bluuebunny/crossref_metadata_2025_split huggingface dataset:
Angioimmunoblastic T-Cell Lymphoma: Patient Characteristics and Survival Outcomes
Authors: Ermann Daniel A. , Vardell Victoria A. , Silberstein Peter T. 
Published: November 2019

Background
Angioimmunoblastic T-cell lymphoma (AITL) is a rare and aggressive malignancy, representing approximately 18.5% of Peripheral T-cell lymphomas. The clinical presentation varies greatly, and literature describing this disease is limited. In this study we utilized the National Cancer Database (NCDB) to describe the patient characteristics, demographics, and overall survival of AITL.
Methods
The NCDB for non-Hodgkin's lymphoma was used to identify 3,708 patients diagnosed with AITL between 2004 and 2016. We examined demographic information including age, race, gender, stage, and treatment modality. Kaplan-Meier analysis was used to analyze overall survival and compare survival by patient age, stage, and year of diagnosis. Bivariate and multivariate analysis was used to obtain hazard ratios and assess the association of patient characteristics and treatment methods with survival.
Results
The majority of AITL patients were white 87.8%, males 53%, with an average age of 67 years. 90% of patients received treatment, with 77.4% receiving chemotherapy, 10.8% receiving hematopoietic transplant, and 2.6% receiving radiation. B symptoms were present in 57% of patients. 43% were diagnosed with Stage III disease and 43.5% at Stage IV.
Median survival was 22 months (CI 19.7-24.4), with a five- and ten-year survival of 30% and 22%. Median survival for patients aged 35-50 was 74 months, 50-65 was 37.7 months, 65-80 was 20.5 months, and for patients aged >80 years old median survival was 6.4 months. Patients with Stage I disease survived 35.1 months whereas those with Stage IV disease survived 17.2 months. On multivariate analysis black race, increasing age, charleson-deyo comorbidity score, and stage at diagnoses were significantly associated with increased mortality risk. All forms of treatment, including chemotherapy, hematopoietic transplant, and radiation were all associated with improved survival.
Discussion
Our study found that the majority of AITL patients present with late stage disease, often with B symptoms, and have poor prognosis. We found a five-year survival of 30% for this malignancy when all stages of disease were combined. Knowledge of the patient characteristics, treatment modalities, and overall survival in AITL can serve to enhance the care of providers who encounter this uncommon diagnosis.

Disclosures
No relevant conflicts of interest to declare.
Hemoglobin Levels Vary in Infants in Relation in Occurrence of Influenza Virus Infections
Authors: Adamkiewicz Tom , Dada Omolaya , O'Neil Patrick , Wong Erica , Tran McKinley 
Published: November 2019

Iron deficiency anemia (IDA) screening in children, and its treatment is standard in general pediatrics. IDA has been linked to developmental concerns. However, iron supplementation recently has been shown to have risks in resource limited environments as it seems to be associated with increased risks of infections. The role of iron in bacterial survival is well established. However more difficult to explain are reports linking iron supplementation to higher rates of respiratory illness in children. Recent studies have identified hepcidin as an important mediator between inflammation from common infections, and iron repletion status (Prentice et al 2019). In the current study we hypothesized that overall hemoglobin levels in infants may fluctuate depending on birth cohorts, as 1) exposure to respiratory illnesses peaks in winter months, and 2) children aged 6-12 months have the highest incidence of respiratory illness of all age groups (up to 6-8 upper respiratory infections per year). Institutional review board permission (Children Health Care of Atlanta), was obtained and the billing registry, laboratory and patient records from an multiethinic urban clinic (n= 7,616) were reviewed. Influenzas' infection was defined as a patient presenting with an acute illness and a positive rapid influenza test. Hemoglobin was obtained at 9 to 12 months routine visit by capillary draw and point of care measure (HemoCue hb). A total of 1236 patient files were reviewed from 2007 until 2018. Each year was examined separately and then overlapped. Influenza rates were lowest in the summer, rose starting September, and peaked during the winter months. In the first year of life, hemoglobin levels peaked in March, with lowest levels observed in July and December. Infants with a diagnosis of influenza had lower hemoglobin levels and more pronounced fluctuations. At age 7-9 months, medial hemoglobin was 12.1 (95% confidence interval [CI] ±0.026) g/dl and for those infected with influenza 9.8% 95% CI ±0.138). These observations have implications regarding screening, lower limits of normal may vary during the year. supplement. Other viruses also occur during the winter months and could play a role. These results require further validations.
Figure

Disclosures
No relevant conflicts of interest to declare.
Copper Deficiency and Cytopenia: A Systematic Review
Authors: Kharel Prakash , Gnanapandithan Karthik , Pandey Ramesh Kumar , Jha Samir , Grimshaw Alyssa , Giri Smith 
Published: November 2019

Copper Deficiency and Cytopenia: A Systematic Review
Prakash Kharel, Karthik Gnanapandithan, Ramesh Kumar Pandey, Samir Jha, Alyssa Grimshaw, Smith Giri
Introduction: Copper deficiency is rare in humans unless there is a condition that affects either copper uptake or metabolism, or dietary deficiency. However, the incidence appears to be rising due to increasing gastric bypass surgery and total parenteral nutrition (TPN) use. Published data on hematological manifestations due to copper deficiency are limited to case reports, case series and small retrospective studies, creating confusion among clinicians and hematologists. We performed a systematic review of all published case reports and series to characterize hematological manifestations associated copper deficiency with a focus on risk factors, clinical manifestations, treatments and outcomes.
Methods:
Using a combination of free text and controlled vocabulary, a systematic search of the electronic literature using MEDLINE and EMBASE for published material from inception to March 2019 was performed. Two authors independently screened the titles, abstracts, and the full text of the selected papers. Subsequently, the full text of each article was assessed for eligibility and details. From the 97 reports, we included 116 cases in which the clinical course, management and outcomes were described.
Results: Of 5374 articles screened, a total of 268 articles were selected for full text review and a total of 97 reports describing 116 cases met our eligibility criteria. The median age at the time of presentation was 44 (interquartile range (IQR) 25-57) year, and 64 (55%) were males. Total of 37(32 %) had coexisting neurological symptoms. The median Hb was 7.7 gm/dl (IQR 6.2-9.5) and median WBC 2.3 (1.6-3.1). 94 (81%) of the patients had hemoglobin (Hb)< 10, 41(35%) had severe anemia Hb <7 at presentation. 80(69%) had leukopenia with white blood cell (WBC) <4K, of them only one patient had lymphopenia (1.28%), rest had neutropenia (98.72 %). Nearly half of these patients had macrocytic anemia (38, 55%) and only 3 cases had microcytic anemia. Of 78 patients with available data, 23(29%) had low platelet counts and 8 (10 %) had elevated platelet count. Zinc excess was implicated in almost half of these cases (39/87, 45%) and total parenteral nutrition (TPN) in 9 out of 87 cases (10%)
Conclusion:
Copper deficiency should be one of the reflexes in evaluation of patient who is at risk of copper deficiency specially as there is rise of bariatric surgery, survivors of significant bowel surgery patient requiring total parenteral nutrition or jejunal feed along with the baby boomers who will be the high number of patients using dentures and patient on zinc supplementation. There should always be a high degree of suspicion among clinicians when dealing with at-risk individuals to prevent irreversible complications and morbidity.

Disclosures
No relevant conflicts of interest to declare.
Clinical implications of incidental venous thromboembolism in cancer patients
Authors: Mulder Frits I. , Di Nisio Marcello , Ay Cihan , Carrier Marc , Bosch Floris T.M. , Segers Annelise , Kraaijpoel Noémie , Grosso Michael A. , Zhang George , Verhamme Peter , Wang Tzu-Fei , Weitz Jeffrey I. , Middeldorp Saskia , Raskob Gary , Beenen Ludo F.M. , Büller Harry R. , van Es Nick 
Published: November 2019

IntroductionIn cancer patients, current guidance suggests similar treatment for incidental and symptomatic venous thromboembolism (VTE), mainly based on retrospective data. We aimed to evaluate anticoagulant therapy in cancer patients with incidental and symptomatic VTE.MethodsThe Hokusai VTE Cancer Study was a randomised controlled trial comparing edoxaban with dalteparin for cancer-associated VTE. The primary outcome was the composite of first recurrent VTE or major bleeding. Secondary outcomes included major bleeding, recurrent VTE and mortality. Outcomes in patients with incidental and symptomatic VTE were evaluated during the 12-month study period.Results331 patients with incidental VTE and 679 patients with symptomatic VTE were enrolled, of whom the index event was confirmed by an independent radiologist. Median durations of anticoagulant treatment were 195 and 189 days, respectively. In patients with incidental VTE, the primary outcome occurred in 12.7% of patients, major bleeding in 6.6% of patients and recurrent VTE in 7.9% of patients. Out of the 26 VTE recurrences in patients with incidental VTE, five (31%) were incidental, seven (44%) were symptomatic and four (25%) were deaths for which pulmonary embolism could not be ruled out. In patients with symptomatic VTE, the primary outcome occurred in 13.8% of patients, major bleeding in 4.9% of patients and recurrent VTE in 10.9% of patients. All-cause mortality was similar in both groups.ConclusionClinical adverse outcomes are substantial in both cancer patients with incidental and symptomatic VTE, supporting current guideline recommendations that suggest treating incidental VTE in the same manner as symptomatic VTE.
The proteolytic activity of Listeria monocytogenes HtrA
Authors: Abfalter Carmen M. , Bernegger Sabine , Jarzab Miroslaw , Posselt Gernot , Ponnuraj Karthe , Wessler Silja 
Published: November 2019

Abstract
Background
High temperature requirement A (HtrA) is a widely expressed chaperone and serine protease in bacteria. HtrA proteases assemble and hydrolyze misfolded proteins to enhance bacterial survival under stress conditions. Listeria monocytogenes (L. monocytogenes) is a foodborne pathogen that induces listeriosis in humans. In previous studies, it was shown that deletion of htrA in the genome of L. monocytogenes increased the susceptibility to cellular stress and attenuated virulence. However, expression and protease activity of listerial HtrA (LmHtrA) were never analyzed in detail.

Results
In this study, we cloned LmHtrA wildtype (LmHtrAwt) and generated a proteolytic inactive LmHtrASA mutant. Recombinant LmHtrAwt and LmHtrASA were purified and the proteolytic activity was analyzed in casein zymography and in vitro cleavage assays. LmHtrA activity could be efficiently blocked by a small molecule inhibitor targeting bacterial HtrA proteases. The expression of LmHtrA was enhanced in the stationary growth phase of L. monocytogenes and significantly contributed to bacterial survival at high temperatures.

Conclusions
Our data show that LmHtrA is a highly active caseinolytic protease and provide a deeper insight into the function and mechanism, which could lead to medical and biotechnological applications in the future.
Functional characterization of a liverworts bHLH transcription factor involved in the regulation of bisbibenzyls and flavonoids biosynthesis
Authors: Zhao Yu , Zhang Yu-Ying , Liu Hui , Zhang Xiao-Shuang , Ni Rong , Wang Piao-Yi , Gao Shuai , Lou Hong-Xiang , Cheng Ai-Xia 
Published: November 2019

AbstractBackgroundThe basic helix-loop-helix (bHLH) transcription factors (TFs), as one of the largest families of TFs, play important roles in the regulation of many secondary metabolites including flavonoids. Their involvement in flavonoids synthesis is well established in vascular plants, but not as yet in the bryophytes. In liverworts, both bisbibenzyls and flavonoids are derived through the phenylpropanoids pathway and share several upstream enzymes.ResultsIn this study, we cloned and characterized the function of PabHLH1, a bHLH family protein encoded by the liverworts speciesPlagiochasma appendiculatum. PabHLH1 is phylogenetically related to the IIIf subfamily bHLHs involved in flavonoids biosynthesis. A transient expression experiment showed that PabHLH1 is deposited in the nucleus and cytoplasm, while the yeast one hybrid assay showed that it has transactivational activity. When PabHLH1 was overexpressed inP. appendiculatumthallus, a positive correlation was established between the content of bibenzyls and flavonoids and the transcriptional abundance of corresponding genes involved in the biosynthesis pathway of these compounds. The heterologous expression of PabHLH1 inArabidopsis thalianaresulted in the activation of flavonoids and anthocyanins synthesis, involving the up-regulation of structural genes acting both early and late in the flavonoids synthesis pathway. The transcription level of PabHLH1 inP. appendiculatumthallus responded positively to stress induced by either exposure to UV radiation or treatment with salicylic acid.ConclusionPabHLH1 was involved in the regulation of the biosynthesis of flavonoids as well as bibenzyls in liverworts and stimulated the accumulation of the flavonols and anthocyanins in Arabidopsis.
Dynamic predictive accuracy of electrocardiographic biomarkers of sudden cardiac death within a survival framework: the Atherosclerosis Risk in Communities (ARIC) study
Authors: Perez-Alday Erick A. , Bender Aron , German David , Mukundan Srini V. , Hamilton Christopher , Thomas Jason A. , Li-Pershing Yin , Tereshchenko Larisa G. 
Published: November 2019

AbstractBackgroundThe risk of sudden cardiac death (SCD) is known to be dynamic. However, the accuracy of a dynamic SCD prediction is unknown. We aimed to measure the dynamic predictive accuracy of ECG biomarkers of SCD and competing non-sudden cardiac death (non-SCD).MethodsAtherosclerosis Risk In Community study participants with analyzable ECGs in sinus rhythm were included (n = 15,716; 55% female, 73% white, age 54.2 ± 5.8 y). ECGs of 5 follow-up visits were analyzed. Global electrical heterogeneity and traditional ECG metrics (heart rate, QRS, QTc) were measured. Adjudicated SCD was the primary outcome; non-SCD was the competing outcome. Time-dependent area under the receiver operating characteristic curve (ROC(t) AUC) analysis was performed to assess the prediction accuracy of a continuous biomarker in a period of 3,6,9 months, and 1,2,3,5,10, and 15 years using a survival analysis framework. Reclassification improvement as compared to clinical risk factors (age, sex, race, diabetes, hypertension, coronary heart disease, stroke) was measured.ResultsOver a median 24.4 y follow-up, there were 577 SCDs (incidence 1.76 (95%CI 1.63–1.91)/1000 person-years), and 829 non-SCDs [2.55 (95%CI 2.37–2.71)]. No ECG biomarkers predicted SCD within 3 months after ECG recording. Within 6 months, spatial ventricular gradient (SVG) elevation predicted SCD (AUC 0.706; 95%CI 0.526–0.886), but not a non-SCD (AUC 0.527; 95%CI 0.303–0.75). SVG elevation more accurately predicted SCD if the ECG was recorded 6 months before SCD (AUC 0.706; 95%CI 0.526–0.886) than 2 years before SCD (AUC 0.608; 95%CI 0.515–0.701). Within the first 3 months after ECG recording, only SVG azimuth improved reclassification of the risk beyond clinical risk factors: 18% of SCD events were reclassified from low or intermediate risk to a high-risk category. QRS-T angle was the strongest long-term predictor of SCD (AUC 0.710; 95%CI 0.668–0.753 for ECG recorded within 10 years before SCD).ConclusionShort-term and long-term predictive accuracy of ECG biomarkers of SCD differed, reflecting differences in transient vs. persistent SCD substrates. The dynamic predictive accuracy of ECG biomarkers should be considered for competing SCD risk scores. The distinction between markers predicting short-term and long-term events may represent the difference between markers heralding SCD (triggers or transient substrates) versus markers identifying persistent substrate.
Age at menarche and risk of multiple sclerosis (MS): a systematic review and meta-analysis
Authors: Azimi Amirreza , Hanaei Sara , Sahraian Mohammad Ali , Mohammadifar Mehdi , Ramagopalan Sreeram V. , Ghajarzadeh Mahsa 
Published: November 2019

Abstract
Background
Some studies have looked at the age at menarche and risk of Multiple Sclerosis (MS).We aimed to conduct a systematic review and meta-analysis to estimate a pooled odds ratio of developing MS by increasing age at menarche.

Methods
We searched PubMed, Scopus, EMBASE, CINAHL, Web of Science, Ovid, google scholar and gray literature (references of references, congress abstracts) up to 10th April 2019.

Results
The literature search found 312 articles. After eliminating duplicates, reviews, case reports and trials, 18 articles remained. Three articles were ultimately included in the final analysis. Two studies were from Iran, and one from Canada. The pooled odds ratio (OR) for increasing 1 year of age at menarche was 0.88 (95% CI:0.82-0.94), with no significant heterogeneity (I2 = 49%, p = 0.1). Mean age at menarche was significantly different between case and control groups (mean difference = − 0.22, 95% CI = -0.42,-0.02).

Conclusion
The result of this systematic review showed that the risk of MS decreases by increasing age at menarche.
Relationship between WBRT total dose, intracranial tumor control, and overall survival in NSCLC patients with brain metastases - a single-center retrospective analysis
Authors: Li Zhensheng , Shen Dongxing , Zhang Jian , Zhang Jun , Yang Fang , Kong Deyou , Kong Jie , Zhang Andu 
Published: November 2019

Abstract
Background
The relationship between whole brain radiotherapy (WBRT) dose with intracranial tumor control and overall survival (OS) in patients with non-small cell lung cancer (NSCLC) brain metastases (BM) is largely unknown.

Methods
We retrospectively analyzed 595 NSCLC BM patients treated consecutively at the Fourth Hospital of Hebei Medical University between 2013 to 2015. We assigned the patients into 4 dose groups of WBRT: none, < 30, 30–39, and ≥ 40 Gy and assessed their relationship with OS and intracranial progression-free survival (iPFS). Cox models were utilized. Covariates included sex, age, KPS, BM lesions, extracranial metastasis, BM and lung tumor resection, chemotherapy, targeted therapy, and focal radiotherapy modalities.

Results
Patients had a mean age of 59 years and were 44% female. Their median survival time (MST) of OS and iPFS were 9.3 and 8.9 months. Patients receiving none (344/58%), < 30 (30/5%), 30–39 (93/16%), and ≥ 40 (128/22%) Gy of WBRT had MST of OS (iPFS) of 7.3 (6.8), 6.0 (5.4), 10.3 (11.9) and 11.9 (11.9) months, respectively. Compared to none, other WBRT groups had adjusted HRs for OS - 1.23 (p > 0.20), 0.72 (0.08), 0.61 (< 0.00) and iPFS - 1.63 (0.03), 0.71 (0.06), 0.67 (< 0.01). Compared to 30–39 Gy, WBRT dose ≥40 Gy was not associated with improved OS and iPFS (all p > 0.40). Stratified analyses by 1–3 and ≥ 4 BM lesions and adjustment analyses by each prognostic index of RPA class, Lung-GPA and Lung-molGPA supported these relationships as well.

Conclusions
Compared to none, WBRT doses ≥30 Gy are invariably associated with improved intracranial tumor control and survival in NSCLC BM patients.
Anxiety at age 15 predicts psychiatric diagnoses and suicidal ideation in late adolescence and young adulthood: results from two longitudinal studies
Authors:   NTR, Doering Sabrina , Lichtenstein Paul , Gillberg Christopher , Middeldorp Christel M. , Bartels Meike , Kuja-Halkola Ralf , Lundström Sebastian 
Published: November 2019

Abstract
Background
Anxiety disorders in adolescence have been associated with several psychiatric outcomes. We sought to describe the prospective relationship between various levels of adolescent anxiety and psychiatric diagnoses (anxiety-, bipolar/psychotic-, depressive-, and alcohol and drug misuse disorders) and suicidal ideation in early adulthood while adjusting for childhood attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and developmental coordination disorder (DCD). Furthermore, we aimed to estimate the proportion attributable to the various anxiety levels for the outcomes.

Methods
We used a nation-wide population-based Swedish twin study comprising 14,106 fifteen-year-old twins born in Sweden between 1994 and 2002 and a replication sample consisting of 9211 Dutch twins, born between 1985 and 1999. Adolescent anxiety was measured with parental and self-report. Psychiatric diagnoses and suicidal ideation were retrieved from the Swedish National Patient Register and via self-report.

Results
Adolescent anxiety, of various levels, predicted, in the Swedish National Patient Register, anxiety disorders: hazard ratio (HR) = 4.92 (CI 3.33–7.28); depressive disorders: HR = 4.79 (3.23–7.08), and any psychiatric outcome: HR = 3.40 (2.58–4.48), when adjusting for ADHD, ASD, and DCD. The results were replicated in the Dutch data. The proportion of psychiatric outcome attributable to adolescent anxiety over time (age 15–21) was 29% for any psychiatric outcome, 43–40% for anxiety disorders, and 39–38% for depressive disorders.

Conclusion
Anxiety in adolescence constitutes an important risk factor in the development of psychiatric outcomes, revealing unique predictions for the different levels of anxiety, and beyond the risk conferred by childhood ADHD, ASD, and DCD. Developmental trajectories leading into psychiatric outcomes should further empirically investigated.