bluuebunny/crossref_metadata_2025_split huggingface dataset:
The genetic basis for medium‐dependent bacteriophage infection
Authors: Weiner Iddo Nadav 
Published: April 2020

While broad spectrum antibiotics have served a major role in combatting bacterial pathogens over the past decades, we are currently witnessing the rise of antibiotic‐resistant pathogenic strains. Moreover, the harmful effects of broad spectrum antibiotics on the natural human microbiome have been demonstrated in numerous cases. For these reasons, bacteriophages have been recently gaining attention as promising candidates for treatment of bacterial‐related diseases. Bacteriophages are natural viruses that infect and often kill specific bacterial strains; it is the phages’ high accuracy and specificity, alongside their natural origin, that highlights their value as an alternative treatment for diseases with bacterial involvement.However, a major challenge in screening for bacteriophages relevant for treatment of human diseases is the phages’ medium‐dependent infection trait. Several factors have been suggested to take a role in explaining this discrepancy, including the mechanism of infection, the spatial structure of the phage capsid, the biochemical characteristics of the bacterial cell wall, and other phage life‐cycle features. However, a comprehensive model for characterizing the media‐range for phage infection is still missing. This uncertainty often translates into multiple laborious screening rounds, since common practice in vitro assays are typically based on either liquid or solid medium infection, whereas the state of matter relevant for in vivo application is often hard to determine; thus, one must screen the same phages using multiple assays.In attempt to lay the groundwork for such a model, in this work we set out to determine the genetic‐basis for medium‐dependent infection of pathogenic Klebsiella pneumoniae phages. To this end we obtained 285 K. pneumonia strains, that span across the entire domain of known K. pneumonia genotypes. Subsequently we obtained 50 phages that were able to propagate on at least some of these hosts. For each phage‐host pair we determined whether infection occurs in two different assays: in liquid culture, and on solid agar plates. As expected, the results show that liquid medium enables more phage infections compared to solid; this is traditionally associated with the higher mobility enabled by the liquid. However, cases where a phage was able to infect its host in solid, but not in liquid, were observed as well. Finally, by analyzing genomic differences between the phages in the experiment we were able to discern several genetic features that correlate with the observed phenotype. Further exploration of these genetic features are the basis for a constructing a model for characterizing the media‐range for phage infection.
Mitochondrial Signatures in Circulating Extracellular Vesicles of Older Adults with Parkinson’s Disease: Results from the EXosomes in PArkiNson’s Disease (EXPAND) Study
Authors: Picca Anna 
Published: April 2020

Systemic inflammation and mitochondrial dysfunction are involved in neurodegeneration in Parkinson’s disease (PD). Extracellular vesicle (EV) trafficking may link inflammation and mitochondrial dysfunction. In the present study, circulating small EVs (sEVs) from 16 older adults with PD and 12 controls were purified and characterized. A panel of circulating inflammatory biomolecules was measured by multiplex immunoassay. Protein levels of three tetraspanins (CD9, CD63, and CD81) and selected mitochondrial markers [adenosine triphosphate 5A (ATP5A), mitochondrial cytochrome C oxidase subunit I (MTCOI), NADH:ubiquinone oxidoreductase subunit B8 (NDUFB8), NADH:ubiquinone oxidoreductase subunit S3 (NDUFS3), succinate dehydrogenase complex iron sulfur subunit B (SDHB), and ubiquinol‐cytochrome C reductase core protein 2 (UQCRC2)] were quantified by immunoblotting. Relative to controls, PD participants showed a greater amount of circulating sEVs. Levels of CD9 and CD63 were lower in the sEV fraction of PD participants, while those of CD81 were similar between groups. Lower levels of ATP5A, NDUFS3, and SDHB were detected in sEVs from PD participants. No signal was retrieved for UQCRC2, MTCOI, or NDUFB8 in either participant group. To identify a molecular signature in circulating sEVs in relationship to systemic inflammation, a low level‐fused (multi‐platform) partial least squares ‐ discriminant analysis was applied. The model correctly classified 94.2±6.1% PD participants and 66.7±5.4% controls, and identified as relevant seven biomolecules (CD9, NDUFS3, C‐reactive protein, fibroblast growth factor 21, interleukin 9, macrophage inflammatory protein 1b, and tumor necrosis factor alpha). In conclusion, a mitochondrial signature was identified in circulating sEVs from older adults with PD, in association with a specific inflammatory profile. In‐depth characterization of sEV trafficking may allow identifying new biomarkers for PD and possible targets for personalized interventions.Support or Funding InformationInnovative Medicine Initiative‐Joint Undertaking (IMI‐JU #115621)
Acute Effects of Caffeinated Chewing Gum on Central Arterial Stiffness and Hemodynamics
Authors: Lapierre Stephanie , Holmer Brady , Lim Jisok , Hwang Chueh-Lung , Sakarya Yasemin , New William , Eagle Michael , Schwartz Cody , Bhattal Gurjaspreet , Maharrey Phillip , Handberg Eileen M. , Alviar Carlos L. , Christou Demetra D. 
Published: April 2020

Caffeine is widely consumed daily as a stimulant, ergogenic aid or performance enhancer. In addition to the traditional forms of caffeine consumption (e.g., coffee, tea and caffeinated soft drinks), alternative sources are becoming increasingly popular such as caffeinated tablets/capsules and gum. Caffeinated chewing gum offers rapid caffeine absorption and is commercially available. Although the acute cardiovascular effects of caffeine consumption from traditional sources are well documented, the effects of caffeinated chewing gum are unknown. Therefore, this double‐blinded, randomized, placebo‐controlled, crossover study sought to investigate the acute effects of caffeinated chewing gum on central arterial stiffness and aortic blood pressure, independent predictors of cardiovascular disease. Sixteen young (21±1 yrs, means±SE), male, light caffeine users, free of clinical disease, who did not use tobacco products, or medications participated in this study. Central arterial stiffness (carotid to femoral pulse wave velocity; cfPWV) and aortic blood pressures (systolic and diastolic blood pressure; aoSBP and aoDBP, and pulse pressure; aoPP) were assessed using SphygmoCor XCEL (AtCor Medical) on two visits, separated by at least one week. During each visit, vascular measures were obtained before, and 1‐ and 2‐hrs following consumption of caffeinated or placebo chewing gum. We found that cfPWV increased at 2‐hrs following consumption of caffeinated chewing gum (6.3±0.1 vs. 6.5±0.1 m·s−1; pre vs. 2‐hrs; P=0.017), but did not change after placebo (P>0.05). AoMAP and aoDBP increased by 6±2 and 6±1 mmHg, respectively, at 1‐hr following caffeinated chewing gum (P≤0.008) and remained elevated at 2‐hrs, but did not change in response to placebo (P>0.05). AoSBP, aoPP and heart rate did not significantly change in response to caffeinated or placebo chewing gum (P>0.05). In conclusion, caffeinated chewing gum acutely increases central arterial stiffness and aortic blood pressure in young healthy men. Future investigations should confirm these findings in women and examine whether the response is exaggerated in individuals who are hypertensive or have other risk factors for cardiovascular disease.Support or Funding InformationThis work was supported by the Gatorade Trust through funds distributed by the University of Florida, Department of Medicine.
Repetitive Sequences Within Human PKD1 Adopt G‐quadruplex Structures
Authors: Larson Erik , Madsen Aimee , Lorber Amy , Dewey John , Alvarado Gloria , Su Kemin 
Published: April 2020

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is caused by the loss of PKD1 expression, leading to the formation of cysts and lethal kidney disease. Human PKD1 appears to be prone to inactivating mutagenesis, but the mechanisms are undefined. Interestingly, murine PKD1 is comparatively stable, and ADPKD does not naturally occur in mice. We have identified extensive guanine quadruplex repeats in human, but not murine, PKD1. Guanine quadruplex (G4) DNA is a four stranded structure that forms from patterns of tandem guanine repeats. It has been identified in gene regulatory domains and is a functional partner with oncogenic rearrangements. The abundance of G4 sequence motifs in human PKD1 implicates G4 structure formation in the mechanism of PKD1 mutagenesis. Therefore, we examined the ability of G4 sequences encoded by PKD1 to adopt G4 structures in vitro. Using more than one biophysical approach, we find that sequence repeats within human PKD1 adopt G4 conformations, but only under physiological conditions and when the G4 sequence motifs are present. The repetitive character of human PKD1 also suggests that non‐canonical G4 sequence motifs support G4 DNA structures in vivo, where they increase the potential for mutagenesis and gene inactivation. Since G4 DNA is already connected with site‐specific genetic instability, the formation of this structure within PKD1 may explain how the gene becomes somatically inactivated, leading to ADPKD.Support or Funding InformationThis research is supported by Western Michigan University Homer Stryker School of Medicine and by the NIH/NIDDK, R15DK119864 to EL
BAP-1 Expression Status by Immunohistochemistry in Cellular Blue Nevus and Blue Nevus–like Melanoma
Authors: Chen Pei-Ling , Neishaboori Nastaran , Tetzlaff Michael T. , Chen Wei-Shen , Aung Phyu P. , Curry Jonathan L. , Nagarajan Priyadharsini , Ivan Doina , Hwu Wen-Jen , Prieto Victor G. , Torres-Cabala Carlos A. 
Published: April 2020

Abstract:
The family of blue nevi includes the common blue nevus (BN), cellular blue nevus (CBN), and atypical BN, while melanomas with BN-like morphology can either arise in association with a blue nevus (MABN) or in the de novo setting mimicking cellular blue nevus (MMCBN). Recent molecular and immunohistochemical studies have demonstrated loss of BAP-1 in MABN/MMCBN but not in BN/CBN, suggesting that loss of BAP-1 correlates with a malignant phenotype in these lesions. In this study, we applied anti–BAP-1 antibodies to a series of CBN/BN (n = 11) and MABN/MMCBN (n = 4). Nuclear BAP-1 expression was detected in the majority of CBN/BN (n = 10/11) but was lost in 1 case. Most cases of MABN/MMCBN showed loss of nuclear BAP-1 expression (n = 3/4), with one case of MMCBN showing preserved BAP-1 expression. Demonstration of BAP-1 loss in a single case of CBN and preservation of BAP-1 expression in 1 case of MMCBN may indicate that detection of alterations in BAP-1 protein expression by immunohistochemistry may not be a completely reliable biomarker for the distinction of BN/CBN from MABN/MMCBN. Further investigation of the significance of BAP-1 loss/preservation in BN-like tumors is warranted.
Immunohistochemical Localization of Phosphorylated and Unphosphorylated Form of β-catenin With Regard to Shadow Cell and Squamous Differentiation in Cutaneous Pilomatricoma
Authors: Nakamura Toshitsugu , Fujiwara Masayuki 
Published: April 2020

Abstract:
Pilomatricoma usually contains a mutation in CTNNB1 that encodes β-catenin (BC). It also shows nuclear accumulation of BC protein, which plays an important role in tumorigenesis of pilomatricoma. In vitro studies have indicated that mutant BC protein is unphosphorylated and shows nuclear accumulation, but this theory has not been confirmed in various tumors with CTNNB1 mutation. We examined immunohistochemical localization of phosphorylated BC (pBC) and unphosphorylated BC (npBC) with regard to the modes of cell death or differentiation in 25 cases of pilomatricoma. As for the component showing shadow cell differentiation, BC was detected in cytoplasm/nucleus and along cell membrane in basaloid cells, whereas only in the latter in transitional cells in all cases. Meanwhile, npBC was localized along cell membrane of transitional cells, but not in basaloid cells, nor in nucleus of any components. The components with squamous differentiation also revealed the staining patterns similar to those seen in shadow cell differentiation in some cases. pBC was found in some cell fragments in the amorphous debris containing apoptotic bodies among shadow cell nests. These results suggested that npBC plays an important role in cell adhesion during differentiation and that pBC expression is associated with apoptosis of basaloid cells in pilomatricoma. BC accumulated in the nucleus was not immunoreactive for npBC possibly due to post-translational modification or conformational changes that resulted in loss of or masked antigenicity when BC is assumed to be unphosphorylated.
mHealth Assessment and Intervention of Depression and Anxiety in Older Adults
Authors: Grossman Jason T. , Frumkin Madelyn R. , Rodebaugh Thomas L. , Lenze Eric J. 
Published: April 2020

AbstractMobile technology is increasingly being used to enhance health and wellness, including in the assessment and treatment of psychiatric disorders. Such applications have been referred to collectively asmHealth, and this article provides a comprehensive review and clinical perspective of research regarding mHealth in late-life mood and anxiety disorders. The novel data collection offered by mHealth has contributed to a broader understanding of psychopathology, to an increased diversity of psychological interventions, and to novel methods of assessment that may ultimately provide individually adaptive mental health care for this population. Older adults face challenges (e.g., transportation, mobility) that limit their ability to receive medical and mental health care services, and mHealth may improve the capacity to reach this population. Although several mobile interventions exist for health-related issues in older adults (e.g., balance, diabetes, medication management), mHealth targeting psychiatric disorders is limited and most often focuses on problems related to dementia, cognitive dysfunction, and memory loss. Given that depression and anxiety are two of the most common mental health concerns among this population, mHealth has strong potential for broad public health interventions that may improve effectiveness of mental health care via individualized assessments and treatments.
The Titanium Angular Clip Prosthesis for Ossicular Chain Reconstruction: Long-Term Results
Authors: Stuermer Konrad Johannes , Hüttenbrink Karl-Bernd , Luers Jan Christoffer 
Published: April 2020

Objectives:
To describe the long-term results of the titanium angular clip prosthesis 10 years after its initial description.

Study Design:
Clinical retrospective study.

Setting:
Tertiary referral center.

Patients:
Sixty three patients with isolated defects of the long process of the incus where the ossicular chain was reconstructed by a titanium angular clip prosthesis.

Interventions:
Therapeutic.

Main Outcome Measures:
The mean air-bone gap was calculated over the frequencies of 0.5, 1, 2, 3, and 4 kHz.

Results:
The placement of the prosthesis was straightforward in all patients, without any complication. During the first follow-up visit after 3 weeks (n = 61) the mean air-bone gap (ABG) was reduced by 10 dB HL, and from 24 dB HL preoperatively to 14 dB HL. At the long-term follow-up appointment—4 years after implantation (n = 29)—the mean ABG was still reduced by 8 dB HL, from a mean of 26 dB HL preoperatively to 18 dB HL.

Conclusion:
The use of the titanium angular clip prosthesis is a safe and reliable way to bridge an isolated erosion of the long process of the incus, leading to significant and long-lasting improvement of the ABG both in the short and long-term follow-up. A similarly large improvement of the sound transmission can be achieved both in patients with a Type A and a Type B/C tympanogram.
Prevalence, predictors, prognostic significance, and effect of techniques on outcomes of coronary lesion calcification following implantation of drug-eluting stents: a patient-level pooled analysis of stent-specific, multicenter, prospective IRIS-DES registries
Authors: Lee Cheol Hyun , Ahn Jung-Min , Lee Kyu Sup , Kang Do-Yoon , Lee Pil Hyung , Lee Seung-Whan , Lee Cheol Whan , Park Seong-Wook , Park Duk-Woo , Park Seung-Jung 
Published: April 2020

Aims
There is limited information on the clinical relevance and procedural impact of coronary artery calcification (CAC) in the contemporary percutaneous coronary intervention (PCI) setting. This study sought to determine the incidence and clinical significance of procedural techniques on the outcomes in ‘real-world’ patients with CAC undergoing PCI with drug-eluting stents (DESs).

Methods and results
Using patient-level data from seven stent-specific, prospective DES registries, we evaluated 17 084 patients who underwent PCI with various DES types between July 2007 and July 2015. The primary outcome was target-vessel failure (TVF), defined as a composite of cardiac death, target-vessel myocardial infarction, or target-vessel revascularization. Outcomes through 3 years (and between 0–1 and 1–3 years) were assessed according to CAC status (none/mild vs. moderate/severe) and stenting technique (predilation or post-dilation). Among 17 084 patients with 22 739 lesions included in the pooled dataset, moderate to severe CAC was observed in 11.3% of patients (10.1% of lesions). Older age, lower BMI, diabetes, hypertension, family history of coronary artery disease, and renal failure were independent predictors of moderate/severe CAC. The presence of moderate/severe CAC was significantly associated with an adjusted risk of TVF at 3 years [hazard ratio, 1.37; 95% confidence interval (CI), 1.19–1.58; P < 0.001]. For severe CAC, optimal lesion preparation with predilation was associated with a lower 3-year rate of TVF (no vs. yes, 22.3 vs. 12.8%), in which the effect of predilation was prominent at the late period of 1–3 years (hazard ratio, 0.28; 95% CI, 0.12–0.69; P = 0.003) than at the early period through 1 year (hazard ratio, 1.16; 95% CI, 0.37–3.71; P = 0.80). However, post-dilation (with a high-pressure noncompliant balloon) had no effect on the outcome.

Conclusions
In this study, moderate/severe CAC was common (~10%) and strongly associated with TVF during 3 years of follow-up. For severe CAC, optimal lesion preparation with pre-balloon dilation has a significant effect on long-term outcomes, especially during the late period beyond 1 year. Clinical Trial Registration – URL: http://www.clinicaltrials.gov. Unique identifier: NCT01186133.
Major acute cardiovascular events in patients with inflammatory bowel disease
Authors: Gill Gauravpal S. , Fernandez Stephen J. , Malhotra Nidhi , Mete Mihriye , Garcia-Garcia Hector M. 
Published: April 2020

Background
Systemic inflammation and immune-mediated diseases have been associated with ischemic heart disease in addition to traditional risk factors. In this study, we investigate associations between inflammatory bowel disease (IBD) and acute cardiovascular events.

Methods
An observational study where patient data were extracted from our health system patient pool of 3 917 894. Propensity scores were calculated for all 15 292 patients (0.39%) with IBD to assemble a 1:1 matched cohort balanced for age, gender, race and known cardiovascular risk factors including hypertension, hyperlipidemia, diabetes mellitus and smoking (current and former). Secondary analyses were performed independently for 6658 patients with ulcerative colitis and 9406 patients with Crohn’s disease. ICD-9 and ICD-10 codes were used to identify cardiovascular risk factors and outcomes.

Results
Matched patients (n = 30 584) had a mean age of 51 years, with 58% being women, and 63% Caucasian. During the median follow-up of 4.4 years, all-cause mortality was observed in 1.7 versus 1.2% of patients from IBD and non-IBD groups, respectively [hazard ratio, 1.31; 95% confidence interval (CI), 1.08–1.58; P = 0.005]. Combined outcome for myocardial infarction or cardiovascular mortality was noted in 2.3 and 2.1% from IBD and non-IBD groups, respectively (hazard ratio, 1.04; 95% CI, 0.90–1.21; P = 0.588), while hazard ratios for cardiovascular mortality, myocardial infarction and unstable angina were 1.04 (0.74–1.47; P = 0.833), 1.05 (0.89–1.23; P = 0.591) and 1.10 (0.83–1.46; P = 0.524), respectively.

Conclusions
Among patients with IBD, incidence of acute coronary events did not show a statistically significant difference when compared to the matched cohort.
Antithrombotic therapy in patients with atrial fibrillation and acute coronary syndrome undergoing percutaneous coronary intervention; insights from a meta-analysis
Authors: Kuno Toshiki , Ueyama Hiroki , Ando Tomo , Briasoulis Alexandros , Takagi Hisato 
Published: April 2020

Background
The optimal antithrombotic regimen for patients undergoing percutaneous coronary intervention in acute coronary syndrome with concomitant atrial fibrillation is largely under investigation.

Method
PUBMED and EMBASE were searched through October 2019 for randomized trials or subgroup analyses of randomized trials investigating different antithrombotic strategies in patients with atrial fibrillation and acute coronary syndrome undergoing percutaneous coronary intervention. We compared dual antithrombotic therapy versus triple antithrombotic therapy. Dual antithrombotic therapy was defined as vitamin K antagonist or direct oral anticoagulant plus P2Y12 inhibitor. Triple antithrombotic therapy was defined as vitamin K antagonist or direct oral anticoagulant plus dual antiplatelet therapy (aspirin plus P2Y12 inhibitor). The primary safety outcome was trial outcome was trial defined major adverse cardiovascular events.

Results
Our search identified 5 eligible subgroup analyses of randomized controlled trials that enrolled a total of 4733 patients. Dual antithrombotic therapy significantly decreased the bleeding risk when compared with triple antithrombotic therapy (hazard ratio: 0.61; 95% confidential interval [0.51–0.71], P < 0.001, I
2 = 31%). However, there were no significant differences in major adverse cardiovascular event between dual antithrombotic therapy versus triple antithrombotic therapy (hazard ratio: 1.08; 95% confidential interval: 0.89–1.31, P = 0.44, I
2 = 0%).

Conclusion
In patients with atrial fibrillation and acute coronary syndrome undergoing percutaneous coronary intervention, dual antithrombotic therapy was associated with lower bleeding risk compared with triple antithrombotic therapy while conferring similar major adverse cardiovascular event risk. Our results should be interpreted cautiously because we did not analyze the risk of stent thrombosis.