bluuebunny/crossref_metadata_2025 huggingface dataset:
Contrast-Enhanced Ultrasound: A Superior Method for Surveillance and Follow-up to Detect and Classify Endoleaks Following EVAR
Authors: Hasan Muhammad , Schiro Brian J. , Benenati James F.
Published: July 2020

Endovascular aneurysm repair (EVAR) has become the standard of care for many patients with abdominal aortic aneurysms. Because of the delayed complications associated with EVAR, namely the development of endoleaks, yearly surveillance of the endograft and aneurysm sac is required. Surveillance has traditionally been carried out with 3-phase computed tomography angiography of the abdomen and pelvis with the use of intravenous iodinated contrast. This incurs cumulative doses of radiation over the remainder of the patient’s life and exposes these patients to repeated administrations of potentially nephrotoxic contrast agents. Contrast-enhanced ultrasound (CEUS) has emerged as an excellent method of evaluating and categorizing endoleaks without the use of radiation or nephrotoxic agents. This educational article centers around CEUS and its use in EVAR follow-up.
Dual solution of boundary-layer flow driven by variable plate and streaming-free velocity
Authors: Ferdows M , Alzahrani Faris , Sun Shuyu
Published: July 2020

This article presents a numerical study to investigate boundary-layer heat transfer fluid associated with a moving flat body in cooperation of variable plate and streaming-free velocity along the boundary surface in the laminar flow. The thermal conductivity is supposed to vary linearly with temperature. Similarity transformations are applied to render the governing partial differential equations for mass, momentum and energy into a system of ordinary differential equations to reveal the possible existence of dual solutions. MATLAB package has been used to solve the boundary value problem numerically. We present the effects of various parameters such as velocity ratio, thermal conductivity and variable viscosity on velocity and temperature distribution. The analysis of the results concerning Skin friction and Nusselt number near the wall is also presented. It is focused on the detection and description of the dual solutions. The study reveals that the undertaken problem admits dual solutions in particular range of values of different physical parameters. It can be seen that for the first branch solution, the fluid velocity decreases near the sheet, but it increases far away from the sheet for velocity ratio parameter, whereas the opposite effect is induced for second branch solution. Skin friction coefficient and rate of heat transfer increase due to increase in thermal conductivity parameter.
Multiple duplications of the superficial femoral artery – Case report and review of the literature
Authors: Kim Tanner I , Chaar Cassius Iyad Ochoa , Guzman Raul J , Fischer Uwe M
Published: July 2020

Objectives

Lower extremity arterial anatomic variations are rare, with duplication of the superficial femoral artery being an extremely uncommon variant with few prior reports in the literature. Methods/Results: We report the case of a 68-year-old male with calf claudication who underwent angiography and was found to have two separate areas of vessel duplication along the superficial femoral artery, which has not previously been described in the literature.

Conclusion

Although uncommon, recognition of a duplicated superficial femoral artery is important to avoid difficulties and complications that may arise during open or endovascular procedures.
Ultrasound in paediatric anaesthesia – A comprehensive review
Authors: Haroon-Mowahed Yumna , Cheen Ng Su , Barnett Sarah , West Simeon
Published: July 2020

The use of ultrasound is becoming more widespread in anaesthesia. In this review, we discuss the use of ultrasound in various aspects of paediatric anaesthesia and how it can be used to assist diagnostic and therapeutic interventions and the evidence available. We explore the use of ultrasound as an adjunct for regional anaesthesia, vascular access, airway management, bedside cardiac, pulmonary and abdominal imaging and intracranial pressure monitoring.
Performing a task jointly enhances the sound-induced flash illusion
Authors: Wahn Basil , Rohe Tim , Gearhart Anika , Kingstone Alan , Sinnett Scott
Published: July 2020

Our senses are stimulated continuously. Through multisensory integration, different sensory inputs may or may not be combined into a unitary percept. Simultaneous with this stimulation, people are frequently engaged in social interactions, but how multisensory integration and social processing interact is largely unknown. The present study investigated if, and how, the multisensory sound-induced flash illusion is affected by a social manipulation. In the sound-induced flash illusion, a participant typically receives one visual flash and two auditory beeps and she or he is required to indicate the number of flashes that were perceived. Often, the auditory beeps alter the perception of the flashes such that a participant tends to perceive two flashes instead of one flash. We tested whether performing a flash counting task with a partner (confederate), who was required to indicate the number of presented beeps, would modulate this illusion. We found that the sound-induced flash illusion was perceived significantly more often when the flash counting task was performed with the confederate compared with performing it alone. Yet, we no longer find this effect if visual access between the two individuals is prevented. These findings, combined with previous results, suggest that performing a multisensory task jointly—in this case an audiovisual task—lowers the extent to which an individual attends to visual information, which in turn affects the multisensory integration process.
Snoring and sleep apnoea
Authors: Agarwal Tanvi
Published: July 2020

Snoring and sleep apnoea lie at the two extremes of sleep-disordered breathing, one mild and one serious. Sleep-disordered breathing can impair a person’s ability to have normal restorative sleep, which is essential for health and well-being. It can lead to significant negative health outcomes and cause chronic disorders such as hypertension, pulmonary hypertension, heart disease and even stroke. It is imperative to differentiate simple snoring from obstructive sleep apnoea, as the management and morbidity differ drastically. This article aims to describe the pathophysiology of sleep-disordered breathing, the impact on lifestyle and health, the differentiation of simple snoring from sleep apnoea, when to refer and interim treatment for paediatric and adult patients.
Targeting the FGFR signaling pathway in cholangiocarcinoma: promise or delusion?
Authors: Wang Jing , Xing Xiaokang , Li Qijun , Zhang Ge , Wang Tao , Pan Hongming , Li Da
Published: July 2020

Cholangiocarcinoma (CCA) is a refractory cancer with limited treatment options and poorly understood molecular mechanisms underlying tumor development. The most effective treatment is surgical resection; however, patients are highly prone to recurrence. Moreover, considering that most patients are diagnosed in advanced stages, treatment options are restricted to palliative care, which results in poor prognosis. Due to the limited effect of chemotherapy and radiotherapy, targeted therapy is becoming a hot topic in the field of biliary cancer treatment. The fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) signaling pathway involves a variety of key biological processes for cell survival, differentiation, and metabolism. Next-generation sequencing data mining has shown that high levels of FGF/FGFR expression are associated with reduced overall survival (OS) in CAA, which indicates that the FGF/FGFR pathway may be an effective target for CAA treatment. This paper reviews the effect of FGF/FGFR signaling on CCA from onset to treatment and highlights the promise of FGF/FGFR signaling pathway inhibitors for targeting CCA.
#PolarizedFeeds: Three Experiments on Polarization, Framing, and Social Media
Authors: Banks Antoine , Calvo Ernesto , Karol David , Telhami Shibley
Published: July 2020

Does exposure to social media polarize users or simply sort out like-minded voters based on their preexisting beliefs? In this paper, we conduct three survey experiments to assess the direct and unconditioned effect of exposure to tweets on perceived ideological polarization of candidates and parties. We show that subjects treated with negative tweets see greater ideological distance between presidential nominees and between their parties. We also demonstrate that polarization increases with processing time. We demonstrate a social media effect on perceived polarization beyond that due to the self-selection of like-minded users into different media communities. We explain our results as the result of social media frames that increase contrast effects between voters and candidates.
Dreaming of Silence
Authors: Henson Donna F.
Published: July 2020

Situated in the interplay between and among the creative and critical, the lyrical and liminal, the communicative and performative, this fractured, layered essay explores the hopeless/hopeful flight of tales of trauma in this time of the Crisis Ordinary. In the safe space, safe place afforded by autoethnography, I reflect on the luxury of silence and dream of world peace.
A Diversity Ideology Intervention: Multiculturalism Reduces the Racial Achievement Gap
Authors: Birnbaum Hannah J. , Stephens Nicole M. , Townsend Sarah S. M. , Hamedani MarYam G.
Published: July 2020

In the United States, underrepresented racial minority (URM) students continue to face psychological barriers that undermine their achievement and fuel disparities in academic outcomes. In the current research, we tested whether a multicultural ideology intervention could improve URM students’ grade point averages (GPAs) during the first 2 years of college and thereby reduce the racial achievement gap. Specifically, first-year college students ( N = 407) read a diversity statement that represented the schools’ diversity ideology in terms of either multiculturalism or colorblindness. URM students who read a multicultural diversity statement earned higher GPAs 2 years later compared to those who read a colorblind diversity statement. Furthermore, they earned higher GPAs compared to a nonparticipant campus-wide control group. The current study is the first to demonstrate that multiculturalism can increase the long-term academic outcomes of URM students in college.
Severe chronic bowel obstruction associated with brown bowel syndrome
Authors: Chen Wongworawat Yan , Propst Robert , Raza Anwar , Rohweller Bonnie , Swentek Lourdes , Zuppan Craig William , Cobb Camilla
Published: July 2020

A 61-year-old alcoholic male with history of cholecystectomy presented with a 20-year history of recurrent bowel obstruction and a 30 lb weight loss. After numerous attempts at conservative management, exploratory laparotomy was performed, which showed no mechanical cause. Despite no clear etiology, the obstruction persisted and intensified. A follow-up computed tomography scan revealed a small bowel obstruction with concurrent megacolon. A total abdominal colectomy was performed, with ileostomy. Grossly, there was intestinal dilation up to 15 cm with prominent brown discoloration of bowel wall. No strictures or other fixed obstruction were identified. Microscopic examination revealed prominent lipofuscin-like pigment deposition, involving the muscularis propria, muscularis mucosae, and vascular smooth muscle. Histochemical staining was positive for periodic acid–Schiff and negative for iron and calcium, consistent with lipofuscin. The gross and histologic findings fit with brown bowel syndrome. Brown bowel syndrome is a very rare condition characterized by lipofuscin deposits predominantly within the smooth muscle of the muscularis mucosae and/or muscularis propria that imparts a brown color to the bowel. It is generally thought to be a smooth muscle mitochondrial myopathy due to chronic vitamin E deficiency secondary to fat malabsorption syndromes, resulting in free radicals causing peroxidation of unsaturated membrane lipids with accumulation of lipofuscin. Brown bowel syndrome may be seen in patients with alcohol abuse, maldigestion, chronic bowel inflammation, and intestinal lymphangiectasia. Our patient’s severe chronic intestinal pseudo-obstruction, low levels of certain fat-soluble vitamins (A, D, and E), significant weight loss and history of cholecystectomy with alcohol abuse correlates with brown bowel syndrome clinically.
Efficacy and Safety of Surgical Kidney Stone Interventions in Autosomal Dominant Polycystic Kidney Disease: A Systematic Review
Authors: Kalatharan Vinusha , Jandoc Racquel , Grewal Gary , Nash Danielle M. , Welk Blayne , Sarma Sisira , Pei York , Garg Amit X.
Published: July 2020

Background:

Reduced kidney function and distorted kidney anatomy in patients with autosomal dominant polycystic kidney disease (ADPKD) may complicate stone interventions more compared with the general population.

Objectives:

To review studies describing the safety and efficacy of the 3 main stone interventions in adults with ADPKD: shock wave lithotripsy (SWL), ureteroscopy, and percutaneous nephrolithotomy (PCNL).

Design:

Systematic review.

Setting:

Any country of origin.

Patients:

Adults with ADPKD who underwent SWL, ureteroscopy, or PCNL.

Measurements:

Being stone free after the intervention and postoperative complications as reported by each study, which included pain, bleeding, and fever.

Methods:

Relevant studies published until February 2019 were identified through a comprehensive search of MEDLINE, EMBASE, Web of Science, BIOSIS PREVIEW, and CINAHL. Studies were eligible for review if they reported at least one outcome following SWL, ureteroscopy, and/or PCNL in adults with ADPKD. We then abstracted information on study characteristics, patient characteristics, intervention details, and postintervention outcomes and assessed the methodological quality of each study using a modified Downs and Black checklist.

Results:

We screened 221 citations from which we identified 24 studies that met our review criteria. We identified an additional article when manually reviewing the reference list of an included article, yielding a total of 25 studies describing 311 patients (32 SWL, 42 ureteroscopy, and 237 PCNL). The percentage of patients who were stone free after 1 session ranged from 0% to 69% after SWL, 73% to 100% after ureteroscopy, and 45% to 100% after PCNL. The percentage of patients with ADPKD that experienced at least one postoperative complication ranged from 0% to 33% for SWL, 0% to 27% for ureteroscopy, and 0% to 100% for PCNL.

Limitations:

The number and quality of studies published to date are limited.

Conclusions:

The efficacy and safety of stone interventions in patients with ADPKD remains uncertain, with wide-ranging estimates reported in the literature.

Trial Registration:

We did not register the protocol of this systematic review.
Serum peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 in combination with C-reactive protein and white blood cell as novel predictors for infants with community-acquired pneumonia
Authors: Xue Heng , Liu Hui , Xu Liangpu , Liu Qiaoling , Zhuo Bimin , Dai Meifeng , Wu Zhihui , Chen Min , Chen Qingquan
Published: July 2020

The aim of this study was to investigate the predictive value of peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) with C-reactive protein (CRP) and white blood cell (WBC) count for community-acquired pneumonia (CAP) in infants. A total of 84 hospitalized infants with CAP and 69 healthy infants were included in this study. The clinical manifestations and laboratory assay results of infants were recorded. Serum Pin1 level was estimated by enzyme-linked immunosorbent assay. The median serum Pin1 concentration in infants with CAP was significantly higher than that in controls (1.44 vs. 0.21 ng/mL, P < 0.0001). Receiver operating characteristic (ROC) curve analysis showed that the area under the ROC curve (AUC) of the combination Pin1, CRP and WBC (Pin1 + CRP + WBC, 0.943) was higher than Pin1, CRP, WBC alone or the combination of Pin1 and CRP ( P < 0.05). The sensitivity of Pin1 + CRP + WBC (94.0%) was higher than that of Pin1, CRP, WBC alone, or any two combined ( P < 0.05). Pin1 + CRP + WBC also had a high negative predictive value (91.4%). Moreover, serum Pin1 alone had a high specificity (97.0%) and excellent positive predictive value (96.6%) for infants with CAP, which were higher than WBC, Pin1 and WBC in combination, CRP and WBC in combination, and Pin1 + CRP + WBC ( P < 0.05). Therefore, serum Pin 1 was highly expressed in infants with CAP and can singly or in combination with CRP and WBC represent promising novel predictors for infants with CAP.
Case- Versus Lecture-Based Learning in a Public Health Course for OptometryStudents: A Pretest–Posttest Design
Authors: Foutch Brian K. , Awad-Amani Catherine , Conner Amy Belloli
Published: July 2020

Optometrists play a vital role in the prevention and management of many eye diseases. The expansion of optometrists’ prescribing and overall medical privileges has placed a burden on the optometric curriculum, limiting hours in professional topics courses such as practice management and public health. While the overall objectives may differ, the pedagogical challenges would be similar in public health training programs. That is, reduced hours and limited contact with students during the current COVID-19 (coronavirus disease 2019) pandemic both place pedagogical demands on the optometric and public health educator alike to meet learning objectives and course outcomes using atypical methods. As the current evidence about problem- or scenario-based versus lecture-based outcomes is equivocal, we randomly assigned half the students in an epidemiology/public health course to a case-based learning (CBL) group using three instructors naïve to problem-based teaching. The other half of the students attended lectures covering the same topics. Performance gains—the differences between the pretest and posttest scores—were compared between the two learning groups. The mean performance gain for the CBL group ( M = 25.5%) was slightly higher than for the lecture-based learning group ( M = 23.6%), but the difference was not statistically significant, t(56) = 0.71, p = .48. Inferences are discussed in the context of the study’s design and limitations. Overall, we believe our results can be extended to public health and health professions programs needing creative methods to reach health promotion learning objectives with limited student contact.
Research to Resource: Developing a Sense of Community in Online Learning Environments
Authors: Adams Kari
Published: July 2020

Many music educators are concerned about building healthy classroom communities as they prepare to transition to online or blended learning environments. Research involving distance education has indicated that several techniques in the design and delivery of online instruction can increase students’ sense of community, commitment to the course, and overall learning experience. The purpose of this research-to-resource article is to provide music educators with research-based strategies for establishing and connecting students to a sense of community in courses delivered partially or entirely online.
High metabolic tumor volume is associated with decreased efficacy of axicabtagene ciloleucel in large B-cell lymphoma
Authors: Dean Erin A. , Mhaskar Rahul S. , Lu Hong , Mousa Mina S. , Krivenko Gabriel S. , Lazaryan Aleksandr , Bachmeier Christina A. , Chavez Julio C. , Nishihori Taiga , Davila Marco L. , Khimani Farhad , Liu Hien D. , Pinilla-Ibarz Javier , Shah Bijal D. , Jain Michael D. , Balagurunathan Yoganand , Locke Frederick L.
Published: July 2020

High metabolic tumor volume (MTV) predicts worse outcomes in lymphoma treated with chemotherapy. However, it is unknown if this holds for patients treated with axicabtagene ciloleucel (axi-cel), an anti-CD19 targeted chimeric antigen receptor T-cell therapy. The primary objective of this retrospective study was to investigate the relationship between MTV and survival (overall survival [OS] and progression-free survival [PFS]) in patients with relapsed/refractory large B-cell lymphoma (LBCL) treated with axi-cel. Secondary objectives included finding the association of MTV with response rates and toxicity. The MTV values on baseline positron emission tomography of 96 patients were calculated via manual methodology using commercial software. Based on a median MTV cutoff value of 147.5 mL in the first cohort (n = 48), patients were divided into high and low MTV groups. Median follow-up for survivors was 24.98 months (range, 10.59-51.02 months). Patients with low MTV had significantly superior OS (hazard ratio [HR], 0.25; 95% confidence interval [CI], 0.10-0.66) and PFS (HR, 0.40; 95% CI, 0.18-0.89). Results were successfully validated in a second cohort of 48 patients with a median follow-up for survivors of 12.03 months (range, 0.89-25.74 months). Patients with low MTV were found to have superior OS (HR, 0.14; 95% CI, 0.05-0.42) and PFS (HR, 0.29; 95% CI, 0.12-0.69). In conclusion, baseline MTV is associated with OS and PFS in axi-cel recipients with LBCL.
Men with sickle cell disease experience greater sexual dysfunction when compared with men without sickle cell disease
Authors: Idris Ibrahim M. , Abba Akib , Galadanci Jamil A. , Mashi Sharfuddeen A. , Hussaini Nafiu , Gumel Sagir Ahmed , Burnett Arthur L. , DeBaun Michael R.
Published: July 2020

Recurrent ischemic priapism is a common complication of sickle cell disease (SCD). We assessed the burden, characteristics, and types of priapism, including sexual dysfunction, in a cohort of men with and those without SCD, to test the hypothesis that sexual dysfunction is more prevalent in men with SCD. In Kano, Nigeria, we conducted a comparative cross-sectional survey that included 500 and 250 men 18 to 40 years of age, with and without SCD, respectively. The survey used the Priapism Questionnaire and the International Index of Erectile Function for sexual function assessment. All eligible participants approached for the study gave informed consent and were enrolled. Stuttering and major priapism were defined based on the average duration of priapism experiences that lasted ≤4 and >4 hours, respectively. The prevalence of priapism was significantly higher in men with SCD than in those without it (32.6% vs 2%; P < .001). Stuttering priapism accounted for 73.6% of the priapism episodes in men with SCD. Nearly 50% of the participants with SCD-related priapism had never sought medical attention for this complication. The majority of the men with SCD-related priapism used exercise as a coping mechanism. Priapism affected the self-image of the men with SCD, causing sadness, embarrassment, and fear. The percentage of the men with SCD who had erectile dysfunction was more than twofold higher than that of those without SCD who had erectile dysfunction (P = .01). The men with SCD had a higher prevalence of priapism and sexual dysfunction than the men without SCD.
Pirfenidone plus inhaled N-acetylcysteine for idiopathic pulmonary fibrosis: a randomised trial
Authors: Sakamoto Susumu , Kataoka Kensuke , Kondoh Yasuhiro , Kato Motoyasu , Okamoto Masaki , Mukae Hiroshi , Bando Masashi , Suda Takafumi , Yatera Kazuhiro , Tanino Yoshinori , Kishaba Tomoo , Hattori Noboru , Taguchi Yoshio , Saito Takefumi , Nishioka Yasuhiko , Kuwano Kazuyoshi , Kishi Kazuma , Inase Naohiko , Sasaki Shinichi , Takizawa Hajime , Johkoh Takeshi , Sakai Fumikazu , Homma Sakae
Published: July 2020

Background

A randomised controlled trial in Japan showed that inhaled N-acetylcysteine monotherapy stabilised serial decline in forced vital capacity (FVC) in some patients with early idiopathic pulmonary fibrosis (IPF). However, the efficacy and tolerability of combination therapy with an antifibrotic agent and inhaled N-acetylcysteine are unknown.

Methods

This 48-week, randomised, open-label, multicentre phase 3 trial compared the efficacy and tolerability of combination therapy with pirfenidone plus inhaled N-acetylcysteine 352.4 mg twice daily with the results for pirfenidone alone in patients with IPF. The primary end-point was annual rate of decline in FVC. Exploratory efficacy measurements included serial change in diffusing capacity of the lung for carbon monoxide (DLCO) and 6-min walk distance (6MWD), progression-free survival (PFS), incidence of acute exacerbation, and tolerability.

Results

81 patients were randomly assigned in a 1:1 ratio to receive pirfenidone plus inhaled N-acetylcysteine (n=41) or pirfenidone (n=40). The 48-week rate of change in FVC was −300 mL and −123 mL, respectively (difference −178 mL, 95% CI −324–−31 mL; p=0.018). Serial change inDLCO, 6MWD, PFS and incidence of acute exacerbation did not significantly differ between the two groups. The incidence of adverse events (n=19 (55.9%) for pirfenidone plus N-acetylcysteine; n=18 (50%) for pirfenidone alone) was similar between groups.

Conclusions

Combination treatment with inhaled N-acetylcysteine and pirfenidone is likely to result in worse outcomes for IPF.
The effect of pain conditioning on experimentally evoked cough: evidence of impaired endogenous inhibitory control mechanisms in refractory chronic cough
Authors: Hilton Emma , Satia Imran , Holt Kimberley , Woodcock Ashley A. , Belcher John , Smith Jaclyn A.
Published: July 2020

The pathophysiology of refractory chronic cough (RCC) is unclear. We hypothesised that endogenous inhibitory control mechanisms, such as those activated by noxious stimuli inducing pain (conditioned pain modulation) may be capable of inhibiting coughing and urge to cough evoked by inhaled capsaicin. Furthermore, these mechanisms may be impaired in patients with RCC.

The objective was to investigate the effects of pain on cough and urge to cough in healthy volunteers and RCC patients. Healthy volunteers and RCC patients underwent a randomised, controlled, four-way crossover study comparing the effect of four interventions on capsaicin-evoked coughing and urge to cough. The interventions comprised immersing a hand in 1) noxious cold water; 2) warm water; 3) warm water, but subjects were instructed to voluntarily supress coughing; and 4) no intervention. The co-primary outcomes were numbers of evoked coughs and urge to cough scores.

20 healthy volunteers (mean±sdage 50.1±14.2 years, male:female 10:10) and 20 RCC patients (age 60.1±7.9 years, male:female 9:11) participated. Overall, noxious cold water reduced capsaicin-evoked urge-to-cough scores and cough numbers compared with warm water (1.6 (95% CI 1.3–2.0)versus2.2 (1.8–2.6), p<0.001 and 4.8 (3.7–6.2) coughsversus7.9 (6.7–9.5) coughs, p<0.001, respectively). Healthy volunteers and RCC patients demonstrated similar reductions in the urge to cough during noxious cold-water immersion, but noxious cold water and voluntary suppression interventions were less effective at reducing capsaicin-evoked cough in RCC patients than in healthy volunteers (p=0.041).

Endogenous inhibitory control mechanisms, specifically those activated by pain, can reduce both coughing and the urge to cough. Impairment of endogenous inhibitory control mechanisms may contribute to excessive coughing in RCC.
A performant bridge between fixed-size and variable-size seeding
Authors: Kutzner Arne , Kim Pok-Son , Schmidt Markus
Published: July 2020

Background

Seeding is usually the initial step of high-throughput sequence aligners. Two popular seeding strategies are fixed-size seeding (k-mers, minimizers) and variable-size seeding (MEMs, SMEMs, maximal spanning seeds). The former strategy supports fast seed computation, while the latter one benefits from a high seed uniqueness. Algorithmic bridges between instances of both seeding strategies are of interest for combining their respective advantages.

Results

We introduce an efficient strategy for computing MEMs out of fixed-size seeds (k-mers or minimizers). In contrast to previously proposed extend-purge strategies, our merge-extend strategy prevents the creation and filtering of duplicate MEMs. Further, we describe techniques for extracting SMEMs or maximal spanning seeds out of MEMs. A comprehensive benchmarking shows the applicability, strengths, shortcomings and computational requirements of all discussed seeding techniques. Additionally, we report the effects of seed occurrence filters in the context of these techniques.

Aside from our novel algorithmic approaches, we analyze hierarchies within fixed-size and variable-size seeding along with a mapping between instances of both seeding strategies.

Conclusion

Benchmarking shows that our proposed merge-extend strategy for MEM computation outperforms previous extend-purge strategies in the context of PacBio reads. The observed superiority grows with increasing read size and read quality. Further, the presented filters for extracting SMEMs or maximal spanning seeds out of MEMs outperform FMD-index based extension techniques. All code used for benchmarking is available via GitHub at https://github.com/ITBE-Lab/seed-evaluation.
SimuSCoP: reliably simulate Illumina sequencing data based on position and context dependent profiles
Authors: Yu Zhenhua , Du Fang , Ban Rongjun , Zhang Yuanwei
Published: July 2020

Background

A number of simulators have been developed for emulating next-generation sequencing data by incorporating known errors such as base substitutions and indels. However, their practicality may be degraded by functional and runtime limitations. Particularly, the positional and genomic contextual information is not effectively utilized for reliably characterizing base substitution patterns, as well as the positional and contextual difference of Phred quality scores is not fully investigated. Thus, a more effective and efficient bioinformatics tool is sorely required.

Results

Here, we introduce a novel tool, SimuSCoP, to reliably emulate complex DNA sequencing data. The base substitution patterns and the statistical behavior of quality scores in Illumina sequencing data are fully explored and integrated into the simulation model for reliably emulating datasets for different applications. In addition, an integrated and easy-to-use pipeline is employed in SimuSCoP to facilitate end-to-end simulation of complex samples, and high runtime efficiency is achieved by implementing the tool to run in multithreading with low memory consumption. These features enable SimuSCoP to gets substantial improvements in reliability, functionality, practicality and runtime efficiency. The tool is comprehensively evaluated in multiple aspects including consistency of profiles, simulation of genomic variations and complex tumor samples, and the results demonstrate the advantages of SimuSCoP over existing tools.

Conclusions

SimuSCoP, a new bioinformatics tool is developed to learn informative profiles from real sequencing data and reliably mimic complex data by introducing various genomic variations. We believe that the presented work will catalyse new development of downstream bioinformatics methods for analyzing sequencing data.
The NETest liquid biopsy is diagnostic for gastric neuroendocrine tumors: observations on the blood-based identification of microscopic and macroscopic residual disease
Authors: Malczewska A. , Procner A. , Walter A. , Kusnierz K. , Zajecki W. , Aslanian H. , Kos-Kudla B.
Published: July 2020

Background

NETest, a novel multi-gene liquid biopsy has utility in neuroendocrine tumor (NET) diagnosis and identification of residual disease. We independently assessed utility of the NETest to diagnose gastric neuroendocrine neoplasms (GNENs) and identify micro- and macroscopic residual disease.

Methods

Cohorts comprised histologically confirmed GNENs at biopsy, n = 46; GNETs Type 1: 42 (32 NET G1, 10 NET G2), a GNET Type 3: 1 well-differentiated NET G3, neuroendocrine carcinomas (NECs) (n = 3), and controls (n = 63). Disease status at sampling was assessed by gastroscopy, histology (resection margin [R] positivity of polypectomy or biopsy), EUS, CT or MRI, and/or 68Ga-DOTA-TATE PET/CT. Groups included image- (gastroscopy, EUS, and anatomical and/or functional imaging) positive or image negative disease. NETest assay by PCR (spotted plates, normal cut-off: 20). Data: mean ± SD.

Results

Disease extent: Image-negative (n = 30) (21 R0, 9 R1); Image-positive, n = 16.

Diagnosis: NETest was increased in GNETs (23 ± 11) vs. controls (7 ± 4, p < 0.0001). In histology-positive, the NETest accuracy was 100% (25/25).

Microscopic disease: In image-negative but R1, NETest was elevated in 100% (9/9; 28 ± 9). Levels were elevated vs. controls (7 ± 4, p < 0.0001), or R0 (16 ± 11, p = 0.02). Eight of 21 R0, exhibited positive NETest.

Macroscopic disease: Gastric lesions were multiple: 38%, single: 62%, submucosal: 13%, or ulcerated: 13%. Lesions size was ≤5 mm (50%), > 5–9.9 mm (17%), 10–19.9 mm (17%), ≥20 mm (17%) [≥10 mm: 34%). The NETest accuracy was 100% (16/16). Levels (28 ± 7) were higher than controls (7 ± 4, p < 0.0001) or R0 (16 ± 11, p = 0.002) but not to R1 (28 ± 9, p = 0.5).

Conclusions

NETest is diagnostic for gastric NETs. Elevated levels identify both microscopic and macroscopic residual disease. In histology/image-negative disease, elevated NETest may reflect early evidence of increased neuroendocrine gene expression of hypergastrinemia-induced neoplastic transformation of enterochromaffin-like (ECL) cells to tumor status. A sensitive liquid biopsy has utility in the management and surveillance of gastric NET disease.
Healthy aging in elderly cochlear implant recipients: a multinational observational study
Authors: Marx M. , Mosnier I. , Belmin J. , Wyss J. , Coudert-Koall C. , Ramos A. , Manrique Huarte R. , Khnifes R. , Hilly O. , Martini A. , Cuda D.
Published: July 2020

Background

Given an increase in the aging population and its impact on healthcare systems, policy makers for provision of health and social services are aiming to keep older adults in good health for longer, in other words towards ‘healthy aging’. Our study objective is to show that rehabilitation with cochlear implant treatment in the elderly with hearing impairment improves the overall health-related quality of life and general well-being that translate into healthy aging.

Methods

The multicentre, prospective, repeated measures, single-subject, clinical observational study will accrue 100 elderly, first-time, unilateral CI recipients (≥ 60 years) and analyze changes on specific measurement tools over ca. 20 months from preimplant to postimplant. Evaluations will consist of details collected through case history and interview questionnaires by clinicians, data logging, self-report questionnaires completed by the recipients and a series of commonly used audiometric measures and geriatric assessment tools. The primary indicator of changes in overall quality of life will be the HUI-3.

Discussion

The protocol is designed to make use of measurement tools that have already been applied to the hearing-impaired population in order to compare effects of CI rehabilitation in adults immediately before their implantation, (pre-implant) and after gaining 1–1.5 years of experience (post-implant). The broad approach will lead to a greater understanding of how useful hearing impacts the quality of life in elderly individuals, and thus improves potentials for healthy aging. Outcomes will be described and analyzed in detail.

Trial registration

This research has been registered in ClinicalTrials.gov (http://www.clinicaltrials.gov/), 7 March 2017 under the n° NCT03072862.
Cerebral and pulmonary aspergillosis, treatment and diagnostic challenges of mixed breakthrough invasive fungal infections: case report study
Authors: Amanati Ali , Lotfi Mehrzad , Masoudi Mohammad Sadegh , Jafarian Hadis , Ghasemi Fatemeh , Bozorgi Haleh , Badiee Parisa
Published: July 2020

Background

Breakthrough invasive fungal infections (bIFIs) are an area of concern in the scarcity of new antifungals. The mixed form of bIFIs is a rare phenomenon but could be potentially a troublesome challenge when caused by azole-resistant strains or non-Aspergillus fumigatus. To raise awareness and emphasize diagnostic challenges, we present a case of mixed bIFIs in a child with acute lymphoblastic leukemia.

Case presentation

A newly diagnosed 18-month-old boy with acute lymphoblastic leukemia was complicated with prolonged severe neutropenia after induction chemotherapy. He experienced repeated episodes of fever due to extended-spectrum beta-lactamase-producing Escherichia coli bloodstream infection and pulmonary invasive fungal infection with Aspergillus fumigatus (early-type bIFIs) while receiving antifungal prophylaxis. Shortly after pulmonary involvement, his condition aggravated by abnormal focal movement, loss of consciousness and seizure. Cerebral aspergillosis with Aspergillus niger diagnosed after brain tissue biopsy. The patient finally died despite 108-day antifungal therapy.

Conclusions

Mixed bIFIs is a rare condition with high morbidity and mortality in the patients receiving immunosuppressants for hematological malignancies. This case highlights the clinical importance of Aspergillus identification at the species level in invasive fungal infections with multiple site involvement in the patients on antifungal prophylaxis.
Analysis of 4 imaging features in patients with COVID-19
Authors: Jin Jun , Gao De-hong , Mo Xin , Tan Si-ping , Kou Zhen-xia , Chen Yi-bo , Cao Jin-bo , Chen Wen-jing , Zhang Ya-ming , Li Bing-qing , Huang Kuan-long , Xu Bing-ren , Tang Xiao-li , Wang Yu-li
Published: July 2020

Background

The aim of this was to analyze 4 chest CT imaging features of patients with coronavirus disease 2019 (COVID-19) in Shenzhen, China so as to improve the diagnosis of COVID-19.

Methods

Chest CT of 34 patients with COVID-19 confirmed by the nucleic acid test (NAT) were retrospectively analyzed. Analyses were performed to investigate the pathological basis of four imaging features(“feather sign”,“dandelion sign”,“pomegranate sign”, and “rime sign”) and to summarize the follow-up results.

Results

There were 22 patients (65.2%) with typical “feather sign”and 18 (52.9%) with “dandelion sign”, while few patients had “pomegranate sign” and “rime sign”. The “feather sign” and “dandelion sign” were composed of stripe or round ground-glass opacity (GGO), thickened blood vessels, and small-thickened interlobular septa. The “pomegranate sign” was characterized as follows: the increased range of GGO, the significant thickening of the interlobular septum, complicated with a small amount of punctate alveolar hemorrhage. The “rime sign” was characterized by numerous alveolar edemas. Microscopically, the wall thickening, small vascular proliferation, luminal stenosis, and occlusion, accompanied by interstitial infiltration of inflammatory cells, as well as numerous pulmonary interstitial fibrosis and partial hyaline degeneration were observed. Repeated chest CT revealed the mediastinal lymphadenectasis in one patient. Re-examination of the NAT showed another positive anal swab in two patients.

Conclusion

“Feather sign” and “dandelion sign” were typical chest CT features in patients withCOVID-19; “pomegranate sign” was an atypical feature, and “rime sign” was a severe feature. In clinical work, accurate identification of various chest CT signs can help to improve the diagnostic accuracy of COVID-19 and reduce the misdiagnosis or missed diagnosis rate.
An overview of the multi-pronged approach in the diagnosis of Alport syndrome for 22 children in Northeast China
Authors: Zhang Li , Sun Bai-chao , Zhao Bing-gang , Ma Qing-shan
Published: July 2020

Background

Alport syndrome (AS) is a kind of progressive hereditary nephritis induced by mutations of different genes that encode collagen IV. The affected individuals usually develop hematuria during childhood, accompanying with gradual deterioration of renal functions. In this study, the multi-pronged approach was employed to improve the diagnosis of AS.

Methods

Twenty-two children were diagnosed and treated at the Department of Pediatric Nephrology of Jilin University First Hospital between January 2017 and January 2020 using the multi-pronged approach. The following information was collected from patients, including age of onset, age at diagnosis, clinical manifestations, family history, renal pathology and genotype.

Results

All these 22 children were diagnosed with Alport syndrome according to the diagnostic criteria formulated by the Japanese Society of Nephrology (2015), among them, only 13 children met the diagnostic criteria released in 1988. All the 22 patients presented with hematuria, and proteinuria to varying degrees was observed in some patients. Three children suffered from hearing loss, but no child in the cohort had any visual problem or renal failure. Meanwhile, five patients were estimated to be at Stage 2, whereas the remaining 17 cases were at Stage 0. Renal biopsies were performed in 18 patients, including 14 showing glomerular basement membranes (GBM)-specific abnormalities. Moreover, 13 children were detected with mutations of genes encoding collagen IV.

Conclusions

The multi-pronged approach helps to improve the diagnosis of AS. Most patients do not have renal failure during childhood, but close assessment and monitoring are necessary. Also, the advancements in treatment are reviewed.
Differential associations of proinflammatory and anti-inflammatory cytokines with depression severity from noncancer status to breast cancer course and subsequent chemotherapy
Authors: Tzang Bor-Show , Chen Vincent Chin-Hung , Hsieh Ching-Chuan , Wang Wen-Ke , Weng Yi-Ping , Ho Hsing-Ying , Hsu Ya-Ting , Hsaio Han-Pin , Weng Jun-Cheng , Chen Yi-Lung
Published: July 2020

Background

In this study, we examined the differential associations of various proinflammatory and anti-inflammatory cytokines with depression severity from the development of breast cancer to subsequent chemotherapy treatment.

Methods

A cross-sectional study was conducted on a sample of 116 women: 29 controls without cancer, 55 patients with breast cancer who were not receiving chemotherapy, and 32 patients with breast cancer who were receiving chemotherapy. Blood samples were assayed to evaluate serum levels of the following cytokines: interferon-γ, interleukin (IL)-12 (p70), IL-1β, IL-2, tumor necrosis factor (TNF)-α, IL-4, IL-5, IL-10, IL-13, IL-6, and IL-17A. Depression severity was assessed using the Patient Health Questionnaire.

Results

After adjustment for sociodemographics, consistent patterns of the association between cytokine and depression were noted in the different groups. No significant associations were observed in the controls. Inverse associations were observed between cytokines levels and depression severity in patients with breast cancer who were not receiving chemotherapy, whereas positive associations were noted in patients with breast cancer who were receiving chemotherapy. Specific differential relationships between IL-5 levels and depression severity were found between patients with breast cancer who were receiving and not receiving chemotherapy.

Conclusions

Our study revealed differential relationships between cytokine levels and depression severity with the development of cancer. Immunostimulation and immunosuppression in breast cancer and cancer treatment may account for the differential responses with the development of breast cancer.
Relationship between pulmonary function and albuminuria in type 2 diabetic patients with preserved renal function
Authors: He Yun-Yun , Chen Zhe , Fang Xiang-Yang , Chang Jing , Lu Yong , Wang Xiao-Juan
Published: July 2020

Background

Albuminuria is the early manifestation of the pathogenesis of diabetic nephropathy (DN). The current study was to investigate the relationship of pulmonary function with albuminuria in type 2 diabetic patients with preserved renal function to evaluate the role of pulmonary function in the early stage of DN.

Methods

A total of 326 patients with type 2 diabetes mellitus (T2DM) including 270 without albuminuria and 56 with albuminuria, and 265 non-diabetic patients were enrolled. The patients’ general information, and the parameters of pulmonary function, including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC, total lung capacity (TLC), diffusion capacity for carbon monoxide of lung (DLCO) were compared between T2DM and control groups, as well as T2DM patients with and without albuminuria groups. All pulmonary function parameters were expressed as a percentage of those predicted (%pred). Logistic regression models were constructed to test the association of albuminuria and pulmonary function.

Results

The values of FVC%pred, FEV1%pred, TLC%pred and DLCO%pred were lower, and the proportion of subjects with FVC%pred < 80, FEV1%pred < 80, and DLCOc%pred < 80 was higher in T2DM subjects than controls (all P < 0.05). Subgroup analysis of diabetic patients showed that the values of FVC%pred, FEV1%pred, TLC%pred, and DLCOc%pred (97.18 ± 13.45, 93.95 ± 14.51, 90.64 ± 9.97, 87.27 ± 13.13, respectively) were significantly lower in T2DM subjects with albuminuria than those without albuminuria (103.94 ± 14.12, 99.20 ± 14.25, 93.79 ± 10.36, 92.62 ± 13.45, all P < 0.05). There was a significantly negative correlation between the urine albumin-to-creatinine ratio (UACR) and DLCOc%pred (r = − 0.143, P = 0.010) in spearman linear correlation test. In logistic regression analysis, the FVC%pred (OR 0.965, 95%CI 0.944–0.988), FEV1%pred (OR 0.975, 95%CI 0.954–0.996), and DLCOc%pred (OR 0.974, 95%CI 0.951–0.998) were independently associated with albuminuria after adjustments for smoking index, duration, HbA1c, FBG, and TG.

Conclusion

Our results demonstrated albuminuria is associated with a restrictive pulmonary function as well as pulmonary diffusion function in T2DM with preserved renal function, which remind us to be alert of the pulmonary function decline even in the early stage of DN.