foundations of the field. Through their contributions and those of many others, rapid progress has been made in the last 100 years in understanding the sources, evolution, and composition of the atmospheric aerosol, the interactions of particles with atmospheric water vapor, and cloud microphysical processes. Major breakthroughs in measurement capabilities and in theoretical understanding have elucidated the characteristics of cloud condensation nuclei and ice nucleating particles and the role these play in shaping cloud microphysical properties and the formation of precipitation. Despite these advances, not all their impacts on cloud formation and evolution have been resolved. The resulting radiative forcing on the climate system due to aerosol–cloud interactions remains an unacceptably large uncertainty in future climate projections. Process-level understanding of aerosol–cloud interactions remains insufficient to support technological mitigation strategies such as intentional weather modification or geoengineering to accelerating Earth-system-wide changes in temperature and weather patterns.
Meta-Analysis Comparing Steroids and Diuretics in the Treatment of Acute Low-Tone Sensorineural Hearing Loss
Authors: Zhu Yueying , Li Guangqi , Zhuang Huiwen , Yang Zijun , Sun JinCangjian , Xiong Guangxia , Wang Xianren 
Published: October 2019

Objective: Our objective was to perform a meta-analysis to compare the effectiveness of steroids and diuretics in the treatment of acute low-tone sensorineural hearing loss (ALHL). Methods: PubMed, Google Scholar, and Sci databases were searched for randomized controlled trials (RCTs) examining the treatment of ALHL with steroids and diuretics. The Cochrane Reviewer’s Handbook 5.0 evaluation criteria were used to evaluate the quality of the included RCTs. Meta-analysis was performed using Revman 5.3 software to compare the recovery rate of low-tone hearing levels between patients treated with steroids and diuretics. Results: A total of 3 RCTs were included. There was no heterogeneity between the 3 studies (χ2 = 2.61, P = .27, I2 = 23%); thus, a fixed-effects model of analysis was used. Meta-analysis showed there was no significant difference in the recovery rate of patients treated with steroids and those treated with diuretics (odds ratio = 1.48, 95% confidence interval: 0.64-3.40, P = .36). Conclusion: Steroids and diuretics are equally effective for the treatment of ALHL.
Clinical manifestations and outcome analysis of invasive pulmonary aspergillosis infection: a retrospective study in 43 nonneutropenic patients
Authors: Zhang Lihong , Che Chunli 
Published: October 2019

Objective To investigate clinical characteristics of early-onset invasive pulmonary aspergillosis (IPA) in nonneutropenic patients. Methods Retrospective analysis was used to investigate clinical manifestations and auxiliary examination characteristics in 43 patients with IPA and 51 patients with community-acquired pneumonia in the early stage. Results Risk factors of IPA were dust and mold exposure, bronchiectasis, old pulmonary tuberculosis, and nasosinusitis. The incidence rate of complex clinical manifestations was 60.47% during the first week of IPA. The incidence rate of white blood cell (WBC) count >20.0 × 109/L was 51.16%. Lung CT findings indicated incidence rates of single or multiple nodules with a halo sign and central airway expansion with ground glass opacity were 27.9% and 37.21%, respectively. Mortality rates of patients with IPA given empirical and targeted antifungal treatments were 12.0% and 42.9%, respectively. Conclusions Bronchiectasis, old pulmonary tuberculosis, nasosinusitis, and dust and mold exposure may increase the risk of IPA. Single or multiple nodules with a halo sign and central airway expansion with ground glass opacity may be early-stage lung CT findings in patients with IPA. A WBC count >20.0 × 109/L may aid in early diagnosis, and empirical antifungal therapy may reduce mortality in patients with IPA.
Symptomatic Venous Thromboembolism After Achilles Tendon Rupture: A Nationwide Danish Cohort Study of 28,546 Patients With Achilles Tendon Rupture
Authors: Pedersen Melissa Hornbæk , Wahlsten Liv Riisager , Grønborg Henrik , Gislason Gunnar Hilmar , Petersen Michael Mørk , Bonde Anders Nissen 
Published: October 2019

Background: Venous thromboembolism (VTE) is a well-known complication of Achilles tendon rupture (ATR) and carries a high risk of morbidity and mortality. Although routine thromboprophylaxis for patients with ATR is not recommended, sparse knowledge is available regarding risk factors associated with VTE in patients with ATR. Purpose: To use Danish nationwide registers to identify incidence rates for symptomatic VTE and risk factors associated with increased risk of developing VTE in patients with ATR. Study Design: Cohort study; Level of evidence, 3. Methods: By crosslinking nationwide registers, we identified all patients with diagnosed ATR in Denmark from 1997 to 2015. We stratified patients into 4 groups by age and treatment modality (ie, operative vs nonoperative treatment). The main outcome was VTE within 180 days. We calculated crude incidence rates and considered age, sex, year, comorbidities, and medications as risk factors for VTE in Poisson regression models. Results: We identified 28,546 patients with ATR, of whom 389 (1.36%) were hospitalized with VTE during the follow-up period: 278 due to deep vein thromboses and 138 due to pulmonary embolism. Incidence rates were highest during the first month and ranged from 4.6 to 14.6 events per 100 person-years. VTEs were most frequent among nonoperatively treated patients aged ≥50 years. In Poisson regression analyses, having had VTE beforehand was associated with an increased risk of VTE, as was male sex in the nonoperative treatment group aged ≥50 years; among women <50 years of age, hormonal contraceptives led to a 4- to 6-fold higher risk of VTE compared with patients in the same group without the equivalent risk factor. Conclusion: In this nationwide cohort of patients with ATR, 1.36% developed symptomatic VTE during follow-up. Hormonal contraception, previous VTE, older age group, and male sex increased the risk of VTE. Taken together, the results of the present study suggest that focus on risk stratification and initiatives to prevent VTE might be warranted. A randomized controlled trial could answer this question.
Phage constructs targeting gonadotropin-releasing hormone for fertility control: evaluation in cats
Authors: Johnson Aime K , Jones Rebecca L , Kraneburg Carol J , Cochran Anna M , Samoylov Alexandre M , Wright James C , Hutchinson Cynthia , Picut Catherine , Cattley Russell C , Martin Douglas R , Samoylova Tatiana I 
Published: October 2019

Objectives Phage–gonadotropin-releasing hormone (GnRH) constructs with potential contraceptive properties were generated in our previous study via selection from a phage display library using neutralizing GnRH antibodies as selection targets. In mice, these constructs invoked the production of antibodies against GnRH and suppressed serum testosterone. The goal of this study was to evaluate this vaccine against GnRH for its potential to suppress reproductive characteristics in cats. Methods Sexually mature male cats were injected with a phage–GnRH vaccine using the following treatment groups: (1) single phage–GnRH vaccine with adjuvant; (2) phage–GnRH vaccine without adjuvant and half-dose booster 1 month later; or (3) phage–GnRH vaccine with adjuvant and two half-dose boosters with adjuvant 3 and 6 months later. Anti-GnRH antibodies and serum testosterone, testicular volume and sperm characteristics were evaluated monthly for 7–9 months. Results All cats developed anti-GnRH antibodies following immunization. Serum antibody titers increased significantly after booster immunizations. In group 3, serum testosterone was suppressed 8 months after primary immunization. Total testicular volume decreased in group 1 by 24–42% and in group 3 by 15–36% at 7 months after immunization, indicating potential gonadal atrophy. Vacuolation of epididymides was observed histologically. Although all cats produced sperm at the conclusion of the study, normal morphology was decreased as much as 38%. Phage alone produced no local or systemic reactions. Immunization of phage with AdjuVac produced unacceptable injection site reactions. Conclusions and relevance Our phage-based vaccine against GnRH demonstrated a potential for fertility impairment in cats. Future research is required to optimize vaccine regimens and identify animal age groups most responsive to the vaccine. If permanent contraception (highly desirable in feral and shelter cats) cannot be achieved, the vaccine has a potential use in zoo animals or pets where multiple administrations are more practical and/or reversible infertility is desirable.
Novel USH1G homozygous variant underlying USH2-like phenotype of Usher syndrome
Authors: D’Esposito Fabiana , Randazzo Viviana , Cennamo Gilda , Centore Nicola , Maltese Paolo Enrico , Malesci Rita , D’Andrea Luca , Bertelli Matteo , Marciano Elio , de Crecchio Giuseppe , Pioppo Antonino , Magli Adriano , Cordeiro Maria Francesca 
Published: October 2019

Purpose: Usher syndrome (USH) is an autosomal recessive disorder characterized by congenital sensorineural hearing impairment and retinitis pigmentosa. Classification distinguishes three clinical types of which type I (USH1) is the most severe, with vestibular dysfunction as an added feature. To date, 15 genes and 3 loci have been identified with the USH1G gene being an uncommon cause of USH. We describe an atypical USH1G-related phenotype caused by a novel homozygous missense variation in a patient with profound hearing impairment and relatively mild retinitis pigmentosa, but no vestibular dysfunction. Methods: A 26-year-old female patient with profound congenital sensorineural hearing loss, nyctalopia and retinitis pigmentosa was studied. Audiometric, vestibular and ophthalmologic examination was performed. A panel of 13 genes was tested by next-generation sequencing (NGS). Results: While the hearing loss was confirmed to be profound, the vestibular function resulted normal. Although typical retinitis pigmentosa was present, the age at onset was unusually late for USH1 syndrome. A novel homozygous missense variation (c.1187T>A, p.Leu396Gln) in the USH1G gene has been identified as causing the disease in our patient. Conclusions: Genetic and phenotypic heterogeneity are very common in both isolated and syndromic retinal dystrophies and sensorineural hearing loss. Our findings widen the spectrum of USH allelic disorders and strength the concept that variants in genes that are classically known as underlying one specific clinical USH subtype might result in unexpected phenotypes.
Risk of cancer among multiple sclerosis patients, siblings, and population controls: A prospective cohort study
Authors: Grytten Nina , Myhr Kjell-Morten , Celius Elisabeth G , Benjaminsen Espen , Kampman Margitta , Midgard Rune , Vatne Anita , Aarseth Jan H , Riise Trond , Torkildsen Øivind 
Published: October 2019

Background: Risk of cancer in multiple sclerosis (MS) patients compared to their siblings is unknown. Objective: The objective was to prospectively investigate the risk of cancer among MS patients compared to siblings without MS and to population controls. Methods: We retrieved data on MS patients born between 1930 and 1979 from the Norwegian Multiple Sclerosis Registry and population studies and on cancer diagnosis from the Cancer Registry of Norway. We used adjusted Cox proportional hazard regression to estimate cancer risk among 6883 MS patients, 8918 siblings without MS, and 37,919 population controls. Results: During 65 years of follow-up, cancer risk among MS patients was higher than that among population controls (hazard ratio (HR) = 1.14, 95% confidence interval (CI): 1.05–1.23) in respiratory organs (HR = 1.66, 95% CI: 1.26–2.19), urinary organs (HR = 1.51, 95% CI: 1.12–2.04), and the central nervous system (HR = 1.52, 95% CI: 1.11–2. 09). Siblings had higher risk of hematological cancers compared with MS patients (HR = 1.82, 95% CI: 1.21–2.73) and population controls (HR = 1.72, 95% CI: 1.36–2.18). Conclusion: MS patients were associated with increased risk of cancer compared to population controls. Siblings had increased risk of hematological cancer. This indicates that MS and hematological cancer could share a common etiology.